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Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork. Teams should ideally include adult and paediatric endocrinologists, oncologists, cardiologists, surgeons, geneticists, pathologists, radiologists, clinical psychologists and nuclear medicine physicians. Provision of an international Consensus Statement should improve care and outcomes for children and adolescents with these tumours., (© 2024. Crown.)

Objective: Variation exists in approaches to delivery of spine stereotactic radiosurgery (SSRS). Here, the authors describe outcomes following single-fraction SSRS performed using a simultaneous integrated boost for the treatment of prostate cancer spine metastases., Methods: Health records of patients with prostate cancer spine metastases treated with single-fraction SSRS at the authors' institution were reviewed. Treatment was uniform, with 16 Gy to the clinical tumor volume and 18 Gy to the gross tumor volume. The primary endpoint was local recurrence, with secondary endpoints including vertebral fracture and overall survival. Univariate and multivariate competing risk regression models made using the Fine and Gray method were used to identify factors predictive of local recurrence, considering death to be a competing event for local recurrence., Results: A total of 87 targets involving 108 vertebrae in 68 patients were included, with a median follow-up of 22.5 months per treated target. The 1-, 2-, and 4-year cumulative incidence rates of local failure for all targets were 4.6%, 8.4%, and 19%, respectively. The presence of epidural disease (subdistribution hazard ratio [sHR] 5.43, p = 0.04) and SSRS as reirradiation (sHR 16.5, p = 0.02) emerged as significant predictors of local failure in a multivariate model. Hormone sensitivity did not predict local control. Vertebral fracture incidence rates leading to symptoms or requiring intervention at 1, 2, and 4 years were 1.1%, 3.7%, and 8.4%, respectively. In an exploratory analysis of patterns of failure, 3 (25%) failures occurred in the epidural space and only 1 (8%) occurred clearly in the clinical tumor volume. There were several lesions for which the precise location of failure with regard to target volumes was unclear., Conclusions: High rates of local control were observed, particularly for radiotherapy-naïve lesions without epidural disease. Hormone sensitivity was not predictive of local control in this cohort and fracture risk was low. Further research is needed to better predict which patients are at high risk of recurrence and who might benefit from treatment escalation.

(1) Background: Myxopapillary ependymoma (MPE) is a rare tumor of the spine, typically slow-growing and low-grade. Optimal management strategies remain unclear due to limited evidence given the low incidence of the disease. (2) Methods: We analyzed data from 1197 patients with spinal MPE from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2020). Patient demographics, treatment modalities, and survival outcomes were examined using statistical analyses. (3) Results: Most patients were White (89.9%) with a median age at diagnosis of 42 years. Surgical resection was performed in 95% of cases. The estimated 10-year overall survival was 91.4%. Younger age (hazard ratio (HR) = 1.09, p < 0.001) and receipt of surgery (HR = 0.43, p = 0.007) were associated with improved survival. Surprisingly, male sex was associated with worse survival (HR = 1.86, p = 0.008) and a younger age at diagnosis compared to females. (4) Conclusions: This study, the largest of its kind, underscores the importance of surgical resection in managing spinal MPE. The unexpected association between male sex and worse survival warrants further investigation into potential sex-specific pathophysiological factors influencing prognosis. Despite limitations, our findings contribute valuable insights for guiding clinical management strategies for spinal MPE.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm., (© 2024. The Author(s).)

