Search

The development of breast cancer (BC) brain metastases (BrM) is a common complication of advanced disease, occurring in up to half of the patients with advanced disease depending on the subtype. The management of BCBrM requires complex multidisciplinary care including local therapy, surgical resection and/or radiotherapy, palliative care, and carefully selected systemic therapies. Significant progress has been made in the human epidermal growth factor receptor 2-positive (HER2+) BCBrM population due to novel brain penetrable systemic therapies. Increased inclusion of patients with BCBrM in clinical trials using brain-penetrant systemic therapies recently led to the first FDA approval of a HER2-directed therapy specifically in the BCBrM population in the last year. Advances for the treatment of HR+/HER2− and TNBC BCBrM subgroups continue to evolve. In this review, we will discuss the diagnosis and multidisciplinary care of BCBrM. We focus on recent advances in neurosurgery, radiation therapy, and systemic treatment therapies with intracranial activity. We also provide an overview of the current clinical trial landscape for patients with BCBrM.

Background To determine if proton radiotherapy (PT), compared to intensity-modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma (GBM). Methods Eligible patients were randomized unblinded to PT vs IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes (PROs). Results A total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45-1.75; P = .74). PT was associated with a lower rate of fatigue (24% vs 58%, P = .05), but otherwise, there were no significant differences in PROs at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44-1.23; P = .24) or OS (HR, 0.86; 95% CI, 0.49-1.50; P = .60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P = .02). Conclusions In this signal-seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient-reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for GBM and cognitive preservation in patients with lower-grade gliomas with a longer survival time.

A large proportion of patients with cancer are unresponsive to treatment with immune checkpoint blockade and other immunotherapies. Here, we report a mathematical model of the time course of tumour responses to immune checkpoint inhibitors. The model takes into account intrinsic tumour growth rates, the rates of immune activation and of tumour-immune cell interactions, and the efficacy of immune-mediated tumour killing. For 124 patients, four cancer types and two immunotherapy agents, the model reliably described the immune responses and final tumour burden across all different cancers and drug combinations examined. In validation cohorts from four clinical trials of checkpoint inhibitors (with a total of 177 patients), the model accurately stratified the patients according to reduced or increased long-term tumour burden. We also provide model-derived quantitative measures of treatment sensitivity for specific drug-cancer combinations. The model can be used to predict responses to therapy and to quantify specific drug-cancer sensitivities in individual patients.

Background This retrospective study investigated the impact of, in addition to age, the management and outcomes of elderly patients with glioblastoma (GBM). Methods The National Cancer Database was queried between 2004 and 2015 for GBM patients age 60 years and older. Three age groups were created: 60 to 69, 70 to 79, and 80 years and older, and 4 age/KPS groups: “age ≥ 60/ KPS Results A total of 48 540 patients with a median age of 70 years (range, 60-90 years) at diagnosis, and a median follow-up of 6.8 months (range, 0-151 months) were included. Median survival was 5.0, 15.2, 9.6, and 6.8 months in groups 1, 2, 3, and 4, respectively (P Conclusions In elderly patients with newly diagnosed GBM, those with good KPS fared best with combined ChT and RT across all age groups. Performance status is a key prognostic factor that should be considered for management decisions in these patients.

Introduction This study proposes contouring recommendations for radiation treatment planning target volumes and organs-at-risk (OARs) for both low grade and high grade gliomas. Methods Ten cases consisting of 5 glioblastomas and 5 grade II or III gliomas, including their respective gross tumor volume (GTV), clinical target volume (CTV), and OARs were each contoured by 6 experienced neuro-radiation oncologists from 5 international institutions. Each case was first contoured using only MRI sequences (MRI-only), and then re-contoured with the addition of a fused planning CT (CT-MRI). The level of agreement among all contours was assessed using simultaneous truth and performance level estimation (STAPLE) with the kappa statistic and Dice similarity coefficient. Results A high level of agreement was observed between the GTV and CTV contours in the MRI-only workflow with a mean kappa of 0.88 and 0.89, respectively, with no statistically significant differences compared to the CT-MRI workflow (p = 0.88 and p = 0.82 for GTV and CTV, respectively). Agreement in cochlea contours improved from a mean kappa of 0.39 to 0.41, to 0.69 to 0.71 with the addition of CT information (p Conclusions Consensus contouring recommendations for low grade and high grade gliomas were established using the results from the consensus STAPLE contours, which will serve as a basis for further study and clinical trials by the MR-Linac Consortium.

Background We investigated differences in radiation-induced grade 3+ lymphopenia (G3+L), defined as an absolute lymphocyte count (ALC) nadir of Methods Patients enrolled in a randomized phase II trial received PT (n = 28) or XRT (n = 56) concomitantly with temozolomide. ALC was measured before, weekly during, and within 1 month after radiotherapy. Whole-brain mean dose (WBMD) and brain dose-volume indices were extracted from planned dose distributions. Univariate and multivariate logistic regression analyses were used to identify independent predictive variables. The resulting model was evaluated using receiver operating characteristic (ROC) curve analysis. Results Rates of G3+L were lower in men (7/47 [15%]) versus women (19/37 [51%]) (P < 0.001), and for PT (4/28 [14%]) versus XRT (22/56 [39%]) (P = 0.024). G3+L was significantly associated with baseline ALC, WBMD, and brain volumes receiving 5‒40 Gy(relative biological effectiveness [RBE]) or higher (ie, V5 through V40). Stepwise multivariate logistic regression analysis identified being female (odds ratio [OR] 6.2, 95% confidence interval [CI]: 1.95‒22.4, P = 0.003), baseline ALC (OR 0.18, 95% CI: 0.05‒0.51, P = 0.003), and whole-brain V20 (OR 1.07, 95% CI: 1.03‒1.13, P = 0.002) as the strongest predictors. ROC analysis yielded an area under the curve of 0.86 (95% CI: 0.79–0.94) for the final G3+L prediction model. Conclusions Sex, baseline ALC, and whole-brain V20 were the strongest predictors of G3+L for patients with GBM treated with radiation and temozolomide. PT reduced brain volumes receiving low and intermediate doses and, consequently, reduced G3+L.

Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting.Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (4 BMV), intermediate (4-13 BMV), and high-risk groups (13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS.Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV 4, BMV 4-13, and BMV 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p 0.0001). After multivariate regression modeling, melanoma histology (β: 10.10, SE: 1.89, p 0.0001) and number of initial brain metastases (β: 1.52, SE: 0.34, p 0.0001) remained predictive of BMV (adjusted RThis multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation versus salvage SRS after DBF.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

To understand portal vein embolization (PVE), associated liver partition and portal vein ligation (ALPPS) and radiation lobectomy (RL) outcomes in hepatocellular carcinoma (HCC) patients. Systematic reviews of future liver remnant (FLR) percent hypertrophy, proportion undergoing hepatectomy and proportion with major complications following PVE, ALPPS, and RL were performed by searching Ovid MEDLINE, Ovid EMBASE, The Cochrane Library, and Web of Science. Separate meta-analyses using random-effects models with assessment of study heterogeneity and publication bias were performed whenever allowable by available data. Of the 10,616 articles screened, 21 articles with 636 subjects, 4 articles with 65 subjects, and 4 articles with 195 subjects met the inclusion criteria for systematic reviews and meta-analyses for PVE, ALPPS, and RL, respectively. The pooled estimate of mean percent FLR hypertrophy was 30.9% (95%CI: 22–39%, Q = 4034.8, p < 0.0001) over 40.3 +/− 26.3 days for PVE, 54.9% (95%CI: 36–74%, Q = 73.8, p < 0.0001) over 11.1 +/− 3.1 days for ALPPS, and 29.0% (95%CI: 23–35%, Q = 56.2, p < 0.0001) over 138.5 +/− 56.5 days for RL. The pooled proportion undergoing hepatectomy was 91% (95%CI: 83–95%, Q = 43.9, p = 0.002) following PVE and 98% (95%CI: 50–100%, Q = 0.0, p = 1.0) following ALPPS. The pooled proportion with major complications was 5% (95%CI: 2–10%, Q = 7.3, p = 0.887) following PVE and 38% (95%CI: 18–63%, Q = 10.0, p = 0.019) following ALPPS. Though liver hypertrophy occurs following all three treatments in HCC patients, PVE balances effective hypertrophy with a short time frame and low major complication rate.

Background This secondary image analysis of a randomized trial of proton radiotherapy (PT) vs. photon intensity modulated radiotherapy (IMRT) compares tumor progression based on clinical radiological assessment vs. Response Assessment in Neuro-Oncology (RANO). Methods Eligible patients were enrolled in the randomized trial and had MR imaging at baseline and follow-up beyond 12 weeks from completion of radiotherapy. ‘Clinical progression’ was based on a clinical radiology report of progression and/or change in treatment for progression. Results Of 90 enrolled patients, 66 were evaluable. Median clinical progression-free survival (PFS) was 10.8 (Range: 9.4-14.7) months; 10.8 months IMRT vs. 11.2 months PT (p=0.14). Median RANO PFS was 8.2 (Range: 6.9, 12): 8.9 months IMRT vs. 6.6 months PT (p=0.24). RANO PFS was significantly shorter than clinical PFS overall (p=0.001) and for both the IMRT (p=0.01) and PT (p=0.04) groups. There were 31 (46.3%) discrepant cases of which 17 had RANO progression more than a month prior to clinical progression, and 14 had progression by RANO but not clinical criteria. Conclusion Based on this secondary analysis of a trial of PT vs. IMRT for GBM, while no difference in PFS was noted relative to treatment technique, RANO criteria identified progression more often and earlier than clinical assessment. This highlights the disconnect between measures of tumor response in clinical trials versus clinical practice. With growing efforts to utilize real-world data and personalized treatment with timely adaptation, there is a growing need to improve the consistency of determining tumor progression within clinical trials and clinical practice.

A magnetic resonance (MR) biologic marker (biomarker) is a measurable quantitative characteristic that is an indicator of normal biological and pathogenetic processes or a response to therapeutic intervention derived from the MR imaging process.1 There is significant potential for MR biomarkers to facilitate personalized approaches to cancer care through more precise quantification of normal vs pathologic tissue function, response to therapy as well as toxicity to both radiation and chemotherapy. The ongoing integration of MR into routine clinical radiation therapy (RT) planning and the development of MR‐guided radiation therapy systems are providing new opportunities for MR biomarkers to personalize and improve clinical outcomes. Their appropriate use, however, must be based on knowledge of the physical origin of the biomarker signal, the relationship to the underlying biological processes, and their strengths and limitations. Additionally, while significant literature exists providing quantitative values associated with a range of MR biomarkers, these values would not be considered compliant with the stringent requirements necessary to classify the parameter as a quantitative MR biomarker. This is particularly true within the context of using these values to drive radiation oncology (RO) treatment decisions, the most notable of which relate to adaptive treatment planning and delivery. The overall objective of this report is to provide physicists and clinicians with a basic understanding of MR biomarkers within the context of RO. Clarification is provided in terms of the definition of an imaging biomarker as well as the criteria by which a biomarker is considered quantitative. Their physical bases, strengths and limitations, values for normative and disease processes, as well as response to therapy when known are presented. Finally, standardized approaches to quality control and quality assurance programs are described. This educational report serves several purposes: (i) To describe the framework used to define an imaging biomarker and establish clinical validation, utility, and quantification, (ii) to identify MR biomarkers known to provide information relevant to RO, (iii) to describe standardized processes necessary for the quantification and validation of MR biomarkers in RO, and (iv) to provide quantitative values of these biomarkers under both normative and pathologic conditions. While not all potential MR biomarkers for RO are described here, those considered most common and promising are reported. For those measurements that remain undiscovered or unclassified, it is the intent of this report to describe the framework required to translate such measurements into imaging biomarkers for RO application.

Brain metastases are a major clinical problem, and immunotherapy offers a novel treatment paradigm with the potential to synergize with existing focal therapies like surgery and radiosurgery or even replace them in future. The brain is a unique microenvironment structurally and immunologically. The immune response is likely to be crucial to the adaptation of systemic immune modulating agents against this disease. Imaging is frequently employed in the clinical diagnosis and management of brain metastasis, so it is logical that brain imaging techniques are investigated as a source of biomarkers of the immune response in these tumors. Current imaging techniques in clinical use include structural MRI (post-contrast T1W sequences, T2, and FLAIR), physiological sequences (perfusion- and diffusion-weighted imaging), and molecular imaging (MR spectroscopy and PET). These are reviewed for their application to predicting and measuring the response to immunotherapy in brain metastases.

