PMID- 361226 OWN - NLM STAT- MEDLINE DCOM- 19790126 LR - 20191210 IS - 0361-5960 (Print) IS - 0361-5960 (Linking) VI - 62 IP - 10 DP - 1978 Oct TI - Phase I clinical study of quelamycin. PG - 1527-34 AB - A phase I clinical study was done with quelamycin, a recently synthesized triferric derivative of adriamycin. Twenty-one good-risk patients were studied: 19 patients with non-small cell carcinoma of the lung and two patients with metastatic sarcoma. Acute toxicity occurred in all patients and consisted of high fever, flushing, hypertension, generalized body aches, tremors, and confusion, which lasted 3-6 hours. Potentially dangerous cardiotoxicity occurred in eight patients who had previous minor rhythm disturbances, and was characterized by tachycardia, atrial extrasystoles, atrial fibrillation, and branch block which lasted 6-14 hours. The dose-limiting hematologic toxicity was found to occur at 125 mg/m2 iv single-dose. Objective responses were observed in three of 19 patients with lung cancer and in one patient with metastatic osteogenic sarcoma resistant to adriamycin therapy. In conclusion, quelamycin is a new derivative of adriamycin with potential interest. However, the acute generalized toxicity and the immediate cardiotoxicity found in the presently used schedule are excessive. Further studies directed to suppress these side effects are in progress. FAU - Brugarolas, A AU - Brugarolas A FAU - Pachon, N AU - Pachon N FAU - Gosalvez, M AU - Gosalvez M FAU - Llanderal, A P AU - Llanderal AP FAU - Lacave, A J AU - Lacave AJ FAU - Buesa, J M AU - Buesa JM FAU - Marco, M G AU - Marco MG LA - eng PT - Clinical Trial PT - Journal Article PL - United States TA - Cancer Treat Rep JT - Cancer treatment reports JID - 7607107 RN - 0 (Ferric Compounds) RN - 64719-39-7 (quelamycin) RN - 80168379AG (Doxorubicin) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Arrhythmias, Cardiac/chemically induced MH - Carcinoma/*drug therapy MH - Clinical Trials as Topic MH - Doxorubicin/adverse effects/*analogs & derivatives/therapeutic use MH - Drug Evaluation MH - Female MH - Ferric Compounds/adverse effects/therapeutic use MH - Hematologic Diseases/chemically induced MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Sarcoma/*drug therapy EDAT- 1978/10/01 00:00 MHDA- 1978/10/01 00:01 CRDT- 1978/10/01 00:00 PHST- 1978/10/01 00:00 [pubmed] PHST- 1978/10/01 00:01 [medline] PHST- 1978/10/01 00:00 [entrez] PST - ppublish SO - Cancer Treat Rep. 1978 Oct;62(10):1527-34. PMID- 8094467 OWN - NLM STAT- MEDLINE DCOM- 19930316 LR - 20190512 IS - 0027-8874 (Print) IS - 0027-8874 (Linking) VI - 85 IP - 5 DP - 1993 Mar 3 TI - Phase II study of taxol, merbarone, and piroxantrone in stage IV non-small-cell lung cancer: The Eastern Cooperative Oncology Group Results. PG - 388-94 AB - BACKGROUND: Patients with metastatic (stage IV) non-small-cell lung cancer usually have a poor prognosis and disease refractory to chemotherapy. Three new agents--taxol, merbarone, and piroxantrone--have shown promising antitumor treatment in vitro and in animals. Taxol is an antimicrotubular agent that interferes with mitosis during cell division. Merbarone, a conjugate of thiobarbituric acid and aniline, is a topoisomerase II inhibitor, which thus inhibits DNA synthesis and tumor growth. Piroxantrone, an anthracenedione derivative, is a DNA intercalating agent that has shown potent antitumor activity in animal studies. PURPOSE: Our randomized phase II study was designed to evaluate the efficacy and toxicity of these agents in the treatment of stage IV metastatic non-small-cell lung cancer. METHODS: Eligible patients (119) were randomly assigned to receive one of the three treatments given every 3 weeks: 250 mg/m2 taxol by a 24-hour intravenous infusion, 1000 mg/m2 merbarone by continuous intravenous infusion through a central catheter daily for 5 days, or 150 mg/m2 piroxantrone by intravenous infusion over 1 hour. Patients had received no chemotherapy. Response and toxicity were evaluated every 3 weeks. RESULTS: Twenty-five patients were randomly assigned to receive taxol, 47 to receive merbarone, and 47 to receive piroxantrone. One of 44 assessable patients (2.3%) treated with piroxantrone had a complete response. Rates for partial response were 20.8% (five of 24 patients) and 5.7% (two of 35) for assessable patients treated with taxol or merbarone, respectively. One-year survival rates were 41.7%, 21.6%, and 22.6%, and median survival times were 24.1, 19.9, and 29.3 weeks for taxol, merbarone, and piroxantrone, respectively. These differences were not statistically significant, but this study was not designed to compare survival. In general, toxicity was manageable. With premedication, no anaphylaxis was observed with taxol. The most common toxic effects were leukopenia with taxol or piroxantrone treatment and thromboembolic complications with merbarone. Death directly related to treatment occurred in 4% (one patient), 11.4% (four), and 5% (two) of the assessable patients receiving taxol, merbarone, and piroxantrone, respectively. Cardiotoxicity and neurotoxicity occurred only occasionally in all three arms. CONCLUSION: On the basis of the response rate (20.8% partial response) and 1-year survival rate (41.7%), taxol is an active agent for the treatment of metastatic non-small-cell lung cancer. Merbarone and piroxantrone are relatively inactive. IMPLICATIONS: Further study of taxol is warranted. In future studies, taxol should be combined with other agents, and granulocyte colony-stimulating factor should be used to ameliorate myelosuppression. FAU - Chang, A Y AU - Chang AY AD - Department of Medicine, University of Rochester Cancer Center, N.Y. 14607. FAU - Kim, K AU - Kim K FAU - Glick, J AU - Glick J FAU - Anderson, T AU - Anderson T FAU - Karp, D AU - Karp D FAU - Johnson, D AU - Johnson D LA - eng GR - CA-06594/CA/NCI NIH HHS/United States GR - CA-14548/CA/NCI NIH HHS/United States GR - CA-21115/CA/NCI NIH HHS/United States GR - etc. PT - Clinical Trial PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Natl Cancer Inst JT - Journal of the National Cancer Institute JID - 7503089 RN - 0 (Anthraquinones) RN - 0 (Antineoplastic Agents) RN - 0 (Pyrazoles) RN - 0 (Thiobarbiturates) RN - P88XT4IS4D (Paclitaxel) RN - YL4TY9WH22 (piroxantrone) RN - YWB9IF596V (merbarone) SB - IM CIN - J Natl Cancer Inst. 1993 Mar 3;85(5):346-7. doi: 10.1093/jnci/85.5.346. PMID: 8094465 MH - Adult MH - Aged MH - Aged, 80 and over MH - Anthraquinones/adverse effects/*therapeutic use MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Atrial Fibrillation/chemically induced MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/pathology MH - Drug Administration Schedule MH - Female MH - Heart/drug effects MH - Humans MH - Lung Neoplasms/*drug therapy/mortality/pathology MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Paclitaxel/adverse effects/*therapeutic use MH - Pyrazoles/adverse effects/*therapeutic use MH - Remission Induction MH - Survival Analysis MH - Thiobarbiturates/adverse effects/*therapeutic use EDAT- 1993/03/03 00:00 MHDA- 1993/03/03 00:01 CRDT- 1993/03/03 00:00 PHST- 1993/03/03 00:00 [pubmed] PHST- 1993/03/03 00:01 [medline] PHST- 1993/03/03 00:00 [entrez] AID - 10.1093/jnci/85.5.388 [doi] PST - ppublish SO - J Natl Cancer Inst. 1993 Mar 3;85(5):388-94. doi: 10.1093/jnci/85.5.388. PMID- 9146330 OWN - NLM STAT- MEDLINE DCOM- 19970528 LR - 20131121 IS - 0003-4975 (Print) IS - 0003-4975 (Linking) VI - 63 IP - 5 DP - 1997 May TI - Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy. PG - 1374-81; discussion 1381-2 AB - BACKGROUND: This prospective study was designed to determine whether diltiazem is superior to digoxin for the prophylaxis of supraventricular dysrhythmias (SVD) after pneumonectomy or extrapleural pneumonectomy (EPP) and to assess the influence of these drugs on perioperative cardiac function. METHODS: Seventy consecutive patients without previous SVD were randomly allocated immediately after pneumonectomy or EPP to receive diltiazem (n = 35) or digoxin (n = 35). Diltiazem-treated patients received a slow intravenous loading dose of 20 mg, followed by 10 mg intravenously every 4 hours for 24 to 36 hours, then 180 to 240 mg orally daily for 1 month. Digoxin-treated patients received a 1-mg intravenous loading in the first 24 to 36 hours, then 0.125 to 0.25 mg orally daily for 1 month. A concurrent prospective cohort of 40 patients without previous SVD, who did not participate in the study and underwent pneumonectomy or EPP without prophylaxis, served as a comparison group for SVD occurrence. Serial Doppler echocardiograms were performed to assess cardiac function and all patients were continuously monitored with Holter recorders for 3 days. Data were analyzed by intent-to-treat. RESULTS: In patients undergoing standard or intrapericardial pneumonectomy, diltiazem prevented the overall incidence of postoperative SVD when compared with digoxin, 0 of 21 patients versus 8 of 25 patients, respectively, p < 0.005. When EPP patients were included in the analysis, diltiazem decreased the incidence of all SVD from 11 of 35 patients (31%) to 5 of 35 patients (14%) when compared with digoxin, p = 0.09. Digoxin-treated patients had a similar incidence of all SVD (31%) as concurrent controls (11 of 40 patients [28%]). The two treated groups did not differ in right or left atrial size, left ventricular ejection fraction, or right heart pressure. When all patients were combined, those in whom SVD developed were significantly older (65 +/- 12 years versus 55 +/- 11 years, p = 0.004) and had a longer median hospital stay (9 versus 6 days, p = 0.03), when compared with those in whom SVD did not develop, respectively. The subset of patients undergoing EPP had a greater incidence of atrial fibrillation and electrocardiographic changes suggestive of postoperative pericarditis than all other pneumonectomy patients. CONCLUSIONS: Diltiazem was both safe and more effective than digoxin in reducing the overall incidence of SVD after standard or intrapericardial pneumonectomy. Digoxin therapy had no effect on the incidence of postoperative SVD and is not recommended for prophylaxis of SVD. Dysrhythmias after pneumonectomy or EPP occur in older patients and are associated with a greater length of hospital stay. FAU - Amar, D AU - Amar D AD - Department of Anesthesiology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. FAU - Roistacher, N AU - Roistacher N FAU - Burt, M E AU - Burt ME FAU - Rusch, V W AU - Rusch VW FAU - Bains, M S AU - Bains MS FAU - Leung, D H AU - Leung DH FAU - Downey, R J AU - Downey RJ FAU - Ginsberg, R J AU - Ginsberg RJ LA - eng PT - Clinical Trial PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PL - Netherlands TA - Ann Thorac Surg JT - The Annals of thoracic surgery JID - 15030100R RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Calcium Channel Blockers) RN - 73K4184T59 (Digoxin) RN - EE92BBP03H (Diltiazem) SB - IM MH - Aged MH - Anti-Arrhythmia Agents/pharmacology/*therapeutic use MH - Arrhythmias, Cardiac/*drug therapy/etiology MH - Calcium Channel Blockers/pharmacology/*therapeutic use MH - Digoxin/pharmacology/*therapeutic use MH - Diltiazem/pharmacology/*therapeutic use MH - Echocardiography, Doppler MH - Female MH - Heart/*drug effects MH - Humans MH - Lung Neoplasms/surgery MH - Male MH - Middle Aged MH - Pleural Neoplasms/surgery MH - *Pneumonectomy/adverse effects MH - Prospective Studies MH - Treatment Outcome MH - Ventricular Pressure/drug effects EDAT- 1997/05/01 00:00 MHDA- 1997/05/01 00:01 CRDT- 1997/05/01 00:00 PHST- 1997/05/01 00:00 [pubmed] PHST- 1997/05/01 00:01 [medline] PHST- 1997/05/01 00:00 [entrez] AID - S000349759700235X [pii] PST - ppublish SO - Ann Thorac Surg. 1997 May;63(5):1374-81; discussion 1381-2. PMID- 9803048 OWN - NLM STAT- MEDLINE DCOM- 19981201 LR - 20190915 IS - 0885-3924 (Print) IS - 0885-3924 (Linking) VI - 16 IP - 4 DP - 1998 Oct TI - Dyspnea in the advanced cancer patient. PG - 212-9 AB - Optimal management of dyspnea in terminal cancer patients requires an understanding of the responsible pathophysiological mechanisms. This prospective study assessed visual analogue scales (VAS) of shortness of breath (SOB) and anxiety, bedside spirometry, maximum inspiratory pressure (MIP), chest radiography, arterial blood gases, hemoglobin, and electrocardiogram, if indicated, in 100 terminally ill cancer patients. Forty-nine percent of the patients had lung cancer. The median VAS scores for SOB and anxiety were 53 mm and 29 mm, respectively. Spirometry was abnormal in 93% of patients, with 5% having obstructive, 41% restrictive, and 47% mixed patterns. The median MIP was 16 cm H2O. Sixty-five percent of the patients had parenchymal or pleural involvement on chest radiograph. Twenty-nine percent had evidence of cardiac ischemia, recent or current myocardial infarction or atrial fibrillation. Patients had a median of five different abnormalities that could have contributed to their shortness of breath. Only anxiety (p = 0.001), a history of smoking (p = 0.02), and pCO2 levels were statistically significantly correlated with SOB VAS scores. The potentially correctable causes of dyspnea included hypoxia (40%), anemia (20%), and bronchospasm (52%). The finding of very low MIPs suggests severe respiratory muscle weakness may contribute significantly to dyspnea in this patient population. Further studies are needed to confirm this finding and characterize the underlying pathophysiology. FAU - Dudgeon, D J AU - Dudgeon DJ AD - Department of Internal Medicine, Queen's University, Kingston, Ontario, Canada. FAU - Lertzman, M AU - Lertzman M LA - eng PT - Clinical Trial PT - Controlled Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Pain Symptom Manage JT - Journal of pain and symptom management JID - 8605836 SB - IM CIN - J Pain Symptom Manage. 1999 Nov;18(5):313-5. doi: 10.1016/s0885-3924(99)00089-5. PMID: 10584452 MH - Adult MH - Aged MH - Aged, 80 and over MH - Dyspnea/*etiology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Neoplasms/*complications MH - Prospective Studies EDAT- 1998/11/06 00:00 MHDA- 1998/11/06 00:01 CRDT- 1998/11/06 00:00 PHST- 1998/11/06 00:00 [pubmed] PHST- 1998/11/06 00:01 [medline] PHST- 1998/11/06 00:00 [entrez] AID - S0885392498000657 [pii] AID - 10.1016/s0885-3924(98)00065-7 [doi] PST - ppublish SO - J Pain Symptom Manage. 1998 Oct;16(4):212-9. doi: 10.1016/s0885-3924(98)00065-7. PMID- 11268491 OWN - NLM STAT- MEDLINE DCOM- 20010412 LR - 20221207 IS - 0250-7005 (Print) IS - 0250-7005 (Linking) VI - 20 IP - 5C DP - 2000 Sep-Oct TI - New triplet chemotherapy combination with carboplatin, paclitaxel and gemcitabine plus amifostine support in advanced non small cell lung cancer: a phase II study. PG - 3999-4003 AB - New triplet chemotherapy combinations are under investigation in advanced non small cell lung cancer (NSCLC). Carboplatin, plus paclitaxel, plus gemcitabine is among the most active and promising regimens. The use of more aggressive chemotherapy in order to improve results can increase toxicity. Amifostine (WR-2721) reduces toxicity of radiotherapy and chemotherapy and protects selectively a number of normal, but not neoplastic, tissue. Based on this background, we performed a phase II study on carboplatin, plus paclitaxel, plus gemcitabine with amifostine support in advanced NSCLC. Patients received chemotherapy at the following dosage: carboplatin AUC 5, i.v., at day 1; paclitaxel 175 mg/m2, i.v. by 3-hour infusion, at day 1; gemcitabine 1000 mg/m2, i.v. by 3-hour infusion, at days 1 and 8; every 3 weeks for a maximum of 6 cycles. Amifostine was administered at the dose of 740 mg/m2, i.v., at day 1 of each cycle. Seventeen patients entered the study. They were prevalently male, median age was 62 years, PS (ECOG) was 0 in 10 cases (58.8%), 1 in 6 (35.3%) and 2 in 1 (5.9%). Histology was epidermoid in 8 cases (47%) and adenocarcinoma in 9 (53%). We observed 8 (47.5%) objective responses with 2 (11.7%) complete responses. Median time to progression and median survival were 24 and 36 weeks, respectively. Treatment was well tolerated. The main toxicity was as follows: grade 3 neutropenia, grade 2 thrombocytopenia and grade 3 anemia in one (5.8%) case; grade 2 peripheral neurologic toxicity in 3 (17.6%) patients; grade 2 cardiac toxicity (atrial fibrillation) in one case; and grade 3 respiratory toxicity (dispnoea) in one patient. These data indicate that this combination has promising activity and tolerability. A randomized trial comparing carboplatin plus paclitaxel, plus gemcitabine versus carboplatin, plus paclitaxel, plus gemcitabine, plus amifostine in advanced NSCLC is warranted. FAU - Illiano, A AU - Illiano A AD - VI Divisione di Pneumologia, Ospedale Monaldi, Napoli, Italy. FAU - Barletta, E AU - Barletta E FAU - De Marino, V AU - De Marino V FAU - Battiloro, C AU - Battiloro C FAU - Barzelloni, M AU - Barzelloni M FAU - Scognamiglio, F AU - Scognamiglio F FAU - Rossi, N AU - Rossi N FAU - Zampa, G AU - Zampa G FAU - De Bellis, M AU - De Bellis M FAU - Gridelli, C AU - Gridelli C LA - eng PT - Clinical Trial PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Radiation-Protective Agents) RN - 0W860991D6 (Deoxycytidine) RN - BG3F62OND5 (Carboplatin) RN - M487QF2F4V (Amifostine) RN - P88XT4IS4D (Paclitaxel) RN - 0 (Gemcitabine) SB - IM MH - Adenocarcinoma/drug therapy/pathology MH - Aged MH - Amifostine/administration & dosage/adverse effects/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology MH - Carcinoma, Squamous Cell/drug therapy/pathology MH - Deoxycytidine/administration & dosage/analogs & derivatives MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/pathology MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Paclitaxel/administration & dosage MH - Radiation-Protective Agents/administration & dosage/adverse effects/therapeutic use MH - Gemcitabine EDAT- 2001/03/28 10:00 MHDA- 2001/04/17 10:01 CRDT- 2001/03/28 10:00 PHST- 2001/03/28 10:00 [pubmed] PHST- 2001/04/17 10:01 [medline] PHST- 2001/03/28 10:00 [entrez] PST - ppublish SO - Anticancer Res. 2000 Sep-Oct;20(5C):3999-4003. PMID- 11165408 OWN - NLM STAT- MEDLINE DCOM- 20010510 LR - 20221207 IS - 0169-5002 (Print) IS - 0169-5002 (Linking) VI - 31 IP - 2-3 DP - 2001 Feb-Mar TI - Activity and toxicity of gemcitabine and gemcitabine + vinorelbine in advanced non-small-cell lung cancer elderly patients: Phase II data from the Multicenter Italian Lung Cancer in the Elderly Study (MILES) randomized trial. PG - 277-84 AB - BACKGROUND: Following the demonstration that vinorelbine improves survival and quality of life compared with best supportive care in elderly patients with advanced non-small-cell lung cancer (NSCLC), we started the three-arm prospective Multicenter Italian Lung Cancer in the Elderly Study (MILES) trial of vinorelbine, gemcitabine and gemcitabine + vinorelbine. DESIGN: Within the randomized phase 3 trial, pilot single-stage phase 2 studies were planned for gemcitabine and for gemcitabine + vinorelbine. Eligible patients are aged 70 or more, with stage IV or IIIb (with metastatic supraclavear nodes or malignant pleural effusion) NSCLC. Single-agent gemcitabine is given at 1200 