MiR-214-3p targets Ras-related protein 14 (RAB14) to inhibit cellular migration and invasion in esophageal Cancer cells.

BACKGROUND: MicroRNA (miR)-214-3p is emerging as an important tumor suppressor in esophageal cancer. In this study, we examined the interaction between miR-214-3p and RAB14, a membrane trafficking protein shown to exert oncogenic functions in other malignancies, in esophageal cancer cells. METHODS: Studies were performed in a human esophageal epithelial cell line and a panel of esophageal cancer cell lines, as well in human specimens. MiR-214-3p expression was measured by digital PCR. Biotinylated RNA pull-down and luciferase reporter assays assessed binding. The xCELLigence RTCA system measured cell migration and invasion in real time. A lentiviral expression vector was used to create an esophageal cancer cell line stably expressing miR-214-3p. RESULTS: MiR-214-3p expression was decreased in esophageal cancer cell lines and human specimens compared to non-malignant controls. RAB14 mRNA stability and protein expression were decreased following miR-214-3p overexpression. Binding between miR-214-3p and RAB14 mRNA was observed. Either forced expression of miR-214-3p or RAB14 silencing led to a marked decrease in cellular migration and invasion. Esophageal cancer cells stably expressing miR-214-3p demonstrated decreased growth in a subcutaneous murine model. CONCLUSIONS: These results further support the tumor-suppressive role of miR-214-3p in esophageal cancer cells by demonstrating its ability to regulate RAB14 expression.

MiR-199a-5p Decreases Esophageal Cancer Cell Proliferation Partially through Repression of Jun-B.

MicroRNA (miR)-199a-5p has been shown to function as a tumor suppressor in some malignancies but its role in esophageal cancer is poorly understood. To further explore its role in esophageal cancer, we sought to investigate the interaction between miR-199a-5p and Jun-B, an important component of the AP1 transcription factor, which contains a potential binding site for miR-199a-5p in its mRNA. We found that levels of miR-199a-5p are reduced in both human esophageal cancer specimens and in multiple esophageal cancer cell lines compared to esophageal epithelial cells. Jun-B expression is correspondingly elevated in these tumor specimens and in several cell lines compared to esophageal epithelial cells. Jun-B mRNA expression and stability, as well as protein expression, are markedly decreased following miR-199a-5p overexpression. A direct interaction between miR-199a-5p and Jun-B mRNA was confirmed by a biotinylated RNA-pull down assay and luciferase reporter constructs. Either forced expression of miR-199a-5p or Jun-B silencing led to a significant decrease in cellular proliferation as well as in AP-1 promoter activity. Our results provide evidence that miR-199a-5p functions as a tumor suppressor in esophageal cancer cells by regulating cellular proliferation, partially through repression of Jun B.

Limited Left Thoracoscopic Sympathectomy Effectively Silences Refractory Electrical Storm.

BACKGROUND: An electrical storm (ES) is a life-threatening condition that affects up to 20% of patients with implantable cardioverter defibrillators. In this small retrospective study, we report our results with left video-assisted thoracoscopic sympathectomy/ganglionectomy (VATSG) to treat refractory ES in low-ejection fraction patients who were not candidates for catheter ablation. METHODS: We identified 12 patients who presented with ES and underwent a total of 14 video-assisted thoracoscopic sympathectomy/ganglionectomy, including 3 patients on venoarterial extracorporeal membrane oxygenation. We reviewed demographic data, survival to discharge, number of cardioversions (before and after VATSG), need for readmissions, and need for right-sided procedures. RESULTS: In the 30 days before a left VATSG, mean number of shocks was 22.67 for all patients. For the patients who survived to discharge, the mean was 3.55 since surgery and the median was zero shocks after a median follow-up of 358 days. Six patients did not experience further cardioversions since the last VATSG and 5 were not readmitted for ventricular tachycardia. Two patients had staged bilateral procedures owing to recurrences; of those, 1 did not require further cardioversions. CONCLUSIONS: Limited left VATSG is an appropriate and effective initial treatment for ES patients who are not candidates for catheter ablation, including those on venoarterial extracorporeal membrane oxygenation for hemodynamic support.