Purpose: A dedicated magnetic resonance imaging simulation (MRsim) for radiation treatment (RT) planning in patients with high-grade glioma (HGG) can detect early radiologic changes, including tumor progression after surgery and before standard of care chemoradiation. This study aimed to determine the effect of using postoperative magnetic resonance imaging (MRI) versus MRsim as the baseline for response assessment and reporting pseudoprogression on follow-up imaging at 1 month (FU1) after chemoradiation., Methods and Materials: Histologically confirmed patients with HGG were planned for 6 weeks of RT in a prospective study for adaptive RT planning. All patients underwent postoperative MRI, MRsim, and follow-up MRI scans every 2 to 3 months. Tumor response was assessed by 3 independent blinded reviewers using Response Assessment in Neuro-Oncology criteria when baseline was either postoperative MRI or MRsim. Interobserver agreement was calculated using Light's kappa., Results: Thirty patients (median age, 60.5 years; IQR, 54.5-66.3) were included. Median interval between surgery and RT was 34 days (IQR, 27-41). Response assessment at FU1 differed in 17 patients (57%) when the baseline was postoperative MRI versus MRsim, including true progression versus partial response or stable disease in 11 (37%) and stable disease versus partial response in 6 (20%) patients. True progression was reported in 19 patients (63.3%) on FU1 when the baseline was postoperative MRI versus 8 patients (26.7%) when the baseline was MRsim (P = .004). Pseudoprogression was observed at FU1 in 12 (40%) versus 4 (13%) patients, when the baseline was postoperative MRI versus MRsim (P = .019). Interobserver agreement between observers was moderate (κ = 0.579; P < .001)., Conclusions: Our study demonstrates the value of acquiring an updated MR closer to RT in patients with HGG to improve response assessment, and accuracy in evaluation of pseudoprogression even at the early time point of first follow-up after RT. Earlier identification of patients with true progression would enable more timely salvage treatments including potential clinical trial enrollment to improve patient outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS)., Materials and Methods: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI)., Results: 70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7-27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm 3 (IQR 5-32) and 52.7 cm 3 (IQR 29.5-87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/β = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7-18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7-25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8-25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782-0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25)., Conclusion: This study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Carbon fiber reinforced polyetheretherketone (CFRP) is a nonmetallic material that is a subject of growing interest in the field of spinal instrumentation manufacturing. The radiolucency and low magnetic susceptibility of CFRP has potential to create less interference with diagnostic imaging compared with titanium implants. However, an objective comparison of the image artifact produced by titanium and CFRP implants has not been described. Spinal oncology, particularly after resection of spinal tumors and at the time of spinal stereotactic radiosurgery planning, relies heavily on imaging interpretation for evaluating resection, adjuvant treatment planning, and surveillance. We present a study comparing measurements of postoperative magnetic resonance imaging artifacts between titanium and CFRP pedicle screw constructs in the setting of separation surgery for metastatic disease., Methods and Materials: The diameter of the signal drop around the screws (pedicle screw artifact) and the diameter of the spinal canal free from artifacts (canal visualization) were measured in consecutive patients who had spinal instrumentation followed by spinal stereotactic radiosurgery in the June 2019 to May 2022 timeframe. The spinal cord presented a shift at the screw level in sagittal images which was also measured (Sagittal Distortion, SagD)., Results: Fifty patients, corresponding to 356 screws and 183 vertebral levels, were evaluated overall. CFRP produced less artifacts in all the 3 parameters compared with titanium: mean pedicle screw artifact (CFRP = 5.8 mm, Ti = 13.2 mm), canal visualization (CFRP = 19.2 mm, Ti = 15.5 mm), and SagD (CFRP = .5 mm, Ti = 1.9 mm), all P < .001. In practice, these findings translate into better-quality magnetic resonance imaging., Conclusions: The initial perceived advantages are easier evaluation of postoperative imaging, facilitating radiation treatment planning, recurrence detection, and avoidance in repeating a suboptimal computed tomography myelogram. Further clinical studies analyzing long-term outcomes of patients treated with CFRP implants are necessary., Competing Interests: Disclosures Amol J. Ghia reports receiving honorarium, speakership, and a grant from Brainlab. Laurence D. Rhines reports receiving consulting fees, research support, and support for attending meetings from icotec ag and Stryker. Martin C. Tom reports receiving a grant from Blue Earth Diagnostics, consulting fees from ViewRay, and payment from Elsevier for lectures/presentations. Robert Y. North has received support for travel/food from Stryker Corporation and Globus Medical, Inc. Claudio E. Tatsui has research support from icotec ag., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Glioblastoma (GBM) poses therapeutic challenges due to its aggressive nature, particularly for patients with poor functional status and/or advanced disease. Hypofractionated radiotherapy (RT) regimens have demonstrated comparable disease outcomes for this population while allowing treatment to be completed more quickly. Here, we report our institutional outcomes of patients treated with 2 hypofractionated RT regimens: 40 Gy/15fx (3w-RT) and 50 Gy/20fx (4w-RT)., Methods: A single-institution retrospective analysis was conducted of 127 GBM patients who underwent 3w-RT or 4w-RT. Patient characteristics, treatment regimens, and outcomes were analyzed. Univariate and multivariable Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). The impact of chemotherapy and RT schedule was explored through subgroup analyses., Results: Median OS for the entire cohort was 7.7 months. There were no significant differences in PFS or OS between 3w-RT and 4w-RT groups overall. Receipt and timing of temozolomide (TMZ) emerged as the variable most strongly associated with survival, with patients receiving adjuvant-only or concurrent and adjuvant TMZ having significantly improved PFS and OS ( P < .001). In a subgroup analysis of patients that did not receive TMZ, patients in the 4w-RT group demonstrated a trend toward improved OS as compared to the 3w-RT group ( P = .12)., Conclusions: This study demonstrates comparable survival outcomes between 3w-RT and 4w-RT regimens in GBM patients. Receipt and timing of TMZ were strongly associated with survival outcomes. The potential benefit of dose-escalated hypofractionation for patients not receiving chemotherapy warrants further investigation and emphasizes the importance of personalized treatment approaches., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: The management of chordoma or chondrosarcoma involving the spine is often challenging due to adjacent critical structures and tumor radioresistance. Spine stereotactic radiosurgery (SSRS) has radiobiologic advantages compared with conventional radiotherapy, though there is limited evidence on SSRS in this population. We sought to characterize the long-term local control (LC) of patients treated with SSRS., Methods: We retrospectively reviewed patients with chordoma or chondrosarcoma treated with dose-escalated SSRS, defined as 24 Gy in 1 fraction to the gross tumor volume. Overall survival (OS) was calculated by Kaplan-Meier functions. Competing risk analysis using the cause-specific hazard function estimated LC time., Results: Fifteen patients, including 12 with chordoma and 3 with chondrosarcoma, with 22 lesions were included. SSRS intent was definitive, single-modality in 95% of cases (N = 21) and post-operative in 1 case (5%). After a median censored follow-up time of 5 years (IQR 4 to 8 years), median LC time was not reached (IQR 8 years to not reached), with LC rates of 100%, 100%, and 90% at 1 year, 2 years, and 5 years. The median OS was 8 years (IQR 3 years to not reached). Late grade 3 toxicity occurred after 23% of treatments (N = 5, fracture), all of which were managed successfully with stabilization., Conclusion: Definitive dose-escalated SSRS to 24 Gy in 1 fraction appears to be a safe and effective treatment for achieving durable local control in chordoma or chondrosarcoma involving the spine, and may hold particular importance as a low-morbidity alternative to surgery in selected cases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: WHO grade 4 gliomas are rare in the pediatric and adolescent and young adult (AYA) population. We evaluated prognostic factors and outcomes in the pediatric versus AYA population., Methods: This retrospective pooled study included patients less than 30 years old (yo) with grade 4 gliomas treated with modern surgery and radiotherapy. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analysis., Results: Ninety-seven patients met criteria with median age 23.9 yo at diagnosis. Seventy-seven patients were ≥ 15 yo (79%) and 20 patients were < 15 yo (21%). Most had biopsy-proven glioblastoma (91%); the remainder had H3 K27M-altered diffuse midline glioma (DMG; 9%). All patients received surgery and radiotherapy. Median PFS and OS were 20.9 months and 79.4 months, respectively. Gross total resection (GTR) was associated with better PFS in multivariate analysis [HR 2.00 (1.01-3.62), p = 0.023]. Age ≥ 15 yo was associated with improved OS [HR 0.36 (0.16-0.81), p = 0.014] while female gender [HR 2.12 (1.08-4.16), p = 0.03] and DMG histology [HR 2.79 (1.11-7.02), p = 0.029] were associated with worse OS. Only 7% of patients experienced grade 2 toxicity. 62% of patients experienced tumor progression (28% local, 34% distant). Analysis of salvage treatment found that second surgery and systemic therapy significantly improved survival., Conclusion: Age is a significant prognostic factor in WHO grade 4 glioma, which may reflect age-related molecular alterations in the tumor. DMG was associated with worse OS than glioblastoma. Reoperation and systemic therapy significantly increased survival after disease progression. Prospective studies in this population are warranted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC., Patients and Methods: This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS)., Results: Thirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7-24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophagocytic lymphohistiocytosis. The estimated 4-month intracranial PFS rate was 70.7%., Conclusion: Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for intracranial treatment response., Competing Interests: Competing interests: MA reports research funding (to institution) from Genentech, Nektar Therapeutics, Merck, GlaxoSmithKline, Novartis, Jounce Therapeutics, Bristol-Myers Squibb, Eli Lilly, Adaptimmune, Shattuck Lab, and Gilead; consulting fees from GlaxoSmithKline, Shattuck Lab, Bristol-Myers Squibb, and AstraZeneca; speaker fees from AstraZeneca, Nektar Therapeutics, Society for Immunotherapy of Cancer (SITC) outside of the submitted work. JW reports research funding (to institution) from GlaxoSmithKline, Bristol-Meyers Squibb, Merck, Nanobiotix, RefleXion, Alkermes, Artidis, Mavu Pharma, Takeda, Varian, Checkmate Pharmaceuticals, HotSpot Therapeutics, Gilead and Kiromic; consulting fees from Lifescience Dynamics Limited; speaker fees from Ventana Medical Systems, US Oncology, Alkermes, Boehringer Ingelheim, Accuray and RSS; support for attending meetings and/or travel from Nanobiotix, RefleXion, Varian, Shandong University, The Korea Society of Radiology, Aileron Therapeutics and Ventan; patents planned, issued or pending MP470 (amuvatinib), MRX34 regulation of PD-L1, XRT technique to overcome immune resistance; participation in a data safety monitoring board or advisory board for Legion Healthcare Partners, RefleXion Medical, MolecularMatch, Merck, AstraZeneca, Aileron Therapeutics, OncoResponse, Checkmate Pharmaceuticals, Mavu Pharma, Alpine Immune Sciences, Ventana Medical Systems, Nanobiotix, China Medical Tribune, GI Innovation, Genentech and Nanorobotix. He has stock or stock options from Alpine Immune Sciences, Checkmate Pharmaceuticals, Healios, Mavu Pharma, Legion Healthcare Partners, MolecularMatch, Nanorobotix, OncoResponse, and RefleXion outside of the submitted work. CT reports research funding (to institution) from Noxopharm; consulting/advisory role for Bayer, Diffusion Pharmaceuticals, and Siemens; royalties or licenses from Wolter Kluwer, Stanford OTL, and Osler Institute; consulting fees from Bayer, Diffusion Pharmaceuticals, and Siemens outside of the submitted work. GRB reports research funding (to institution) from Amgen, Bayer, Adaptimmune, Elelixis, Daiichi Sankyo, GlaxoSmithKline, Immatics, Immunocore, Incyte, Kite Pharma, Macrogenics, Torque, AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, MedImmune, Merck, Novartis, Roche, Sanofi, Xcovery, Tmunity Therapeutics, Regeneron, BeiGene, Repertoire Immune Medicines, Verastem, CytomX Therapeutics, Duality Biologics, and Mythic Therapeutics; consulting fees from AbbVie, Adicet, Amgen, Ariad, Bayer, Clovis Oncology, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Instil Bio, Genentech, Genzyme, Gilead, Lilly, Janssen, MedImmune, Merck, Novartis, Roche, Sanofi, Tyme Oncology, Xcovery, Virogin Biotech, Maverick Therapeutics, BeiGene, Regeneron, CytomX Therapeutics, InterVenn Biosciences, Onconova Therapeutics, and Seagen; participation in a data safety monitoring board or advisory board for Virogin Biotech and Maverick Therapeutics; stock or stock options for Virogin Biotech, and other financial or non-financial interest from Johnson & Johnson/Janssen (immediated family member employed) outside of the submitted work. KDW reports employment and stock options from Merck (financial relationship started after the conduct of study) outside of the submitted work. YYE reports research funding (to institution) from Spectrum, AstraZeneca, Takeda, Eli Lilly, Xcovery, Tuning Point Therapeutics, BluPrint, Elevation Oncology; consulting fees from AstraZeneca, Eli Lilly, Takeda, Spectrum and Turning Point; support for attending meetings and/or travel from Eli Lilly outside of the submitted work. XL reports research funding (to institution) from Eli Lilly, EMD Serono, Regeneron, and Boehringer Ingelheim; consulting fees from EMD Serono (Merck KGaA), AstraZeneca, Spectrum Pharmaceutics, Novartis, Eli Lilly, Boehringer Ingelheim, Hengrui Therapeutics, Janssen, Blueprint Medicines, Sensei Biotherapeutics, and AbbVie outside of the submitted work. TC reports research funding (to institution) from MedImmune/AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and EMD Serono; consulting fees from MedImmune/AstraZeneca, Bristol-Myers Squibb, EMD Serono, Merck & Co, Genentech, Arrowhead Pharmaceuticals, and Regeneron; speaker fees from SITC, Bristol-Myers Squibb, Roche, Medscape, and PeerView; support for attending meetings and/or travel from Dava Oncology and Bristol-Myers Squibb outside of the submitted work. MVN reports research funding (to institution) from Mirati, Novartis, Checkmate, Alaunos/Ziopharm, AstraZeneca, Pfizer, and Genentech; consulting fees from Mirati, Merck/MSD, and Genentech outside of the submitted work. FS reports research funding (to institution) from Amgen, Mirati Therapeutics, Revolution Medicines, Pfizer, Novartis, and Merck & Co; consulting fees from AstraZeneca, Amgen, Novartis, BeiGene, Guardant Health, BergenBio, Navire Pharma, Tango Therapeutics, and Calithera Biosciences; speaker free from European Society for Medical Oncology, Japanese Lung Cancer Society, Medscape, Intellisphere, VSPO McGill Universite de Montreal, RV Mais Promocao Eventos, MJH Life Sciences, IdeoLogy Health, MI&T, PER, and CURIO; support for attending meetings and/or travel from Dava Oncology, Tango Therapeutics, America Association for Cancer Research, International Association for the Study of Lung Cancer, MJH Life Sciences, IdeoLogy Health, MI&T, PER, and CURIO; participation in a data safety monitoring board or advisory board for AstraZeneca, Amgen, Novartis, BeiGene, Guardant Health, BergenBio, and Calithera Biosciences; stock or stock options from BioNTech and Moderna outside of the submitted work. RF reports research funding (to the institution) from Prelude, Ayala, Merck, Genentech, Pfizer, Rakuten, Nanobiotix, EMD Serono, ISA, Viracta, and Gilead; consulting fees from Regeneron, Sanofi, Ayala, Prelude, Elevar, G1, Guidepoint, Expert Connect, Remix, and Eisai outside of the submitted work. JVH reports research funding (to the institution) from AstraZeneca, Bristol-Myers Squibb, Spectrum, and Takeda; personal fees and other support from AstraZeneca, EMD Serono, Boehringer Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Hengrui Therapeutics, Eli Lilly, Spectrum, Sanofi, Takeda, Mirati Therapeutics, BMS, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, Pneuma Respiratory, Kairos Venture Investments, Roche, Leads Biolabs, RefleXion, and Chugai Pharmaceuticals; royalties and licensing fees: Spectrum outside the submitted work. JL reports support from Bristol-Myers Squibb (study funding support for the investigator-initiated trial presented in this manuscript); grants or contracts from Bristol-Myers Squibb. No disclosures have been reported by the other authors., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Dose constraints for reirradiation of recurrent primary brain tumors are not well-established. This study was conducted to prospectively evaluate composite dose constraints for conventionally fractionated brain reirradiation., Methods and Materials: A single-institution, prospective study of adults with previously irradiated, recurrent brain tumors was performed. For 95% of patients, electronic dosimetry records from the first course of radiation (RT1) were obtained and deformed onto the simulation computed tomography for the second course of radiation (RT2). Conventionally fractionated treatment plans for RT2 were developed that met protocol-assigned dose constraints for RT2 alone and the composite dose of RT1 + RT2. Prospective composite dose constraints were based on histology, interval since RT1, and concurrent bevacizumab. Patients were followed with magnetic resonance imaging including spectroscopy and perfusion studies. Primary endpoint was the rate of symptomatic brain necrosis at 6 months after RT2., Results: Patients were enrolled from March 2017 to May 2018; 20 were evaluable. Eighteen had glioma, 1 had atypical choroid plexus papilloma, and 1 had hemangiopericytoma. Nineteen patients were treated with volumetric modulated arc therapy, and one was treated with protons. Median RT1 dose was 57 Gy (range, 50-60 Gy). Median RT1-RT2 interval was 49 months (range, 9-141 months). Median RT2 dose was 42.4 Gy (range, 36-60 Gy). Median planning target volume was 186 cc (range, 8-468 cc). Nineteen of 20 patients (95%) were free of grade 3+ central nervous system necrosis. One patient had grade 3+ necrosis 2 months after RT2; the patient recovered fully and lived another 18 months until dying of disease progression. Median overall survival from RT2 start for all patients was 13.3 months (95% credible interval, 6.3-20.7); for patients with glioblastoma, 11.5 months (95% credible interval, 6.1-20.1)., Conclusions: Brain reirradiation can be safely performed with conventionally fractionated regimens tailored to previous dose distributions. The prospective composite dose constraints described here are a starting point for future studies of conventionally fractionated reirradiation., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Though metastasis-directed therapy (MDT) has the potential to improve overall survival (OS), appropriate patient selection remains challenging. We aimed to develop a model predictive of OS to refine patient selection for clinical trials and MDT., Patients and Methods: We assembled a multi-institutional cohort of patients treated with MDT (stereotactic body radiation therapy, radiosurgery, and whole brain radiation therapy). Candidate variables for recursive partitioning analysis were selected per prior studies: ECOG performance status, time from primary diagnosis, number of additional non-target organ systems involved (NOS), and intracranial metastases., Results: A database of 1,362 patients was assembled with 424 intracranial, 352 lung, and 607 spinal treatments (n=1,383). Treatments were split into training (TC) (70%, n=968) and internal validation (IVC) (30%, n=415) cohorts. The TC had median ECOG of 0 (interquartile range [IQR]: 0-1), NOS of 1 (IQR: 0-1), and OS of 18 months (IQR: 7-35). The resulting model components and weights were: ECOG = 0, 1, and > 1 (0, 1, and 2); 0, 1, and > 1 NOS (0, 1, and 2); and intracranial target (2), with lower scores indicating more favorable OS. The model demonstrated high concordance in the TC (0.72) and IVC (0.72). The score also demonstrated high concordance for each target site (spine, brain, and lung)., Conclusion: This pre-treatment decision tool represents a unifying model for both intracranial and extracranial disease and identifies patients with the longest survival after MDT who may benefit most from aggressive local therapy. Carefully selected patients may benefit from MDT even in the presence of intracranial disease, and this model may help guide patient selection for MDT., Competing Interests: The wife of RK is a senior technical product manager for GE Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kowalchuk, Mullikin, Breen, Gits, Florez, De, Harmsen, Rose, Siontis, Costello, Morris, Lucido, Olivier, Stish, Laack, Park, Owen, Ghia, Brown and Merrell.)

Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

Background: This study was aimed at developing and validating a decision-making tool predictive of overall survival (OS) for patients receiving stereotactic body radiation therapy (SBRT) for spinal metastases., Methods: Three hundred sixty-one patients at one institution were used for the training set, and 182 at a second institution were used for external validation. Treatments most commonly involved one or three fractions of spine SBRT. Exclusion criteria included proton therapy and benign histologies., Results: The final model consisted of the following variables and scores: Spinal Instability Neoplastic Score (SINS) ≥ 6 (1), time from primary diagnosis < 21 months (1), Eastern Cooperative Oncology Group (ECOG) performance status = 1 (1) or ECOG performance status > 1 (2), and >1 organ system involved (1). Each variable was an independent predictor of OS (p < .001), and each 1-point increase in the score was associated with a hazard ratio of 2.01 (95% confidence interval [CI], 1.79-2.25; p < .0001). The concordance value was 0.75 (95% CI, 0.71-0.78). The scores were discretized into three groups-favorable (score = 0-1), intermediate (score = 2), and poor survival (score = 3-5)-with 2-year OS rates of 84% (95% CI, 79%-90%), 46% (95% CI, 36%-59%), and 21% (95% CI, 14%-32%), respectively (p < .0001 for each). In the external validation set (182 patients), the score was also predictive of OS (p < .0001). Increasing SINS was predictive of decreased OS as a continuous variable (p < .0001)., Conclusions: This novel score is proposed as a decision-making tool to help to optimize patient selection for spine SBRT. SINS may be an independent predictor of OS., (© 2022 American Cancer Society.)

Purpose: There has been limited work assessing the use of re-irradiation (re-RT) for local failure following stereotactic spinal radiosurgery (SSRS). We reviewed our institutional experience of conventionally-fractionated external beam radiation (cEBRT) for salvage therapy following SSRS local failure., Materials and Methods: We performed a retrospective review of 54 patients that underwent salvage conventional re-RT at previously SSRS-treated sites. Local control following re-RT was defined as the absence of progression at the treated site as determined by magnetic resonance imaging., Results: Competing risk analysis for local failure was performed using a Fine-Gray model. The median follow-up time was 25 months and median overall survival (OS) was 16 months (95% confidence interval [CI], 10.8-24.9 months) following cEBRT re-RT. Multivariable Cox proportional-hazards analysis revealed Karnofsky performance score prior to re-RT (hazard ratio [HR] = 0.95; 95% CI, 0.93-0.98; p = 0.003) and time to local failure (HR = 0.97; 95% CI, 0.94-1.00; p = 0.04) were associated with longer OS, while male sex (HR = 3.92; 95% CI, 1.64-9.33; p = 0.002) was associated with shorter OS. Local control at 12 months was 81% (95% CI, 69.3-94.0). Competing risk multivariable regression revealed radioresistant tumors (subhazard ratio [subHR] = 0.36; 95% CI, 0.15-0.90; p = 0.028) and epidural disease (subHR = 0.31; 95% CI, 0.12-0.78; p =0.013) were associated with increased risk of local failure. At 12 months, 91% of patients maintained ambulatory function., Conclusion: Our data suggest that cEBRT following SSRS local failure can be used safely and effectively. Further investigation is needed into optimal patient selection for cEBRT in the retreatment setting.

