Anal squamous cell carcinoma: a retrospective case series.

BACKGROUND: Anal cancer is a relatively rare cancer with 660 cases diagnosed in 2000-2015 in Ireland (1). The current standard treatment is radical chemoradiotherapy (CRT). The aim of our study was to review the treatment and outcomes of patients with localised anal squamous cell carcinoma (SCC), who received radical treatment in our radiation oncology network between 2008 and 2014 inclusive. METHODS: Data were collected retrospectively from ARIA® oncology information system and patient charts. Statistical analyses were performed using IBM® SPSS® statistical software version 25.0. RESULTS: Seventy-nine cases of anal SCC were identified. Mean age of patients at commencement of radiotherapy (RT) was 60.2 years (standard deviation: 13.1 years). The most common total RT dose was 50.4 Gy in 28 fractions (N = 58; 73.4%). Median follow-up was 5.6 years. Two (2.6%) patients had persistent disease, seventeen (21.8%) patients developed loco-regional recurrence and nine (11.5%) patients developed solid organ metastases, four of whom had complete treatment response at the primary site. Eight patients underwent salvage anal surgery following completion of RT. Median overall survival was 10.5 years (95% confidence interval (CI) 5.1-15.8 years), median loco-regional relapse-free survival was 10.4 years (95% CI 4.4-16.3 years) and median disease-free survival was 9.3 years (95% CI 6.3-12.2 years). CONCLUSION: Our study demonstrates that treatment for anal SCC and outcomes following definitive CRT in Ireland during the study period were comparable to international standards.

A novel dynamic arc treatment planning solution to reduce dose to small bowel in preoperative radiotherapy for rectal cancer.

Preoperative radiotherapy or combined chemoradiotherapy for locally advanced rectal cancer (LARC) can cause acute and late gastrointestinal (GI) side-effects. There is thought to be a dose-volume relationship between small bowel irradiation and the development of these effects. A planning study was undertaken to compare small bowel sparing for a range of 3D conformal and dynamic arc planning solutions. A planning study was carried out for 20 LARC patients. Organs at risk (OAR) contoured included bowel loops and peritoneal space (PS). For each of the 20 patients, 5 plans were created: (1) standard 3D conformal plan; (2) standard dual dynamic arc plan; (3) dual dynamic arc plan with 90° avoidance sector through the anterior portion of the patient; (4) dual dynamic arc plan with an anterior avoidance structure in the optimizer; (5) dual dynamic arc plan with both an anterior avoidance structure and an avoidance sector. The prescription was 50.4 Gy in 28 fractions to the planning target volume (PTV). Five Dose Volume Levels (DVLs; V15 Gy, V20 Gy, V25 Gy, V35 Gy, V40 Gy, and V50.4 Gy) for bowel and PS were selected. The DVLs were compared between the plans using Friedman Tests and Wilcoxon Signed Rank Tests. Comparison of the 5 plans revealed that a dual dynamic arc plan containing both an anterior avoidance sector and structure significantly improved the dose to the bowel compared to a standard 3D conformal plan and to a standard dual dynamic arc plan. This improvement was achieved while maintaining PTV coverage. This novel dual dynamic arc planning technique that uses both an avoidance sector and structure reduces the dose to the bowel and PS, which may lead to a reduction in GI toxicity.

Mucinous Rectal Adenocarcinoma Is Associated with a Poor Response to Neoadjuvant Chemoradiotherapy: A Systematic Review and Meta-analysis.

