Patterns of recurrence in anal cancer: a detailed analysis

Abstract

Background: Anal cancer is a rare disease, which might be the reason for the "one size fits all" approach still used for radiotherapy target contouring. To refine and individualize future guidelines, detailed and contemporary pattern of recurrence studies are needed. Methods: Consecutive anal cancer patients, all treated with curative intent intensity-modulated radiotherapy (IMRT), were retrospectively studied (n = 170). Data was extracted from medical records and radiological images. Radiotherapy planning CT's and treatment plans were reviewed, and recurrences were mapped and categorized according to radiation dose. Results: The mean dose to the primary tumor was 59.0 Gy. With a median follow-up of 50 months (range 14-117 months), 5-year anal cancer specific survival was 86.1%. Only 1 of 20 local recurrences was located outside the high dose (CTVT) volume. More patients experienced a distant recurrence (n = 34; 20.0%) than a locoregional recurrence (n = 24; 14.1%). Seven patients (4.2%) had a common iliac and/or para-aortic (CI/PA) recurrence. External iliac lymph node involvement (P = 0.04), and metastases in ≥3 inguinal or pelvic lymph node regions (P = 0.02) were associated with a 15-18% risk of CI/PA recurrence. Following chemoradiotherapy, 6 patients with recurrent or primary metastatic CI/PA lymph nodes were free of recurrence at last follow-up. The overall rate of ano-inguinal lymphatic drainage (AILD) recurrence was 2 of 170 (1.2%), and among patients with inguinal metastases at initial diagnosis it was 2 of 65 (3.1%). Conclusions: We conclude that other measures than increased margins around the primary tumor are needed to improve local control. Furthermore, metastatic CI/PA lymph nodes, either at initial diagnosis or in the recurrent setting, should be considered potentially curable. Patients with certain patterns of metastatic pelvic lymph nodes might be at an increased risk of harboring tumor cells also in the CI/PA lymph nodes.

Treatment-related leukopenia in anal cancer patients associated with worse outcome: results of a retrospective cohort study

“…With a median follow-up of 50 months (range 14À117 months), the number of events were: LR (n ¼ 20), DR (n ¼ 34), OS (n ¼ 36), ACSS (n ¼ 23), and NACD (n ¼ 13). As previously reported, 5-year OS and ACSS were 79.9% and 86.1%, respectively [14].…”

“…The study population has been described previously [14]. Briefly, consecutive patients with non-metastatic squamous cell carcinoma of the anus (anal cancer), who received intensity-modulated radiotherapy (IMRT) with curative intent at Skåne University Hospital, Sweden, during the time period August 2009-December 2017 were included (n ¼ 170).…”

“…The following time to event endpoints was analyzed: local recurrence (LR), distant recurrence (DR), overall survival (OS), anal cancer-specific survival (ACSS), and non-anal cancer death (NACD) [14]. Follow-up and time to endpoint were defined from the date of diagnosis, except for LR, where it was defined from the end of radiotherapy.…”

Volumetric Modulated Arc Therapy Improves Outcomes in Definitive Radiochemotherapy for Anal Cancer Whilst Reducing Acute Toxicities and Increasing Treatment Compliance

“…Especially in locally advanced tumors, the cure rates remain suboptimal and locoregional recurrences are a frequent site of failure [ 3 , 4 ]. Additionally, distant metastases occur in about 20% of patients during follow-up [ 6 ]. Radiotherapy delivery with IMRT leads to a reduction in CRT-related toxicities, to better treatment compliance, and to better oncologic outcomes [ 11 , 14 , 17 , 18 , 19 , 20 , 40 ].…”

“…In locally advanced tumors (T3–4/N+), survival rates of about 60% require further improvements [ 3 , 4 ]. Recent studies have reported that locoregional recurrences are a major site of failure [ 5 , 6 ]. At the same time, definitive CRT is associated with high rates of acute and hematologic toxicities [ 7 ].…”