mg/m(2) on days 1 and 8; in the combination, gemcitabine is given at 1000 mg/m(2) and vinorelbine at 25 mg/m(2), both on days 1 and 8, every 3 weeks. RESULTS: As planned 49 patients were enrolled in each group. Median age was 74 in both groups. Two-thirds of patients had stage IV disease. The response rate was 18.4% (95% exact CI 8.8-32.0) with both treatments. With single-agent gemcitabine main toxicities were grade 4 thrombocytopenia and grade 2 hepatic toxicity, in one patient each, and grade 2 pulmonary toxicity in two patients. With gemcitabine + vinorelbine combination there were grade 4 neutropenia and thrombocytopenia (one patient each), grade 3 anemia requiring red blood cell transfusion (two patients), and grade 4 fever in two patients. Four patients, with severe cardiac comorbidities, suffered grade 3 heart toxicity with atrial flutter or fibrillation, followed by congestive heart failure responsive to treatment. CONCLUSION: Both single-agent gemcitabine and the gemcitabine + vinorelbine combination are sufficiently active and tolerable to allow continuation of the MILES study. FAU - Gridelli, C AU - Gridelli C AD - Divisione di Oncologioca Medica B, Istituto Nazionale per lo Studio e la Cura dei Tumori, via M. Semmola, 80131 Naples, Italy. cgridelli@sirio-oncology.it FAU - Cigolari, S AU - Cigolari S FAU - Gallo, C AU - Gallo C FAU - Manzione, L AU - Manzione L FAU - Ianniello, G P AU - Ianniello GP FAU - Frontini, L AU - Frontini L FAU - Ferraù, F AU - Ferraù F FAU - Robbiati, S F AU - Robbiati SF FAU - Adamo, V AU - Adamo V FAU - Gasparini, G AU - Gasparini G FAU - Novello, S AU - Novello S FAU - Perrone, F AU - Perrone F CN - MILES Investigators LA - eng PT - Clinical Trial PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Antimetabolites, Antineoplastic) RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0W860991D6 (Deoxycytidine) RN - 5V9KLZ54CY (Vinblastine) RN - Q6C979R91Y (Vinorelbine) RN - 0 (Gemcitabine) SB - IM MH - Age Factors MH - Aged MH - Antimetabolites, Antineoplastic/adverse effects/*pharmacology MH - Antineoplastic Agents, Phytogenic/adverse effects/*pharmacology MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Atrial Fibrillation/chemically induced MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology MH - Chemical and Drug Induced Liver Injury MH - Deoxycytidine/adverse effects/analogs & derivatives/*pharmacology MH - Female MH - Fever/chemically induced MH - Humans MH - Infusions, Intravenous MH - Lung Neoplasms/*drug therapy/pathology MH - Male MH - Neutropenia/chemically induced MH - Thrombocytopenia/chemically induced MH - Vinblastine/adverse effects/*analogs & derivatives/*pharmacology MH - Vinorelbine MH - Gemcitabine EDAT- 2001/02/13 11:00 MHDA- 2001/05/22 10:01 CRDT- 2001/02/13 11:00 PHST- 2001/02/13 11:00 [pubmed] PHST- 2001/05/22 10:01 [medline] PHST- 2001/02/13 11:00 [entrez] AID - S0169-5002(00)00194-X [pii] AID - 10.1016/s0169-5002(00)00194-x [doi] PST - ppublish SO - Lung Cancer. 2001 Feb-Mar;31(2-3):277-84. doi: 10.1016/s0169-5002(00)00194-x. PMID- 11750714 OWN - NLM STAT- MEDLINE DCOM- 20020531 LR - 20190921 IS - 0169-5002 (Print) IS - 0169-5002 (Linking) VI - 35 IP - 1 DP - 2002 Jan TI - Single-agent pegylated liposomal doxorubicin (Caelix) in chemotherapy pretreated non-small cell lung cancer patients: a pilot trial. PG - 59-64 AB - Polyethylene glycol-coated (pegylated) liposomal doxorubicin (PLD) is a new formulation of doxorubicin with peculiar pharmacokinetic and pharmacodinamic properties, a favorable toxic profile and a demonstrated activity in solid tumors. We tested PLD in locally advanced or metastatic NSCLC patients, progressed after a platinum-based first-line chemotherapy. PLD was administered at the dose of 35 mg/m(2) every 21 days. After the first six patients had been accrued, due to the low toxicity shown in the first six patients, the dose was escalated to 45 mg/m(2). Seventeen patients were enrolled in the study and were considered eligible for evaluation of toxicity and response. Stomatitis, palmar-plantar erythrodysaesthesia (PPE) and asthenia were the most common toxicities and affected approximately half of the treated patients. Stomatitis occurred in 8/17 patients and was grade 3-4 in three. PPE was seen in 9/17 and was grade 3 in one. In the group treated at the dose of 45 mg/m(2) PPE was more frequent and severe and required treatment delay in some cases. Other toxicities were equally distributed among the two groups. Hematological toxicity was not common and never reached grade 3-4. However, one patient with grade 2 leucopenia had pneumonia and died. Clinically evident heart failure was never recorded. Left ventricular ejection fraction was assessed in three patients after PLD treatment (in one case after the first course, due to the occurrence of atrial fibrillation, and in two cases after six courses) and was unchanged compared to pre-treatment assessment. One confirmed partial response was observed (5.8%); five patients (29.4%) had stable disease (including one minor response) and nine (52.9%) had disease progression. Median time to progression was 9.5 weeks, median survival 18.6 weeks. PLD at the doses employed in this study can be safely administered and has shown activity in platinum pretreated NSCLC patients. FAU - Numico, Gianmauro AU - Numico G AD - Medical Oncology Unit, S.Croce e Carle General Hospital, Cuneo, Italy. gnumico@libero.it FAU - Castiglione, Federico AU - Castiglione F FAU - Granetto, Cristina AU - Granetto C FAU - Garrone, Ornella AU - Garrone O FAU - Mariani, Gabriella AU - Mariani G FAU - Costanzo, Gianna Di AU - Costanzo GD FAU - Ciura, Pietro La AU - Ciura PL FAU - Gasco, Milena AU - Gasco M FAU - Ostellino, Oliviero AU - Ostellino O FAU - Porcile, Gianfranco AU - Porcile G FAU - Merlano, Marco AU - Merlano M LA - eng PT - Clinical Trial PT - Clinical Trial, Phase II PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Antineoplastic Agents) RN - 0 (Liposomes) RN - 0 (Organoplatinum Compounds) RN - 0 (Surface-Active Agents) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 80168379AG (Doxorubicin) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Doxorubicin/*administration & dosage/adverse effects MH - Female MH - Humans MH - Infusions, Intravenous MH - Liposomes MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Organoplatinum Compounds/therapeutic use MH - Pilot Projects MH - *Polyethylene Glycols MH - Radiography, Thoracic MH - Salvage Therapy MH - Surface-Active Agents/chemistry MH - Tomography, X-Ray Computed MH - Treatment Outcome EDAT- 2001/12/26 10:00 MHDA- 2002/06/01 10:01 CRDT- 2001/12/26 10:00 PHST- 2001/12/26 10:00 [pubmed] PHST- 2002/06/01 10:01 [medline] PHST- 2001/12/26 10:00 [entrez] AID - S0169500201002690 [pii] AID - 10.1016/s0169-5002(01)00269-0 [doi] PST - ppublish SO - Lung Cancer. 2002 Jan;35(1):59-64. doi: 10.1016/s0169-5002(01)00269-0. PMID- 12738723 OWN - NLM STAT- MEDLINE DCOM- 20040112 LR - 20181130 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 9 IP - 5 DP - 2003 May TI - Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study. PG - 1698-704 AB - PURPOSE: To determine the maximum-tolerated dose of docetaxel (DOC) in combination with carboplatin (CAR) and thoracic radiotherapy (RT), in the setting of trimodality treatment of patients with stage III non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Thirty-two patients with biopsy-proven stage IIIA (n = 20) or IIIB (n = 12) NSCLC were given two initial cycles of CAR (area under the curve = 6) and DOC (75 mg/m(2)), subsequent RT (54 Gy) with concurrent weekly CAR (area under the curve = 2), and DOC at six dose levels from 10 to 40 mg/m(2), then surgery if the patient's disease was resectable. RESULTS: Three patients did not complete induction computed tomography (CT). Twenty-nine patients received concurrent CT/RT. Fifteen patients were eligible for surgery. Dose-limiting toxicities occurred in 2 patients, at dose levels two (atrial fibrillation) and three (transaminitis). The maximum-tolerated dose, as defined by the protocol, was not reached, although grade 3 and 4 toxicities were encountered at all dose levels. The most common more than or equal to grades 3 toxicities were neutropenia, nausea, vomiting, and fatigue. Four patients (13.3%) responded to induction CT. Ten patients (38.5%) responded to CT/RT. Eight surgical patients (57.1%) were downstaged, including 3 pathologic complete responses. Median relapse free and overall survivals are 8.5 and 12 months. One-year and estimated 2-year survival rates are 56.3 and 34.3%. CONCLUSION: This new regimen for stage III NSCLC of induction CAR/DOC, then weekly CAR/DOC with concurrent RT followed by surgery, can be safely administered and offers encouraging results. DOC at 30 mg/m(2) in combination with CAR and RT is recommended for Phase II study. FAU - Wirth, Lori J AU - Wirth LJ AD - Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. FAU - Lucca, Joan AU - Lucca J FAU - Ostler, Patricia AU - Ostler P FAU - Fidias, Panos AU - Fidias P FAU - Lynch, Cathy AU - Lynch C FAU - Jänne, Pasi A AU - Jänne PA FAU - Herbst, Roy S AU - Herbst RS FAU - Johnson, Bruce E AU - Johnson BE FAU - Sugarbaker, David J AU - Sugarbaker DJ FAU - Mathisen, Douglas J AU - Mathisen DJ FAU - Lukanich, Jeanne M AU - Lukanich JM FAU - Choi, Noah C AU - Choi NC FAU - Berman, Stuart M AU - Berman SM FAU - Skarin, Arthur T AU - Skarin AT LA - eng PT - Clinical Trial PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Taxoids) RN - 15H5577CQD (Docetaxel) RN - BG3F62OND5 (Carboplatin) SB - IM CIN - Clin Cancer Res. 2004 Apr 15;10(8):2902-3; author reply 2904. PMID: 15102699 MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/drug therapy/radiotherapy/surgery/*therapy MH - Combined Modality Therapy MH - Docetaxel MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Lung Neoplasms/drug therapy/radiotherapy/surgery/*therapy MH - Male MH - Maximum Tolerated Dose MH - Middle Aged MH - Neoplasm Staging MH - Remission Induction MH - Taxoids/administration & dosage MH - Treatment Outcome EDAT- 2003/05/10 05:00 MHDA- 2004/01/13 05:00 CRDT- 2003/05/10 05:00 PHST- 2003/05/10 05:00 [pubmed] PHST- 2004/01/13 05:00 [medline] PHST- 2003/05/10 05:00 [entrez] PST - ppublish SO - Clin Cancer Res. 2003 May;9(5):1698-704. PMID- 14505155 OWN - NLM STAT- MEDLINE DCOM- 20060419 LR - 20181113 IS - 0941-4355 (Print) IS - 0941-4355 (Linking) VI - 12 IP - 1 DP - 2004 Jan TI - Evaluation of intrapericardial cisplatin administration in cases with recurrent malignant pericardial effusion and cardiac tamponade. PG - 53-7 AB - GOALS: To evaluate the effectiveness and side effects of intrapericardial administration of cisplatin in prevention of recurrent malignant pericardial effusion. PATIENTS AND METHODS: Forty-six patients (33 men, 13 women; mean age 55.6+/-10.5 years) entered this study. The diagnosis of malignancy was based upon histological examination of samples from primary tumor. The majority of patients suffered from a neoplasm localized in the thorax (41 out of 46 patients; 89%). In 35 cases, pericardiocentesis, and in 11 cases, video-assisted thoracoscopic surgery (VATS) of pericardium was performed. Malignant etiology of pericardial fluid was confirmed by cytological examination, histology being obtained by VATS pericardial biopsy or by echocardiography (ECG). If daily drainage of pericardial fluid observed during 5-7 days exceeded 50 ml, cisplatin was instilled according to one of three regimens: (1) 10 mg of cisplatin dissolved in 20 ml of normal saline administered over 5 min during 5 consecutive days directly into the pericardial space (39 patients); (2) 50 mg of cisplatin dissolved in 100 ml of normal saline administered during 30 min (six patients); and (3) 20 mg of cisplatin dissolved in 40 ml of normal saline administered over 10 min during 5 consecutive days (one patient). Treatment was considered as successful when recurrence of symptoms of large pericardial effusion was not observed in ECG and other interventions directed to the pericardium were not required. Efficacy of investigated treatment was assessed also in the group of patients with survival longer than 30 days. Safety of treatment was assessed in the whole group of patients. RESULTS: Because of advanced malignancy eight out of 46 patients (17.4%) survived less than 30 days. Thirty-eight out of 46 cases (82.6%) survived more than 30 days. Positive effect of intrapericardial treatment with cisplatin was achieved in 43 out of 46 patients (93.5%) in the entire investigated group and in 35 out of 38 patients (92%) who survived more than 30 days. In the subgroup of patients with non-small cell lung cancer (NSCLC) and survival longer than 30 days, high efficacy was documented (29 out of 31 cases; 93.5%). Median survival time in the group of 38 patients who survived more than 30 days was 102.5 days. Atrial fibrillation due to cisplatin administration was observed in seven out of 46 patients (15.2%). Sclerosis of the pericardial space without symptoms of constriction occurred in five out of 46 cases (10.9%). CONCLUSIONS: Cisplatin administered directly into the pericardial space is a very effective and relatively safe method of treatment of recurrent malignant pericardial effusion, especially in the course of NSCLC. FAU - Tomkowski, Witold Zbyszek AU - Tomkowski WZ AD - National Tuberculosis and Lung Diseases Research Institute, Płocka 26, 01-138 Warsaw, Poland. w.tomkowski@igichp.edu.pl FAU - Wiśniewska, Joanna AU - Wiśniewska J FAU - Szturmowicz, Monika AU - Szturmowicz M FAU - Kuca, Paweł AU - Kuca P FAU - Burakowski, Janusz AU - Burakowski J FAU - Kober, Jarosław AU - Kober J FAU - Fijałkowska, Anna AU - Fijałkowska A LA - eng PT - Clinical Trial PT - Journal Article DEP - 20030923 PL - Germany TA - Support Care Cancer JT - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer JID - 9302957 RN - 0 (Antineoplastic Agents) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents/*administration & dosage MH - Carcinoma, Non-Small-Cell Lung/surgery MH - Carcinoma, Small Cell/surgery MH - Cardiac Tamponade/*etiology MH - Cisplatin/*administration & dosage MH - Drainage MH - Female MH - Humans MH - Injections, Intralesional MH - Lung Neoplasms/*surgery MH - Male MH - Middle Aged MH - Pericardial Effusion/*drug therapy/etiology MH - Pericardiocentesis/adverse effects MH - Pericardium MH - Recurrence MH - Survival Analysis MH - Thoracic Surgery, Video-Assisted/adverse effects MH - Treatment Outcome EDAT- 2003/09/25 05:00 MHDA- 2006/04/20 09:00 CRDT- 2003/09/25 05:00 PHST- 2003/05/07 00:00 [received] PHST- 2003/08/19 00:00 [accepted] PHST- 2003/09/25 05:00 [pubmed] PHST- 2006/04/20 09:00 [medline] PHST- 2003/09/25 05:00 [entrez] AID - 10.1007/s00520-003-0533-x [doi] PST - ppublish SO - Support Care Cancer. 2004 Jan;12(1):53-7. doi: 10.1007/s00520-003-0533-x. Epub 2003 Sep 23. PMID- 15191616 OWN - NLM STAT- MEDLINE DCOM- 20041112 LR - 20250608 IS - 1471-2482 (Electronic) IS - 1471-2482 (Linking) VI - 4 DP - 2004 Jun 11 TI - Is amiodarone a safe antiarrhythmic to use in supraventricular tachyarrhythmias after lung cancer surgery? PG - 7 AB - BACKGROUND: Supraventricular arrhythmias after thoracotomy for pulmonary resections are well documented. There has been considerable interest in their incidence, nature, predictability from preoperative assessment and treatment. The purpose of this study is to define prevalence, type, risk factors for post-thoracotomy supraventricular arrhythmias and to assess the efficacy of amiodarone as an antiarrhythmic drug. METHODS: The records of 250 patients undergoing pulmonary resection for lung cancer during last two years were followed up in this prospective study with particular attention to possible risk factors (gender, age, extent and side of resection, diabetes mellitus, hypertension, tobacco smoking, beta-blocker ingestion). Patients underwent biopsy only were excluded. Once onset of supraventricular arrhythmia was monitored or documented in the electrocardiogram, intravenous infusion of amiodarone was started with a loading dose of 5 mg/kg in 30 minutes and a maintenance dose of 15 mg/kg until remission of it. RESULTS: Forty-three episodes (21.6%) of supraventricular arrhythmias were documented with atrial fibrillation being the most common (88.3%). Rhythm disturbances were most likely to develop on the second postoperative day. Pneumonectomy, lobectomy and age >65 years were the statistically significant factors. The overall postoperative mortality was 3.2% and 2.3% for the patients with postoperative supraventricular arrhythmias. In none of the cases did supraventricular arrhythmia cause cardiac failure leading to death. Sinus rhythm was achieved with amiodarone in 37 out of 43 patients (86%). Electrical cardioversion was necessary for 6 patients who were hemodynamically unstable. The most common amiodarone-related complication was bradycardia (13.5%). CONCLUSIONS: Postoperative supraventricular arrhythmias are a common complication in elderly patients undergoing lung resection surgery (especially pneumonectomy or lobectomy). Amiodarone is both safe and effective in establishing sinus rhythm. FAU - Barbetakis, Nikolaos AU - Barbetakis N AD - Cardiothoracic Surgery Department, Theagenio Cancer Hospital, Thessaloniki, Greece. nibarb@otenet.gr FAU - Vassiliadis, Michalis AU - Vassiliadis M LA - eng PT - Clinical Trial PT - Journal Article DEP - 20040611 PL - England TA - BMC Surg JT - BMC surgery JID - 100968567 RN - 0 (Anti-Arrhythmia Agents) RN - N3RQ532IUT (Amiodarone) SB - IM MH - Adult MH - Age Distribution MH - Aged MH - Amiodarone/*therapeutic use MH - Anti-Arrhythmia Agents/*therapeutic use MH - Atrial Fibrillation/drug therapy/epidemiology/etiology MH - Female MH - Humans MH - Incidence MH - Lung Neoplasms/*surgery MH - Male MH - Middle Aged MH - Postoperative Care/*methods MH - Prevalence MH - Prospective Studies MH - Risk Factors MH - Sex Distribution MH - Survival Rate MH - Tachycardia, Supraventricular/*drug therapy/*epidemiology/etiology MH - Thoracotomy/adverse effects/*statistics & numerical data PMC - PMC434512 EDAT- 2004/06/12 05:00 MHDA- 2004/11/13 09:00 PMCR- 2004/06/11 CRDT- 2004/06/12 05:00 PHST- 2004/02/25 00:00 [received] PHST- 2004/06/11 00:00 [accepted] PHST- 2004/06/12 05:00 [pubmed] PHST- 2004/11/13 09:00 [medline] PHST- 2004/06/12 05:00 [entrez] PHST- 2004/06/11 00:00 [pmc-release] AID - 1471-2482-4-7 [pii] AID - 10.1186/1471-2482-4-7 [doi] PST - epublish SO - BMC Surg. 2004 Jun 11;4:7. doi: 10.1186/1471-2482-4-7. PMID- 16224275 OWN - NLM STAT- MEDLINE DCOM- 20060428 LR - 20191109 IS - 1524-9557 (Print) IS - 1524-9557 (Linking) VI - 28 IP - 6 DP - 2005 Nov-Dec TI - A phase 2 study of moderate dose interleukin-2 and granulocyte-macrophage colony-stimulating factor in patients with metastatic or unresectable renal cell carcinoma. PG - 576-81 AB - Interleukin-2 (IL-2) has been shown to produce durable complete remission in patients with renal cell carcinoma (RCC). A phase 2 study was conducted to evaluate the potential therapeutic synergy as well as the toxic side effects of the concurrent administration of IL-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with advanced stage