Cohort Of Esophageal Cancer Patients Research Articles

340. THE IMPACT OF OBESITY ON SURGICAL OUTCOMES AFTER ESOPHAGECTOMY FOR CANCER IN SWEDEN

Abstract Background Global obesity rates continue to rise and are closely linked to an increase in esophageal adenocarcinoma. While obesity is associated with an increased risk of postoperative complications, its influence on long-term survival is less clear. Some studies suggest that obese patients have poorer outcomes due to higher comorbidity rates, while others indicate comparable or even better survival, possibly due to better nutritional reserves. This study aims to investigate whether obesity affects the survival and risk of postoperative complications in a national cohort of esophageal cancer patients. Methods This retrospective population-based register study included all individuals who underwent esophageal resection between 2006 and 2018 in Sweden. Data were extracted from the national quality registry for esophageal and gastric cancer (NREV). The cohort was grouped based on body mass index (BMI) into underweight (BMI < 20), normal (BMI 20-25), overweight (BMI 25-30), and obese (BMI > 30). Kaplan-Meier was used for survival analysis, and logistic regression and Cox regression were used for adjusted analyses (adjusting for sex, age, marital status, education level, Charlson comorbidity index score, histopathology, disease stage, and year of diagnosis). Results In total, 1742 individuals (79.9% males, mean age 66) were included, of whom 242 (13.9%) were obese. Obese individuals had more comorbidities at surgery, more commonly had adenocarcinoma, and underwent surgery more frequently in the later time period. The risk of surgical complications (e.g., anastomotic leak, bleeding) for obese individuals was not increased compared to those with normal weight (OR: 0.83 [0.56-1.21]), but an increased risk of non-surgical complications (e.g., pneumonia, cardiopulmonary events) was observed (OR: 1.78 [1.22-2.60]). The risk of death of any cause was decreased in obese individuals compared to those with normal weight (HR: 0.74 [0.58-0.95]), resulting in superior overall survival. Conclusion Despite the presence of more comorbidities among obese individuals undergoing esophagectomy, their risk of surgical complications remained comparable to those with normal weight. However, obese individuals exhibited a heightened susceptibility to other postoperative complications. Surprisingly, obese individuals demonstrated an improved overall survival at 5 years compared to those with normal weight.

Prognostic value of systemic inflammation score in patients with esophageal cancer.

The systemic inflammatory score (SIS), a new inflammatory marker based on a combination of the lymphocyte-to-monocyte ratio (LMR) and serum albumin concentration, has been reported to be a useful prognostic marker for several malignancies. The authors conducted this retrospective study on data from a cohort of esophageal cancer patients undergoing potentially curative resection to clarify the value of SIS as a prognostic marker for clinical outcome in this population. This retrospective cohort study included 32 patients who underwent thoracoscopic esophagectomy after neoadjuvant chemotherapy for esophageal cancer between January 2016 and December 2019. Blood samples were collected within one week prior to the initiation of preoperative chemotherapy. Three inflammatory and nutritional markers; SIS, the neutrophil-to-lymphocyte ratio (NLR), and prognostic nutrition index (PNI) were examined in this study. Disease-free survival was assessed using the Kaplan-Meier method, and univariable and multivariable Cox models were applied to evaluate the predictive value of SIS, NLR and PNI. NLR and PNI were not associated with recurrence, while SIS scores of 1 and 2 were significantly associated with recurrence. In multivariate analysis, SIS scores of 1 or 2 were found to be independently associated with recurrence, each with a hazard ratio of 1.98. In addition, when examining immunologic and nutritional factors and survival rates, there was no significant difference in the survival rate for NLR and PNI; for SIS, however, the survival rate was significantly worse in patients with SIS scores of 1 or 2. The authors demonstrated that a novel and easily obtained prognostic score, termed SIS, based on pre-treatment serum albumin and LMR, can serve as an independent prognostic factor in postoperative esophageal cancer patients. It could be incorporated into conventional clinical and pathological algorithms to enhance the prognostic accuracy in this population.

