Pelvic Insufficiency Fractures and Bone Pain after Radiation Therapy for Anal Cancer: Relation to Pelvic Bone Dose-Volume Parameters.

Purpose: Chemoradiation therapy is the primary treatment for anal cancer. Radiation therapy (RT) can weaken the pelvic bone structure, but the risk of pelvic insufficiency fractures (PIFs) and derived pain in anal cancer is not yet established. We determined the frequency of symptomatic PIFs after RT for anal cancer and related this to radiation dose to specific pelvic bone substructures. Methods and Materials: In a prospective setting, patients treated with RT for anal cancer had magnetic resonance imaging 1 year after RT. PIFs were mapped to 17 different bone sites, and we constructed a guideline for detailed delineation of pelvic bone substructures. Patients were interviewed regarding pain and scored according to Common Terminology Criteria for Adverse Effects. Dose-volume relationships for specific pelvic bone substructures and PIFs were determined for V20 to V40 Gy mean and maximum doses. Results: Twenty-seven patients were included, and 51.9% had PIFs primarily located in the alae of the sacral bone. Patients with PIFs had significantly more pelvic pain (86% vs 23%, P = .001) and 43% had grade 2 bone pain. Dose-volume parameters for sacral bone and sacral alae were significantly higher in patients with PIFs (P < .05). V30 Gy (%) for sacral bone and alae implied an area under the curve of 0.764 and 0.758, respectively, in receiver operating characteristic analyses. Conclusions: We observed a high risk of PIFs in patients treated with RT for anal cancer 1 year after treatment. A significant proportion had pain in the sites where PIFs were most frequently found. Radiation dose to pelvic bone substructures revealed relation to risk of PIFs and can be used for plan optimization in future clinical trials.

One-Year Treatment-Related Side Effects and Quality of Life After Chemoradiotherapy in Squamous Cell Carcinoma of the Anus.

PURPOSE: Patient-reported outcome (PRO) and National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) data for patients with squamous cell carcinoma of the anus (SCCA) treated with modern radiation therapy (RT) are lacking. The primary aim of this study was to report bowel and bladder PRO and NCI-CTCAE for patients with SCCA 1 year after RT. METHODS AND MATERIALS: From 2015 to 2020, we included patients in a prospective Danish national study. Data were collected before treatment (PT) and 1 year after treatment (1Y) using NCI-CTCAE version 4.0, as well as European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and CR29. We evaluated the combined PRO scores according to the European Organisation for Research and Treatment of Cancer scoring guidelines, and classified changes according to score difference from PT to 1Y as no change (0-5), minor (5-10), moderate (11-20), and major (>20). Raw scores were reported as frequencies of each of the scores: Not at all, a little, quite a bit, and very much. RESULTS: Of the 270 patients, 81% had complete data sets, including PT and 1Y answers. Functional mean scores were equal to a matched normal population cohort at PT and 1Y. From PT to 1Y, C30 scores were stable despite minor improvements in global health status/quality of life (7.3), emotional functioning (9.3), insomnia (8.0), and appetite loss (7.8). For questionnaire CR29, bowel and bladder symptoms and sore skin improved with minor change (6.2), and buttocks, anal, or rectal pain improved with moderate change (18.3). Flatulence worsened moderately (12.6), and fecal incontinence had minor worsening (7.8). Agreement between PROs and NCI-CTCAE was generally only fair to moderate, especially for quantitative symptoms, such as pain (κ = 0.25). CONCLUSIONS: For patients with SCCA who underwent definitive RT, only a few patients had high scores (indicating quite a bit or very much frequency of bother) regarding bowel and bladder symptoms.

Measurement of circulating free DNA in squamous cell carcinoma of the anus and relation to risk factors and recurrence.

BACKGROUND: Measuring circulating-free-deoxyribonucleic-acid (cfDNA) has created a new framework for personalized treatment in oncology. The aim of this study was to analyze the relation between cfDNA and risk factors and outcome in squamous cell carcinoma of the anus (SCCA). METHODS: Patients treated with radiotherapy for localized SCCA were included in Aarhus, Denmark from 2016 to 2019. Serum samples from baseline, during and after therapy, were measured for the level of cfDNA in copies per mL by a direct fluorescent assay. RESULTS: Eighty patients were included. Samples were available at baseline (n = 73) mid-therapy (n = 74), end-therapy (n = 67) and one-year follow-up (1Y) (n = 29). P16-positivity was found in 89% (n = 55). The median level of cfDNA was higher for P16 negative tumors (1.48) compared with the P16 positive tumors (0.90, P = 0.04). Data showed a correlation between baseline cfDNA levels and Gross Tumor Volume (R2 = 0.13, P < 0.01), and increasing levels with increasing T-stage (T1 = 0.80, T2 = 0.94, T3 = 1.11, T4 = 1.3). Higher cfDNA levels were observed in patients with poor performance status (P < 0.01). The cfDNA level decreased from baseline to mid-therapy (0.92-0.78, P < 0.01) and from baseline to 1Y (0.92-0.71, P < 0.01). Baseline levels for patients with treatment failure (n = 8) were above the 25th percentile (p = 0.05) which translates into difference in disease free survival. CONCLUSION: Results indicate an association between baseline cfDNA levels and risk factors in SCCA and a low baseline level correlates to lower risk of treatment failure. Findings contribute with new knowledge of the biological role of cfDNA in SCCA and holds potential knowledge for personalized treatment of SCCA.