Toxicities and outcomes of neoadjuvant treatment in elderly patients with locally advanced rectal cancer: A scoping review.

Abstract

91 Background: Neoadjuvant treatment (NAT) followed by surgery has become the standard treatment for locally advanced rectal cancer (LARC). This scoping review aims to assess the toxicity and outcomes of the currently available NAT of rectal cancer in elderly patients with age-associated frailty. Methods: Six thousand seventy-nine records were identified on Ovid Medline, Embase, Cochrane database, and CINAHL. Two independent reviewers screened the articles. Fifteen articles were identified through a hand search. Articles on NAT in LARC in elderly patients were included. Results: Thirty-three studies from 2005 to 2022 met inclusion criteria, including 27 retrospective reviews, 4 clinical trials (Phase 1 and 2) and 2 prospective studies; 5 were multicentred. The median age of the sample was 70-75 in 24 studies and 76-83 in 11 studies. One study examined only patients above 80. Twenty-four studies examined NAT with long course concurrent chemoradiotherapy (LCCRT), 5 examined both LCCRT and RT alone, 3 examined short-course radiotherapy (SCRT), one examined SCRT with sequential chemotherapy (CT), and one study examined neoadjuvant CT followed by LCCRT. Concurrent CT with 5 FU-based treatments was given in 23 studies with either intravenous or oral, and oxaliplatin was added to 5 FU in 10 studies. Interruption of concurrent treatment was reported with dose reduction, delay or discontinuation in 26 studies. Diarrhea, nausea/vomiting and radiation dermatitis were reported as significant side effects (G3 -4), with G3-4 diarrhea reported in 18 studies. Haematological toxicities were very frequent, with a 20-60% rate in the studies. No dose interruption of RT was required in the three studies that included only SCRT, except for one patient. The study on CT followed by LCCRT showed that CT was completed in 82% and LCCRT in 76% of patients. A preliminary result of PRODIGE 42-GERICO 12 NACRE, a randomised trial comparing SCRT with chemoradiotherapy (CRT), showed that 14% of patients in the CRT arm did not receive all of the planned treatment compared to 0% in SCRT arm, and the 6 months death rate was 10.0% in CRT arm and 3.92% in SCRT. Conclusions: Toxicities are frequently reported with Neoadjuvant LCCRT in the elderly and lead to treatment interruption. SCRT is well tolerated and probably associated with better survival (pending final results of the NACRE trial). Studies in this scoping review are over-represented by retrospective studies, and we suggest that future clinical trials focus on elderly patients to investigate treatment strategies with fewer toxicities.