Deep Learning-Based Natural Language Processing to Automate Esophagitis Severity Grading from the Electronic Health Records

Radiotherapy (RT) toxicities can impair survival and quality-of-life, yet their risk factors and optimal management are under-studied. Real-world evidence holds enormous potential to improve our understanding of RT adverse events, but this information is often only documented in clinic notes and cannot, at present, be automatically extracted. To address this unmet need, we developed natural language processing (NLP) algorithms to automatically identify the presence and severity of esophagitis from notes of patients treated with thoracic RT. Our corpus consisted of (1) a gold-labeled dataset of 1524 clinic notes from 124 lung cancer patients treated with RT (in-domain), manually annotated for CTCAE v5.0 esophagitis grade, and (2) a silver-labeled dataset of 2420 notes from 1832 patients on whom toxicity grades had been collected as structured data during clinical care. We developed a fine-tuning pipeline for pre-trained BERT-based neural models for 3 tasks: 1) classifying the presence of esophagitis, 2) classifying grade 0-1 vs. > = 2 esophagitis and 3) classifying grade 0 vs. 1 vs. 2-3. A note sectionizer was used to let the model focus on the most informative sections. Independent validation in a separate clinical cohort of esophageal cancer patients was selected for out-of-domain transferability testing. Such cohorts consist of a manually annotated dataset of 345 notes from 75 esophageal cancer patients treated with RT. We also report patient-level results by evaluating the maximum predicted grade per patient. Fine-tuning PubmedBERT yielded the best-performing models. Performance is shown in the table. Selecting the most informative note sections (primarily Interval History, Assessment & Plan) during fine-tuning improved macro-F1 by > = 2% for all tasks. Including silver-labeled data improved the macro-F1 by > = 3% across all tasks. To the best of our knowledge, this is the first effort to automatically extract toxicity severity according to CTCAE guidelines from clinic notes, providing proof-of-concept for NLP to support detailed toxicity reporting. Fine-tuning on note sections and leveraging silver-labeled data enabled promising performance despite small datasets, informing future research into NLP for automated toxicity monitoring. Future work will extend these methods to other cancer diagnoses and toxicities, and to toxicity risk prediction.

Food Deserts Increase Readmission After Esophagectomy for Cancer: A Multi-institutional Study

BackgroundFood deserts are low-income census tracts with poor access to supermarkets and are associated with worse outcomes in breast, colon, and a small number of esophageal cancer patients. This study investigated residency in food deserts on readmission rates in a multi-institutional cohort of esophageal cancer patients undergoing trimodality therapy. MethodsA retrospective review of patients who underwent trimodality therapy at 6 high-volume institutions from January 2015 to July 2019 was performed. Food desert status was defined by the United States Department of Agriculture by patient ZIP Code. The primary outcome was 30-day readmission after esophagectomy. Multilevel, multivariable logistic regression was used to model readmission on food desert status adjusted for diabetes, insurance type, length of stay, and any complication, treating the institution as a random factor. ResultsOf the 453 records evaluated, 425 were included in the analysis. Seventy-three patients (17.4%) resided in a food desert. Univariate analysis demonstrated food desert patients had significantly increased 30-day readmission. No differences were seen in length of stay, complications, or 30-day mortality. In the adjusted logistic regression model, residing in a food desert remained a significant risk factor for readmission (odds ratio, 2.11; 95% CI, 1.07-4.15). There were no differences in 30-day, 90-day, or 1-year mortality based on food desert status, although readmission was associated with worse 90-day and 1-year mortality. ConclusionsFood desert residence was associated with 30-day readmission after esophagectomy in patients undergoing trimodality treatment for esophageal cancer in this multi-institutional population. Identification of patients residing in a food desert may allow surgeons to focus preventative interventions during treatment and postoperatively to improve outcomes.

