This story was originally published in 2017 and was last updated in September 2026 to reflect “Breakthrough Therapy” designation by the FDA.
After a decade of research seeking ways to make radiation treatment easier for patients, doctors at Memorial Sloan Kettering Cancer Center (MSK) have confirmed that many HPV-positive throat cancer patients can be treated with significantly less radiation and still survive the disease.
“This has been an absolute game changer for treating certain people with throat cancers caused by the human papillomavirus or HPV,” says MSK radiation oncologist Nancy Lee, MD, who pioneered the approach. “The difference in toxicity is dramatic.” Dr. Lee 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.
Now the U.S. Food and Drug Administration (FDA) has granted “Breakthrough Therapy” designation to an essential component of this low-dose approach — a specialized imaging tracer that can identify HPV-positive patients who could safely receive less-intensive treatment. The tracer is used in an imaging technique called FMISO PET that can reveal whether a tumor is hypoxic (has low oxygen levels). Tumors that are hypoxic are less likely to respond to the low-dose approach.
The Breakthrough Therapy designation was given to 18F-fluoromisonidazole, or FMISO, a first-in-class hypoxia tracer licensed by Juniper Biosciences from MSK. Using FMISO PET enables doctors to precisely select patients eligible to receive the low-dose treatment.
The FDA designation was supported by a growing body of clinical evidence showing that FMISO PET is a reliable guide for evaluating patients for de-escalated radiation treatment.
Radiation dosage is measured in units called Gray (Gy). The standard dosage for throat cancer has long been 70 Gy, along with three cycles of chemotherapy. At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Lee presented a new analysis of multiple studies conducted over 10 years that included 430 patients — 75% of whom were eligible for and received a substantially reduced radiation dose at 30 Gy for three weeks instead of the standard 70 Gy over 7 weeks.
In addition, an ongoing phase 3 clinical trial expected to complete at the end of 2027 is comparing the FMISO PET–guided approach against standard therapy.
Substantially reducing the radiation dose keeps the cancer away while dramatically cutting down on the debilitating side effects that often make eating and swallowing difficult.
“We are excited that the FDA has granted Breakthrough Therapy designation, and we look forward to completing this phase 3 trial and generating the pivotal evidence needed to support potential FDA approval,” Dr. Lee says.
Breakthrough Therapy designation is a process designed to speed the review of drugs to treat a serious condition, for which preliminary clinical evidence indicates a potentially substantial improvement over available therapy.
Reducing radiation by more than half
The standard radiation therapy approach achieves high survival rates, but it takes a major toll on patients. They often experience mouth sores, difficulty swallowing, dry mouth, changes in taste, and nausea. Weight loss of 20 to 30 pounds is common, and many patients cannot work for months during and after treatment.
Pioneering work by Dr. Lee showed that many HPV-positive head and neck tumors can be safely treated with a 30-Gy dose and two cycles of chemotherapy.
“We are challenging the traditional dogma of using a one-size-fits-all approach to treat cancer and changing it to a more personalized treatment,” Dr. Lee says.
FMISO PET scans identify patients eligible for low-dose radiation
The success of the reduced-intensity treatment hinges on precise patient selection. While researchers have long sought ways to identify HPV-positive patients who could safely receive less-intensive treatment, traditional factors, such as smoking history, were not reliable.
Dr. Lee and colleagues pioneered a novel approach: selecting patients based on oxygen levels in their tumors. This distinction is critical because hypoxic (low oxygen) tumors are more resistant to radiation and chemotherapy, making them poor candidates for dose reduction.
Fortunately, most head and neck cancers, including throat cancers, are nonhypoxic, which means they have normal levels of oxygen. Patients with these types of cancers are eligible for the reduced treatment.
FMISO PET can reveal whether a tumor is hypoxic and therefore rule out patients who would not be successfully treated with a lower radiation dose.
“Dr. Lee has really led the way using hypoxia imaging to pick out tumors that are more sensitive for this deescalated regimen,” MSK radiation oncologist Nadeem Riaz, MD, MSc, says.
Expanding access by standardizing image interpretation
MSK researchers are investigating how the FMISO PET approach can become more widely available. While MSK’s nuclear medicine physicians are highly trained in interpreting FMISO PET images, there have been no standardized criteria to guide physicians with less experience. The absence of standardized interpretation has been a significant obstacle — one that has hindered FDA approval for widespread use FMISO PET scans.
Developing universal training
To address this barrier, nuclear medicine physicians Heiko Schöder, MD, and Rick Wray, MD, developed a training program so physicians at all levels of experience can accurately evaluate the hypoxic status of the tumor. In 2024, they reported results in the Journal of Nuclear Medicine, validating that the standardized method worked well for nuclear medicine physicians with different levels of expertise.
“Doctors have to be confident the right patients are being selected for the low-dose approach,” Dr. Wray says. “A standardized way of interpreting the images makes it possible for this method to be used almost anywhere FMISO PET is available.”
An alternative for patients ineligible for low-dose radiation treatment
Not all people with HPV-positive cancers are eligible for the 30 Gy protocol. Those with larger tumors or who lack access to specialized imaging and frequent monitoring require a different strategy.
For these patients, MSK developed a slightly different plan that’s more accessible to people living far from major cancer centers:
- Give a lower dose over three weeks to the visible tumor and surrounding tissue to kill any stray cancer cells.
- Deliver additional doses using highly precise techniques only to the visible tumor. The tumor still receives a total of 70 Gy — the standard-dose protocol — but the surrounding healthy tissue is spared radiation, thereby reducing side effects.
Dr. Lee and other MSK colleagues published results validating this hybrid technique in JAMA Oncology in 2022, demonstrating its potential to be used for more patients
The research continues with an ambitious goal: making 80% to 85% of people diagnosed with HPV-related head and neck cancers eligible 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.”
MSK’s history of improving quality of life for patients
Dr. Lee first recognized an opportunity for the low-dose approach more than 10 years ago based on earlier research she had read showing that the method worked for HPV-positive anal cancers. It raised the question: Could certain HPV-related head and neck cancers be treated with a similar dose reduction?
The results have been transformative: Patients had less throat pain, less fatigue, and fewer radiation burns.
“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 want them not only to be cancer free, but also to have a good quality of life after all of this is done.”
Key Takeaways
- HPV-related throat cancer is usually treated with 70 Gy of radiation and three rounds of chemotherapy.
- MSK researchers have shown most of these cancers can be treated with 30 Gy radiation and two rounds of chemotherapy.
- This approach greatly reduces debilitating side effects that often make eating and swallowing difficult.
- The FDA has granted Breakthrough Therapy designation to an imaging tracer used to select patients for this reduced radiation. This could be an important step toward full FDA approval.
Dr. Lee’s research receives essential philanthropic support from the MSK Giving community, including James and Diane Rowen and Nancy and Howard Marks.
MSK and Dr. Lee have financial interests in Juniper. A full listing of Dr. Lee’s relationships and financial interests can be found on her profile page.
