Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors.

PURPOSE: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers. METHODS: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions. RESULTS: During 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions. CONCLUSION: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management.

Ca2+/Calmodulin-Dependent Protein Kinase II Enhances Retinal Ganglion Cell Survival But Suppresses Axon Regeneration after Optic Nerve Injury.

Neuroprotection after injury or in neurodegenerative disease remains a major goal for basic and translational neuroscience. Retinal ganglion cells (RGCs), the projection neurons of the eye, degenerate in optic neuropathies after axon injury, and there are no clinical therapies to prevent their loss or restore their connectivity to targets in the brain. Here we demonstrate a profound neuroprotective effect of the exogenous expression of various Ca2+/calmodulin-dependent protein kinase II (CaMKII) isoforms in mice. A dramatic increase in RGC survival following the optic nerve trauma was elicited by the expression of constitutively active variants of multiple CaMKII isoforms in RGCs using adeno-associated viral (AAV) vectors across a 100-fold range of AAV dosing in vivo. Despite this neuroprotection, however, short-distance RGC axon sprouting was suppressed by CaMKII, and long-distance axon regeneration elicited by several pro-axon growth treatments was likewise inhibited even as CaMKII further enhanced RGC survival. Notably, in a dose-escalation study, AAV-expressed CaMKII was more potent for axon growth suppression than the promotion of survival. That diffuse overexpression of constitutively active CaMKII strongly promotes RGC survival after axon injury may be clinically valuable for neuroprotection per se. However, the associated strong suppression of the optic nerve axon regeneration demonstrates the need for understanding the intracellular domain- and target-specific CaMKII activities to the development of CaMKII signaling pathway-directed strategies for the treatment of optic neuropathies.

Sarcopenia predicts short-term treatment-related toxicity in patients undergoing curative-intent therapy for head and neck cancer: A systematic review and meta-analysis.

Sarcopenia is an increasingly recognized biomarker associated with poorer outcomes. The objective of this study was to ascertain the effect of sarcopenia on treatment tolerance and short-term toxicity in head and neck cancer (HNC). A systematic review was performed using multiple databases. An inverse-variation, random-effects model was used to perform the meta-analysis to evaluate the effect of sarcopenia on severe treatment toxicity and poor treatment tolerance. Sixteen observational studies, including 3187 patients with HNC, were analyzed. The combined odds ratio (OR) for severe treatment toxicity and tolerance was 2.22 (95%CI 1.50-3.29) and 1.40 (95%CI 0.84-2.32), respectively. The effect of sarcopenia on short-term severe treatment toxicity was similar with upfront surgery (OR 2.03, 95%CI 1.22-3.37) and definitive radiotherapy (OR 2.24, 95%CI 1.18-4.27) Patients with sarcopenia are more than twice as likely to suffer a short-term treatment-related toxicity when undergoing curative-intent HNC treatment.

Prediction of Normal Tissue Complication Probability (NTCP) After Radiation Therapy Using Imaging and Molecular Biomarkers and Multivariate Modelling.

The aim of this study was to design a predictive radiobiological model of normal brain tissue in low-grade glioma following radiotherapy based on imaging and molecular biomarkers. Fifteen patients with primary brain tumors prospectively participated in this study and underwent radiation therapy. Magnetic resonance imaging (MRI) was obtained from the patients, including T1- and T2-weighted imaging and diffusion tensor imaging (DTI), and a generalized equivalent dose (gEUD) was calculated. The radiobiological model of the normal tissue complication probability (NTCP) was performed using the variables gEUD; axial diffusivity (AD) and radial diffusivity (RD) of the corpus callosum; and serum protein S100B by univariate and multivariate logistic regression XLIIIrd Sir Peter Freyer Memorial Lecture and Surgical Symposium (2018). Changes in AD, RD, and S100B from baseline up to the 6 months after treatment had an increasing trend and were significant in some time points (P-value < 0.05). The model resulting from RD changes in the 6 months after treatment was significantly more predictable of necrosis than other univariate models. The bivariate model combining RD changes in Gy40 dose-volume and gEUD, as well as the trivariate model obtained using gEUD, RD, and S100B, had a higher predictive value among multivariate models at the sixth month of the treatment. Changes in RD diffusion indices and in serum protein S100B value were used in the early-delayed stage as reliable biomarkers for predicting late-delayed damage (necrosis) caused by radiation in the corpus callosum. Current findings could pave the way for intervention therapies to delay the severity of damage to white matter structures, minimize cognitive impairment, and improve the quality of life of patients with low-grade glioma.

