Evidence-based indications for proton therapy in adults determined using the GRADE approach

Area of Science:

• Radiation Oncology
• Medical Physics
• Oncology

Background:

• Proton therapy (PT) offers potential dosimetric advantages over conventional X-ray radiotherapy (XRT) for reducing toxicity and sparing healthy tissues.
• A Health Technology Assessment was conducted to evaluate PT's safety and effectiveness for unapproved cancer indications in Spain.

Purpose of the Study:

• To summarize findings on the safety and clinical performance of proton therapy (PT) in adult cancer patients compared to X-ray radiotherapy (XRT).
• To assess PT for cancer indications not yet approved in Spain.

Main Methods:

• Systematic review of primary studies (2012-2024) adhering to Cochrane standards, PRISMA guidelines, and GRADE approach.
• PICO-DT framework used for eligibility criteria, focusing on adult cancer patients and comparative study designs.
• Outcomes included serious adverse events, mortality, overall survival, and progression-free survival; risk of bias assessed using RoB 2.0 and ROBINS-I.

Main Results:

• 76 studies (5 RCTs, 71 observational) across 16 tumor types were included from 6958 screened records.
• Evidence certainty was generally low or very low due to limited RCTs, methodological concerns, and heterogeneity.
• For specific indications like leptomeningeal metastases, lung cancer, and anal cancer, PT may be equivalent or superior to XRT, but certainty is limited.

Conclusions:

• Proton therapy demonstrates variable, cancer-specific outcomes and does not consistently outperform XRT.
• Certain indications show promise for PT, but significant evidence gaps remain.
• High-quality comparative studies and systematic clinical data collection are crucial for further evaluation.