Effect of Anemia on Tumor Response to Preoperative Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Abstract

Preoperative neoadjuvant chemoradiotherapy (nCRT) and total rectal mesenteric resection (TME) are the primary treatment options for locally advanced rectal cancer (LARC), but their efficacy varies. This study aimed to investigate the impact of anemia on the tumor response of patients with LARC receiving preoperative neoadjuvant chemoradiotherapy. This study was a retrospective analysis of clinical and pathological data from patients with LARC who underwent nCRT and TME from January 2019 to May 2022 at a single institution. The tumor response was evaluated based on the tumor regression grade (TRG) and T-stage change of the primary tumor. Hemoglobin concentration was measured and graded to determine the presence of anemia. Anemia was categorized into four groups based on the hemoglobin levels: mild anemia (90-120 g/L), moderate anemia (60-90 g/L), severe anemia (30-60 g/L), and extreme anemia (less than 30 g/L). Finally, tumor response was quantified histologically using the AJCC 8th edition tumor regression grading system for rectal cancer and pre- and post-treatment T-grading. A total of 88 patients with LARC who received nCRT and TME were included in the study, with 17 females and 71 males. Of these patients, 9 were moderately anemic and 37 were mildly anemic. The radiation therapy regimen was administered at a dose of 1.8-2 Gy per fraction, five times a week, for a total dose of 45-50.4 Gy. Capecitabine chemotherapy was also administered orally (825 mg/m2, twice a day) on the days of radiation therapy. Other chemotherapy regimens included XELOX and mFOLFOX6. The TRG was significantly different in anemic patients compared to non-anemic patients (P = 0.039). Only 2 out of 46 anemic patients (4%) showed an excellent response (TRG0), while 8 out of 42 non-anemic patients (19%) showed an excellent response (p = 0.043). There was also a significant difference in the incidence of anemia between cT3 and cT4 stages (p = 0.048), with 44% of cT3 patients and 67% of cT4 patients being anemic. The number of patients with poor response (TRG2-3) decreased as the degree of anemia decreased, but no significant difference was found. The incidence of TRG3 was 11% in patients with moderate anemia and 7% in non-anemic patients (P = 0.863). There was no significant difference in postoperative pathological T-stage between anemic and non-anemic patients. 89% of anemic patients had a pathological stage of ypT3 or less after chemoradiotherapy, while 95% of non-anemic patients did (P = 0.167). The pre- and post-treatment pathological staging did not significantly differ between anemic and non-anemic patients. 67% of anemic patients had descending tumors, while 59.5% of non-anemic patients had descending tumors (p = 0.509). Patients with LARC who have normal hemoglobin concentrations during nCRT have better tumor regression compared to patients with anemia. Additionally, the incidence of anemia was higher among patients with advanced T-stage prior to treatment.