Checkpoint inhibitor therapy of cancer has led to markedly improved survival of a subset of patients in multiple solid malignant tumor types, yet the factors driving these clinical responses or lack thereof are not known. Here we present a translational mathematical model dependent on three key parameters for describing efficacy of checkpoint inhibitors in human cancer: tumor growth rate (α), tumor immune infiltration (Λ), and immunotherapy-mediated amplification of anti-tumor response (µ). The model was validated by fitting it to a compiled clinical tumor response dataset (n = 189 patients) obtained from published anti-PD-1 and anti-PD-L1 clinical trials, and then validated on an additional validation cohort (n = 64 patients) obtained from our in-house clinical trials. The derived parameters Λ and µ were both significantly different between responding versus non-responding patients. Of note, our model appropriately classified response in 81.4% of patients by using only tumor volume measurements and within two months of treatment initiation in a retrospective analysis. The model reliably predicted clinical response to the PD-1/PD-L1 class of checkpoint inhibitors across multiple solid malignant tumor types. Comparison of model parameters to immunohistochemical measurement of PD-L1 and CD8+ T cells confirmed robust relationships between model parameters and their underlying biology, demonstrating reliable methods to inform model parameters directly from biopsy samples, which are conveniently obtainable as early as the start of treatment. Together, these results suggest that the model parameters may serve as early and robust biomarkers of the efficacy of checkpoint inhibitor therapy on an individualized per-patient basis.SIGNIFICANCECheckpoint inhibitors have revolutionized cancer immunotherapy, but only a subset of patients with solid tumors responds clinically. The ability to predict tumor responses a priori or soon after starting therapy would allow for personalized and timely adaptive clinical applications of checkpoint inhibitor- based immunotherapy in patients. By applying a mechanistic mathematical model, we show that checkpoint inhibitor therapeutic effectiveness is accurately predictable in most patients within two months after treatment initiation. Our method may be implemented directly into clinical practice, as it relies on standard-of-care imaging and pathology. If successful in prospective studies, this model will improve selection of cancer patients for checkpoint inhibitor therapy, and perhaps for other forms of humoral- or cell-based immunotherapy.

Several studies evaluating stereotactic radiosurgery (SRS) for patients with4 brain metastases (BM) demonstrated similar outcomes after treatment of 1, 2 to 4, and 5 to 15 BM; others found clinically significant survival decrements in the latter group. In this review of 8 academic centers, we compared outcomes of patients undergoing initial SRS for 1, 2 to 4, and 5 to 15 BM.A total of 2089 patients treated with initial SRS for BM were included. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Patient and disease characteristics were evaluated for association with OS and cumulative incidence of distant brain failure (DBF) using stepwise multivariable Cox proportional hazards and competing risk regression modeling.In this series, 989 (47%) patients had 1 metastasis, 882 (42%) had 2 to 4 metastases, and 212 (10%) had 5 to 15 metastases treated. Median OS for the 1, 2 to 4, and 5 to 15 BM groups was 14.6, 9.5, and 7.5 months, respectively (log-rank P .01). Univariate and multivariable analyses revealed no difference in survival between 2 to 4 and 5 to 15 BM. DBF at 1 year was 30%, 41%, and 50%, respectively (Gray's P .01). Two-year cumulative incidence of salvage SRS decreased with increasing number of BM (1: 21% vs 2-4: 19% vs 5-15: 13%; P .01), but no difference in salvage whole brain radiation therapy was observed (1: 12% vs 2-4: 15% vs 5-15: 16%, P = .10). At the time of DBF, median brain metastasis velocity was 3.9, 6.1, and 11.7 new metastases per year in the 1, 2 to 4, and 5 to 15 BM groups, respectively (P .01).Patients treated with initial SRS for 5 to 15 BM experienced survival similar to that in patients with 2 to 4 BM. Lower rates of salvage SRS were observed in the 5 to 15 BM group, with no difference in rates of salvage whole brain radiation therapy.

Purpose This study aimed to report on the safety, feasibility, and workflow of using magnetic resonance imaging (MRI) simulation, while immobilized in the treatment position, for radiation therapy treatment planning in the pediatric population. Methods and Materials Between May and December 2017, 10 pediatric patients completed both MRI and computed tomography imaging simulation in treatment immobilization for radiation therapy planning for central nervous system disease. We report our initial institutional experience and workflow of the use of MRI simulation in immobilization for treatment planning in this population. Results Ten pediatric patients successfully underwent MRI and computed tomography imaging simulation for CNS disease. Two patients required anesthesia for sedation during the simulations. From our initial experience, MRI simulation was tolerated by all 10 pediatric patients without any safety or clinical issues, including those who required anesthesia. Conclusions Our initial experience supports the use of MRI simulation for radiation treatment planning in the pediatric population, with and without anesthetic sedation, as a safe and feasible image-guidance tool. This is particularly useful in the treatment of pediatric patients because MRI simulation enables superior, soft-tissue, anatomic imaging for a more robust delineation of organs at risk and target volumes without increasing radiation exposure.

Background Gadolinium-based contrast is often used when acquiring MR images for radiation therapy planning for better target delineation. In some situations, patients may still have residual MRI contrast agents in their tissue while being treated with high-energy radiation. This is especially true when MRI contrast agents are administered during adaptive treatment replanning for patients treated on MR-Linac systems. Purpose The purpose of this study was to analyze the molecular stability of MRI contrast agents when exposed to high energy photons and the associated secondary electrons in a 1.5T MR-Linac system. This was the first step in assessing the safety of administering MRI contrast agents throughout the course of treatment. Materials and methods Two common MRI contrast agents were irradiated with 7 MV photons to clinical dose levels. The irradiated samples were analyzed using liquid chromatography-high resolution mass spectrometry to detect degradation products or conformational alterations created by irradiation with high energy photons and associated secondary electrons. Results No significant change in chemical composition or displacement of gadolinium ions from their chelates was discovered in samples irradiated with 7 MV photons at relevant clinical doses in a 1.5T MR-Linac. Additionally, no significant correlation between concentrations of irradiated MRI contrast agents and radiation dose was observed. Conclusion The chemical composition stability of the irradiated contrast agents is promising for future use throughout the course of patient treatment. However, in vivo studies are needed to confirm that unexpected metabolites are not created in biological milieus.

