Feasibility and toxicity of hypofractionated radiotherapy (5x5 Gy) with a simultaneous integrated boost (5x6 Gy) in locally advanced rectal cancer: 2023 update

Hypofractionated RT (5x5 Gy) with or without subsequent chemotherapy (CTx) is a standard of care used at National Institute of Oncology, Warsaw, Poland as a preoperative treatment for locally advanced rectal cancer. In order to maximize the chance of achieving complete response (CR) in case of clinically involved lymph nodes located outside of the standard TME field or when surgery is not planned RT can be augmented with a simultaneous integrated boost (SIB) delivering 5x6 Gy. The aim of this updated report is to further evaluate feasibility and safety of hypofractionated RT with a SIB in rectal cancer. From Dec 2018 to Sep 2022 total 78 consecutive pts with a stage II (n=14), III (n=55) and IV (n=9) rectal adenocarcinoma and with a median age of 67 years (range 36-89 years) received hypofractionated RT utilizing a SIB-VMAT technique. The radiation dose fractionation was 5x5 Gy to the rectum, mesorectum and elective lymph nodes and a SIB to the nodal or the rectal tumor GTV to a total dose of 30 Gy. 30 pts (38.5%) received a SIB to the rectal tumor from which 15 pts (19.2%) were deemed unfit for surgery, 10 pts (12.8%) refused surgical treatment, 3 pts (3.8%) had an oligometastatic disease and 2 pts (2.6%) had an advanced primary tumor. 48 pts (61.5%) received a SIB to the clinically involved lymph nodes located outside of the standard TME field. All 78 pts completed RT as planned without interruptions or dose modifications. After a median follow-up of 273 days (range 5-1388 days) there was a 9.0 % (n =7) incidence of grade 2 diarrhea, 9.0% (n=7) grade 2 proctitis, 3.8% (n=3) grade 2 skin toxicity, 2.6% (n=2) grade 2 cystitis, 2.6% (n=2) grade 2 lumbosacral plexus neuropathy. 1 patient experienced grade 3 proctitis and required outpatient treatment. 2 pts experienced grade 3 diarrhea of which 1 required outpatient treatment and the other had to be hospitalized. There were no grade 2-5 hematological toxicities. Out of 51 pts who were initially qualified to receive subsequent CTx after completion of RT, 39 pts (76.5 %) received CTx without delay. In 10 cases (19.6%) CTx had to be postponed for a median of 7 days (range 2-11 days) due to grade 2 proctitis (n=5), grade 2 diarrhea (n = 3) or both proctitis and diarrhea (n=2). 2 pts (3.9%) were ultimately disqualified from CTx due to grade 3 toxicities (diarrhea and proctitis). Hypofractionated RT with VMAT-SIB delivering a dose of 30 Gy/25 Gy/5 fractions has the acceptable toxicity profile and remains a viable option for patients who will not undergo surgery and for patients with involved lymph nodes located outside of the standard TME field to maximize the chance of achieving CR.