LBA 11 - REDEL Trial: Phase II Trial of Reduced Elective Nodal Dose for Anal Cancer Toxicity Mitigation

08:05am - 08:10am ET

Room 254

Presenter(s)

Jordan Kharofa, MD - University of Cincinnati, Cincinnati, OH

J. R. Kharofa¹, E. D. Miller², B. Nelson³, K. Wang³, O. Olowokure⁴, A. Rojan⁵, D. Sohal⁵, I. Paquette⁵, J. Snyder⁵, C. Justiniano⁵, S. Rai⁶, E. Thompson⁵, M. H. Sueyoshi⁷, S. Gillett⁸, J. Moore⁹, R. F. Palm¹⁰, A. Noonan¹¹, E. Huang¹², L. A. Kachnic¹³, and C. J. Anker¹⁴; ¹Department of Radiation Oncology, University of Cincinnati Cancer Center, Cincinnati, OH, ²Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, ³Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, ⁴University of Cincinnati Division of Hematology& Oncology, Cincinnati, OH, ⁵University of Cincinnati, Cincinnati, OH, ⁶Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, ⁷University of Vermont, Burlington, VT, ⁸University of Vermont Medical Center, Burlington, VT, ⁹University of Vermont, Department of Surgery, Burlington, VT, ¹⁰The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Columbus, OH, ¹¹Ohio State University, Columbus, OH, ¹²Division of Colon and Rectal Surgery and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH, ¹³Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY, ¹⁴University of Utah Health Science Center, Salt Lake City, UT

Purpose/Objective(s): Guidelines recommend 42–45 Gy (1.5–1.8 Gy/fx) to elective pelvic lymph nodes for anal cancer treatment. Historic trials employed lower doses with AP:PA non-conformal fields and large nodal boosts, with dose heterogeneity. The Toxicity Index (TI) captures cumulative adverse event burden across Dermatologic (Derm)/Gastrointestinal (GI)/Genitourinary (GU)/Hematologic (Hem) domains, compared to max-grade reporting. This phase II trial (n=33) evaluated whether conformal, reduced elective nodal dose with sequential boost to gross disease reduces the composite Derm/GI/GU/Hem TI while preserving regional nodal control.

Materials/Methods: Thirty-three patients were enrolled across three sites from 8/2023–11/2025. Patients were treated with VMAT using sequential boosts: 30.6 Gy/17 fx to elective lymph nodes (LN) and GTV boost to 50.4 Gy (<3 cm) or 54 Gy (=3 cm); CTV expansion: 5 mm for LN and 1 cm for GTV; PTV 5–7 mm. Patients received mitomycin and fluoropyrimidine. A composite TI was calculated using CTCAE events from treatment initiation to 90 days post-RT. The primary endpoint was the Derm/GI/GU/Hem TI for all CTCAE events with 80% power to detect an effect size of 0.4 compared to RTOG 0529. Secondary endpoints included elective nodal failure (stopping rule at 10%), DFS, OS, PRO-CTCAE scores, and FISI patient-survey sphincter function scores.

Results: Median age was 66 (range 40–78) with AJCCv8 stage I 9%, IIA 24%, IIB 39%, IIIA 18%, IIIC 6%, and 48% N+. The majority were female (79%) and received capecitabine (88%). Adverse events =Grade 3 occurred in 49% of patients. Grade =3 events by domain included: Hem 27% (9/33), GI 21% (7/33), Derm 9% (3/33), and GU 3% (1/33) when only maximum grade events are considered. Accounting for all events, the mean TI was 3.344 (SD 0.661; 95% CI 3.109–3.578), significantly lower than RTOG 0529 (mean 3.858, p<0.001; Cohen's d=0.577) and RTOG 9811 (mean 4.037). A treatment break (=3 days) was required in 6% of patients. At median follow-up of 16 months, zero elective nodal failures were observed. Six-month complete clinical response was 97% with 4 DFS events (3 distant metastases, 1 incomplete response). The 18-month DFS and OS were 90% (95% CI 72–97%) and 96% (95% CI 72–99%), respectively. High-grade PRO-CTCAE diarrhea (score =4) occurred in 50% at week 5 and 12% at 6 months. High grade PRO-CTCAE fecal incontinence (score =4) at week 5 and 6 months was 20% and 4%. However, longitudinal FISI assessment revealed severe sphincter leakage (FISI =30) in 39% at baseline with an increase to 61% at 6 months.

Conclusion: The REDEL trial demonstrates a significant reduction in the CTCAE Derm/GI/GU/Hem toxicity while maintaining high rates of disease control in elective lymph node regions warranting further study. Patient-reported GI symptoms during RT remain high but decrease at 6 months. However, significant sphincter dysfunction persists at 6 months in most patients. Mitigation strategies are needed.