MSK Reducing Side Effects of HPV Head and Neck Cancer Treatment With Low-Dose Radiation

MSK radiation oncologist Nancy Lee, who treats head and neck cancers

Nancy Lee, MD, has developed a way to control head and neck cancer giving lower radiation doses, which eases the burden on patients. “In our world, less is more,” she says.

Nancy Lee is on a quest to not only cure cancer but also to ease the burden of treatment on patients. At the beginning of her career as a radiation oncologist, she knew there was no question that radiation worked against head and neck cancers related to human papillomavirus (HPV) infection. The cure rate was nearly 90% for people receiving radiation along with surgery and chemotherapy.

But standard radiation for head and neck cancers took a toll. Patients often developed side effects such as:

  • Mouth sores
  • Difficulty swallowing
  • Loss of taste
  • Nausea
  • Weight loss

People typically lost 20 to 30 pounds and often had to go on work disability for months. Dr. Lee, now MSK’s Service Chief, Head & Neck Radiation Oncology, wondered how she could spare her patients from these awful side effects.

“I remembered a study demonstrating anal cancer that was HPV-positive could be safely controlled with a much lower radiation dose,” she recalls. “Could a lower dose work for head and neck tumors, too?”

Testing Low-Dose Radiation in Patients

Radiation dosage is measured in units called Gray (Gy). The standard approach for treating head and neck cancer with radiation had long been 70 Gy to any visible tumor and 50–60 Gy to a large surrounding area that can harbor invisible tumor cells.

Dr. Lee launched a study testing whether cutting the radiation dose by more than half would be effective for select patients with HPV-positive head and neck cancers. The participants received only 30 Gy to both the visible tumor and all surrounding areas over three weeks, with only two cycles of chemotherapy.

The benefit for patients was striking. Lowering the dosage proved safe and effective, and the difference in toxicity was dramatic.
Nancy Y. Lee radiation oncologist

The key to success was understanding exactly who would benefit. Most HPV-positive tumors respond well to treatment with chemotherapy and radiation, but a fraction are more resistant and aggressive. Dr. Lee developed a method to determine which tumors would respond to the lower dose. PET imaging technology looked for oxygen concentration in a tumor, which can determine radiation effectiveness. The researchers also analyzed the tumors’ genetic makeup — their “mutational signature,” which could make them especially sensitive to radiotherapy. The radiation was personalized for each patient — a sea change in approach.

“The benefit for patients was striking,” says Dr. Lee. “Lowering the dosage proved safe and effective, and the difference in toxicity was dramatic. Patients had less throat pain, less fatigue, and less radiation burn. They had a much better quality of life not only during treatment but also afterward. They were able to return to work sooner — or never miss any work at all.”

Which Patients Are Eligible for Reduced Radiation?

Dr. Lee and her colleagues are seeking to help even more patients. The lower 30 Gy dose isn’t appropriate for all types of head and neck disease, and the special imaging and frequent monitoring required might not be feasible for everyone. So MSK developed a slightly different treatment plan.

It involves first giving 30 Gy over three weeks to both the visible tumor and the surrounding area to kill any stray cancer cells. Then, 40 more Gy are delivered only to the visible tumor — not the surrounding areas — thereby significantly cutting the radiation dose compared with conventional therapy.

MSK radiation oncologist C. Jillian Tsai

C. Jillian Tsai, MD, PhD, Director, Metastatic Disease Radiation Oncology Research

MSK began using this hybrid approach for certain patients beginning in 2017. It’s available at all MSK locations, including the seven outpatient facilities in New Jersey and New York State.

“Our approach of ‘30 Gy, followed by 40 Gy to the tumor only’ works just as well as the higher conventional doses, while greatly reducing side effects,” says MSK radiation oncologist C. Jillian Tsai, Director of Metastatic Disease Radiation Oncology Research. In January 2022, Drs. Tsai and Lee and other MSK colleagues reported the success of this technique in JAMA Oncology.

Reduced Radiation Patient Success Story

Robert Rosenfeld is one of the lucky ones benefiting from this more recent advance. When he learned he had stage 2 HPV-positive cancer at the base of his tongue and nearby lymph nodes, he met with cancer doctors near his home on Long Island. They told him treatment with the standard three rounds of chemotherapy and seven weeks of radiation would be rough.

It became clear to me that the side effects would be much less if I were treated at MSK.
Robert Rosenfeld

The 69-year-old car salesman came to MSK for a second opinion. Dr. Tsai told him about the hybrid, reduced-radiation approach for HPV-positive head and neck cancer, and Robert was immediately on board. “It became clear to me that the side effects would be much less if I were treated at MSK,” he says.

Dr. Tsai told Robert he would be a good fit for another protocol — a phase 2 clinical trial she was leading at MSK that could provide even further benefits. This experimental technique continually adjusts the radiation plan based on how the tumor is changing or shrinking.

Robert Rosenfeld and his wife

Robert Rosenfeld and his wife, Suzanne

Robert received this protocol involving chemotherapy and radiation, most of it at MSK Commack on Long Island. Since completing all treatments at the end of January 2019, he says, “I’m at 100%.” He and his wife, Suzanne, enjoy having dinner with friends, going to Broadway shows, and dancing. Dr. Tsai says Robert’s prognosis is excellent, with no evidence of disease. He sees her every six months at MSK Nassau for follow-up examinations.

“Dr. Tsai is absolutely the finest doctor I have ever dealt with,” Robert says. “And no hospital could treat you better than Memorial Sloan Kettering.”

New Radiation Treatments on the Horizon

MSK continues to push the envelope to ease treatment side effects on patients. A clinical trial is now investigating whether some might avoid surgery altogether, and a second trial will test whether other patients can avoid radiation after surgery.

“We are already changing the way practitioners think about radiation therapy,” Dr. Lee says. “We’re leaders in high-precision radiation therapy and believe it can help even more patients with other kinds of cancers. In our world, less is more.”

MSK 2021 Annual Report
Our three pillars — patient care, scientific research, and education — supported extraordinary progress in 2021. Learn about just some of our achievements in this Annual Report.