Modelling carcinogenesis after radiotherapy using Poisson statistics: implications for IMRT, protons and ions

Area of Science:

• Radiation oncology
• Medical physics
• Cancer research

Background:

• Current radiotherapy techniques like intensity modulated radiotherapy (IMRT) aim to improve cancer targeting and minimize dose to healthy tissues.
• Charged particle therapy (CPT), using proton and ion beams, offers superior dose conformity and reduced integral dose compared to IMRT, but at a higher cost.
• Assessing long-term risks, including normal tissue complications and secondary carcinogenesis, is crucial for evaluating radiotherapy techniques.

Purpose of the Study:

• To compare the dose distributions and potential risks associated with IMRT and CPT.
• To explore advanced modeling approaches for estimating carcinogenesis risk in CPT.
• To inform potential adjustments in CPT delivery, such as beam placement and fractionation, based on theoretical risk reduction.

Main Methods:

• Comparison of physical dose distribution plans for IMRT and CPT.
• Application of standard linear radioprotection models to estimate CPT's carcinogenesis risk reduction.
• Tentative application of the linear-quadratic model and Poissonian statistics to simultaneously model cell kill and chromosome breakage for risk estimation.

Main Results:

• IMRT can lead to a 'dose bath' of low to medium dose, potentially increasing carcinogenesis risk due to dose transfer.
• Standard models suggest CPT can reduce carcinogenesis risk by two- to 15-fold, but these models have limitations regarding fractionation and dose limits.
• An alternative modeling approach incorporating fractionation and relative biological effects (RBE) suggests pseudo-linear dose-response relationships and an inverse relationship between dose per fraction and cancer induction.

Conclusions:

• CPT presents significant advantages over IMRT in reducing integral dose and potentially lowering the risk of secondary cancers.
• Advanced modeling incorporating fractionation and RBE offers a more nuanced estimation of carcinogenesis risk with CPT.
• Theoretical findings suggest potential modifications to CPT protocols, emphasizing the need for experimental validation through cellular and tissue studies.