Diffusion-weighted magnetic resonance imaging as an early prognostic marker of chemoradiotherapy response in squamous cell carcinoma of the anus: An individual patient data meta-analysis.

Background and purpose: Squamous cell carcinoma of the anus (SCCA) can recur after chemoradiotherapy (CRT). Early prediction of treatment response is crucial for individualising treatment. Existing data on radiological biomarkers is limited and contradictory. We performed an individual patient data meta-analysis (IPM) of four prospective trials investigating whether diffusion-weighted (DW) magnetic resonance imaging (MRI) in weeks two to three of CRT predicts treatment failure in SCCA. Material and methods: Individual patient data from four trials, including paired DW-MRI at baseline and during CRT, were combined into one dataset. The association between ADC volume histogram parameters and treatment failure (locoregional and any failure) was assessed using logistic regression. Pre-defined analysis included categorising patients into a change in the mean ADC of the delineated tumour volume above and below 20%. Results: The study found that among all included 142 patients, 11.3 % (n = 16) had a locoregional treatment failure. An ADC mean change of <20 % and >20 % resulted in a locoregional failure rate of 16.7 % and 8.0 %, respectively. However, no other ADC-based histogram parameter was associated with locoregional or any treatment failure. Conclusions: DW-MRI standard parameters, as an isolated biomarker, were not found to be associated with increased odds of treatment failure in SCCA in this IPM. Radiological biomarker investigations involve multiple steps and can result in heterogeneous data. In future, it is crucial to include radiological biomarkers in large prospective trials to minimize heterogeneity and maximize learning.

Magnetic resonance imaging of anal cancer: tumor characteristics and early prediction of treatment outcome.

PURPOSE: To analyze tumor characteristics derived from pelvic magnetic resonance imaging (MRI) of patients with squamous cell carcinoma of the anus (SCCA) before and during chemoradiotherapy (CRT), and to compare the changes in these characteristics between scans of responders vs. nonresponders to CRT. METHODS: We included 52 patients with a pelvic 3T MRI scan prior to CRT (baseline scan); 39 of these patients received an additional scan during week 2 of CRT (second scan). Volume, diameter, extramural tumor depth (EMTD), and external anal sphincter infiltration (EASI) of the tumor were assessed. Mean, kurtosis, skewness, standard deviation (SD), and entropy values were extracted from apparent diffusion coefficient (ADC) histograms. The main outcome was locoregional treatment failure. Correlations were evaluated with Wilcoxon's signed rank-sum test and Pearson's correlation coefficient, quantile regression, univariate logistic regression, and area under the ROC curve (AUC) analyses. RESULTS: In isolated analyses of the baseline and second MRI scans, none of the characteristics were associated with outcome. Comparison between the scans showed significant changes in several characteristics: volume, diameter, EMTD, and ADC skewness decreased in the second scan, although the mean ADC increased. Small decreases in volume and diameter were associated with treatment failure, and these variables had the highest AUC values (0.73 and 0.76, respectively) among the analyzed characteristics. CONCLUSION: Changes in tumor volume and diameter in an early scan during CRT could represent easily assessable imaging-based biomarkers to eliminate the need for analysis of more complex MRI characteristics.

Treatment outcomes and prognostic factors after chemoradiotherapy for anal cancer.

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare malignancy with rising incidence, associated with human papilloma virus (HPV). Chemoradiotherapy (CRT) is the preferred treatment. The purpose was to investigate treatment failure, survival and prognostic factors after CRT. MATERIAL AND METHODS: In this prospective observational study from a large regional centre, 141 patients were included from 2013 to 2017, and 132 were eligible for analysis. The main inclusion criteria were SCCA, planned radiotherapy, and performance status (ECOG) ≤2. Patient characteristics, disease stage, treatment, and treatment response were prospectively registered. Disease-free survival (DFS), overall survival (OS), and locoregional treatment failure after CRT were analysed. Hazard ratios (HRs) were estimated with Cox`s proportional hazards model. RESULTS: Median follow-up was 54 (range 6-71) months. Eighteen patients (14%) had treatment failures after CRT; of these 10 (8%) had residual tumour, and 8 (6%) relapse as first failure. The first treatment failure was locoregional (11 patients), distant (5 patients), and both (2 patients). Salvage abdomino-perineal resection was performed in 10 patients, 2 had resections of metastases, and 3 both. DFS was 85% at 3 years and 78% at 5 years. OS was 93% at 3 years and 86% at 5 years. In analyses adjusted for age and gender, HPV negative tumours (HR 2.5, p = 0.024), N3 disease (HR 2.6, p = 0.024), and tumour size ≥4 cm (HR 2.4, p = 0.038) were negative prognostic factors for DFS. CONCLUSION: State-of-the-art chemoradiotherapy for SCCA resulted in excellent outcomes, and improved survival compared with previous national data, with <15% treatment failures and a 3-year DFS of >80%.