BACKGROUND/AIM The problem of lack of standardisation in target delineation and herewith the variability of target contours in Gamma Knife radiosurgery is as severe as in linac-based radiotherapy in general. The first aim of this study was to quantify the contouring variability for a group of five radiosurgery targets and estimate their true-volume based on multiple delineations using the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm. The second aim was to assess the robustness of the STAPLE method for the assessment of the true-volume, with respect to the number of contours available as input. PATIENTS AND METHODS A multicentre analysis of the variability in contouring of five cases was performed. Twelve contours were provided for each case by experienced planners for Gamma Knife. To assess the robustness of the STAPLE method with respect to the number of contours used as input, sets of contours were randomly selected in the analysis. RESULTS A high similarity was observed between the STAPLE generated true-volume and the 50%-agreement volume when all 12 available contours were used as input (90-100%). Lower similarity was observed with smaller sets of contours (10-70%). CONCLUSION If a high number of input contours is available, the STAPLE method provides a valuable tool in the estimation of the true volume of a target based on multiple contours as well as the sensitivity and specificity for each input contour relative to the true volume of that structure. The robustness of the STAPLE method for rendering the true target volume depends on the number of contours provided as input and their variability with respect to shape, size and position.

Objectives Stereotactic radiosurgery is a common treatment for brain metastases and is typically planned on magnetic resonance imaging (MRI). However, the MR acquisition parameters used for patient selection and treatment planning for stereotactic radiosurgery can vary within and across institutions. In this work, we investigate the effect of MRI slice thickness on the detection and contoured volume of metastatic lesions in the brain. Methods and Materials A retrospective cohort of 28 images acquired with a slice thickness of 1 mm were resampled to simulate acquisitions at 2- and 3-mm slice thickness. A total of 102 metastases ranging from 0.0030 cc to 5.08 cc (75-percentile 0.36 cc) were contoured on the original images. All 3 sets of images were recontoured by experienced physicians. Results Of all the images detected and contoured on the 1 mm images, 3% of lesions were missed on the 2 mm images, and 13% were missed on the 3 mm images. One lesion that was identified on both the 2 mm and 3 mm images was determined to be a blood vessel on the 1 mm images. Additionally, the lesions were contoured 11% larger on the 2 mm and 43% larger on the 3 mm images. Conclusions Using images with a slice thickness >1 mm effects detection and segmentation of brain lesions, which can have an important effect on patient management and treatment outcomes.

Treatment for glioblastoma (GBM) includes surgical resection and adjuvant radiotherapy (RT) and chemotherapy. The optimal time interval between surgery and RT remains unclear. The National Cancer Database (NCDB) was queried for patients with GBM. Overall survival (OS) was estimated using Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariable Cox regression (MVA) modeling was used to determine predictors of OS. A total of 45,942 patients were included. On MVA: younger age, female gender, black ethnicity, higher KPS, obtaining a gross total resection (GTR), MGMT promoter-methylated gene status, unifocal disease, higher RT dose, and RT delay of 4–8 weeks had improved OS. Patients who underwent a subtotal resection (STR) had worsened survival with RT delay ≤4 weeks and patients with GTR had worsened survival when RT was delayed >8 weeks. This analysis suggests that an interval of 4–8 weeks between resection and RT results in better survival. Delays >8 weeks in patients with a GTR and delays

Glioblastoma is an aggressive brain tumor with a propensity for intracranial recurrence. We hypothesized that tumors can be visualized with diffusion tensor imaging (DTI) before they are detected on anatomical magnetic resonance (MR) images. We retrospectively analyzed serial MR images from 30 patients, including the DTI and T1-weighted images at recurrence, at 2 months and 4 months before recurrence, and at 1 month after radiation therapy. The diffusion maps and T1 images were deformably registered longitudinally. The recurrent tumor was manually segmented on the T1-weighted image and then applied to the diffusion maps at each time point to collect mean FA, diffusivities, and neurite density index (NDI) values, respectively. Group analysis of variance showed significant changes in FA (p = 0.01) and NDI (p = 0.0015) over time. Pairwise t tests also revealed that FA and NDI at 2 months before recurrence were 11.2% and 6.4% lower than those at 1 month after radiation therapy (p &lt, 0.05), respectively. Changes in FA and NDI were observed 2 months before recurrence, suggesting that progressive microstructural changes and neurite density loss may be detectable before tumor detection in anatomical MR images. FA and NDI may serve as non-contrast MR-based biomarkers for detecting subclinical tumors.

Brain metastases are the most common intracranial tumors, occurring in more than 15% of cancer patients. The treatment of brain metastases involves a multidisciplinary approach that may consist of surgery, radiation therapy (stereotactic radiosurgery or whole-brain radiation therapy), and/or systemic therapy. Unfortunately, all these treatment strategies, as well as the disease process itself, can be associated with debilitating and life-altering neurocognitive adverse effects. Balancing the benefits and toxicities of brain metastasis treatment is a challenging task that medical, radiation, and surgical oncologists face daily. Strategies have been developed to try mitigating these toxicities, such as stereotactic radiosurgery, hippocampal avoidance whole-brain radiation therapy, and “neuroprotective” drugs. Efforts have also been deployed in developing formal instruments/battery of tests to capture neurocognitive changes consistently in patients with brain metastases.

