Study objective-To demonstrate the efficacy, safety, and appropriate mode of instillation of talc for sclerosis in treatment of malignant pleural effusions (MPEs).Design-A prospective, randomized trial was designed to compare thoracoscopy with talc insufflation (TTI) to thoracostomy and talc slurry (TS) for patients with documented MPE.Measurements-The primary end point was 30-day freedom from radiographic MPE recurrence among surviving patients whose lungs initially re-expanded > 90%. Morbidity, mortality, and quality of life were also assessed.Results-Of 501 patients registered, those eligible were randomized to TTI (n = 242) or TS (n = 240). Patient demographics and primary malignancies were similar between study arms. Overall, there was no difference between study arms in the percentage of patients with successful 30-day outcomes (TTI, 78%; TS, 71%). However, the subgroup of patients with primary lung or breast cancer had higher success with TTI than with TS (82% vs 67%). Common morbidity included fever, dyspnea, and pain. Treatment-related mortality occurred in nine TTI patients and seven TS patients. Respiratory complications were more common following TTI than TS (14% vs 6%).Correspondence to: Carolyn Dresler, MD, MPA, Head, Tobacco Unit, International Agency for Research on Cancer, Lyon, France; Carolyn_dresler@ksg03.harvard.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptRespiratory failure was observed in 4% of TS patients and 8% of TTI patients, accounting for five toxic deaths and six toxic deaths, respectively. Quality-of-life measurement demonstrated less fatigue with TTI than TS. Patient ratings of comfort and safety were also higher for TTI, but there were no differences on perceived value or convenience of the procedures. Since that time, a significant number of single institution reports have been published, primarily using thorascopically insufflated talc. However, a growing number of authors have advocated talc slurry via a percutaneously placed chest tube as a simpler and equally effective method for control of MPE with minimal short-term morbidity. However, several reports 10,11 of serious respiratory complications with talc have also been published. Conclusions-BothThe objectives of the current trial Cooperative Groups Cancer and Leukemia Group B (CALGB) 9334 compare tube thoracostomy with talc slurry (TS) to surgical thoracoscopy with talc insufflation (TTI), and assesses their efficacy at 30 days, in addition to the safety and associated quality of life in a randomized multicenter trial. Portions of this work have been presented in abstract form. 12 Materials and MethodsThis was an intergroup cooperative trial led by the CALGB and monitored semiannually by its Data and Safety Monitoring Board, with participation by the Radiation Therapy Oncology Group, the Eastern Cooperative Oncology Group (ECOG), and the North Central Cooperative Oncology Group, encompassing both private and teaching hospitals. Credentialing of participating surgeon...

Sublobar resection and lobectomy have equivalent survival for patients with clinical stage IA non-small cell lung cancer in the context of computed tomography screening for lung cancer.

These results indicate that examining a greater number of lymph nodes in patients with stage I NSCLC treated with resection increases the likelihood of proper staging and affects patient outcome. Such information is important not only for therapy and prognosis of individuals but also for identifying those who may benefit from adjuvant therapy.

Objective The recent increased detection of small-sized peripheral non-small cell lung cancer (NSCLC) has renewed interest in sub-lobar resection in-lieu of lobectomy, the traditional standard of care. CALGB/ALLIANCE 140503 is a multicenter international non-inferiority phase III trial in which NSCLC patients clinically staged as T1aN0 were randomly assigned to lobar or sub-lobar resection. The primary endpoint is disease-free survival. We conducted an exploratory comparative analysis of the perioperative mortality and morbidity associated with both arms of the trial. Patients and Methods Between June 15/2007 and March 13/2017, 697 patients with peripheral NSCLC clinically staged as T1aN0 were intraoperatively randomized (after pathological confirmation of absence of nodal metastases in major hilar and mediastinal nodes) to either lobar (Arm A: 357) or sublobar resection (Arm B: 340; 58% wedge resections). Randomization assignment was based on a stratified permuted-block randomization scheme without concealment. Randomized was stratified according to radiographic tumor size (< 1 cm, 1–1.5 cm, and > 1.5– 2.0 cm), histology (squamous carcinoma, adenocarcinoma and other) and smoking status (never, former, current). The assignment was not concealed. Perioperative mortality was defined as death from any cause within 30 and 90 days of surgical intervention and was calculated on all randomized patients. Morbidity was graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). All analyses were done on an intention to treat basis. Results Overall 30 and 90- day mortality for 697 randomized patients were 0.86% (n=6) and 1.4% (n=10). Thirty and 90-day mortality were 1.1% (n=4) and 1.7% (n=6) after lobar resection and 0.6% (n=2) and 1.2% (n=4) after sub-lobar resection yielding a difference between arms of 0.5% (95%CI: −1.1,2.3) and 0.5% (95%CI: −1.5,2.6), respectively, without reaching statistical significance. No complications were observed in 47% of patients (Arm A: 46%, Arm B: 49%). Grade 3/4/5 AEs occurred in 15.2% in Arm A and 14.2% in Arm B. There were no differences between the two arms in cardiac or pulmonary complications. Grade 3 hemorrhage (requiring transfusion) occurred in 6 patients (1.6%) in Arm A and 8 patients (2.3%) in Arm B. Prolonged air leak occurred in 9 patients (2.5%) in Arm A and 2 patients (0.6%) in Arm B. Conclusions In this large, multicenter randomized international trial, post-hoc analysis showed no significant differences in perioperative mortality and morbidity between lobar and sub-lobar resection in physically and functionally fit patients with clinical T1aN0 NSCLC. These data may impact the daily choices made by patients and their physicians in determining the optimal treatment approach for stage I lung cancer. Trial registration This trial is registered as an international standard randomized trial with ClinicalTrials.gov Identifier: NCT00499330 Role of funding source The Cancer Therapy Evaluation Program of the National Cancer Institute (CTEP) approved the t...

