Top Line: A recent US phase 3 trial made headlines with a suggestion of less toxicity translating to better survival with proton versus photon therapy for oropharyngeal squamous cell carcinoma (SCC).
The Study: It’s important to note neither toxicity nor overall survival nor the interplay between the two were primary endpoints, largely because they lack clear biologic plausibility. And now we have results from the other side of the pond. In the UK phase 3 trial TORPEdO, 205 patients receiving definitive chemoradiation for locally advanced oropharyngeal SCC were randomized 2:1 to IMPT vs IMRT 70 Gy in 33 fractions with concurrent cisplatin. Co-primary endpoints at 12 months were (1) gastrostomy dependence or ≥20% weight loss and (2) quality-of-life scores. It turns out long-term G-tube dependence was similarly rare (2% vs 2%), while severe weight loss actually trended worse with protons (18% vs 6%; OR 2.8, p=0.079). It’s important here to note G-tube use at any time was lower with protons (45% total / 26% prophylactic) than with photons (58% total / 38% prophylactic), mirroring the US trial. QoL scores were nearly identical (78 vs 77, p=0.56), and, at two years, there were no significant differences in locoregional control (94% vs 97%) or overall survival (95% vs 95%). Interestingly, while acute grade 3 events were more common with photons (72%) than protons (50%), late grade 3 events other than hearing loss (attributed to cisplatin) were less common with photons (6%) than protons (18%), largely due to discrepancies in lingering weight loss. “The apparent divergence in rates of acute and late events between IMRT (more acute) and IMPT (more late descriptively) suggests differential mechanisms predominate—eg, acute inflammation versus late vascular effects or fibrosis.” Ultimately, with long-term G-tube use that is very low among this large definitive head and neck radiation cohort, this is more of a win for IMRT than a loss for protons. “The TORPEdO trial optimised plans to spare 20 OARs and used contemporary outlining of target volumes” resulting in “fully optimised function-sparing radiotherapy” regardless of modality.
TBL: In the era of modern, optimized IMRT, proton therapy did not translate dosimetric advantages into clinically meaningful long-term quality-of-life gains in the definitive treatment of oropharyngeal cancer. What’s more, toxicity outcomes may depend on the time point used and appear to favor protons earlier and photons later. | Thomson, Lancet 2026
The Study: It’s important to note neither toxicity nor overall survival nor the interplay between the two were primary endpoints, largely because they lack clear biologic plausibility. And now we have results from the other side of the pond. In the UK phase 3 trial TORPEdO, 205 patients receiving definitive chemoradiation for locally advanced oropharyngeal SCC were randomized 2:1 to IMPT vs IMRT 70 Gy in 33 fractions with concurrent cisplatin. Co-primary endpoints at 12 months were (1) gastrostomy dependence or ≥20% weight loss and (2) quality-of-life scores. It turns out long-term G-tube dependence was similarly rare (2% vs 2%), while severe weight loss actually trended worse with protons (18% vs 6%; OR 2.8, p=0.079). It’s important here to note G-tube use at any time was lower with protons (45% total / 26% prophylactic) than with photons (58% total / 38% prophylactic), mirroring the US trial. QoL scores were nearly identical (78 vs 77, p=0.56), and, at two years, there were no significant differences in locoregional control (94% vs 97%) or overall survival (95% vs 95%). Interestingly, while acute grade 3 events were more common with photons (72%) than protons (50%), late grade 3 events other than hearing loss (attributed to cisplatin) were less common with photons (6%) than protons (18%), largely due to discrepancies in lingering weight loss. “The apparent divergence in rates of acute and late events between IMRT (more acute) and IMPT (more late descriptively) suggests differential mechanisms predominate—eg, acute inflammation versus late vascular effects or fibrosis.” Ultimately, with long-term G-tube use that is very low among this large definitive head and neck radiation cohort, this is more of a win for IMRT than a loss for protons. “The TORPEdO trial optimised plans to spare 20 OARs and used contemporary outlining of target volumes” resulting in “fully optimised function-sparing radiotherapy” regardless of modality.
TBL: In the era of modern, optimized IMRT, proton therapy did not translate dosimetric advantages into clinically meaningful long-term quality-of-life gains in the definitive treatment of oropharyngeal cancer. What’s more, toxicity outcomes may depend on the time point used and appear to favor protons earlier and photons later. | Thomson, Lancet 2026