Neha Bhooshan

Multi-institutional analysis of radiation modality use and postoperative outcomes of neoadjuvant chemoradiation for esophageal cancer

PURPOSE Relative radiation dose exposure to vital organs in the thorax could influence clinical outcomes in esophageal cancer (EC). We assessed whether the type of radiation therapy (RT) modality used was associated with postoperative outcomes after neoadjuvant chemoradiation (nCRT). PATIENTS AND METHODS Contemporary data from 580 EC patients treated with nCRT at 3 academic institutions from 2007 to 2013 were reviewed. 3D conformal RT (3D), intensity modulated RT (IMRT) and proton beam therapy (PBT) were used for 214 (37%), 255 (44%), and 111 (19%) patients, respectively. Postoperative outcomes included pulmonary, GI, cardiac, wound healing complications, length of in-hospital stay (LOS), and 90-day postoperative mortality. Cox model fits, and log-rank tests both with and without Inverse Probability of treatment Weighting (IPW) were used to correct for bias due to non-randomization. RESULTS RT modality was significantly associated with the incidence of pulmonary, cardiac and wound complications, which also bore out on multivariate analysis. Mean LOS was also significantly associated with treatment modality (13.2days for 3D (95%CI 11.7-14.7), 11.6days for IMRT (95%CI 10.9-12.7), and 9.3days for PBT (95%CI 8.2-10.3) (p<0.0001)). The 90day postoperative mortality rates were 4.2%, 4.3%, and 0.9%, respectively, for 3D, IMRT and PBT (p=0.264). CONCLUSIONS Advanced RT technologies (IMRT and PBT) were associated with significantly reduced rate of postoperative complications and LOS compared to 3D, with PBT displaying the greatest benefit in a number of clinical endpoints. Ongoing prospective randomized trial will be needed to validate these results.

Neutrophil‐Lymphocyte Ratio Is a Prognostic Marker in Patients with Locally Advanced (Stage IIIA and IIIB) Non‐Small Cell Lung Cancer Treated with Combined Modality Therapy

BACKGROUND Neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in localized and advanced non-small cell lung cancer (NSCLC). Increased systemic inflammation portends a poorer prognosis in cancer patients. We hypothesized that low NLR at diagnosis is associated with improved overall survival (OS) in locally advanced NSCLC (LANSCLC) patients. PATIENTS AND METHODS Records from 276 patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation with or without surgery between 2000 and 2010 with adequate data were retrospectively reviewed. Baseline demographic data and pretreatment peripheral blood absolute neutrophil and lymphocyte counts were collected. Patients were grouped into quartiles based on NLR. OS was estimated using the Kaplan-Meier method. The log-rank test was used to compare mortality between groups. A linear test-for-trend was used for the NLR quartile groups. The Cox proportional hazards model was used for multivariable analysis. RESULTS The NLR was prognostic for OS (p < .0001). Median survival in months (95% confidence interval) for the first, second, third, and fourth quartile groups of the population distribution of NLR were 27 (19-36), 28 (22-34), 22 (12-31), and 10 (8-12), respectively. NLR remained prognostic for OS after adjusting for race, sex, stage, performance status, and chemoradiotherapy approach (p = .004). CONCLUSION To our knowledge, our series is the largest to demonstrate that baseline NLR is a significant prognostic indicator in LANSCLC patients who received definitive chemoradiation with or without surgery. As an indicator of inflammatory response, it should be explored as a potential predictive marker in the context of immunotherapy and radiation therapy. IMPLICATIONS FOR PRACTICE Neutrophil-lymphocyte ratio measured at the time of diagnosis was associated with improved overall survival in 276 patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) treated with definitive chemoradiation with or without surgery. To our knowledge, our series is the largest to demonstrate that baseline neutrophil-lymphocyte ratio is a significant prognostic indicator in locally advanced NSCLC patients who received definitive chemoradiation with or without surgery. Neutrophil-lymphocyte ratio is an inexpensive biomarker that may be easily utilized by clinicians at the time of locally advanced NSCLC diagnosis to help predict life expectancy.

