Proton versus photon radiotherapy is a safe and effective treatment for patients with advanced-stage oropharyngeal cancer, according to a study published December 11 in The Lancet.
The finding is from a phase III trial involving 440 patients treated at 21 sites in the U.S., with intensity-modulated proton therapy (IMPT) leading to improvements in overall survival and a 42% reduction of the hazard of death compared with photon radiotherapy, noted lead author Steven Frank, MD, of The University of Texas MD Anderson Cancer Center in Houston, and colleagues.
“This is important, level one evidence that proton therapy has both a survival benefit and quality-of-life improvement for these patients and should be the standard of care for advanced cases of oropharyngeal cancer,” Frank said, in a news release from the university.
The incidence and mortality of oropharyngeal cancer have increased over the past three decades, owing to the increasing prevalence of human papillomavirus-mediated disease, the researchers wrote. Treatment of the disease with state-of-the-art photon radiotherapy, called intensity-modulated radiation therapy (IMRT), results in significant toxicity and has prompted the search for alternative, less toxic therapies, they noted.
One alternative could be IMPT, according to the group. The treatment targets tumors with charged particles rather than the high-energy x-rays of photon therapy, with early reports suggesting it can achieve similar disease control rates as IMRT, they wrote.
To further evaluate the treatment, the researchers enrolled 440 patients (median age, 61; 91% male) with stage III or stage IV oropharyngeal cancer in a phase III trial between October 2013 and May 2022. Out of the group, 221 were allocated to the IMPT group (with 160 [72%] receiving IMPT) and 219 to the IMRT group (with 136 [62%] receiving IMRT).
According to the findings, progression-free survival rates for the IMPT group were 82.5% at three years and 81.3% at five years, while corresponding rates for the IMRT group were 83% and 76.2% (p = 0.005 for noninferiority of IMPT). Overall survival rates after IMPT were 90.9% at five years versus 81% after IMRT (p = 0.045).
Treatment-related deaths occurred in nine patients, six in the IMRT group and three in the IMPT group, and deaths from disease progression occurred in 27 patients, 18 in the IMRT group and nine in the IMPT group, the researchers reported.
Finally, toxicities were more frequent in the IMRT group: severe lymphopenia was more common in the IMRT group (89% vs. 6%), as were dysphagia (49% vs. 31%), xerostomia (45% vs. 33%), and gastrostomy tube dependence (40.2% vs. 26.8%).
“This study shows that IMPT is a safe and effective treatment that deintensifies concurrent chemoradiation strategies with IMRT,” the researchers wrote.
While long-term follow-up analysis and additional phase III trial data will be needed to provide a more robust assessment, the evidence from the trial points to IMPT being a new standard-of-care treatment option for the management of oropharyngeal tumors, the group concluded.
The full study is available here.