Abstract

Background: Esophageal cancer is the fourth most common cause of cancer-related deaths in India. In 2012, the CROSS trial evaluated the benefit of induction therapy using weekly carboplatin-paclitaxel with 41.4 Gy radiation versus surgery alone. Pathological complete response (pCR) rates were 28%. Overall survival was improved in the combined therapy arm. However, there is limited data regarding the outcomes of preoperative chemoradiation in Indian scenario. This study was conducted to determine the response to preoperative chemoradiation at a tertiary cancer center in India. Aims: Primary objective was to evaluate the rates of pCR. Secondary objective was to determine recurrence rate and patterns of recurrence. Materials and Methods: We retrospectively reviewed patients with locally advanced esophageal cancer and gastroesophageal junction treated from September 2013 to July 2015. Patients who received preoperative radiotherapy 41.4 Gy with chemotherapy (weekly paclitaxel-carboplatin or cisplatin-5 FU or cisplatin-capecitabine) were included in this study. Chi-square test and Fischer's exact test were used for analysis. Results:: Fifty patients were included in the analysis (76% – squamous cell carcinoma [SCC] and 24% – adenocarcinomas [ACC]). About 60% patients received weekly paclitaxel-carboplatin (CROSS protocol), 32% cisplatin-5 FU, and 8% cisplatin-capecitabine. pCR rate was 39.6%. pCR rate was higher in SCC versus ACC (44.7% vs. 20%) and in paclitaxel-carboplatin than cisplatin-5FU or cisplatin-capecitabine (48.3% vs. 25% vs. 33.3%). At a median follow-up of 12 months, 38 patients were alive, 8 died, and 4 lost to follow-up. Of the 10 patients that recurred, 8 were distant recurrences. Conclusion: Our study results show favorable pCR rate after preoperative CRT with significant higher rate in SCC and patients receiving CROSS regimen. Majority of the recurrences were distant recurrences.

Introduction

Esophageal cancer is the fourth most common cause of cancer-related deaths in India. Squamous cell carcinoma is the most common histology (80%) although there has been a recent relative increase in the incidence of adenocarcinoma.[1]

In 2012, a multi-institutional Phase III study (CROSS trial) evaluated the benefit of induction therapy using weekly carboplatin and paclitaxel with 41.4 Gy radiation versus surgery alone.[2] The pathological complete response (pCR) rate was 28%, and overall survival was much improved in the combined therapy arm. However, there is limited data regarding the outcomes of preoperative chemoradiation in Indian scenario. Esophageal cancer in India has a unique etiological basis (alternative forms of tobacco and tea drinking).[1] Most patients present in advanced stage and poor general health at diagnosis. This retrospective study was conducted to determine the response to preoperative chemoradiation at a tertiary care center in India.

Aims

Primary objective was to evaluate the rates of pCR and to determine the significance of various factors affecting pCR. Secondary objective was to determine the recurrence rate and patterns of recurrence.

Materials and Methods

We retrospectively reviewed patients with locally advanced esophageal cancer (middle and lower third) and gastroesophageal junction (Siewert I and II) treated at our hospital from September 2013 to July 2015. These patients were selected from a larger cohort of operable esophageal cancer patients as they were planned for neoadjuvant chemoradiation followed by surgery. Information on demographic data, initial investigations, and treatment administered were recorded from our hospital database for 50 patients. The pretreatment workup included a physical examination, esophagogastroscopy and biopsy, chest and abdominal computed tomography (CT), and 18F-fluorodeoxyglucose-positron emission tomography, if necessary. After completion of neoadjuvant chemoradiotherapy and before surgery, all patients were imaged with CT abdomen and pelvis. Patients who received preoperative radiotherapy dose of 41.4 Gy with chemotherapy (weekly paclitaxel-carboplatin or cisplatin-5 FU or cisplatin-capecitabine) were included in this study. The outcomes analyzed were pCR, recurrence rate, and recurrence patterns. An ethics committee approval was taken before starting the study. An informed consent was taken from all study participants.

Treatment

Radiotherapy

External beam radiotherapy was administered using LINAC 6MV or 15MV photons. Radiation technique was based on the discretion of the radiation oncologist. Total dose delivered was 41.4 Gy in 23 fractions of 1.8 Gy, 5 fractions per week. Thirty-nine patients were treated by conventional technique, 4 patients by 3DCRT, and 7 patients by IMRT technique. The gross tumor volume (GTV) was defined by the primary tumor and any enlarged regional lymph nodes. The planning target volume was defined by giving a proximal and distal margin of 4 cm. In case of tumor extension into the stomach, a distal margin of 3 cm was chosen. A 2 cm radial margin around the GTV was provided to include the area of subclinical involvement and to compensate for tumor motion and set up variations.

Chemotherapy

Chemotherapy was administered concurrently on the 1st day of radiotherapy (RT). Only patients who received concurrent chemotherapy regimen of paclitaxel and carboplatin or cisplatin and 5 fluorouracil or cisplatin and capecitabine were included in the analysis.

Surgery

Surgery was scheduled for 6–8 weeks after preoperative chemoradiotherapy. Complete resection (R0) was characterized by negative margins on microscopic examination. Incomplete resection was determined by the presence of microscopic residual disease (R1) or gross residual disease (R2)

Evaluation of response

Pathologic response evaluation was performed by analyzing surgical specimens. A pCR was defined by the absence of histologically identifiable residual cancer in the tumor and lymph nodes and fibrosis extending through the different layers of the esophagus.

Follow-up

The patients were followed up postsurgery at 1 month initially, then every 3 months for first 2 years and every 6 months till 5 years and yearly thereafter, to determine recurrence rates, recurrence patterns, and mortality.

Statistical analysis

Patients were followed up periodically until the last follow-up or death. Postoperative mortality was defined as death on the day of surgery or within 30 days postsurgery. The relationship of various prognostic factors with pCR was computed using Chi-square test and Fischer's exact test SPSS is a statistical software (statistical package for the social sciences). P < 0>

Results

A total of 50 patients were included in the analysis (females – 32, males – 18). The median age was 50 years (22–70 years). All patients had ECOG PS <2 href="https://www.thieme-connect.com/products/ejournals/html/10.4103/ijmpo.ijmpo_16_16#TB_1" xss=removed>Table 1].