Critical Appraisal of Proton Therapy for Patients with Central Nervous System (CNS) Malignancies.

OPINION STATEMENT: As more hospital-based proton treatment centres become operational, the indications for proton beam therapy (PBT) are being evaluated. Recent advances in PBT technology are expanding the indications for the use of protons in the treatment of central nervous system (CNS) tumours. Prospective trials that assess the late toxicity of different radiation therapy (RT) techniques are needed to confirm any expected reduction in long-term side effects with PBT. The ASTRO Model Policy on proton beam therapy currently supports the reasonable use of protons in the treatment of specific CNS tumour types. Specifically, PBT plays a key role in the management of CNS tumours where anatomy, extent of disease or previous treatment cannot be satisfactorily addressed with conventional RT. As the availability of PBT rises around the world, the number of patients with CNS disease treated with PBT will continue to grow.

Framework for Quality Assurance of Ultrahigh Dose Rate Clinical Trials Investigating FLASH Effects and Current Technology Gaps.

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology FLASH working group on quality assurance of potential UHDR clinical trials and reviews current technology gaps to overcome. An important but separate consideration is the appropriate design of trials to most effectively answer clinical and scientific questions about FLASH. This paper begins with an overview of UHDR RT delivery methods. UHDR beam delivery parameters are then covered, with a focus on electron and proton modalities. The definition and control of safe UHDR beam delivery and current and needed dosimetry technologies are reviewed and discussed. System and site credentialing for large, multi-institution trials are reviewed. Quality assurance is then discussed, and new requirements are presented for treatment system standard analysis, patient positioning, and treatment planning. The tables and figures in this paper are meant to serve as reference points as we move toward FLASH-RT clinical trial performance. Some major questions regarding FLASH-RT are discussed, and next steps in this field are proposed. FLASH-RT has potential but is associated with significant risks and complexities. We need to redefine optimization to focus not only on the dose but also on the dose rate in a manner that is robust and understandable and that can be prescribed, validated, and confirmed in real time. Robust patient safety systems and access to treatment data will be critical as FLASH-RT moves into the clinical trials.

NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma.

PURPOSE: To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities. METHODS: NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression ≥ 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression. RESULTS: From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; P = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; P = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, P = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM. CONCLUSION: To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS.

Proceedings of the Survivorship Care in Neuro-Oncology Workshop sponsored by the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT).

Background: Survivorship for those living with primary CNS cancers begins at diagnosis, continues throughout a person's life, and includes caregivers. Opportunities and challenges exist to advance survivorship care for those living with primary CNS cancers that necessitate stakeholder involvement. Methods: In June 2021, NCI-CONNECT convened a two-day virtual workshop about survivorship care in neuro-oncology. Two expert panels provided key recommendations and five working groups considered critical questions to identify strengths, weaknesses, opportunities, and threats to the advancement of survivorship care and developed recommendations and action items. Results: The following action items emanated from the workshop: seek endorsement of meeting report from stakeholder organizations; address barriers in access to survivorship care and provider reimbursement; advance survivorship research through NIH and private grant support; develop a survivorship tool kit for providers, people living with primary CNS cancers and their caregivers; provide accessible educational content for neuro-oncology, neurology, and oncology community providers about survivorship care in neuro-oncology; and establish core competencies for survivorship care for neuro-oncology providers to be included in training and standardized exams. Conclusions: Action items aim to address access and reimbursement barriers, expand patient and provider education, develop core competencies, and support survivorship research through funding and other supports.

Irradiation-Modulated Murine Brain Microenvironment Enhances GL261-Tumor Growth and Inhibits Anti-PD-L1 Immunotherapy.