341. SEX-RELATED DIFFERENCES IN TREATMENT STRATEGY AND OUTCOMES AFTER ESOPHAGECTOMY FOR CANCER

Abstract Esophageal cancer predominantly occurs in men, accounting for 75–89% of patients. Chosen treatment modalities and their related toxicities among male and female esophago-gastric cancer patients show significant variabilities, but there are only scarce data on the outcomes. This multicenter study aimed to assess potential sex-related differences in treatment allocation and outcomes, i.e. long-term survival in a large cohort of esophageal cancer patients. All consecutive patients who underwent oncological esophagectomy from 2009 to 2015 in the 20 ENSURE study group centers (NCT03461341) were included bar patients with missing data on gender, histologic type and treatment protocol. We used univariable and multivariable logistic regression for gender-related differences in treatment allocation and types, such as surgical approach, neoadjuvant treatment regimen, and use of cancer-specific treatment in case of tumor recurrence. Time-to-event outcomes, such as overall survival (OS), disease free survival (DFS), and disease-specific survival (DSS) were assessed with univariate and multivariate Cox regression. Results are shown as hazard ratios (HR) and 95% confidence intervals (CI). Overall, 3974 patients were analyzed, 3083 males (77.6%) and 891 females (22.4%). The median age was similar, whereas the histological type was adenocarcinoma in 77.5% of male and 52.2% of female patients. Gender was not predictive for neoadjuvant treatment or systemic cancer-specific therapy in case of tumor recurrence. Minimally invasive surgery was performed more frequently in male patients compared to females (OR 1.29, 95%CI 1.00–1.66). In multivariate analysis, even after adjustment for age, histology, postoperative complications and treatment protocol, male patients had poorer OS (HR 1.29 95%CI 1.12–1.48), DFS (HR 1.26, 95%CI 1.09–1.46) and DSS (HR 1.34, 95%CI 1.15–1.56). Patient sex was not associated with the use of systemic cancer-related treatment, although minimally invasive surgery was more frequently performed in male patients. Females had more favorable long-term overall and cancer-specific survival, even when age, histology, treatment modalities, and complications were accounted for. This sex-related prognostic difference has been previously suggested, especially for squamous cell cancer, although the precise mechanism by which gender influences esophageal cancer outcomes remains poorly understood and warrants further assessment.

Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: a case-control study

BackgroundPlasma cell-free DNA (cfDNA) methylation has shown promising results in the early detection of multiple cancers recently. Here, we conducted a study to investigate the performance of cfDNA methylation in the early detection of esophageal cancer (ESCA).MethodsSpecific methylation markers for ESCA were identified and optimized based on esophageal tumor and paired adjacent tissues (n = 24). Age-matched participants with ESCA (n = 85), benign esophageal diseases (n = 10), and healthy controls (n = 125) were randomized into the training and test sets to develop a classifier to differentiate ESCA from healthy controls and benign esophageal disease. The classifier was further validated in an independent plasma cohort of ESCA patients (n = 83) and healthy controls (n = 98).ResultsIn total, 921 differentially methylated regions (DMRs) between tumor and adjacent tissues were identified. The early detection classifier based on those DMRs was first developed and tested in plasma samples, discriminating ESCA patients from benign and healthy controls with a sensitivity of 76.2% (60.5–87.9%) and a specificity of 94.1% (85.7–98.4%) in the test set. The performance of the classifier was consistent irrespective of sex, age, and pathological diagnosis (P > 0.05). In the independent plasma validation cohort, similar performance was observed with a sensitivity of 74.7% (64.0–83.6%) and a specificity of 95.9% (89.9–98.9%). Sensitivity for stage 0–II was 58.8% (44.2–72.4%).ConclusionWe demonstrated that the cfDNA methylation patterns could distinguish ESCAs from healthy individuals and benign esophageal diseases with promising sensitivity and specificity. Further prospective evaluation of the classifier in the early detection of ESCAs in high-risk individuals is warranted.

Impact of Radiation on Cardiovascular Outcomes in Older Resectable Esophageal Cancer Patients With Medicare.

Preoperative radiotherapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiotherapy and different radiation techniques on cardiovascular morbidity among a cohort of esophageal cancer patients. We identified 1125 patients aged 65 and older diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation from the Surveillance Epidemiology and End Results (SEER)-Medicare database. We used Medicare claims to identify severe perioperative and late cardiovascular events. Multivariable logistic regression and Fine-Gray models were used to determine the effect of presurgery treatment on the risk of perioperative and late cardiovascular disease. Preoperative chemotherapy or chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared with surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a late cardiovascular event compared with patients treated with surgery alone (subdistribution hazard ratio [SDHR]: 1.36; P=0.035). There was no significant increase in late cardiovascular events among patients treated with preoperative chemotherapy (SDHR: 1.18; P=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy had a 68% decreased risk of having a late cardiovascular event compared with patients receiving conventional radiation (SDHR: 0.32; P=0.007). This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as intensity modulated radiotherapy.

Selecting esophageal cancer patients for lymphadenectomy after neoadjuvant chemoradiotherapy: a modeling study

ObjectivesTwo-thirds of patients do not harbor lymph node (LN) metastases after neoadjuvant chemoradiotherapy (nCRT). Our aim was to explore under which circumstances a selective lymph node dissection (LND) strategy, which...

