Pamela Samson

Lobectomy versus stereotactic body radiotherapy for stage I non–small cell lung cancer: Post hoc analysis dressed up as level-1 evidence?

From the Division of Cardiothoracic Surgery, Washington University in St Louis, St Louis, Mo. Disclosures: Dr Meyers served on the Data Safety and Monitoring Board of the STARS trial that is the subject of the submitted editorial. As a member of the DSMB, DrMeyers was compensated by Accuray, the sponsor of the trial. Dr Meyers also reports consulting and lecture fees from Varian. Received for publication June 18, 2015; accepted for publication June 23, 2015. Address for reprints: Bryan F. Meyers, MD, MPH, Washington University in St Louis, Queeny Tower Ste 3108, One Barnes Jewish Hospital, St Louis, MO 63110-1013 (E-mail: meyersb@wustl.edu). J Thorac Cardiovasc Surg 2015;-:1-4 0022-5223/

Treatment of stage I non–small cell lung cancer: What's trending?

36.00 Copyright 2015 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2015.06.086 Trial Name An cipated enrollment Number actually accrued An cipated events required for analysis Actual events observed Phase III Study to Compare Cyberknife® Stereotac c Radiotherapy with Surgical Resec on in Stage I NSCLC (STARS) 1,030 36 Not stated 5

Adjuvant Chemotherapy for Patients with T2N0M0 NSCLC

Objectives: Stage I non–small cell lung cancer traditionally is treated with lobectomy. Sublobar resection and stereotactic body radiation therapy provide alternative treatments for higher‐risk groups. The purpose of this study was to determine the national treatment trends for stage I lung cancer. Methods: The National Cancer Database was queried for patients with clinical stage I non–small cell lung cancer between 1998 and 2012. Patients were compared across treatment groups, and trends in treatment and disease were evaluated over the 15‐year time period. Results: The National Cancer Database contained 369,931 patients with clinical stage I non–small cell lung cancer. After removing patients who received chemotherapy as a first course of treatment and patients with pathologic stage IV, 357,490 patients were analyzed. The first recorded cases of stereotactic body radiation therapy are in 2003 and rapidly increased to 6.6% (2063) of all patients treated in 2012. The number of diagnoses of stage I non–small cell lung cancer steadily increased over the 15‐year period, whereas the rate of lobectomy decreased from 55% in 1998 to 50% in 2012 (P < .001). Most of the decrease in lobectomy can be explained by the increase in the rate of sublobar resection from 12% to 17% (P < .001). The percentage of untreated patients remained stable at approximately 7% (P = .283). Conclusions: Although the number of stage I non–small cell lung cancer cases continues to increase, lobectomy rates are decreasing while sublobar resection and stereotactic body radiation therapy rates are increasing. Although the increasing popularity of alternative therapies to lobectomy for treatment of stage I non–small cell lung cancer should allow more patients to undergo treatment, we did not observe this trend in the data.

Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients

Background: Adjuvant chemotherapy improves survival in patients with completely resected stage II and III NSCLC. However, its role in patients with stage IB NSCLC disease remains unclear. We evaluated the role of adjuvant chemotherapy in a large data set of patients with completely resected T2N0M0 NSCLC. Methods: Patients with pathologic stage T2N0M0 NSCLC who underwent complete (R0) resection between 2004 and 2011 were identified from the National Cancer Data Base and classified into four groups based on tumor size: 3.1 to 3.9 cm, 4 to 4.9 cm, 5 to 5.9 cm, and 6 to 7 cm. Patients who died within 1 month after their operation were excluded. Survival curves were estimated by the Kaplan‐Meier product‐limit method and compared by log‐rank test. Results: Among the 25,267 patients who met the inclusion criteria, there were 4996 (19.7%) who received adjuvant chemotherapy. Adjuvant chemotherapy was associated with improved median and 5‐year overall survival compared with observation for all tumor size groups. In patients with T2 tumors smaller than 4 cm, adjuvant chemotherapy was associated with improved median and 5‐year overall survival in univariate (101.6 versus 68.2 months [67% versus 55%], hazard ratio [HR] = 0.66, 95% confidence interval [CI]: 0.61–0.72, p < 0.0001) and multivariable analysis (HR = 0.77, 95% CI: 0.70–0.83, p < 0.001) as well as propensity‐matched score (101.6 versus 78.9 months [68% versus 60%], HR = 0.75, 95% CI: 0.70–0.86; p < 0.0001). Conclusions: In patients with completely resected T2N0M0, adjuvant chemotherapy is associated with improved survival in all tumor size groups. The benefit in patients with tumors smaller than 4 cm strongly suggests a role for chemotherapy in this patient population and counters its current status as an exclusion criteria for adjuvant trials.

