Identification of patient benefit from proton beam therapy in brain tumour patients based on dosimetric and NTCP analyses

Background: The limited availability of proton beam therapy (PBT) requires individual treatment selection strategies, such as the model-based approach. In this study, we assessed the dosimetric benefit of PBT compared to photon therapy (XRT), analysed the corresponding changes in normal tissue complication probability (NTCP) on a variety of available models, and illustrated model-based patient selection in an in-silico study for patients with brain tumours. Methods: For 92 patients treated at two PBT centres, volumetric modulated arc therapy treatment plans were retrospectively created for comparison with the clinically applied PBT plans. Several dosimetric parameters for the brain excluding tumour and margins, cerebellum, brain stem, frontal and temporal lobes, hippocampi, cochleae, chiasm, optic nerves, lacrimal glands, lenses, pituitary gland, and skin were compared between both modalities using Wilcoxon signed-rank tests. NTCP differences (DNTCP) were calculated for 11 models predicting brain necrosis, delayed recall, temporal lobe injury, hearing loss, tinnitus, blindness, ocular toxicity, cataract, endocrine dysfunction, alopecia, and erythema. A patient was assumed to be selected for PBT if DNTCP exceeded a threshold of 10 percentage points for at least one of the side-effects. Results: PBT substantially reduced the dose in almost all investigated OARs, especially in the low and intermediate dose ranges and for contralateral organs. In general, NTCP predictions were significantly lower for PBT compared to XRT, in particular in ipsilateral organs. Considering DNTCP of all models, 80 patients (87.0%) would have been selected for PBT in this in-silico study, mainly due to predictions of a model on delayed recall (51 patients). Conclusion: In this study, substantial dose reductions for PBT were observed, mainly in contralateral organs. However, due to the sigmoidal dose response, NTCP was particularly reduced in ipsilateral organs. This underlines that physical dose-volume parameters alone may not be sufficient to describe the clinical relevance between different treatment techniques and highlights potential benefits of NTCP models. Further NTCP models for different modern treatment techniques are mandatory and existing models have to be externally validated in order to implement the model-based approach in clinical practice for cranial radiotherapy. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 160 (2021) 69-77

Automated summary

This study found that PBT can substantially reduce doses in most organs at risk compared to XRT, particularly in contralateral organs. NTCP predictions were significantly lower for PBT compared to XRT overall, especially in ipsilateral organs. Analysis of DNTCP values from multiple NTCP models revealed that 80 patients might be selected for PBT, primarily due to predictions from the delayed recall model.