Background: Leptomeningeal disease (LMD), also known as neoplastic meningitis, leptomeningeal carcinomatosis, or carcinomatous meningitis, is a rare cancer complication occurring in ~5% of cases and ultimately leads to significant morbidity and mortality. In the modern era, incidence of this condition continues to rise with longer survival of patients with advanced and even metastatic disease due to continued improvements in systemic therapies that are providing prolonged control of distant disease, but with limited effect in the central nervous system (CNS). Typical treatment strategies include optimal systemic therapy for the primary disease, as well as neuroaxis directed therapies, which may include intrathecal chemotherapy (ITC) or radiotherapy (RT). Methods: A systematic review of radiotherapy for LMD was performed. Medline, EMBASE, and Cochrane databases were searched from 1946 to 2018 for clinical trials, retrospective/prospective reviews, and case series with ≥2 human subjects that used radiation therapy techniques in the treatment of LMD. The outcome measures of interest included: characteristics of trial participants, inclusion/exclusion criteria, study type, number of participants, primary cancer histology, type of intervention for LMD, survival results if reported, length of follow up, and study conclusion. Results: Of 547 unique citations, 62 studies met the pre-specified eligibility criteria. These studies included 36 retrospective cohorts, 11 prospective series, 12 case series, and a single citation of guidelines, NCDB analysis, and a randomized control trial. Owing to study heterogeneity, meta-analyses of the endpoint data could not be performed. Conclusions: LMD is a devastating complication of cancer with reported survivals ranging from 2 to 4 months. Based on this systematic review, the recommendation for the treatment of LMD is for multimodality discussion of cases and treatment, including the use of radiotherapy, for LMD. However, with continued advances in systemic therapy as well as imaging advances, the landscape of LMD is evolving rapidly and the role of RT will likely also continue to evolve and advance. There is limited high-quality evidence to guide the optimal use of RT for the treatment of LMD, and there is a great need for prospective, histology specific investigation of the role of radiotherapy for LMD in the era of modern systemic therapies.

Brain metastases are the most common intracranial tumors, with an incidence rate ranging from 7 to 14 per 100,000. Both the disease process itself and its treatments can be associated with debilitating and life-altering neurocognitive adverse effects. The treatment of brain metastases involves a multidisciplinary team that aims to maximize the benefits and minimize the toxicities of treatment, which may include surgical resection, radiation therapy (stereotactic radiosurgery or whole-brain radiation therapy), and/or systemic therapy. Additionally, strategies have been investigated to prevent and treat these toxicities, such as stereotactic radiosurgery, hippocampal avoidance whole-brain radiation therapy, and “neuroprotective” drugs, respectively. In order to better detect and measure treatment toxicity, efforts have also been deployed in tracking neurocognitive changes consistently in patients with brain metastases.

To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis.In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.0 vs2.0 and ≥2.5 vs2.5).A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ≥2.0, and 23.0% of patients had DS-GPA scores ≥2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ≥2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ≥2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53).We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases.

PURPOSE We investigated the long term impact of SRS and WBRT in two large prospective phase III trials. METHODS Patients with 1–4 BMs +/- resection were randomized to SRS or WBRT. Cognitive deterioration was a drop of >1 standard deviation from baseline in >2/6 cognitive measures (CM). Quality of life (QOL) scores were scored 0–100 point scale. CM and QOL scores were modeled using baseline adjusted Linear Mixed Models (LMM) with uncorrelated random intercept for subject and random slopes for time. Differences over time between groups and the effect of >2 cognitive scores with >2 SD change from baseline were assessed. RESULTS 88 patients were included with median follow up of 24 months. We observed decreasing CM over time (SRS: 4/6; WBRT: 5/6). Mean CM was significantly higher in SRS for Total recall and Delayed Recall at 3, 6, 9, 12 months. More patients in WBRT arm declined 1 SD in >1 and >2 CM at the 3, 6, 9, and 12 months. A 1 SD decline in >3 CM at 1 year was 21% SRS vs 47% WBRT (p=0.02). SRS had fewer patients with a 2 SD decline in >1 CM at every time point. SRS had fewer patients with a 2 SD decline at >2 and >3 CM. WBRT had lower QOL at 3 months, but switched to SRS having lower QOL at 24 months for PWB, EWB, FWB, FactG, BR, and FactBR (p< 0.05). A 2 SD decline in cognition decreased mean FWB by 6.4 units (95% CI: -11, -1.75; p=0.007) and decreased QOL by 5.1 units (95% CI: -7.7, -2.5; p< 0.001). CONCLUSIONS We report the first pooled prospective study demonstrating the long term outcomes of patients with BMs after cranial radiation. WBRT was associated with worse cognitive outcomes. Impaired cognition is associated with worse QOL.

Introduction Brain metastases in EGFR / ALK -driven NSCLC frequently pose treatment dilemmas. Tyrosine kinase inhibitors (TKIs) can control extracranial disease, but radiotherapy is often required for intracranial control. We aimed to evaluate the impact of first-line whole brain radiotherapy (WBRT), stereotactic radiotherapy (SRS) or TKI alone on outcomes of patients with brain metastases from EGFR / ALK -driven NSCLC. Methods This single center retrospective review included 184 patients with brain metastases from EGFR / ALK -driven NSCLC, and analyzed effect of treatment choice on time to intracranial progression (TTIP) and overall survival (OS). Results First-line treatment for brain metastases consisted of WBRT in 120 patients, SRS in 37 and TKI alone in 27. WBRT-treated patients had more brain metastases, and more baseline symptoms. Median TTIP was longer in the WBRT group at 50.5months than SRS or TKI groups at 12 and 15months ( p =0.0038). No significant difference was seen in median OS: 21.6months in the WBRT group, 23.9months in the SRS group and 22.6months in the TKI group ( p =0.67). In multivariable analysis, age>65years (HR 2.2, p =0.0014), greater number of brain metastases (HR 2.48, p =0.0002) and greater number of extracranial metastatic sites (2 vs 0–1 HR=2.05, p =0.014 and 3+ vs 0–1 HR=2.95, p =0.0001 were associated with shorter OS. No independent effect was seen from first-line CNS treatment choice. Conclusions First-line WBRT for brain metastases from EGFR / ALK -driven NSCLC was associated with longer TTIP than SRS or TKI alone, with no difference in OS. These results could support deferral of WBRT until intracranial progression in selected patients who are closely monitored.

