Intensity-Modulated Radiation, Proton Therapy Show Similar OPSCC Outcomes

Intensity-modulated radiation therapy (IMRT) conferred similar outcomes vs intensity-modulated proton therapy (IMPT) among patients with locally advanced oropharyngeal squamous cell carcinoma (OPSCC), according to findings from the phase 3 TORPEdO trial (NCT01893307) published in The Lancet.

Among 205 patients with OPSCC treated in the trial with IMRT (n = 67) or IMPT (n = 132), gastrostomy-tube dependence was observed in 2% (95% CI, <1% to 10%) vs 2% (95% CI, <1% to 7%) of each group, and feeding tube use at any time was observed in 58% vs 45% of evaluable patients. Prophylaxis placements were observed in 38% of the IMRT group vs 26% with IMPT. Additionally, the median end-of-treatment weight loss was 7% (IQR, 5%-11%) vs 6% (IQR, 3%-9%) in each respective group.

No patients experienced grade 3 weight loss by end of chemoradiotherapy (CRT) in either arm. By contrast, the grade 3 weight loss rates at 6 months post-CRT was 5% with IMRT vs 17% with IMPT. Additionally, the rate of grade 2 weight loss or higher, defined as 10% or more, from week 6 to month 24 was 11% (95% CI, 9%-16%) vs 14% (95% CI, 10%-20%).

Among patients evaluable for UW-QoL physical composite score in the IMRT (n = 55) and IMPT (n = 99) arms, the adjusted mean scores were 77.1 (95% CI, 73.1-81.0) vs 78.3 (95% CI, 75.4-81.3), respectively, for a mean difference of 1.3 (95% CI, –3.7 to 6.2; P = .56). Across both arms, scores decreased with CRT and increased up to 12 months post-treatment. Moreover, the respective 3- and 24-month adjusted scores were 66.8 (95% CI, 62.4-71.3) vs 70.8 (95% CI, 67.8-73.9) and 79.9 (95% CI, 75.5-84.3) vs 81.6 (95% CI, 78.8-84.5).

“IMPT and IMRT showed similar late effects, physical QOL, gastrostomy dependence, swallow function, local control, and overall survival [OS],” lead TORPEdO investigator, David J. Thomson, MD, professor of Clinical Oncology at the University of Liverpool and clinical lead for Head and Neck for NHS Greater Manchester, wrote in the publication with coinvestigators. “The trial provides robust data on [adverse] effect [AE] profiles and trajectories with modern treatments. Contemporary radiation contouring and advanced IMRT planning improved outcomes compared with previous series. Both modalities are effective and in health-care settings where IMPT is not used routinely for [OPSCC], IMRT remains the standard of care.”

The 24-month freedom from loco-regional recurrence rate among patients in the IMRT and IMPT arms were 97% (99% CI, 82%-100%) vs 94% (99% CI, 86%-98%), with an HR of 2.6 (95% CI, 0.5-12.4; P = .24). Additionally, the 24-month OS rates were 95% (99% CI, 81%-99%) and 95% (99% CI, 86%-98%), respectively, for an HR of 1.6 (95% CI, 0.4-5.9; P = .47).

Patients with newly diagnosed OPSCC suitable for concurrent CRT were enrolled on the trial and randomly assigned 2:1 to receive IMPT or IMRT, stratified by center, site of disease, T stage, presence of bilateral neck nodes, and smoking status, among other characteristics. A total of 70 Gy to the therapeutic target volume and 56 Gy to areas at lower risk of microscopic disease were given in 33 daily fractions over 6.5 weeks. Chemotherapy was given with cisplatin at 100 mg/m² on days 1 and 22 of radiotherapy. Carboplatin at area under the concentration-time curve 5 substitution was considered on day 22 in the event of cisplatin-related AEs.

The co-primary end points of the trial were UW-QoL physical composite score and gastrectomy-tube dependency. Secondary end points included weight loss, tube status, acute and late AEs, functional outcomes, loco-regional control, and OS.

Grade 3 radiotherapy-related AEs occurred in 72% of the IMRT group vs 50% of the IMPT group (P = .0035), with grade 3 late AEs occurring in 14% vs 25% of the respective arms (P = .081). Excluding late hearing loss and weight loss, the rate of grade 3 radiotherapy-related AEs was 6% vs 18%, respectively (P = .029). No grade 4 radiotherapy-related AEs were reported.

The most common reasons for IMRT interruptions were acute adverse effects (n = 2) and bank holiday (n = 1). Moreover, the most common reasons for interruption of IMPT were cyclotron breakdown (n = 47), service (n = 6), and acute AEs (n = 5).

Reference

Thomson DJ, Price JM, Tyler M, et al. Proton beam therapy for oropharyngeal cancer (TORPEdO): a phase 3, randomised controlled trial. Lancet. 2026;407(10535):1259-1275. doi:10.1016/S0140-6736(26)00314-4