Feasibility of weekly cisplatin and radiotherapy for localized anal cancer - A Danish anal cancer group report.

BACKGROUND: Chemoradiotherapy (CRT) with flourouracil and mitomycin is the standard treatment for squamous cell carcinoma of the anus (SCCA), however the associated acute toxicity often hinders compliance. Although weekly cisplatin is a well-established treatment for other squamous cell carcinomas, it has not been explored in SCCA. PURPOSE: To investigate if radiotherapy (RT) with weekly cisplatin is a feasible option for SCCA and to report the acute toxicity. MATERIAL/METHODS: Patients were treated with RT and weekly cisplatin 40 mg/m2 between 1998-2020. Retrospective data from medical records (n = 65) and prospectively collected data from an observational study (n = 51) comprising physicianassessed toxicity (NCI-CTCAE 4.0), patient-reported outcomes (EORTC-QlQC30 + CR29) baseline, mid-therapy, end of treatment and 2-4 weeks post-treatment were included. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: We included 116 patients. T-stages were T1:4 %, T2: 71 %, T3: 17 %, T4: 8 % and 47 % has N + disease. RT doses were 53.75-64 Gy/45-51.2 Gy and the mean cumulative dose of cisplatin was 307.5 mg. The median overall treatment time was 43 days. Within 6 months after CRT 88.9 % had complete response. The median follow-up time was 4.5 years and 5-year DFS and OS were 77 % (95 %CI 68.7-84.5 %) and 86.4 % (95 %CI 78.3-91.7 %), respectively. Hospitalization occured in 20 % with 2.6 % being admitted due to febrile neutropenia. Hematological toxicty was low with 13.7 % grade 3 and 3.9 % grade 4. Anal pain, skin, gastrointestinal and urogenital toxicity were mild. CONCLUSION: RT and weekly cisplatin for SCCA showed good outcome results and an acceptable acute toxicity profile.

Estimated dose to site of loco-regional recurrence after radiotherapy in anal cancer using point of origin methods.

Background and purpose: Loco-regional recurrence (LRR) dominates the failure pattern after curative radiotherapy in anal cancer. The aim of this study was to estimate dose of LRRs in anal cancer using a point of origin-based method. Method and materials: Of 321 patients with squamous cell carcinoma of the anus, 31 patients with LRR (29 local recurrences and 5 regional lymph node recurrences) were available for analysis. The recurrence volumes were delineated on recurrence magnetic resonance imaging (rMRI). Rigid and subsequent deformable co-registration of planning computerised tomography scans and rMRI were performed. Point of origin was estimated as the centre of mass (COM) and an observer-based point of origin (obs-PO). Doses to COM and obs-PO, as well as the full recurrence volume, were estimated and the relation to target volumes was extracted. Results: The median minimum dose to COM was 63.8 Gy (range 32.5-65.1 Gy) and 63.7 Gy (range 35.5-65.2 Gy) to obs-PO of local recurrences. COM was included in the high dose volume (64 Gy) in 86 % of cases, and obs-PO was included in 75 % of cases. There was no difference in minimum dose to COM and obs-PO, and the median distance between the two points was 3.3 mm (range 0.6-19.8 mm). No recurrences occurred in primarily boosted lymph nodes. Conclusion: The majority of LLRs were located within the high dose volume indicating radioresistance as the primary cause of recurrence in anal cancer. No difference between the use of COM and obs-PO was evident.