Elevated neutrophil–lymphocyte ratio (NLR) may predict worse outcomes in cancer, including glioblastoma (GBM). This study assessed whether change in NLR during focal radiotherapy and concomitant temozolomide (RT-TMZ) provides further prognostic information. This was a retrospective review of patients treated with RT-TMZ for histologically confirmed GBM from January 2004 to September 2010. Variables assessed included age, ECOG performance status (PS), dexamethasone use and extent of surgery. Hematological results were collected at baseline, during and 4 weeks post RT-TMZ. Kaplan–Meier method was used to calculate overall survival (OS). Multivariable analysis (MVA) assessed for joint effect of covariates on OS and Pearson Correlation Coefficients assessed for association between dexamethasone dose and NLR change. With a median age of 55 (range 18–70), 369 patients were included. Median follow up was 15.1 month (range 1.6–134.6). The OS was 66.1% (95% CI 61.2–70.6) and 31.4 (95% CI 26.8–36.1) at 1 and 2 years, respectively. On univariate analysis, both decrease in NLR post RT-TMZ (HR 0.641, p

Glioblastoma is the most common primary brain tumor in the United States and despite aggressive multimodal therapy with maximum safe resection, radiotherapy in combination with concurrent and adjuvant temozolomide, the median survival of glioblastoma in clinical trial populations is 16 months. While the introduction of temozolomide into first-line standard of care (1) achieved some survival improvement, nearly all patients relapse and treatment options for recurrent disease remain limited and largely ineffective. Even under optimal circumstances with use of ‘state of the art’ diagnostic and therapeutic interventions, less than 15% of patients will survive 5 years (2-4).

Background To evaluate and establish a digital workflow for the custom designing and 3D printing of mouth opening tongue-depressing (MOTD) stents for patients receiving radiotherapy for head and neck cancer. Methods We retrospectively identified 3 patients who received radiation therapy (RT) for primary head and neck cancers with MOTD stents. We compared two methods for obtaining the digital impressions of patients’ teeth. The first method involved segmentation from computed tomography (CT) scans, as previously established by our group, and the second method used 3D scanning of the patients’ articulated stone models that were made during the conventional stent fabrication process. Three independent observers repeated the process to obtain digital impressions which provided data to design customized MOTD stents. For each method, we evaluated the time efficiency, dice similarity coefficient (DSC) for reproducibility, and the 3D printed stents’ accuracy. For the 3D scanning method, we evaluated the registration process using manual and automatic approaches. Results For all patients, the 3D scanning method demonstrated a significant advantage over the CT scanning method in terms of time efficiency with over 60% reduction in time consumed (p

Spinal ependymomas are rare, with an incidence of 1 per 100,000. Given the paucity of data for higher grade II and III disease, the management and patterns of care require further investigation.Our study of 1345 patients with higher-grade spinal ependymoma used χMost grade II patients received surgery alone (81.1%) compared with 36.8% of grade III. Approximately 60% of patients with grade III ependymomas received radiotherapy (RT) versus 15.3% of grade II (P0.001). Patients living ≤32 km (20 miles) from a facility were more likely to receive RT (P0.001) than were those living further away. On multivariable logistic regression, grade (grade III, odds ratio, 8.6; P0.001) and facility distance were significantly associated with receipt of RT (P 0.0001). The 5-year and 10-year OS was 94.7%/85.1% for patients with grade II disease and 58.2%/46.4% for grade III disease (P0.0001). OS was highest at facilities treating an average of 15 patients over 10 years, corresponding to the top 81st percentile in volume. The 10-year OS was 92.6% at facilities treating at least 15 patients and 88.0% at facilities treating 6-14 patients.Approximately 40% of patients with grade III ependymomas do not receive immediate adjuvant therapy, which may be related to distance from a facility. Patients with this rare tumor may benefit from multidisciplinary care at facilities with a larger volume.

OBJECTIVES: This retrospective study evaluates the impact of Karnofsky performance status (KPS) in addition to age on the management and outcomes of elderly patients with glioblastoma (GBM). METHODS: The National Cancer Database (NCDB) was queried between 2004–2015 for GBM patients with age 60 and reported KPS. Four groups were created: Age 60/ KPS

Background Cystic vestibular schwannomas (VS) are associated with unpredictable growth behavior and potentially worse surgical outcomes compared with their solid counterparts. Growth control and potential adverse effects of radiosurgery for cystic VS have created concerns surrounding this modality. We sought to compare the treatment efficacy and safety profile of radiosurgery between cystic and solid VS through a systematic review. Methods PubMed, EMBASE, Web of Science, and Cochrane were searched for related terms and studies reporting radiosurgical outcomes of cystic and solid VS. A meta-analysis was performed to compare the rates of tumor control. Random-effect models with generic inverse variance method was used to calculate overall pooled estimates. Study quality was assessed with the Newcastle Ottawa Criteria. Results In total, 2989 studies were retrieved, and 6 including 1358 VS (79.89% solid; 20.11% cystic, median follow-up range 31.8–150 months) were selected. The median maximal dose was 25 Gy (range, 13–36 Gy) and the median marginal tumor dose was 12 Gy (10–18 Gy). There was no difference between cystic and solid VS (risk ratio, 1.02; 95% confidence interval 0.94–1.10; P = 0.69; I2 = 78%). Transient enlargement of cystic tumors may be associated with trigeminal or facial neuropathy. Conclusions The evidence collected by this study suggests that radiosurgery for cystic VS exhibits effective tumor control probabilities similar to solid VS. Consensus definitions and standard criteria are needed in the future to better understand the patterns of tumor growth and response to treatment following radiosurgery for cystic VS, as well as long-term neurological and functional outcomes.

INTRODUCTION We evaluated outcomes of patients with newly diagnosed MBM treated with concurrent immune checkpoint inhibition (ICI) and stereotactic radiosurgery (SRS) (concurrentTx), defined as treatment delivery within 30 days of each other. METHODS Screening of 2,617 melanoma patients who received ICI (anti-CTLA4/anti-PD1/both) between 2011-2019 identified 151 pts who received concurrentTx for MBM. Among these, 51 had newly-diagnosed MBM and received no prior ICI or SRS, and were included in the current study. Overall survival (OS) and distant brain failure (DBF) were estimated using the Kaplan-Meier method. Incidence of radiation necrosis (RN) was captured. RESULTS Median follow up from treatment initiation (either ICI or SRS, whichever occurred first) was 37 months. Median OS was 30 months. Median interval between ICI/SRS was 12 days (range: 1-29). Twenty-two patients received ICI first and 29 received SRS first, without differences in OS (p=0.22), DBF (p=0.91), or development of RN (p=0.86). However, the interval between ICI and SRS was significant. Patients who received concurrentTx 1-11 days apart (n=25, “early”) experienced a significant improvement in OS and DBF compared to 12-29 days apart (n=26, “delayed”) (p=0.01, HR 2.8; 95%CI 1.3-6.2 for OS and p=0.02, HR 2.5; 95%CI 1.2-5.6 for DBF). OS and DBF at 36 months were 67% vs. 26% and 60% vs. 27%, respectively, for the early vs. delayed groups. Time to concurrentTx as a continuous variable was significantly associated with DBF (p=0.02), but not OS (p=0.06). Although not significant, more patients developed RN in the early (26.0%) versus delayed (3.8%) group (p=0.07). No additional patient or treatment differences were identified. CONCLUSIONS Early concurrentTx was associated with prolonged OS and improved DBF in newly diagnosed MBM patients who did not receive prior CNS-directed therapy. This finding suggests therapeutic synergism related to combined early treatment and should be validated in a prospective clinical trial.

