Dose escalated neoadjuvant chemoradiotherapy with dose-painting intensity-modulated radiation therapy and improved pathologic complete response in locally advanced esophageal cancer

Abstract

We compared pathologic complete response (pCR) rate, toxicity, and postoperative complications between patients treated preoperatively with 50.4 Gy versus dose escalation with dose-painting intensity-modulated radiation therapy (dp-IMRT) to 56 Gy in locally advanced esophageal cancer. We evaluated esophageal cancer patients treated between 2006 and 2014 with preoperative IMRT chemoradiation to a dose of 50.4 Gy versus 56 Gy. The endpoints were pCR and toxicity. We identified 113 patients (50.4 Gy: n = 40; 56 Gy: n = 73). There were no significant differences in tumor or patient characteristics. Patients treated with 56 Gy demonstrated a higher pCR rate (56.2% vs. 30.0%) and lower pathologic nonresponse rate (4.1% vs. 20.0%) compared to patients treated to 50.4 Gy (P = 0.008). This remained significant on multivariate analysis (OR 3.375 95%CI 1.3-8.8, P = 0.013). Patients treated to 56 Gy also had an improved 3-year locoregional control rate compared to those treated to 50.4 Gy (93.8% vs. 78.5%; P = 0.022). The estimated 3-year freedom from failure was also superior in the 56 Gy arm (73.7% vs. 52.2%; P = 0.051), approaching significance. There were no differences in treatment related grade ≥3 toxicities, hospital admissions, feeding tube, esophageal stent placement, or dilation. There was, however, a statistically significant increase in postoperative atrial fibrillation in patients treated with 56 Gy (30.1% vs. 12.5%; P = 0.036). There was no difference in postoperative 30 or 60 day mortality. Dose escalation to 56 Gy with dp-IMRT is safe and results in significantly higher complete pathologic response rates in esophageal cancer without an increase in treatment-related toxicity. Prospective trials using dp-IMRT are needed to address the role of dose escalation on pCR rate and survival in esophageal cancer.

Pretreatment CT and 18F‐FDG PET‐based radiomic model predicting pathological complete response and loco‐regional control following neoadjuvant chemoradiation in oesophageal cancer

“…In our selected population, we observed pCR in 34 (50%) patients following NACRT, which is in accordance with published reports 1–3,5 . The CROSS study reported pCR rates of 29% with a radiation dose of 41.4 Gy.…”

Neoadjuvant and Definitive Radiochemotherapeutic Approaches in Esophageal Cancer: A Retrospective Evaluation of 122 Cases in Daily Clinical Routine

“…This is in agreement with our results. On the other hand, a study published in 2017 showed a higher rate of local control with no increase in therapy-related toxicity [32].…”

“…This is in agreement with our results. On the other hand, a study published in 2017 showed a higher rate of local control with no increase in therapy-related toxicity [32]. The literature published so far proclaims the need of further studies especially with regard to improved radiation techniques, tumor histology, tumor localization, therapeutic alternatives, and salvage options in cases of local failure, e.g.…”

A FDG-PET radiomics signature detects esophageal squamous cell carcinoma patients who do not benefit from chemoradiation

“…Two randomized phase-III studies compared definitive CRT and preoperative CRT followed by surgery and did not find a statistical significant OS benefit in favor of the additional surgery but an increased number of loco-regional recurrences in the organ preservation arm 6 , 7 . After preoperative CRT tumor specimens of up to 20% of patients do not show major signs of regression 2 , these patients would be candidates for alternative treatment approaches that might comprise immediate surgery, checkpoint inhibition, image based radiation dose escalation or other 8 – 12 .…”