Purpose: Treatment effect or radiation necrosis after stereotactic radiosurgery (SRS) for brain metastases is a common phenomenon often indistinguishable from true progression. Radiomics is an emerging field that promises to improve on conventional imaging. In this study, we sought to apply a radiomics-based prediction model to the problem of diagnosing treatment effect after SRS. Methods and Materials: We included patients in the Johns Hopkins Health System who were treated with SRS for brain metastases who subsequently underwent resection for symptomatic growth. We also included cases of likely treatment effect in which lesions grew but subsequently regressed spontaneously. Lesions were segmented semiautomatically on preoperative T1 postcontrast and T2 fluid-attenuated inversion recovery magnetic resonance imaging, and radiomic features were extracted with software developed in-house. Top-performing features on univariate logistic regression were entered into a hybrid feature selection/classification model, IsoSVM, with parameter optimization and further feature selection performed using leave-one-out cross-validation. Final model performance was assessed by 10-fold cross-validation with 100 repeats. All cases were independently reviewed by a board-certified neuroradiologist for comparison. Results: We identified 82 treated lesions across 66 patients, with 77 lesions having pathologic confirmation. There were 51 radiomic features extracted per segmented lesion on each magnetic resonance imaging sequence. An optimized IsoSVM classifier based on top-ranked radiomic features had sensitivity and specificity of 65.38% and 86.67%, respectively, with an area under the curve of 0.81 on leave-one-out cross-validation. Only 73% of cases were classifiable by the neuroradiologist, with a sensitivity of 97% and specificity of 19%. Conclusions: Radiomics holds promise for differentiating between treatment effect and true progression in brain metastases treated with SRS. A predictive model built on radiomic features from an institutional cohort performed well on cross-validation testing. These results warrant further validation in independent datasets. Such work could prove invaluable for guiding management of individual patients and assessing outcomes of novel interventions.

Purpose To analyze baseline CT/MR-based image features of salivary glands to predict radiation-induced xerostomia 3-months after head-and-neck cancer (HNC) radiotherapy. Methods A retrospective analysis was performed on 266 HNC patients who were treated using radiotherapy at our institution between 2009 and 2018. CT and T1 post-contrast MR images along with NCI-CTCAE xerostomia grade (3-month follow-up) were prospectively collected at our institution. CT and MR images were registered on which parotid/submandibular glands were contoured. Image features were extracted for ipsilateral/contralateral parotid and submandibular glands relative to the location of the primary tumor. Dose-volume-histogram (DVH) parameters were also acquired. Features were pre-selected based on Spearman correlation before modelling by examining the correlation with xerostomia ( p < 0.05). A shrinkage regression analysis of the pre-selected features was performed using LASSO. The internal validity of the variable selection was estimated by repeating the entire variable selection procedure using a leave-one-out-cross-validation. The most frequently selected variables were considered in the final model. A generalized linear regression with repeated ten-fold cross-validation was developed to predict radiation-induced xerostomia at 3-months after radiotherapy. This model was tested in an independent dataset ( n = 50) of patients who were treated at the same institution in 2017–2018. We compared the prediction performances under eight conditions (DVH-only, CT-only, MR-only, CT + MR, DVH + CT, DVH + CT + MR, Clinical+CT + MR, and Clinical+DVH + CT + MR) using the area under the receiver operating characteristic curve (ROC-AUC). Results Among extracted features, 7 CT, 5 MR, and 2 DVH features were selected. The internal cohort ( n = 216) ROC-AUC values for DVH, CT, MR, and Clinical+DVH + CT + MR features were 0.73 ± 0.01, 0.69 ± 0.01, 0.70 ± 0.01, and 0.79 ± 0.01, respectively. The validation cohort ( n = 50) ROC-AUC values for DVH, CT, MR, and Clinical+DVH + CT + MR features were 0.63, 0.57, 0.66, and 0.68, respectively. The DVH-ROC was not significantly different than the CT-ROC ( p = 0.8) or MR-ROC ( p = 0.4). However, the CT + MR-ROC was significantly different than the CT-ROC ( p = 0.03), but not the Clinical+DVH + CT + MR model ( p = 0.5). Conclusion Our results suggest that baseline CT and MR image features may reflect baseline salivary gland function and potential risk for radiation injury. The integration of baseline image features into prediction models has the potential to improve xerostomia risk stratification with the ultimate goal of truly personalized HNC radiotherapy. Electronic supplementary material ...

Object Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole brain radiotherapy (WBRT) remains the standard of care with the rate of local control >90%. However, WBRT is delivered over 10–15 days, which can delay other therapy and is associated with acute and long-term toxicities. Intra-operative permanent Cesium-131 (Cs-131) implants can be performed at the time of surgery, thereby avoiding any additional therapy. We evaluate the safety, feasibility and efficacy of a novel treatment approach of brain metastases with a permanent intra-operative Cs-131 brachytherapy. Methods After IRB approval, 24 patients with a newly diagnosed metastasis to the brain (n=24) were accrued on a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung (16), breast (2), kidney (2), melanoma (2), colon (1), and cervix (1). Cs-131 stranded seeds were placed as a permanent volume implant. Prescription dose was 80Gy at 5mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. Primary end point was resection cavity freedom from progression (FFP). Secondary end points included distant metastases FFP, median survival, overall survival (OS), and toxicity. Results Median follow-up was 19.3 months (range, 12.89 – 29.57 months). Median age was 65 years (range, 45–84 years). Median volume of resected tumor was 10.31 cc (range, 1.77 - 87.11 cc). Median number of seeds employed was 12 (range, 4–35) with median activity per seed of 3.82 mCi (range, 3.31–4.83 mCi) and total activity of 46.91 mCi (range, 15.31–130.70 mCi). Local recurrence FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI = 63.2%, 99.1%). Distant metastasis FFP was 48.4% (95% CI = 26.3%, 67.4%). Median OS was 9.9 months (95% CI = 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI = 29.1%, 67.8%). Complications included cerebrospinal fluid leak (1), seizure (1), infection (1). There was no radiation necrosis. Conclusions Cs-131 post-resection permanent brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment approach was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rates, and minimal toxicity. These results merit further study with a multicenter trial.