Intensity-modulated radiation therapy (IMRT) and proton beam therapy both provide very good tumor control and notably fewer long-term side effects in the treatment of locally advanced throat cancer, according to phase III clinical trial results presented September 29 at the American Society for Radiation Oncology (ASTRO) annual meeting.
However, findings observed as part of the landmark U.K. TORPEdO (TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer) trial confirm that high-quality IMRT is a very good treatment for this disease, noted David Thomson, MD, chief investigator and consultant clinical oncologist at The Christie NHS Foundation Trust in Manchester, England.
“There’s been interest in the use of proton beam therapy specifically for head and neck cancers because of the intricate nature of treating this area, with nearby organs for chewing, swallowing, speech, hearing, and other important functions,” Thomson explained for ASTRO. TORPEdO investigated proton beam therapy for reducing long-term side effects.
Oropharyngeal squamous cell carcinoma is a head and neck cancer affecting the middle part of the throat. Standard treatment involves IMRT combined with chemotherapy. However, severe side effects from IMRT can include difficulty with swallowing that may require the use of a feeding tube.
Proton therapy, a newer approach, uses proton beams that deposit less radiation, but it requires specialized facilities and training that are less widely available. Proton therapy is substantially more expensive than IMRT, according to Thomson.
The TORPEdO trial focused on 205 patients (median age 57.1), 79.5% of whom were males treated at 20 U.K. centers between 2020 and 2023 — including 136 who received fractionated intensity-modulated proton therapy (IMPT), and 69 who received IMRT with concurrent cisplatin chemotherapy.
Co-primary endpoints combined two groups: clinician-assessed feeding tube use and severe weight loss, and patients’ self-reported side effects. Analysis accounted for tumor and nodal stage, smoking status, chemotherapy received, baseline body mass index (BMI), and baseline University of Washington quality of life (UW-QOL) physical composite score.
According to the results, only 1.7% of patients in both groups needed a feeding treatment in the long term (one year later) because of treatment-related toxicities. Patients in the proton arm had more weight loss than those who underwent IMRT — 18.2% vs. 5.7%.
“Because of that, the composite end, which looked at both of those factors, favored IMRT,” Thomson said in an ASTRO briefing. In addition, at 24 months, freedom from local recurrence after IMPT was 94.3% and 96.8% after IMRT, with 94.6% overall survival after IMPT, compared to 95.3% with IMRT, according to the results.
Furthermore, TORPEdO showed that one year after treatment, patients who had IMPT or IMRT reported very similar scores using both the UW-QOL questionnaire (78.3 vs. 77.1) and the MD Anderson Dysphasia Inventory questionnaire (79.5 vs. 79.7).
“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,” Thomson pointed out.
Furthermore, dosimetric analyses showed that proton therapy was able to lower radiation exposure to nearby swallowing and salivary gland structures, but that did not translate into measurable differences in patient-reported outcomes, function, or quality of life, according to Thomson.
Providing expert commentary, C. Jillian Tsai, MD, PhD, of University of Toronto’s Princess Margaret Cancer Center, said TORPEdO is a reminder about the importance of patient selection, especially for oropharyngeal cancer patients.
“Unilateral versus bilateral, neck irradiation will be different,” Tsai said. “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.”
The next step, in addition to having newer technology, is to refine strategy, to maintain the high cure rate while minimizing the side effects.
“We should probably also consider, in addition to protons, we want to reduce the radiation volume and dose while safe and then personalize the treatment in real time with onboard imaging and newer liquid biopsy techniques,” Tsai added.
TORPEdO was a randomized, controlled, multicenter trial funded by Cancer Research UK. Thomson noted that a strength of the trial was that treatment planning and delivery in both arms met standards overseen by the U.K. National Radiotherapy Trials Quality Assurance Group.