39 Background: Pelvic radiation and myelosuppressive chemotherapy can lead to lymphopenia during the course of preoperative chemoradiation when treating rectal cancer. Lymphopenia during chemoradiation has been associated with higher risks of recurrence in other cancers, possibly due to decreased immunosurveillance. The effect in rectal cancer is not well described. We hypothesize that high-grade lymphopenia is associated with worse progression-free survival (PFS) and overall survival (OS) in rectal cancer patients undergoing preoperative chemoradiation. Methods: All patients treated at our institution with neoadjuvant chemoradiation between 2013 and 2019 were reviewed (n = 99). The study was limited to patients with Stage II – IV (AJCC 8th edition) rectal adenocarcinoma. Patients were excluded if they had prior systemic therapy (n = 13) or if lymphocyte data was unavailable (n = 30). Lymphopenia which arose during or within 30 days of completion of chemoradiation was graded by the CTCAE v.4.0. Neoadjuvant Rectal (NAR) scores, indicators of pathologic response, were calculated for each surgical patient. Kaplan-Meier analysis was used to calculate PFS and OS. Two-tailed t-tests (a=0.05) were used to detect differences between subgroups. Results: Fifty-six patients met inclusion criteria. Grade 2 (G2) or higher lymphopenia occurred in 43 (76.8%) patients (G2 = 22, G3 = 20, G4 = 1). In patients with G2 vs G3-4 lymphopenia, there were no differences in baseline, treatment, or demographic characteristics. The median PFS for these patients was 20.0 months. Patients with G3-4 lymphopenia had significantly worse 2-year PFS compared to those with G2 lymphopenia (83.3% vs 59.3% p = 0.03). The two-year OS did not differ between groups (100% vs 60.3%, p = 0.10). Lymphocyte nadir did not correlate with pathologic response, as measured by the NAR score (r = -0.28, p = 0.07). Conclusions: In this study, G3-4 lymphopenia was associated with worse PFS in rectal cancer patients treated with neoadjuvant chemoradiation, despite a small sample size. The prognostic implications of lymphopenia in rectal cancer should be confirmed in larger cohorts and the underlying mechanisms explored.

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