ASCO 2021: Management of Long-term Toxicity From Pelvic Radiation Therapy

( Radiation toxicity is defined as the transient or long-term sequelae to normal tissues due to pelvic radiotherapy. The most common pelvic radiation toxicity is gastrointestinal, and it is estimated that 10-20% of patients may develop GI toxicities over a ten-year period following pelvic radiation. Diarrhea, bleeding, and incontinence are the most common GI toxicities, with their severity depending on the radiation regimen and area irradiated. Acute toxicity is defined as within the first three months, whereas chronic toxicity is after the three-month time point. Risk factors for developing late GI toxicity include diabetes, inflammatory bowel disease, low BMI, collagen vascular disease, prior surgery, HIV, chemotherapy, tobacco use. While there are several therapies for the management of the side effects of pelvic radiation, they are often under-used, sometimes because late toxicities are under-recognized. The mechanism whereby late radiotherapy toxicity emerges is thought to be more related to ischemic changes in small vessels, which may explain why anti-inflammatory medications are less effective in late toxicity.

Dr. Field Willingham then focused on chronic radiation proctitis, which is probably the most type of late GI toxicity from pelvic radiotherapy. Symptoms of this disease include diarrhea, tenesmus, abdominal discomfort, fecal urgency, fecal incontinence, cramping, and mucous in the stool. Rectal bleeding results from radiation-induced formation of telangiectasias and neo-vascularization. Chronic radiation proctitis places patients at risk for fistulas, strictures, obstruction, and perforation. Many small randomized controlled trials have been conducted to determine effective management strategies for this disease. With regards to medial therapy, 5-aminosalicylic acid preparations and steroids (either oral or enema) can be helpful. If these are ineffective, then patients can try sucralfate enemas. The addition of oral metronidazole may help bleeding and diarrhea as an adjunct to these other therapies. The role of antioxidants like Vitamins A, C, and E, has some support based on the hypothesis that these reduce oxidative damage to tissue. If refractory to medical management, then endoscopic coagulation with argon plasma coagulation (APC) or other modalities has been shown to approach 90% effectiveness with an adverse event rate of 4%. He ended this discussion with a summary of consensus guidelines for radiation proctitis, which is shown below.


With regards to chronic radiation enteritis, patients may present with nausea, vomiting, diarrhea, cramping, tenesmus, anorexia, abdominal pain, and sometimes malabsorption. Relative to chronic radiation proctitis, bleeding, fistulas and abscesses are less common. Evaluation is based on the likely location of symptoms (upper versus lower) and focused endoscopy or start with non-invasive imaging via enterography. In total, up to 89% of patients may experience long-term changes in their bowel habits after pelvic radiation therapy, half of whom report that this causes a decrease in their quality of life. Non-invasive first-line options for managing radiation enteritis include dietary modification with multiple small meals, lactose avoidance, low residue, full liquid. Extreme cases that mimic short gut syndrome may require total parenteral nutrition. Diarrhea is managed with antidiarrheals like loperamide and can further be managed with bile acid sequestration. Radiation therapy can also cause small intestinal bacterial overgrowth, which is treated with antibiotics. If refractory to non-invasive measures, APC, enteroscopy, or surgery may be required for the management of radiation enteritis. Hyperbaric oxygen is a treatment modality that may have utility, but currently, prospective randomized trials are not available to support its use.

Dr. Willingham concluded that GI toxicity from radiation requires a multi-disciplinary approach (oncology, GI, surgery). Further advances in radiotherapy dosing and delivery are likely to help reduce the risk of long-term toxicity.

Presented by: Field F. Willingham, MD, MPH, Professor in the Department of Internal Medicine and Director of Endoscopy, Division of Digestive Disease, Emory University School of Medicine and the Winship Cancer Institute, Atlanta, GA

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021
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