disease. Twenty-one patients with unresectable or metastatic RCC having an Eastern Oncology Cooperative Group performance status of 0 or 1 were enrolled. Six patients had received prior immunotherapy with interferon (IFN)-alpha, IFN-gamma, and IL-12, whereas the remaining 15 subjects were previously untreated. Thirteen patients were assigned to a moderate-dose bolus of IL-2 at 72,000 IU/kg every 8 hours on days 1 through 5 and days 15 through 19, whereas 8 patients were given IL-2 as an intravenous continuous infusion at a dose of 5 MU/m2/d on days 1 through 5 and days 15 through 19. Subcutaneous GM-CSF at 125 microg/d on days 1 through 21 was administered concomitantly with IL-2. The median number of IL-2 bolus doses was 23 of a scheduled 28 (85%), whereas with the continuous infusion, 93% of planned IL-2 was given. All patients received 100% of GM-CSF doses. There were no complete or partial responses in this study. Of 13 patients treated in the bolus IL-2 arm, 10 had systemic progression of disease at 4 to 8 weeks, 1 developed metastasis in the brain at 4 weeks, and 2 had stable disease for 4 and 17 months. Among the 8 subjects treated with continuous infusion IL-2, 3 progressed with brain lesions at 3 to 8 weeks and 5 had stable disease at 6+, 7, 8+, 15+, and 17+ months. The median survival for the whole group was 10 months, with a range of 0.5 to 40+ months. There were no regimen-related deaths, and most of the observed toxicities were grade 1 and 2. Serious toxicities (grade 3 and 4) included anemia, atrial fibrillation, oliguria, abnormal liver function, and neurologic events like agitation or confusion. The combination of recombinant IL-2 and GM-CSF administered in the designed schedule and doses was not effective in patients with metastatic RCC and may even interfere with the therapeutic potential of moderate-dose IL-2 and increase its adverse events. FAU - Koulova, Lydia AU - Koulova L AD - Comprehensive Cancer Center at Our Lady of Mercy Medical Center, Bronx, New York 10466, USA. FAU - Novik, Yelena AU - Novik Y FAU - Caliendo, Geralyn AU - Caliendo G FAU - Wiernik, Peter AU - Wiernik P FAU - Dutcher, Janice AU - Dutcher J LA - eng PT - Clinical Trial, Phase II PT - Journal Article PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Interleukin-2) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Brain Neoplasms/secondary MH - Carcinoma, Renal Cell/*drug therapy/secondary MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage/adverse effects MH - Humans MH - Interleukin-2/administration & dosage/adverse effects MH - Kidney Neoplasms/*drug therapy/pathology MH - Liver Neoplasms/drug therapy/secondary MH - Lung Neoplasms/drug therapy/secondary MH - Male MH - Middle Aged EDAT- 2005/10/15 09:00 MHDA- 2006/04/29 09:00 CRDT- 2005/10/15 09:00 PHST- 2005/10/15 09:00 [pubmed] PHST- 2006/04/29 09:00 [medline] PHST- 2005/10/15 09:00 [entrez] AID - 00002371-200511000-00008 [pii] AID - 10.1097/01.cji.0000177998.57713.c9 [doi] PST - ppublish SO - J Immunother. 2005 Nov-Dec;28(6):576-81. doi: 10.1097/01.cji.0000177998.57713.c9. PMID- 16028099 OWN - NLM STAT- MEDLINE DCOM- 20060213 LR - 20161124 IS - 0344-5704 (Print) IS - 0344-5704 (Linking) VI - 57 IP - 3 DP - 2006 Feb TI - Phase I and pharmacokinetic study of amrubicin, a synthetic 9-aminoanthracycline, in patients with refractory or relapsed lung cancer. PG - 282-8 AB - Amrubicin is a novel synthetic 9-aminoanthracycline derivative and is converted enzymatically to its C-13 hydroxy metabolite, amrubicinol, whose cytotoxic activity is 10-100 times that of amrubicin. We aimed to determine the maximum tolerated dose (MTD) of amrubicin and to characterize the pharmacokinetics of amrubicin and amrubicinol in previously treated patients with refractory or relapsed lung cancer. The 15 patients were treated with amrubicin intravenously at doses of 30, 35, or 40 mg/m(2) on three consecutive days every 3 weeks for a total of 43 courses. Neutropenia was the major toxicity (grade 4, 67%). The MTD was 40 mg/m(2), with the specific dose-limiting toxicities being grade 4 neutropenia persisting for >4 days, febrile neutropenia, or grade 3 arrhythmia in the three patients treated at this dose. A patient with non-small-cell lung cancer showed a partial response, and ten individuals experienced a stable disease. The area under the plasma concentration versus time curve (AUC) for amrubicin and that for amrubicinol increased with amrubicin dose. The amrubicin AUC was significantly correlated with the amrubicinol AUC. The recommended phase II dose of amrubicin for patients with lung cancer refractory to standard chemotherapy is thus 35 mg/m(2) once a day for three consecutive days every 3 weeks. FAU - Okamoto, Isamu AU - Okamoto I AD - Department of Respiratory Medicine, Graduate School of Medical Science, Kumamoto University, Japan. okamoto@dotd.med.kindai.ac.jp FAU - Hamada, Akinobu AU - Hamada A FAU - Matsunaga, Yusuke AU - Matsunaga Y FAU - Sasaki, Ji-ichiro AU - Sasaki J FAU - Fujii, Shinji AU - Fujii S FAU - Uramoto, Hideshi AU - Uramoto H FAU - Yamagata, Haruhiko AU - Yamagata H FAU - Mori, Ichiro AU - Mori I FAU - Kishi, Hiroto AU - Kishi H FAU - Semba, Hiroshi AU - Semba H FAU - Saito, Hideyuki AU - Saito H LA - eng PT - Clinical Trial, Phase I PT - Journal Article DEP - 20050719 PL - Germany TA - Cancer Chemother Pharmacol JT - Cancer chemotherapy and pharmacology JID - 7806519 RN - 0 (Anthracyclines) RN - 0 (Antineoplastic Agents) RN - 0 (Steroids) RN - 0 (amrubicinol) RN - 93N13LB4Z2 (amrubicin) RN - GFO928U8MQ (Disopyramide) SB - IM MH - Aged MH - Anthracyclines/administration & dosage/adverse effects/*pharmacokinetics MH - Antineoplastic Agents/administration & dosage/adverse effects/pharmacokinetics MH - Area Under Curve MH - Atrial Fibrillation/chemically induced/drug therapy MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism MH - Carcinoma, Small Cell/*drug therapy/metabolism MH - Chromatography, High Pressure Liquid/methods MH - Disopyramide/therapeutic use MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Dyspnea/chemically induced/drug therapy MH - Female MH - Half-Life MH - Humans MH - Hypoxia/chemically induced/drug therapy MH - Infusions, Intravenous MH - Leukopenia/chemically induced MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local MH - Neutropenia/chemically induced/therapy MH - Platelet Transfusion MH - Pneumonia/chemically induced/drug therapy MH - Steroids/therapeutic use MH - Thrombocytopenia/chemically induced/therapy EDAT- 2005/07/20 09:00 MHDA- 2006/02/14 09:00 CRDT- 2005/07/20 09:00 PHST- 2005/02/07 00:00 [received] PHST- 2005/05/06 00:00 [accepted] PHST- 2005/07/20 09:00 [pubmed] PHST- 2006/02/14 09:00 [medline] PHST- 2005/07/20 09:00 [entrez] AID - 10.1007/s00280-005-0051-2 [doi] PST - ppublish SO - Cancer Chemother Pharmacol. 2006 Feb;57(3):282-8. doi: 10.1007/s00280-005-0051-2. Epub 2005 Jul 19. PMID- 18317067 OWN - NLM STAT- MEDLINE DCOM- 20080522 LR - 20181201 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 3 IP - 3 DP - 2008 Mar TI - Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB non-small cell lung cancer. PG - 250-7 LID - 10.1097/JTO.0b013e3181653cf4 [doi] AB - INTRODUCTION: Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT). METHODS: Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m(2) weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy. RESULTS: Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44-82), 52% female, 61% stage IIIA, 61% performance status 0, 17% > or =5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7-13 months) and 16 months (95% CI: 10-20 months), respectively. CONCLUSIONS: Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing. FAU - Stinchcombe, Thomas E AU - Stinchcombe TE AD - Multidisciplinary Thoracic Oncology Program, 3009 Old Clinic Building CB 7305, Chapel Hill, NC 27599-7305, USA. Thomas_Stinchcombe@med.unc.edu FAU - Morris, David E AU - Morris DE FAU - Lee, Carrie B AU - Lee CB FAU - Moore, Dominic T AU - Moore DT FAU - Hayes, D Neil AU - Hayes DN FAU - Halle, Jan S AU - Halle JS FAU - Rivera, M Patricia AU - Rivera MP FAU - Rosenman, Julian G AU - Rosenman JG FAU - Socinski, Mark A AU - Socinski MA LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Quinazolines) RN - 0 (Radiation-Sensitizing Agents) RN - 7673326042 (Irinotecan) RN - BG3F62OND5 (Carboplatin) RN - EC 2.7.10.1 (ErbB Receptors) RN - P88XT4IS4D (Paclitaxel) RN - S65743JHBS (Gefitinib) RN - XT3Z54Z28A (Camptothecin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Camptothecin/administration & dosage/analogs & derivatives MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/diagnosis/*drug therapy/*radiotherapy MH - Contraindications MH - ErbB Receptors/antagonists & inhibitors MH - Female MH - Follow-Up Studies MH - Gefitinib MH - Humans MH - Irinotecan MH - Lung Neoplasms/diagnosis/*drug therapy/*radiotherapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Paclitaxel/administration & dosage MH - *Pneumonectomy MH - Quinazolines/administration & dosage MH - Radiation-Sensitizing Agents MH - Radiotherapy, Conformal/*methods MH - Retrospective Studies MH - Time Factors MH - Tomography, X-Ray Computed MH - Treatment Outcome EDAT- 2008/03/05 09:00 MHDA- 2008/05/23 09:00 CRDT- 2008/03/05 09:00 PHST- 2008/03/05 09:00 [pubmed] PHST- 2008/05/23 09:00 [medline] PHST- 2008/03/05 09:00 [entrez] AID - S1556-0864(15)31368-X [pii] AID - 10.1097/JTO.0b013e3181653cf4 [doi] PST - ppublish SO - J Thorac Oncol. 2008 Mar;3(3):250-7. doi: 10.1097/JTO.0b013e3181653cf4. PMID- 19549643 OWN - NLM STAT- MEDLINE DCOM- 20090903 LR - 20180126 IS - 1471-6771 (Electronic) IS - 0007-0912 (Linking) VI - 103 IP - 3 DP - 2009 Sep TI - Influence of patient-controlled i.v. analgesia with opioids on supraventricular arrhythmias after pulmonary resection. PG - 364-8 LID - 10.1093/bja/aep172 [doi] AB - BACKGROUND: Postoperative supraventricular arrhythmias (SVA) are common after pulmonary resection and autonomic imbalance is thought to be one of the triggers. Opioids can increase parasympathetic activity and may balance heightened sympathetic tone after operation. We have examined the effect of postoperative patient-controlled analgesia (PCA) with opioids on postoperative SVA. METHODS: Forty-eight patients were randomly assigned to two groups. The GA group received general anaesthesia PCA and PCA with opioids (fentanyl 6 microg ml(-1) and tramadol 3 mg ml(-1)). The GEA group received combined general/epidural anaesthesia plus patient-controlled epidural analgesia (PCEA). Holter recording was completed for 12 h before operation and 12 and 48 h after operation. The incidence of supraventricular tachycardias (SVT), atrial fibrillation, and supraventricular ectopic beats (SVEBs) was evaluated. RESULTS: The incidence of postoperative SVT was significantly lower in the GA group than in the GEA group (3/22 vs 10/22, P=0.021). The incidence of postoperative SVEBs was not statistically different between the groups, but the frequency of postoperative SVEBs increased less in the GA than the GEA group (7/22 vs 15/22, P=0.016). CONCLUSIONS: PCA with opioids (fentanyl and tramadol) can reduce postoperative SVA after pulmonary resection compared with PCEA with ropivacaine. FAU - Jiang, Z AU - Jiang Z AD - Department of Anesthesiology, Liuhuaqiao Hospital, Guangzhou, People's Republic of China. FAU - Dai, J Q AU - Dai JQ FAU - Shi, C AU - Shi C FAU - Zeng, W S AU - Zeng WS FAU - Jiang, R C AU - Jiang RC FAU - Tu, W F AU - Tu WF LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20090623 PL - England TA - Br J Anaesth JT - British journal of anaesthesia JID - 0372541 RN - 0 (Analgesics, Opioid) RN - 0 (Drug Combinations) RN - 39J1LGJ30J (Tramadol) RN - UF599785JZ (Fentanyl) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Analgesia, Epidural MH - Analgesia, Patient-Controlled/*methods MH - Analgesics, Opioid/administration & dosage/*therapeutic use MH - Atrial Fibrillation/etiology/prevention & control MH - Atrial Premature Complexes/etiology/prevention & control MH - Drug Combinations MH - Electrocardiography, Ambulatory/methods MH - Female MH - Fentanyl/administration & dosage/therapeutic use MH - Humans MH - Infusions, Intravenous MH - Lung Neoplasms/surgery MH - Male MH - Middle Aged MH - Pain Measurement/methods MH - Pneumonectomy/adverse effects MH - Tachycardia, Supraventricular/etiology/*prevention & control MH - Tramadol/administration & dosage/therapeutic use EDAT- 2009/06/25 09:00 MHDA- 2009/09/04 06:00 CRDT- 2009/06/25 09:00 PHST- 2009/06/25 09:00 [entrez] PHST- 2009/06/25 09:00 [pubmed] PHST- 2009/09/04 06:00 [medline] AID - S0007-0912(17)33972-7 [pii] AID - 10.1093/bja/aep172 [doi] PST - ppublish SO - Br J Anaesth. 2009 Sep;103(3):364-8. doi: 10.1093/bja/aep172. Epub 2009 Jun 23. PMID- 19699916 OWN - NLM STAT- MEDLINE DCOM- 20090914 LR - 20131121 IS - 1552-6259 (Electronic) IS - 0003-4975 (Linking) VI - 88 IP - 3 DP - 2009 Sep TI - A randomized trial evaluating amiodarone for prevention of atrial fibrillation after pulmonary resection. PG - 886-93; discussion 894-5 LID - 10.1016/j.athoracsur.2009.04.074 [doi] AB - BACKGROUND: Atrial fibrillation (AF) occurs commonly after anatomic pulmonary resection. In this study, the efficacy of amiodarone for prevention of post-pulmonary resection AF was investigated. METHODS: One hundred thirty patients undergoing lobectomy, bilobectomy, or pneumonectomy were randomly assigned prospectively to receive amiodarone (n = 65) or no prophylaxis (control group, n = 65). The amiodarone group received 1,050 mg by continuous intravenous infusion over 24 hours, initiated at the time of anesthesia induction, followed by 400 mg orally twice daily until hospital discharge or for a maximum of 6 days. The primary endpoint was AF requiring treatment during hospitalization. Secondary endpoints included postoperative length of hospital and intensive care unit stays. RESULTS: There were no significant differences between the amiodarone and control groups in demographics, comorbid conditions, extent of pulmonary resection, or preoperative or postoperative use of beta-blockers or calcium-channel blockers. The incidence of AF was lower in the amiodarone group than in the control group (13.8% versus 32.3%, p = 0.02; relative risk reduction = 57%). There was no difference between the amiodarone and control groups in median length of hospital stay (7 versus 8 days, p = 0.79), but median length of intensive care unit stay was shorter in the amiodarone group (46 versus 84 hours, p = 0.03). There was no significant difference between the amiodarone and control groups in the incidence of pulmonary complications or other adverse effects. CONCLUSIONS: Amiodarone prophylaxis significantly reduces the incidence of AF after anatomic pulmonary resection, and is associated with a significant reduction in length of intensive care unit stay. FAU - Tisdale, James E AU - Tisdale JE AD - Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Purdue University, Indianapolis, Indiana 46202, USA. jtisdale@iupui.edu FAU - Wroblewski, Heather A AU - Wroblewski HA FAU - Wall, Donna S AU - Wall DS FAU - Rieger, Karen M AU - Rieger KM FAU - Hammoud, Zane T AU - Hammoud ZT FAU - Young, Jerry V AU - Young JV FAU - Kesler, Kenneth A AU - Kesler KA LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Ann Thorac Surg JT - The Annals of thoracic surgery JID - 15030100R RN - 0 (Anti-Arrhythmia Agents) RN - N3RQ532IUT (Amiodarone) SB - IM MH - Administration, Oral MH - Aged MH - Amiodarone/*administration & dosage/adverse effects MH - Anti-Arrhythmia Agents/*administration & dosage/adverse effects MH - Atrial Fibrillation/*prevention & control MH - Carcinoma, Non-Small-Cell Lung/*surgery MH - Electrocardiography/drug effects MH - Female MH - Humans MH - Infusions, Intravenous MH - Intensive Care Units MH - Length of Stay MH - Lung Diseases/*surgery MH - Lung Neoplasms/*secondary/*surgery MH - Male MH - Middle Aged MH - *Pneumonectomy MH - Postoperative Complications/*prevention & control MH - Premedication MH - Prospective Studies EDAT- 2009/08/25 09:00 MHDA- 2009/09/15 06:00 CRDT- 2009/08/25 09:00 PHST- 2009/01/28 00:00 [received] PHST- 2009/04/17 00:00 [revised] PHST- 2009/04/21 00:00 [accepted] PHST- 2009/08/25 09:00 [entrez] PHST- 2009/08/25 09:00 [pubmed] PHST- 2009/09/15 06:00 [medline] AID - S0003-4975(09)00809-1 [pii] AID - 10.1016/j.athoracsur.2009.04.074 [doi] PST - ppublish SO - Ann Thorac Surg. 2009 Sep;88(3):886-93; discussion 894-5. doi: 10.1016/j.athoracsur.2009.04.074. PMID- 21992849 OWN - NLM STAT- MEDLINE DCOM- 20120228 LR - 20151119 IS - 1097-685X (Electronic) IS - 0022-5223 (Linking) VI - 143 IP - 2 DP - 2012 Feb TI - Effect of low-dose human atrial natriuretic peptide on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer: a double-blind, placebo-controlled study. PG - 488-94 LID - 10.1016/j.jtcvs.2011.09.003 [doi] AB - OBJECTIVES: We previously reported that patients with preoperative B-type natriuretic peptide levels of 30 pg/mL or more have increased risk of postoperative atrial fibrillation after pulmonary resection. This study evaluated the effects of human atrial natriuretic peptide on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer. METHODS: A prospective, randomized study was conducted with 40 patients who had preoperative elevated B-type natriuretic peptide (≥ 30 pg/mL) and underwent a scheduled pulmonary resection for lung cancer. Results were compared between patients who received low-dose human atrial natriuretic peptide and those who received a placebo. The primary end point was the incidence of postoperative atrial fibrillation during the first 4 days after surgery. RESULTS: The incidence of postoperative atrial fibrillation was significantly lower in the human atrial natriuretic peptide group than in the placebo group (10% vs 60%; P < .001). Patients in the human atrial natriuretic peptide group also showed significantly lower white blood cell counts and C-reactive protein levels after surgery. CONCLUSIONS: Continuous infusion of low-dose human atrial natriuretic peptide during lung cancer surgery had a prophylactic effect against postoperative atrial fibrillation after pulmonary resection in patients with preoperative elevation of B-type natriuretic peptide levels. A larger sample size is needed to establish the safety and efficacy of this intervention. CI - Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved. FAU - Nojiri, Takashi AU - Nojiri T AD - Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Toyonaka-City, Osaka, Japan. nojirit@thoracic.med.osaka-u.ac.jp FAU - Yamamoto, Kazuhiro AU - Yamamoto K FAU - Maeda, Hajime AU - Maeda H FAU - Takeuchi, Yukiyasu AU - Takeuchi Y FAU - Funakoshi, Yasunobu AU - Funakoshi Y FAU - Inoue, Masayoshi AU - Inoue M FAU - Okumura, Meinoshin AU - Okumura M LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20111010 PL - United States TA - J Thorac Cardiovasc Surg JT - The Journal of thoracic and cardiovascular surgery JID - 0376343 RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Biomarkers) RN - 0 (Placebos) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 85637-73-6 (Atrial Natriuretic Factor) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Aged