From standard to stratified: Modeling NTCP and EAR to personalize daily MV-CBCT in radiotherapy

To evaluate the cumulative radiobiological impact of daily megavoltage cone-beam computed tomography (MV-CBCT) imaging dose based on normal tissue complication probability (NTCP) and excess absolute risk (EAR) of secondary malignancies among radiotherapy patients treated for breast, pelvic, and head & neck cancers. This study investigated whether MV-CBCT imaging dose warrants protocol personalization according to patient age, anatomical treatment site, and organ-specific radiosensitivity.

This retrospective study included cohorts of breast (n = 30), pelvic (n = 17), and head & neck (n = 20) cancer patients undergoing radiotherapy with daily MV-CBCT. Imaging dose distributions employing two common MV-CBCT protocols (5 and 10 MU per fraction) were analyzed. NTCP values were estimated using logistic models, while EAR were calculated using Schneider's organ equivalent dose (OED)-based model, integrating organ-specific dose, patient age, and established tissue-specific risk coefficients. Comparative statistical analyses were conducted using paired t-tests, and results were further stratified by patient age (< 40, 40-60, > 60 years).

In breast cancer patients, NTCP values increased significantly for lung tissue when comparing the 10 MU protocol to the 5 MU one (p < 0.001), while those for heart and breast tissues showed minimal and insignificant differences. EAR estimations revealed substantial risk increases among younger breast cancer patients (< 40 years), with some exceeding 15 cases per 10 000 person-years under the 10 MU protocol. Conversely, pelvic and head & neck cohorts demonstrated consistently low NTCP and EAR values (< 1%), with no meaningful differences observed between the two imaging protocols. Across all cancer sites, younger age consistently correlated with higher secondary cancer risks.

Routine daily MV-CBCT imaging at the 10 MU protocol possesses minimal additional risk in pelvic and head & neck radiotherapy. However, among breast cancer patients, particularly those under 40 years, the 10 MU protocol significantly elevates the theoretical secondary cancer risk estimates and lung NTCP. These findings support transitioning from conventional uniform imaging approach toward personalized MV-CBCT protocols, tailored according to patient age, anatomical site, and organ radiosensitivity. A stratified imaging framework is proposed to optimize clinical outcomes, balancing treatment accuracy, and long-term patient safety.