Background Identifying strong markers of prognosis is critical to optimize treatment and survival outcomes in patients with non-small cell lung cancer (NSCLC). We investigated the prognostic significance of preoperative cardiorespiratory fitness (VO2peak) among operable candidates with NSCLC. Methods Using a prospective design, 398 patients with potentially resectable NSCLC enrolled in Cancer and Leukemia Group B (CALGB) 9238 were recruited between 1993 and 1998. Participants performed a cardiopulmonary exercise test to assess VO2peak and were observed for death or until June 2008. Cox proportional models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO2peak tertiles (<0.96 / 0.96–1.29 / >1.29 L.min−1) with adjustment for age, gender, performance status. Results Median follow-up was 30.8 months, 294 deaths were reported during this period. Compared with patients achieving a VO2peak <0.96 L.min−1, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% CI, 0.46 to 0.88) for a VO2peak of 0.96–1.29 L.min−1, and 0.56 (95% CI, 0.39 to 0.80) for a VO2peak of >1.29 L.min−1 (ptrend= 0.0037). The corresponding HRs for resected patients were 0.66 (95% CI, 0.46 to 0.95) and 0.59 (95% CI, 0.40 to 0.89) relative to the lowest VO2peak category (ptrend=0.0247), respectively. For non-resected patients, the HRs were 0.78 (95% CI, 0.34 to 1.79) and 0.39 (95% CI, 0.16 to 0.94) relative to the lowest category (ptrend=0.0278). Conclusions VO2peak is a strong independent predictor of survival in NSCLC that may complement traditional markers of prognosis to improve risk stratification and prognostication.

p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.

Background The short term superiority of video-assisted thoracoscopic surgery (VATS) lobectomy compared to open lobectomy for early stage lung cancer has been suggested by single institution studies. Lack of equipoise limits the feasibility of a randomized study to confirm this. The hypothesis of this study (CALGB 31001) was that VATS lobectomy results in shorter length of hospital stay and fewer complications compared to open lobectomy in stages I and II non-small cell lung cancer in a multi-institutional setting. Methods 519 patients whose tumors had been collected as part of CALGB 140202 (lung cancer tissue bank) were eligible. Propensity-scoring using age, race, gender, performance status, comorbidities, histology, tumor stage and size as independent variables was used to create a 1:1 matched group of 175 pairs of patients. McNemar’s test for binary and Wilcoxon signed-rank test for continuous variables were used to assess differences in length of hospital stay, complications, and discharge dispositions between the groups. Comparison of disease-free and overall survival between the two approaches was done using the log-rank test. P-values < 0.05 were considered significant. Results The matched data on length of hospital stay, complications and discharge dispositions significantly favored the VATS group. There was no statistically significant difference in survival between the two approaches. Conclusion This multi-institutional study supports the assertion that thoracoscopic lobectomy results in shorter hospital length of stay, fewer peri-operative complications and greater likelihood of independent home discharge compared to open lobectomy for early stage lung cancer. Survival was comparable between the two groups.

Our data provide multicenter validation for the use of exercise Vo2 for preoperative assessment of lung cancer patients, and we encourage an aggressive approach when evaluating these patients for surgery.