Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI "usual fatigue" at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.