Pathologic complete response (pCR) rates and outcomes after neoadjuvant chemoradiotherapy with proton or photon radiation for adenocarcinomas of the esophagus and gastroesophageal junction.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is associated with improved survival in patients treated for esophageal cancer. While proton beam therapy (PBT) has been demonstrated to reduce toxicities with nCRT, no data comparing pCR rates between modalities exist to date. We investigated pCR rates in patients with distal esophageal/GEJ adenocarcinomas undergoing trimodality therapy with nCRT-PBT or photon-based nCRT with the hypothesis that pathologic responses with PBT would be at least as high as with photon therapy. METHODS: A single-institutional review of patients with distal esophageal adenocarcinoma treated with trimodality therapy from 2015-2018 using PBT was completed. PBT patients were matched 1:2 to patients treated with photons. Chi square and two-sample t-tests were utilized to compare characteristics, and the Kaplan Meier method was used to estimate oncologic endpoints. RESULTS: Eighteen consecutive PBT patients were identified and compared to 36 photon patients. All patients received concurrent chemotherapy; 98% with carboplatin/paclitaxel. Most patients were male (91%) and White (89%); median age was 62 years (range, 31-76 years). Median radiation dose in both cohorts was 50.4 Gy (range, 41.4-50.4 Gy); all courses were delivered in 1.8Gy fractions. Age, gender and race were well balanced. Patients treated with PBT had a significantly higher pre-treatment nodal stage (N) and AJCC 7th edition stage grouping (P=0.02, P=0.03). Despite this, tumoral and nodal clearance and pCR rates were equivalent between cohorts (P=0.66, P=0.11, P=0.63, respectively). Overall pCR and individual primary and nodal clearance rates, overall survival (OS), locoregional control (LRC), and distant metastatic control did not significantly differ between modalities (all P>0.05). Major perioperative events were balanced; however, there were 5 (14%) perioperative deaths in the photon cohort compared to 0 (0%) in the proton cohort (P=0.06). CONCLUSIONS: The use of PBT in trimodality therapy for distal esophageal adenocarcinoma yields pCR rates comparable to photon radiation and historical controls. Pathologic responses and oncologic outcomes in this study did not differ significantly between modalities despite PBT patients having higher AJCC stages and nodal disease burdens.

Assessing Outcomes of Patients Treated With Re-Irradiation Utilizing Proton Pencil-Beam Scanning for Primary or Recurrent Malignancies of the Esophagus and Gastroesophageal Junction.

INTRODUCTION: Re-irradiation (re-RT) for locoregionally recurrent esophageal and gastroesophageal junction (GEJ) cancer and de novo esophageal + GEJ cancer arising in-field after a course of prior radiation poses considerable treatment challenges given the sensitivity of surrounding organs at risk (OARs). Guidelines for treatment of this presentation are not well established. Pencil-beam scanning (PBS) proton therapy has the ability to decrease radiation dose to OARs relative to photon plans. We present the first published series to date of re-RT with PBS for esophageal + GEJ malignancies and hypothesize that re-RT with proton PBS will be feasible and improve the safety profile of re-RT for this cohort of patients. METHODS: Consecutive esophageal + GEJ cancers treated with PBS re-RT within a single institution were analyzed. Comparative volumetric-modulated arc therapy photon plans were generated. A total of 17 patients were included for analysis. RESULTS: At a median follow-up of 11.6 months, 1-year local control was 75.3% and overall survival was 68.9%. There were five (27.8%) grade 3 or higher late toxicities. When matched for clinical target volume coverage, proton PBS plans delivered significantly lower doses to the spinal cord, lungs, liver, and heart (all p < 0.05); five volumetric-modulated arc therapy plans would have been undeliverable on the basis of physician-specified OAR constraints. CONCLUSIONS: Re-RT for de novo or recurrent malignancies of the esophagus + GEJ, when delivered with PBS proton therapy, yields high rates of local control with acceptable acute and late toxicities in a high-risk population and decreased radiation dose to OARs relative to comparative photon plans. This is the largest series of proton re-RT for esophageal malignancies and the first that exclusively used PBS.

Insurance Status is an Independent Predictor of Overall Survival in Patients With Stage III Non-small-cell Lung Cancer Treated With Curative Intent.

