Reduced Radiation Dose After Surgery May Improve Survival Rates in HPV-Related Throat Cancer

Transoral robotic surgery followed by low-dose radiation may reduce treatment intensity and improve long-term quality of life compared to usual care, which consists of high-dose radiation and chemotherapy, in patients with HPV-associated throat cancer, recent study findings demonstrate.

Positive results from the E3311 study led by the ECOG-ACRIN Cancer Research Group may have been related to the ability of researchers to categorize patients by risk before undergoing surgery.

“The study was very helpful in that it gave us a big national sample of people getting transoral surgery,” said Dr. Barbara Burtness, a professor of medicine at Yale School of Medicine, lead of the Head/Neck Cancer Research Program at Yale and a co-leader of the Developmental Therapeutics Program at the Yale Cancer Center, in an interview with CURE®. “It helped us to understand if our rules for deciding who was low risk, intermediate risk and high risk reflected the real natural biology of the cancer. I think that they gave us the first signs that with pathologic staging in HPV-associated cancer, you can actually reduce the intensity of the postoperative treatment. So we actually reported extremely remarkable results.”

Increased Incidence of HPV-Associated Throat Cancer

Over the past few decades, there has been an increase in throat cancer associated with HPV, which is usually transmitted through sexual contact or kissing, Burtness said.

She added, “As the number of people who have more sexual partners and more romantic partners has gone up over the decades, there’s been more transmission of the virus. It is quite fortunate that there are now very effective HPV vaccines. We recommend that both boys and girls, men and women who are aged 9 to 45 should get these vaccines. The vaccines clearly prevent cervical cancer and genital warts. Although we are still following the population, because tonsil cancer takes a long time to develop, we believe that the vaccines are also going to reduce the incidence of tonsil cancer.”

Patients with HPV-associated throat cancer often respond positively to treatment with either surgery and adjuvant therapy or with chemoradiation, but long-term toxicity from chemoradiation may be a concern as patients live longer, according to the introduction of the study published in the Journal of Clinical Oncology.

“We treat patients (with HPV-associated throat cancer) with approaches — either surgical approaches or chemotherapy approaches — that were actually developed in an era when most of the head/neck cancer was not HPV related,” Burtness explained. “One of the early things that was recognized by investigators … was that HPV-associated cancers were very sensitive to treatment, so they were more likely to shrink with chemotherapy and radiation. So one question was, could you get the same curative effects with less treatment and, with that, spare some of the side effects of treatment.”

Burtness added that the development of new surgical techniques for throat cancer using a robot and magnifying lenses allowed patients to be operated on in a less invasive way.

To study the potential benefit of deintensification of radiation and/or chemotherapy after surgery, researchers compared reduced dose of postoperative radiation therapy with a standard dose in 495 patients with stage 3 to 4a HPV-associated throat cancer. Patients were assigned to treatment based on their risk profile:

• Group A: low risk (38 patients) underwent observation after surgery
• Group B: intermediate risk (100 patients) underwent reduced radiation therapy after surgery
• Group C: intermediate risk (108 patients) underwent standard dose of radiation therapy after surgery
• Group D: high risk (113 patients) underwent chemoradiation

Several outcomes of interest throughout the study included progression-free survival (the time during and after treatment when a patient with cancer lives with the disease without worsening) at two years, quality of life and swallowing capabilities.

After a median follow-up of 35.2 months of 359 patients, three-year progression-free survival was 96.9% in group A, 94.9% in group B, 93.4% in group C and 90.7% in group D. There was also a trend towards improved quality of life in patients who underwent treatment with reduced radiation therapy and chemotherapy.

Improved Swallowing Recovery After Surgery

Findings from the study also demonstrated recovery of patient’s swallowing after surgery.

“Our hypothesis was that by making the postoperative treatment less intensive, we would spare toxicity, patients would be less likely to need a feeding tube, they’d be more likely to have normal recovery of their swallowing and their swallowing would be more likely to recover quickly,” Burtness explained. “Our initial analysis does show that there’s a benefit to giving five weeks of radiation compared to six weeks of radiation in terms of the patient’s function.”

It’s important to note that not everyone who has throat cancer is a good candidate for transoral surgery, which is performed through the natural orifice of the mouth.

“If the tumor is too close to a blood vessel, the person might not be a good candidate,” Burtness said. “If the tumor has a very infiltrative growth pattern and the surgeon can’t readily define what the margins should be, if it’s too close to the midline of the tongue or it crosses the midline of the tongue, and you realize that it could well have spread to lymph nodes on both sides of the neck. If the lymph nodes in the neck are very matted together and you can tell from the baseline scan, that this is a person who’s going to need chemoradiation anyway — in those cases, we wouldn’t recommend surgery upfront.”