Patient-Reported Outcome Measures during Chemoradiotherapy for Esophageal Cancer and Relationship with Pathologic Response

Abstract

Locally advanced esophageal cancer is generally treated with neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy. Pathologic complete response (pCR) has been shown to correlate with recurrence free and overall survival. Patients’ self-reported outcomes (PROs) for symptoms and quality of life (QOL) are increasingly measured. We seek to characterize the trajectories of PROs for patients undergoing CRT for esophageal cancer and investigate their relationship to pCR. This retrospective study included 60 patients with esophageal squamous cell or adenocarcinoma, stage cT2N0 or higher, treated with CRT between 2014 and 2016, who reported PROs weekly. Patients answered 16 questions relating to GI symptoms, derived from an EORTC questionnaire, and 10 questions relating to general well-being derived from the patient-reported outcomes measurement information system (PROMIS). Logistic regression was used to evaluate the relationship between PROs and pCR. P-values were not reported given the small sample size. Median follow-up was 24.0 months. Median age was 66.4 years, 20% of patients were female, and 85% had adenocarcinoma. Of the patients, 76.7% received 50.4 Gy in 28 fractions. All patients received concurrent chemotherapy, mainly carboplatin and paclitaxel; 66.7% underwent esophagectomy. Among patients who had surgery, 45% achieved pCR or near pCR. At last follow-up, 66.7% were alive. A total of 74.1% and 75.3% of patients responded to the EORTC and PROMIS questions, respectively. Response rates were lowest for week 1 (53.3% and 51.7% for EORTC and PROMIS, respectively) and highest for week 4 (83.1% and 81.4%). While patients had stable composite physical and mental health scores, they reported worsening GI symptoms and fatigue over time, with the largest changes in fatigue, “feeling weak,” ability to swallow, pain with swallowing, heartburn, and early satiety. Overall, no symptoms trended toward improvement; all symptoms progressively worsened over time. There was a correlation between pCR and some PROs, including worsening ability to swallow solid foods (OR 0.39; 95% CI 0.15-0.98) or liquids (OR 0.24; 95% CI 0.06-0.92), heartburn (OR 0.38; 95% CI 0.14-1.0), early satiety (OR 0.28; 95% CI 0.09-0.88), and overall QOL (OR 0.44; 95% CI 0.21-0.90). The OR for pCR <1 was calculated for all PROs, suggesting that worsening symptoms correlated with less pathologic response. Patients with esophageal cancer self-reported worsening fatigue and gastrointestinal symptoms, particularly dysphagia, heartburn, and early satiety, during neoadjuvant CRT. There was an association between worse symptoms and reduced pathologic response.