e14004 Background: Brain metastases (BM) is one of the most feared complications of cancer due to substantial neurologic sequalae, neuro-cognitive morbidity and grim prognosis. In the past decade, targeted therapies and checkpoint inhibitors have resulted in meaningfully improved overall survival for a minority of these patients. Accordingly, there is a growing need to identify issues surrounding patient survivorship and to standardize physician practice patterns for these patients. To date, there has not been a well-conducted formal study to specifically explore these questions of survivorship and practice standardization for BM patients. Methods: Here, we present results from a cross-sectional survey in which we analyzed responses from 237 BM patients, 209 caregivers, and 239 physicians. Surveys contained questions about BM symptoms, discussion of BM diagnosis by the clinician, psychosocial concerns, available treatment options for BM, BM patient advocacy resources, and BM-specific clinical trials. Results: Our survey revealed compelling findings about current care of BM patients. There were discrepancies in the perceived discussion of the implications of the diagnosis of BM, from the patient/caregiver and physician perspective. Important topics, such as prognosis and worrisome symptoms, were felt to have been discussed more frequently by physicians than by patients or caregivers. In our physician survey, private practice physicians, compared to academic physicians, were significantly more likely to recommend whole brain radiotherapy (61.1 vs 39.7%; p = 0.009). Participation in a clinical trial was one of the least recommended treatment options. Many physicians (59.1% private; 71.9% academic) stated that BM patients in their care are denied participation in a clinical trial, specifically due to the presence of BM. The consensus among physicians, patients and caregivers was that the highest yield area for federal assistance is increased treatment and research funding for BM. Conclusions: Our hope is that these findings will serve as a basis for future quality improvement measures to enhance patient-physician communication and patient well-being, continuing medical education activities detailing latest advances in BM for oncologists, and lobbying efforts to the federal government in prioritizing BM research, clinical trials, and patient survivorship.

2020 Background: The Response Assessment in Neuro-Oncology (RANO) and modified RANO (mRANO) criteria are the two most widely used criteria to evaluate treatment response in glioblastoma (GBM) clinical trials. Unlike RANO, mRANO omits the evaluation of FLAIR sequence and requires a repeat scan to confirm responses. It also uses the post-radiation (RT) MRI as a baseline MRI in the newly diagnosed setting instead of the pre-RT MRI used in RANO. We sought to compare the 2 response assessment criteria and evaluate the differences between them in a large patient population. We also sought to compare them to immunotherapy RANO (iRANO) in patients who received immunotherapy. Methods: We conducted a retrospective review of consecutive patients with newly diagnosed (nGBM) and recurrent (rGBM) IDH wild-type GBM treated at Dana-Farber Cancer Institute from 2014 to 2020. Bidimensional measurements of enhancing disease and evaluation of FLAIR sequences were performed by two independent readers on patients’ brain MRIs obtained before change of treatment, and discrepancies were evaluated by a third reader. Dates of disease progression (PD) were identified using RANO, mRANO, iRANO, and other response assessment criteria variations. Spearman’s correlations between PFS and OS were calculated using an iterative multiple imputation method to account for any right-censoring. Results: 526 and 580 patients were included in the newly diagnosed and recurrent cohorts, respectively. Spearman’s correlations were not significantly different between RANO and mRANO in the nGBM (0.69 [95% CI 0.62 to 0.75] vs. 0.67 [0.60, 0.73]) and rGBM (0.45 [0.37, 0.52] vs. 0.50 [0.42, 0.57]) cohorts. Evaluation of FLAIR sequences did not improve the correlation between PFS and OS in patients who received antiangiogenic therapy. Addition of confirmation scans was associated with stronger Spearman’s correlations only when PD was identified within 12 weeks of completion of RT in the nGBM cohort, but did not affect the Spearman’s correlations in the rGBM cohort. The use of the post-RT MRI as a baseline was associated with a higher Spearman’s correlation in nGBM than the use of pre-RT MRI (0.67 [0.60, 0.73] vs. 0.53 [0.42, 0.62]). Among 98 patients with nGBM and 175 patients with rGBM who received immunotherapy, the Spearman’s correlations (nGBM and rGBM) with iRANO (0.63 [0.44, 0.76] and 0.34 [0.17, 0.49]) were similar to RANO (0.73 [0.60, 0.82] and 0.42 [0.28, 0.54]) and mRANO (0.65 [0.48, 0.77] and 0.43 [0.28, 0.56]). Conclusions: RANO and mRANO demonstrated similar correlation between PFS and OS. The evaluation of FLAIR can be omitted, while confirmation scans appear to be only beneficial in the nGBM settings during the first 12 weeks of completion of RT. There was a nonsignificant trend in favor of the use of post-RT MRI as the baseline scan in the nGBM setting. The application of iRANO criteria did not add significant benefit in patients who received immunotherapy.

e14003 Background: The Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) is the standard for therapeutic response assessment in brain metastases (BM) patients. The criteria relies on a human reader to annotate target (≥10 mm) and non-target (<10mm) lesions of interest based on unidimensional measurement of lesion diameter on brain MRI. The change in the sum largest axial diameter of 5 target lesions (RANO-BM diameter) is then used to categorize intracranial response into 4 categories: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Methods: Automating the RANO-BM criteria (AUTO-RANO-BM) has enabled the rapid modulation of the threshold diameter required for inclusion of a brain metastasis as a target lesion. In this study, diameters below the RANO-BM 10mm recommendation were utilized when calculating the RANO-BM diameter. The ability of the RANO-BM diameter to predict overall survival for BM patients was then evaluated in a Cox Proportional Hazards model. In a cohort of 175 immunotherapy-treated BM patients, the optimal threshold for the RANO-BM diameter as measured by Concordance Index (C-Index) was 5mm, suggesting that the RANO-BM criteria should be amended.

2529 Background: Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) for melanoma and lung cancer. This breakthrough has prompted interest in evaluating ICI in BM of other histologies. However, accurately assessing intracranial response in patients undergoing ICI is a challenge, as current measures cannot distinguish pseudoprogression from true tumor progression. To shed light on potential biomarkers of response, we prospectively use perfusion MRI to identify characteristic vascular signatures in a BM-specific trial of ICI. Methods: As part of an ongoing phase II study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology, patients underwent advanced MRI that includes tumor volume measurements and perfusion imaging with dynamic susceptibility contrast MRI. To calculate volumetric radiographic response, all enhancing voxels were summated. A volumetric increase of >40% was categorized as progressive disease (PD), a decrease of >60% as partial response (PR), and stable disease (SD) as between -60% and +40%. Results: 53 patients have been enrolled, of whom 44 have received at least baseline advanced MR imaging. Histologies include 21 with breast cancer, 5 with non-small cell lung cancer, 4 with melanoma, and 13 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 33 evaluable patients include 4 PR, 10 SD, and 19 PD. On preliminary analysis, there was a correlation between increased tumor cerebral blood volume/flow with tumor progression. Correlation of additional vascular physiologic parameters (e.g. vessel caliber, tissue oxygenation) and volumetric response to patient outcome and standardized response criteria (iRANO) are ongoing. Conclusions: Pembrolizumab likely has anti-tumor efficacy in BM. Our data provides potential evidence that effective ICI is associated with a decrease in perfusion. Ongoing analyses to uncover additional vascular changes – specifically longitudinal metrics reflecting vascular structure and function - within BM to ICI are pending. These findings have potential to illustrate mechanisms of efficacy for ICI and biomarkers of response in this patient population.

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