Proceed with Caution
As exciting as the concept of de-escalating treatment for patients with HPV+ oropharynx cancers might be, Andrew Sikora, MD, PhD, associate professor and vice chair for research in the department of otolaryngology at Baylor College of Medicine in Houston, said that it’s important to make sure that the desire to improve patients’ quality of life doesn’t lead to worsening excellent survival outcomes. “Any de-escalation strategy needs to be based on a foundation of solid clinical trials evidence,” he added.
Explore This Issue
November 2019Another important point is that a significant number of patients with HPV+ oropharynx cancer have extensive smoking histories. “We don’t know as much about this population as we should,” Dr. Sikora said. “We know that they have worse outcomes than HPV+ oropharynx cancer patients without a history of tobacco use, but this is not reflected in our current staging system, which automatically downstages patients with a HPV+ tumor. Therefore, these patients are at serious risk for undertreatment.”
Overall, rather than focusing single-mindedly on de-escalation of HPV-associated oropharynx cancer, Dr. Sikora believes tools need to be developed that will allow clinicians to risk assess individual patients and deliver the treatment they need. “In many cases, this will involve de-escalating treatment relative to what has been the standard, but for others we will need to intensify treatment,” he said. “We need to invest in the necessary research to develop the algorithms and predictive markers that will allow us to evaluate a patient’s tumor, and determine with confidence the treatment with the greatest chance of cure and lowest risk of long-term toxicity.”
Dr. Ramey added that radiotherapy is an excellent treatment option for many patients and that patients should have the chance to discuss this highly successful treatment option with a radiation oncologist. “However, there is no one right way to treat every patient with oropharyngeal cancer, since treating physicians need to take into account a patient’s preferences, the specifics of each patient’s cancer, and a patient’s other medical co-morbidities,” he said. “Therefore, clinicians must be a part of a team helping patients make an informed decision.”
Outlook
Radiotherapy is going to be part of the treatment strategy for patients with HPV+ oropharynx cancer for a long time, Dr. Sikora said. “Right now, standard chemo-radiotherapy regimens are very effective, but also very difficult for patients,” he said. “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. Even patients treated with surgery often require adjuvant radiotherapy or chemo-radiotherapy to maximize their chance of a long-term cure. So radiotherapy is not going anywhere anytime soon.”
Nevertheless, the way radiation is delivered has evolved, and will continue to do so. “The development of intensity-modulated radiotherapy (IMRT), which focuses radiation on the tumor and decreases the dose received by normal tissues, was an important step toward decreasing toxicity,” Dr. Sikora said. “We are now actively discussing the de-escalation of radiation for patients with HPV+ oropharynx cancer with favorable characteristics. There is also the future possibility, if supported by clinical trials, of reducing or replacing chemotherapy with immunotherapy for some patients, since overall it has a less punishing toxicity profile.”
Dr. Page also believes that radiotherapy will remain in use for the foreseeable future, despite its drawbacks. “It’s still the main curative therapy, particularly for patients with locally advanced oropharyngeal squamous cell carcinomas,” she said. “While current clinical trial efforts include examining de-escalation therapy to try to reduce either chemotherapy or radiotherapy or both, more work needs to be done to further elucidate the extent of therapy needed to adequately treat this disease.”