Validation of a Nomogram Predicting Survival After Trimodality Therapy for Esophageal Cancer

Recently, a nomogram was developed for the prediction of overall survival (OS) after treatment with neoadjuvant chemoradiotherapy (nCRT) combined with surgery for esophageal or junctional cancer. The nomogram included clinical nodal category, pathologic tumor category, and number of positive lymph nodes in the resection specimen. The aim of this study was to externally validate the nomogram in an international multiinstitutional cohort of patients, and to explore the prognostic use of the nomogram for the prediction of progression-free survival (PFS) after nCRT plus surgery. Patients with potentially resectable esophageal or junctional carcinoma that underwent nCRT plus surgery between 1998 and 2015 at 3 academic centers were included. The discriminative ability of thenomogram for the prediction of OS and PFS wasquantified by Harrell's C-statistic. Calibration of the nomogram was visually assessed by plotting actualOS and PFS probabilities against predicted probabilities. Some 975 patients were included. The discriminative ability of the nomogram for OS was moderate (C-statistic, 0.61) and comparable to that of the initial cohort (C-statistic, 0.63). The nomogram was also useful for the prediction of PFS (C-statistic, 0.64). Calibration of the nomogram was accurate for both OS and PFS, with predicted estimates corresponding closely with the actual observed estimates. The nomogram accurately predicted OS and PFS after nCRT plus surgery in an independent international cohort of esophageal cancer patients. The current validated model may enable risk-stratified adjuvant treatment allocation and identify patients in need of routine surveillance after treatment.

Impact of lung and heart dose on survival after radiotherapy for esophageal cancer.

3 Background: Chemoradiation is an essential tool in treatment of localized esophageal cancer. Recent data indicates that cardiac dose is an independent predictor of survival after chemoradiation for locally advanced lung cancer. However, the impact of normal tissue dose in esophageal cancer has not been well characterized. We investigated cardiac and pulmonary dose-volume histogram (DVH) metrics as potential predictors of overall survival (OS) after chemoradiation for esophageal cancer. Methods: We reviewed 453 consecutive patients with stage I-III esophageal cancer treated with definitive or preoperative chemoradiation (median dose 50.4 Gy in 28 fractions) between 2007 and 2015 at our center. Most (n = 442) received intensity-modulated radiation therapy. Radiation plans were reviewed and multiple DVH metrics for heart (max and mean dose, V5Gy, V10Gy, V20Gy, V30Gy, and V40Gy) and lung (mean dose, V5Gy, and V20Gy) were extracted for analysis. Other clinical covariates (surgery, performance status, stage, and histology) were recorded. Cox univariate (UVA) and multivariate (MVA) regression was used to analyze the association of these factors with overall survival. Results: Median follow-up for surviving patients was 28.4 months. On UVA, older age, lower performance status, Stage III disease, lack of surgery, heart V40Gy, lung V5Gy, lung V20Gy, and lung mean dose were significantly associated with decreased survival. On MVA, surgery (p = 0.008), stage III disease (p < 0.0002) and lung V20Gy (p = 0.0389) remained significant, while heart V40Gy did not (p = 0.211). Patients with lung V20Gy< 20% had a median survival of 44.0 months, compared to 24.0 months for patients with lung V20Gy≥20%. Conclusions: This comprehensive dosimetric analysis of heart and lung dose in a large cohort of esophageal cancer patients suggests that lung dose is a significant independent predictor of survival. Cardiac dose was not independently predictive after adjusting for lung dose and other clinical factors. This data suggests that esophageal cancer outcomes may be improved by minimizing lung dose, particularly the volume receiving 20Gy or more, and provides further rationale for pursuing new techniques to reduce lung dose, such as proton therapy.

Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or Intensity-modulated radiation therapy

PurposeTo compare heart and cardiac substructure radiation exposure using intensity-modulated radiotherapy (IMRT) vs. proton beam therapy (PBT) for patients with mid- to distal esophageal cancer who received chemoradiation therapy. Methods and materialsWe identified 727 esophageal cancer patients who received IMRT (n=477) or PBT (n=250) from March 2004 to December 2015. All patients were treated to 50.4Gy with IMRT or to 50.4 cobalt Gray equivalents with PBT. IMRT and PBT dose–volume histograms (DVHs) of the whole heart, atria, ventricles, and four coronary arteries were compared. For PBT patients, passive scattering proton therapy (PSPT; n=237) and intensity-modulated proton therapy (IMPT; n=13) DVHs were compared. ResultsCompared with IMRT, PBT resulted in significantly lower mean heart dose (MHD) and heart V5, V10, V20, V30, and V40as well as lower radiation exposure to the four chambers and four coronary arteries. Compared with PSPT, IMPT resulted in significantly lower heart V20, V30, and V40 but not MHD or heart V5 or V10. IMPT also resulted in significantly lower radiation doses to the left atrium, right atrium, left main coronary artery, and left circumflex artery, but not the left ventricle, right ventricle, left anterior descending artery, or right coronary artery. Factors associated with lower MHD included PBT (P<0.001), smaller planning target volume (PTV; P<0.001), and gastroesophageal junction (GEJ) tumor (P<0.001). Among PBT patients, factors associated with lower MHD included IMPT (P=0.038), beam arrangement other than AP/PA (P<0.001), smaller PTV (P<0.001), and GEJ tumor (P<0.001). ConclusionsIn patients with mid- to distal esophageal cancer, PBT results in significantly lower radiation exposure to the whole heart and cardiac substructures than IMRT. Long-term studies are necessary to determine how this cardiac sparing effect impacts the development of coronary artery disease and other cardiac complications.

Variation by stage in the effects of prediagnosis weight loss on mortality in a prospective cohort of esophageal cancer patients.

Cancer cachexia is increasingly recognized as a poor prognostic marker for various tumor types. Weight loss in esophageal cancer is multifactorial, as patients with bulky tumors also have reduced ability to eat. We aimed to investigate the relationship between prediagnosis weight loss and mortality in esophageal cancer and to determine whether these associations vary with tumor stage. We conducted a prospective cohort study of esophageal cancer patients at two tertiary centers. We recorded baseline patient characteristics including medications, smoking, body mass index, and weight loss in the year prior to diagnosis, and collected data on treatment and outcomes. We used Cox regression modeling to determine the associations between percent weight loss and outcomes. The main outcome of interest was all-cause mortality; secondary endpoints were esophageal cancer-specific mortality and development of metastases. We enrolled 134 subjects, the majority of whom had adenocarcinoma (82.1%); median percent weight loss was 4.7% (IQR: 0%-10.9%). Increasing percent weight loss was not associated with all-cause mortality (ptrend =0.36). However, there was evidence of significant interaction by tumor stage (p =0.02). There was a strong and significant association between prediagnosis weight loss and mortality in patients with T stages 1 or 2 (adjusted HR 8.26 for highest versus lowest tertile, 95%CI 1.11-61.5, ptrend =0.03) but not for T stages 3 or 4 (ptrend =0.32). Body mass index one year prior to diagnosis was not associated with mortality. Prediagnosis weight loss was associated with increased all-cause mortality only in patients with early stage esophageal cancer. This suggests that tumor-related cachexia can occur early in esophageal cancer and represents a poor prognostic marker.

Statin use after esophageal cancer diagnosis and survival: A population based cohort study

BackgroundA recent epidemiological study of esophageal cancer patients concluded statin use post-diagnosis was associated with large (38%) and significant reductions in cancer-specific mortality. We investigated statin use and cancer-specific mortality in a large population-based cohort of esophageal cancer patients. MethodsNewly diagnosed [2009–2012] esophageal cancer patients were identified from the Scottish Cancer Registry and linked with the Prescribing Information System and Scotland Death Records (to January 2015). Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by post-diagnostic statin use (using a 6 month lag to reduce reverse causation) and to adjust these HRs for potential confounders. Results1921 esophageal cancer patients were included in the main analysis, of whom 651 (34%) used statins after diagnosis. There was little evidence of a reduction in esophageal cancer-specific mortality in statin users compared with non-users after diagnosis (adjusted HR=0.93, 95% CI, 0.81, 1.07) and no dose response associations were seen. However, statin users compared with non-users in the year before diagnosis had a weak reduction in esophageal cancer-specific mortality (adjusted HR=0.88, 95% CI, 0.79, 0.99). ConclusionsIn this large population-based esophageal cancer cohort, there was little evidence of a reduction in esophageal cancer-specific mortality with statin use after diagnosis.