2531 Background: Nivolumab (nivo) and ipilimumab (ipi) were found in the recent phase III CheckMate 227 trial to have an overall survival benefit over chemotherapy for advanced non-small cell lung cancer (NSCLC). However, patients (pts) with untreated brain metastasis (mets) were excluded from that trial. Because 30% of NSCLC pts develop brain mets, we tested nivo/ipi with concurrent stereotactic radiosurgery (SRS) for NSCLC pts with active brain mets. Methods: We report the safety data from the phase I portion of an ongoing phase I/II single-institution trial in which one treatment group was given SRS with nivo (3 mg/kg) every 2 weeks (wks) plus ipi (1 mg/kg) every 6 wks x 4 cycles, followed by maintenance nivo (480 mg) every 4 wks until disease progression, unacceptable toxicity, or withdrawal of consent. Brain SRS was delivered within 7 days of initiation of nivo/ipi. The primary endpoints were safety and 4-month (mo) intracranial progression-free survival (PFS). Dose-limiting toxicity (DLT) was defined as > 15% intracranial toxicity (>G3 hypophysitis / neurologic toxicity) or > 30% extracranial toxicity (>G3 non-dermatologic non-lab toxicity or >G4 dermatologic / lab toxicity), refractory to medical management, assessed at 8 wks after treatment initiation. Target accrual for phase I was 10 evaluable pts, with enrollment suspended after every 5 pts for DLT assessment. Results: Since June 15, 2018, 13 pts were enrolled and 10 were evaluable for DLT. The median follow-up time was 6.8 mo (range 1.2‒18). As of January 6, 2020, only 1 pt had DLT-defined toxicity and thus the predefined stopping criteria were not met. This pt had G3 seizure right after SRS that resolved within a week, and then had increased but asymptomatic CNS edema 4 wks later. Aside from DLTs, 3 pts (25%) developed treatment-related G3 (elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis) or G4 events (pneumonitis/acute respiratory distress syndrome in 1 pt with confirmed influenza at 7 mos after treatment initiation). This pt subsequently died of hemophagocytic lymphohistiocytosis (considered possibly related to the study drugs). Median intracranial PFS time was 9.7 mo, and the 4-mo intracranial PFS rate was 75%. Extracranial objective response rate was 33% in the 12 evaluable pts with a median response duration of 9.1 mo. Conclusions: Concurrent SRS withnivo/ipi was safe for pts with active NSCLC brain mets. Preliminary analyses of efficacy were encouraging for durable intracranial and extracranial response. Clinical trial information: NCT02696993 .

Gamma-Knife (GK), Perfexion (PFX) has 8 sectors that can be blocked compared with the older model 4C, which has 201 independent source blocking options using plugs. This limits the ability of PFX to shape a single isocenter plan, such as trigeminal neuralgia. In this retrospective review and prospective re-planning comparison study of trigeminal neuralgia radiosurgery plans, a hybrid isocenter technique (HIT) is compared with single isocenter GK radiosurgery plans on 2 models (4C and PFX) dosimetric parameters. With ethics approval, patients treated on 4C (n = 100) and PFX (n = 50) between 2005 and 2014 for trigeminal neuralgia were reviewed. All clinical plans were produced using 1 isocenter with a 4-mm collimator and a prescription dose of 80 Gy at 100% while limiting brainstem dose to D 1 mm 3 ). Dose shaping was performed using plugs in 4C and sector blocking in PFX to optimize the plan, if required. Re-planning using HIT was retrospectively attempted for PFX plans with brainstem dose > 15 Gy. In the implementation of HIT, we used 2 shots at the same isocenter, but with different sector block configuration and weights, to further reduce brainstem dose while optimizing dose coverage of the nerve. Planning parameters such as dose to the treated nerve, brainstem, and surrounding tissue were compared between the clinical plans and the new plans with HIT. Source blocking was applied in 66/100 4C plans with mean blocked sources of 40.2/201 (ranging 1 to 99) and in 36/50 PFX plans with mean blocked sectors of 2.2/8 (1 to 4). There is no significant differences in mean dose, integral dose, irradiated volume of the treated nerve between 4C, and PFX plans. The 4C plans had smaller irradiated volume of tissue (90.6 mm3) than PFX plans (103.5 mm3) (p D 1 mm 3 was 15.8 Gy on average (15.2 to 16.5 Gy) and D 10 mm 3 was 12.2 Gy (11.4 to 13.2 Gy). Re-plans of these 9 cases using HIT resulted in a significant reduction in D 1 mm 3 to 13.5 Gy (12.2 to 15.1) and D 10 mm 3 to 10.5 Gy (8.1 to 12.2) (p

Radiation oncology has long required quantitative imaging approaches for the safe and effective delivery of radiation therapy. The past 10 years has seen a remarkable expansion in the variety of novel imaging signals and analyses that are starting to contribute to the prescription and design of the radiation treatment plan. These include a rapid increase in the use of magnetic resonance imaging, development of contrast-enhanced imaging techniques, integration of fluorinated deoxyglucose-positron emission tomography, evaluation of hypoxia imaging techniques, and numerous others. These are reviewed with an effort to highlight challenges related to quantification and reproducibility. In addition, several of the emerging applications of these imaging approaches are also highlighted. Finally, the growing community of support for establishing quantitative imaging approaches as we move toward clinical evaluation is summarized and the need for a clinical service in support of the clinical science and delivery of care is proposed.