Purpose: Intensity modulated radiation therapy (RT) for spine metastases using a simultaneous integrated boost (SSIB) was shown as an alternative to the treatment of select osseous metastases that are not amenable to spine stereotactic radiosurgery. We sought to update our clinical experience using SSIB in patients for whom dose escalation was warranted but spine stereotactic radiosurgery was not feasible., Methods and Materials: A total of 58 patients with 63 spinal metastatic sites treated with SSIB between 2012 and 2021 were retrospectively reviewed. The gross tumor volume and clinical target volume were prescribed 40 and 30 Gy in 10 fractions, respectively., Results: The median follow-up time was 31 months. Of 79% of patients who reported pain before RT with SSIB, 82% reported an improvement following treatment. Patient-reported pain scores on a 10-point scale revealed a significant decrease in pain at 1, 3, 6, and 12 months after SSIB (P < .0001). Additionally, there were limited toxicities; only 1 patient suffered grade 3 toxicity (pain) following RT. There were no reports of radiation-induced myelopathy at last follow-up, and 8 patients (13%) experienced a vertebral column fracture post-treatment. Local control was 88% (95% confidence interval [CI], 80%-98%) and 74% (95% CI, 59%-91%) at 1 and 2 years, respectively. Overall survival was 64% (95% CI, 53%-78%) and 45% (95% CI, 34%-61%) at 1 and 2 years, respectively. The median overall survival was 18 months (95% CI, 13-27 months). Multivariable analysis using patient, tumor, and dosimetric characteristics revealed that a higher Karnofsky performance status before RT (hazard ratio, 0.44, 0.22-0.89; P = .02) was associated with longer survival., Conclusions: These data demonstrate excellent pain relief and local control with limited acute toxicities following treatment with RT using SSIB to 40 Gy. Collectively, our data suggest that dose escalation to spine metastases using SSIB can be safe and efficacious for patients, especially those with radioresistant disease. Further investigation is warranted to validate these findings., (Published by Elsevier Inc.)

Spine is the most frequently involved site of osseous metastases. With improved disease-specific survival in patients with Stage IV cancer, durability of local disease control has become an important goal for treatment of spinal metastases. Herein, we review the multidisciplinary management of spine metastases, including conventional external beam radiation therapy, spine stereotactic radiosurgery, and minimally invasive and open surgical treatment options. We also present a simplified framework for management of spinal metastases used at The University of Texas MD Anderson Cancer Center, focusing on the important decision points where the radiologist can contribute.

Purpose: The benefit of local consolidative therapy (LCT) for oligometastasis across histologies remains uncertain. EXTernal beam radiation to Eliminate Nominal metastatic Disease (EXTEND; NCT03599765) is a randomized phase 2 basket trial evaluating the effectiveness of LCT for oligometastatic solid tumors. We report here the prospective results of the single-arm "lead-in" phase intended to identify histologies most likely to accrue to histology-specific endpoints in the randomized phase., Methods and Materials: Eligible histologies included colorectal, sarcoma, lung, head and neck, ovarian, renal, melanoma, pancreatic, prostate, cervix/uterine, breast, and hepatobiliary. Patients received LCT to all sites of active metastatic disease and primary/regional disease (as applicable) plus standard-of-care systemic therapy or observation. The primary endpoint in EXTEND was progression-free survival (PFS), and the primary endpoint of the lead-phase was histology-specific accrual feasibility. Adverse events were graded by Common Terminology Criteria for Adverse Events version 4.0., Results: From August 2018 through January 2019, 50 patients were enrolled and 49 received definitive LCT. Prostate, breast, and kidney were the highest enrolling histologies and identified for independent accrual in the randomization phase. Most patients (73%) had 1 or 2 metastases, most often in lung or bone (79%), and received ablative radiation (62%). Median follow-up for censored patients was 38 months (range, 16-42 months). Median PFS was 13 months (95% confidence interval, 9-24), 3-year overall survival rate was 73% (95% confidence interval, 57%-83%), and local control rate was 98% (93 of 95 tumors). Two patients (4%) had Common Terminology Criteria for Adverse Events grade 3 toxic effects related to LCT; no patient had grade 4 or 5 toxic effects., Conclusions: The prospective lead-in phase of the EXTEND basket trial demonstrated feasible accrual, encouraging PFS, and low rates of severe toxic effects at mature follow-up. The randomized phase is ongoing with histology-based baskets that will provide histology-specific evidence for LCT in oligometastatic disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Spine stereotactic body radiation therapy (SBRT) uses highly conformal dose distributions and sharp dose gradients to cover targets in proximity to the spinal cord or cauda equina, which requires precise patient positioning and immobilization to deliver safe treatments., Aims: Given some limitations with the BodyFIX system in our practice, we sought to evaluate the accuracy and efficiency of the Klarity SBRT patient immobilization system in comparison to the BodyFIX system., Methods: Twenty-three patients with 26 metastatic spinal lesions (78 fractions) were enrolled in this prospective observational study with one of two systems - BodyFIX (n = 11) or Klarity (n = 12). All patients were initially set up to external marks and positioned to match bony anatomy on ExacTrac images. Table corrections given by ExacTrac during setup and intrafractional monitoring and deviations from pre- and posttreatment CBCT images were analyzed., Results: For initial setup accuracy, the Klarity system showed larger differences between initial skin mark alignment and the first bony alignment on ExacTrac than BodyFIX, especially in the vertical (mean [SD] of 5.7 mm [4.1 mm] for Klarity vs. 1.9 mm [1.7 mm] for BodyFIX, p-value < 0.01) and lateral (5.4 mm [5.1 mm] for Klarity vs. 3.2 mm [3.2 mm] for BodyFIX, p-value 0.02) directions. For set-up stability, no significant differences (all p-values > 0.05) were observed in the maximum magnitude of positional deviations between the two systems. For setup efficiency, Klarity system achieved desired bony alignment with similar number of setup images and similar setup time (14.4 min vs. 15.8 min, p-value = 0.41). For geometric uncertainty, systematic and random errors were found to be slightly less with Klarity than with BodyFIX based on an analytical calculation., Conclusion: With image-guided correction of initial alignment by external marks, the Klarity system can provide accurate and efficient patient immobilization. It can be a promising alternative to the BodyFIX system for spine SBRT while providing potential workflow benefits depending on one's practice environment., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

The modern management of spinal metastases requires a multidisciplinary approach that includes radiation oncologists, surgeons, medical oncologists, and diagnostic and interventional radiologists. The diagnostic radiologist can play an important role in the multidisciplinary team and help guide assessment of disease and selection of appropriate therapy. The assessment of spine metastases is best performed on MRI, but imaging from other modalities is often needed. We provide a review of the clinical and imaging features that are needed by the multidisciplinary team caring for patients with spine metastases and stress the importance of the spine radiologist taking responsibility for synthesizing imaging features across multiple modalities to provide a report that advances patient care.

Purpose: We evaluated a cohort of patients with cardiac angiosarcomas (CA) who developed brain metastases (BM) to define outcomes and intracranial hemorrhage (IH) risk., Methods: We reviewed 26 consecutive patients with BM treated between 1988 and 2020 identified from a departmental CA (n=103) database. Causes of death were recorded, and a terminal hemorrhage (TH) was defined as an IH that caused death or prompted a transfer to hospice., Results: The prevalence of BM was 25% (n=26/103). A total of 23 patients (88%) had IH, including 21 (81%) at initial BM diagnosis, of which 18 (86%) required hospitalization. The median platelet count at the time of IH was 235k (interquartile range, 108 to 338k).Nearly all patients died of disease (n=23, 88%) and most patients died from TH (n=13, 57%). TH occurred at BM presentation in 6 (46%) patients, whereas 3 (23%) had TH from known but untreated lesions, 2 (15%) had continued uncontrolled IH during radiation therapy, and 2 (15%) from new BM. Platelet count <50k was not associated with TH (P=0.25).Subsequent IH occurred in 9 patients (35%), and importantly, no patients who completed radiation therapy (n=10) for BM died from TH., Conclusion: Patients with CA frequently develop BM, and the risk of IH is high, resulting in an alarming rate of TH despite normal platelet counts. Therefore, early diagnosis and intervention are warranted. We recommend surveillance brain imaging, and importantly, once BM is detected, prompt local therapy is warranted to try and mitigate the risk of TH., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To study whether delivering definitive radiotherapy (RT) to sites of oligoprogression in metastatic renal cell carcinoma (mRCC) enabled deferral of systemic therapy (ST) changes without compromising disease control or survival., Patients and Methods: We identified patients with mRCC who received RT to three or fewer sites of extracranial progressive disease between 2014 and 2019 at a large tertiary cancer centre. Inclusion criteria were: (1) controlled disease for ≥3 months before oligoprogression, (2) all oligoprogression sites treated with a biologically effective dose of ≥100 Gy, and (3) availability of follow-up imaging. Time-to-event end-points were calculated from the start of RT., Results: A total of 72 patients were identified (median follow-up 22 months, 95% confidence interval [CI] 19-32 months), with oligoprogressive lesions in lung/mediastinum (n = 35), spine (n = 30), and non-spine bone (n = 5). The most common systemic therapies before oligoprogression were none (n = 33), tyrosine kinase inhibitor (n = 23), and immunotherapy (n = 13). At 1 year, the local control rate was 96% (95% CI 87-99%); progression-free survival (PFS), 52% (95% CI 40-63%); and overall survival, 91% (95% CI 82-96%). At oligoprogression, ST was escalated (n = 16), maintained (n = 49), or discontinued (n = 7), with corresponding median (95% CI) PFS intervals of 19.7 (8.2-27.2) months, 10.1 (6.9-13.2) months, and 9.8 (2.4-28.9) months, respectively. Of the 49 patients maintained on the same ST at oligoprogression, 21 did not subsequently have ST escalation., Conclusion: Patients with oligoprogressive mRCC treated with RT had comparable PFS regardless of ST strategy, suggesting that RT may be a viable approach for delaying ST escalation. Randomised controlled trials comparing treatment of oligoprogression with RT vs ST alone are needed., (© 2021 The Authors BJU International © 2021 BJU International.)