PURPOSE: Clinical evidence suggests radiation induces changes in the brain microenvironment that affect subsequent response to treatment. This study investigates the effect of previous radiation, delivered six weeks prior to orthotopic tumor implantation, on subsequent tumor growth and therapeutic response to anti-PD-L1 therapy in an intracranial mouse model, termed the Radiation Induced Immunosuppressive Microenvironment (RI2M) model. METHOD AND MATERIALS: C57Bl/6 mice received focal (hemispheric) single-fraction, 30-Gy radiation using the Leksell GammaKnife® Perfexion™, a dose that does not produce frank/gross radiation necrosis. Non-irradiated GL261 glioblastoma tumor cells were implanted six weeks later into the irradiated hemisphere. Lesion volume was measured longitudinally by in vivo MRI. In a separate experiment, tumors were implanted into either previously irradiated (30 Gy) or non-irradiated mouse brain, mice were treated with anti-PD-L1 antibody, and Kaplan-Meier survival curves were constructed. Mouse brains were assessed by conventional hematoxylin and eosin (H&E) staining, IBA-1 staining, which detects activated microglia and macrophages, and fluorescence-activated cell sorting (FACS) analysis. RESULTS: Tumors in previously irradiated brain display aggressive, invasive growth, characterized by viable tumor and large regions of hemorrhage and necrosis. Mice challenged intracranially with GL261 six weeks after prior intracranial irradiation are unresponsive to anti-PD-L1 therapy. K-M curves demonstrate a statistically significant difference in survival for tumor-bearing mice treated with anti-PD-L1 antibody between RI2M vs. non-irradiated mice. The most prominent immunologic change in the post-irradiated brain parenchyma is an increased frequency of activated microglia. CONCLUSIONS: The RI2M model focuses on the persisting (weeks-to-months) impact of radiation applied to normal, control-state brain on the growth characteristics and immunotherapy response of subsequently implanted tumor. GL261 tumors growing in the RI2M grew markedly more aggressively, with tumor cells admixed with regions of hemorrhage and necrosis, and showed a dramatic loss of response to anti-PD-L1 therapy compared to tumors in non-irradiated brain. IHC and FACS analyses demonstrate increased frequency of activated microglia, which correlates with loss of sensitivity to checkpoint immunotherapy. Given that standard-of-care for primary brain tumor following resection includes concurrent radiation and chemotherapy, these striking observations strongly motivate detailed assessment of the late effects of the RI2M on tumor growth and therapeutic efficacy.

A Bayesian dose-finding design for outcomes evaluated with uncertainty.

INTRODUCTION: In some phase I trial settings, there is uncertainty in assessing whether a given patient meets the criteria for dose-limiting toxicity. METHODS: We present a design which accommodates dose-limiting toxicity outcomes that are assessed with uncertainty for some patients. Our approach could be utilized in many available phase I trial designs, but we focus on the continual reassessment method due to its popularity. We assume that for some patients, instead of the usual binary dose-limiting toxicity outcome, we observe a physician-assessed probability of dose-limiting toxicity specific to a given patient. Data augmentation is used to estimate the posterior probabilities of dose-limiting toxicity at each dose level based on both the fully observed and partially observed patient outcomes. A simulation study is used to assess the performance of the design relative to using the continual reassessment method on the true dose-limiting toxicity outcomes (available in simulation setting only) and relative to simple thresholding approaches. RESULTS: Among the designs utilizing the partially observed outcomes, our proposed design has the best overall performance in terms of probability of selecting correct maximum tolerated dose and number of patients treated at the maximum tolerated dose. CONCLUSION: Incorporating uncertainty in dose-limiting toxicity assessment can improve the performance of the continual reassessment method design.

Evaluation of interim MRI changes during limited-field radiation therapy for glioblastoma and implications for treatment planning.

