Comparing Toxicity and Outcomes Between Twice-Daily (BID) vs. Pulsed Low-Dose Rate (PLDR) Radiotherapy (RT) for Reirradiation of Anorectal Cancers.

Purpose/objective(s) Reirradiation (RI) can cause significant toxicity. BID-RT is a known regimen for rectal cancer recurrence. PLDR-RT is a promising alternative in which doses are delivered in pulses of small doses, with an effective rate of 0.07 Gy/minute. PLDR-RT widens the therapeutic window by making use of poor repair mechanisms of tumor cells. A previous phase I trial demonstrates its safety. We compared toxicity and local control between BID-RI and PLDR-RI of anorectal cancers. Materials/methods This is a single institutional IRB-approved retrospective review of patients previously treated with pelvic RT who underwent BID-RI or PLDR-RI for rectal or anal cancers between 2005-2020. Wilcoxon rank-sum and Fisher's exact tests were used to compare continuous and categorical variables. Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was used to grade toxicities. Univariable logistic regression was used to assess the association between toxicity Grade ≥2 and radiation modalities. Cumulative incidence function was used to estimate local progression distribution. Difference between modalities and dose groups was compared using Chi-square tests. Results Twenty-six patients were included, with 24 rectal and 2 anal cancers. Median age was 59. 73% were males. 11 were in the BID-RI and 15 in PLDR-RI cohorts. Concurrent chemotherapy was more prevalent with BID-RI (81.8 vs. 33.3%; P = 0.021). No differences in age, sex, incidence or post-RT surgery were present. Median EQD2 of previous RT were 50 and 49.6 Gy (P = 0.60). PLDR-RI had higher total EQD2 (103.6 vs. 87.4 Gy; P = 0.07), median RI dose (50 vs. 39 Gy; P = 0.009), and proportion with RI dose ≥50 Gy (66.7 vs. 18.2%; P = 0.021). BID-RI had higher incidence of any grade GI/GU toxicity (81.8 vs. 33.3%; P = 0.021) (Table 1). PLDR-RI had no grade ≥3 GI and grade 4 toxicities. PLDR-RI was less likely to have any toxicity (OR = 0.15, CI:0.02-0.94, P = 0.04) and GI/GU toxicity (OR = 0.11, CI:0.02-0.72, P = 0.02). PLDR-RI trended toward less likelihood of grade ≥2 GI/GU toxicity (OR = 0.21; P = 0.07). No differences in local progression-free survival alone (0.66) or with death as a competing risk (P = 0.22) were found. Dose ≥50 Gy had no impact on local progression (P = 0.62). Conclusion PLDR-RI of anorectal cancers appears to demonstrate a significant improvement in incidence and severity of toxicity compared to BID-RI. This is possible without compromising local progression-free survival. Increased utilization of PLDR-RI may be indicated.