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

170 Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict for survival in cancer patients. In patients receiving multi-modality therapy, the effect of each specific therapy on the NLR and PLR is not well understood. We therefore evaluated changes in NLR and PLR among locally advanced esophageal cancer patients who received trimodality therapy. Methods: We performed a retrospective analysis of non-metastatic patients with esophageal cancer who received neoadjuvant chemoradiation (CRT) followed by esophagectomy at our institution between March 2000 and April 2012. NLR and PLR values were obtained the following time points (TP): 1) at diagnosis before CRT, 2) after CRT prior to surgery, and 3) after surgery. We also evaluated change in NLR and PLR using the difference and ratio between TPs. Overall survival (OS) was evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of NLR and PLR. Results: 83 patients with stage II-IV esophageal cancer and median age 60 years were included. Median follow up was 29.3 months. Median dose of 50.4 Gy (50.4-59.4) in 28 fractions (28-33) was used. Median NLR and PLR at the each TP: 1) 3.3 and 157.2, 2) 12 and 645, and 11.5 and 391.7, respectively. On multivariate analysis, inferior OS was associated with PLR ≥250 at TP 3 (p=.03), PLR decrease ≥609.2 from TP 2-3 (p=.02), and PLR ratio (TP 1/TP3) ≥1.08 (p=.03). Inferior progression free survival (PFS) was associated with NLR at TP 2 ≥36 (p=.0008), NLR increase ≥28.3 from TP 1-2 (p=.0005), PLR increase from TP 1-3 ≥19 (p=.01), and PLR ratio (TP 2/TP 3) ≥0.34 (p=0.1). Pathologic complete response (pCR) was less likely for adenocarcinoma histology (p=.03), NLR at TP 2 ≥10.6 (p=.04), and NLR increase from TP 1 to TP 2 ≥4.6 (p=.03). Conclusions: This is the first study to demonstrate that changes in NLR and PLR throughout trimodality therapy for esophageal cancer correlate with OS, PFS, and pCR. Further evaluation is warranted to better define which of the identified cut-off values are most clinically significant.

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Next-generation sequencing to identify predictors of survival after trimodality therapy for esophageal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.153 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 153-153

Author(s):

Patrick Oh ◽

Minsi Zhang ◽

Paul Brady ◽

Smita Sihag ◽

Daniela Molena ◽

...

Keyword(s):

Overall Survival ◽

Esophageal Cancer ◽

Next Generation Sequencing ◽

Prognostic Factor ◽

Cancer Patients ◽

Pathologic Response ◽

Next Generation ◽

Trimodality Therapy ◽

Generation Sequencing ◽

Mutation Profiling

153 Background: Tumor mutation profiling has changed the prognostication and treatment of a wide variety of malignances. However, little is known about whether mutation profiles affect outcome in localized esophageal cancer treated with multimodality therapy. SMAD4 is a gene involved in the regulation of the TGF-β signal transduction pathway by negatively controlling the growth of epithelial cells and has been implicated as a prognostic factor in pancreatic cancer. We undertook an exploratory analysis of tumor mutation profiles, including SMAD4 status, in localized esophageal cancer patients treated with trimodality therapy at our institution. Methods: We identified 66 Stage II-III esophageal cancer patients treated with chemoradiation followed by surgery who had some form of tumor mutation profiling available. Only patients with mutation profiling from pre-treatment biopsy or post-chemoradiation surgical specimen (i.e. not from a subsequent metastatic lesion) were included. Twenty-two patients underwent next-generation sequencing assessing 341 candidate genes via targeted sequencing. Log-rank test was used to assess correlation of mutations to overall survival, and to pathologic response. Results: The median follow-up was 17.1 months. SMAD4 loss was identified in 3 of 22 patients (13.6%) who underwent next-generation sequencing, and was significantly associated with inferior overall survival (p=0.023). No other candidate genes were significantly associated with survival, and no genes were significantly associated with pathologic response. Conclusions: To our knowledge, this is the first analysis of next-generation mutation profiling and outcome in non-metastatic esophageal cancer patients treated with trimodality therapy. Due to the limited numbers, this was an exploratory analysis only. We identified SMAD4 loss as a potential adverse prognostic factor for survival. More next-generation sequencing data from non-metastatic esophageal cancer patients treated with multimodality therapy is needed to further elucidate the potential relationship of SMAD4 loss or other mutations with outcome.

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Pre-treatment pulmonary function testing as a predictor of cardiopulmonary toxicity in esophageal cancer patients treated with trimodality therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.121 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 121-121

Author(s):

Na Lu Smith ◽

Christopher Leigh Hallemeier ◽

Grant M. Spears ◽

Thorvardur Ragnar Halfdanarson ◽

Michelle A. Neben-Wittich ◽

...