INTRODUCTION: Population studies suggest an impact of insurance status on oncologic outcomes. We sought to explore this in a large single-institution cohort of patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively analyzed 342 consecutive patients (January 2000 to December 2013) curatively treated for stage III NSCLC. Patients were categorized by insurance status as uninsured (U), Medicare/Medicaid + Veterans Affairs (M/M + VA), or Private (P). The χ2 test was utilized to compare categorical variables. The Kaplan-Meier approach and the Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence (FFR). RESULTS: Compared with M/M + VA patients, P insurance patients were more likely to be younger (P < .001), married (P < .001), Caucasian (P = .001), reside in higher median income zip codes (P < .001), have higher performance status (P < .001), and undergo consolidation chemotherapy (P < .001) and trimodality therapy (P < .001). Diagnosis to treatment was delayed > 30 days in U (67.3%), M/M + VA (68.1%), and P (52.6%) patients (P = .017). Compared with the M/M + VA and U cohorts, P insurance patients had improved OS (median/5-year: 30.7 months/34.2%, 19 months/17%, and 16.9 months/3.8%; P < .001) and FFR (median/5-year: 18.4 months/27.3%, 15.2 months/23.2%, and 11.4 months/4.8%; P = .012), respectively. On multivariate analysis, insurance status was an independent predictor for OS (P = .017) but not FFR. CONCLUSION: Compared with U or M/M + VA patients, P insurance patients with stage III NSCLC were more likely to be optimally diagnosed and treated, resulting in a doubling of median OS for P versus U patients. Improved access to affordable health insurance is critical to combat inequities in access to care and has potential for improvements in cancer outcomes.

Organizing pneumonia co-existing with carcinoid tumour: complete resolution with bronchoscopic tumour resection.

Organizing pneumonia is a well-known clinical entity resulting in response to noxious stimuli causing lung injury. It is known to occur with infectious disease processes, neoplasms, post lung surgery or radiation therapy and when idiopathic, is called cryptogenic organizing pneumonia. We present an unusual case of a 48-year-old woman who presented with chronic cough and progressive dyspnoea while being on macrolide therapy for Lyme disease. Computerized tomography of chest demonstrated a well-circumscribed nodule in the lingula and bilateral central ground glass opacities. Transbronchial biopsies were consistent with carcinoid tumour in the lingula and organizing pneumonia in bilateral lung fields. Bronchoscopic relief of obstruction was performed by mechanical debulking of the tumour, with subsequent complete resolution of bilateral opacities, consistent with resolution of organizing pneumonia without the need for steroid therapy.

Morbidity and 30-day mortality after decortication for parapneumonic empyema and pleural effusion among patients in the Society of Thoracic Surgeons' General Thoracic Surgery Database.

OBJECTIVE: We analyzed the Society of Thoracic Surgeons' Database to describe the results of surgical decortication. METHODS: A review of patients undergoing pulmonary decortication, excluding hemothorax and malignancy, from 2009 to 2016 was performed. Preoperative factors, length of stay, discharge status, readmission, morbidity, and mortality were compared between open and video-assisted thoracoscopic surgery approaches. Multivariable models identified risk factors for morbidity and mortality. RESULTS: Of 7316 patients undergoing decortication, 6961 (95.2%) had a primary diagnosis of empyema. Video-assisted thoracoscopic surgery was used in 4435 patients (60.6%) and increased during the study period. Median length of stay was 4 days (interquartile range, 2-7) preoperatively and 7 days (interquartile range, 5-11) postoperatively. Mortality occurred in 228 patients (3.1%). Complications occurred in 2875 patients (39.3%), and major morbidity occurred in 1138 patients (15.6%). Transitional care after discharge occurred in 1922 patients (26.3%). Readmission within 30 days occurred in 452 patients (8.7%). Compared with video-assisted thoracoscopic surgery, mortality, major morbidity, prolonged length of stay, and discharge to other than home were higher with thoracotomy. In multivariable analysis, age, estimated glomerular filtration rate less than 60, chronic obstructive pulmonary disease, body mass index, American Society of Anesthesiologists level, Zubrod score, and thoracotomy were associated with increased mortality, morbidity, discharge to transitional care, and prolonged length of stay. Each additional preoperative hospital day (up to 5 days) increased mortality. Readmission, major morbidity, prolonged length of stay, and discharge to transitional care were all higher when preoperative hospitalization extended beyond 5 days. CONCLUSIONS: Surgeons participating in the Society of Thoracic Surgeons General Thoracic Surgery Database perform decortication for parapneumonic empyema and pleural effusion with limited mortality despite substantial postoperative morbidity. Further study is required to describe selection criteria for video-assisted thoracoscopic surgery and determine indications for surgical intervention to reduce delays in operative intervention.

