Interpretable AI-assisted clinical decision making for treatment selection for brain metastases in radiation therapy

AI modeling CDM can improve the quality and efficiency of clinical practice or provide secondary opinion consultations for patients with limited medical resources to address healthcare disparities.

In this study, we developed an interpretable AI model to select radiotherapy treatment options, that is, whole-brain radiation therapy (WBRT) versus stereotactic radiosurgery (SRS), for patients with brain metastases.

A total of 232 patients with brain metastases treated by radiation therapy from 2018 to 2023 were obtained. CT/MR images with contoured target lesions and organs-at-risk (OARs) as well as non-image-based clinical parameters were extracted and digitized as inputs to the model. These parameters included (1) tumor size, shape, location, and proximity of lesions to OARs; (2) age; (3) the number of brain metastases; (4) Eastern Cooperative Oncology Group (ECOG) performance status; (5) presence of neurologic symptoms; (6) if surgery was performed (either pre/post-op RT); (7) newly diagnosed cancer with brain metastases (de-novo) versus re-treatment (either local or distant in the brain); (8) primary cancer histology; (9) presence of extracranial metastases; (10) extent of extracranial disease (progression vs. stable); and (11) receipt of systemic therapy. One vanilla and two interpretable 3D convolutional neural networks (CNN) models were developed. The vanilla one-path model (VM-1) uses only images as input, while the two interpretable models use both images and clinical parameters as inputs with two (IM-2) and 11 (IM-11) independent paths, respectively. This novel design allowed the model to calculate a class activation score for each input to interpret its relative weighting and importance in decision-making. The actual radiotherapy treatment (WBRT or SRS) used for the patients was used as ground truth for model training. The model performance was assessed by Stratified-10-fold cross-validation, with each fold consisting of selected 184 training, 24 validation, and 24 testing subjects.

A total of 232 brain metastases patients treated by WBRT or SRS were evaluated, including 80 WBRT and 152 SRS patients. Based on the images alone, the VM-1 model prescribed correctly for 143 (94%) SRS and 67 (84%) WBRT cases. Based on both images and clinical parameters, the IM-2 model prescribed correctly for 149 (98%) SRS and 74 (93%) WBRT cases. IM-11 provided the most interpretability with a relative weighting for each input as follows: CT image (59.5%), ECOG performance status (7.5%), re-treatment (5%), extracranial metastases (1.5%), number of brain metastases (9.5%), neurologic symptoms (3%), pre/post-surgery (2%), primary cancer histology (2%), age (1%), progressive extracranial disease (6%), and receipt of systemic therapy (4.5%), reflecting the importance of all these inputs in clinical decision-making.

Interpretable CNN models were successfully developed to use CT/MR images and non-image-based clinical parameters to predict the treatment selection between WBRT and SRS for brain metastases patients. The interpretability makes the model more transparent, carrying profound importance for the prospective integration of these models into routine clinical practice, particularly for informing real-time clinical decision-making.