Incidence and Impact of Lymphopenia Associated With Total Neoadjuvant Therapy for Low-Lying Rectal Tumors.

Purpose/Objective(s) To assess incidence of lymphopenia and its association with outcomes in patients treated with total neoadjuvant therapy (TNT) for low-lying rectal tumors. Materials/Methods Patients with Stage II-III, low rectal adenocarcinomas treated from 2015-2018 with TNT were retrospectively reviewed. All patients were candidates for an APR surgical resection, but were treated with intent to omit surgery if they had a clinical complete response. All patients received definitive radiation (median dose 54 Gy, range 50-56 Gy, at 1.8-2 Gy/fx) with concurrent capecitabine, with additional chemotherapy (CT) delivered either prior to or following chemoradiation (CRT). Institutional results on patient outcomes have previously been reported with a clinical complete response rate of 75%; with only 19% of those ultimately requiring surgery for local recurrence. Absolute lymphocyte counts (ALC) were collected prior to initiating CRT and at 3-month intervals following CRT and graded based on severity of lymphopenia (absolute lymphocyte count Results A total of 28 patients with low rectal cancers were treated with TNT during this period, with ALC analyzed for the 26 who had detailed lymphocyte data available. 7 patients were treated with CT followed by CRT, receiving a median of 8 (range 4-8) cycles of CT, and 18 patients were treated with CRT followed by CT, receiving a median of 6 cycles (range 1-9). One patient refused CT after CRT. Prior to initiating CRT, the median ALC was 1,665/mm3 (range, 710-3,060/mm3), with lymphopenia present in only 4 patients (1 neoadjuvant CT and 3 adjuvant CT). The median ALC nadir during CRT was 450/mm3 (range, 230-900/mm3), with all 26 patients experiencing lymphopenia during the course of CRT: 4% Grade 1, 35% Grade 2, 61% Grade 3, and 0% Grade 4. Rates of lymphopenia at 3-, 6-, and 12-months post CRT were 73%, 81%, and 42%, respectively. On Cox regression analysis, increased pre-CRT and 12-month post-CRT lymphocyte counts were associated with a decreased risk of need for surgery (P 0.05). Conclusion Despite the frequency of lymphopenia during CRT, the degree of lymphopenia during and up to 6 months after CRT did not appear to predict future surgery. However, increased pre-CRT and 12-month post-CRT ALC were associated with decrease need of surgery. CRT produces both oxidative stress and immune response stimulation to kill cancer cells. Patients with higher pre-CRT and 12-month post-CRT ALC may represent a population with more robust immune systems, producing more favorable tumor responses. Additional studies are warranted.