Lymph Node Size Predicts for Asymptomatic Brain Metastases in Patients With Non-small-cell Lung Cancer at Diagnosis.

BACKGROUND: We questioned whether the National Comprehensive Cancer Network recommendations for brain magnetic resonance imaging (MRI) for patients with stage ≥ IB non-small-cell lung cancer (NSCLC) was high-yield compared with American College of Clinical Pharmacy and National Institute for Health and Care Excellence guidelines recommending stage III and above NSCLC. We present the prevalence and factors predictive of asymptomatic brain metastases at diagnosis in patients with NSCLC without extracranial metastases. MATERIALS AND METHODS: A retrospective analysis of 193 consecutive, treatment-naïve patients with NSCLC diagnosed between January 2010 and August 2015 was performed. Exclusion criteria included no brain MRI staging, symptomatic brain metastases, or stage IV based on extracranial disease. Univariate and multivariate logistic regression was performed. RESULTS: The patient characteristics include median age of 65 years (range, 36-90 years), 51% adenocarcinoma/36% squamous carcinoma, and pre-MRI stage grouping of 31% I, 22% II, 34% IIIA, and 13% IIIB. The overall prevalence of brain metastases was 5.7% (n = 11). One (2.4%) stage IA and 1 (5.6%) stage IB patient had asymptomatic brain metastases at diagnosis, both were adenocarcinomas. On univariate analysis, increasing lymph nodal stage (P = .02), lymph nodal size > 2 cm (P = .009), multi-lymph nodal N1/N2 station involvement (P = .027), and overall stage (P = .005) were associated with asymptomatic brain metastases. On multivariate analysis, increasing lymph nodal size remained significant (odds ratio, 1.545; P = .009). CONCLUSION: Our series shows a 5.7% rate of asymptomatic brain metastasis for patients with stage I to III NSCLC. Increasing lymph nodal size was the only predictor of asymptomatic brain metastases, suggesting over-utilization of MRI in early-stage disease, especially in lymph node-negative patients with NSCLC. Future efforts will explore the utility of baseline MRI in lymph node-positive stage II and all stage IIIA patients.

Intrapleural Therapy for Empyema in the Setting of a Bronchopleural Fistula: A Novel Use of an Intrabronchial Valve.

Postsurgical empyema with bronchopleural fistula can be difficult to manage. We present a patient with postoperative empyema with bronchopleural fistula who was successfully treated nonoperatively by placing an intrabronchial valve to address the bronchopleural fistula, which allowed for safe administration of intrapleural fibrinolytics and antibiotics for definitive treatment of the empyema. Although the presence of a bronchopleural fistula is considered a contraindication to the administration of intrapleural tissue plasminogen activator and deoxyribonuclease, this case demonstrates a novel use of the intrabronchial valve that allowed these medications to be used.

Thoracoscopic Sympathectomy for Refractory Electrical Storm After Coronary Artery Bypass Grafting.

We report a patient with refractory electrical storm after coronary artery bypass grafting who was successfully treated with thoracoscopic sympathectomy. Cardiac arrest with ventricular tachycardia occurred on postoperative day 2, and the patient required emergency support with venoarterial extracorporeal membrane oxygenation. Frequent episodes of ventricular tachycardia prevented cardiac recovery and weaning from mechanical circulatory support. A percutaneous left stellate ganglion block initially demonstrated successful prevention of ventricular tachycardia, and definitive sympathetic denervation was achieved by a left thoracoscopic sympathectomy. The patient remained in normal sinus rhythm and gained recovery of baseline ventricular function, permitting successful decannulation and weaning of inotropic support.

