Proton Therapy Leads to Positive Survival and Quality of Life Outcomes for Patients with Lower Grade Glioma

Mass General Brigham study highlights the efficacy of proton therapy in reducing toxicity while enhancing outcomes for patients with lower grade gliomas compared to traditional radiotherapy.

A new study by investigators from Mass General Brigham Cancer Institute evaluates the efficacy and safety of proton therapy for patients with lower grade gliomas (LGGs). The single-arm prospective phase 2 trial results demonstrated that proton therapy can achieve excellent tumor control rates while reducing incidence of side effects compared to traditional radiotherapy. Their results are published in Neuro-Oncology.

Proton therapy limits radiation exposure to healthy tissue, which may protect cognition, hormone function, and long-term quality of life better than photon therapy. But the clinical benefit of proton therapy in patients with LGG, a population with long life expectancy, has not been well studied. Traditional treatment options for LGGs typically include surgery, radiotherapy (using conventional X-rays), and chemotherapy.

"Our findings suggest that proton therapy not only achieves high rates of survival without cancer progression but also reduces the long-term cognitive and hormonal side effects often seen with conventional radiation treatments,” said Helen Shih, MD, MS, MPH, FASTRO, a radiation oncologist with Mass General Brigham Cancer Institute and Vice Chair of New Technologies and Proton Therapy at Mass General Brigham Radiation Oncology. “Proton therapy demonstrates the potential for improved quality of life in patients.”

Lower grade gliomas, classified as WHO grade 1-2 and favorable grade 3 gliomas, predominantly affect younger adults and are associated with favorable long-term survival rates. As these patients often live for five to ten years or more after treatment, with an increasing number surviving beyond two decades, minimizing long-term treatment-related toxicities becomes crucial. Standard radiation therapy, while highly effective for tumor control, carries risks of neurocognitive and neuroendocrine deficits, which can significantly impact quality of life.

The study was conducted at MGH, which enrolled 63 patients between 2010 and 2018. The trial included participants aged 18 or older, with tumors of various mutations. The primary goal of the trial was to determine how long patients could live without cancer worsening, known as progression-free survival. Secondary outcomes included assessments of cognitive function, hormonal function, quality of life, and overall survival (OS). Researchers also monitored any side effects that may arise from treatment. Follow-up evaluations were scheduled at minimally annually for five years or more.

Results of this study showed that 79.1% of patients were without tumor progression after five years, and overall survival was at 85.6%. The study also found that patients had significantly better progression-free survival compared to older data on traditional photon therapy. At the beginning of the study, 34% of patients had issues with brain function, which increased to 43% after five years. However, only one patient experienced severe side effects. This suggests that proton therapy is a safer option compared to traditional radiation.

“The main advantage of proton therapy is that it minimizes radiation exposure to surrounding healthy tissues, which helps preserve important functions like neurocognitive and hormonal health,” said Shih. “These findings are encouraging and support further research into the role of proton therapy in the management of brain tumor patients.”

A limitation of this study includes its single-arm design without a comparative control group, which may impact the generalizability of the results. Ongoing randomized controlled trials will further evaluate the comparative effectiveness of proton therapy versus traditional photon therapy. Additionally, long-term follow-up beyond the seven years is needed to assess durability of benefits and long-term toxicities, particularly concerning neurocognitive function.

Authorship: In addition to Shih, Mass General Brigham authors include Nora Horick, Lisa Nachtigall, Micheal Parsons, Nicholas Tritos, Alexander Faje, Jorg Dietrich, Janet Sherman, William Curry, Isabel Arrillaga-Romany, Daniel Cahill, Brian Nahed, Thomas Botticello, Kevin Oh, and Beow Yeap. Other authors include Jason M. Slater, Barabara Fullerton, and Irene Wang.

Disclosures: Jorg Dietrich Research Funding: Novartis, Ono Pharmaceuticals; Consulting: Amgen, Novartis, Johnson & Johnson, Ono Pharmaceuticals; Royalties: Wolters Kluwer (UpToDate). Helen Shih Research Funding: AbbVie; Consulting: Servier Pharmaceuticals, Advanced Accelerator Applications. Advisory Board: Ion Beam Applications; Royalties: Wolters Kluwer (UpToDate).

Funding: National Cancer Institute grant (5U19CA021239-38).

Paper cited: Shih, H., et al. “Cognitive Function, Quality of Life, and Survival Outcomes in Patients with Lower Grade Gliomas Treated with Proton Radiation Therapy: A Phase II Study” Neuro-Oncology DOI:10.1093/neuonc/noag008/8440769