Robustness of tumor control (TCP) and normal tissue complication probabilities (NTCP) for intensity modulated particle radiotherapy in locally advanced lung cancer: a scenario-based uncertainty analysis compared to photon radiotherapy (IMRT)

Xue Ming; Yinxiangzi Sheng; Jian Chen; Kailiang Wu; Xufei Wang; Jingfang Mao; Ningyi Ma

doi:10.21037/jtd-2026-1-0266

Robustness of tumor control (TCP) and normal tissue complication probabilities (NTCP) for intensity modulated particle radiotherapy in locally advanced lung cancer: a scenario-based uncertainty analysis compared to photon radiotherapy (IMRT)

J Thorac Dis. 2026 May 31;18(5):471. doi: 10.21037/jtd-2026-1-0266. Epub 2026 May 27.

Authors

Xue Ming^{1

2}, Yinxiangzi Sheng¹, Jian Chen³, Kailiang Wu³, Xufei Wang², Jingfang Mao³, Ningyi Ma³

Affiliations

¹ Department of Medical Physics, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai Key Laboratory of Radiation Oncology, Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China.
² Institute of Modern Physics, Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China.
³ Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai Key Laboratory of Radiation Oncology, Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China.

Abstract

Background: Particle radiotherapy offers significant dose sparing but is more susceptible to dose perturbations caused by physical uncertainties. This study aimed to assess the impact of dosimetric uncertainties on tumor control probability (TCP) and normal tissue complication probability (NTCP) for locally advanced lung cancer (LA-LC) among intensity-modulated proton radiotherapy (IMPT), intensity-modulated carbon-ion radiotherapy (IMCT), and intensity-modulated photon radiotherapy (IMRT).

Methods: Ten LA-LC patients were enrolled in this retrospective study with three radiation modalities of IMPT, IMCT and IMRT for treatment planning. The nominal IMPT/IMCT plans were recalculated according to the four major uncertainty factors respectively, including the type of calculation engine, range uncertainty, setup uncertainty and intra-fractional respiratory movement uncertainty. TCP values were assessed by the model for curative intent. Radiation-induced esophageal injury (RIEI) and radiation-induced lung injury (RILI) were studied as the NTCP endpoints. NTCP and the difference of NTCP between the particle radiotherapy (PT) and IMRT (∆NTCP) values were evaluated through the 6 Lyman-Kutcher-Burman models (4 models for RIEI and 2 for RILI).

Results: Under the same prescription doses and similar dose distribution to the targets, deviations of the mean TCP values were less than 0.7% in IMPT, IMCT and IMRT plans under all the uncertainty scenarios. The deviations of the mean values of the ∆NTCP evaluation were -3.3-2.9% for the four models for RIEI and -0.8-1.9% for the two models for RILI under different uncertainty scenarios. The mean values of ∆NTCP_L1 (the ∆NTCP values assessed through the first RILI-NTCP model) was -6.0%±6.1%/-6.9%±5.7% in the nominal IMPT/IMCT plans, while of ∆NTCP_L2 (the ∆NTCP values assessed through the second RILI-NTCP model) was -12.0%±10.9%/-12.8%±10.1%.

Conclusions: For non-robustly optimized IMPT and IMCT plans, the stability of TCP and reduction of NTCP of RILI, especially for larger tumor volumes, maintained in IMPT and IMCT after considering the calculation engine, range uncertainty, setup uncertainty and intra-fractional respiratory motions respectively with the application of several planning strategies. Proper TCP, NTCP and ∆NTCP evaluation may support the individual model-based selection for PT to maximize the clinical benefit for LA-LC.

Keywords: Normal tissue complication probability (NTCP); carbon-ion radiotherapy; proton radiotherapy; robustness evaluation; tumor control probability (TCP).