Chemoradiotherapy For Anal Cancer Research Articles

OC-0831 Standard vs dose reduced chemoradiotherapy in anal cancer: short-term results of the PLATO-ACT4 RCT

OC-0831 Standard vs dose reduced chemoradiotherapy in anal cancer: short-term results of the PLATO-ACT4 RCT

International Validation of the EORTC QLQ-ANL27, a Field Study to Test the Anal Cancer-Specific Health-Related Quality-of-Life Questionnaire

The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.

A five-year review of chemoradiotherapy in anal cancer: Audit results from a cancer centre in Wales, UK

A five-year review of chemoradiotherapy in anal cancer: Audit results from a cancer centre in Wales, UK

OC-0269 Standard vs dose escalated chemoradiotherapy in anal cancer: Phase II results of the PLATO-ACT5 RCT

OC-0269 Standard vs dose escalated chemoradiotherapy in anal cancer: Phase II results of the PLATO-ACT5 RCT

Vaginal Sparing Radiotherapy Using IMPT and Daily Dilator Placement for Women with Anal Cancer.

IntroductionSexual dysfunction is a common toxicity and detrimental for the quality of life of women treated with chemoradiotherapy for anal cancer. Sexual dysfunction occurs because the vagina is closely approximated to the anal canal and typically receives substantial doses of radiation. Strategies for mitigation have largely been focused on posttreatment therapy and symptom management. The use of daily vaginal dilator placement during radiotherapy to mitigate dose to the vagina has been previously explored with modest gains, while proton therapy is under active investigation for the treatment of anal cancer. Use of proton therapy for anal cancer reduces dose to some organs at risk but may inadvertently increase vaginal toxicity if the proton beam terminates in the vaginal tissue. Herein, we present the case histories of 2 women treated for squamous cell carcinoma of the anal canal with the novel combination of intensity-modulated proton therapy and daily vaginal dilator placement to maximally reduce dose to the vagina and protect it from areas of increased energy deposition at the end of the proton range.

PH-0114 Pelvic insufficiency fractures detected by MRI one-year after chemoradiotherapy for anal cancer.

PH-0114 Pelvic insufficiency fractures detected by MRI one-year after chemoradiotherapy for anal cancer.

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%.

Outcomes of surgery following chemoradiotherapy for anal cancer: A 10-year retrospective study

Treatment for Anal cancer is carried out in regional cancer centres but when chemoradiation fails or is ineffective then there is a role for salvage surgery but carries considerable morbidity and mortality.

OC-0313: Patient reported outcome and toxicity one-year after IMRT based chemoradiotherapy for anal cancer.

OC-0313: Patient reported outcome and toxicity one-year after IMRT based chemoradiotherapy for anal cancer.

518P Treatment outcome and prognostic factors after chemoradiotherapy for anal cancer

518P Treatment outcome and prognostic factors after chemoradiotherapy for anal cancer

Patient-reported outcomes including LARS score and quality of life one year after chemoradiotherapy for anal cancer

Patient-reported outcomes including LARS score and quality of life one year after chemoradiotherapy for anal cancer

Chemoradiotherapy for anal cancer: A population-based study of treatment interruption, treatment completion, and associated outcomes.