BACKGROUND AND PURPOSE: Consensus for defining gross tumor volume (GTV) and clinical target volume (CTV) for limited-field radiation therapy (LFRT) of GBM are not well established. We leveraged a department MRI simulator to image patients before and during LFRT to address these questions. MATERIALS AND METHODS: Supratentorial GBM patients receiving LFRT (46 Gy + boost to 60 Gy) underwent baseline MRI (MRI1) and interim MRI during RT (MRI2). GTV1 was defined as T1 enhancement + surgical cavity on MRI1 without routine inclusion of T2 abnormality (unless tumor did not enhance). The initial CTV margin was 15 mm from GTV1, and the boost CTV margin was 5-7 mm. The GTV1 characteristics were categorized into three groups: identical T1 and T2 abnormality (Group A), T1 only with larger T2 abnormality not included (Group B), and T2 abnormality when tumor lacked enhancement (Group C). GTV2 was contoured on MRI2 and compared with GTV1 plus 5-15 mm expansions. RESULTS: Among 120 patients treated from 2014-2019, 29 patients (24%) underwent replanning based on MRI2. On MRI2, 84% of GTV2 were covered by GTV1 + 5 mm, 93% by GTV1 + 7 mm, and 98% by GTV1 + 15 mm. On MRI1, 43% of GTV1 could be categorized into Group A, 39% Group B, and 18% Group C. Group B's patterns of failure, local control, or progression-free survival were similar to Group A/C. CONCLUSIONS: Initial CTV margin of 15 mm followed by a boost CTV margin of 7 mm is a reasonable approach for LFRT of GBM. Omitting routine inclusion of T2 abnormality from GTV delineation may not jeopardize disease control.

Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients - a report of the PET/RANO group.

The management of patients with glioma usually requires multimodality treatment including surgery, radiotherapy, and systemic therapy. Accurate neuroimaging plays a central role for radiotherapy planning and follow-up after radiotherapy completion. In order to maximize the radiation dose to the tumor and to minimize toxic effects on the surrounding brain parenchyma, reliable identification of tumor extent and target volume delineation is crucial. The use of positron emission tomography (PET) for radiotherapy planning and monitoring in gliomas has gained considerable interest over the last several years, but Class I data are not yet available. Furthermore, PET has been used after radiotherapy for response assessment and to distinguish tumor progression from pseudoprogression or radiation necrosis. Here, the Response Assessment in Neuro-Oncology (RANO) working group provides a summary of the literature and recommendations for the use of PET imaging for radiotherapy of patients with glioma based on published studies, constituting levels 1-3 evidence according to the Oxford Centre for Evidence-based Medicine.

Dosimetric predictors of symptomatic radiation necrosis after five-fraction radiosurgery for brain metastases.

BACKGROUND: To identify factors predictive of developing symptomatic radiation necrosis (sRN) among patients with either intact or resected brain metastases undergoing five-fraction stereotactic radiosurgery (5fSRS). METHODS: Multi-institutional retrospective review of 117 brain metastases from 83 patients treated with 5fSRS. The cumulative incidence of sRN and predictors of sRN were calculated using Gray's competing risks and Cox regression. RESULTS: The median dose of 5fSRS was 30 Gy (range: 25-40), and 21 lesions (18%) had prior SRS. After a median follow-up of 10.3 months (range: 3-52), the cumulative sRN incidence was 15%, with a median time to sRN of 6.9 months (range: 1.8-31.7). sRN incidence was significantly higher among the lesions treated with prior SRS: hazard ratio (HR): 7.48 [95% confidence interval: 2.57-21.8]. Among lesions without prior SRS, higher volume of uninvolved brain receiving 25 Gy (BrainV25; HR: 1.07 [1.02-1.12]) and 30 Gy (BrainV30; HR: 1.07 [1.01-1.33]) were the most significant factors associated with sRN. Similar results were also observed among the patients with prior SRS. For lesions without prior SRS, BrainV25 > 16 cm3 (HR: 11.7 [1.47-93.3]) and BrainV30 > 10 cm3 (HR: 7.08 [1.52-33.0]) were associated with significantly higher risk of sRN. At two years, the sRN incidence was 21% if violating either dosimetric threshold and 2% if violating neither (p = .007). CONCLUSION: BrainV25 and BrainV30 are significant dosimetric predictors of sRN of brain metastases treated with 5fSRS. In the absence of prior SRS, maintaining BrainV25Gy < 16 cm3 and BrainV30Gy < 10 cm3 may minimize sRN risk.

Parametric Response Mapping of FLAIR MRI Provides an Early Indication of Progression Risk in Glioblastoma.

