Practical robustness evaluation in radiotherapy - A photon and proton-proof alternative to PTV-based plan evaluation

Background and purpose: A planning target volume (PTV) in photon treatments aims to ensure that the clinical target volume (CTV) receives adequate dose despite treatment uncertainties. The underlying static dose cloud approximation (the assumption that the dose distribution is invariant to errors) is problematic in intensity modulated proton treatments where range errors should be taken into account as well. The purpose of this work is to introduce a robustness evaluation method that is applicable to photon and proton treatments and is consistent with (historic) PTV-based treatment plan evaluations. Materials and methods: The limitation of the static dose cloud approximation was solved in a multi-scenario simulation by explicitly calculating doses for various treatment scenarios that describe possible errors in the treatment course. Setup errors were the same as the CTV-PTV margin and the underlying theory of 3D probability density distributions was extended to 4D to include range errors, maintaining a 90% confidence level. Scenario dose distributions were reduced to voxel-wise minimum and maximum dose distributions; the first to evaluate CTV coverage and the second for hot spots. Acceptance criteria for CTV D98 and D2 were calibrated against PTV-based criteria from historic photon treatment plans. Results: CTV D98 in worst case scenario dose and voxel-wise minimum dose showed a very strong correlation with scenario average D98 (R-2 > 0.99). The voxel-wise minimum dose visualised CTV dose conformity and coverage in 3D in agreement with PTV-based evaluation in photon therapy. Criteria for CTV D98 and D2 of the voxel-wise minimum and maximum dose showed very strong correlations to PTV D98 and D2 (R-2 > 0.99) and on average needed corrections of -0.9% and +2.3%, respectively. Conclusions: A practical approach to robustness evaluation was provided and clinically implemented for PTV-less photon and proton treatment planning, consistent with PTV evaluations but without its static dose cloud approximation. (C) 2019 The Authors. Published by Elsevier B.V

Individualized early death and long-term survival prediction after stereotactic radiosurgery for brain metastases of non-small cell lung cancer:Two externally validated nomograms

Introduction Commonly used clinical models for survival prediction after stereotactic radiosurgery (SRS) for brain metastases (BMs) are limited by the lack of individual risk scores and disproportionate prognostic groups. In this study, two nomograms were developed to overcome these limitations. Methods 495 patients with BMs of NSCLC treated with SRS for a limited number of BMs in four Dutch radiation oncology centers were identified and divided in a training cohort (n = 214, patients treated in one hospital) and an external validation cohort n = 281, patients treated in three other hospitals). Using the training cohort, nomograms were developed for prediction of early death (<3 months) and long-term survival (>12 months) with prognostic factors for survival. Accuracy of prediction was defined as the area under the curve (AUC) by receiver operating characteristics analysis for prediction of early death and long term survival. The accuracy of the nomograms was also tested in the external validation cohort. Results Prognostic factors for survival were: WHO performance status, presence of extracranial metastases, age, GTV largest BM, and gender. Number of brain metastases and primary tumor control were not prognostic factors for survival. In the external validation cohort, the nomogram predicted early death statistically significantly better (p < 0.05) than the unfavorable groups of the RPA, DS-GPA, GGS, SIR, and Rades 2015 (AUC = 0.70 versus range AUCs = 0.51–0.60 respectively). With an AUC of 0.67, the other nomogram predicted 1 year survival statistically significantly better (p < 0.05) than the favorable groups of four models (range AUCs = 0.57–0.61), except for the SIR (AUC = 0.64, p = 0.34). The models are available on www.predictcancer.org. Conclusion The nomograms predicted early death and long-term survival more accurately than commonly used prognostic scores after SRS for a limited number of BMs of NSCLC. Moreover these nomograms enable individualized probability assessment and are easy into use in routine clinical practice

Stereotactic Radiosurgery for Multiple Brain Metastases

Purpose of review: To give an overview on the current evidence for stereotactic radiosurgery of brain metastases with a special focus on multiple brain metastases. Recent findings: While the use of stereotactic radiosurgery in patients with limited brain metastases has been clearly defined, its role in patients with multiple lesions (> 4) is still a matter of controversy. Whole-brain radiation therapy (WBRT) has been the standard treatment approach for patients with multiple brain lesions and is still the most commonly used treatment approach worldwide. Although distant brain failure is improved by WBRT, the overall survival is not readily impacted. As WBRT is associated with significant neurocognitive decline compared to stereotactic radiosurgery (SRS), SRS has been explored and increasingly utilized for selected patients with multiple brain metastases. Recent clinical data indicated the feasibility of stereotactic radiosurgery to multiple brain metastases with a similar survival in patients with more than 4 brain metastases versus patients with a maximum of 4 brain metastases. Also, neurocognitive function and quality of life was maintained after stereotactic radiosurgery which is essential in a palliative setting. The application of stereotactic radiosurgery with Gamma Knife, Cyberknife, or LINAC-based equipment has emerged as an effective and widely available treatment option for patients with limited brain metastases. Although not formally proven in prospective studies, SRS may also be considered as a safe and effective treatment option in selected patients with multiple brain metastases. Especially in patients with a favorable prognosis, survival over several years is observed also in the setting of multiple BM. For these patients, avoidance of the neurocognitive damage of WBRT is desirable, and SRS is often a more appropriate treatment in the current multimodality treatment of BM in which systemic treatment is often the cornerstone of the treatment. For patients with an intermediate (3-12 months) and poor prognosis (< 3 months), the application of WBRT becomes more and more controversial, because of its acute side effects, such as hair loss and fatigue and, thereby, detrimental effect on quality of life. For these patients, best supportive care, primary systemic treatment, and even SRS may be preferred over WBRT on an individualized patient basis