3573 Background: Chemoradiotherapy (CRT) is the standard treatment for squamous cell anal carcinoma (SCCA). Here, we describe CRT delivery in routine practice and explore the association between treatment interruption, non-completion and outcomes. Methods: The Ontario Cancer Registry was used to identify all incident cases of SCCA treated with curative intent RT in Ontario, Canada (2007-2015). Treatment interruption was defined a priori as &gt; 7 days between consecutive fractions. Completed CRT was defined as receiving ≥50 Gy and 30+ fractions of RT along with 2 concurrent doses of chemotherapy. Log-binomial regression models were used to estimate risk ratios (RR) between patient characteristics and 1) failure to complete CRT and 2) salvage abdominoperineal resection (APR). Cox proportional hazard models were used to estimate hazards ratios (HR) between treatment interruption or non-completion and 1) cancer specific survival (CSS) and 2) overall survival (OS). Results: We identified 1593 patients with SCCA; 73% (n = 1161) initiated curative intent RT. Median RT dose and duration was 54 Gy (IQR, 50.4-67.8) and 46 days (IQR, 42-53), respectively. Treatment interruption &gt; 7 days occurred in 23%. CRT was completed by 59%. Factors associated with CRT non-completion were age &gt; 70 vs. &lt; 50 (RR 0.70, 95% CI: 0.59-0.93) and greater comorbidity (1+ vs. 0, RR 0.57, 95% CI: 0.39-0.85). Treatment interruption &gt; 7 days appears to be associated with salvage APR (RR 1.39, 95% CI: 0.91-2.12). In an exploratory analysis, the association between treatment interruption &gt; 10 days and salvage APR reached statistical significance (RR 1.63, 95% CI, 1.06-2.53). Treatment interruption was not associated with inferior CSS (HR 0.87, 95% CI: 0.60-1.25) nor OS (HR 0.96, 95% CI: 0.76-1.23). Failure to complete CRT was not associated with higher rates of salvage APR nor inferior CSS, but was associated with inferior OS (HR 1.40, 95% CI: 1.13-1.72). Conclusions: In routine clinical practice, treatment interruption and non-completion among patients with SCCA are common. Quality improvement initiatives to optimize treatment continuity and completion are needed. The observed association between failure to complete CRT and OS is likely a reflection of confounding by indication, which is highlighted by the lack of association between CRT completion and CSS. Publisher's Note The abstract by Raphael et al entitled, “Chemoradiotherapy for anal cancer: A population-based study of treatment interruption, treatment completion, and associated outcomes,” published in the Journal of Clinical Oncology 37, no. 15 suppl (May 20 2019) 3573–3573, contained errors. In updated analyses, the authors discovered that the main exposure (radiation therapy) may have been incorrectly coded into the population-level databases from several individual treatment centers. Some of the coded radiation doses and fractionation numbers are considerably beyond what would be clinically plausible. Until this issue has been resolved, the authors believe the results of their study cannot be considered reliable. This article was retracted on 17-07-2019.

Chemoradiotherapy for anal cancer: are we as good as we think?

Definitive chemoradiotherapy (CRT) is the standard treatment for anal squamous cell carcinoma (ASCC). Data regarding treatment outcome according to TNM classification is scarce. Here, we review data of randomized trials and retrospective cohorts suggesting apoor 3‑year disease-free survival (DFS; or progression-free survival, PFS) of approximately 60%, or even lower, in patients with locally advanced T3-4 and/or N+ disease, while patients with T1-2N0 ASCC have 3‑year DFS/PFS rates exceeding 80%. These results are in line with our data in acohort of 210 patients with ASCC treated with definitive 5‑fluorouracil/mitomycin C‑based CRT to atotal dose of 50.4 Gy plus aboost of 3.6-10.8 Gy. The implications of these findings and the current trials testing radiotherapy dose escalation/de-escalation strategies are reported. Finally, we will discuss the strong rationale for testing immune checkpoint blockade (ICB) with CRT in clinical trials to improve results, especially in patients with advanced ASCC.

Intensity-modulated Radiotherapy for Anal Cancer: Dose–Volume Relationship of Acute Gastrointestinal Toxicity and Disease Outcomes

AimsIntensity-modulated radiotherapy (IMRT) is increasingly used in the treatment delivery of chemoradiotherapy in anal cancer with the ability to reduce toxicity. We report on 4 year outcomes since the introduction of IMRT and identify the most predictive bowel organ at risk that correlates with acute diarrhoea. Materials and methodsFifty-eight patients receiving definitive chemoradiotherapy for squamous or basaloid cell anal carcinoma (T1-4NanyM0) were reviewed. Fifty-four per cent of patients had stage III disease and most (79%) were treated with a dose of 54 Gy in 30 fractions. Patient acute gastrointestinal toxicity was recorded using Common Terminology Criteria of Adverse Events (CTCAE) diarrhoea grading. Four different methods of bowel were re-contoured for each patient and correlated with acute diarrhoea. Locoregional control and overall survival were analysed. ResultsCTCAE grade 3 or more diarrhoea occurred in 11/58 patients (19%). Seven patients did not complete treatment; 10 patients (17%) required a treatment break of 3 or more days. ‘Bowel cavity’ was the best predictor of acute grade 3 toxicity using volume (P = 0.002) or volume to bowel cavity in 5 Gy bins (V5–V50Gy); P < 0.05. Bowel cavity V30Gy ≤ 300 cm3 predicts a 6% grade 3 diarrhoea risk versus > 300 cm3 predicts a 42% risk. Four year progression-free survival was 84% (95% confidence interval 73–92%) and overall survival was 88% (95% confidence interval 75–95%). ConclusionChemoradiation using IMRT provides excellent local control and acceptable acute gastrointestinal toxicity. Bowel cavity is the most sensitive predictor for grade 3 versus grade 0–2 diarrhoea, with any volume receiving 5–50 Gy discriminatory.