Prediagnosis aspirin use and outcomes in a prospective cohort of esophageal cancer patients.

Background:Esophageal cancer remains associated with poor outcomes, yet little is known regarding factors that influence survival. Aspirin use prior to cancer diagnosis may influence outcomes. We aimed to assess the effects of prediagnosis aspirin use in patients with esophageal cancer.Methods:We conducted a prospective cohort study of newly-diagnosed esophageal cancer patients at two tertiary care centers. We assessed history of prediagnosis aspirin use, and prospectively followed patients and assessed mortality, cause of death, and development of metastases.Results:We enrolled 130 patients, the majority of whom were male (81.5%) and had adenocarcinoma (80.8%). Overall, 57 patients (43.9%) were regular aspirin users. In unadjusted analyses, we found no difference in all-cause mortality between aspirin users and nonusers. In multivariate analyses, prediagnosis aspirin use was not associated with all-cause mortality [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.48–1.57] or esophageal cancer-specific mortality (HR 1.07, 95% CI 0.52–2.21). Prediagnosis aspirin use was associated with a significantly increased risk of interval metastasis (HR 3.59, 95% CI 1.08–11.96).Conclusions:In our cohort of esophageal cancer patients, prediagnosis aspirin use was not associated with all-cause or cancer-specific mortality. However, risk of interval metastatic disease was increased among those who took aspirin regularly prediagnosis. Future studies are warranted to assess whether aspirin influences the molecular characteristics of esophageal tumors, with potential prognostic and therapeutic implications.

Abstract 2637: Impact of pre-diagnosis weight loss on outcomes in a prospective cohort of esophageal cancer patients

Abstract Background: Esophageal cancer survival rates remain extremely low and factors influencing outcomes for this malignancy are not well understood. Tumor cachexia is a poor prognostic factor for certain tumor types, but is not well-studied in esophageal cancer. Weight loss in esophageal cancer is likely multifactorial; it can be due to tumor cachexia as well as dysphagia from obstructing tumors. In this present study, we aimed to investigate the relationship between weight loss and overall survival in a cohort of esophageal cancer patients and to determine whether these associations differed with tumor size. Methods: We prospectively enrolled subjects with recently diagnosed esophageal cancer at two tertiary care centers. Using a baseline questionnaire, we assessed demographics, medical history, medication use, and lifestyle factors. We recorded self-reported height and weight one year prior to and at diagnosis, which we used to calculate body mass index (BMI) and percent weight change, categorized by tertile. We ascertained from the medical records tumor characteristics including T stage (T1/2 or T3/4), location, pathology, and metastasis status, and collected follow-up data on treatment, imaging, and death. We used Cox regression to assess the association between percent weight loss and all-cause mortality. Results: We included 134 subjects in the analyses, the majority of whom were male (81.3%) and had adenocarcinoma (82.1%). The median BMI one year prior to diagnosis was 28.3 (IQR 24.4 - 31.0) and median percent weight loss was 4.7% (IQR 0 - 10.9%). There was no association between BMI one year prior and all-cause mortality (HR 0.98, 95% CI 0.93 - 1.03). Increasing percent weight loss was associated with increased risk of all-cause mortality (unadjusted HR 2.74 for highest vs. lowest tertile, 95% CI 1.34 - 5.58, Ptrend = 0.005) and this remained significant when adjusted for BMI one year prior (HR 2.87 for highest vs. lowest tertile, 95% CI 1.40 - 5.89, Ptrend = 0.003). We found significant interaction between weight loss and T stage. Percent weight loss was significantly associated with all-cause mortality, adjusted for BMI one year prior, among patients with T stages 1 or 2 (HR 6.49 for highest vs. lowest tertile, 95% CI 1.30 - 32.4, Ptrend = 0.012), but not T stages 3 or 4 (HR 1.42 for highest vs. lowest tertile, 95% CI 0.54 - 3.71). In the final multivariable model, there remained a significant association between percent weight loss and all-cause mortality among patients with T stages 1 or 2 (HR 6.34 for highest vs. lowest tertile, 95% CI 1.22 - 33.1, Ptrend = 0.022). Conclusions: In this cohort of esophageal cancer patients, we found that pre-diagnosis weight loss was associated with increased risk of all-cause mortality in patients with earlier stage tumors, independent of baseline BMI. We suspect that weight loss in early stage esophageal cancer may be due to tumor cachexia, a potential marker of more aggressive disease and worse prognosis. Citation Format: Sherry Shen, James L. Araujo, Nasser K. Altorki, Joshua R. Sonett, Adriana Rodriguez, Kivilcim Sungur-Stasik, Alfred I. Neugut, Julian A. Abrams. Impact of pre-diagnosis weight loss on outcomes in a prospective cohort of esophageal cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2637.

