The use of intensity-modulated proton therapy (IMPT) did not improve patient quality of life over the standard of care, intensity-modulated radiation therapy (IMRT), for the treatment of oropharyngeal squamous cell carcinoma (OPSCC).

Results from the study also indicate that rates of local recurrence and survival are similar for well-planned IMRT and IMPT, offering reassurance to patients without access to the more advanced IMPT treatment that they are getting really good care with IMRT, said principal investigator David Thomson, MD. He presented these and other findings of the phase 3 TORPEdO trial at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“We found no evidence of a difference in late patient-reported physical side effects or quality of life between proton beam therapy and IMRT, with contemporary IMRT performing better than we anticipated,” said Thomson, who is a consultant clinical oncologist at The Christie NHS Foundation Trust in Manchester, England, in a press release. “Our results confirm that high-quality IMRT is a very good treatment for this disease.”

IMRT vs IMPT

IMRT is a type of external beam radiation that uses x-rays (photons) and advanced computer planning to shape and modulate the radiation dose much more accurately than traditional RT, reducing the dose to healthy tissue. It’s now a part of standard of care for head and neck cancer when combined with chemotherapy because it balances disease control with fewer side effects. It’s attractive because it is widely available and is generally covered by insurance. The pair is highly effective with high cure rates. However, severe long-term side effects can occur, according to an ASTRO patient site.

Proton beam therapy is a type of external beam radiation that uses protons instead of x-rays (photons) to kill cancer cells. High-energy protons deposit most of their energy at a specific depth in tissue and then stop, meaning they don’t affect healthy tissue beyond the tumor, unlike radiation treatment with x-rays. IMPT is a form of proton beam therapy that uses pencil-beam scanning to “paint” the dose across a tumor in layers, adjusting beam intensity spot by spot. It has been speculated that because of a lower dose delivered to healthy tissue, IMPT results in fewer side effects. However, IMPT requires specialized facilities and training, is less widely available, and is substantially more expensive, the ASTRO site says.

Methods and Results

The TORPEdO study included 205 patients with OPSCC requiring chemoradiotherapy including bilateral neck treatment, who were randomly assigned 2:1 to receive either IMPT or IMRT in combination with cisplatin (100 mg/m² on days 1 and 22). Thomson explained that the trial used a 2:1 randomization so it could finish quickly, provide more current results, and gather extra data on the proton arm for research purposes. 

The researchers found that feeding tube use at 12 months, one of the co-primary endpoints, was 1.7% and 1.7% for IMPT and IMRT respectively. Grade 3 weight loss at 12 months was 18.2% for IMPT and 5.7% for IMRT. Overall, 17.6% had feeding tube use or grade 3 weight loss in the IMPT arm, compared with 6.8% in the IMRT arm at 12 months.

IMPT did not improve physical health-related quality of life (HRQOL) — a co-primary endpoint — as measured with the University of Washington Quality of Life Questionnaire physical composite score for saliva, taste, chewing, swallowing, appearance, and speech. After 12 months, the adjusted mean score was 78.3 and 77.1 for the IMPT and IMRT arms, respectively, a difference that was not significant. The tool has a range of 0-100.

Mean swallowing scores were also similar for IMPT vs IMRT: 79.5 vs 79.7 using the MD Anderson Dysphagia Inventory (MDADI). The measurement tool is a head and neck cancer–specific questionnaire designed to measure how swallowing problems affect a patient’s quality of life by assessing the emotional, functional, and physical impact of the cancer.

The researchers also found that freedom from local recurrence at 24 months was comparable for the two treatments: 94.3% and 96.8% for IMPT and IMRT, respectively. Likewise, survival at 24 months was comparable: 94.6% and 95.3% for IMPT and IMRT, respectively.

“IMRT performed better than expected based on historical data involving patient-reported outcomes, and long-term feeding tube dependence was much lower than reported in previous trials,” Thomson said. “It’s an encouraging finding that patients with this type of cancer can receive excellent care at their local treatment centers with this advanced technology.”

Thomson noted that a strength of the TORPEdO trial was its rigorous quality assurance, which he credited for the improved performance of IMRT in this trial compared with earlier research. Treatment planning and delivery in both arms met strict standards overseen by the UK’s National Radiotherapy Trials Quality Assurance Group, he said. 

C. Jillian Tsai, MD, PhD (University of Toronto, Princess Margaret Cancer Centre), applauded the study results. 

“The results are very clear. Proton beam therapy produces overall lower doses to normal tissues … but when it comes to patient outcomes especially at 1 year, there [were] no significant differences … This tells us two things. First, [the] TORPEdO trial is a success in its own right... Second, it reminds us about the importance of patient selection, especially for oropharyngeal cancer patients. Unilateral vs bilateral radiation will be different.

“So, I believe that the most logical way of moving forward is to be selective, reserving protons for patients who are predicted to benefit most based on their anatomic risk and the side effects,” she said during a press conference.

Tsai concluded by saying that TORPEdO reassures clinicians that with the modern technology of IMRT and high-quality planning, results seen with IMRT are equivalent to IMPT, especially for bilateral oropharyngeal cancer patients.

The study was funded by The Christie NHS Foundation Trust. 

Dr Thomson reported a significant financial relationship with Merck & Co. 

Dr Tsai reported that she has no relevant disclosures.