Pretreatment high cholesterol and low neutrophils predict complete pathological response after neoadjuvant short‑course radiotherapy followed by chemotherapy and immunotherapy in locally advanced rectal cancer

Abstract

The present study was aimed at looking for hematological indicators that could predict pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with short-course radiotherapy (SCRT) followed by chemotherapy and immunotherapy. A total of 171 patients were enrolled in this observational retrospective study. Pretreatment values of albumin, total cholesterol, lactate dehydrogenase, neutrophil, platelet and lymphocytes were available. Univariate and multivariate logistics analyses were used to determine the prognostic factor for pCR. SCRT followed by chemotherapy and immunotherapy was demonstrated to double the pCR rate (50.5%) compared with long-course chemoradiotherapy. For the former group, baseline high platelet to lymphocyte ratio (P=0.047), high cholesterol (P=0.026) and low neutrophils (P=0.012) level were associated with high pCR rate and baseline high cholesterol (P=0.016) and low neutrophils (P=0.020) level were the independent prognostic factors for pCR. In conclusion, pretreatment high cholesterol and low neutrophils were the independent prognostic predictors of pCR in patients with LARC treated with SCRT followed by chemotherapy and immunotherapy. Clinical trial no. NCT04928807, June 16, 2021.

Keywords: immunotherapy; locally advanced rectal cancer; pathological complete response; short-course radiotherapy.

Figure 1.

Treatment regimen. CAPOX course, oxaliplatin 130 mg/m² intravenously, day 1; capecitabine 1,000 mg/m² oral twice daily, days 1–14. Camrelizumab, 200 mg intravenous drip, day 1. LC-CRT course, 28×1.8 Gy on 5 days per week, oral capecitabine (825 mg/m², bid, days 1–5) during radiotherapy. Surgery was performed according to total mesorectal excision principles. CAPOX, capecitabine plus oxaliplatin; SCRT, short-course radiotherapy; LC-CRT, long-course chemoradiotherapy; SCRT, 5×5 Gy over 5 days.

Figure 2.

Rates (%) of pCR, TRG, T-downstaging and N-downstaging and the differences between different groups. (A) pCR rate and (B) TRG rate were significantly different between Arm A and Arm B and between Arm A and Arm C (A, P=0.002; B, P=0.003). There was no difference between Arm B and Arm C. (C) Rate of T-downstaging was significantly different between Arm A and Arm B. There was no difference between Arm A and Arm C and between Arm B and Arm C (P=0.026). (D) Rate of N-downstaging showed no difference between the three groups (P=0.388). *P<0.05; NS, no significance; pCR, pathological complete response; TRG, tumor regression grade.

Figure 3.

Change of (A) T-stage and (B) N-stage from baseline in Arm A. The percentage of patients in Arm A with different preoperative (cT or cN) and postoperative (ypT or ypN) (C) T-stage and (D) N-stage. *Patient with a postoperative T-stage of tis. cT, clinical-stage; cN, clinical T-stage; pT, pathologic T-stage; pN, pathologic N-stage; tis, tumor in situ.