MiR-199a-3p decreases esophageal cancer cell proliferation by targeting p21 activated kinase 4.

Although microRNA (miR) 199a-3p functions as a tumor suppressor in multiple malignancies, its expression and role in esophageal cancer have not been studied. Based on our previous observation that miR-199a-3p is markedly downregulated in esophageal cancer cell lines relative to esophageal epithelial cells, we examined the function of miR-199a-3p in these cells. MiR-199a-3p is predicted to bind with high affinity to the mRNA of p21 activated kinase 4 (PAK4). This kinase has been shown to be overexpressed in several malignancies and to modulate proliferation and motility. The current study is designed to determine whether miR-199a-3p regulates the expression of PAK4 in esophageal cancer cells and to understand the functional consequences of this interaction. Herein, we demonstrate reduced expression of miR-199a-3p in human esophageal cancer specimens and cell lines compared to esophageal epithelial cells, with associated increased expression of PAK4. Forced expression of miR-199a-3p decreases expression of PAK4 in esophageal cancer cell lines. Mechanistic studies reveal that miR-199a-3p binds to the 3'UTR of PAK4 mRNA. This interaction results in reduced levels of PAK4 mRNA due to decreased mRNA stability. Downregulation of PAK4 leads to decreased cyclin D1 (CD1) transcription and protein expression, resulting in markedly impaired cellular proliferation. When PAK4 expression is rescued, both CD1 transcription and protein return to baseline levels. Our results show that miR-199a-3p functions as a tumor suppressor in esophageal cancer cells through repression of PAK4. These findings suggest that both miR-199a-3p and PAK4 may be novel therapeutic targets in the treatment of esophageal cancer.

Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer.

PURPOSE: To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). METHODS AND MATERIALS: At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. RESULTS: Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74% (82 of 111 patients) and pCR rate of 48% (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.272-0.763, P = .004; FFR: HR 0.426, 95% CI 0.250-0.726, P = .002) and multivariate analysis (OS: HR 0.460, 95% CI 0.239-0.699, P = .001; FFR: HR 0.455, 95% CI 0.266-0.778, P = .004). However, pCR did not independently impact OS (P = .918) or FFR (P = .474). CONCLUSIONS: Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone.

Anatomical lung resection after neoadjuvant chemoradiotherapy.

The critical role for anatomical lung resection -- segmentectomy, lobectomy, pneumonectomy -- in the treatment of Stage I and II non-small cell lung cancer is undisputed. In contrast, the primacy of surgery in the management of Stage III disease is not established. Increasingly, however, the multimodality approach to locally advanced lung cancer has gained acceptance, and the integration of surgery into the treatment algorithms for Stage III cancers, particularly N2 spread, has evolved. Herein, the important steps in this evolution are defined. The concept of induction or neoadjuvant chemoradiotherapy followed by resection is emphasized, and evidence supporting surgery's therapeutic value in this schema is provided. Our center's strategy for the successful and safe delivery of trimodality care is comprehensively outlined.

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.

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.

The Benefit of Chemotherapy in Esophageal Cancer Patients With Residual Disease After Trimodality Therapy.

INTRODUCTION: The objective of this retrospective study was to determine the potential benefits of chemotherapy in esophageal cancer patients treated with chemoradiation followed by surgery. MATERIALS AND METHODS: At our institution, 145 patients completed trimodality therapy from 1993 to 2009. Neoadjuvant treatment predominantly consisted of 5-fluorouracil and cisplatin with a concurrent median radiation dose of 50.4 Gy. Sixty-two patients received chemotherapy postoperatively. The majority (49/62) received 3 cycles of docetaxel. RESULTS: Within the entire cohort, a 5-year overall survival (OS) benefit was found in those who received postoperative chemotherapy, OS 37.1% versus 18.0% (P=0.024). The response after neoadjuvant chemoradiation was as follows: 33.8% had a pathologic complete response and 62.8% with residual disease. A 5-year OS and cause-specific survival (CSS) advantage were associated with postoperative chemotherapy among those with macroscopic residual disease after neoadjuvant therapy: OS 38.7% versus 13.9% (P=0.016), CSS 42.8% versus 18.8% (P=0.048). This benefit was not seen in those with a pathologic complete response or those with microscopic residual. A stepwise multivariate Cox regression model evaluating the partial response group revealed that postoperative chemotherapy and M stage were independent predictors of overall and CSS. CONCLUSIONS: This analysis revealed that patients with gross residual disease after trimodality therapy for esophageal cancer who received postoperative chemotherapy had an improved overall and CSS. These data suggest that patients with residual disease after trimodality therapy and a reasonable performance status may benefit from postoperative chemotherapy. Prospective trials are needed to confirm these results to define the role of postoperative treatment after trimodality therapy.