Extent of Lymphadenectomy Is Associated With Improved Overall Survival After Esophagectomy With or Without Induction Therapy

Objectives: The aim of this study was to evaluate differences in pathologic complete response (pCR) rates and overall survival among patients receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy for locally advanced esophageal cancer. Methods: Patients with esophageal cancer receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy were identified using the National Cancer Database. Univariate analysis compared patient, tumor, and postoperative outcome characteristics. Logistic regression was performed to identify variables associated with achieving pCR. Kaplan‐Meier analysis was performed to compare overall median survival by neoadjuvant therapy type and pCR status. Finally, a Cox proportional hazards model was fitted to identify variables associated with increased mortality hazard. Results: From 2006 to 2012, a total of 916 of 7338 of patients (12.5%) received neoadjuvant chemotherapy whereas 6422 (87.5%) received neoadjuvant chemoradiation. Patients who received neoadjuvant chemoradiation were more likely to achieve a pCR (17.2% versus 6.4%, p < 0.001) and less likely to have positive margins (5.6% versus 11.5%, p < 0.001) than were patients who received neoadjuvant chemotherapy, with no difference in 30‐ or 90‐day mortality. Achieving a pCR was associated with improved overall median survival (59.5 ± 4.0 months versus 30.1 ± 0.76 months for those with persistent disease, p < 0.001). On logistic regression, neoadjuvant chemoradiation therapy was independently associated with achieving a pCR (OR = 2.75, 95% confidence interval: 2.01–3.77, p < 0.001). Despite improvement in the pCR rate with neoadjuvant chemoradiation, neoadjuvant therapy type was not independently associated with long‐term survival (hazard ratio = 1.12; 95% confidence interval: 0.97–1.30, p = 0.12). Conclusions: Although neoadjuvant chemoradiation is more successful in downstaging esophageal cancer before esophagectomy, it was not independently prognostic for improved long‐term survival. Other factors affecting long‐term survival among pathologic complete responders and among patients with persistent disease should be investigated to clarify this association.

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions

BACKGROUND National Comprehensive Cancer Network (NCCN) guidelines recommend sampling 15 or more lymph nodes during esophagectomy. The proportion of patients meeting this guideline is unknown, as is its influence on overall survival (OS). METHODS Univariate analysis and logistic regression were performed to identify variables associated with sampling 15 or more lymph nodes among patients undergoing esophagectomy in the National Cancer Data Base (NCDB). The NCCN guideline was evaluated in Cox proportional hazards modeling, along with alternative lymph node thresholds. Positive to examined node (PEN) ratios were calculated, and OS was compared using Kaplan-Meier analysis. RESULTS From 2006 to 2012, only 6,961 of 18,777 (37.1%) patients undergoing esophagectomy had sampling of 15 or more lymph nodes. Variables associated with sampling 15 or more lymph nodes included income greater than or equal to

Multidisciplinary Treatment for Stage IIIA Non-Small Cell Lung Cancer: Does Institution Type Matter?

38,000, procedure performed in an academic facility, and increasing clinical T and N stages. Induction therapy was associated with a decreased likelihood of 15 or more lymph nodes being sampled. The largest decrease in mortality hazard in patients undergoing upfront esophagectomy was detected when 25 lymph nodes or more were sampled (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.67-0.89; p < 0.001), whereas for patients undergoing induction therapy, sampling of 10 or 15 or more lymph nodes was associated with optimal survival benefit (HR, 0.81; 95% CI, 0.74-0.90; p < 0.001). PEN ratios of 0 to 0.10 were associated with maximum survival benefit among all patients undergoing esophagectomy. For patients with a PEN ratio of 0, increases in OS were detected with higher lymph node sampling (85.3 months for sampling of 20 or more lymph nodes versus 52.0 months for sampling 1-9 lymph nodes; p < 0.001). CONCLUSIONS For patients undergoing upfront esophagectomy, there may be an increased survival benefit for examining 20 to 25 lymph nodes, which is higher than current recommendations. However, only a minority of patients are meeting current guidelines.