MH - Aged, 80 and over MH - Analysis of Variance MH - Anti-Arrhythmia Agents/*administration & dosage/adverse effects MH - Atrial Fibrillation/blood/etiology/physiopathology/*prevention & control MH - Atrial Natriuretic Factor/*administration & dosage/adverse effects MH - Biomarkers/blood MH - C-Reactive Protein/metabolism MH - Chi-Square Distribution MH - Double-Blind Method MH - Female MH - Hemodynamics/drug effects MH - Humans MH - Infusions, Parenteral MH - Japan MH - Leukocyte Count MH - Lung Neoplasms/blood/*surgery MH - Male MH - Middle Aged MH - Natriuretic Peptide, Brain/blood MH - Placebos MH - Pneumonectomy/*adverse effects MH - Time Factors MH - Treatment Outcome MH - Up-Regulation EDAT- 2011/10/14 06:00 MHDA- 2012/03/01 06:00 CRDT- 2011/10/14 06:00 PHST- 2010/07/29 00:00 [received] PHST- 2011/04/26 00:00 [revised] PHST- 2011/09/14 00:00 [accepted] PHST- 2011/10/14 06:00 [entrez] PHST- 2011/10/14 06:00 [pubmed] PHST- 2012/03/01 06:00 [medline] AID - S0022-5223(11)00971-8 [pii] AID - 10.1016/j.jtcvs.2011.09.003 [doi] PST - ppublish SO - J Thorac Cardiovasc Surg. 2012 Feb;143(2):488-94. doi: 10.1016/j.jtcvs.2011.09.003. Epub 2011 Oct 10. PMID- 22516832 OWN - NLM STAT- MEDLINE DCOM- 20121001 LR - 20220409 IS - 1552-6259 (Electronic) IS - 0003-4975 (Linking) VI - 94 IP - 2 DP - 2012 Aug TI - Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer. PG - 339-44; discussion 345-6 LID - 10.1016/j.athoracsur.2011.12.096 [doi] AB - BACKGROUND: Postoperative atrial fibrillation occurs in 5% to 65% of patients undergoing thoracic surgery. Although postoperative atrial fibrillation often is regarded as a temporary, benign, operation-related problem, it is associated with a twofold to threefold increase in risk of adverse events, including transient or permanent stroke, acute myocardial infarction, and death. METHODS: A total of 254 consecutively eligible enrolled patients undergoing surgery for lung cancer were included in this randomized, controlled, double-blinded trial. Patients received 300 mg of amiodarone or placebo intravenously over 20 minutes immediately after surgery and an oral dose of 600 mg of amiodarone or placebo twice daily during the first 5 postoperative days. RESULTS: The patients in the amiodarone prophylaxis group had a reduction in the risk of atrial fibrillation of 23% (12 to 31); number needed to treat was 4.4 (3.1 to 7.8). A total of 38 in the control group and 11 in the amiodarone group experienced atrial fibrillation (p<0.001). Adverse effects were observed in 10 patients equally distributed in both trial arms. CONCLUSIONS: Postoperative prophylaxis with a high dose of oral amiodarone after an intravenous bolus infusion is a safe, practical, feasible, and effective regimen for patients with lung cancer undergoing surgery. It significantly reduced the incidence of postoperative atrial fibrillation. CI - Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. FAU - Riber, Lars P AU - Riber LP AD - Department of Cardiothoracic and Vascular Surgery and Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark. larspeterriber@gmail.com FAU - Christensen, Thomas D AU - Christensen TD FAU - Jensen, Henrik K AU - Jensen HK FAU - Hoejsgaard, Anette AU - Hoejsgaard A FAU - Pilegaard, Hans K AU - Pilegaard HK LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20120418 PL - Netherlands TA - Ann Thorac Surg JT - The Annals of thoracic surgery JID - 15030100R RN - N3RQ532IUT (Amiodarone) SB - IM MH - Aged MH - Aged, 80 and over MH - Amiodarone/*therapeutic use MH - Atrial Fibrillation/*prevention & control MH - Double-Blind Method MH - Female MH - Humans MH - Lung Neoplasms/*surgery MH - Male MH - Middle Aged MH - Postoperative Complications/*prevention & control MH - Prospective Studies EDAT- 2012/04/21 06:00 MHDA- 2012/10/02 06:00 CRDT- 2012/04/21 06:00 PHST- 2011/10/23 00:00 [received] PHST- 2011/12/12 00:00 [revised] PHST- 2011/12/14 00:00 [accepted] PHST- 2012/04/21 06:00 [entrez] PHST- 2012/04/21 06:00 [pubmed] PHST- 2012/10/02 06:00 [medline] AID - S0003-4975(12)00425-0 [pii] AID - 10.1016/j.athoracsur.2011.12.096 [doi] PST - ppublish SO - Ann Thorac Surg. 2012 Aug;94(2):339-44; discussion 345-6. doi: 10.1016/j.athoracsur.2011.12.096. Epub 2012 Apr 18. PMID- 23438357 OWN - NLM STAT- MEDLINE DCOM- 20130919 LR - 20130312 IS - 1651-226X (Electronic) IS - 0284-186X (Linking) VI - 52 IP - 3 DP - 2013 Apr TI - Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer. PG - 506-13 LID - 10.3109/0284186X.2013.769063 [doi] AB - BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). MATERIAL AND METHODS: Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. RESULTS: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. CONCLUSION: In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT. FAU - Colaco, Rovel J AU - Colaco RJ AD - University of Florida Proton Therapy Institute, Jacksonville, Florida 32206, USA. FAU - Huh, Soon AU - Huh S FAU - Nichols, Romaine C AU - Nichols RC FAU - Morris, Christopher G AU - Morris CG FAU - D'Agostino, Harry AU - D'Agostino H FAU - Flampouri, Stella AU - Flampouri S FAU - Li, Zuofeng AU - Li Z FAU - Pham, Dat C AU - Pham DC FAU - Bajwa, Abubakr A AU - Bajwa AA FAU - Hoppe, Bradford S AU - Hoppe BS LA - eng PT - Clinical Trial PT - Journal Article DEP - 20130226 PL - Sweden TA - Acta Oncol JT - Acta oncologica (Stockholm, Sweden) JID - 8709065 SB - IM MH - Aged MH - Chemoradiotherapy/adverse effects/*methods MH - Florida MH - Follow-Up Studies MH - Hospitals, University MH - Humans MH - Lung Neoplasms/epidemiology/pathology/*therapy MH - Middle Aged MH - Neoplasm Staging MH - Proton Therapy/adverse effects/*methods MH - Radiation Injuries/epidemiology/etiology MH - *Radiotherapy Dosage MH - Retrospective Studies MH - Small Cell Lung Carcinoma/epidemiology/pathology/*therapy MH - Time Factors EDAT- 2013/02/27 06:00 MHDA- 2013/09/21 06:00 CRDT- 2013/02/27 06:00 PHST- 2013/02/27 06:00 [entrez] PHST- 2013/02/27 06:00 [pubmed] PHST- 2013/09/21 06:00 [medline] AID - 10.3109/0284186X.2013.769063 [doi] PST - ppublish SO - Acta Oncol. 2013 Apr;52(3):506-13. doi: 10.3109/0284186X.2013.769063. Epub 2013 Feb 26. PMID- 23757357 OWN - NLM STAT- MEDLINE DCOM- 20140128 LR - 20250529 IS - 1557-3265 (Electronic) IS - 1078-0432 (Linking) VI - 19 IP - 13 DP - 2013 Jul 1 TI - First-in-human phase I dose-escalation study of the HSP90 inhibitor AUY922 in patients with advanced solid tumors. PG - 3671-80 LID - 10.1158/1078-0432.CCR-12-3404 [doi] AB - PURPOSE: A phase I study was conducted with the primary objective of determining the maximum tolerated dose (MTD) of AUY922 in patients with advanced solid tumors. Secondary objectives included characterization of the safety, pharmacokinetic, and pharmacodynamic profiles. PATIENTS AND METHODS: Patients with advanced solid tumors received 1-hour i.v. infusions of AUY922 once a week in a 28-day cycle. An adaptive Bayesian logistic regression model that employed observed dose-limiting toxicities (DLT) in the first treatment cycle was used to guide dose-escalation decisions, with the established MTD to be used in phase II studies. RESULTS: One hundred and one patients were enrolled and explored at doses in the range of 2 to 70 mg/m(2). DLTs occurred in 8 patients (22-70 mg/m(2)) and included diarrhea, asthenia/fatigue, anorexia, atrial flutter, and visual symptoms. At 70 mg/m(2), the AUY922 concentration achieved was consistent with active concentrations in a range of xenograft models. There was evidence of target inhibition in peripheral blood mononuclear cells (HSP70 induction) and tumor (client protein depletion and reduction of metabolic activity by (18)F-FDG PET). The recommended phase II dose (RP2D) of 70 mg/m(2) was proposed on the basis of toxicity and pharmacokinetic and pharmacodynamic profiles. CONCLUSIONS: At the RP2D of 70 mg/m(2), AUY922 exhibited acceptable tolerability, and phase II single-agent and combination studies have been initiated in patients with HER2-positive breast, gastric, and non-small cell lung cancers. CI - ©2013 AACR. FAU - Sessa, Cristiana AU - Sessa C AD - Instituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland. FAU - Shapiro, Geoffrey I AU - Shapiro GI FAU - Bhalla, Kapil N AU - Bhalla KN FAU - Britten, Carolyn AU - Britten C FAU - Jacks, Karen S AU - Jacks KS FAU - Mita, Monica AU - Mita M FAU - Papadimitrakopoulou, Vali AU - Papadimitrakopoulou V FAU - Pluard, Tim AU - Pluard T FAU - Samuel, Thomas A AU - Samuel TA FAU - Akimov, Mikhail AU - Akimov M FAU - Quadt, Cornelia AU - Quadt C FAU - Fernandez-Ibarra, Cristina AU - Fernandez-Ibarra C FAU - Lu, Hong AU - Lu H FAU - Bailey, Stuart AU - Bailey S FAU - Chica, Sandra AU - Chica S FAU - Banerji, Udai AU - Banerji U LA - eng GR - 11566/CRUK_/Cancer Research UK/United Kingdom PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130611 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide) RN - 0 (Antineoplastic Agents) RN - 0 (HSP90 Heat-Shock Proteins) RN - 0 (Isoxazoles) RN - 0 (Resorcinols) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents/adverse effects/pharmacokinetics/*therapeutic use MH - Female MH - HSP90 Heat-Shock Proteins/antagonists & inhibitors MH - Humans MH - Isoxazoles/adverse effects/pharmacokinetics/*therapeutic use MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Neoplasms/*drug therapy/*pathology MH - Resorcinols/adverse effects/pharmacokinetics/*therapeutic use MH - Treatment Outcome EDAT- 2013/06/13 06:00 MHDA- 2014/01/29 06:00 CRDT- 2013/06/13 06:00 PHST- 2013/06/13 06:00 [entrez] PHST- 2013/06/13 06:00 [pubmed] PHST- 2014/01/29 06:00 [medline] AID - 1078-0432.CCR-12-3404 [pii] AID - 10.1158/1078-0432.CCR-12-3404 [doi] PST - ppublish SO - Clin Cancer Res. 2013 Jul 1;19(13):3671-80. doi: 10.1158/1078-0432.CCR-12-3404. Epub 2013 Jun 11. PMID- 23644703 OWN - NLM STAT- MEDLINE DCOM- 20140922 LR - 20150225 IS - 1873-734X (Electronic) IS - 1010-7940 (Linking) VI - 45 IP - 1 DP - 2014 Jan TI - Amiodarone is a cost-neutral way of preventing atrial fibrillation after surgery for lung cancer. PG - 120-5 LID - 10.1093/ejcts/ezt169 [doi] AB - OBJECTIVES: Our aim was to estimate the costs and health benefits of routinely administered postoperative amiodarone as a prophylactic agent in reducing the risk of atrial fibrillation in patients undergoing surgery for lung cancer. METHODS: This was a cost-effectiveness study, based on the randomized, controlled, double-blinded PASCART study, using avoidance of atrial fibrillation as the measure of benefit. Two hundred and fifty-four eligible, consecutively enrolled patients, undergoing surgery for lung cancer at the department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Denmark, were included and randomized to receive either 300 mg of amiodarone or placebo (5% aqueous dextrose solution), administered intravenously over 20 min immediately after surgery, followed by 600 mg of amiodarone/placebo orally twice per day (8 a.m. and 6 p.m.) for the first five postoperative days. RESULTS: In the amiodarone group there were 11 cases of atrial fibrillation, compared with 38 in the control group (P < 0.001). There were no differences in the length of hospital stay or resources used. The mean total costs per patient were equal and amounted to €7288 per patient (P = 0.23). There were no signs of adverse developments referable to amiodarone in this prophylactic regime. CONCLUSIONS: For patients undergoing surgery for lung cancer, routine use of postoperative prophylactic intravenous bolus and five subsequent days of oral amiodarone therapy reduces the risk of atrial fibrillation in a cost-neutral manner. FAU - Riber, Lars P AU - Riber LP AD - Department of Cardiothoracic and Vascular Surgery & Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Christensen, Thomas D AU - Christensen TD FAU - Pilegaard, Hans K AU - Pilegaard HK LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20130503 PL - Germany TA - Eur J Cardiothorac Surg JT - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery JID - 8804069 RN - 0 (Anti-Arrhythmia Agents) RN - N3RQ532IUT (Amiodarone) SB - IM CIN - Eur J Cardiothorac Surg. 2015 Feb;47(2):393. doi: 10.1093/ejcts/ezu172. PMID: 24787475 CIN - Eur J Cardiothorac Surg. 2015 Feb;47(2):392. doi: 10.1093/ejcts/ezu189. PMID: 24787477 MH - Adult MH - Aged MH - Aged, 80 and over MH - Amiodarone/administration & dosage/economics/*therapeutic use MH - Anti-Arrhythmia Agents/administration & dosage/economics/*therapeutic use MH - Atrial Fibrillation/*drug therapy/*prevention & control MH - Denmark MH - Female MH - Humans MH - Length of Stay MH - Lung Neoplasms/*surgery MH - Male MH - Middle Aged MH - Pneumonectomy/adverse effects MH - Postoperative Complications/drug therapy/prevention & control MH - Prospective Studies OTO - NOTNLM OT - Atrial fibrillation OT - Pharmacology (cardiovascular) OT - Postoperative care OT - Statistics (clinical trial) OT - Surgery for lung cancer EDAT- 2013/05/07 06:00 MHDA- 2014/09/23 06:00 CRDT- 2013/05/07 06:00 PHST- 2013/05/07 06:00 [entrez] PHST- 2013/05/07 06:00 [pubmed] PHST- 2014/09/23 06:00 [medline] AID - ezt169 [pii] AID - 10.1093/ejcts/ezt169 [doi] PST - ppublish SO - Eur J Cardiothorac Surg. 2014 Jan;45(1):120-5. doi: 10.1093/ejcts/ezt169. Epub 2013 May 3. PMID- 24636159 OWN - NLM STAT- MEDLINE DCOM- 20150212 LR - 20211021 IS - 1444-2892 (Electronic) IS - 1443-9506 (Print) IS - 1443-9506 (Linking) VI - 23 IP - 7 DP - 2014 Jul TI - Association between serum angiotensin-converting enzyme 2 level with postoperative morbidity and mortality after major pulmonary resection in non-small cell lung cancer patients. PG - 661-6 LID - S1443-9506(14)00035-3 [pii] LID - 10.1016/j.hlc.2013.12.013 [doi] AB - BACKGROUND: To explore the association between serum angiotensin-converting enzyme 2 (ACE2) levels and postoperative morbidity and mortality after major pulmonary resection in non-small cell lung cancer (NSCLC) patients. METHODS: Preoperative and postoperative serum ACE2 levels in 320 NSCLC patients who underwent major pulmonary resection were measured. The serum ACE2 levels on postoperative day 1 were divided into quartile categories. RESULTS: After adjustment for age, sex, body mass index, current smoking status, forced expiratory volume in 1 second, coronary heart disease, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and tumour clinical stages, the risk of developing postoperative morbidities was significantly higher in the lowest serum ACE2 level quartile than in the highest quartile (hazard ratio, 2.12; 95% CI, 1.57-6.23; p=0.008). NSCLC patients with a serum ACE2 level ≤3.21 ng/mL had significantly higher rates of pneumonia, pleural effusion, atrial fibrillation as well as higher in-hospital mortality after major pulmonary resection, compared with those with a serum ACE2 level >3.21 ng/mL. CONCLUSIONS: The serum ACE2 level one day post surgery is an independent risk factor for postoperative morbidities after major pulmonary resection in NSCLC patients. Thus, it could be used as a prognostic factor for postoperative morbidities after major pulmonary resection in NSCLC patients. CI - Copyright © 2014. Published by Elsevier B.V. FAU - Li, Xiaobing AU - Li X AD - Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China 410011. FAU - Zhou, Changwei AU - Zhou C AD - Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China 410011. FAU - Hu, Wen AU - Hu W AD - Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China 410011. Electronic address: huwenppk@163.com. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140124 PL - Australia TA - Heart Lung Circ JT - Heart, lung & circulation JID - 100963739 RN - 0 (Biomarkers, Tumor) RN - EC 3.4.15.1 (Peptidyl-Dipeptidase A) RN - EC 3.4.17.23 (ACE2 protein, human) RN - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) SB - IM MH - Aged MH - Aged, 80 and over MH - Angiotensin-Converting Enzyme 2 MH - Biomarkers, Tumor/*blood MH - *Carcinoma, Non-Small-Cell Lung/blood/mortality/surgery MH - Disease-Free Survival MH - Female MH - Humans MH - *Lung Neoplasms/blood/mortality/surgery MH - Male MH - Middle Aged MH - Peptidyl-Dipeptidase A/*blood MH - Postoperative Period MH - Retrospective Studies MH - Risk Factors MH - Survival Rate PMC - PMC7106509 OTO - NOTNLM OT - Angiotensin-converting enzyme 2 OT - Morbidity OT - Mortality OT - Non-small cell lung cancer OT - Pulmonary resection EDAT- 2014/03/19 06:00 MHDA- 2015/02/13 06:00 PMCR- 2014/01/24 CRDT- 2014/03/19 06:00 PHST- 2013/07/27 00:00 [received] PHST- 2013/10/26 00:00 [revised] PHST- 2013/12/24 00:00 [accepted] PHST- 2014/03/19 06:00 [entrez] PHST- 2014/03/19 06:00 [pubmed] PHST- 2015/02/13 06:00 [medline] PHST- 2014/01/24 00:00 [pmc-release] AID - S1443-9506(14)00035-3 [pii] AID - 10.1016/j.hlc.2013.12.013 [doi] PST - ppublish SO - Heart Lung Circ. 2014 Jul;23(7):661-6. doi: 10.1016/j.hlc.2013.12.013. Epub 2014 Jan 24. PMID- 25086910 OWN - NLM STAT- MEDLINE DCOM- 20150804 LR - 20141208 IS - 1444-2892 (Electronic) IS - 1443-9506 (Linking) VI - 24 IP - 1 DP - 2015 Jan TI - Morbidity and mortality after major pulmonary resections in patients with locally advanced stage IIIA non-small cell lung carcinoma who underwent induction therapy. PG - 69-76 LID - S1443-9506(14)00607-6 [pii] LID - 10.1016/j.hlc.2014.07.055 [doi] AB - BACKGROUND: The optimal treatment for patients with locally advanced stage IIIA non-small cell lung carcinoma (NSCLC) remains controversial, but induction therapy is increasingly used. The aim of this study was to evaluate mortality, morbidity, hospital stay and frequency of postoperative complications in stage IIIA NSCLC patients that underwent major pulmonary resections after neoadjuvant chemotherapy or chemoradiation. METHODS: We conducted a retrospective analysis of all patients who underwent major pulmonary resections after induction therapy for locally advanced NSCLC from October 2009 to February 2014. Forty-one patients were included in the study. RESULTS: Complete resection was achieved in 40 patients (97.5%). A complete pathologic response was seen in 10 patients (24.4%). Mean hospital stay was 17.7 days (ranged 5-129 days). Early (in-hospital) mortality occurred in 2.4% (one patient after bilobectomy), late (six months) mortality in 4.9% (two patients after right pneumonectomy and bilobectomy), and overall morbidity in 58.5% (24 patients). Postoperative complications included: bronchopleural fistula (BPF) with empyema - three patients, empyema without BPF - five patients, air leak - eight patients, atrial fibrillation - eight patients, pneumonia - eight patients, and lobar atelectasis - four patients. CONCLUSION: Following neoadjuvant therapy for stage IIIA NSCLC, pneumonectomy can be performed with low early and late mortality (0% and 5.8%, respectively), bilobectomy is a high risk operation (16.7% early and 16.7% late mortality); and lobectomy a low risk operation (0% early and late mortality). The need for major pulmonary resections should not be a reason to exclude patients from a potentially curative procedure if it can be performed with acceptable morbidity and mortality rates at an experienced medical centre. CI - Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved. FAU - Peer, Michael AU - Peer M AD - Department of Thoracic