We establish an open framework for developing plan optimization models for knowledge-based planning (KBP) in radiotherapy. Our framework includes reference plans for 100 patients with head-and-neck cancer and high-quality dose predictions from 19 KBP models that were developed by different research groups during the OpenKBP Grand Challenge. The dose predictions were input to four optimization models to form 76 unique KBP pipelines that generated 7600 plans. The predictions and plans were compared to the reference plans via: dose score, which is the average mean absolute voxel-by-voxel difference in dose a model achieved; the deviation in dose-volume histogram (DVH) criterion; and the frequency of clinical planning criteria satisfaction. We also performed a theoretical investigation to justify our dose mimicking models. The range in rank order correlation of the dose score between predictions and their KBP pipelines was 0.50 to 0.62, which indicates that the quality of the predictions is generally positively correlated with the quality of the plans. Additionally, compared to the input predictions, the KBP-generated plans performed significantly better (P<0.05; one-sided Wilcoxon test) on 18 of 23 DVH criteria. Similarly, each optimization model generated plans that satisfied a higher percentage of criteria than the reference plans. Lastly, our theoretical investigation demonstrated that the dose mimicking models generated plans that are also optimal for a conventional planning model. This was the largest international effort to date for evaluating the combination of KBP prediction and optimization models. In the interest of reproducibility, our data and code is freely available at https://github.com/ababier/open-kbp-opt.

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e. 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that undergone gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.