Single centre outcomes of surgery following chemoradiotherapy for anal cancer

Single centre outcomes of surgery following chemoradiotherapy for anal cancer

Utilization of intensity modulated radiation therapy for anal cancer in the United States.

Chemoradiotherapy for anal cancer (AC) can incur substantial treatment-related toxicities. Whereas radiotherapy (RT) for AC has historically been delivered with two- or three-dimensional conformal RT (2D/3DCRT) techniques, intensity-modulated RT (IMRT) is associated with improved target conformality and lower doses to organs-at-risk (OARs). This is the first investigation to date evaluating trends of IMRT utilization in the United States. The National Cancer Data Base (NCDB) was queried [2004-2015] for AC patients receiving definitive chemoradiotherapy with a defined RT technique (3DCRT versus IMRT). Following analysis based on temporal trends, multivariate logistic regression determined factors associated with receipt of IMRT. Secondarily, Kaplan-Meier analysis compared OS between the 3DCRT and IMRT groups, and Cox proportional hazards modeling determined variables associated with OS. Altogether, 11,396 patients met study criteria; 1,288 (11%) were treated with 3DCRT and 10,108 (89%) with IMRT. Temporally, utilization of IMRT rose significantly, from 28% in 2004 to 96% in 2015, corresponding with a progressive decrease in 3DCRT usage. IMRT was more likely delivered in node-positive disease, at academic centers, and in southern/western regions (P<0.05 for all). T3-4 disease was less likely to receive IMRT (P<0.05). As expected, there were no OS differences based on RT technique (P=0.402). Predictors of worse OS included advancing age, male gender, increasing comorbidities, advanced T-stage, and nodal positivity (P<0.05 for all). In addition to racial- and insurance-related factors, receipt of therapy at academic centers independently predicted for improved OS (P<0.05 for all). Based on findings from this large, contemporary dataset, IMRT is now the most widely utilized RT technique for AC, and 3DCRT is used in a very small minority of patients. IMRT utilization is impacted by multiple characteristics, such as disease- and regional-related factors. These observations have implications for payers and insurance coverage; improved survival at academic centers has ramifications for patient counseling.

Peripheral Leukocytosis Is Inversely Correlated with Intratumoral CD8+ T-Cell Infiltration and Associated with Worse Outcome after Chemoradiotherapy in Anal Cancer.

Peripheral blood leukocytosis has been implicated in promoting tumor progression leading to worse survival, but the mechanisms behind this phenomenon remain unexplored. Here, we examined the prognostic role of pretreatment white blood cell (WBC) count and clinicopathologic parameters in the context of CD8+ tumor-infiltrating lymphocytes (TIL) and myeloperoxidase+ tumor-associated neutrophils (TANs) in patients with anal squamous cell carcinoma (ASCC) treated with definitive chemoradiotherapy (CRT). After a median follow-up of 26 months, leukocytosis correlated with advanced T-stage (p < 0.001) and N-stage (p < 0.001), and predicted for worse distant-metastasis-free survival (p = 0.006), disease-free-survival (DFS, p = 0.029), and overall survival (p = 0.013). Importantly, leukocytosis was associated with a lower intraepithelial CD8+ TIL density (p = 0.014), whereas low CD8+ TIL expression in the intraepithelial compartment was associated with worse DFS (p = 0.028). Additionally, high TAN expression in the peritumoral compartment was associated with a significantly lower density of CD8+ TIL (p = 0.039), albeit, TAN expression lacked prognostic value. In conclusion, leukocytosis constitutes an important prognostic marker in ASCC patients treated with CRT. In conjunction with intratumoral TIL and TAN, these data provide for the first time important insight on the correlation of peripheral blood leukocytosis with the intratumoral immune contexture and could be relevant for future patient stratification using immunotherapies in ASCC.

No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

Background:The majority of anal cancers (84–95%) are driven by infection with human papillomavirus (HPV). HPV-positive tumours show significantly better responses to chemo-radiotherapy when compared with HPV-negative tumours. HPV infection is linked to alterations in DNA damage response proteins, including MRE11. MRE11 is a potential predictive biomarker for response to radiotherapy in muscle-invasive bladder cancer and may hold predictive power in other cancers.Methods:Using a previously reported cohort, we evaluated the levels of MRE11 in anal cancer and assessed its predictive value in this disease.Results:We found no association between the level of MRE11 and relapse-free survival following chemo-radiotherapy.Conclusions:MRE11 has no predictive value in the analysis of relapse-free survival after chemo-radiotherapy in anal cancer and does not add to the prognostic value of p16 and tumour-infiltrating lymphocyte scores. Further investigation into the role of DNA repair proteins in anal cancer is required.

