A national study to assess outcomes of definitive chemoradiation regimens in proximal esophageal cancer

Abstract

Background: Proximal esophageal cancer (EC) is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone are still under debate. The objective of this study was to compare the treatment outcomes of contemporary CRT regimens. Material and Methods: In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal esophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004 and 2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin-paclitaxel (CP) combined with low (50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) weighted model. Safety profiles were compared using a multilevel logistic regression model. Results: Two hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cislow-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI: 47.9-77.2 months). Median OS (21.9 months; 95% CI: 16.9-27.0 months) was comparable between treatment groups (logrank p ¼ .88), confirmed in the fully adjusted and PS weighted model (p > .05). Grades 3-5 acute adverse events were less frequent in patients treated with CP-low-dose RT versus Cis-high-dose RT (OR 3.78; 95% CI: 1.31-10.87; p ¼ .01). The occurrence of grades 3-5 late toxicities was not different between treatment groups. Conclusion: Our study was unable to demonstrate a difference in OS between the CRT regimens, probably related to the relatively small sample size. Based on the superior safety profile, carboplatin and paclitaxel-based CRT regimens are preferred in patients with locally advanced proximal EC.

Patterns of recurrence following definitive chemoradiation for patients with proximal esophageal cancer

“…Patients were identified in site-specific databases, complemented with the Netherlands Cancer Registry, a population-based cancer registry of all newly diagnosed malignancies in the Netherlands. We identified 200 consecutive patients who underwent definitive CRT for proximal EC, from January 2004 to December 2014 [15]. All patients had histologically confirmed SCC of the proximal esophagus, with maximum distal extension up to 24 cm of the incisors, in which supraclavicular nodal involvement was allowed.…”

“…Since the TNM classification did not essentially change, no coding was performed to a uniform TNM version, except nodal status which was converted into N1 excluding subdivision of N1/2/3. Further information on the study protocol was described previously [15].…”

“…Prognosis of proximal esophageal cancer (EC) is poor, providing three-year overall survival (OS) rates in patients treated with CRT of about 35e45% [4e11]. Our previous retrospective cohort study showed comparable OS between four different CRT regimens including cisplatin or carboplatin and paclitaxel backbones and low (50.4 Gy) or high dose (>50.4 Gy) radiotherapy (RT) [12]. Longterm survival is only achieved in complete responders to CRT [7,9,13,14].…”

Treatment patterns and survival in advanced unresectable esophageal squamous cell cancer: A population‐based study

“…Twenty‐three percent of patients with SCLNM who received chemoradiotherapy and/or had resection were still alive after 3 years. The 3‐year survival rate was higher in previous studies of patients with esophageal cancer who had received definitive chemoradiotherapy (36%‐46%) 5,21 . A population‐based study of the CROSS regimen reported 5‐year survival rates of 62% and 38%, depending on response after neoadjuvant chemoradiotherapy 22 .…”

“…The 3-year survival rate was higher in previous studies of patients with esophageal cancer who had received definitive chemoradiotherapy (36%-46%). 5,21 A population-based study of the CROSS regimen reported 5-year survival rates of 62% and 38%, depending on response after neoadjuvant chemoradiotherapy. 22 Similarly, survival after definitive chemoradiotherapy predominantly depended on response, with complete responders showing a 3-year survival rate of 58%.…”