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Pattern of failure after radiotherapy for squamous cell carcinoma of the anus
Background
Squamous cell carcinoma of the anus (SCCA) is primarily treated with radiotherapy (RT). Treatment failure is predominantly locoregional within the pelvic area. Information on the pattern of failure is important when optimizing treatment strategies. The aim of this study was to evaluated pattern of failure and outcome after radiotherapy for SCCA.
Methods
A single center, retrospective study was conducted, including patients with histopathological proven SCCA diagnosed between 1998 and 2018 and treated with RT with curative intention. Data was collected from medical records and included patient-, disease-, and treatment characteristics, and outcome data. Disease stage was reclassified according to the 8th edition of the TNM staging system. Locoregional failure (LRF) was defined as failure within the pelvis, and distant failure (DF) as failure outside the pelvis. Survival data were estimated using the Kaplan-Meier method.
Results
In total 420 patients treated with curative RT were identified. Median age was 60 years (range 28-89), 75.0% were female, 68.8% had T1-T2 tumors, and 30.9% were diagnosed with lymph node (LN) positive disease. All patients received RT, RT only (79.8%) or with concomitant chemotherapy (19.3%), further 30.7% received induction chemotherapy. Treatment planning was done with IMRT/VMAT in 76.4% of cases, and median prescribed dose to tumor was 64Gy (range 45-64), 64Gy (range 50-64) to pathological LN and 51.2Gy (range 39-54) to the elective nodal areas. Median follow-up (FU) time was 6.1 years (range 0.05-23.6). Overall survival for all stages at 3- and 5 years was 84.0% and 75.5%, respectively and disease-free survival was 73.2% and 69.9% at 3 and 5 years. 85.9% (n=361) achieved complete response (CR) after RT whereas 13.8% (n=58) was diagnosed with progressive or persistent disease, of whom 94.8% had salvage surgery performed. Of patients with CR after RT 19.1% (n=69) experienced treatment failure during FU. As first site of recurrence 13.0% had LRF (n=47), 5.0% had DF (n=18), and 1.1% had both LRF and DF (n=4). When combining both persistent disease and later recurrence 30.2% experience treatment failure. In general, few regional LN recurrences were observed (1.7% of first failures including 0.6% with LN only failures). Recurrence in regional LN was located to the mesorectal LN (n=2), inguinal LN (n=3) or iliac LN (n=1). DF as first site of failure was seen in 22 cases (6.1%) located to either the lung (n=11), liver (n=7) distant LN (n=8), bone (n=1), brain (n=1) or other (n=2) with 8 patients having failure to more than one site. When looking at subsequent failures DF was seen in further 14 cases with a total DF rate of 8.6%.
Conclusions
Recurrences to regional LN and DF were low, and the majority of recurrences were thus located within the standard irradiated area. Consequently, it is highly relevant to investigate the exact anatomical location and its relation to specific treatment dose. A dose-mapping study is therefore ongoing.
Legal entity responsible for the study
The authors.
Funding
Aarhus University Hospital Danish Society of Cancer Danish Comprehensive Cancer Center – Radiotherapy Health Research Foundation of Central Denmark Region.
Disclosures
All authors have declared no conflicts of interest.
