Structured Abstract Objective To examine the association between extent of surgery and overall survival (OS) in a large contemporary cohort of patients with papillary thyroid cancer (PTC). Background Guidelines recommend total thyroidectomy for PTC tumors >1 cm based on older data demonstrating an OS advantage for total thyroidectomy over lobectomy. Methods Adult patients with PTC tumors 1.0–4.0 cm undergoing thyroidectomy in the National Cancer Database, 1998–2006, were included. Cox proportional hazards models were applied to measure the association between extent of surgery and OS while adjusting for patient demographic and clinical factors, including comorbidities, extrathyroidal extension, multifocality, nodal and distant metastases, and radioiodine treatment. Results Among 61,775 PTC patients, 54,926 underwent total thyroidectomy and 6,849 lobectomy. Compared to lobectomy, total thyroidectomy patients had more nodal (7% vs. 27%), extrathyroidal (5% vs.16%), and multifocal disease (29% vs. 44%), all p<0.001. Median follow-up was 82 months (60–179 months). After multivariable adjustment, OS was similar for total thyroidectomy vs. lobectomy in patients with tumors 1.0–4.0 cm (HR 0.96 [0.84–1.09], p=0.54), and when stratified by tumor size: 1.0–2.0 cm (HR 1.05 [0.88–1.26], p=0.61) and 2.1–4.0 cm (HR 0.89 [0.73–1.07], p=0.21). Older age, male gender, black race, lower income, tumor size, and presence of nodal or distant metastases were independently associated with compromised survival (p<0.0001). Conclusions Current guidelines suggest total thyroidectomy for PTC tumors >1 cm. However, we did not observe a survival advantage associated with total thyroidectomy compared to lobectomy. These findings call into question whether tumor size should be an absolute indication for total thyroidectomy.

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...

Purpose Erlotinib is clinically effective in patients with non–small-cell lung cancer (NSCLC) who have adenocarcinoma, are never or limited former smokers, or have EGFR mutant tumors. We investigated the efficacy of erlotinib alone or in combination with chemotherapy in patients with these characteristics. Patients and Methods Patients with advanced NSCLC (adenocarcinoma) who were epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy naive never or light former smokers (smokers of > 100 cigarettes and ≤ 10 pack years and quit ≥ 1 year ago) were randomly assigned to continuous erlotinib or in combination with carboplatin and paclitaxel (ECP) for six cycles followed by erlotinib alone. The primary end point was progression-free survival (PFS). Tissue collection was mandatory. Results PFS was similar (5.0 v 6.6 months; P = .1988) in patients randomly assigned to erlotinib alone (arm A; n = 81) or to ECP (arm B; n = 100). EGFR mutation analysis was possible in 91% (164 of 181) of patients, and EGFR mutations were detected in 40% (51 of 128) of never smokers and in 42% (15 of 36) of light former smokers. In arm A, response rate (70% v 9%), PFS (14.1 v 2.6 months), and overall survival (OS; 31.3 v 18.1 month) favored EGFR-mutant patients. In arm B, response rate (73% v 30%), PFS (17.2 v 4.8 months), and OS (38.1 v 14.4 months) favored EGFR-mutant patients. Incidence of grades 3 to 4 hematologic (2% v 49%; P < .001) and nonhematologic (24% v 52%; P < .001) toxicity was greater in patients treated with ECP. Conclusion Erlotinib and erlotinib plus chemotherapy have similar efficacy in clinically selected populations of patients with advanced NSCLC. EGFR mutations identify patients most likely to benefit.

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.

Arm A reached the primary end point with an estimated MST longer than 18 months and will be compared with a standard dose of TRT in a planned randomized phase III trial in the United States cooperative groups.

The combination of sorafenib and IFN-alpha-2b has substantial activity in treatment-naïve and IL-2-treated patients with RCC. The toxicity exceeded that of either drug alone, but dose reductions and breaks between cycles allowed for chronic therapy. A larger, randomized trial would determine whether there is any advantage to this regimen compared with sorafenib alone.

Background-Premenopausal women treated for early stage breast cancer (ESBC) are at risk for chemotherapy-related amenorrhea (CRA). Prospectively-validated, predictive markers of CRA are needed.

Survival of poor-risk patients with wild type or mutated EGFR receiving sequential CRT with gefitinib was promising. Survival for good-risk patients receiving concurrent CRT plus gefitinib was disappointing even for tumors with activating EGFR mutations.