Purpose: To present interobserver variability in thecal sac (TS) delineation based on contours generated by 8 radiation oncologists experienced in spine stereotactic body radiation therapy and to propose contouring recommendations to standardize practice., Methods and Materials: In the setting of a larger contouring study that reported target volume delineation guidelines specific to sacral metastases, 8 academically based radiation oncologists with dedicated spine stereotactic body radiation therapy programs independently contoured the TS as a surrogate for the cauda equina and intracanal spinal nerve roots. Uniform treatment planning simulation computed tomography datasets fused with T1, T2, and T1 post gadolinium magnetic resonance imaging for each case were distributed to each radiation oncologist. All contours were analyzed and agreement was calculated using both Dice similarity coefficient and simultaneous truth and performance level estimation with kappa statistics., Results: A fair level of simultaneous truth and performance level estimation agreement was observed between practitioners, with a mean kappa agreement of 0.38 (range, 0.210.55) and the mean Dice similarity coefficient (± standard deviation, with range) was 0.43 (0.36 ± 0.1 to -0.53 ±0.1). Recommendations for a reference TS contour, accounting for the variations in practice observed in this study, include contouring the TS to encompass all the intrathecal spinal nerve roots, and caudal to the termination of the TS, the bony canal can be contoured as a surrogate for the extra thecal nerves roots that run within it., Conclusions: This study shows that even among high-volume practitioners, there is a lack of uniformity when contouring the TS. Further modifications may be required once dosimetric data on nerve tolerance to ablative doses, and pattern of failure analyses of clinical data sets using these recommendations, become available. The contouring recommendations were designed as a guide to enable consistent and safe contouring across general practice., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This secondary image analysis of a randomized trial of proton radiotherapy (PT) versus photon intensity-modulated radiotherapy (IMRT) compares tumor progression based on clinical radiological assessment versus 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 versus 11.2 months PT ( P = .14). Median RANO-PFS was 8.2 (range: 6.9, 12): 8.9 months IMRT versus 6.6 months PT ( P = .24). RANO-PFS was significantly shorter than clinical PFS overall ( P = .001) and for both the IMRT ( P = .01) and PT ( P = .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., Conclusions: Based on this secondary analysis of a trial of PT versus IMRT for glioblastoma, 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., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Patients with previously irradiated metastatic epidural spinal cord compression (MESCC) who are not surgical candidates are at high risk of neurologic deterioration due to disease in the setting of limited treatment options. We seek to establish the feasibility of using salvage spine stereotactic radiosurgery (SSRS) allowing for spinal cord dose constraint relaxation as the primary management of MESCC in inoperable patients monitoring for radiation related toxicity and radiographic local control (LC)., Methods: Inoperable patients with previously irradiated MESCC were enrolled on this prospective Phase 1 single institution protocol. Single fraction SSRS was delivered to a prescription dose of 18 Gy. Spinal cord constraint relaxation was performed incrementally from an initial allowable Dmax cohort of 8 Gy to 14 Gy in the final planned cohort. Patients were monitored every 3 months with follow-up visits and MRI scans., Results: The trial was closed early due to slow accrual. From 2011 to 2014, 11 patients were enrolled of which 9 patients received SSRS. Five patients were in the 8 Gy cord Dmax cohort and 4 in the 10 Gy cord Dmax cohort.The median overall survival (OS) was 11.9 months (95% CI 7.1, 22 months). Of the 9 patients treated with SSRS, 1 died prior to post-SSRS evaluation. Of the remaining 8 patients, 5 experienced a local failure. Three of the five were treated with surgery while two received systemic therapy. Two of the five failures ultimately resulted in loss of neurologic function. The median LC was 9.1 months (95%CI 4.8, 20.1 months). With a median clinical follow-up of 6.8 months, there were no cases of RM., Conclusions: Despite the limited life expectancy in this high-risk cohort of patients, strategies to optimize LC are necessary to prevent neurologic deterioration. Larger prospective trials exploring optimal dose/fractionation and cord constraints are required., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: We investigated differences in radiation-induced grade 3+ lymphopenia (G3+L), defined as an absolute lymphocyte count (ALC) nadir of <500 cells/µL, after proton therapy (PT) or X-ray (photon) therapy (XRT) for patients with glioblastoma (GBM)., 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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The objective of this study was to present the results of a consecutive series of 120 cases treated with spinal laser interstitial thermal therapy (sLITT) to manage epidural spinal cord compression (ESCC) from metastatic tumors., Methods: The electronic records of patients treated from 2013 to 2019 were analyzed retrospectively. Data collected included demographic, pathology, clinical, operative, and imaging findings; degree of epidural compression before and after sLITT; length of hospital stay; complications; and duration before subsequent oncological treatment. Independent-sample t-tests were used to compare means between pre- and post-sLITT treatments. Survival was estimated by the Kaplan-Meier method. Multivariate logistic regression was used to analyze predictive factors for local recurrence and neurological complications., Results: There were 110 patients who underwent 120 sLITT procedures. Spinal levels treated included 5 cervical, 8 lumbar, and 107 thoracic. The pre-sLITT Frankel grades were E (91.7%), D (6.7%), and C (1.7%). The preoperative ESCC grade was 1c or higher in 92% of cases. Metastases were most common from renal cell carcinoma (39%), followed by non-small cell lung carcinoma (10.8%) and other tumors (35%). The most common location of ESCC was in the vertebral body (88.3%), followed by paraspinal/foraminal (7.5%) and posterior elements (4.2%). Adjuvant radiotherapy (spinal stereotactic radiosurgery or conventional external beam radiation therapy) was performed in 87 cases (72.5%), whereas 33 procedures (27.5%) were performed as salvage after radiotherapy options were exhausted. sLITT was performed without need for spinal stabilization in 87 cases (72.5%). Post-sLITT Frankel grades were E (85%), D (10%), C (4.2%), and B (0.8%); treatment was associated with a median decrease of 2 ESCC grades. The local control rate at 1 year was 81.7%. Local control failure occurred in 25 cases (20.8%). The median progression-free survival was not reached, and overall survival was 14 months. Tumor location in the paraspinal region and salvage treatment were independent predictors of local recurrence, with hazard ratios of 6.3 and 3.3, respectively (p = 0.01). Complications were observed in 22 cases (18.3%). sLITT procedures performed in the lumbar and cervical spine had hazard ratios for neurological complications of 15.4 and 17.1 (p < 0.01), respectively, relative to the thoracic spine., Conclusions: sLITT is safe and provides effective local control for high-grade ESCC from vertebral metastases in the thoracic spine, particularly when combined with adjuvant radiotherapy. The authors propose considering sLITT as an alternative to open surgery in selected patients with spinal metastases.

