The Volume of PET-Defined, Active Bone Marrow Spared Predicts Acute Hematologic Toxicities in Anal Cancer Patients Receiving Concurrent Chemoradiation Therapy

Abstract

To report long-term outcomes for anal squamous cell carcinoma (SCC) treated at a single center with concurrent chemotherapy and intensity-modulated radiation therapy (IMRT). The prognostic impact of human papillomavirus (HPV) and p16 status was explored. Materials/Methods: 52 patients with anal SCC were treated with IMRT and concurrent fluorouracil/mitomycin (87%) or fluorouracil/cisplatin (10%). Radiation was delivered sequentially to the pelvis (30.6 Gy), low pelvis and inguinal lymph nodes (45 Gy), and anal tumor (median dose, 54 Gy) at 1.8 Gy/fx. Five patients received a simultaneous integrated boost to involved lymph nodes at 2.0-2.2 Gy/fx over the first 25 days. Prospective bone marrow-sparing guidelines were used to treat 20 patients. Evaluation of HPV genotype using a multiplex real-time PCR for seven clinically relevant high-risk HPV subtypes (16, 18, 31, 33, 45, 52, and 58) (nZ22) and p16 immunohistochemistry (nZ21, rated on a 0, 1, and 2+ scale) were performed on available specimens. Survival was estimated using Kaplan-Meier analysis, and acute and late RTOG toxicities were recorded. Results: Median follow-up was 33 months. Most patients were female (71%) with T2/T3 (79%), N0 (62%) disease. 7 patients (14%) were HIV+. 32 patients had a treatment break (median 4 days), most often for hematologic (40%) or skin (20%) toxicity. Five-year freedom from locoregional failure (FFLRF), freedom from distant metastasis (FFDM), freedom from colostomy (FFC), and overall survival (OS) were 94%, 85%, 91%, and 82%, respectively. Acute grade 2 skin, GI, and GU toxicities occurred in 83%, 71%, and 19% of evaluable patients, respectively. For patients with evaluable late toxicity data (62%), the rates of late grade 2 GI and GU toxicities were 17% and 6%, respectively. Of patients with available pathology, 91% and 71% were positive for HPV and p16 (2+), respectively. HPV genotypes included 16 (nZ17), 33 (nZ2), 18 (nZ1), and 45 (nZ1). HPV and p16 status were associated on Chi-square analysis (p Z 0.07). Neither HPV nor p16 status was significantly associated with any clinical outcome. For HPV+ patients, 5-year FFLRF, FFDM, FFC, and OS were 100%, 69%, 100%, and 66%, respectively. Conclusion: In this cohort of patients with anal cancer receiving concurrent chemotherapy and IMRT, disease control was excellent. Treatment was generally well tolerated. Although HPV and p16 status were not prognostic for treatment outcomes, the high locoregional control in HPV+ patients supports the concept of treatment de-intensification.

Radiotherapy of Squamous Cell Carcinoma of the Anal Canal: Search for Optimal Solutions

“…С 2010 г. расширение и совершенствование парка оборудования радиотерапевтического отделения для проведения лучевого лечения способствовало модификации технологии облучения. Применение современных диагностических методов визуализации, в том числе мультипараметрической магнитнорезонансной томографии (МРТ), позволило создавать четкое объемное 3D представление облучаемой области и выявлять первичную опухоль и/или метастазы в регионарных лимфатических узлах различных размеров и конфигураций [15][16][17][18][19].…”