Background
For patients with operable locally advanced esophageal carcinoma (LA-EC), we hypothesized that pre-operative induction chemotherapy followed by chemoradiotherapy (IC-CRT) would improve progression-free survival (PFS) and overall survival (OS) when compared to chemoradiotherapy (CRT).
Methods
This was a single institution retrospective cohort study including patients with LA-EC who received preoperative-intent IC-CRT
vs.
CRT between 2013–2019. The Kaplan-Meier method was used to estimate OS and PFS. Cox proportional hazards regression was used to assess for variables associated with survival. The impact of treatment group on pathologic response was assessed by chi-square.
Results
Ninty-five patients were included for analysis (IC-CRT n=59; CRT n=36) and the median follow-up was 37.7 months (IQR: 16.8–56.1). There was no difference in median PFS or OS for IC-CRT or CRT, 22 months (95% CI: 12–59)
vs.
32 months (95% CI: 10–57) (P=0.64) and 39 months (95% CI: 23–not reached)
vs.
56.5 months (95% CI: 38–not reached) (P=0.36), respectively. Amongst the subset of patients with adenocarcinoma histology, there was no difference in median PFS or OS, nor was there when analyses were further restricted to those who received ≥3 cycles of induction 5-fluorouracil and platinum, or for those who underwent esophagectomy. Pathologic complete response occurred in 45%
vs.
29% (P=0.24) and N-stage regression occurred in 72%
vs.
58% (P=0.28) of patients in the IC-CRT and CRT cohorts, respectively. Distant metastasis occurred in 44% of patients in each treatment cohort.
Conclusions
For patients with LA-EC, preoperative-intent IC-CRT was not associated with improved PFS or OS when compared with CRT.
was defined as chemotherapy and radiation starting within 14 days of each other, followed by chemotherapy, followed by definitive surgery four to six months later. Minimum follow up was 6 months, in order to account for immortal time bias. Multivariable logistic regression was performed to assess whether upfront chemotherapy followed by chemoradiation versus upfront chemoradiation followed by chemotherapy was significantly associated with pCR, defined as ypT0N0. Overall survival (OS) was analyzed via Kaplan-Meier method with the log-rank test. Multivariable Cox regression analysis was used to assess the impact of covariates on OS. Results: There were 9,393 TNT cases identified. Of these, 1522(16.2%) received C-CRT and 7871(83.8%) received CRT-C. The pCR was 12.2% in both groups. On multivariable logistic regression analyses, there was no difference in pCR based on the timing of the radiation (OR 0.987, 95% CI 0.824-1.183, P = .89). Kaplan-Meier analysis revealed that the 5-year OS rates for TNT was superior for C-CRT over CRT-C, with 5-year OS of 66.5% vs. 65.9% (P = 0020). However, on multivariable Cox regression, there was no significant difference in OS between C-CRT and CRT-C (HR = 0.981, 95% CI 0.864-1.115, P = 0772). Conclusion: In this large hospital-based study, most patients receiving TNT received chemoradiation upfront. There were no differences in pCR or overall survival based on the timing of the radiation treatments.
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