Definitive Intent Locoregional IMRT In Oligometastatic Anal Squamous Cell Carcinoma

Abstract

The role of locoregional intensity modulated radiation therapy (IMRT) in patients with metastatic anal squamous cell carcinoma (SCC) remains undefined. There is growing evidence of the potential benefit of local therapy even in the setting of oligometastatic disease to prevent the morbidity of uncontrolled pelvic disease. We queried an institutional database of 358 consecutive patients with SCC of the anal canal treated with definitive intent pelvic IMRT from 2005 to 2018 to identify patients with de novo metastatic disease. Locoregional control (LRC), progression-free survival (PFS), and overall survival (OS) were computed using the Kaplan-Meier method. Acute and late toxicities were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Twenty-five patients with a median follow-up of 26 months including 19 (76%) women and 6 (24%) men with a median age of 60 years comprised the evaluable cohort. Eight (32%) patients had a solitary metastasis, 10 (40%) had two metastatic lesions, 2 (8%) had three metastatic lesions, 5 (20%) had four or more metastatic lesions. Non-regional lymph nodes were the most common site of metastatic disease (N = 16, 49%) followed by liver (N = 10, 30%), lung (N = 4, 12%), and others (N = 3, 9%). Sixteen patients had HPV related disease and 3 patients were HIV+. The median dose to the primary tumor was 56Gy (range, 50-58Gy) in a median of 28 fractions (range, 25-29) over a median of 39 elapsed days (range, 35-55). Twelve (48%) patients received induction chemotherapy and all patients received concurrent chemotherapy predominately mitomycin and capecitabine based. Twenty-one (84%) patients had metastatic-directed ablative therapy which included radiation (N = 20, 80%) and IR-ablation (N = 1, 4%). No patients underwent metastasectomy or received additional chemotherapy, targeted therapy, or immunotherapy prior to progression of disease. The 3-year LRC was 81%, PFS was 27%, and OS was 53%. In comparing patients with non-regional lymph node involvement to patients with visceral organ involvement there was no significant difference in LRC (86% vs. 79%, p = 0.950) but a trend for improved PFS (71% vs. 18%, p = 0.069) and OS (86% vs. 49%, p = 0.365). Grade 3+ acute toxicity included dermatitis (12%), proctitis (4%), and diarrhea (4%). Late grade 2+ toxicity rate was 12%. Definitive intent pelvic IMRT provides excellent locoregional control in patients with oligometastatic anal SCC. Local and extended regional nodal radiation is important to prevent the significant morbidity of uncontrollable pelvic disease given durable PFS and OS in patients with oligometastatic anal SCC.