BACKGROUND: Mucinous adenocarcinoma represents a potentially poor prognostic subgroup of rectal cancer. A consensus on the effect of mucinous cancer on outcomes following neoadjuvant chemoradiotherapy and curative resection for rectal cancer has not been reached. OBJECTIVE: The aim of the current study is to use meta-analytical techniques to assess the association between mucinous histology and response to neoadjuvant chemoradiotherapy in rectal cancer. DATA SOURCES: A comprehensive literature search of PubMed, Embase, and The Cochrane Library was performed. STUDY SELECTION: All studies examining the effect of mucinous histology on chemotherapeutic response in rectal cancer were included. INTERVENTIONS: No direct interventions were performed. MAIN OUTCOME MEASURES: Outcomes of mucinous rectal adenocarcinoma were compared with nonmucinous tumors by using random-effects methods to analyze data. Data are presented as ORs with 95% CIs. The main outcomes measured were the rates of pathological complete response, tumor and nodal downstaging, positive resection margin rate, local recurrence, and overall mortality. RESULTS: Eight comparative series describing outcomes in 1724 patients were identified, 241 had mucinous tumors (14%). Mucinous tumors had a reduced rate of pathological complete response (OR, 0.078; 95% CI, 0.015-0.397; p = 0.002) and tumor downstaging (OR, 0.318; 95% CI, 0.185-0.547; p < 0.001) following neoadjuvant chemoradiotherapy with an increased rate of positive resection margin (OR, 5.018; 95% CI, 3.224-7.810; p < 0.001) and poorer overall survival (OR, 1.526; 95% CI, 1.060-2.198; p = 0.023) following resection. Mucin expression did not significantly affect nodal downstaging (OR, 0.706; 95% CI, 0.295-1.693; p = 0.435) or local recurrence (OR, 1.856; 95% CI, 0.933-3.693; p = 0.078). There was no across-study heterogeneity for any end point. LIMITATIONS: Most studies were retrospectively designed, and there were variations in patient populations and duration of follow-up. CONCLUSIONS: Mucinous rectal adenocarcinoma represents a biomarker for poor response to preoperative chemoradiotherapy and is an adverse prognostic indicator.

Chemoradiotherapy for anal squamous cell carcinoma.

BACKGROUND AND PURPOSE: Anal cancer is a relatively rare cancer, making up approximately 0.4% of all new diagnoses of cancer.(1) The incidence of anal cancer, however, has increased in recent years.(2) The aim of this paper is to review current treatment of anal squamous cell carcinoma (SCC), the most common type of anal cancer. METHODS: This review article focuses on recent and ongoing trials studying the outcomes of various chemoradiotherapy (CRT) regimens in the treatment of anal SCC. PubMed was initially searched for relevant trials. This search was then supplemented by hand searches of reference lists and abstracts of relevant conferences. MAIN FINDINGS: CRT with mitomycin C (MMC) and 5-fluorouracil (5-FU) has been proven to have effective results in the treatment of anal SCC. Salvage surgery has a role in some patients in the treatment of persistent or recurrent disease beyond 26 weeks. The addition of induction or maintenance chemotherapy to CRT has not been shown to have any benefit. CONCLUSIONS: Primary CRT with MMC and 5-FU is the current standard treatment for anal SCC. There is currently no role for induction or maintenance chemotherapy.

The curative management of synchronous rectal and prostate cancer.

OBJECTIVE: Neoadjuvant "long-course" chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. METHODS: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. RESULTS: Pelvic external beam radiotherapy (RT) 45-50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2-6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. CONCLUSION: Patients proceeding to synchronous radical treatment of both primary sites should receive 45-50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. ADVANCES IN KNOWLEDGE: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients.

Non-operative treatment after neoadjuvant chemoradiotherapy for rectal cancer.

The past decade has seen pronounced changes in the treatment of locally advanced rectal cancer. Historically, the standard of care involved surgery followed by adjuvant radiotherapy or chemoradiotherapy. More recently, the emergence of neo-adjuvant chemoradiotherapy has fundamentally changed the management of patients with locally advanced disease. In clinical trials, pathological complete responses of up to 25% have raised the question as to whether surgery can be avoided in a select cohort of patients. A trial of omission of surgery for selected patients with complete response after preoperative chemoradiotherapy has shown favourable long-term results. In this article, we outline emerging factors for achieving pathological complete response, non-operative strategies to date, methods for prediction of response to chemoradiotherapy, and future directions with the addition of MRI as a radiological guide to complete response.