Baseline and temporal patterns of fatigue predict pathological response in patients treated with preoperative chemoradiation therapy (CRT) for rectal cancer

14522 Background: We investigated whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathological response, a surrogate for treatment outcome. Methods: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Most patients had T3 tumors (94%) and hemoglobin > 12 (85%). Symptom burden was prospectively assessed prior to (baseline) and weekly during CRT by a patient self-reported questionnaire, the MD Anderson Symptom Inventory (MDASI). Survival probabilities were estimated non-parametrically using Kaplan-Meier’s product limit method. Lowess curves were plotted for symptom burden across time. Logistic regression was used to determine whether symptom burden levels predicted for pathological response. Results: Among 51 patients evaluable for pathological response, 9 patients (18%) achieved pCR, and 26 patients (51%) had TDS. The actuarial rates of local control (LC), disease-free survival (DFS), and overall survival (OS) at 2 years were 93%, 76%, and 98%, respectively. Patients with TDS had lower levels of fatigue at baseline and at completion (week 5) of CRT compared to those without TDS (p = 0.03 for both). A similar trend was not observed for other symptom burden parameters of pain, sleep disturbance, appetite, nausea, or feeling of sadness. Evaluation of the potential effect of symptom burden on pCR, LC, DFS, or OS was not possible because of the low number of events during the 2-year median follow-up. Conclusions: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathological response, as gauged by TDS. Unlike studies that have documented improved quality of life among responders, our study demonstrates the converse, i.e. fatigue, a measure of symptom burden, independently predicted for tumor response. This provocative finding could potentially be used to stratify patients into prognostic groups, influence treatment decisions, and/or modify treatment. An evaluation of changes in cytokine profile during CRT is ongoing to determine the molecular basis of this phenomenon. No significant financial relationships to disclose.