Obesity is associated with long-term improved survival in definitively treated locally advanced non-small cell lung cancer (NSCLC)

OBJECTIVES To determine the prognostic effect of Body Mass Index (BMI) in definitively treated locally advanced NSCLC patients. MATERIALS AND METHODS In this single institution retrospective cohort study, we evaluated 291 patients who were treated for locally advanced NSCLC from 2000 to 2010. They were stratified into four BMI groups based on World Health Organization criteria: underweight (<18.5kg/m2), normal weight (18.5 to <25kg/m2), overweight (25 to <30kg/m2), and obese (≧30kg/m2). Overall survival was analyzed by BMI group. RESULTS Baseline patient characteristics and treatment parameters were similar between obese and normal weight patients. Increasing BMI was associated with improved overall survival (P=0.011), even when underweight cases were excluded. There was a sustained 31%-58% reduction in mortality of obese relative to normal weight patients (HR 0.68±0.21, 0.61±0.19, and 0.42±0.19, for each year post-treatment respectively). Statin use after diagnosis was highly associated with increasing BMI (P<0.001) and predicted improved survival in a multivariate analysis (HR 0.60, 95% CI 0.41-0.89, P=0.011). CONCLUSION Obese patients in this retrospective study had significantly improved survival relative to normal weight patients. Our data suggest that the protective effect of obesity in locally advanced NSCLC is not solely due to short-term treatment effects, decreased smoking exposure, or poor prognostic factors from underweight patients. Notably, statin use was also associated with improved survival. Additional studies are needed to clarify the mechanisms and possible concomitant factors underlying the obesity paradox in NSCLC.

Oncological outcomes from trimodality therapy receiving definitive doses of neoadjuvant chemoradiation (≥60 Gy) and factors influencing consideration for surgery in stage III non-small cell lung cancer

Purpose Guidelines for locally advanced non-small cell lung cancer (LA-NSCLC) recommend definitive chemoradiation therapy (CRT) for cN2-N3 disease, reserving surgery for patients with minimal nodal involvement at presentation. The current literature suggests that surgery after CRT for stage III NSCLC can improve freedom-from-recurrence (FFR) but has not consistently demonstrated an improvement in overall survival, perhaps partly due to the low (45-50.4 Gy) preoperative doses delivered that result in low rates of mediastinal nodal clearance. We therefore analyzed factors associated with trimodality therapy receipt and determined outcomes in patients with LA-NSCLC who were treated with definitive doses (≥60 Gy) of neoadjuvant CRT prior to surgery. Methods and materials We retrospectively analyzed 355 consecutive patients with LA-NSCLC who were treated with curative intent between January 2000 and December 2013. The Kaplan-Meier method was used to estimate the overall survival and FFR of patients who were initially planned to receive trimodality treatment but never underwent surgery (unplanned bimodality) compared with those who were never considered to be surgical candidates (planned bimodality) and those who underwent surgical resection after CRT (trimodality). Cox proportional hazards regression with forward selection was used for multivariate analyses, and the Fisher exact test was used to test contingency tables. Results Patients who received trimodality therapy had a longer median survival than those with unplanned or planned bimodality therapy at 59.9, 20.1, and 17.3 months, respectively (P < .001). The survival benefit with surgery persisted in patients with stage IIIB (P < .001) and N3 (P = .010) nodal disease when mediastinal nodal clearance was achieved. FFR was also improved with surgical resection (P = .001). Race (P < .001), stage (P < .001), performance status (P < .001), age (P < .001), and diagnosis of chronic obstructive pulmonary disease (P = .009) were significant indicators that influenced both the decision to initially choose trimodality therapy at consultation and to actually perform surgical resection. Conclusions Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres

BACKGROUND Yttrium-90 (90Y)-resin microspheres can prolong intrahepatic disease control and improve overall survival (OS) in patients with metastatic colorectal cancer (CRC). Prognostic factors for improved outcomes in patients undergoing selective internal radiation therapy (SIRT) have been studied, but the relationship between pre-SIRT liver tumor volume and outcomes has not well described. METHODS We retrospectively reviewed the records of patients with metastatic CRC who were treated at our institution with 90Y-resin microspheres. Each patient underwent either MR or CT imaging of the liver with intravenous (IV) contrast before and within ~2-3 months after SIRT. Imaging data were transferred into our treatment planning system. Each metastatic liver lesion was contoured, and the volume of each lesion was summed to determine the total liver tumor volume at a given time point. We evaluated whether pretreatment liver tumor volume was related to OS. We also evaluated the relationship between pre-SIRT tumor volume and radiographic treatment response by either unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) or three-dimensional volumetric criteria. RESULTS We included 60 patients with a median age of 59 years (range, 38-97 years); 60% of patients received sequential lobar treatment. The median number of chemotherapy cycles received prior to SIRT was 2. Median follow-up from first SIRT was 8.9 months. Pre- and post-SIRT tumor volumes were primarily calculated on CT (87%). The median pre-SIRT tumor volume was 77 cc (range, 4.5-2,170.4 cc). The median intervals between the first SIRT and the first, second, and third follow-up scans were 2.2, 4.4, and 7.7 months, respectively. No patient experienced a radiographic complete response. Pretreatment volume was a significant predictor for estimating the odds of a patient having stable disease or partial response using volumetric response criteria at first (P=0.016), second (P=0.023), and third (P=0.015) follow-ups. For each unit increase in log volume, a patients odds of having a stable or partial response were 0.57, 0.63, and 0.61 times as likely at first, second, and third follow-up, respectively. OS was not significantly associated with pretreatment tumor volume. CONCLUSIONS Patients with metastatic CRC with larger overall pretreatment liver tumor volumes, regardless of number of individual liver lesions, are less likely to have radiographic evidence of stable disease or partial response following SIRT using volumetric response criteria. However, pretreatment volume was not significantly associated with OS, and thus SIRT should be considered for patients with larger pretreatment volumetric tumor burden.

Clinical outcomes of black vs. non-black patients with locally advanced non–small cell lung cancer

OBJECTIVES The black population remains underrepresented in clinical trials despite reports suggesting greater incidence and deaths from locally advanced non-small cell lung cancer (NSCLC). We determined outcomes for black and non-black patients in a well-annotated cohort treated with either definitive chemoradiation (CRT; bimodality) or CRT followed by surgery (trimodality therapy). MATERIALS AND METHODS A retrospective analysis of 355 stage III NSCLC patients treated with curative intent at the University of Maryland, Medical Center, between January 2000-December 2013 was performed. The Kaplan-Meier approach and the Cox proportional hazards models were used to analyze overall survival (OS) and freedom-from-recurrence (FFR) in black and non-black patients. The chi-square test was used to compare categorical variables. RESULTS Black patients comprised 42% of the cohort and were more likely to be younger (p<0.0001), male (p=0.030), single (p<0.0001), reside in lower household income zipcodes (p<0.0001), have an Eastern Cooperative Oncology Group (ECOG) performance status >0 (p<0.001), and less likely to undergo surgery (p<0.0001). With a median follow-up of 15 months for all patients and 89 months for surviving patients (range:1-186 months), median OS times for black and non-black patients were 22 and 24 months, respectively (p=0.698). FFR rates were also comparable between the two groups (p=0.468). Surgery improved OS in both cohorts. Race was not a significant predictor for OS or FFR even when adjusted for other factors. CONCLUSIONS We found similar oncologic outcomes in black and non-black NSCLC patients when treated with curative intent in a comprehensive cancer center setting, despite epidemiologic differences in presentation and receipt of care. Future efforts to improve outcomes in black patients could focus on addressing modifiable social disparities.