Surgery, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel. Electronic address: michaelp@asaf.health.gov.il. FAU - Stav, David AU - Stav D AD - Department of Pulmonology, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel. FAU - Cyjon, Arnold AU - Cyjon A AD - Department of Oncology, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel. FAU - Sandbank, Judith AU - Sandbank J AD - Department of Pathology, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel. FAU - Vasserman, Margarita AU - Vasserman M AD - Institute of Diagnostic Imaging, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel. FAU - Haitov, Zoya AU - Haitov Z AD - Department of Anesthesiology, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel. FAU - Sasson, Lior AU - Sasson L AD - Department of Cardiothoracic Surgery, Edith Wolfson Medical Center, Holon, Israel, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Schreiber, Letizia AU - Schreiber L AD - Department of Pathology, Edith Wolfson Medical Center, Holon, Israel, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Ezri, Tiberiu AU - Ezri T AD - Department of Anesthesiology, Edith Wolfson Medical Center, Holon, Israel, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Priel, Israel E AU - Priel IE AD - Department of Pulmonary Medicine, Edith Wolfson Medical Center, Holon, Israel, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Hayat, Henri AU - Hayat H AD - Department of Oncology, Edith Wolfson Medical Center, Holon, Israel, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20140714 PL - Australia TA - Heart Lung Circ JT - Heart, lung & circulation JID - 100963739 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - *Carcinoma, Non-Small-Cell Lung/mortality/pathology/therapy MH - Chemoradiotherapy, Adjuvant MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - Hospital Mortality MH - Humans MH - *Induction Chemotherapy MH - Length of Stay MH - *Lung Neoplasms/mortality/pathology/therapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - *Pulmonary Surgical Procedures MH - Survival Rate OTO - NOTNLM OT - Chemoradiation OT - Chemotherapy OT - Lobectomy OT - Lung cancer surgery OT - Pneumonectomy OT - Thoracotomy EDAT- 2014/08/05 06:00 MHDA- 2015/08/05 06:00 CRDT- 2014/08/04 06:00 PHST- 2014/05/20 00:00 [received] PHST- 2014/06/25 00:00 [revised] PHST- 2014/07/02 00:00 [accepted] PHST- 2014/08/04 06:00 [entrez] PHST- 2014/08/05 06:00 [pubmed] PHST- 2015/08/05 06:00 [medline] AID - S1443-9506(14)00607-6 [pii] AID - 10.1016/j.hlc.2014.07.055 [doi] PST - ppublish SO - Heart Lung Circ. 2015 Jan;24(1):69-76. doi: 10.1016/j.hlc.2014.07.055. Epub 2014 Jul 14. PMID- 25312529 OWN - NLM STAT- MEDLINE DCOM- 20151204 LR - 20150219 IS - 1873-734X (Electronic) IS - 1010-7940 (Linking) VI - 47 IP - 1 DP - 2015 Jan TI - A pilot prospective randomized, controlled trial comparing LigaSure™ tissue fusion technology with the ForceTriad™ energy platform to the electrosurgical pencil on rates of atrial fibrillation after pulmonary lobectomy and mediastinal lymphadenectomy. PG - e13-8 LID - 10.1093/ejcts/ezu391 [doi] AB - OBJECTIVES: The use of bipolar sealing devices during pulmonary resection is particularly useful in thoracoscopic surgery. Theoretically, a bipolar device, which contains the current in a smaller area and completes the current cycle only through the tissue between the electrodes, may reduce the proportion of patients experiencing atrial fibrillation compared with monopolar devices such as the electrosurgical pencil using which the current completes the cycle through the patient. We investigated the impact of the LigaSure™ (LS) tissue fusion technology with the ForceTriad™ energy platform device on the incidence of postoperative atrial fibrillation and on the reduction of postoperative chest tube output and hospital length of stay after open pulmonary lobectomy. METHODS: A pilot prospective randomized, controlled trial comparing LS tissue fusion technology with the ForceTriad™ energy platform to the conventional electrosurgical pencil. Overall, 146 patients with resectable lung cancer were recruited at the Division of Thoracic Surgery of the Istituto Nazionale Tumori, Fondazione Pascale, IRCCS, between January 2011 and July 2013. Of these, 119 candidates to open lobectomy for non-small-cell lung cancer were randomized to either LS tissue fusion technology with the ForceTriad™ energy platform (LS: 57 patients) or standard haemostatic procedure (standard treatment, ST: 62 patients) for hilar and mediastinal nodal dissection. The primary end-point was to compare the incidence of postoperative atrial fibrillation of LS compared with ST. The secondary end-point was to compare the efficacy of LS compared with ST in terms of total chest tube drainage, daily chest tube drainage and chest tube duration. RESULTS: There was no statistically significant difference between LS and ST in terms of postoperative atrial fibrillation (P=0.31). However, LS was associated to significant reduction of duration of both mediastinal nodal dissection (P=0.017) and the cumulative chest tube drainage (P=0.025). CONCLUSIONS: The incidence of atrial fibrillation with LS tissue fusion technology with the ForceTriad™ energy platform is not reduced as compared with conventional electrosurgical pencil. However, the use of LS during mediastinal nodal dissection is associated to shorter duration of lymphadenectomy and duration of chest tube drainage. CI - © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. FAU - Martucci, Nicola AU - Martucci N AD - Division of Thoracic Surgery, Department of Thoracic Surgery and Oncology, Istituto Nazionale Tumori, Fondazione "G. Pascale" IRCCS, Naples, Italy. FAU - Tracey, Maura AU - Tracey M AD - Division of Thoracic Surgery, Department of Thoracic Surgery and Oncology, Istituto Nazionale Tumori, Fondazione "G. Pascale" IRCCS, Naples, Italy. FAU - La Rocca, Antonello AU - La Rocca A AD - Division of Thoracic Surgery, Department of Thoracic Surgery and Oncology, Istituto Nazionale Tumori, Fondazione "G. Pascale" IRCCS, Naples, Italy. FAU - La Manna, Carmine AU - La Manna C AD - Division of Thoracic Surgery, Department of Thoracic Surgery and Oncology, Istituto Nazionale Tumori, Fondazione "G. Pascale" IRCCS, Naples, Italy. FAU - De Luca, Giuseppe AU - De Luca G AD - Division of Thoracic Surgery, Department of Thoracic Surgery and Oncology, Istituto Nazionale Tumori, Fondazione "G. Pascale" IRCCS, Naples, Italy. FAU - Rocco, Gaetano AU - Rocco G AD - Division of Thoracic Surgery, Department of Thoracic Surgery and Oncology, Istituto Nazionale Tumori, Fondazione "G. Pascale" IRCCS, Naples, Italy g.rocco@istitutotumori.na.it. LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20141013 PL - Germany TA - Eur J Cardiothorac Surg JT - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery JID - 8804069 SB - IM MH - Aged MH - Atrial Fibrillation/*etiology MH - Electrocoagulation/adverse effects/*instrumentation/methods MH - Electrosurgery/adverse effects/*instrumentation/methods MH - Female MH - Humans MH - Length of Stay/statistics & numerical data MH - Lung Neoplasms/pathology/surgery MH - Lymph Node Excision/adverse effects/*methods MH - Male MH - Mediastinum/*surgery MH - Middle Aged MH - Pilot Projects MH - Pneumonectomy/adverse effects/*methods OTO - NOTNLM OT - Atrial fibrillation OT - Lobectomy OT - Lung cancer OT - Lymphadenectomy EDAT- 2014/10/15 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/10/15 06:00 PHST- 2014/10/15 06:00 [entrez] PHST- 2014/10/15 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - ezu391 [pii] AID - 10.1093/ejcts/ezu391 [doi] PST - ppublish SO - Eur J Cardiothorac Surg. 2015 Jan;47(1):e13-8. doi: 10.1093/ejcts/ezu391. Epub 2014 Oct 13. PMID- 26204331 OWN - NLM STAT- MEDLINE DCOM- 20160218 LR - 20170614 IS - 1931-3543 (Electronic) IS - 0012-3692 (Linking) VI - 148 IP - 5 DP - 2015 Nov TI - A Double-Blind Placebo-Controlled Study of the Effects of Olprinone, a Specific Phosphodiesterase III Inhibitor, for Preventing Postoperative Atrial Fibrillation in Patients Undergoing Pulmonary Resection for Lung Cancer. PG - 1285-1292 LID - S0012-3692(15)50240-7 [pii] LID - 10.1378/chest.15-0852 [doi] AB - BACKGROUND: We previously reported that patients with elevated preoperative B-type natriuretic peptide (BNP) levels have an increased risk for postoperative atrial fibrillation following lung cancer surgery. The present study evaluated whether the specific phosphodiesterase III inhibitor olprinone can reduce the incidence of postoperative atrial fibrillation in patients with elevated BNP levels undergoing pulmonary resection for lung cancer. METHODS: A prospective randomized study was conducted with 40 patients who had elevated preoperative BNP levels (≥ 30 pg/mL) and underwent scheduled lung cancer surgery. All patients were in sinus rhythm at surgery. Low-dose olprinone or placebo was continuously infused for 24 h and started just before anesthesia induction. The primary end point was the incidence of postoperative atrial fibrillation. The secondary end points were perioperative hemodynamics and levels of BNP, WBC counts, and C-reactive protein. RESULTS: The incidence of postoperative atrial fibrillation was significantly lower in the olprinone group than in the placebo group (10% vs 60%, P < .001). Patients in the olprinone group showed significantly lower BNP, WBC counts, and C-reactive protein levels after surgery. CONCLUSIONS: Continuous infusion of olprinone during lung cancer surgery was safe and reduced the incidence of postoperative atrial fibrillation following pulmonary resection in patients with elevated preoperative BNP levels. TRIAL REGISTRY: Japan Primary Registries Network; No.: JPRN-UMIN2404; URL: http://www.umin.ac.jp/ctr/. FAU - Nojiri, Takashi AU - Nojiri T AD - Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Osaka; Department of Biochemistry, Research Institute, National Cerebral and Cardiovascular Center, Osaka; Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka. Electronic address: nojirit@thoracic.med.osaka-u.ac.jp. FAU - Yamamoto, Kazuhiro AU - Yamamoto K AD - Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Tottori, Japan. FAU - Maeda, Hajime AU - Maeda H AD - Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Osaka. FAU - Takeuchi, Yukiyasu AU - Takeuchi Y AD - Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Osaka. FAU - Ose, Naoko AU - Ose N AD - Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Osaka. FAU - Susaki, Yoshiyuki AU - Susaki Y AD - Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Osaka. FAU - Inoue, Masayoshi AU - Inoue M AD - Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka. FAU - Okumura, Meinoshin AU - Okumura M AD - Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka. LA - eng SI - JPRN/UMIN2404 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Chest JT - Chest JID - 0231335 RN - 0 (Imidazoles) RN - 0 (Phosphodiesterase 3 Inhibitors) RN - 0 (Pyridones) RN - 4Y8BMI9YGC (olprinone) SB - IM MH - Aged MH - Atrial Fibrillation/epidemiology/etiology/*prevention & control MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Follow-Up Studies MH - Humans MH - Imidazoles/*administration & dosage MH - Incidence MH - Japan/epidemiology MH - Lung Neoplasms/*surgery MH - Male MH - Phosphodiesterase 3 Inhibitors/administration & dosage MH - Pneumonectomy/*adverse effects MH - *Postoperative Complications MH - Prospective Studies MH - Pyridones/*administration & dosage MH - Treatment Outcome EDAT- 2015/07/24 06:00 MHDA- 2016/02/19 06:00 CRDT- 2015/07/24 06:00 PHST- 2015/07/24 06:00 [entrez] PHST- 2015/07/24 06:00 [pubmed] PHST- 2016/02/19 06:00 [medline] AID - S0012-3692(15)50240-7 [pii] AID - 10.1378/chest.15-0852 [doi] PST - ppublish SO - Chest. 2015 Nov;148(5):1285-1292. doi: 10.1378/chest.15-0852. PMID- 26317683 OWN - NLM STAT- MEDLINE DCOM- 20151229 LR - 20181202 IS - 1473-5741 (Electronic) IS - 0959-4973 (Linking) VI - 26 IP - 10 DP - 2015 Nov TI - Phase I study evaluating the safety and efficacy of oral panobinostat in combination with radiotherapy or chemoradiotherapy in patients with inoperable stage III non-small-cell lung cancer. PG - 1069-77 LID - 10.1097/CAD.0000000000000282 [doi] AB - Panobinostat is a radiosensitizing agent and targets the epigenetics of malignancy. This phase I study evaluated the safety and efficacy of combining oral panobinostat with radiotherapy (RT) or chemoradiotherapy (CRT) in patients with inoperable stage III non-small-cell lung cancer. This study had a parallel dose-escalating design combining oral panobinostat twice a week (dose escalations 20, 30, 45 mg) with either palliative RT (group A) or radical CRT (group B) using a standard chemotherapy protocol of cisplatin and etoposide. In group A (RT), nine recruited patients received treatment with oral panobinostat (doses 20, 30, 45 mg) with RT. Two serious adverse events, rapid atrial fibrillation and tracheo-oesophageal fistula, were not attributable to study treatment. The most common grade 3/4 toxicities were thrombocytopenia and lymphopenia, which resolved promptly after cessation of panobinostat. The disease control rate was 66%, the progression-free survival was 3 months and the median overall survival was 9 months. In group B (CRT), panobinostat dose was not escalated beyond 20 mg because of infection-related complications. Serious adverse events included opportunistic infection associated with treatment-related lymphopenia and febrile neutropenia without a source. One patient had cerebral infarct that was not attributed to study treatment. All patients achieved a partial response to treatment. At 33 months of follow-up, all patients were still alive. Panobinostat can be combined with palliative-dose RT at doses up to 45 mg twice a week with tolerable toxicity. Dose-limiting toxicities prevented the dose escalation of the panobinostat with CRT. FAU - Takhar, Harminder S AU - Takhar HS AD - aCancer Clinical Trials Unit bDepartment of Medical Oncology cDepartment of Radiation Oncology dDepartment of Medical Imaging, Royal Adelaide Hospital eCentre for Cancer Biology, SA Pathology and University of South Australia fDiscipline of Medicine, University of Adelaide, Adelaide, Australia. FAU - Singhal, Nimit AU - Singhal N FAU - Gowda, Raghu AU - Gowda R FAU - Penniment, Michael AU - Penniment M FAU - Takhar, Parineet AU - Takhar P FAU - Brown, Michael P AU - Brown MP LA - eng PT - Clinical Trial, Phase I PT - Journal Article PL - England TA - Anticancer Drugs JT - Anti-cancer drugs JID - 9100823 RN - 0 (Hydroxamic Acids) RN - 0 (Indoles) RN - 0 (Radiation-Sensitizing Agents) RN - 9647FM7Y3Z (Panobinostat) SB - IM MH - Administration, Oral MH - Aged MH - Carcinoma, Non-Small-Cell Lung/pathology/radiotherapy/*therapy MH - Chemoradiotherapy MH - Disease-Free Survival MH - Feasibility Studies MH - Female MH - Humans MH - Hydroxamic Acids/*therapeutic use MH - Indoles/*therapeutic use MH - Lung Neoplasms/pathology/radiotherapy/*therapy MH - Male MH - Maximum Tolerated Dose MH - Middle Aged MH - Neoplasm Staging MH - Panobinostat MH - Radiation-Sensitizing Agents/*therapeutic use EDAT- 2015/09/01 06:00 MHDA- 2015/12/30 06:00 CRDT- 2015/08/29 06:00 PHST- 2015/08/29 06:00 [entrez] PHST- 2015/09/01 06:00 [pubmed] PHST- 2015/12/30 06:00 [medline] AID - 10.1097/CAD.0000000000000282 [doi] PST - ppublish SO - Anticancer Drugs. 2015 Nov;26(10):1069-77. doi: 10.1097/CAD.0000000000000282. PMID- 26764872 OWN - NLM STAT- MEDLINE DCOM- 20170531 LR - 20220318 IS - 1528-1140 (Electronic) IS - 0003-4932 (Linking) VI - 264 IP - 2 DP - 2016 Aug TI - Prevention of Atrial Fibrillation in High-risk Patients Undergoing Lung Cancer Surgery: The PRESAGE Trial. PG - 244-51 LID - 10.1097/SLA.0000000000001626 [doi] AB - OBJECTIVE: We performed a prospective, randomized clinical study to assess whether prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, reduces the incidence of postoperative atrial fibrillation. BACKGROUND: Postoperative atrial fibrillation is a well recognized complication after lung cancer surgery, with an incidence as high as 30%. Perioperative increase of NT-proBNP has been demonstrated to be a strong independent predictor of postoperative atrial fibrillation in this setting. METHODS: NT-proBNP concentration was measured 24 hours before surgery and soon after surgery in 1116 patients. Three hundred twenty (29%) patients showed a high NT-proBNP value and were enrolled: 108 were assigned to the metoprolol group, 102 to the losartan group, and 110 to the control group. RESULTS: Overall, the incidence of postoperative atrial fibrillation was 20% (n = 64); it was significantly lower in the metoprolol and losartan groups compared with the control group [6%, 12%, and 40%, respectively; relative risk 0.19, 95% confidence intervals (CIs), 0.09-0.37; P < 0.001 in the metoprolol group; and 0.29, 95% CI, 0.16-0.52; P < 0.001 in the losartan group). No significant difference was found when the metoprolol and losartan groups were directly compared (P = 0.21). CONCLUSIONS: A prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with high NT-proBNP levels, significantly reduced the occurrence of postoperative atrial fibrillation. FAU - Cardinale, Daniela AU - Cardinale D AD - *Cardioncology Unit, European Institute of Oncology, I.R.C.C.S., Milan, Italy†Laboratory Medicine Division, European Institute of Oncology, I.R.C.C.S., Milan, Italy.‡Cardiology Division, European Institute of Oncology, I.R.C.C.S., Milan, Italy.§Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Milan, Italy.||Department of Thoracic Surgery, European Institute of Oncology, I.R.C.C.S., Milan, Italy.¶Department of Thoracic Surgery, European Institute of Oncology, I.R.C.C.S., University of Milan School of Medicine, Milan, Italy.