P53 gene protein overexpression predicts results of trimodality therapy in esophageal cancer patients

1999 ◽  
Vol 68 (6) ◽  
pp. 2021-2024 ◽  
Author(s):  
Mark J Krasna ◽  
You Sheng Mao ◽  
Joshua R Sonett ◽  
Gen Tamura ◽  
Ray Jones ◽  
...  
2016 ◽  
Vol 39 (2) ◽  
pp. 136-141 ◽  
Author(s):  
Grace J. Kim ◽  
Matthew Koshy ◽  
Alexandra L. Hanlon ◽  
M. Naomi Horiba ◽  
Martin J. Edelman ◽  
...  

2014 ◽  
Vol 9 (4) ◽  
pp. 534-540 ◽  
Author(s):  
Aditya Juloori ◽  
Susan L. Tucker ◽  
Ritsuko Komaki ◽  
Zhongxing Liao ◽  
Arlene M. Correa ◽  
...  

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 170-170
Author(s):  
Jalal Hyder ◽  
Drexell Boggs ◽  
Andrew Hanna ◽  
Mohan Suntharalingam ◽  
Michael David Chuong

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.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 153-153
Author(s):  
Patrick Oh ◽  
Minsi Zhang ◽  
Paul Brady ◽  
Smita Sihag ◽  
Daniela Molena ◽  
...  

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.


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 ◽  
...  

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]


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 195-195
Author(s):  
Edwin Chan ◽  
Catherine Vanderwater ◽  
Rachel Woo ◽  
Charles Cho ◽  
Jason Wong ◽  
...  

195 Background: To document pattern of recurrence and its relationship to the radiation treatment volume in esophageal cancer patients treated with trimodality therapy. Methods: Patients with adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus, T1-4N0-3 (AJCC 7thEd.) treated with chemoradiation (CRT) and esophageal resection between June 2010 and November 2015 participated in a prospective cohort study. Patients were planned using 4DCT and IMRT or VMAT. GTV and CTV were contoured on 4D exhale, inhale phases and voluntary exhale helical CT. CTV margins were 3-4cm superiorly and inferiorly, and 1cm circumferentially. CTVs were combined to form the ITV. PTV margin was 0.5cm. Site of first disease recurrence was classified as in-field (within 90% isodose), marginal (between 50-90%), or out-of-field (outside 50%). Results: Fifty-eight patients participated. Median age was 66 years (range: 40–78); 52 males: 6 females. 49 had adenocarcinoma, 7 SCC, and 2 mixed histology. 52 (90%) had clinically node positive disease. 31 received concurrent radiation 45-50Gy/25fr with Cisplatin/5FU and 27 received 41.4Gy/23fr with Carboplatin/Paclitaxel (CROSS protocol). 15 (27%) achieved a pathological complete response (pCR). Median follow up was 1.6 years (range: 0.2-4.8), 2-year overall survival 71%, disease-free survival 59%, median survival 4.4 years and median time to relapse 2.3 years. 17 patients (29%) had disease recurrence of which, at initial diagnosis, all were clinically node positive and 3 had pCR after CRT. Five developed locoregional recurrence (2 anastomatic, 3 locoregional nodes), 4 both locoregional and distant, and 8 distant recurrence alone. Of 9 patients with locoregional recurrence, 1 had in-field, 6 out-of-field and 2 had disease traversing in and out-of-field areas. 4 of 17 (24%) were treated with curative intent (1 surgery, 3 CRT) and all were alive at the latest follow up (time from first recurrence: 6 to 49 months). Conclusions: Survival and recurrence outcomes in this small cohort are similar to those reported in the literature. Only a small proportion of patients experienced in-field relapse. Of those who relapsed, 24% received curative salvage therapy.


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