Background and Purpose: Spine stereotactic radiosurgery (SSRS) offers high rates of local control in a critical anatomic area by delivering precise, ablative doses of radiation for treatment of spine metastases. However, the dose tolerance of the spinal cord (SC) after SSRS with relation to radiation myelopathy (RM) is not well-described., Materials and Methods: We reviewed patients who underwent single fraction, de novo SSRS from 2012-2017 and received >12 Gy Dmax to the SC, defined using MRI-CT fusion without PRV expansion. The standard SC constraint was D0.01cc ≤ 12 Gy. Local control was estimated with the Kaplan-Meier method. Bayesian analysis was used to compute posterior probabilities for RM., Results: A total of 146 SSRS treatments among 132 patients were included. The median SC Dmax was 12.6 Gy (range, 12.1-17.1 Gy). The SC Dmax was >12 and <13 Gy for 109 (75%) treatments, ≥13 and <14 Gy for 28 (19%) treatments, and ≥14 Gy for 9 (6%) treatments. The 1-year local control rate was 94%. With a median follow-up time of 42 months, there were zero (0) RM events observed. Assuming a prior 4.3% risk of RM, the true rate of RM for SC Dmax of ≤14 Gy was computed as <1% with 98% probability., Conclusion: In one of the largest series of patients treated with single fraction, de novo SSRS, there were no cases of RM observed with a median follow-up of 42 months. These data support safe relaxation of MRI-defined SC dose up to D0.01cc ≤ 12 Gy, which corresponds to <1% risk of RM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Dose escalation via stereotactic radiation therapy techniques has been necessary for hepatobiliary malignancies in the primary and oligometastatic setting, but such dose escalation is challenging for spine metastases due to spinal cord proximity. Here, we investigate the role of spine stereotactic radiosurgery (SSRS) in the management of such metastases., Methods: We retrospectively reviewed patients treated with SSRS to spinal metastases from hepatobiliary malignancies between 2004 and 2017 at our Institution. We used the Kaplan-Meier method to calculate overall survival (OS) and local control (LC) and Cox regression analysis to identify factors associated with disease-related outcomes., Results: We identified 28 patients treated to 43 spinal metastases with SSRS for either HCC or cholangiocarcinoma. The 1-year LC and OS were 85% and 23%, respectively. The median time to death was 6.2 months, while median time to local failure was not reached. Tumor volume > 60 cc (SHR 6.65, p = 0.03) and Bilsky ≥ 1c (SHR 4.73, p = 0.05) predicted for poorer LC, while BED 10  > 81 Gy trended towards better local control (SHR 4.35, p = 0.08). Child-Pugh Class (HR 3.02, p = 0.003), higher PRISM Group (HR 3.49, p = 0.001), and systemic disease progression (HR 3.65, p = 0.001) were associated with worse mortality based on univariate modeling in patients treated with SSRS; on multivariate analysis, PRISM Group (HR 2.28, p = 0.03) and systemic disease progression (HR 2.67, p = 0.03) remained significant. Four patients (10%) developed compression deformity and one patient (2%) developed radiation neuritis., Conclusion: SSRS provides durable local control in patients with metastatic hepatobiliary malignancies, with higher BED necessary to ensure excellent LC. PRISM scoring is a promising prognostic tool to aid SSRS patient selection.

We describe the institutional guidelines of a major tertiary cancer center with regard to using hypofractionated radiation regimens to treat glioblastoma as a measure to minimize exposure to coronavirus disease 2019 (COVID-19) while not sacrificing clinical outcomes. Our guidelines review level one evidence of various hypofractionated regimens, and recommend a multidisciplinary approach while balancing the risk of morbidity and mortality among individuals at high risk for severe illness from COVID-19 infection. We also briefly outline strategies our department is taking in mitigating risk among our cancer patients undergoing radiation., (© 2020 The Author(s).)

Spinal laser interstitial thermotherapy in combination with spinal stereotactic radiosurgery has been developed as a percutaneous minimally invasive approach for the treatment of spinal metastasis. The rational and indications for this hybrid therapy are discussed, along with a brief description of the surgical technique and results. It has been the authors' experience that selected cases of high-grade metastatic epidural spinal cord compression can be effectively treated, achieving durable local control. Lessons learned during the performance of more than 100 cases are reported in addition to future directions for this treatment modality., Competing Interests: Disclosure Drs R.A. Vega and A.J. Ghia have nothing to disclose. Dr C.E. Tatsui receives research support from Medtronic inc., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose: To interrogate inter-observer variability in gross tumour volume (GTV) and clinical target volume (CTV) delineation specific to the treatment of sacral metastases with spinal stereotactic body radiation therapy (SBRT) and develop CTV consensus contouring recommendations., Materials and Methods: Nine specialists with spinal SBRT expertise representing 9 international centres independently contoured the GTV and CTV for 10 clinical cases of metastatic disease within the sacrum. Agreement between physicians was calculated with an expectation minimisation algorithm using simultaneous truth and performance level estimation (STAPLE) and with kappa statistics. Optimised confidence level consensus contours were obtained using a voxel-wise maximum likelihood approach and the STAPLE contours for GTV and CTV were based on an 80% confidence level., Results: Mean GTV STAPLE agreement sensitivity and specificity was 0.70 (range, 0.54-0.87) and 1.00, respectively, and 0.55 (range, 0.44-0.64) and 1.00 for the CTV, respectively. Mean GTV and CTV kappa agreement was 0.73 (range, 0.59-0.83) and 0.59 (range, 0.41-0.70), respectively. Optimised confidence level consensus contours were identified by STAPLE analysis. Consensus recommendations for the CTV include treating the entire segment containing the disease in addition to the immediate adjacent bony anatomic segment at risk of microscopic extension., Conclusion: Consensus recommendations for CTV target delineation specific to sacral metastases treated with SBRT were established using expert contours. This is a critical first step to achieving standardisation of target delineation practice in the sacrum and will serve as a baseline for meaningful pattern of failure analyses going forward., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Several treatment options for spinal metastases exist, including multiple radiation therapy (RT) techniques: three-dimensional (3D) conventional RT (3D-RT), intensity-modulated RT (IMRT), and spine stereotactic radiosurgery (SSRS). Although data exist regarding reimbursement differences across regimens, differences in provider care delivery costs have yet to be evaluated. We quantified institutional costs associated with RT for spinal metastases, using a time-driven activity-based costing model., Methods: Comparisons were made between (1) 10-fraction 3D-RT to 30 Gy, (2) 10-fraction IMRT to 30 Gy, (3) 3-fraction SSRS (SSRS-3) to 27 Gy, and (4) single-fraction SSRS (SSRS-1) to 18 Gy. Process maps were developed from consultation through follow-up 30 days post-treatment. Process times were determined through panel interviews, and personnel costs were extracted from institutional salary data. The capacity cost rate was determined for each resource, then multiplied by activity time to calculate costs, which were summed to determine total cost., Results: Full-cycle costs of SSRS-1 were 17% lower and 17% higher compared with IMRT and 3D-RT, respectively. Full-cycle costs for SSRS-3 were only 1% greater than 10-fraction IMRT. Technical costs for IMRT were 50% and 77% more than SSRS-3 and SSRS-1. In contrast, personnel costs were 3% and 28% higher for SSRS-1 than IMRT and 3D-RT, respectively ( P < .001)., Conclusions: Resource utilization varies significantly among treatment options. By quantifying provider care delivery costs, this analysis supports the institutional resource efficiency of SSRS-1. Incorporating clinical outcomes with such resource and cost data will provide additional insight into the highest value modalities and may inform alternative payment models, operational workflows, and institutional resource allocation.

Objective: Patients with metastatic thyroid cancer have prolonged survival compared to those with other primary tumors. The spine is the most common site of osseous involvement in cases of metastatic thyroid cancer. As a result, obtaining durable local control (LC) in the spine is crucial. This study aimed to evaluate the efficacy of spine stereotactic radiosurgery (SSRS) in patients with metastatic thyroid cancer., Methods: Information on patients with metastatic thyroid cancer treated with SSRS for spinal metastases was retrospectively evaluated. SSRS was delivered with a simultaneous integrated boost technique using single- or multiple-fraction treatments. LC, defined as stable or reduced disease volume, was evaluated by examining posttreatment MRI, CT, and PET studies., Results: A total of 133 lesions were treated in 67 patients. The median follow-up duration was 31 months. Dose regimens for SSRS included 18 Gy in 1 fraction, 27 Gy in 3 fractions, and 30 Gy in 5 fractions. The histology distribution was 36% follicular, 33% papillary, 15% medullary, 13% Hurthle cell, and 3% anaplastic. The 1-, 2-, and 5-year LC rates were 96%, 89%, and 82%, respectively. The median overall survival (OS) was 43 months, with 1-, 2-, and 5-year survival rates of 86%, 74%, and 44%, respectively. There was no correlation between the absolute biological equivalent dose (BED) and OS or LC. Patients with effective LC had a trend toward improved OS when compared to patients who had local failure: 68 versus 28 months (p = 0.07). In terms of toxicity, 5 vertebral compression fractures (2.8%) occurred, and only 1 case (0.6%) of greater than or equal to grade 3 toxicity (esophageal stenosis) was reported., Conclusions: SSRS is a safe and effective treatment option with excellent LC and minimal toxicity for patients with metastatic thyroid cancer. No association with increased radiation dose or BED was found, suggesting that such patients can be effectively treated with reduced dose regimens.