**Department of Anaesthesiology, European Institute of Oncology, I.R.C.C.S., Milan, Italy. FAU - Sandri, Maria T AU - Sandri MT FAU - Colombo, Alessandro AU - Colombo A FAU - Salvatici, Michela AU - Salvatici M FAU - Tedeschi, Ines AU - Tedeschi I FAU - Bacchiani, Giulia AU - Bacchiani G FAU - Beggiato, Marta AU - Beggiato M FAU - Meroni, Carlo A AU - Meroni CA FAU - Civelli, Maurizio AU - Civelli M FAU - Lamantia, Giuseppina AU - Lamantia G FAU - Colombo, Nicola AU - Colombo N FAU - Veglia, Fabrizio AU - Veglia F FAU - Casiraghi, Monica AU - Casiraghi M FAU - Spaggiari, Lorenzo AU - Spaggiari L FAU - Venturino, Marco AU - Venturino M FAU - Cipolla, Carlo M AU - Cipolla CM LA - eng PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Ann Surg JT - Annals of surgery JID - 0372354 RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Peptide Fragments) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - GEB06NHM23 (Metoprolol) RN - JMS50MPO89 (Losartan) SB - IM MH - Aged MH - Anti-Arrhythmia Agents/*therapeutic use MH - Atrial Fibrillation/blood/epidemiology/*prevention & control MH - Female MH - Humans MH - Incidence MH - Losartan/therapeutic use MH - Lung Neoplasms/blood/*surgery MH - Male MH - Metoprolol/therapeutic use MH - Middle Aged MH - Natriuretic Peptide, Brain/blood MH - Peptide Fragments/blood MH - Pneumonectomy/*adverse effects MH - Postoperative Complications/blood/epidemiology/*prevention & control MH - Prospective Studies EDAT- 2016/01/15 06:00 MHDA- 2017/06/01 06:00 CRDT- 2016/01/15 06:00 PHST- 2016/01/15 06:00 [entrez] PHST- 2016/01/15 06:00 [pubmed] PHST- 2017/06/01 06:00 [medline] AID - 10.1097/SLA.0000000000001626 [doi] PST - ppublish SO - Ann Surg. 2016 Aug;264(2):244-51. doi: 10.1097/SLA.0000000000001626. PMID- 29258674 OWN - NLM STAT- MEDLINE DCOM- 20190403 LR - 20220408 IS - 1552-6259 (Electronic) IS - 0003-4975 (Linking) VI - 105 IP - 3 DP - 2018 Mar TI - Surgical Outcomes After Neoadjuvant Chemotherapy and Ipilimumab for Non-Small Cell Lung Cancer. PG - 924-929 LID - S0003-4975(17)31276-6 [pii] LID - 10.1016/j.athoracsur.2017.09.030 [doi] AB - BACKGROUND: The objective of this study was to evaluate the safety and feasibility of using neoadjuvant chemotherapy plus ipilimumab followed by surgery as a treatment strategy for stage II-IIIA non-small cell lung cancer. METHODS: From 2013 to 2017, postoperative data from patients who underwent surgery after neoadjuvant chemotherapy plus ipilimumab in the TOP1201 trial, an open label phase II trial (NCT01820754), were prospectively collected. The surgical outcomes from TOP1201 were compared with outcomes in a historical cohort of patients receiving standard preoperative chemotherapy followed by surgery identified from our institution's prospectively collected thoracic surgery database. RESULTS: In the TOP1201 trial, 13 patients were treated with preoperative chemotherapy and ipilimumab followed by surgery. In the historical cohort, 42 patients received preoperative chemotherapy by a platinum doublet regimen preoperative chemotherapy by a platinum doublet regimen without ipilimumab followed by lobectomy or pneumonectomy. The 30-day mortality in both groups was 0%. The most frequently occurring perioperative complications in the TOP1201 group were prolonged air leak (n = 2, 15%) and urinary tract infection (n = 2, 15%). The most common perioperative complication in the preoperative chemotherapy alone group was atrial fibrillation (n = 6, 14%). One patient (8%) had atrial fibrillation in the TOP1201 group. There was no apparent increased occurrence of adverse surgical outcomes for patients in the TOP1201 group compared with patients receiving standard of care neoadjuvant chemotherapy alone before surgery for stage II-IIIA non-small cell lung cancer. CONCLUSIONS: This report is the first to demonstrate the safety and feasibility of surgical resection after treatment with ipilimumab and chemotherapy in stage II-IIIA non-small-cell lung cancer. CI - Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. FAU - Yang, Chi-Fu Jeffrey AU - Yang CJ AD - Duke University Medical Center, Durham, North Carolina. FAU - McSherry, Frances AU - McSherry F AD - Duke University Medical Center, Durham, North Carolina. FAU - Mayne, Nicholas R AU - Mayne NR AD - Duke University Medical Center, Durham, North Carolina. FAU - Wang, Xiaofei AU - Wang X AD - Duke University Medical Center, Durham, North Carolina. FAU - Berry, Mark F AU - Berry MF AD - Department of Cardiothoracic Surgery, Stanford University, Stanford, California. FAU - Tong, Betty AU - Tong B AD - Duke University Medical Center, Durham, North Carolina. FAU - Harpole, David H Jr AU - Harpole DH Jr AD - Duke University Medical Center, Durham, North Carolina. FAU - D'Amico, Thomas A AU - D'Amico TA AD - Duke University Medical Center, Durham, North Carolina. FAU - Christensen, Jared D AU - Christensen JD AD - Duke University Medical Center, Durham, North Carolina. FAU - Ready, Neal E AU - Ready NE AD - Duke University Medical Center, Durham, North Carolina. FAU - Klapper, Jacob A AU - Klapper JA AD - Duke University Medical Center, Durham, North Carolina. Electronic address: jacob.klapper@duke.edu. LA - eng SI - ClinicalTrials.gov/NCT01820754 PT - Clinical Trial, Phase II PT - Journal Article DEP - 20171216 PL - Netherlands TA - Ann Thorac Surg JT - The Annals of thoracic surgery JID - 15030100R RN - 0 (Antineoplastic Agents) RN - 0 (Ipilimumab) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/pathology/*therapy MH - Chemotherapy, Adjuvant MH - Female MH - Humans MH - Ipilimumab/*therapeutic use MH - Lung Neoplasms/pathology/*therapy MH - Male MH - Middle Aged MH - *Neoadjuvant Therapy MH - Neoplasm Staging MH - *Pneumonectomy MH - Treatment Outcome EDAT- 2017/12/21 06:00 MHDA- 2019/04/04 06:00 CRDT- 2017/12/21 06:00 PHST- 2017/04/06 00:00 [received] PHST- 2017/08/04 00:00 [revised] PHST- 2017/09/11 00:00 [accepted] PHST- 2017/12/21 06:00 [pubmed] PHST- 2019/04/04 06:00 [medline] PHST- 2017/12/21 06:00 [entrez] AID - S0003-4975(17)31276-6 [pii] AID - 10.1016/j.athoracsur.2017.09.030 [doi] PST - ppublish SO - Ann Thorac Surg. 2018 Mar;105(3):924-929. doi: 10.1016/j.athoracsur.2017.09.030. Epub 2017 Dec 16. PMID- 29800033 OWN - NLM STAT- MEDLINE DCOM- 20180710 LR - 20221207 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 319 IP - 21 DP - 2018 Jun 5 TI - Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices. PG - 2212-2222 LID - 10.1001/jama.2018.4653 [doi] AB - IMPORTANCE: Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial. OBJECTIVE: To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices. DESIGN, SETTING, AND PARTICIPANTS: Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017. EXPOSURES: Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (-80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used. MAIN OUTCOMES AND MEASURES: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. RESULTS: Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men [65%]). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells. CONCLUSIONS AND RELEVANCE: In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01331863. FAU - Martinod, Emmanuel AU - Martinod E AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Chirurgie Thoracique et Vasculaire, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. AD - Université Paris Descartes, Fondation Alain Carpentier, Laboratoire de Recherche Bio-chirurgicale, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. FAU - Chouahnia, Kader AU - Chouahnia K AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Oncologie, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Radu, Dana M AU - Radu DM AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Chirurgie Thoracique et Vasculaire, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. AD - Université Paris Descartes, Fondation Alain Carpentier, Laboratoire de Recherche Bio-chirurgicale, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. FAU - Joudiou, Pascal AU - Joudiou P AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Pneumologie, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Uzunhan, Yurdagul AU - Uzunhan Y AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Pneumologie, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Bensidhoum, Morad AU - Bensidhoum M AD - B2OA UMR CNRS 7052, Université Paris Diderot, Sorbonne Paris Cité, CNRS, F-75010 Paris, France. AD - Ecole Nationale Vétérinaire d'Alfort, Université, Paris-Est, Maisons-Alfort, France. FAU - Santos Portela, Ana M AU - Santos Portela AM AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Chirurgie Thoracique et Vasculaire, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Guiraudet, Patrice AU - Guiraudet P AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Chirurgie Thoracique et Vasculaire, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. AD - Université Paris Descartes, Fondation Alain Carpentier, Laboratoire de Recherche Bio-chirurgicale, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. FAU - Peretti, Marine AU - Peretti M AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Chirurgie Thoracique et Vasculaire, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Destable, Marie-Dominique AU - Destable MD AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Chirurgie Thoracique et Vasculaire, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Solis, Audrey AU - Solis A AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Anesthésie-Réanimation, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Benachi, Sabiha AU - Benachi S AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Anesthésie-Réanimation, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Fialaire-Legendre, Anne AU - Fialaire-Legendre A AD - Assistance Publique-Hôpitaux de Paris, EFS Ile de France, Banque des Tissus, Creteil, France. FAU - Rouard, Hélène AU - Rouard H AD - Assistance Publique-Hôpitaux de Paris, EFS Ile de France, Banque des Tissus, Creteil, France. FAU - Collon, Thierry AU - Collon T AD - Hôpital Le Raincy-Montfermeil, Pneumologie, Montfermeil, France. FAU - Piquet, Jacques AU - Piquet J AD - Hôpital Le Raincy-Montfermeil, Pneumologie, Montfermeil, France. FAU - Leroy, Sylvie AU - Leroy S AD - Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Pneumologie, Chirurgie Thoracique, Oto-Rhino-Laryngologie, Nice, France. FAU - Vénissac, Nicolas AU - Vénissac N AD - Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Pneumologie, Chirurgie Thoracique, Oto-Rhino-Laryngologie, Nice, France. FAU - Santini, Joseph AU - Santini J AD - Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Pneumologie, Chirurgie Thoracique, Oto-Rhino-Laryngologie, Nice, France. FAU - Tresallet, Christophe AU - Tresallet C AD - Assistance Publique-Hôpitaux de Paris, Hôpital La Pitié-Salpêtrière, Chirurgie Digestive et Endocrinienne, Université Paris 6 Pierre et Marie Curie, Paris, France. FAU - Dutau, Hervé AU - Dutau H AD - Assistance Publique-Hôpitaux de Marseille, Pneumologie, Hôpital Universitaire Nord, Marseille, France. FAU - Sebbane, Georges AU - Sebbane G AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Gériatrie, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Cohen, Yves AU - Cohen Y AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Anesthésie-Réanimation, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Beloucif, Sadek AU - Beloucif S AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Anesthésie-Réanimation, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - d'Audiffret, Alexandre C AU - d'Audiffret AC AD - Division of Vascular Surgery, West Virginia University, Morgantown. FAU - Petite, Hervé AU - Petite H AD - B2OA UMR CNRS 7052, Université Paris Diderot, Sorbonne Paris Cité, CNRS, F-75010 Paris, France. AD - Ecole Nationale Vétérinaire d'Alfort, Université, Paris-Est, Maisons-Alfort, France. FAU - Valeyre, Dominique AU - Valeyre D AD - Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Pneumologie, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny, France. FAU - Carpentier, Alain AU - Carpentier A AD - Université Paris Descartes, Fondation Alain Carpentier, Laboratoire de Recherche Bio-chirurgicale, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. FAU - Vicaut, Eric AU - Vicaut E AD - Assistance Publique-Hôpitaux de Paris, Unité de Recherche Clinique, Hôpitaux Saint Louis-Lariboisière-Fernand Widal, Université Paris Diderot, Paris, France. LA - eng SI - ClinicalTrials.gov/NCT01331863 PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA JT - JAMA JID - 7501160 SB - IM CIN - JAMA. 2018 Jun 5;319(21):2177-2178. doi: 10.1001/jama.2018.4652. PMID: 29800016 MH - Adult MH - Aged MH - Aorta/*transplantation MH - Autografts MH - Bioengineering/*methods MH - Bronchi/*surgery MH - Feasibility Studies MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/*surgery MH - Male MH - Middle Aged MH - Pneumonectomy MH - Plastic Surgery Procedures/methods MH - *Stents MH - Trachea/pathology/*surgery MH - Tracheal Diseases/pathology/*surgery MH - Tracheal Stenosis/surgery PMC - PMC6134437 COIS- Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Uzunhan reported receiving personal fees from Roche; personal fees and nonfinancial support from Bohringer Ingelheim; and nonfinancial support from Oxyvie. Dr Valeyre reported being a member of advisory boards on idiopathic pulmonary fibrosis treatment that are supported by Roche and Boehringer Ingelheim; receiving personal fees from AstraZeneca and Isis France; and receiving travel support to attend scientific meetings from Roche and Boehringer Ingelheim. Dr Carpentier reported being a cofounder and shareholder of Carmat SA. Dr Vicaut reported receiving grant support from Bristol-Myers Squibb; and personal fees from Bristol-Myers Squibb, Pfizer, Novartis, Pierre Fabre, and Ottobock. No other disclosures were reported. EDAT- 2018/05/26 06:00 MHDA- 2018/07/11 06:00 PMCR- 2018/11/20 CRDT- 2018/05/26 06:00 PHST- 2018/05/26 06:00 [pubmed] PHST- 2018/07/11 06:00 [medline] PHST- 2018/05/26 06:00 [entrez] PHST- 2018/11/20 00:00 [pmc-release] AID - 2681944 [pii] AID - jpc180003 [pii] AID - 10.1001/jama.2018.4653 [doi] PST - ppublish SO - JAMA. 2018 Jun 5;319(21):2212-2222. doi: 10.1001/jama.2018.4653. PMID- 33985811 OWN - NLM STAT- MEDLINE DCOM- 20220131 LR - 20260305 IS - 1097-685X (Electronic) IS - 0022-5223 (Linking) VI - 163 IP - 2 DP - 2022 Feb TI - Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. PG - 427-436 LID - S0022-5223(21)00583-3 [pii] LID - 10.1016/j.jtcvs.2021.02.099 [doi] AB - OBJECTIVES: Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science. METHODS: Patients with untreated clinical stage IB to IIIA non-small cell lung cancer were enrolled. Two cycles of pembrolizumab (200 mg) were administered before surgery. Standard adjuvant chemotherapy and radiation were encouraged but not required. Four cycles of adjuvant pembrolizumab were provided. RESULTS: Of 35 patients enrolled, 30 received neoadjuvant pembrolizumab and 25 underwent lung resection. Only 1 patient had a delay before surgery attributed to pembrolizumab; this was due to thyroiditis. All patients underwent anatomic resection and mediastinal lymph node dissection; the majority (18/25%, 72%) of patients underwent lobectomy. Of the 25 patients, 23 had an initial minimally invasive approach (92%); 5 of these were converted to thoracotomy (21.7%). R0 resection was achieved in 22 patients (88%), and major pathologic response was observed in 7 of 25 patients (28%). The most common postoperative adverse event was atrial fibrillation, affecting 6 of 25 patients (24%). Median chest tube duration and length of stay were 3 and 4 days, respectively. One patient required readmission to the hospital within 30 days. There was no mortality within 90 days of surgery. CONCLUSIONS: In this study, pembrolizumab was safe and well tolerated in the neoadjuvant setting, and its use was not associated with excess surgical morbidity or mortality. Minimally invasive approaches are feasible in this patient population, but may be more challenging than in cases without neoadjuvant immunotherapy. Pathologic response was higher than typically observed with standard neoadjuvant chemotherapy. CI - Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved. FAU - Tong, Betty C AU - Tong BC AD - Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, NC. Electronic address: betty.tong@duke.edu. FAU - Gu, Lin AU - Gu L AD - Duke Cancer Institute Biostatistics Shared Resource, Duke University School of Medicine, Durham, NC. FAU - Wang, Xiaofei AU - Wang X AD - Duke Cancer Institute Biostatistics Shared Resource, Duke University School of Medicine, Durham, NC. FAU - Wigle, Dennis A AU - Wigle DA AD - Department of Thoracic Surgery, Mayo Clinic, Rochester, Minn. FAU - Phillips, Joseph D AU - Phillips JD AD - Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH. FAU - Harpole, David H Jr AU - Harpole DH Jr AD - Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, NC. FAU - Klapper, Jacob A AU - Klapper JA AD - Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, NC. FAU - Sporn, Thomas AU - Sporn T AD - Department of Pathology, Duke University Medical Center, Durham, NC. FAU - Ready, Neal E AU - Ready NE AD - Division of Medical Oncology, Duke University Medical Center, Durham, NC. FAU - D'Amico, Thomas A AU - D'Amico TA AD - Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, NC. LA - eng SI - ClinicalTrials.gov/NCT02818920 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20210409 PL - United States TA - J Thorac Cardiovasc Surg JT - The Journal of thoracic and cardiovascular surgery JID - 0376343 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Immune Checkpoint Inhibitors) RN - DPT0O3T46P (pembrolizumab) SB - IM CIN - J Thorac Cardiovasc Surg. 2022 Feb;163(2):437-438. doi: 10.1016/j.jtcvs.2021.03.086. PMID: 33941374 CIN - J Thorac Cardiovasc Surg. 2022 Feb;163(2):438-439. doi: 10.1016/j.jtcvs.2021.04.027. PMID: 33972108 CIN - J Thorac Cardiovasc Surg. 2022 Feb;163(2):439-440. doi: 10.1016/j.jtcvs.2021.04.056. PMID: 34024619 MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects MH - Carcinoma, Non-Small-Cell Lung/pathology/*therapy MH - Chemotherapy, Adjuvant MH - Disease-Free Survival MH - Female MH - Humans MH - Immune Checkpoint Inhibitors/*administration & dosage/adverse effects MH - Lung Neoplasms/pathology/*therapy MH - Male MH - Middle Aged MH - *Neoadjuvant Therapy/adverse effects MH - Neoplasm Staging MH - *Pneumonectomy/adverse effects MH - Postoperative Complications/therapy MH - *Thoracic Surgery, Video-Assisted/adverse effects MH - *Thoracotomy/adverse effects MH - Time Factors MH - United States OTO - NOTNLM OT - immunotherapy OT - non–small cell lung cancer OT - pembrolizumab OT - surgery EDAT- 2021/05/15 06:00 MHDA- 2022/02/01 06:00 CRDT- 2021/05/14 05:48 PHST- 2020/05/14 00:00 [received] PHST- 2021/02/28 00:00 [revised] PHST- 2021/02/28 00:00 [accepted] PHST- 2021/05/15 06:00 [pubmed] PHST- 2022/02/01 06:00 [medline] PHST- 2021/05/14 05:48 [entrez] AID - S0022-5223(21)00583-3 [pii] AID - 10.1016/j.jtcvs.2021.02.099 [doi] PST - ppublish SO - J Thorac Cardiovasc Surg. 2022 Feb;163(2):427-436. doi: 10.1016/j.jtcvs.2021.02.099. Epub 2021 Apr 9. PMID- 35358455 OWN - NLM STAT- MEDLINE DCOM- 20230522 LR - 20250530 IS - 1474-5488 (Electronic) IS - 1470-2045 (Print) IS - 1470-2045 (Linking) VI - 23 IP - 4 DP - 2022 Apr TI - Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial. PG - 540-552 LID - S1470-2045(22)00061-4 [pii] LID - 10.1016/S1470-2045(22)00061-4 [doi] AB - BACKGROUND: Few treatment options exist for second-line treatment of malignant pleural mesothelioma. We aimed to assess the antibody-drug conjugate anetumab ravtansine versus vinorelbine in patients with unresectable locally advanced or metastatic disease overexpressing mesothelin who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. METHODS: In this phase 2, randomised, open-label study, done at 76 hospitals in 14 countries, we enrolled adults (aged ≥18 years) with unresectable locally advanced or metastatic malignant pleural mesothelioma, an Eastern Cooperative Oncology Group performance status of 0-1, and who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. Participants were prospectively screened for mesothelin overexpression (defined as 2+ or 3+ mesothelin membrane staining intensity on at least 30% of viable tumour cells by immunohistochemistry) and were randomly assigned (2:1), using an interactive voice and web response system provided by the sponsor, to receive intravenous anetumab ravtansine (6·5 mg/kg on day 1 of each 21-day cycle) or intravenous vinorelbine (30 mg/m(2) once every week) until progression, toxicity, or death. The primary endpoint was progression-free survival according to blinded central radiology review, assessed in the intention-to-treat population, with safety assessed in all participants who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02610140, and is now completed. FINDINGS: Between Dec 3, 2015, and May 31, 2017, 589 patients were enrolled and 248 mesothelin-overexpressing patients were randomly allocated to the two treatment groups (166 patients were randomly assigned to receive anetumab ravtansine and 82 patients were randomly assigned to receive vinorelbine). 