Esophageal Cancer Patients Have a High Incidence of Severe Periodontitis and Preoperative Dental Care Reduces the Likelihood of Severe Pneumonia after Esophagectomy

Background: Poor oral health is a risk factor for causing upper aerodigestive tract tumors, including esophageal cancer. Our aim was to determine the periodontitis rate in our cohort of esophageal cancer patients. We also analyzed whether preoperative dental examination and care reduces the likelihood of severe pneumonia after esophagectomy. Study Design: Between 2003 and 2014, 529 esophageal cancer patients received esophagectomy at Akita University Hospital. We studied 232 patients who had preoperative dental examinations and care (dental care group) retrospectively and assessed the severity of their periodontitis. The dental care group was compared to 297 patients who did not have preoperative dental care (control group) with respect to the incidence of severe pneumonia after esophagectomy. Results: Ninety-one patients (39.2%) in the dental care group were diagnosed with slight periodontitis and 69 (29.7%) were diagnosed with severe periodontitis. Among all the patients, 69 patients (13.0%) were diagnosed with grade 3B postoperative severe pneumonia. The dental care group had a significantly lower incidence of severe pneumonia than the control group. Moreover, multivariable logistic regression analysis revealed that anastomotic leakage, preoperative dental care, gender and %VC were correlated significantly with the occurrence of postoperative severe pneumonia. Conclusion: Preoperative dental examination and care by a dentist are essential to reduce the likelihood of postoperative severe pneumonia in esophageal cancer patients.

High dose-rate endoluminal brachytherapy for primary and recurrent esophageal cancer : Experience from a large single-center cohort.

The aim of this work was to evaluate outcomes and toxicities of high dose-rate (HDR) endoluminal brachytherapy in acohort of esophageal cancer patients. We analyzed the records of 36patients treated with HDR brachytherapy for histologically confirmed esophageal cancer. Brachytherapy was either applied as aboost treatment for definitive treatment regimens or as salvage therapy for recurrent tumors with single doses between 4and 6Gy. Survival and toxicities were retrospectively analyzed. Brachytherapy was performed as initially planned in all but one patient; 18patients had acomplete endoscopic response at the first follow-up examination. Locoregional recurrence was observed in 24patients after amedian time of 3months; 1‑ and 2‑year recurrence-free survival rates were 51and 51 % for the patients treated for primary tumors and 11and 6 % for patients treated for tumor recurrence, respectively. Median overall survival was 18months; estimated overall survival rates at1, 2,and 3years were 63, 50,and 30 % after primary brachytherapy, and 60, 25,and 6 % after recurrence therapy. Adenocarcinoma histology, non-complete remission after treatment, and treatment for recurrent cancers were associated with significantly reduced prognoses. Mild dysphagia was the most common side effect in 17patients; 8patients suffered from locoregional grade3 toxicities, and no grade4 or5 toxicities were observed. Endoluminal brachytherapy during the course of esophageal cancer treatment can be safely applied and results in good functional outcomes regarding dysphagia with low rates of severe toxicities.

A high body mass index in esophageal cancer patients is not associated with adverse outcomes following esophagectomy.