High-dose radiotherapy in trimodality treatment of Pancoast tumors results in high pathologic complete response rates and excellent long-term survival.

OBJECTIVE: We sought to study the clinical characteristics and outcomes of patients treated with a surgery-inclusive multimodality approach for Pancoast tumors. METHODS: Clinical records of patients with Pancoast lung cancer who were enrolled for multimodality treatment between 1993 and 2003 at our institution were reviewed retrospectively. RESULTS: Thirty-six patients completed neodjuvant chemoradiation followed by en bloc surgical resection, whereas one patient received high-dose radiation alone followed by surgical intervention. There were 22 men and 15 women. Thirty-four lobectomies and 3 pneumonectomies were performed. Pretreatment non-small cell lung cancer stages were IIB, IIIA, IIIB, and IV (presenting with solitary brain metastasis) in 18, 8, 6, and 5 cases, respectively. R0 resection was achieved in 36 (97.3%) patients. Operative mortality was 2.7% (n = 1). High-dose radiotherapy was successfully tolerated in all but 1 patient. Mean total radiation dose was 56.9 Gy. Pathologic complete response was found in 40.5% (n = 15) of patients. Recurrences were found in 50% (n = 18) of patients. Brain metastasis was the most common recurrence (n = 9), followed by other distant recurrences (n = 4) and local recurrences (n = 5). Median survival time for the group is 2.6 years, and median survival time (pathologic complete response) is 7.8 years. It is noteworthy that median survival time of patients with positive pretreatment lymph nodes (12 patients) was not reached. CONCLUSIONS: Surgical resection of Pancoast tumors after neoadjuvant high-dose radiation and chemotherapy can be safely performed. High-dose radiation in trimodality treatment is well tolerated and might be beneficial. Similar to other studies, late central nervous system relapse is problematic and indicates a need for assessing the role of prophylactic cranial irradiation in this disease.

Primary Gross Tumor Volume is an Important Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Trimodality Therapy.

PURPOSE: This study investigated the relationship between tumor volume and outcomes in patients receiving trimodality therapy for locally advanced esophageal cancer. METHODS: Between 2001 and 2012, 67 patients treated for esophageal cancer with chemoradiotherapy followed by esophagectomy who had available gross tumor volume (GTV) information were analyzed (35 node-negative, 32 node-positive patients with primary and nodal GTV contoured as separate regions of interest). All gross tumor volumes (GTVs) were contoured at the time of radiotherapy treatment planning. GTV optimal cutoff values were determined with receiver operating characteristic analysis and deemed significant when χ (2) analysis demonstrated differences in examined prognostic variables. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Cox proportional hazards model. RESULTS: GTVprimary (P = 0.034) and N stage were significant multivariate predictors for improved local control; GTVprimary was the only multivariate predictor of PFS (P = 0.0299) and OS (P = 0.001228) at 5 years. Univariate predictors of 5-year PFS and OS included GTVprimary, node number, and metastatic lymph node ratio. GTVprimary >85 cc was the best predictor for local failure (33.3 %; 8.7 % if ≤85 cc). GTVprimary >46 cc correlated with an increased risk of 5-year distant failure (37.1 %; 6.7 % if ≤46 cc). CONCLUSIONS: GTVprimary was a significant multivariate predictor for improved local control, PFS, and OS. GTVprimary is a more powerful predictor of patient outcomes than traditional TNM staging and should be part of the decision-making process when determining optimal local and systemic options for patients with locally advanced esophageal cancer.