Major pulmonary resection after neoadjuvant chemotherapy or chemoradiation in potentially resectable stage III non-small cell lung carcinoma.

The aim of this study was to identify predictors of postoperative outcome and survival of locally advanced non-small cell lung carcinoma (NSCLC) resections after neoadjuvant chemotherapy or chemoradiation. Medical records of all patients with clinical stage III potentially resectable NSCLC initially treated by neoadjuvant chemotherapy or chemoradiation followed by major pulmonary resections were retrieved from the databases of four Israeli Medical Centers between 1999 to 2019. The 124 suitable patients included, 86 males (69.4%) and 38 females (30.6%), with an average age of 64.2 years (range 37-82) and an average hospital stay of 12.6 days (range 5-123). Complete resection was achieved in 92.7% of the patients, while complete pathologic response was achieved in 35.5%. The overall readmission rate was 16.1%. The overall 5-year survival rate was 47.9%. One patient (0.8%) had local recurrence. Postoperative complications were reported in 49.2% of the patients, mainly atrial fibrillation (15.9%) and pneumonia (13.7%), empyema (10.3%), and early bronchopleural fistula (7.3%). The early in-hospital mortality rate was 6.5%, and the 6-month mortality rate was 5.6%. Pre-neoadjuvant bulky mediastinal disease (lymph nodes > 20 mm) (p = 0.034), persistent postoperative N2 disease (p = 0.016), R1 resection (p = 0.027), preoperative N2 multistation disease (p = 0.053) and postoperative stage IIIA (p = 0.001) emerged as negative predictive factors for survival. Our findings demonstrate that neoadjuvant chemotherapy or chemoradiation in locally advanced potentially resectable NSCLC, followed by major pulmonary resection, is a beneficial approach in selected cases.

Effectiveness and safety of nivolumab in advanced non-small cell lung cancer: The real-life data.

OBJECTIVES: Nivolumab has recently received regulatory approval as a 2nd-line treatment of non-small cell lung cancer (NSCLC). The data regarding its effectiveness and safety in real life setting is lacking. MATERIALS AND METHODS: 260 consecutive patients with advanced NSCLC treated with nivolumab at five Israeli cancer centers between January 2015 and March 2016 were evaluated for overall survival (OS) and toxicity. OS was analyzed by the Cox proportional-hazards regression model. Overall response rate (ORR) and progression-free survival (PFS) were assessed in 49 patients using RECIST, v.1.1. RESULTS: Median age was 67y (41-99); males 68%; smokers 76%; ECOG PS ≥2 46%; non-squamous/squamous/other/NR 70%/23%/6%/1%; brain metastases 21%; liver metastases 21%; treatment line: 1st/2nd/3rd+-line/NR 6%/64%/26%/4%. With median survival follow-up of 18.5 months (range, 12.0-26.9), 155 (60%) patients died; median OS comprised 5.9 months (95% CI 4.7-7.4). In univariate and multivariate analysis, the only variable which significantly correlated with OS was ECOG PS. Median OS of patients with ECOG PS 0/1 and ECOG PS ≥2 comprised 9.5 months (95% CI, 6.7-NR) and 3.5 months (95% CI, 2.6-4.5), respectively. For 49 patients evaluable for response (median follow-up of 8.4 months (range, 2-16.8), ORR was 35%, median PFS was 2.8 months (95% CI, 1.8-7.7), incidence of pseudo-progression was 9%. The nivolumab safety profile was in accordance with the literature data, except for febrile neutropenia and pericarditis (observed in 1 case each). CONCLUSION: In real life setting, the effectiveness of nivolumab is reasonable yet less prominent than it has been demonstrated in clinical trials. ECOG PS ≥2 is associated with poor prognosis.

Morbidity and mortality after major pulmonary resections in patients with locally advanced stage IIIA non-small cell lung carcinoma who underwent induction therapy.

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.

EGFR mutation testing practice in advanced non-small cell lung cancer.

PURPOSE: Testing tumor samples for the presence of a mutation in the epithelial growth factor receptor (EGFR) gene is recommended for advanced non-squamous non-small cell lung cancer (NSCLC) patients. We aimed to collect data about common practice among Medical Oncologists treating lung cancer patients, regarding EGFR mutation testing in advanced NSCLC patients. METHODS: An internet-based survey was conducted among members of the Israeli Society for Clinical Oncology and Radiotherapy involved in the treatment of lung cancer patients. RESULTS: 24 Oncologists participated in the survey. The participants encompass the Oncologists treating most of the lung cancer patients in Israel. 79% of them use EGFR testing routinely for all advanced NSCLC patients. Opinions were split regarding the preferable biopsy site for EGFR testing material. 60% of participants recommend waiting for EGFR test results prior to initiation of first-line therapy. CONCLUSIONS: EGFR testing is requested in Israel routinely by most treating Oncologists for all advanced NSCLC patients, regardless of histology. In most cases, systemic treatment is deferred until the results of this test are received.