105 (63%) of 166 patients treated with anetumab ravtansine (median follow-up 4·0 months [IQR 1·4-5·5]) versus 43 (52%) of 82 patients treated with vinorelbine (3·9 months [1·4-5·4]) had disease progression or died (median progression-free survival 4·3 months [95% CI 4·1-5·2] vs 4·5 months [4·1-5·8]; hazard ratio 1·22 [0·85-1·74]; log-rank p=0·86). The most common grade 3 or worse adverse events were neutropenia (one [1%] of 163 patients for anetumab ravtansine vs 28 [39%] of 72 patients for vinorelbine), pneumonia (seven [4%] vs five [7%]), neutrophil count decrease (two [1%] vs 12 [17%]), and dyspnoea (nine [6%] vs three [4%]). Serious drug-related treatment-emergent adverse events occurred in 12 (7%) patients treated with anetumab ravtansine and 11 (15%) patients treated with vinorelbine. Ten (6%) treatment-emergent deaths occurred with anetumab ravtansine: pneumonia (three [2%]), dyspnoea (two [1%]), sepsis (two [1%]), atrial fibrillation (one [1%]), physical deterioration (one [1%]), hepatic failure (one [1%]), mesothelioma (one [1%]), and renal failure (one [1%]; one patient had 3 events). One (1%) treatment-emergent death occurred in the vinorelbine group (pneumonia). INTERPRETATION: Anetumab ravtansine showed a manageable safety profile and was not superior to vinorelbine. Further studies are needed to define active treatments in relapsed mesothelin-expressing malignant pleural mesothelioma. FUNDING: Bayer Healthcare Pharmaceuticals. CI - Copyright © 2022 Elsevier Ltd. All rights reserved. FAU - Kindler, Hedy L AU - Kindler HL AD - Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA. Electronic address: hkindler@medicine.bsd.uchicago.edu. FAU - Novello, Silvia AU - Novello S AD - Department of Oncology, University of Turin, Orbassano, Turin, Italy. FAU - Bearz, Alessandra AU - Bearz A AD - Department of Medical Oncology and Immune-Related Cancers, CRO-IRCCS Centro di Riferimento Oncologico di Aviano, Aviano, Italy. FAU - Ceresoli, Giovanni L AU - Ceresoli GL AD - Department of Medical Oncology, Oncology Unit, Cliniche Humanitas Gavazzeni, Bergamo, Italy. FAU - Aerts, Joachim G J V AU - Aerts JGJV AD - Department of Pulmonary Medicine, Erasmus MC Cancer Centre, Rotterdam, Netherlands. FAU - Spicer, James AU - Spicer J AD - Comprehensive Cancer Centre, King's College London, London, UK. FAU - Taylor, Paul AU - Taylor P AD - Department of Medical Oncology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Nackaerts, Kristiaan AU - Nackaerts K AD - Laboratory of Respiratory Diseases and Thoracic Surgery, Department of Chronic Diseases and Metabolism, Universitair Ziekenhuis Leuven, KU Leuven, Leuven, Belgium. FAU - Greystoke, Alastair AU - Greystoke A AD - Department of Medical Oncology, Northern Centre for Cancer Care, Newcastle upon Tyne, UK. FAU - Jennens, Ross AU - Jennens R AD - Epworth Cancer Services Clinical Institute, Epworth Healthcare, Richmond, VIC, Australia. FAU - Calabrò, Luana AU - Calabrò L AD - Department of Oncology, Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy. FAU - Burgers, Jacobus A AU - Burgers JA AD - Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands. FAU - Santoro, Armando AU - Santoro A AD - Humanitas University, Milan, Italy; Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy. FAU - Cedrés, Susana AU - Cedrés S AD - Department of Medical Oncology, University Hospital Vall d'Hebron, Barcelona, Spain. FAU - Serwatowski, Piotr AU - Serwatowski P AD - Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain. FAU - Ponce, Santiago AU - Ponce S AD - Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain. FAU - Van Meerbeeck, Jan P AU - Van Meerbeeck JP AD - Department of Thoracic Oncology, Antwerp University and University Hospital and European Reference Network for Rare or Low Prevalence Complex Disease (ERN-LUNG), Antwerp, Belgium. FAU - Nowak, Anna K AU - Nowak AK AD - Medical School, University of Western Australia, Perth, WA, Australia; National Centre for Asbestos Related Diseases, Institute for Respiratory Health, Perth, WA, Australia. FAU - Blumenschein, George Jr AU - Blumenschein G Jr AD - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Siegel, Jonathan M AU - Siegel JM AD - Clinical Statistics Oncology, Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA. FAU - Kasten, Linda AU - Kasten L AD - Statistics, Syneos Health Clinical Solutions, Morrisville, NC, USA. FAU - Köchert, Karl AU - Köchert K AD - Biomarker and Data Insights, Bayer AG Pharma, Berlin, Germany. FAU - Walter, Annette O AU - Walter AO AD - Translational Medicine Oncology, Bayer AG Pharma, Berlin, Germany. FAU - Childs, Barrett H AU - Childs BH AD - Oncology Development, Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA. FAU - Elbi, Cem AU - Elbi C AD - Global Clinical Development, Oncology, Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA. FAU - Hassan, Raffit AU - Hassan R AD - Department of Thoracic and GI Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. FAU - Fennell, Dean A AU - Fennell DA AD - Leicester Cancer Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK. Electronic address: df132@leicester.ac.uk. LA - eng SI - ClinicalTrials.gov/NCT02610140 GR - ZID BC011540/ImNIH/Intramural NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Lancet Oncol JT - The Lancet. Oncology JID - 100957246 RN - M170940PMI (anetumab ravtansine) RN - 0 (Immunoconjugates) RN - 14083FR882 (Maytansine) RN - J27WDC343N (Mesothelin) RN - Q6C979R91Y (Vinorelbine) SB - IM CIN - Lancet Oncol. 2022 Apr;23(4):445-446. doi: 10.1016/S1470-2045(22)00099-7. PMID: 35358447 MH - Adolescent MH - Adult MH - Humans MH - Arthrogryposis MH - *Immunoconjugates/adverse effects MH - Maytansine/analogs & derivatives MH - Mesothelin MH - *Mesothelioma, Malignant/drug therapy MH - Neoplasm Recurrence, Local/pathology MH - Vinorelbine/adverse effects PMC - PMC10512125 MID - NIHMS1925231 COIS- Declarations of interests HLK reports grants paid to the University of Chicago to support clinical trials for Aduro, AstraZeneca, Bayer, Blueprint, Bristol Myers Squibb, Deciphera, GlaxoSmithKline, Harpoon, Inhibrx, MacroGenics, Merck, Polaris, Seattle Genetics, and Vivace; consulting fees from Bristol Myers Squibb, Deciphera, Inventiva, Novocure, and Seattle Genetics; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events for AstraZeneca; support for attending meetings, travel, or both from AstraZeneca and Inventiva; participation on a data safety monitoring board or advisory board for Bristol Myers Squibb, Inventiva, and Seattle Genetics; and leadership or fiduciary role on board of directors for the International Mesothelioma Interest Group. SN reports personal payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Abbvie, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Pfizer, Pharmamar, Roche, and Takeda; and personal fees for participation on a data safety monitoring board or advisory board from AstraZeneca, Bayer, Daiichi Sanko, Eli Lilly, Pfizer, Roche, Sanofi, and Takeda. AB reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, Eli-Lilly, Pfizer, Roche, and Takeda; and support for attending meetings, travel, or both for Boehringer Ingelheim, Merck Sharp and Dohme, and Roche. GLC reports personal consulting fees for their advisory role for Novocure and Zai Lab; personal speaker engagements for Astellas, AstraZeneca, Merck Sharp and Dohme, Novocure, and Zai Lab; and support for attending meetings, travel, or both for Astellas, Novocure, and Merck Sharp and Dohme. JGJVA reports consulting fees for the advisory boards for Amphera, Bayer, Bristol Myers Squibb, Eli-Lilly, and Merck Sharp and Dohme; patents issued on allogenic tumour cell lysate and on combination immuno-oncology, owned by Erasmus MC Cancer Centre; participation on a data safety monitoring board or advisory board for Biocad; unpaid leadership role for the International Association for the Study of Lung Cancer; and stock or stock options for Amphera. JSp reports clinical trial reimbursement to Guy's & St Thomas’ NHS Foundation Trust from Bayer, BergenBio, Boehringer Ingelheim, Bristol Myers Squibb, Genmab, IO Biotech, Lytix, Seattle Genetics, and Starpharma; consulting fees paid to King's College London from Apobec, AVACTA, Bristol Myers Squibb, IO Biotech, and Seattle Genetics; support for attending meetings, travel, or both from Amgen and Janssen; participation on a data safety monitoring board or advisory board for AstraZeneca and Merck; and stock or stock options (co-founder) for Epsilogen. PT reports fees for a symposium presentation from AstraZeneca; and a conference registration fee from AstraZeneca. KN reports personal fees for advisory boards from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb Belgium, and Roche Belgium; personal fees for lectures from Roche Belgium; and support for attending meetings, travel, or both from AstraZeneca, Merck Sharpe and Dohme, and Pfizer. AG reports payment to Newcastle upon Tyne Hospitals NHS Foundation Trust for the care of patients on a study from Bayer (support for this manuscript). JAB reports institutional payment to the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital for support of investigator-initiated study from Merck Sharp and Dohme, consulting fees paid to the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital from Bristol Myers Squibb, and payment to the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital for participation on a data safety monitoring board or advisory board for Roche. AS reports consulting fees from ArQule and Sanofi; payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Abbvie, Amgen, ArQule, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Eisai, Eli-Lilly, Gilead, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sandoz, Servier, and Takeda; and participation on a data safety monitoring board or advisory board for Bayer, Bristol Myers Squibb, Eisai, Gilead, Merck Sharp and Dohme, Pfizer, and Servier. SC reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Amphera, Boehringer Ingelheim, Bristol Myers Squibb, Hoffmann La Roche, Merck Sharp and Dohme Oncology, and Pfizer; and support for attending meetings, travel, or both from Amphera, Boehringer Ingelheim, Bristol Myers Squibb, Hoffmann La Roche, Merck Sharp and Dohme Oncology, and Pfizer. JPVM reports consultancy fees from Amgen, AstraZeneca, Boehringer Ingelheim, Pfizer, and Roche; payment and reimbursement of expenses for services and consultancy from Amgen; registration fees from AstraZeneca, Merck Sharp and Dohme Belgium, Bristol Myers Squibb, GlaxoSmithKline, and Roche; and travel and accommodation support from AstraZeneca, Bristol Myers Squibb, Merck Sharp and Dohme Belgium, and Roche. AKN reports personal fees for consulting for clinical trials, quality of life research, and tumour measurement from Bayer (support for this manuscript); grants or contracts to institution from AstraZeneca and Douglas Pharmaceuticals; consulting fees from Atara Biotherapeutics (personal), Pharmabcine (institutional), and Seagen (personal); personal payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Bristol Myers Squibb; travel support from AstraZeneca; and participation on a data safety monitoring board or advisory board for Bristol Myers Squibb (personal). GBJ reports personal grants or contracts from Adaptimmune, Amgen, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Elelixis, Genentech, GlaxoSmithKline, Immatics, Immunocore, Incyte, Kite Pharma, Macrogenics, MedImmune, Merck, Novartis, Regeneron, Repertoire Immune Medicines, Roche, Tmunity Therapeutics, Torque, Verastem, and Xcovery; personal consulting fees for AbbVie, Adicet, Amgen, Ariad, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Clovis Oncology, Daiichi Sankyo, Genentech, Gilead, Instil Bio, Janssen, Lilly, Maverick Therapeutics, MedImmune, Merck, Novartis, Roche, Tyme Oncology, Viogin Biotech, and Xcovery; participation on a data safety monitoring board or advisory board for Maverick Therapeutics and Virogin Biotech (personal); and stock or stock options for Virogin Biotech. GBJ also has an immediate family member employed by Johnson and Johnson and Janssen. JSi is an employee of Bayer Healthcare Pharmaceuticals with ownership of stock; and reports unpaid leadership roles for the American Statistical Association, International Society for Clinical Biostatistics, and the Pharmaceutical Industry Working Group on Estimands in Oncology. LK is an external employee of Bayer Healthcare Pharmaceuticals. KK is an employee of Bayer AG Pharma with ownership of stock. AOW is an employee of Bayer AG Pharma. BHC and CE are employees of Bayer Healthcare Pharmaceuticals. RH reports institutional support for the conduct of this study via a Cooperative Research and Development Agreement (CRADA) between Bayer and the Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. He also has a CRADA with TCR(2) for conduct of clinical studies unrelated to this manuscript. DAF reports grants from Astex Therapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Merck Sharp and Dohme; personal fees from Aldeyra, Atara, Bristol Myers Squibb, Inventiva, Lab21, Roche, RS Oncology, and Targovax; and non-financial support from Bristol Myers Squibb, Clovis, Eli-Lilly, and Roche. All other authors declare no competing interests. EDAT- 2022/04/01 06:00 MHDA- 2022/04/05 06:00 PMCR- 2023/09/21 CRDT- 2022/03/31 20:10 PHST- 2021/10/13 00:00 [received] PHST- 2022/01/14 00:00 [revised] PHST- 2022/01/21 00:00 [accepted] PHST- 2022/03/31 20:10 [entrez] PHST- 2022/04/01 06:00 [pubmed] PHST- 2022/04/05 06:00 [medline] PHST- 2023/09/21 00:00 [pmc-release] AID - S1470-2045(22)00061-4 [pii] AID - 10.1016/S1470-2045(22)00061-4 [doi] PST - ppublish SO - Lancet Oncol. 2022 Apr;23(4):540-552. doi: 10.1016/S1470-2045(22)00061-4. PMID- 35780243 OWN - NLM STAT- MEDLINE DCOM- 20220706 LR - 20260127 IS - 2047-783X (Electronic) IS - 0949-2321 (Print) IS - 0949-2321 (Linking) VI - 27 IP - 1 DP - 2022 Jul 2 TI - A phase Ib dose-escalation study of troriluzole (BHV-4157), an oral glutamatergic signaling modulator, in combination with nivolumab in patients with advanced solid tumors. PG - 107 LID - 10.1186/s40001-022-00732-w [doi] LID - 107 AB - BACKGROUND: Glutamate signaling activates MAPK and PI3K/AKT pathways in tumor cells. Treatment with riluzole, a glutamate release inhibitor, has been previously shown to be safe in melanoma patients and produced biologic effects, but did not lead to radiographic responses, possibly due to poor pharmacokinetic properties. Therefore, we conducted a phase Ib trial to determine the safety and tolerability of the combination of the riluzole prodrug troriluzole (BHV-4157, trigriluzole) and the PD-1 antibody nivolumab in patients with advanced solid tumors. METHODS: Patients with advanced or refractory solid tumors and measurable disease per RECIST 1.1 were treated with increasing doses of troriluzole using a semi-Bayesian modified toxicity probability interval dose escalation procedure. Troriluzole monotherapy was orally self-administered for a 14-day lead-in period followed by continuation of troriluzole in combination with nivolumab 240 mg IV every 2 weeks. Endpoints included safety, pharmacokinetics (PK) and efficacy. RESULTS: We enrolled 14 patients with advanced solid tumors (melanoma = 3, NSCLC = 3, renal cell carcinoma = 2, bladder/urothelial = 2, ovarian cancer = 1, adenoid cystic carcinoma = 1, pleural mesothelial = 1, head and neck cancer = 1). Eleven patients had cancer progression on prior therapy with PD-1 or PD-L1 agent. Patients received troriluzole total daily doses from 140 to 560 mg (divided). The most common treatment-related adverse events (TRAE) occurring in ≥ 5 patients (> 35%) were transaminitis and increased lipase. DLT (dose-limiting toxicity) occurred in 3 patients: (1) grade 3 anorexia, (2) grade 3 fatigue and, (3) grade 3 atrial fibrillation. Six patients were treated at the MTD (maximum tolerated dose). No subjects discontinued treatment due to AEs. One response occurred (7%), which was a partial response in a subject who had PD-1 refractory disease. The 6-month PFS rate was 21%. PK data showed that the prodrug troriluzole was efficiently cleaved into riluzole by 2-h post-dosing in all dose cohorts tested. CONCLUSION: The combination of troriluzole and nivolumab was safe and well-tolerated. The MTD of troriluzole was determined to be 420 mg total daily dose. The observed antitumor activity, primarily disease stabilization, is of interest in patients with PD-1 resistant tumors. Trial Registration ClinicalTrials.gov Identifier NCT03229278. CI - © 2022. The Author(s). FAU - Silk, Ann W AU - Silk AW AD - Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Room LW503, Boston, MA, USA. ann_silk@dfci.harvard.edu. AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. ann_silk@dfci.harvard.edu. FAU - Saraiya, Biren AU - Saraiya B AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. FAU - Groisberg, Roman AU - Groisberg R AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. FAU - Chan, Nancy AU - Chan N AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. AD - Laura and Isaac Perlmutter Cancer Center and New York University Grossman School of Medicine, New York, NY, USA. FAU - Spencer, Kristen AU - Spencer K AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. FAU - Girda, Eugenia AU - Girda E AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. FAU - Shih, Weichung AU - Shih W AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. AD - Rutgers University School of Public Health, New Brunswick, NJ, USA. AD - Chi-Square Consulting LLC, Piscataway, NJ, USA. FAU - Palmeri, Marisa AU - Palmeri M AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. FAU - Saunders, Tracie AU - Saunders T AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. FAU - Berman, Robert M AU - Berman RM AD - Biohaven Pharmaceuticals, New Haven, CT, USA. FAU - Coric, Vlad AU - Coric V AD - Biohaven Pharmaceuticals, New Haven, CT, USA. FAU - Chen, Suzie AU - Chen S AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. AD - Rutgers University School of Pharmacy, Piscataway, NJ, USA. FAU - Zloza, Andrew AU - Zloza A AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. AD - Rush University Medical Center and Department of Internal Medicine, Rush Medical College, Chicago, IL, USA. FAU - Vieth, Joshua AU - Vieth J AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. AD - JDRF International, New York, NY, USA. FAU - Mehnert, Janice M AU - Mehnert JM AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. AD - Laura and Isaac Perlmutter