The combination of radiotherapy and immunotherapy is being actively tested in clinical trials, and is likely to eventually enter the standard-of-care in one form or another. —Andrew Sikora, MD, PhD
Explore This IssueNovember 2019
Given the downsides, Dr. Clump said it’s important to address side effects with patients. He encourages them to visit survivorship clinics, where preventive techniques are deployed or side effects are identified early on.
Why Radiotherapy Can Be Harmful
In the longest of long-term survivors, Dr. Page has seen localized effects of radiotherapy corresponding to how much radiation a patient receives. “This is most often related to fibrosis and stenosis of the microvasculature and atherosclerosis of microscopic arteries leading to decreased blood flow, and therefore scarring and hardening of musculature and soft tissues,” she said.
Due to microscopic vasculature hardening, as well as organ damage, organs that may have had exposure, such as the thyroid gland, submandibular glands, and parotid glands, may experience hypofunction. “Patients who experience symptomatic hypothyroidism due to radiotherapy exposure have a higher mortality rate if they aren’t placed on a regular monitoring schedule,” Dr. Page said.
Longer term scar tissue can cause increased risk of stroke due to carotid arterial stenosis. Fibrosis and fistulae can cause chronic infections and pain with life-threatening consequences. Osteoradionecrosis, which can cause chronic pain, infections, and decreased ability to chew and eat, is treated with surgery, antibiotics, and controversial and costly treatments, including hyperbaric oxygen or pentoxifylline, Dr. Page said. Before speech and swallowing exercises were introduced during radiotherapy, patients would become dependent on feeding tubes and later experience atrophy of pharyngeal musculature, leading to increased risk of deadly aspiration pneumonia.
Proper and careful implementation of patient education, nursing care, frequent access to physician expertise, and empowerment during radiotherapy are important factors in the management of expected acute term side effects. “In the survivorship phase, patients can work together with their medical team to maximize quality of life,” Dr. Page added.
Should Treatment Protocols Change?
The younger patient population and favorable prognosis associated with HPV+ oropharynx cancers carry with them a need to decrease treatment toxicity, without compromising oncologic outcomes, Dr. Nathan said.
Dr. Ramey agreed, adding that clinicians need to be cautious before moving away from established curative techniques. According to American Society of Clinical Oncology guidelines, treatment de-intensification for HPV+ tumors shouldn’t be done outside of a clinical study (J Clin Oncol. 2019;37:1578–1589).
A variety of early-stage clinical studies have shown that decreased radiation doses to the lymph node regions in the neck greatly reduced the amount of radiation needed after surgery and lowered the overall dose of radiation and/or chemotherapy (J Clin Oncol. 2019 Published online Aug. 14, 2019. doi.org/10.1200/JCO.19.01007; J Clin Oncol. 2019;37:1909–1918). “These studies have promising results with excellent cure rates and decreased side effects,” Dr. Ramey said. “However, they still require testing in larger clinical trials comparing these decreased intensity treatments to the current standard of care.”
Along these lines, Dr. Nathan said that multiple large retrospective database studies and prospective studies have already demonstrated evidence in favor of de-escalation (Laryngoscope. 2012;122 Suppl 2:S13–S33; Oral Oncol. 2018;79:64–70). “Studies have shown that when some clinicians didn’t prescribe radiotherapy for patients with low-risk disease after surgery, that many patients showed improved functional outcomes,” she said. Cramer’s National Cancer Database retrospective study determined that patients had similar outcomes when radiotherapy or chemotherapy with radiotherapy were omitted in low-risk patients (Head Neck. 2018;40:457–466).