A verification-oriented review of reaction-enhanced radiotherapy: Linking nuclear data, transport modeling, and measurable observables

Reaction-enhanced radiotherapy (RER) aims to improve the therapeutic ratio of particle therapy by exploiting isotope-specific nuclear reactions that generate localized high-LET secondary radiation. Absorbed dose remains the central metric for radiotherapy planning and evaluation; however, RER introduces additional verification requirements related to nuclear-reaction data, mixed-field transport, isotope delivery, and measurable secondary-field observables. This review frames RER as a verification-oriented physics problem built on three interdependent pillars: covariance-aware nuclear data, high-fidelity Monte Carlo transport, and reaction-specific secondary-field monitoring. BNCT is treated as the clinically mature benchmark for RER, whereas PBCT and the emerging ¹⁵N(p,α)¹²C-based proton-carbon-alpha therapy (Proton-CAT) are discussed as early-stage comparative cases. BNCT has the strongest clinical evidence base, while PBCT remains constrained by narrow resonances, low reaction yield, and limited observability. Proton-CAT provides a candidate 4.439 MeV prompt-γ observable whose verification value still requires detector-level validation and delivery/selectivity assessment. Overall, clinically credible RER requires coordinated progress in uncertainty-aware nuclear data, detector-integrated transport modeling, isotope delivery and tumour-to-normal biodistribution assessment, and high-sensitivity radiation monitoring for therapy verification.