Objective  The objective of this study was to identify factors associated with improved tumor control at individual sites of recurrence and to define the role of stereotactic radiosurgery (SRS) in the management of local or distant progression following prior radiotherapy. Study Design  Clinical data of patients with recurrent skull base chordoma following prior radiotherapy were retrospectively reviewed. Setting and Participants  This is a single-center retrospective study including 16 patients from the University of Texas MD Anderson Cancer Center Houston, Texas, United States. Main Outcome Measures  Each site of recurrence was considered independently, and the primary outcome was freedom from treatment site progression (FFTSP). Results  There were 40 episodes of either local or distant progression treated in 16 patients with skull base chordoma. Tumor recurrence was classified as either local, distant, or both local and distant involving the skull base, spinal column, or leptomeninges. Patients were treated with repeat surgical resection ( n  = 16), SRS ( n  = 21), or chemotherapy ( n  = 25). In multivariate analysis, SRS was the only treatment modality associated with improved FFTSP ( p  = 0.006). For tumors treated with SRS, there was no evidence of tumor progression or adverse radiation events. Other factors associated with worse FFTSP included the number of progressive episodes (>3), tumor histology, and leptomeningeal disease. Conclusions  For local recurrence following prior radiotherapy, SRS was associated with improved FFTSP. SRS may represent an effective palliative treatment offering durable tumor control at the treated site without significant treatment-related morbidity., Competing Interests: Conflict of Interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this study., (© Thieme Medical Publishers.)

Objective: The proximity of the spinal cord to compressive metastatic lesions limits radiosurgical dosing. Open surgery is used to create safe margins around the spinal cord prior to spinal stereotactic radiosurgery (SSRS) but carries the risk of potential surgical morbidity and interruption of systemic oncological treatment. Spinal laser interstitial thermotherapy (SLITT) in conjunction with SSRS provides local control with less morbidity and a shorter interval to resume systemic treatment. The authors present a comparison between SLITT and open surgery in patients with metastatic thoracic epidural spinal cord compression to determine the advantages and disadvantages of each method., Methods: This is a matched-group design study comprising patients from a single institution with metastatic thoracic epidural spinal cord compression that was treated either with SLITT or open surgery. The two cohorts defined by the surgical treatment comprised patients with epidural spinal cord compression (ESCC) scores of 1c or higher and were deemed suitable for either treatment. Demographics, pre- and postoperative ESCC scores, histology, morbidity, hospital length of stay (LOS), complications, time to radiotherapy, time to resume systemic therapy, progression-free survival (PFS), and overall survival (OS) were compared between groups., Results: Eighty patients were included in this analysis, 40 in each group. Patients were treated between January 2010 and December 2016. There was no significant difference in demographics or clinical characteristics between the cohorts. The SLITT cohort had a smaller postoperative decrease in the extent of ESCC but a lower estimated blood loss (117 vs 1331 ml, p < 0.001), shorter LOS (3.4 vs 9 days, p < 0.001), lower overall complication rate (5% vs 35%, p = 0.003), fewer days until radiotherapy or SSRS (7.8 vs 35.9, p < 0.001), and systemic treatment (24.7 vs 59 days, p = 0.015). PFS and OS were similar between groups (p = 0.510 and p = 0.868, respectively)., Conclusions: The authors' results have shown that SLITT plus XRT is not inferior to open decompression surgery plus XRT in regard to local control, with a lower rate of complications and faster resumption of oncological treatment. A prospective randomized controlled study is needed to compare SLITT with open decompressive surgery for ESCC.

A 52 year-old gentleman with metastatic pheochromocytoma received single fraction spine stereotactic radiosurgery (SSRS) to an isolated L3 metastasis. Two years later, he developed widespread osseous metastatic disease involving nearly every vertebral body level with the striking exception of the treated L3 vertebrae. The "seed and soil" hypothesis of metastatic dissemination was developed over a century ago and states that tumors cells (the "seed") preferentially grow in select host tissue microenvironments (the "soil"). The high-dose radiation delivered by SSRS may have altered the microenvironment "soil" of the treated L3 vertebrae, rendering it inhospitable to the growth of future metastases. With emerging evidence in support of high-dose stereotactic radiation for oligometastatic disease, there will likely be increasing opportunity to observe and understand treatment changes in the tissue microenvironment and how it relates to the potential for metastatic seeding., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose., (© 2020 Old City Publishing, Inc.)

Background and Purpose: To characterize local control and late toxicity in long-term survivors prospectively-treated with spine stereotactic radiosurgery (SSRS)., Materials and Methods: From 2002 to 2011, 228 patients were prospectively-treated on protocol for metastatic disease of 261 vertebral sites. A subset of 52 patients surviving >4 years following treatment were collectively treated for 58 sites (encompassing 69 vertebrae) and underwent secondary analysis. Of all sites, 9% received prior radiation, and 16% encompassed multiple contiguous vertebrae. Radiation prescriptions were most commonly 24 Gy in 1 and 27 Gy in 3 fractions. Outcomes were evaluated via Kaplan-Meier, and associations analyzed via logistic regression., Results: Median follow-up was 6.7 years (range: 49-142 months). Five-year local control by site was 91%, with late failures (>2 years) occurring in 3%. Overall and Grade ≥3 late toxicities (>2 years) were observed in 5% and 2% of sites. The last known neurologic event (grade 2 radiculopathy) was noted 2.1 years post-treatment, while the last documented fracture occurred at 4.1 years. No Grade ≥3 events were witnessed after 3.1 years post-SSRS, and no toxicities were noted after 4.1 years through end of follow-up. Re-irradiation, number of segments treated per site (1 vs. 2-3), and fractionation (1 vs. 3-5) were not associated with failure or toxicity., Conclusion: SSRS maintains excellent disease control and a favorable late toxicity profile even among long-term survivors, with very few failures or toxicities after 2 years in this prospectively-treated population. Overall, these data support the durable control and long-term safety of SSRS with extended follow-up., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nine patients with single fraction spinal stereotactic body radiation therapy (SBRT) treatment were identified to assess both the intra fraction and daily esophageal motion and associated dosimetric deviation in spinal SBRT. We performed a chained deformable registration of 4D CT phase images to estimate the intra fraction motion magnitude of the esophagus in a breathing cycle. The intra fraction esophageal motion mostly exhibited in the superior-inferior direction with the total motion magnitude increased from the T1 (0.7 mm) to the T11 vertebra level (6.5 mm). The actual dose received by a moving esophagus was estimated by accumulating dose from each phase of the 4D dataset using deformable image registration. In comparison, dose recalculated on the average CT reflects the dose received by a stationary esophagus. Intra fraction motion was found to reduce the maximum dose received by a small volume of esophagus  ⩽2 cm 3 , with the largest absolute and relative dose difference being  -80 cGy and  -6.4%, respectively. Its effect on the maximum dose received by 5 cm 3 of esophagus can be higher or lower with a large percentage difference, but did not result in substantial absolute dose increase to violate the dose constraint of 11.9 Gy we used for plan evaluation. In addition, there was no correlation between the dosimetric deviation and the intra fraction motion magnitude. These findings suggest that 4D CT simulation is not essential with regards to the esophageal dose. The daily motion of the esophagus and its dosimetric impact was investigated by examining the difference of esophagus delineated on both treatment and planning CT after they were registered using boney target. The day to day difference of esophagus was negligible for all cases in this study.

Purpose:  Despite aggressive primary treatment, up to 13.5% of patients diagnosed with pheochromocytoma may develop metastases, most often affecting the axial skeleton. Given that systemic therapy options are often inadequate, local therapy remains the cornerstone of palliation for these patients. Historically poor responses to standard fractionated radiotherapy have led to the consideration of stereotactic radiosurgery as an option to overcome potential radioresistance and provide durable local control of these tumors. Here we report our institutional experience in treating spine metastases from pheochromocytoma with spine stereotactic radiosurgery (SSRS)., Methods and Materials: Our clinical databases were retrospectively reviewed for patients with metastatic pheochromocytoma treated with SSRS from 2000-2017. Seven patients with 16 treated metastatic spinal lesions were identified. Local control was evaluated using magnetic resonance imaging (MRI). Pain and symptom data were assessed to evaluate toxicity using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The Kaplan-Meier method was used to assess local control and overall survival (OS)., Results: Median follow-up for treated lesions was 11 months (range 2.2 - 70.8). Most lesions were treated to a dose of 27 Gy in three fractions (62.5%). Other fractionation schemes included 24 Gy in one fraction (25%), 16 Gy in one fraction (6.3%), and 18 Gy in three fractions (6.3%). Treatment sites included the cervical spine (18.8%), thoracic spine (37.5%), lumbar spine (31.3%), and sacrum (12.5%). The crude local control rate was 93.7%, with one thoracic spine lesion progressing 20.7 months after treatment with 24 Gy in one fraction. Kaplan-Meier OS rates at 1 and 2 years after SSRS were 71.4% and 42.9%, respectively. Most common toxicities included acute grade 1-2 pain and fatigue. There was one case of vertebral fracture in a cervical spine lesion treated to 27 Gy in three fractions, which was managed non-surgically., Conclusion: Very few studies have explored the use of SSRS in metastatic pheochromocytoma. Our data suggest this modern radiation modality is effective, safe, and provides durable local control to palliate symptoms and potentially limit further metastatic seeding. Larger patient numbers and longer follow-up will further define the role of SSRS as a treatment option in these patients., Competing Interests: Dr. Shane Mesko has a consulting agreement with Oscar Healthcare, outside the submitted work. Dr. Jing Li has received research funding from Medtronic to support a different clinical trial on SSRS, outside the submitted work Dr. Paul Brown has received personal fees from UpToDate (contributor) and Novella Clinical (DMSB Member), outside the submitted work.