Outcomes of concurrent chemoradiotherapy for anal cancer in Brazil.

e15073 Background: The incidence of anal cancer has increased in the last 30 years and concurrent chemoradiotherapy has been the standard treatment for anal cancer for many decades, since it is a curative treatment in most cases. Although, data from real life outcomes in brazilian patients is lacking. Methods: From October 2001 to November 2016, all the pacientes who were treated with concomitant 5-FU and mitomycin or more recently cisplatin plus radiation at Hospital de Clínicas de Porto Alegre, an academic hospital from South Brazil were identified by electronic database. Medical records were reviewed and demographic data, tumor and treatment characteristics were collected. OS and PFS were estimated by Kaplan-Meier curves. Statistical analysis was performed with SPSS 22. Results: Fifty one patients were analysed for this review. Patient characteristics revealed a mean age of 53 ± 9.03 years, 69% female, with predominantly histology being squamous cell carcinoma (90%). 92% (47) received chemoradiotherapy as a definitive treatment. The chemoterapy regimen used was 5-FU and mitomycin in 69% (35) of the patients and 5-FU plus cisplatin was used in 16 patients (31%). The standard chemoterapy regimen was changed because of lack of supply of mitomycin in our country. Approximately 66% of the patients achieved a complete response while 4 patients (7%) had persistent disease after treatment and 7% had disease progression during treatment. On multivariable analysis, the lymph node status and the size of the tumor were independently associated with worst results. The estimated median PFS was 78 months and the median OS was 92 months. Conclusions: To our knowledge, this is the first report of patients from Brazil treated with concurrent chemoradiation for anal canal cancer. Although we have a delay in the diagnosis and many patients present with locally advanced disease, the CR rate and prognosis are consistent with data from previous studies. We need a longer follow-up to confirm these data and also verify if there will be different outcomes because of the change in the chemoterapy regimen.

Role of 18F-FDG PET/CT in Posttreatment Evaluation of Anal Carcinoma.

The aim of this study was to evaluate the relevance of PET/CT and 18F-FDG as a strategy for response evaluation after chemoradiotherapy for anal cancer. For this, the performance of posttreatment 18F-FDG PET/CT, the impact on patient care, and the predictive value of metabolic response were assessed. Methods: This was a retrospective and multicenter analysis of 87 patients treated by chemoradiotherapy for anal squamous cell carcinoma between October 2007 and October 2013. All patients underwent systematic posttreatment 18F-FDG PET/CT and were followed with at least a clinical examination every 4 mo for 2 y and every 6 mo thereafter. Disease progression was confirmed by biopsy for all patients in the case of local recurrence before surgery. Kaplan-Meier and Cox regression models were used to test for associations between metabolic or clinical endpoints and progression-free survival (PFS) or cause-specific survival (CSS). Results: The median follow-up was 25 mo. 18F-FDG PET/CT was performed 1-8 mo (median, 4 mo) after completion of chemoradiotherapy. Overall, 25 patients relapsed and 13 died. The posttherapy 18F-FDG PET/CT did not show any abnormal 18F-FDG uptake (complete metabolic response [CMR]) in 55 patients whereas 32 displayed incomplete response (non-CMR): 15 patients with partial response and 17 with disease progression. The sensitivity of 18F-FDG PET/CT to detect residual tumor tissue was 92% (95% confidence interval [CI], 75%-97%), specificity was 85% (95% CI, 75%-92%), positive predictive value was 72% (95% CI, 61%-90%), and negative predictive value was 96.4% (95% CI, 90%-98.7%). The 2-y PFS was 96% (95% CI, 90-100) for patients with CMR and 28% (95% CI, 14-47) for non-CMR patients (P < 0.0001). The 2-y CSS was 100% for patients with CMR and 59% (95% CI, 42-84) for those without CMR (P < 0.0001). 18F-FDG PET/CT changed patient management in 14 cases (16%), with relevant modifications in 12 (14%). A Cox proportional hazards model of survival outcome indicated that a CMR was the only significant predictor of PFS and CSS (P < 0.0001). Conclusion:18F-FDG PET/CT shows good accuracy in posttreatment evaluation of anal cancer and has a relevant impact on patient management. Moreover, CMR is associated with good survival outcome. Thus, 18F-FDG PET/CT may play a significant role during posttreatment follow-up of anal cancer.