Keyword(s):

Esophageal Cancer ◽

Pulmonary Function ◽

Cancer Patients ◽

Pulmonary Toxicity ◽

Univariate Analysis ◽

Pulmonary Function Testing ◽

Trimodality Therapy ◽

Tertiary Center ◽

Pre Treatment ◽

Function Testing

121 Background: We evaluated the role of pre-treatment pulmonary function testing (PFT) in predicting the likelihood of cardiac and/or pulmonary toxicity for esophagus cancer patients receiving trimodality therapy. Methods: From 2007 to 2013, 64 patients with esophageal cancer received trimodality therapy at a single tertiary center with pre-treatment PFTs. The odds ratio of pre-treatment PFT as a predictor of cardiopulmonary toxicity was assess with univariate analysis (UVA). FEV1 (forced expiratory volume in 1 second) and DLCO (diffusion capacity for carbon monoxide) were assessed per 0.5-unit decrease. Percent FEV1 and DLCO predicted were assessed per 10% decrease. Results: The median age was 62 years (range, 41-79) with 88% male patients. A total of 70% of patients had adenocarcinoma with 66% having stage 3 disease. Most patients were former (43%) or current smokers (32%) and 18% had COPD. One or more cardiac comorbidities were observed in 54% of patients. The median RT dose was 50 Gy and the most frequent concurrent chemotherapy was cisplatin/5FU (53%). The median pre-treatment FEV1 and DLCO was 2.8 liters (range, 1-4.9) and 22.5 mL/min/mmHg (range, 17.2-25.5), respectively. This correlated to a median percent predicted value for FEV1 and DLCO of 85% (range, 30-124%) and 81.5% (range, 49-119%), respectively. The overall rate of any cardiac and pulmonary toxicity was 35% and 50%, respectively. Percent predicted value of both FEV1 and DLCO was statistically associated with pulmonary but not cardiac toxicity (Table). Conclusions: Patients with compromised pre-treatment pulmonary function are at higher risk of developing post-treatment pulmonary toxicities. Pulmonary function testing should be routinely performed prior to initiation of trimodality therapy for patient risk stratification. [Table: see text]

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777 IS ADJUVANT CHEMOTHERAPY FOR ESOPHAGEAL CANCER WITH RESIDUAL DISEASE AFTER TRIMODALITY THERAPY FUTILE? A NATIONWIDE MULTICENTRIC SURVEY

Diseases of the Esophagus ◽

10.1093/dote/doab052.777 ◽

2021 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Alexandru Lintis ◽

Caroline Gronnier ◽

Clarisse Eveno ◽

Guillaume Piessen

Keyword(s):

Esophageal Cancer ◽

Multivariate Analysis ◽

Residual Disease ◽

Locally Advanced ◽

University Hospitals ◽

Trimodality Therapy ◽

Adjuvant Immunotherapy ◽

Treatment Characteristics ◽

First Choice ◽

Matched Study

Abstract For patients with resectable locally advanced esophageal cancer (EC), trimodality therapy associating neoadjuvant chemoradiation and surgery is the standard of care. However, the risk of recurrence for patients with residual disease (RD) remains high and there is no established adjuvant treatment modality in this setting. Adjuvant immunotherapy recently exhibited promising results but ACT could also play a beneficial role. This study evaluated the potential benefit of ACT in RD after trimodality therapy for EC. Methods A multicenter database for the surgical treatment of EC collected data from 30 university hospitals (2000–2010). Patients with RD in completely resected EC after trimodality therapy where included and separated in an ACT group and a non-ACT group. Demographics, tumor and treatment characteristics, morbidity, overall and recurrence-free survival (OS and RFS) where compared. Uni and multivariate analysis were performed to identify factors associated with OS. Survival analysis of patients treated with and without ACT was performed in a propensity score matched study. Results From 2944 patients included, 484 had RD after trimodality therapy, and 9.3% (n = 45) were treated with ACT. There were no major differences in demographics, preoperative tumor and treatment characteristics between groups. Major complications where higher in the non-ACT group (31 vs 20%, p = 0.018). ACT group had more nodal involvement (78 vs 45%, p < 0.001). OS and RFS were significantly worse in the ACT group (median: 36.0 vs 46.7mo, p < 0.001 and 25.5 vs 47.9mo, p = 0.029 respectively). After multivariate analysis, ACT was independently associated with worse OS (HR = 3.69, p < 0.001). In the propensity matched study, OS and RFS remained worse in ACT group. Conclusion This study supports current recommendations concerning ACT abstention in EC with RD after trimodality therapy. In light of the promising results of the BMS Checkmate 577 study, adjuvant immunotherapy in this setting should therefore be considered as the first choice of treatment.

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