Lobectomy for non-small cell lung cancer: differences in morbidity and mortality between thoracotomy and thoracoscopy.

OBJECTIVE: Until the last decade, lobectomy by thoracotomy (TL) was the "gold standard" for treatment of patients with operable lung carcinoma. Today, video-assisted thoracic surgery lobectomy (VATS-L) has become accepted as a safe and effective procedure to treat early-stage lung cancer. We analyzed and compared postoperative complications, hospital stay, morbidity, and mortality after TL and VATS-L in patients with non-small cell lung carcinoma (NSCLC). METHODS: Between February 1998 and December 2007, we performed 326 TLs in patients with NSCLC. From December 2007, VATS-L was preferentially performed, and 63 cases of NSCLC patients underwent surgery using this method. Comorbidities were scaled according to the Charlson Comorbidity Index, and propensity scores between the TL and VATS-L patients were compared. RESULTS: Postoperative complications occurred in 142 TL patients (43.6%) and 17 VATS-L patients (27%), with 3.6% and 1.6% intrahospital mortality, respectively. There were no significant differences between the TL and VATS-L patients in Charlson Comorbidity Index or propensity scores, which led us to compare complications between TL and VATS-L groups and discovered that VATS-L patients had a shorter median length of stay (P < 0.001) and VATS-L was associated with a reduction in the occurrence of atrial fibrillation (P = 0.011) and offered benefits for patients with more significant comorbidities, for example, congestive heart failure patients (P = 0.042). CONCLUSIONS: Our clinical impression is that VATS-L offers advantages over TL in terms of lower morbidity, fewer and less serious complications, shorter hospital stays, and the possibility to operate on patients with more comorbidities.

Symptom improvement in lung cancer patients treated with erlotinib: quality of life analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21.

PURPOSE: This report describes the quality of life (QOL) findings of a randomized placebo controlled study of erlotinib, an epidermal growth factor receptor inhibitor, in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This double-blind phase III trial randomly assigned 731 patients with NSCLC who had progressed after prior chemotherapy to erlotinib 150 mg daily or placebo, with survival as the primary study outcome. QOL was assessed by European Organisation for Research and Treatment of Cancer QLQ-C30 and the lung cancer module QLQ-LC13. The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms: cough, dyspnea, and pain. RESULTS: Survival was significantly longer (hazard ratio, 0.70; P < .0001) in the erlotinib arm. Compliance with QOL was 87% at baseline and more than 70% during treatment. Patients receiving erlotinib had significantly longer median time to deterioration for all three symptoms (4.9 v 3.7 months for cough [P = .04]; 4.7 v 2.9 months for dyspnea [P = .04], and 2.8 v 1.9 months for pain [P = .03]). QOL response analyses showed that 44%, 34%, and 42% of patients receiving erlotinib had improvement in these three symptoms, respectively. This was accompanied by a significant improvement in the physical function (31% erlotinib v 19% placebo, P = .01), and global QOL (35% v 26%, P < .0001). Patients with complete or partial response were more likely to have improvement in the QOL response than patients with stable or progressive disease (P < .01). CONCLUSION: Erlotinib not only improves survival in previously treated patients with NSCLC, but also improves tumor-related symptoms and important aspects of QOL.

Advanced non-small cell lung cancer: induction chemotherapy and chemoradiation before operation.

BACKGROUND: Induction chemotherapy before operation is beneficial for patients with advanced locoregional non-small cell lung cancer. However, no optimal regimen has been established. This study assesses feasibility, response, resectability, and survival of chemotherapy followed by chemoradiation before operation in patients with non-small cell lung cancer. METHODS: Fifty-seven stage IIIA and selected IIIB patients with non-small cell lung cancer received 2/3 cycles of cisplatin and oral etoposide, followed in 3/4 weeks by chemoradiation with daily cisplatin before each radiation fraction. Patients achieving a resectable status underwent operation. RESULTS: Response to induction treatment was documented in 73%; 69% achieved a resectable status and 53% underwent operation. Median survival was 16 months. The 1-, 2-, and 3-year survival rates were 65%, 35% and 22%, respectively. There was no difference in survival between stage IIIA and IIIB disease. Myelotoxicity was moderate to severe (grade III/IV in 61% of patients). Three patients died of late complications of pneumonectomy. CONCLUSIONS: Our presurgery chemotherapy and chemoradiation protocol yields high response and resectability rates, with moderate to severe myelotoxicity. Pneumonectomy is associated with a relatively high rate of late complications.