Salvage Abdominoperineal Resection for Squamous Cell Anal Cancer: A 30-Year Single-Institution Experience

Background: Failure of chemoradiotherapy (CRT) for anal squamous cell carcinoma (SCC) results in persistent or recurrent anal SCC. Treatment with salvage abdominoperineal resection (APR) can potentially achieve cure. The aims of this study are to analyze oncological and surgical outcomes of our 30-year experience with salvage APR for anal SCC after failed CRT and identify prognostic factors for overall survival (OS). Methods: All consecutive patients who underwent salvage APR between 1990 and 2016 for histologically confirmed persistent or recurrent anal SCC after failed CRT were retrospectively analyzed. Results: Forty-seven patien

Inguinal Lymph Node Recurrence in the Untreated Groin of Patients with Anal Carcinoma

BACKGROUND: Inguinal lymph node metastasis is predictive of locoregional recurrence and poor overall survival in anal carcinoma. Metachronous lymph node metastasis occurs in 10% of all anal cancer patients, but multiple studies have shown that the benefit of elective irradiation of the groin depends on T-stage, and the toxicity of groin irradiation must not be underestimated. OBJECTIVE: To analyze the inguinal recurrence rates among patients with anal carcinoma (T1-4, N0-1) who did not receive elective irradiation therapy to the groin and to determine predictors of inguinal recurrence. DESIGN: Data on 119 patients treated between 1987 and 2005 were retrospectively analyzed. Patients were treated with 3-dimensional radiotherapy. The median dose was 60 Gy. During radiotherapy, 108 patients also received chemotherapy (5-fluorouracil and mitomycin-C). RESULTS: AJCC staging showed a distribution of 21 T1 (18%), 58 T2 (49%), 27 T3 (23%), 13 T4 (11%), 101 N0 (85%) and 18 N1 (15%) tumors. The median follow up was 65 months (range, 1-240 months). The 5-year inguinal recurrence rate was 0% for T1, 10% for T2, 21% for T3 and 19% for T4 tumors (p = 0.034). T2 tumors of the perianal skin and the anal canal had 5-year inguinal recurrence rates of 12% and 8%, respectively. The 5-year inguinal recurrence rate was 21% for tumors = 4 cm vs. 2% for tumors <4 cm in size (p = 0.003). LIMITATIONS: Eleven patients did not receive chemotherapy. CONCLUSIONS: Elective irradiation of the groin should be considered for local control in patients (N0-N1) with T2 tumors = 4 cm in size and/or located in the perianal skin, and in all patients with T3 and T4 tumors

Comprehensive Quantitative Evaluation of Variability in Magnetic Resonance-Guided Delineation of Oropharyngeal Gross Tumor Volumes and High-Risk Clinical Target Volumes: An R-IDEAL Stage 0 Prospective Study

Purpose: Tumor and target volume manual delineation remains a challenging task in head and neck cancer radiation therapy. The purpose of this study was to conduct a multi-institutional evaluation of manual delineations of gross tumor volume (GTV), high-risk clinical target volume (CTV), parotids, and submandibular glands on treatment simulation magnetic resonance scans of patients with oropharyngeal cancer. Methods and Materials: We retrospectively collected pretreatment T1-weighted, T1-weighted with gadolinium contrast, and T2-weighted magnetic resonance imaging scans for 4 patients with oropharyngeal cancer under an institution review board–approved protocol. We provided the scans to 26 radiation oncologists from 7 international cancer centers that participated in this delineation study. We also provide the patients’ clinical history and physical examination findings, along with a medical photographic image and radiologic results. We used both the Simultaneous Truth and Performance Level Estimation algorithm and pair-wise comparisons of the contours, using overlap/distance metrics. Lastly, to assess experience and CTV delineation institutional practices, we had participants complete a brief questionnaire. Results: Large variability was measured between observers’ delineations for GTVs and CTVs. The mean Dice similarity coefficient values across all physicians’ delineations for GTVp, GTVn, CTVp, and CTVn were 0.77, 0.67, 0.77, and 0.69, respectively, for Simultaneous Truth and Performance Level Estimation algorithm comparison, and 0.67, 0.60, 0.67, and 0.58, respectively, for pair-wise analysis. Normal tissue contours were defined more consistently when considering overlap/distance metrics. The median radiation oncology clinical experience was 7 years. The median experience delineating on magnetic resonance imaging was 3.5 years. The GTV-to-CTV margin used was 10 mm for 6 of 7 participant institutions. One institution used 8 mm, and 3 participants (from 3 different institutions) used a margin of 5 mm. Conclusions: The data from this study suggests that appropriate guidelines, contouring quality assurance sessions, and training are still needed for the adoption of magnetic resonance–based treatment planning for head and neck cancers. Such efforts should play a critical role in reducing delineation variation and ensure standardization of target design across clinical practices

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial

Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients’ quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image – guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient’s plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). Methods: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT. Discussion: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC. Trial registration: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017. Keywords: Magnetic resonance imaging guided radiotherapy, Human papilloma virus, Oropharyngeal cancer, Adaptive radiotherap