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Proton Versus Photon Radiotherapy for Non-Small Cell Lung Cancer: Updated Evidence from a Systematic Review and
Chiung-Chen Fang1, Wen-Cheng Chen1, Ming-Shao Tsai2
1Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Chang Gung University, No. 6, Chia-Pu Rd., Chiayi 613, Taiwan.
Cancers
|February 13, 2026
Summary
Proton beam therapy (PBT) shows no long-term survival advantage over photon radiotherapy for non-small cell lung cancer (NSCLC). However, PBT may improve early survival, potentially by reducing acute treatment mortality in NSCLC patients.
Area of Science:
- Radiation Oncology
- Medical Physics
- Thoracic Oncology
Background:
- Proton beam therapy (PBT) offers dosimetric advantages over photon radiotherapy for non-small cell lung cancer (NSCLC).
- Comparative clinical evidence on survival benefits of PBT versus photon radiotherapy for NSCLC remains conflicting.
- Understanding time-dependent survival patterns is crucial for evaluating PBT's efficacy.
Purpose of the Study:
- To systematically review and meta-analyze clinical outcomes of PBT versus photon radiotherapy for NSCLC.
- To evaluate toxicity profiles associated with both treatment modalities.
- To specifically investigate time-dependent survival patterns, including overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS).
Main Methods:
- Systematic literature search of PubMed, EMBASE, and Cochrane CENTRAL databases up to October 10, 2025.
- Inclusion of seven comparative studies (retrospective cohorts, multi-institutional datasets, one RCT) with 244,604 patients.
- Reconstruction of individual patient data (IPD) from Kaplan-Meier curves and calculation of odds ratios (ORs) for time-point survival and toxicity.
Main Results:
- Overall pooled analysis revealed no significant difference in OS, PFS, or LPFS between PBT and photon radiotherapy for NSCLC.
- Sensitivity and subgroup analyses for Stage I and Stage I-II NSCLC also showed no significant survival differences.
- Exploratory analysis indicated improved 1-year OS odds with PBT (OR=0.60), but this advantage diminished by 3 and 5 years; no significant reduction in radiation pneumonitis or severe toxicity was observed.
Conclusions:
- Long-term oncologic control appears comparable between PBT and photon radiotherapy for NSCLC.
- PBT may offer an improved odds of 1-year overall survival, potentially due to mitigation of acute treatment-related mortality.
- Findings suggest PBT could benefit patients at high risk of toxicity, supporting model-based patient selection.
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