Proton therapy for oropharyngeal cancer: a phase 3 trial reports better survival than photon radiotherapy

What happened

The trial, led by MD Anderson Cancer Center in Houston and run at 21 US sites, enrolled 440 patients with stage III or IV oropharyngeal cancer. They were randomly assigned to intensity-modulated proton therapy (IMPT) or intensity-modulated photon radiotherapy (IMRT), both combined with systemic therapy. All received the same dose: 70 Gy in 33 fractions.

The primary endpoint was progression-free survival, and protons proved non-inferior: 82.5% vs 83.0% at 3 years and 81.3% vs 76.2% at 5 years. Five-year overall survival was 90.9% with protons vs 81.0% with photons. Patients treated with protons less often had swallowing difficulties (31% vs 49%), dry mouth (33% vs 45%) and feeding-tube dependence (26.8% vs 40.2%).

The explanation is physical: photons pass through the body and leave a radiation dose at both entry and exit in tissues that are not the target, whereas protons reduce exposure of healthy tissue. In the head and neck, tumours lie close to sensitive organs and tissues.

FLASH: radiotherapy in a fraction of a second

FLASH radiotherapy delivers the dose in a fraction of a second, up to a thousand times faster than standard radiotherapy. On 15 July 2026, the University of Cincinnati announced results of the FAST-02 study, published in Radiotherapy and Oncology: 10 patients with painful bone metastases in the chest, near the heart and lungs, were treated with proton FLASH. There were no serious treatment-related side effects, and 75% of patients assessed at three months reported complete pain relief at the treated site.

What it means for patients now

The Lancet trial was carried out in the US, at centres that offer proton therapy. The lead author, Dr Steven Frank, stresses that both protons and photon radiotherapy are very good treatment options and that it remains important to identify which patients benefit most from protons. FLASH radiotherapy is, for now, only being tested in clinical trials.

What is still unknown

The Lancet results come from a planned interim analysis with a median follow-up of 3.2 years; 91% of patients were men, and the trial was partly funded by Hitachi. Whether the survival benefit holds in other patient groups remains to be seen. For FLASH, the data come from just 10 patients, and the Cincinnati team notes that assessing effects on nearby organs is essential before use in deep-seated tumours.