Source: www.mskcc.org
Author: Memorial Sloan Kettering Cancer Center

Robert Rosenfeld thought the lump he felt in his neck in late 2018 was just a symptom of a cold that wouldn’t go away. He visited an ear, nose, and throat specialist who saw nothing upon first examination, but Robert knew something was wrong and asked for a CT scan. The specialist called him with the bad news: It was almost certainly cancer. A biopsy confirmed he had stage 2 cancer at the base of his tongue and 2 nearby lymph nodes. The tumor was positive for the human papillomavirus (HPV).

Robert, then a 69-year-old car salesman on Long Island, met with cancer doctors near his hometown of Hauppauge, New York, to learn about treatment options. He realized he faced a tough road: Standard treatment would be 7 weeks of radiation, during which he also would receive 3 rounds of chemotherapy. The standard radiation dose would likely cause mouth sores, difficulty swallowing, dry mouth (from damage to salivary glands), loss of taste, and nausea.

Robert wanted a second opinion, and his medical oncologist strongly recommended Memorial Sloan Kettering Cancer Center. When Robert called, he was able to get in to see radiation oncologist C. Jillian Tsai the very next day.

“When I met Dr. Tsai, she was amazing,” Robert says. “She told me what I was up against but also that the cancer I had was curable.”

There was another major plus: Dr. Tsai was able to offer a significantly reduced radiation dose to decrease side effects.

Over the last decade, MSK has been implementing de-escalation approaches for HPV-positive head and neck cancer. One method, developed by Nancy Lee, Service Chief of Head and Neck Radiation Oncology, on behalf of MSK’s Head and Neck disease management team, revolutionized radiation treatment and greatly improved quality of life for patients.

‘An Absolute Game Changer’
Radiation dosage is measured in units called Gray (Gy). The standard approach for treating head and neck cancer had long been 70 Gy to any visible tumor and 50–60 Gy to a large surrounding area that can harbor invisible tumor cells. Due to the high dose and large area treated, this can be difficult for patients, who typically lose 20 to 30 pounds and may have to go on work disability for several months.

But Dr. Lee remembered research from years earlier that showed only 30 Gy was needed to successfully treat HPV-positive anal cancer. She thought the same dose might be possible for certain head and neck cancers.

In 2015, MSK radiation oncologists began treating select patients with HPV-positive head and neck cancers with only 30 Gy to both the visible tumor and all surrounding areas over 3 weeks, with only 2 cycles of chemotherapy. Lowering the dosage has proved safe and effective. Patients have less throat pain, less fatigue, and less radiation burn. They have a much better quality of life not only during treatment but also afterward.

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

“It’s really hard to describe the huge difference this makes,” agrees radiation oncologist Nadeem Riaz. MSK head and neck surgeon Jay Boyle adds that he no longer see the late side effects of radiation that used to be common in his clinic.

Making More Patients Eligible
However, some people with HPV-positive cancers — like Robert’s — are not eligible for the approach of only 30 Gy to treat their cancer because of their disease characteristics. “Also, the special imaging and frequent monitoring required for this approach might not be feasible for a broader population in the communities,” explains radiation oncologist Sean McBride.

For these patients, MSK has developed a slightly different treatment plan that everyone can receive. It involves first giving 30 Gy over 3 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 — as opposed to the conventional 50–60 Gy.

This hybrid approach means a larger patient group can benefit from the reduced radiation plan.

“Patients treated with conventional radiation approaches receive a huge dose in a large area of the head and neck during the first treatment portion of 5 or 6 weeks,” Dr. Tsai says. “That is very toxic, and we have been able to show that it’s not necessary to be effective. Our approach of ‘30 Gy, followed by 40 Gy’ works just as well, while greatly reducing side effects.”

MSK began using the “30 Gy, then 40 Gy” approach as a standard of care for people like Robert beginning in 2017. On January 20, 2022, Drs. Tsai, Lee, and other MSK colleagues reported the effectiveness of this technique in JAMA Oncology. In a study of 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 2 years later. The overall survival rate (those who did not die from any cause) after 2 years was 95%.

The reduced-radiation treatment is available at all locations, including MSK’s 7 outpatient facilities in New Jersey and New York State.

Continuing to Adjust the Dose
In addition to the hybrid “30 Gy, then 40 Gy” approach, Dr. Tsai told Robert he would be a good fit for a phase 2 clinical trial she was leading at MSK that could provide even further benefits. The trial involves continually adjusting the radiation plan based on how the tumor is changing or shrinking.

“We do a weekly MRI scan, which allows us to really personalize the treatment and tailor it to what is actually needed,” Dr. Tsai says. Robert was immediately on board.

“It became clear to me that the side effects would be much less than if I were treated somewhere else,” he says.

Robert started treatment in December 2018, receiving chemotherapy and radiation over 7 weeks, most of it at MSK Commack on Long Island. Dr. Tsai oversaw his radiation treatment, and medical oncologist Juliana Eng directed his chemotherapy. He completed all treatments at the end of January 2019.

Robert says the benefits of the reduced dosage are clear to him every day — especially his lack of dry mouth. Today, at 72, he is “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 6 months at MSK Nassau for follow-up examinations.

“Dr. Tsai is absolutely the finest doctor I have ever dealt with,” Robert says. “Not only is she compassionate and caring, she’s absolutely brilliant in her field. And no hospital could treat you better than Sloan Kettering.”

Key Takeaways
– Radiation for head and neck cancers can have difficult side effects.
– MSK experts have pioneered an approach using lower radiation doses.
– The approach can be used for many patients with HPV-positive cancers.

Note:
In addition to Drs. Tsai, Lee, McBride, and Riaz, other MSK authors on the JAMA Oncology paper are J. Julie Kang, Daniel Spielsinger, Todd Waldenberg, Daphna Gelblum, Yao Yu, Linda Chen, Kaveh Zakeri, Richard Wong, Lara Dunn, David Pfister, and Eric Sherman.

The research was funded by NIH R01CA129182 and NIH/NCI Cancer Center Support Grant P30 CA008748.