Low-Dose Radiation To Treat HPV Throat Cancer a ‘Game Changer’

MSK radiation oncologist Nancy Lee

MSK radiation oncologist Dr. Nancy Lee pioneered a new treatment approach that uses reduced radiation doses for HPV-related throat cancer, which greatly reduces side effects. “The difference in toxicity is dramatic,” she says.

An innovative radiation treatment approach is dramatically improving quality of life for most people with throat cancer and other head and neck cancers caused by the human papillomavirus (HPV). The new method, pioneered by Memorial Sloan Kettering Cancer Center (MSK) radiation oncologist Nancy Lee, MD, greatly reduces the radiation dose to minimize side effects.

“This has been an absolute game changer for treating people with throat cancers,” Dr. Lee says. “The difference in toxicity is dramatic.”

Multiple studies at MSK suggest that de-escalating treatment this way can effectively control the cancer while decreasing often-debilitating side effects that make eating and swallowing difficult and unpleasant.

FMISO PET Scans Identify Low-Dose Radiation Patients

It is critical to determine which patients are suitable for this approach, to ensure that the radiation dose is large enough to treat the specific tumor they have. Now new results from a phase 2 clinical trial show that using a specialized imaging technique called FMISO PET allows doctors to select which patients can benefit from the low-dose treatment.

FMISO PET scans can reveal oxygen levels in tumors. Most head and neck cancers, including throat cancers, have normal levels of oxygen (called non-hypoxic). These patients are eligible for the lower dose of radiation. Tumors with low oxygen (hypoxic) are not suitable, because they don’t respond as well to radiation or chemotherapy.

We've learned radiation levels for non-hypoxic tumors can be reduced by more than half.
Nancy Y. Lee radiation oncologist

“We’ve learned radiation levels for non-hypoxic tumors can be reduced by more than half,” says Dr. Lee, who is Vice Chair of the Department of Radiation Oncology, Service Chief of Head and Neck Radiation Oncology, and Service Chief of Proton Therapy at MSK.

Radiation dosage is measured in units called Gray (Gy). The standard approach for treating head and neck cancer has been 70 Gy. In the latest clinical trial involving MSK patients with throat cancer, Dr. Lee and colleagues showed that FMISO PET reliably identified people with non-hypoxic tumors — making them safe to receive a reduced dose of 30 Gy.

Low-Dose Radiation for HPV Throat Cancer Clinical Trial Results

Results from the trial, published in Journal of Clinical Oncology, showed that most HPV-positive throat cancer patients were eligible for the 30 Gy dose and responded well:

  • 152 patients with HPV-related oropharyngeal carcinoma (throat cancer) had FMISO PET scans. Of these, 128 patients (84%) were eligible for the low (30 Gy) dose. The other 24 patients received the 70 Gy dose.
  • The lower dose controlled the cancers as effectively as did the higher dose. Impressively, the overall survival was 100% — meaning all the low-dose patients survived. For 94% of those low-dose patients, the cancer did not progress for two years (also known as “progression-free survival”). The 6% of patients whose cancers did progress were successfully treated with follow-up radiation. Meanwhile, for patients receiving the higher standard dose, the overall survival rate was 96%, as was the two-year progression-free survival.
  • Serious side effects from the treatment were significantly lower in the 30 Gy group. While nearly 60% of patients who received the standard 70 Gy dose reported severe side effects, they were reported in only 32% of those receiving the lower dose.

“The findings further validate our de-escalated treatment approach by providing a reliable method for choosing or excluding patients to receive lower doses,” says Dr. Lee. “Most patients do not have low-oxygen, hypoxic tumors, so we can feel confident that treating them with reduced doses is effective while sparing them from toxic side effects.”

“Dr. Lee has really pioneered using hypoxia imaging to pick out tumors that are more sensitive for this de-escalated regimen,” radiation oncologist Nadeem Riaz, MD, MSc, says. “MSK is a world leader in this approach.”

MSK’s History of Improving Quality of Life for Patients

HPV-related head and neck cancers have surged in recent years, especially in men. These types of cancer, sometimes grouped together as oropharyngeal cancer, usually respond well to a combination of surgery, radiation, and chemotherapy. In addition to the 70 Gy given with standard treatment, patients also have typically received three rounds of chemotherapy.

This standard treatment produces a high survival rate — close to 90% — but the treatment takes a major toll. Chemotherapy and radiation can cause mouth sores, difficulty swallowing, dry mouth, changes in taste, and nausea. Patients typically lose 20 to 30 pounds and may have to go on work disability for several months.

Noting earlier studies showing that only 30 Gy was needed to successfully treat HPV-positive anal cancer, Dr. Lee wanted to test that lower dose on certain HPV-positive head and neck cancers. In 2015, MSK radiation oncologists began treating select patients with only 30 Gy over three weeks, with only two cycles of chemotherapy. Patients had less throat pain, less fatigue, and less radiation burn.

“It’s really hard to describe the huge difference this makes,” Dr. Riaz says. “Using the smaller dose over just three weeks, they have almost no radiation side effects.”

Decreasing chemotherapy also eases the burden for patients. “Anytime we can safely reduce the amount of chemotherapy someone needs, we go for it,” says head and neck oncologist Anuja Kriplani, MD, MPH. “I always tell patients that I not only want them to be cancer free but also to have a good quality of life after all of this is done.”

How MSK Is Expanding Low-Radiation Treatments to More Patients

In recent years, Dr. Lee and colleagues have sought to broaden the use of the low-dose protocol. For example, some people with HPV-positive cancers are not eligible for the 30 Gy approach because of their tumor characteristics — usually being too large. Also, the special imaging and frequent monitoring required for the de-escalated approach might not be feasible for a widespread population that is further from major hospitals.

For these patients, MSK developed a slightly different, more accessible 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 in a highly precise manner only to the visible tumor. The tumor still gets 70 Gy total, but the large surrounding regions receive only 30 Gy.

This hybrid approach means a larger patient group can benefit from reduced radiation. In 2022, Dr. Lee and other MSK colleagues reported the effectiveness of this technique in JAMA Oncology:

  • Among 276 patients with HPV-positive head and neck cancer who received this radiation treatment along with chemotherapy, 97% had no evidence of cancer cells in the tumor site or surrounding lymph nodes two years later.
  • The overall survival rate (those who did not die from any cause) after two years was 95%.

“Our approach of ‘30 Gy to the larger standard field, followed by 40 Gy customized to the visible tumor only’ works just as well, while significantly reducing side effects,” Dr. Lee says.

Dr. Lee and colleagues continue to investigate numerous ways to deliver less-toxic treatments to even more patients. The goal is to make 80% to 85% of people diagnosed with HPV-related head and neck cancers candidates for lower-dose therapy.

“In addition to dramatic improvement to patients’ quality of life, we’re saving them the hassle of having to come in every day,” Dr. Lee says. “They can get back to doing the things they love.”

To learn more about these clinical trials, email Dr. Lee at [email protected].


This story was originally published in 2017 and has been updated with new information.

Nancy Y. Lee discloses the following relationships and financial interests:

  • Galera Therapeutics, Inc.
    Professional Services and Activities
  • Merck & Co Inc.
    Professional Services and Activities
  • Merck Serono
    Professional Services and Activities
  • Nanobiotix
    Professional Services and Activities (Uncompensated)
  • Shanghai Jo’Ann Medical Technology Co., Ltd
    Professional Services and Activities
  • Shanghai Yingming Consulting Co., Ltd
    Professional Services and Activities