Treatment Patterns and Overall Survival Outcomes of Octogenarians with Muscle Invasive Cancer of the Bladder: An Analysis of the National Cancer Database

Biologic agents, including targeted antibodies as well as immunomodulators, are demonstrating unparalleled development and study across the entire spectrum of human malignancy. This review summarizes the current state of biologic therapies for esophageal, esophagogastric, and gastric malignancies, including those that target human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), c-Met, mechanistic target of rapamycin (mTOR) and immunomodulators. We focus primarily on agents that have been included in phase II and III clinical trials in locally advanced, progressive, or metastatic esophageal and gastric malignancies. At this time, only two biologic therapies are recommended by the National Comprehensive Cancer Network (NCCN): trastuzumab for patients with esophageal/esophagogastric or gastric adenocarcinomas with HER2 overexpression and ramucirumab, a VEGFR-2 inhibitor, as a second-line therapy for metastatic disease. However, recent reports of increases in overall and progression-free survival for agents including pertuzumab, apatinib, and pembrolizumab will likely increase the use of targeted biologic therapy in clinical practice for esophageal and gastric malignancies.

Interpreting survival data from clinical trials of surgery versus stereotactic body radiation therapy in operable Stage I non-small cell lung cancer patients

BACKGROUND Improved survival of patients with early-stage non-small cell lung cancer (NSCLC) undergoing resection at high-volume centers has been reported. However, the effect of institution is unclear in stage IIIA NSCLC, where a variety of neoadjuvant and adjuvant therapies are used. METHODS Treatment and outcomes data of clinical stage IIIA NSCLC patients undergoing resection as part of multimodality therapy was obtained from the National Cancer Database. Multivariable regression models were fitted to evaluate variables influencing 30-day mortality and overall survival. RESULTS From 1998 to 2010, 11,492 clinical stage IIIA patients underwent resection at community centers, and 7,743 patients received resection at academic centers. Academic center patients were more likely to be younger, female, non-Caucasian, have a lower Charlson-Deyo comorbidity score, and to receive neoadjuvant chemotherapy (49.6% vs 40.6%; all p < 0.001). Higher 30-day mortality was associated with increasing age, male gender, preoperative radiotherapy, and pneumonectomy. Patients undergoing operations at academic centers experienced lower 30-day mortality (3.3% vs 4.5%; odds ratio, 0.75; 95% confidence interval [CI], 0.60 to 0.93; p < 0.001). Decreased long-term survival was associated with increasing age, male gender, higher Charlson-Deyo comorbidity score, and larger tumors. Neoadjuvant chemotherapy (hazard ratio, 0.66; 95% CI, 0.62 to 0.70), surgical intervention at an academic center (hazard ratio, 0.92; 95% CI, 0.88 to 0.97), and lobectomy (hazard ratio, 0.72; 95% CI, 0.67 to 0.77) were associated with improved overall survival. CONCLUSIONS Stage IIIA NSCLC patients undergoing resection at academic centers had lower 30-day mortality and increased overall survival compared with patients treated at community centers, possibly due to higher patient volume and an increased rate of neoadjuvant chemotherapy.

Shared Decision Making and Effective Risk Communication in the High-Risk Patient With Operable Stage I Non-Small Cell Lung Cancer

Purpose: Elderly patients with muscle invasive bladder cancer can pose a therapeutic dilemma, given multiple comorbidities which may preclude surgery. In this registry based analysis we investigated treatment patterns and survival outcomes in this group of patients. Materials and Methods: We queried the National Cancer Database for muscle invasive (cT2‐T4aN0M0) bladder cancer in patients 80 years old or older who were diagnosed from 2004 to 2013. Patients included in study underwent transurethral resection of bladder tumor followed by radical cystectomy, radical cystectomy plus chemotherapy, radiation therapy alone, chemotherapy alone, chemoradiation or no treatment. We performed Kaplan‐Meier, log rank and multivariate Cox proportional hazards regression and propensity score matching. Results: A total of 9,270 patients were identified with a median followup of 12.8 months. Median overall survival in patients treated with radical cystectomy alone was 23.2 months (95% CI 19.8–26.6), which was superior to that of chemotherapy alone or radiation therapy alone (p <0.0001). Those treated with chemoradiation had a median overall survival of 27.3 months (95% CI 25.0–29.7), which did not statistically differ from that of radical cystectomy alone (p = 0.39). Surgery plus chemotherapy showed the longest median overall survival of 34.5 months (95% CI 22.2–46.7, vs chemoradiation and radical cystectomy alone p <0.0001). On multivariate analysis and propensity score matching the best overall survival was seen in patients treated with surgery plus chemotherapy and there was no difference in overall survival between chemoradiation and radical cystectomy alone. Conclusions: In elderly patients with muscle invasive bladder cancer chemoradiation is an alternative definitive treatment strategy with survival equal to that of surgery alone and superior to that of chemotherapy alone or radiation therapy alone. If a patient was able to receive neoadjuvant or adjuvant chemotherapy with surgery, additional survival was observed in this nonrandomized study.