Evolution of the Role of Radiotherapy for Anal Cancer

Abstract

Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy’s role in locally persistent or recurrent anal cancer.

Anal Cancer: Emerging Standards in a Rare Disease

“…Image-guided radiation therapy with daily cone beam computed tomography is recommended and may allow tighter clinical target margins, margins of 10-20 mm radially around the primary tumor and anal canal, and planning target volume margins of 5-10 mm. 51, [71][72][73] Vaginal dilator use during and/or after RT may minimize the impact of RT and reduce long-term vaginal stenosis. Constraining total pelvic bone marrow correlates with lower hematologic toxicity.…”

“…79,80 Studies are ongoing, and additional investigations include adaptive planning to amend RT volumes during the treatment course, dose escalation, and de-escalation studies. 73,81 Risk Factors for Recurrence Treatment adherence may have a critical impact on treatment outcomes. Paramount aspects derived from RTOG 98-11 are the determinants for risk of recurrent disease.…”

“…79,80 Studies are ongoing, and additional investigations include adaptive planning to amend RT volumes during the treatment course, dose escalation, and de-escalation studies. 73,81…”

Present and Future Research on Anal Squamous Cell Carcinoma

“…However, some minor changes have been recommended based on phase II trials such as (i) replacement of infusionnel 5FU by oral capecitabine [30,31], (ii) more conformal technique such as intensity-modulated radiotherapy (IMRT) to spare the organs at risk [32,33], and (iii) de-escalation of prophylactic radiotherapy dose to 36 Gy to reduce toxicity [34,35]. Several trials are currently ongoing to evaluate the de-escalation or dose escalation in localized disease depending on the tumor size at diagnosis [36]. PLATO (PersonaLising Anal cancer radioTherapy dOse) is a single protocol platform, comprising three separate trials (ACT3, ACT4, and ACT5) with the aim of personalizing radiotherapy dose from early to locally advanced disease [37].…”

Research on Anal Squamous Cell Carcinoma

“…This Special Issue consists of six articles that provide an in-depth overview of contemporary practice and future areas of investigation. First, Dee et al [ 1 ] and Possiel et al [ 2 ] discuss the evolution of the role of radiotherapy for ASCC, providing key insights into advanced radiotherapy technologies such as the use of intensity-modulated radiotherapy and proton therapy. Carr et al [ 3 ] and Wind et al [ 4 ] discuss the evolution of systemic management for ASCC, including contemporary practice for both locoregional disease and metastatic disease, along with the potential inclusion of induction chemotherapy for select patients with locoregionally advanced disease.…”