Change in chemotherapy during concurrent radiation followed by surgery after a suboptimal positron emission tomography response to induction chemotherapy improves outcomes for locally advanced esophageal adenocarcinoma

Abstract

Background PET scan after induction chemotherapy before pre-operative chemoradiation and surgery for esophageal adenocarcinoma predicts outcomes. Some patients with progression on PET after induction chemotherapy had long-term overall survival (OS) when changed to alternative chemotherapy during radiation. Patients and methods We retrospectively reviewed esophageal adenocarcinoma patients who received induction chemotherapy and chemoradiation prior to planned surgery; all had PET scan before and after induction chemotherapy. Results Of 201 patients, 113 (56%) were PET-responders (≥35% decrease in maximum standardized uptake value of tumor). All PET-responders received the same chemotherapy during radiation, while 38 (43%) of 88 PET non-responders changed chemotherapy. Of 152 operated patients, the pathologic complete response (pCR) rate was 15% in PET-responders vs. 3% in PET non-responders who did not change chemotherapy (p=0.046). Median progression-free survival (PFS; 18.9 vs. 9.6 months, p=0.003) and OS (37 vs. 25.3 months, p=0.02) were significantly better for PET responders vs. PET non-responders who did not change chemotherapy. Median PFS for PET non-responders who changed chemotherapy was 18.0 months and was superior to PET non-responders who did not change chemotherapy (p=0.015). For PET non-responders, the 5-year OS rates were 37% for those who changed chemotherapy vs. 25% for those who did not change chemotherapy (p=0.18). Conclusions PET scan after induction chemotherapy predicts for outcomes in locally advanced esophageal adenocarcinoma patients who undergo chemoradiation and surgery. Median PFS is improved and trends toward improved OS appear possible in PET non-responders who change chemotherapy during radiation. The fully-accrued CALGB 80803 study (NCT01333033) is evaluating this strategy.

Positron-Emission Tomography Scan–Directed Chemoradiation for Esophageal Squamous Cell Carcinoma: No Benefit for a Change in Chemotherapy in Positron-Emission Tomography Nonresponders

“…Preliminary results showed a pCR rate of 17% and 19% in PET nonresponders who changed from carboplatin to FOLFOX and from FOLFOX to carboplatin/ paclitaxel respectively, compared to a historic rate of 3% in a retrospective analysis performed at MSK. 19 Furthermore, median OS was 47.3 months in PET responders versus 28.9 months in PET nonresponders (p ¼ 0.09). 10 Based on comparison with historic controls, changing chemotherapy in PET nonresponders appears to improve survival in this patient population.…”

Combined tumor plus nontumor interim FDG‐PET parameters are prognostic for response to chemoradiation in squamous cell esophageal cancer

“…2,8 The applicability of an interim positron emission tomography (PET) scan with 18 F-fluorodeoxyglucose (FDG) to measure response to CRT is of limited use with current standard PET parameters, especially in ESCC, 9 although PET-tailored treatment has shown some promising results in adenocarcinomas of the esophagus. 10 Currently, the most often investigated FDG-PET/CT parameter is tumor glucose uptake quantified as standardized uptake value (SUV). However, SUV quantification has several wellknown shortcomings, for example, uptake time dependence of the SUV, interstudy variability of the arterial input function and susceptibility to errors in scanner calibration.…”

“…The applicability of an interim positron emission tomography (PET) scan with 18 F‐fluorodeoxyglucose (FDG) to measure response to CRT is of limited use with current standard PET parameters, especially in ESCC, although PET‐tailored treatment has shown some promising results in adenocarcinomas of the esophagus …”

18F-FDG PET Response After Induction Chemotherapy Can Predict Who Will Benefit from Subsequent Esophagectomy After Chemoradiotherapy for Esophageal Adenocarcinoma

“…Changing the chemotherapy regimen during radiation for 18 F-FDG PET nonresponders might also be effective. Ku et al reported that patients who did not respond on 18 F-FDG PET after induction chemotherapy and whose chemotherapy was changed during the chemoradiotherapy had significantly better PFS than did patients whose chemotherapy regimen was not changed (14). On the other hand, whether nonresponders can proceed directly to surgery is unclear.…”

“…Previous studies have suggested that 18 F-FDG PET response after induction chemotherapy could predict pathologic complete response (pCR) and was associated with survival outcomes in esophageal cancer patients treated with induction chemotherapy followed by neoadjuvant or definitive chemoradiotherapy (11)(12)(13). Moreover, an early 18 F-FDG PET response could provide useful information for choosing a chemotherapy regimen to be used during radiation for those who do not show an 18 F-FDG PET response (14). However, the value of 18 F-FDG PET response after induction chemotherapy in terms of identifying which patients will benefit from subsequent surgery after chemoradiotherapy has never, to our knowledge, been investigated.…”