The number of head and neck cancers related to human papillomavirus (HPV) infection has surged in recent years, especially in men. This type of cancer usually responds well to a combination of surgery, radiation, and chemotherapy. The cure rate for the disease is close to 90%. But the side effects of treatment can cause serious discomfort and long-term complications. This is particularly true of radiation.
The outlook for people with HPV-positive head and neck cancer could soon improve markedly. As reported today at the annual meeting of the American Society for Radiation Oncology, many of these cancers might be successfully treated with a sharply reduced radiation dose that could eliminate nearly all radiation-associated side effects.
“This is an absolute game changer for treating HPV-positive cancer,” says MSK radiation oncologist Nancy Lee, who pioneered the approach. “The difference in toxicity is dramatic compared with standard radiation therapy.”
At the meeting, MSK radiation oncologist Nadeem Riaz presented the results of a pilot study. It involved 19 MSK patients with HPV-positive oropharynx (throat) cancer and showed that a low-dose radiation approach could control the cancer while avoiding side effects. Now MSK is leading a larger study that launches this week and will involve patients at multiple sites.
A Dramatic Dose Reduction
Radiation dosage is measured in units called grays (Gy). The standard approach for treating head and neck cancer has been 70 Gy given over seven weeks, along with three cycles of chemotherapy. This level of radiation often causes mouth sores, difficulty swallowing, dry mouth, loss of taste, and nausea.
Dr. Lee’s protocol reduces the dosage to 30 Gy, which is given over three weeks along with only two cycles of chemotherapy.
“It’s hard to describe the huge difference this makes,” Dr. Riaz says. “With the seven-week treatment, patients typically lose 20 to 30 pounds and may have to go on disability for several months. Using the smaller dose over just three weeks, they have almost no radiation side effects. It’s like you’re not even using the same treatment.”Back to top
Careful Selection of HPV-Positive Tumors
Key to the success of the new technique is the careful selection of people who would benefit. Most HPV-positive tumors respond well to treatment with chemotherapy and radiation, but a fraction of them are more resistant and aggressive. Dr. Lee developed a method for detecting which tumors would respond to the lower dose.
The approach involves using PET imaging to see if there’s the presence of hypoxia (low oxygen concentration) in the head and neck tumors. Tumor hypoxia reduces the effectiveness of radiation and chemotherapy. In Dr. Lee’s method, patients are initially given radiation and chemotherapy. PET imaging is then used to determine whether the tumors are hypoxic and resistant.
For people whose tumors are not hypoxic, the radiation dosage is lowered, or de-escalated, to 30 Gy, and the chemotherapy is reduced from three cycles to two. People whose tumors are revealed to be hypoxic receive the standard 70 Gy dose and three cycles of chemotherapy.
In the pilot study, 15 of the 19 people did not have hypoxic tumors and were able to receive the de-escalated therapy. This raises hopes that someday the majority of people with HPV-positive head and neck cancer could safely avoid high radiation doses — and the toxicity accompanying them.Back to top
Effective Control of Throat Cancer
Dr. Riaz explains that reducing the radiation dose to 30 Gy for HPV-positive head and neck cancer seemed feasible because HPV-positive anal cancer has been treated effectively with that dosage. The 30 Gy threshold seems to be critical. Toxicity increases exponentially when the dosage goes higher than that.
But knowing some HPV-positive head and neck cancer is resistant complicated the issue. Nobody wanted to risk undertreating the cancer and having it return or spread.
“Dr. Lee has really pioneered using hypoxia imaging to pick out tumors that are more sensitive for this de-escalatory regimen,” Dr. Riaz says. “This has not been done anywhere else in the world for these tumors.”
The new phase II trial will enroll 76 people at MSK, but it is certain to expand to include many more at other institutions.
Dr. Lee expects that the multicenter trial will provide definitive answers about the effectiveness of the technique in two to three years. Although the treatment lasts only a few weeks, the researchers plan to do meticulous follow-ups to evaluate the long-term effects.
“We hope to use the results to gain FDA approval of hypoxia PET imaging for specific use in the de-escalation of HPV-positive cancer so we can bring this technique to the world,” she says.Back to top