Patterns of Failure in Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiation Followed By Surgery:

Abstract

BACKGROUND: Kashmir valley is a high prevalence zone for esophageal squamous cellcarcinoma(ESCC). Despite significant improvement in treatment modalities in the past few decades, the overall survival in these patients still remains dismal with only upto 20% of patients living till 5years. After curative tri-modality  therapy  with  neo-adjuvant radiation and chemotherapy (NACRT) followed  by surgery, patterns of failure in these patients will provide an insight into the natural history and biology of this disease and can guide our future efforts for intensification of various therapeutic approaches.

AIMS AND OBJECTIVES: All patients of locally advanced ESCC treated with NACRT followed by Surgery were assessed for failure patterns and survival analysis.Primary end point of this study was to find recurrence patterns:local (anastomotic site),regional and distant.Secondary end points were disease free survival and overall survival.

PARTICIPANTS:Patients aged ≥ 18 to 70 years with biopsy proven locally advanced ESCC,who underwent tri-modality treatment, NACRT followed by surgery(R0 resection).

STUDY DESIGN: This study was a hospital based retrospective observational study.

METHODS:All patient data were retrieved from Hospital Based Cancer Registry (HBCR) database, RCC SKIMS from 2013 to 2018. Patients who received curative treatment with NACCRT followed by surgery.Chemotherapy included weekly paclitaxel (50 mg/m²) and carboplatin (AUC2). Radiotherapy included 40 to 50.4 Gray in 20-25 daily fractions to the esophagus and draining lymph nodes. All patients underwent surgery within the three months of completion of NACRT.Recurrence patterns were assessed and reported as local recurrence, loco-regional and distant failure. At the completion of study, survival analysis by using Kaplan Meierwere presented in months. All the analysis were done by using SPSS-v-23.0 and the association between variables was shown byStudents T-test& chi square test.

RESULTS:A total of 40 patients were recruited. Mean±SD age of patients was 56 ± 8 years.Of all 40 patients, 15 patients (37.5%) have recurred, 3 died immediately in post-operative period and 22 patients were on follow up till study completion. The recurrence pattern observed was local in 2(13.30%), regional in 4 (26.60%, and distant failure in 7 (46.60%) patients. In our patients, we observed the mean diseasefree survival (DFS) was 32.891 ± 2.268 months and the mean OS was 42.316 ± 2.573 months.

Tumor regression grading (TRG) was not initially included in primary or secondary end points.However, we observed that out of 40 recruited patients, 21 patients(52.5%) had complete response (TRG-1). TRG-2 and TRG-3 was present in 6 (15%) patients each, TRG-4 in 4 patients (10%) and TRG-5 in 3 patients (7.5%).

CONCLUSION: We noted an overall recurrence rate of 37.5% (15/40), with most of the failures being distant followed by locoregional recurrence. Isolated local recurrence was only 5.0% (2/40). Mean DFS was 34 months and mean OS was 42 months. To conclude, a significant number of patients with locally advanced ESCC fail even after receiving NACCRT, most of them at distant sites (with or without locoregional failure).

IMPLICATIONS:As significant number of patients with locally advanced ESCC patients fail even after receiving trimodality treatment regimen.This emphasizes the need for novel systemic and/or locoregional protocols to further improve the recurrence rates and outcomes in these patients.