Cancer Center and New York University Grossman School of Medicine, New York, NY, USA. FAU - Malhotra, Jyoti AU - Malhotra J AD - Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ, USA. LA - eng SI - ClinicalTrials.gov/NCT03229278 GR - R44 CA156781/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article DEP - 20220702 PL - England TA - Eur J Med Res JT - European journal of medical research JID - 9517857 RN - 0 (Enzyme Inhibitors) RN - 0 (Glutamates) RN - 31YO63LBSN (Nivolumab) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - 0 (Prodrugs) RN - 0 (Programmed Cell Death 1 Receptor) RN - 7LJ087RS6F (Riluzole) SB - IM MH - Bayes Theorem MH - *Carcinoma, Renal Cell MH - Enzyme Inhibitors MH - Glutamates MH - Humans MH - *Kidney Neoplasms MH - *Melanoma MH - Nivolumab MH - Phosphatidylinositol 3-Kinases MH - *Prodrugs MH - Programmed Cell Death 1 Receptor MH - Riluzole PMC - PMC9250196 OTO - NOTNLM OT - Glutamate OT - Immunotherapy resistance OT - Prodrug COIS- AWS has received research funding from Biohaven Pharmaceuticals to the institution. The remaining authors declare that they have no competing interests. EDAT- 2022/07/03 06:00 MHDA- 2022/07/07 06:00 PMCR- 2022/07/02 CRDT- 2022/07/02 23:27 PHST- 2022/05/23 00:00 [received] PHST- 2022/06/17 00:00 [accepted] PHST- 2022/07/02 23:27 [entrez] PHST- 2022/07/03 06:00 [pubmed] PHST- 2022/07/07 06:00 [medline] PHST- 2022/07/02 00:00 [pmc-release] AID - 10.1186/s40001-022-00732-w [pii] AID - 732 [pii] AID - 10.1186/s40001-022-00732-w [doi] PST - epublish SO - Eur J Med Res. 2022 Jul 2;27(1):107. doi: 10.1186/s40001-022-00732-w. PMID- 37925829 OWN - NLM STAT- MEDLINE DCOM- 20231204 LR - 20260127 IS - 1532-2157 (Electronic) IS - 0748-7983 (Linking) VI - 49 IP - 12 DP - 2023 Dec TI - RoboticAssisted (RATS) versus Video-Assisted (VATS) lobectomy: A monocentric prospective randomized trial. PG - 107256 LID - S0748-7983(23)00894-6 [pii] LID - 10.1016/j.ejso.2023.107256 [doi] AB - INTRODUCTION: The study aim is to compare Video-Assisted (VATS) and Robotic-Assisted (RATS) lobectomy in the effort to identify advantages and limits of robotic procedures considering the high costs and specific surgeon training. MATERIALS AND METHODS: This is a monocentric prospective randomized trial in which patients suitable for mini-invasive lobectomy were randomized 1:2 in two groups: Group A, RATS (25 patients), and Group B, VATS (50 patients). The two groups were compared in terms of perioperative and postoperative results with a mean follow up of 37.9 (±10.9) months. RESULTS: We observed a significant reduction of pleural effusion on day 1 (140 ml vs 214, p = 0.003) and day 2 (186 vs 321, p = 0.001) for group A. The Visual Analogue Scale (VAS) showed significantly lower pain in the 1st p.o. day in group A (0,92 vs 1,17, p = 0,005). Surgery time in Group B was significantly lower (160 min vs 180, p = 0.036), but had a higher onset of atrial fibrillation and other cardiac arrhythmias (0/25 vs 9/50, p = 0.038). The OS and DFS were similar between the two groups (95.5 % vs 93.1 %, and 95.5 % vs 89.7 %, respectively). Furthermore, no statistical difference in the evaluation of quality of life during follow-up was found. CONCLUSIONS: The RATS approach, although burdened by higher surgical costs, constitutes a valid alternative to VATS; as it determines a lower inflammatory insult, with a consequent reduction in pleural effusion, less post-operative pain and cardiological comorbidities for the patient, it can potentially determine the shortening in hospitalization. In addition, RATS allows accurate lymph node dissection, which permit to reach results that are not inferior to VATS in terms of long-term outcomes. CI - © 2023 Published by Elsevier Ltd. FAU - Catelli, C AU - Catelli C AD - Division of Thoracic Surgery, Department of Cardiothoracic Surgery and Vascular Sciences, Padua University Hospital, University of Padua, Via Giustiniani 1, Padua, PD, Italy. Electronic address: chiara.catelli1992@gmail.com. FAU - Corzani, R AU - Corzani R AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Zanfrini, E AU - Zanfrini E AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Franchi, F AU - Franchi F AD - Department of Medicine, Surgery and Neuroscience, Anesthesiology and Intensive Care, University Hospital of Siena, Siena, Italy. FAU - Ghisalberti, M AU - Ghisalberti M AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Ligabue, T AU - Ligabue T AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Meniconi, F AU - Meniconi F AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Monaci, N AU - Monaci N AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Galgano, A AU - Galgano A AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Mathieu, F AU - Mathieu F AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Addamo, E AU - Addamo E AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Sarnicola, N AU - Sarnicola N AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Fabiano, A AU - Fabiano A AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Paladini, P AU - Paladini P AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. FAU - Luzzi, L AU - Luzzi L AD - Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20231031 PL - England TA - Eur J Surg Oncol JT - European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology JID - 8504356 SB - IM MH - Humans MH - *Lung Neoplasms/surgery/pathology MH - Thoracic Surgery, Video-Assisted MH - Quality of Life MH - Prospective Studies MH - Pneumonectomy/methods MH - Postoperative Pain MH - *Pleural Effusion OTO - NOTNLM OT - Lobectomy OT - Lung cancer OT - Mini-invasive surgery OT - RATS OT - VATS COIS- Declaration of competing interest None. EDAT- 2023/11/06 00:41 MHDA- 2023/12/04 12:42 CRDT- 2023/11/05 18:06 PHST- 2023/07/17 00:00 [received] PHST- 2023/09/26 00:00 [revised] PHST- 2023/10/29 00:00 [accepted] PHST- 2023/12/04 12:42 [medline] PHST- 2023/11/06 00:41 [pubmed] PHST- 2023/11/05 18:06 [entrez] AID - S0748-7983(23)00894-6 [pii] AID - 10.1016/j.ejso.2023.107256 [doi] PST - ppublish SO - Eur J Surg Oncol. 2023 Dec;49(12):107256. doi: 10.1016/j.ejso.2023.107256. Epub 2023 Oct 31. PMID- 39305357 OWN - NLM STAT- MEDLINE DCOM- 20241209 LR - 20260417 IS - 2038-3312 (Electronic) IS - 2038-131X (Print) IS - 2038-131X (Linking) VI - 76 IP - 8 DP - 2024 Dec TI - Effect of intraoperative hyperthermic intrathoracic chemotherapy after pleurectomy decortication for treatment of malignant pleural mesothelioma: a comparative study. PG - 2893-2901 LID - 10.1007/s13304-024-01986-1 [doi] AB - Malignant pleural mesothelioma (MPM) is an aggressive malignancy with few long-term survivors. Despite the dismal prognosis, hyperthermic intrathoracic chemoperfusion (HITOC) was shown to improve survival in a selective group of patients. We analyzed the influence of HITOC following pleurectomy and decortication on postoperative morbidity and overall survival for patients suffering from localized mesothelioma. From March 2017 until August 2023, 55 patients with localized pleural mesothelioma underwent pleurectomy and decortication. Thirty patients performed only surgery while 25 consecutive patients had surgery followed by HITOC with cisplatin (125 mg/m(2)) infused for 70 min at a temp of 40-43 °C. We analyzed postoperative morbidity, HITOC-related complications, and the influence of HITOC on survival. The trial was registered on 19/08/2022 as NCT05508555. The HITOC group had a mean age of 53.1 ± 8.2 years while the surgery group (non-HITOC) had a mean age of 52.1 ± 8.6 years. The HITOC group had 17 (68%) men, whereas the surgery group included 18 (60%) males. The 30-day mortality in the HITOC group was 0% vs 1 case (3.3%) in the surgery group. HITOC-related transient complications occurred in 4/25 (16%) of the HITOC group (atrial fibrillation, renal impairment and transient hypotension). Progression-free survival in the HITOC group was 8 months (95% CI 4.3-11.6) vs 6 months (95% CI 2.5-9.9) in the surgery-only group (p = 0.79). The overall survival time in the HITOC group was 28 months (95% CI 21.5-34.5) vs 22 months (95% CI 17.5-26.5) in the surgery-only group (p = 0.75). Risk factors analysis for recurrence in the HITOC group confirmed a significant role for early stages (p = 0.03). HITOC following pleurectomy and decortication is a safe therapeutic option that may improve survival for selected patients with localized epithelial pleural mesothelioma. Patients with earlier-stage mesothelioma are more likely to benefit from radical surgery and HITOC. CI - © 2024. The Author(s). FAU - Elsayed, Hany Hasan AU - Elsayed HH AD - Thoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Hanyhassan77@hotmail.com. FAU - Sharkawy, Hazem Youssef AU - Sharkawy HY AD - Cardiothoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. FAU - Ahmed, Mohammed Attia AU - Ahmed MA AD - Cardiothoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. FAU - Abdel-Gayed, Mohammed AU - Abdel-Gayed M AD - Cardiothoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. FAU - Eldewer, Mostafa AU - Eldewer M AD - Cardiothoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. LA - eng PT - Clinical Trial PT - Comparative Study PT - Journal Article DEP - 20240921 PL - Italy TA - Updates Surg JT - Updates in surgery JID - 101539818 RN - 0 (Antineoplastic Agents) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Antineoplastic Agents/administration & dosage MH - *Cisplatin/administration & dosage MH - Combined Modality Therapy MH - *Hyperthermia, Induced/methods MH - Lung Neoplasms/surgery/therapy/mortality MH - Mesothelioma/surgery/therapy/mortality MH - *Mesothelioma, Malignant/surgery/therapy MH - Pleura/surgery MH - *Pleural Neoplasms/surgery/therapy/mortality MH - Survival Rate MH - Thoracic Surgical Procedures/methods MH - Treatment Outcome PMC - PMC11628442 OTO - NOTNLM OT - Chemotherapy OT - HITOC OT - Mesothelioma OT - Survival COIS- Declarations. Conflict of interest: None declared. Ethics approval and consent: Informed consent was obtained from all subjects and/or their legal guardian(s). Ethics approval from Ain shams university ethics committee on 1/8/2022 by the with IRB number: FWA 000017585. EDAT- 2024/09/21 21:47 MHDA- 2024/12/09 17:33 PMCR- 2024/09/21 CRDT- 2024/09/21 11:15 PHST- 2024/06/09 00:00 [received] PHST- 2024/08/30 00:00 [accepted] PHST- 2024/12/09 17:33 [medline] PHST- 2024/09/21 21:47 [pubmed] PHST- 2024/09/21 11:15 [entrez] PHST- 2024/09/21 00:00 [pmc-release] AID - 10.1007/s13304-024-01986-1 [pii] AID - 1986 [pii] AID - 10.1007/s13304-024-01986-1 [doi] PST - ppublish SO - Updates Surg. 2024 Dec;76(8):2893-2901. doi: 10.1007/s13304-024-01986-1. Epub 2024 Sep 21. PMID- 41356247 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20251208 LR - 20251210 IS - 1664-2295 (Print) IS - 1664-2295 (Electronic) IS - 1664-2295 (Linking) VI - 16 DP - 2025 TI - Effects of electroacupuncture on the incidence of postoperative supraventricular arrhythmia and sleep quality in patients undergoing thoracoscopic surgery: a randomized controlled trial. PG - 1580759 LID - 10.3389/fneur.2025.1580759 [doi] LID - 1580759 AB - BACKGROUND: Supraventricular arrhythmia and sleep disturbance frequently occur after thoracoscopic surgery for lung cancer. The present study is designed to evaluate the hypothesis that electroacupuncture is an effective treatment of supraventricular arrhythmia and sleep disorders following thoracoscopic lung cancer surgery. METHODS: Adult patients scheduled for single-port thoracoscopic lung cancer surgery were randomly assigned to the Electroacupuncture (EA) and control groups. The primary outcome of this trial was the incidence of new-onset supraventricular tachycardia (SVT) including atrial flutter, atrial fibrillation, atrial tachycardia and atrioventricular junctional tachycardia during the first 24 h after surgery. RESULTS: The authors analyzed 77 patients (EA, 38; control, 39). The incidence of new-onset SVT was significantly lower in the EA group compared with the control group during the first 24 postoperative hours; 4 (10.5%) vs. 13 (33.3%), respectively, p = 0.02. Patients in the EA group had longer total sleep time (119.0 vs. 209.5, p = 0.02), longer duration of nonrapid eye movement sleep on the first postoperative night (p < 0.05). The awake time was significantly shorter compared with the control group (134.5.0 vs. 225.0, p = 0.01). Dosage of remifentanil and incidence of intraoperative hypotension were significantly reduced in the EA group (911.1 vs. 1095.9, p = 0.01). However, VAS scores after surgery did not differ between groups. In all the patients recruited, adverse effects such as redness, swelling and inflammatory reactions were not observed at the acupuncture site. CONCLUSION: The results of this study suggest that perioperative electroacupuncture treatment could be a promising strategy to reduce the incidence of new-onset SVT and improve sleep disturbance in patients undergoing thoracoscopic surgery for lung cancer. This potential impact on future treatments should inspire hope and optimism in the medical community. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/indexEN.html, identifier ChiCTR2300077984. CI - Copyright © 2025 Liu, Ding, Ma, Wang, Song, Cao and Wu. FAU - Liu, Jie AU - Liu J AD - First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China. FAU - Ding, Longfei AU - Ding L AD - First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Ma, Wuhua AU - Ma W AD - Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China. FAU - Wang, Jiyong AU - Wang J AD - Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China. AD - Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Song, Xiuling AU - Song X AD - Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China. FAU - Cao, Ying AU - Cao Y AD - NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. FAU - Wu, Caineng AU - Wu C AD - Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20251120 PL - Switzerland TA - Front Neurol JT - Frontiers in neurology JID - 101546899 PMC - PMC12676905 OTO - NOTNLM OT - electroacupuncture OT - lung cancer OT - sleep disturbance OT - supraventricular tachycardia OT - thoracoscopic surgery COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/12/08 13:19 MHDA- 2025/12/08 13:20 PMCR- 2025/11/20 CRDT- 2025/12/08 06:09 PHST- 2025/02/21 00:00 [received] PHST- 2025/07/11 00:00 [accepted] PHST- 2025/12/08 13:20 [medline] PHST- 2025/12/08 13:19 [pubmed] PHST- 2025/12/08 06:09 [entrez] PHST- 2025/11/20 00:00 [pmc-release] AID - 10.3389/fneur.2025.1580759 [doi] PST - epublish SO - Front Neurol. 2025 Nov 20;16:1580759. doi: 10.3389/fneur.2025.1580759. eCollection 2025. PMID- 41320620 OWN - NLM STAT- MEDLINE DCOM- 20260319 LR - 20260319 IS - 1532-8422 (Electronic) IS - 1053-0770 (Linking) VI - 40 IP - 4 DP - 2026 Apr TI - The Effects of Nonintubated Anesthesia onNeutrophil-to-Lymphocyte Ratio and Tumor Markers Among Patients Undergoing Thoracoscopic Lung Resection: A Randomized Controlled Trial. PG - 1205-1213 LID - S1053-0770(25)01112-7 [pii] LID - 10.1053/j.jvca.2025.10.046 [doi] AB - OBJECTIVES: To assess the influence of nonintubated anesthesia on the neutrophil-to-lymphocyte ratio (NLR) and tumor marker level in patients undergoing thoracoscopic resection of lung cancer. DESIGN: A prospective, randomized, controlled trial. SETTING: A tertiary medical institution. PARTICIPANTS: Fifty-eight patients underwent video-assisted thoracoscopic lung surgery. INTERVENTION: Patients were randomly divided into the nonintubated video-assisted thoracic surgery group (NIVATS group, n = 29) and the traditional video-assisted thoracic surgery group (VATS group, n = 29) in a 1:1 allocation ratio. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the NLR in peripheral blood, measured 24 hours postoperatively. Secondary outcomes included a range of peripheral blood tumor markers (derived neutrophil to lymphocyte ratio/lactate dehydrogenase (dNLR/LDH), citrullinated histone H3, matrix metalloproteinase 9, programmed death ligand 1, systemic inflammatory immune index, vascular endothelial growth factor) at the same time point, as well as intraoperative minimum blood oxygen saturation, thoracotomy conversion rate, blood loss, recovery metrics (chest tube duration, discharge time), and postoperative complications (chest air leaks, pneumonia, acute respiratory distress syndrome incidence, new-onset atrial fibrillation, hoarseness, sore throat, dysphonia). Notably, 24 hours after surgery, the NLR and neutrophil percentage were significantly lower in the NIVATS group compared to the VATS group (p = 0.031, p = 0.006), accompanied by a higher lymphocyte percentage (p = 0.013). However, enzyme-linked immunosorbent assay results for peripheral blood tumor markers showed no significant differences between the 2 groups, both before and 24 hours after surgery. CONCLUSIONS: Compared to the VATS group, the use of nonintubated anesthesia resulted in less postoperative NLR elevation but had no significant impact on the levels of tumor biomarkers. CI - Copyright © 2025 Elsevier Inc. All rights reserved. FAU - Liu, Zhi-Li AU - Liu ZL AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou,Jiangsu Province, China; Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Zhao, Zhen-Zhen AU - Zhao ZZ AD - Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Xiao, Ya-Qin AU - Xiao YQ AD - Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Zhang, Ying AU - Zhang Y AD - Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Ge, Ling-Ling AU - Ge LL AD - Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Luo, Jie AU - Luo J AD - Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Zhou, Yan AU - Zhou Y AD - Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Bao, Rui AU - Bao R AD - Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Deng, Xiao-Ming AU - Deng XM AD - Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Wang, Jia-Feng AU - Wang JF AD - Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. Electronic address: jfwang@smmu.edu.cn. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20251101 PL - United States TA - J Cardiothorac Vasc Anesth JT - Journal of cardiothoracic and vascular anesthesia JID - 9110208 RN - 0 (Biomarkers, Tumor) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Neutrophils/metabolism/drug effects MH - *Thoracic Surgery, Video-Assisted/methods MH - *Lymphocytes/metabolism/drug effects MH - Aged MH - Prospective Studies MH - *Lung Neoplasms/surgery/blood MH - *Biomarkers, Tumor/blood MH - *Anesthesia/methods MH - *Pneumonectomy/methods OTO - NOTNLM OT - neutrophil-to-lymphocyte ratio OT - nonintubated anesthesia OT - tumor markers OT - video-assisted thoracoscopic surgery COIS- Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/12/01 00:30 MHDA- 2026/03/20 00:59 CRDT- 2025/11/30 21:53 PHST- 2025/06/26 00:00 [received] PHST- 2025/10/21 00:00 [revised] PHST- 2025/10/28 00:00 [accepted] PHST- 2026/03/20 00:59 [medline] PHST- 2025/12/01 00:30 [pubmed] PHST- 2025/11/30 21:53 [entrez] AID - S1053-0770(25)01112-7 [pii] AID - 10.1053/j.jvca.2025.10.046 [doi] PST - ppublish SO - J Cardiothorac Vasc Anesth. 2026 Apr;40(4):1205-1213. doi: 10.1053/j.jvca.2025.10.046. Epub 2025 Nov 1.