Can the mean linear energy transfer of organs be directly related to patient toxicities for current head and neck cancer intensity-modulated proton therapy practice?. (December 2021)

• Record Type: Journal Article
• Authors: Wagenaar, Dirk; Schuit, Ewoud; van der Schaaf, Arjen; Langendijk, Johannes A.; Both, Stefan
• Is Part Of: Radiotherapy and oncology. Volume 165(2021)
• Page Start: 159
• Page End: 165
• Publication Date: 2021-12
• Subjects: Proton beam therapy -- Biological modeling -- Head and neck tumors -- NTCP modeling -- Relative biological effectiveness -- RBE -- Linear energy transfer -- LET; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2021.09.003
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: Relating organ LET to head and neck toxicity not feasible for current practice. Does not contradict previous evidence for increased RBE for high LET. Lack of variation in LET causes high required sample size. Other methods to investigate RBE and LET in clinical practice are suggested. Abstract: Background and purpose: The relative biological effectiveness (RBE) of proton therapy is predicted to vary with the dose-weighted average linear energy transfer (LETd ). However, RBE values may substantially vary for different clinical endpoints. Therefore, the aim of this study was to assess the feasibility of relating mean D⋅LETd parameters to patient toxicity for HNC patients treated with proton therapy. Materials and methods: The delivered physical dose (D) and the voxel-wise product of D and LETd (D⋅LETd ) distributions were calculated for 100 head and neck cancer (HNC) proton therapy patients using our TPS (Raystation v6R). The means and covariance matrix of the accumulated D and D⋅LETd of all relevant organs-at-risk (OARs) were used to simulate 2.500 data sets of different sizes. For each dataset, an attempt was made to add mean D⋅LETd parameters to a multivariable NTCP model based on mean D parameters of the same OAR for xerostomia, tube feeding and dysphagia. The likelihood of creating an NTCP model with statistically significant parameters (i.e. power) was calculated as a function of the simulated sample size for various RBE models. Results: The sample size required to have a power of at least 80% to show an independent effect of mean D⋅LETd parameters on toxicity is over 15, 000 patients for all toxicities. Conclusion: For current clinical practice, it is not feasible to directly model NTCP with both mean D and mean D⋅LETd of OARs. These findings should not be interpreted as a contradiction of previous evidence for the relationship between RBE and LETd .