There is no consensus about the impact of a high BMI on postoperative morbidity and survival after esophagectomy. The aim of this study was to determine the influence of a high BMI on postoperative complications and survival in a large cohort of esophageal cancer patients. From January 2006 to December 2012, 1,342 consecutive esophageal cancer patients who underwent esophagectomy were included in this study. Patients were divided into three groups: 950 patients were classified as normal BMI (BMI 18.5-24.9 kg/m(2)), 279 were classified as high BMI (BMI ≥ 25 kg/m(2)), and 113 as low BMI (BMI < 18.5 kg/m(2)). Multivariate logistic regression models were used to identify confounding factors associated with postoperative complications. The impact of BMI on overall survival (OS) was estimated by the Kaplan-Meier method and Cox proportional hazard models. The predominance of pathological type was esophageal squamous cell carcinoma (n = 1,280, 95.4 %). Overall morbidity, mortality, and hospital stay did not differ among groups. The incidence of pneumonia was higher in patients with high BMI compared with those with normal BMI (14.7 vs. 9.9 %, P = 0.025). However, chylothorax was less frequent in high-BMI group (0.4 % in high-BMI group, 3.1 % in normal group, and 3.5 % in low group, P = 0.011). Logistic regression analysis revealed high BMI was independently associated with decreased incidence of chylothorax [HR 0.86; 95 % confidence interval 0.76-0.97]. Overweight and obese patients had significantly better overall survival than underweight patients (median OS 55.6 vs. 32.5 months, P = 0.013), while the pathological stage was significantly higher in underweight patients (P = 0.001). In multivariate analysis, T status, N status, differentiation grade, and tumor length were identified as independent prognostic factors. A high BMI is not associated with increased overall morbidity following esophagectomy; moreover, it is associated with decreased incidence of chylothorax. The better overall survival in patients with high BMI compared with those with low BMI might be due to a relatively low pathological stage. A high BMI should therefore not be a relative contraindication for esophagectomy.

Functional Polymorphisms Associated with Disease-Free Survival in Resected Carcinoma of the Esophagus

PurposeThe aim of this study was to determine whether clinical outcome after surgical resection of esophageal adenocarcinoma (EAC) or esophageal squamous cell carcinoma (ESCC) could be predicted by functional polymorphisms in different proto-oncogenes and tumor suppressor genes. Experimental DesignSix single nucleotide polymorphisms (SNPs) in the AURKA (rs2273535), ERBB2 (rs1136201), MDM2 (rs2279744), CDH1 (rs5030625), CDKN2A (rs11515), and TP73 (rs2273953) genes were genotyped in a consecutive cohort of 346 esophageal cancer patients, who had underwent surgical resection with curative intent. Associations with disease-free survival (DFS) were analyzed with Kaplan–Meier curves and Cox regression, adjusting for potential confounders. ResultsUnivariate analysis showed no significant associations between the tested polymorphisms and DFS in patients with EAC or ESCC. However, in a multivariate analysis, patients with EAC carrying the heterozygous MDM2 (rs2279744) T/G genotype had significantly improved DFS compared with patients carrying the wild-type genotype (adjusted hazard ratio (AHR), 0.63; 95% confidence interval (CI) [0.45–0.88]). Patients with EAC harboring the homozygous CDH1 (rs5030625) GA/GA genotype had a significantly reduced survival as compared with patients carrying the wild-type genotype AHR 4.0, 95% CI [1.4–11]. ConclusionsIn a large cohort of esophageal cancer patients, the MDM2 T/G and CDH1 GA/GA genotype confer risk of death in patients with EAC. These data suggest that inter-individual differences in germ-line DNA have an impact on DFS in patients with EAC.

High-dose preoperative chemoradiotherapy in esophageal cancer patients does not increase postoperative pulmonary complications: Correlation with dose–volume histogram parameters

Purpose To investigate the association of high-dose preoperative chemoradiotherapy (CRT) and dose–volume histogram (DVH) parameters of lungs with incidence of postoperative pulmonary complications and to identify predictive clinical factors of pulmonary complications. Methods Data of 65 patients were collected retrospectively. Thirty-five patients underwent transthoracic esophagectomy (TTE) alone and 30 received cisplatin and 5-fluorouracil, concomitant with radiotherapy, median dose 66 Gy, and followed by TTE. From the DVH for each lung alone and for both lungs together as one organ we generated total lung volume, mean radiotherapy dose, relative and absolute volumes receiving more than a threshold dose, and relative and absolute volumes receiving less than a threshold dose. Postoperative pulmonary complications were defined as pneumonia or respiratory failure. Results Sixty percent of the patients in the TTE alone group had postoperative pulmonary complications versus 63% in the CRT + TTE group. Postoperative mortality was 8.6% and 16.7% in the respective patient groups ( p = NS). None of the DVH parameters was associated with postoperative pulmonary complications. Squamous cell carcinoma was an adverse factor related to increased postoperative pulmonary complications. Conclusion High-dose preoperative CRT was not associated with increased postoperative pulmonary complications in this cohort of esophageal cancer patients.