RATIONALE AND OBJECTIVES: Glioblastoma image evaluation utilizes Magnetic Resonance Imaging contrast-enhanced, T1-weighted, and noncontrast T2-weighted fluid-attenuated inversion recovery (FLAIR) acquisitions. Disease progression assessment relies on changes in tumor diameter, which correlate poorly with survival. To improve treatment monitoring in glioblastoma, we investigated serial voxel-wise comparison of anatomically-aligned FLAIR signal as an early predictor of GBM progression. MATERIALS AND METHODS: We analyzed longitudinal normalized FLAIR images (rFLAIR) from 52 subjects using voxel-wise Parametric Response Mapping (PRM) to monitor volume fractions of increased (PRMrFLAIR+), decreased (PRMrFLAIR-), or unchanged (PRMrFLAIR0) rFLAIR intensity. We determined response by rFLAIR between pretreatment and 10 weeks posttreatment. Risk of disease progression in a subset of subjects (N = 26) with stable disease or partial response as defined by Response Assessment in Neuro-Oncology (RANO) criteria was assessed by PRMrFLAIR between weeks 10 and 20 and continuously until the PRMrFLAIR+ exceeded a defined threshold. RANO defined criteria were compared with PRM-derived outcomes for tumor progression detection. RESULTS: Patient stratification for progression-free survival (PFS) and overall survival (OS) was achieved at week 10 using RANO criteria (PFS: p <0.0001; OS: p <0.0001), relative change in FLAIR-hyperintense volume (PFS: p = 0.0011; OS: p <0.0001), and PRMrFLAIR+ (PFS: p <0.01; OS: p <0.001). PRMrFLAIR+ also stratified responding patients' progression between weeks 10 and 20 (PFS: p <0.05; OS: p = 0.01) while changes in FLAIR-volume measurements were not predictive. As a continuous evaluation, PRMrFLAIR+ exceeding 10% stratified patients for PFA after 5.6 months (p<0.0001), while RANO criteria did not stratify patients until 15.4 months (p <0.0001). CONCLUSION: PRMrFLAIR may provide an early biomarker of disease progression in glioblastoma.

Internal dose escalation associated with increased local control for melanoma brain metastases treated with stereotactic radiosurgery.

OBJECTIVE: The internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non-small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM. METHODS: The records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC. RESULTS: Two hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31-86 years). The median follow-up was 7.6 months (range 0.5-81.6 months), and the median survival was 9.3 months (range 1.3-81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was ≥ and < 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 ≥ and < 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 ≥ and < 25%, respectively. Lesions > 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 ≥ and < 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30. CONCLUSIONS: For a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 ≥ 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation.

Evaluation of the Metastatic Spine Disease Multidisciplinary Working Group Algorithms as Part of a Multidisciplinary Spine Tumor Conference.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The Metastatic Spine Disease Multidisciplinary Working Group Algorithms are evidence and expert opinion-based strategies for utilizing radiation therapy, interventional radiology procedures, and surgery to treat 5 types of spine metastases: asymptomatic spinal metastases, uncomplicated spinal metastases, stable vertebral compression fractures (VCF), unstable VCF, and metastatic epidural spinal cord compression (MESCC). Evaluation of this set of algorithms in a clinical setting is lacking. The authors aimed to identify rate of treatment adherence to the Working Group Algorithms and, subsequently, update these algorithms based on actual patient management decisions made at a single-institution, multidisciplinary, spine tumor conference. METHODS: Patients with metastatic spine disease from primary non-hematologic malignancies discussed at an institutional spine tumor conference from 2013 to 2016 were evaluated. Rates of Working Group Algorithms adherence were calculated for each type of metastasis. Based on the reasons for algorithm nonadherence, and patient outcomes in such cases, updated Working Group Algorithms recommendations were proposed. RESULTS: In total, 154 eligible patients with 171 spine metastases were evaluated. Rates of algorithm adherence were as follows: asymptomatic (67%), uncomplicated (73%), stable VCF (20%), unstable VCF (32%), and MESCC (41%). The most common deviation from the Working Group Algorithms was surgery for MESCC despite poor prognostic factors, but this treatment strategy was supported based on median survival surpassing 6 months in these patients. CONCLUSIONS: Adherence to the Working Group Algorithm was lowest for MESCC and VCF patients, but many nonadherent treatments were supported by patient survival outcomes. We proposed updates to the Working Group Algorithm based on these findings.