PURPOSE We investigated the long term impact of SRS and WBRT in two large prospective phase III trials. METHODS Patients with 1–4 BMs +/- resection were randomized to SRS or WBRT. Cognitive deterioration was a drop of >1 standard deviation from baseline in >2/6 cognitive measures (CM). Quality of life (QOL) scores were scored 0–100 point scale. CM and QOL scores were modeled using baseline adjusted Linear Mixed Models (LMM) with uncorrelated random intercept for subject and random slopes for time. Differences in trend over time between groups and the effect of >2 cognitive scores with >2 SD change from baseline were assessed. RESULTS 88 patients were included with median follow up of 24 months. We observed decreasing CM over time (SRS: 4/6; WBRT: 5/6). Mean CM was significantly higher in SRS for Total recall and Delayed Recall at 3, 6, 9, 12 months. More patients in WBRT arm declined 1 SD in >1 and >2 CM at the 3, 6, 9, and 12 months. A 1 SD decline in >3 CM at 1 year was 21% SRS vs 47% WBRT (p=0.02). SRS had fewer patients with a 2 SD decline in >1 CM at every time point. SRS had fewer patients with a 2 SD decline at >2 and >3 CM. WBRT had lower QOL at 3 months, but switched to SRS having lower QOL at 24 months for PWB, EWB, FWB, FactG, BR, and FactBR (p CONCLUSIONS We report the first pooled prospective study demonstrating the long term outcomes of patients with BMs after cranial radiation. WBRT was associated with worse cognitive outcomes. Impaired cognition is associated with worse QOL.

BACKGROUND: At our institution, we have historically treated brain metastasis (BM) ≤2 cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes. METHODS: We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariate analyses (MVAs). RESULTS: We evaluated 1533 BM ≤2 cm. Median radiographic follow-up post SRS was 12.7 months (1.4–100). Overall, the 2-year incidence of LF was lower for BM treated with PD ≥21 Gy (9.3%) compared with PD ≤15 Gy (19.5%) (sub–hazard ratio, 2.3; 95% CI: 1.4–3.7; P = 0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21 Gy (9.5%) compared with the PD ≤15 Gy group (7.5%) (P = 0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1 cm) were significantly correlated (P < 0.05) with higher rates of LF and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15 Gy with ≥21 Gy, the risks of LF and RN are equivalent. However, for lesions >1 cm, PD ≥21 Gy is associated with a lower incidence of LF without significantly increasing the risk of RN. CONCLUSION: Our results indicate that rates of LF or RN following SRS for BM are strongly correlated with size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brainstem.

Our objective was to investigate direct voxel-wise relationship between dose and early MR biomarker changes both within and in the high-dose region surrounding brain metastases following stereotactic radiosurgery (SRS). Specifically, we examined the apparent diffusion coefficient (ADC) from diffusion-weighted imaging and the contrast transfer coefficient (Ktrans) and volume of extracellular extravascular space (ve) derived from dynamic contrast-enhanced (DCE) MRI data. We investigated 29 brain metastases in 18 patients using 3 T MRI to collect imaging data at day 0, day 3 and day 20 following SRS. The ADC maps were generated by the scanner and Ktrans and ve maps were generated using in-house software for dynamic tracer-kinetic analysis. To enable spatially-correlated voxel-wise analysis, we developed a registration pipeline to register all ADC, Ktrans and ve maps to the planning MRI scan. To interrogate longitudinal changes, we computed absolute ΔADC, ΔKtrans and Δve for day 3 and 20 post-SRS relative to day 0. We performed a Kruskall-Wallice test on each biomarker between time points and investigated dose correlations within the gross tumour volume (GTV) and surrounding high dose region > 12 Gy via Spearman's rho. Only ve exhibited significant differences between day 0 and 20 (p < 0.005) and day 3 and 20 (p < 0.05) within the GTV following SRS. Strongest dose correlations were observed for ADC within the GTV (rho = 0.17 to 0.20) and weak correlations were observed for ADC and Ktrans in the surrounding > 12 Gy region. Both ΔKtrans and Δve showed a trend with dose at day 20 within the GTV and > 12 Gy region (rho = -0.04 to -0.16). Weak dose-related decreases in Ktrans and ve within the GTV and high dose region at day 20 most likely reflect underlying vascular responses to radiation. Our study also provides a voxel-wise analysis schema for future MR biomarker studies with the goal of elucidating surrogates for radionecrosis.

Background: Although accurate delineation of the target is a key factor of success in radiosurgery there are no consensus guidelines for target contouring. Aim: The aim of the present study was therefore to quantify the variability in target delineation and discuss the potential clinical implications, for six targets regarded as common in stereotactic radiosurgery.Material and methods: Twelve Gamma Knife centers participated in the study by contouring the targets and organs at risks and performing the treatment plans. Analysis of target delineation variability was based on metrics defined based on agreement volumes derived from overlapping structures following a previously developed method. The 50% agreement volume (AV50), the common and the encompassing volumes as well as the Agreement Volume Index (AVI) were determined.Results: Results showed that the lowest AVI (0.16) was found for one of the analyzed metastases (range of delineated volumes 1.27–3.33 cm3). AVI for the other two metastases was 0...

Background Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a review of all available studies reporting SRS treatment for BSM was performed. Methods Twenty-nine retrospective studies investigating SRS for BSM were reviewed. Results The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events, varied from 0 to 9.5% (mean 3.4 ± 2.9%). Overall, the median time to toxicity after SRS was 3 months, with 90% of toxicities occurring before 9 months. A total of 1243 cases had toxicity and location data available. Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811). Conclusions Current data suggest that brainstem substructure location does not predict for toxicity and lesion volume within this cohort with median tumor volumes 0.04–2.8 cc does not predict for toxicity.

Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate gland that can lead to lower urinary tract symptoms (LUTS). The prevalence of LUTS that can include frequency, slow urinary stream, nocturia, and other symptoms due to BPH is over half of men in the United States by the time they are 80 years old. Transurethral needle ablation of the prostate (TUNA) is a minimally invasive procedure, which uses radiofrequency current to induce thermal tissue lesions to relieve patients from LUTS and prevent the progression of BPH into serious genitourinary conditions such as acute urinary retention. TUNA is an option for patients who have failed medical treatment or who cannot or do not want to undergo transurethral resection of the prostate due to risks associated with surgery or concerns of retrograde ejaculation. TUNA can be done under topical anesthesia in the outpatient setting and can be performed on a range of prostate sizes to produce significant improvements in subjective and objective symptoms.