Introduction: NRG protocols for glioblastoma allow for clinical target volume (CTV) reductions at natural barriers; however, literature examining CTV contouring and the relevant white matter pathways is lacking. This study proposes consensus CTV guidelines, with a focus on areas of controversy while highlighting common errors in glioblastoma target delineation., Methods: Ten academic radiation oncologists specializing in brain tumor treatment contoured CTVs on four glioblastoma cases. CTV expansions were based on NRG trial guidelines. Contour consensus was assessed and summarized by kappa statistics. A meeting was held to discuss the mathematically averaged contours and form consensus contours and recommendations., Results: Contours of the cavity plus enhancement (mean kappa 0.69) and T2-FLAIR signal (mean kappa 0.74) showed moderate to substantial agreement. Experts were asked to trim off anatomic barriers while respecting pathways of spread to develop their CTVs. Submitted CTV&#95;4600 (mean kappa 0.80) and CTV&#95;6000 (mean kappa 0.81) contours showed substantial to near perfect agreement. Simultaneous truth and performance level estimation (STAPLE) contours were then reviewed and modified by group consensus. Anatomic trimming reduced the amount of total brain tissue planned for radiation targeting by a 13.6% (range 8.7-17.9%) mean proportional reduction. Areas for close scrutiny of target delineation were described, with accompanying recommendations., Conclusions: Consensus contouring guidelines were established based on expert contours. Careful delineation of anatomic pathways and barriers to spread can spare radiation to uninvolved tissue without compromising target coverage. Further study is necessary to accurately define optimal target volumes beyond isometric expansion techniques for individual patients.

Background: 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., Methods: Our study of 1345 patients with higher-grade spinal ependymoma used χ 2 tests and simple and multivariable logistic regression models to assess demographic and clinical factors associated with therapy. Kaplan-Meier and log-rank tests were used to assess overall survival (OS)., Results: Most 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 (P < 0.001). Patients living ≤32 km (20 miles) from a facility were more likely to receive RT (P < 0.001) than were those living further away. On multivariable logistic regression, grade (grade III, odds ratio, 8.6; P < 0.001) 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 (P < 0.0001). 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., Conclusions: 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Spine stereotactic radiosurgery delivers an ablative dose of radiation therapy (RT) with high conformity relative to standard fractionated RT. This technique is suboptimal for extended targets (>3 vertebral levels) owing to treatment alignment concerns or for patients with marked epidural extension. In these patients, we hypothesized that use of hypofractionated intensity modulated RT/volumetric modulated arc therapy to dose escalate the gross tumor volume (GTV) to 40 Gy as a spinal simultaneous integrated boost (SSIB) would allow for durable local control and palliation., Methods and Materials: We retrospectively analyzed 15 separate spinal sites (12 patients) that were treated with the SSIB technique between 2012 and 2016. The GTV and clinical target volume were prescribed at 40 Gy and 30 Gy, respectively, in 10 fractions. The spinal cord was allowed a maximum point dose of 34 Gy. The GTV was defined as gross tumor. The clinical target volume encompassed the GTV in addition to the involved vertebral bodies, at-risk paraspinal space, and spinal canal, followed by a planning target volume expansion of 3 to 5 mm., Results: The median follow-up for patients in our cohort was 17 months. At 1 year, local control was 93%, and overall survival was 58%, with a median time to death after treatment of 7 months. No grade ≥2 neurologic toxicities were reported for any of the patients. Nine of 12 patients had pain at presentation, of which 7 patients (78%) reported improvement and/or complete resolution of their pain after treatment., Conclusions: Our early experience using a dose of 40 Gy to the GTV delivered via an SSIB technique, in lieu of spine stereotactic radiation surgery but more aggressive than conventional palliative doses, provides durable local control and pain relief. This technique may allow for improved local control and palliation in patients with radioresistant disease compared with conventional 3-dimensional conformal fractionated RT., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors., Methods: From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15-20 Gy) prescribed to the 50% isodose line (range 43%-55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21-27 Gy) prescribed to the 50% isodose line (range 45%-50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS., Results: Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0-34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3-4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2-3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention., Conclusions: GKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Spine stereotactic radiosurgery (SSRS) is a noninvasive treatment for metastatic spine lesions. MD Anderson Cancer Center reports a quality assurance (QA) failure rate approaching 15% for SSRS cases, which we hypothesized is due to difficulties in accurately calculating dose resulting from a large number of small-area segments. Clinical plans typically use 9 beams with an average of 10 segments per beam and minimum segment area of 2-3 cm 2 . The purpose of this study was to identify a set of intensity-modulated radiation therapy (IMRT) planning parameters that attempts to optimize the balance among QA passing rate, plan quality, dose calculation accuracy, and delivery time for SSRS plans. Using Pinnacle version 9.10, we evaluated the effects of 2 IMRT parameters: maximum number of segments and minimum segment area. Initial evaluation of the data revealed that 5 segments per beam along with minimum segment area of 4 cm 2 and 4 monitor units (MU) per segment (5-4-4 plans) was the most promising. IMRT QA was performed using a PTW OCTAVIUS 4D phantom with a 2D detector array. Our data showed no significant plan quality change with decreased number of segments and increased minimum segment area. The average coverage of GTV and CTV was 82.5 ± 13% (clinical) vs 82.5 ± 13% (5-4-4) and 92.3 ± 8% (clinical) vs 91.5 ± 8% (5-4-4). Maximum point dose to cord was 11.4 ± 3.5 Gy (clinical) vs 11.0 ± 4.0 Gy (5-4-4). Total plan delivery time was decreased by an average of 11.3% for the 5-4-4 plans. For IMRT QA, the gamma index passing rate (distance to agreement: 2.5 mm, local dose difference: 4%) for the original plans vs the 5-4-4 plans averaged 90.3% and 91.9%, respectively. In conclusion, IMRT parameters of 5 segments per beam and 4 cm 2 minimum segment areas provided a better balance of plan quality, delivery efficiency, and plan dose calculation accuracy for SSRS., (Copyright © 2018 American Association of Medical Dosimetrists. All rights reserved.)

Purpose: We seek to establish the feasibility of using spine stereotactic radiosurgery (SSRS), allowing for spinal cord dose constraint relaxation, as the primary management of metastatic epidural spinal cord compression (MESCC) in inoperable patients., Methods and Materials: Inoperable patients with thoracic MESCC and no history of radiation were enrolled on this prospective phase 1 single-institution protocol. SSRS was delivered to a histology-dependent prescription dose of 18 or 24 Gy. Incremental spinal cord constraint relaxation was performed from a Dmax cohort of 10 Gy up to 16 Gy only if tumor progression occurred and the risk of radiation-induced myelopathy (RM) remained lower than the risk of tumor progression., Results: Thirty-two patients enrolled on the trial; 4, 12, 9, and 7 patients were in the 10 Gy, 12 Gy, 14 Gy, and 16 Gy cord Dmax cohorts, respectively. At baseline, there were 2 sites with MESCC grade 1A, 10 sites with grade 1B, 10 sites with grade 1C, 9 sites with grade 2, and 1 site with grade 3 disease. Among the 28 evaluable patients, the median overall survival was 28.6 months (95% confidence interval [CI], 9.2-48.0 months), and the 1-year local control was 89% (95% CI, 74%- 97%). With a median follow-up of 17 months, there were no cases of RM (upper 95% CI, 12%). In the cohort receiving a cord Dmax of 16 Gy, there were no cases of RM (upper 95% CI, 39%) with a median follow-up of 17 months (range, 12.7-21.0 months)., Conclusions: SSRS is a safe and effective tool in patients with MESCC. In high-risk inoperable patients with MESCC receiving SSRS, dose constraint relaxation of the cord constraint dmax to 16 Gy may be considered to optimize local control, with the acknowledgment that this is based on 6 evaluable patients who received this dose in this trial., (Copyright © 2018. Published by Elsevier Inc.)