Vestibular schwannomas (VSs) are benign tumors arising from vestibulocochlear nerve Schwann cells. Single or multifractional stereotactic radiation therapy (SRT) is commonly used for treatment of these tumors, and accurate target delineation is critical for the focused radiation delivery, maximizing tumor control while minimizing toxicity. Contrast-enhanced magnetic resonance imaging (MRI) is the gold standard for diagnosis, monitoring of VS and is critical in precise target delineation for SRT planning. Prostate specific membrane antigen (PSMA) positron emission tomography (PET) has established clinical utility for diagnosis and monitoring of prostate cancer. However, other central nervous system neoplasms, including VS, have also been found to be PSMA tracer avid. We present the first clinical use of PSMA PET for SRT in a patient with VS who was unable to undergo MRI.

Trigeminal neuralgia is a common symptom of benign tumors compressing the trigeminal nerve, leading to debilitating pain and a devastating impact on quality of life. Stereotactic radiosurgery is a validated option for intracranial meningiomas with excellent tumor control rates that correlate with symptomatic improvement. Select cases with refractory or recurrent trigeminal neuralgia can benefit from a second treatment targeting the trigeminal nerve. We present a case of refractory trigeminal neuralgia secondary to compression of a previously irradiated petroclival meningioma successfully treated with a second radiosurgery course targeting cranial nerve V (CN V). Multidisciplinary considerations, patient-centered factors, radiobiological considerations, and technical challenges faced in the intracranial reirradiation setting when cumulative dose constraints are previously met or exceeded are discussed.

BACKGROUND:Meningiomas are the most common primary intracranial neoplasms. Gross-total resection, the primary treatment goal, is not achieved in up to 50% of patients, affecting progression-free and overall survival. The traditionally used intraoperative assessment of resection extent using the Simpson grade has recently been shown to be less accurate than postoperative MRI. Improving intraoperative resection extent delineation thus represents a paramount goal. Somatostatin receptor (SSTR)-targeted PET has improved meningioma management. [Cu64]DOTATATE is a clinically approved PET radiotracer that avidly binds to SSTR2 with properties similar to [Ga68]DOTATATE but with a significantly longer half-life of approximately 13 hours. OBSERVATIONS:The authors assessed the feasibility of immediate preoperative [Cu64]DOTATATE PET/MRI and subsequent intraoperative tumor detection using a handheld gamma probe device typically used in sentinel node biopsy. They describe [Cu64]DOTATATE PET-guided surgical debulking of a meningioma and demonstrate the feasibility of intraoperative tumor detection using the gamma probe device, with activity 10 times higher than the background after exposing the tumor, decreasing by 50% after debulking. The authors further demonstrate 3-month clinical and PET/MRI outcomes, with accurate delineation of minimal residual viable tumor. LESSONS:This pilot study for the first time demonstrates the feasibility of preoperative PET with in vivo radio-guided surgery in meningiomas, laying the foundation for larger-scale prospective trials. https://thejns.org/doi/10.3171/CASE24867.

Metastatic intracranial progression drastically impacts prognosis, therapeutic considerations and quality of life. The increasing incidence of lung cancer patients developing brain metastases (BM) parallels the incorporation of more effective systemic agents and improved surveillance. Our evolving knowledge of BM pathophysiology, along with advancements in surgical, radiotherapy and systemic therapy options, is rapidly changing prognostication and treatment paradigms. Optimal management of BM in the modern era is patient-specific, dependent on performance status, comorbidities, intracranial and extracranial disease burden, leptomeningeal disease, and the presence of targetable mutations. The purpose of this review is to provide a detailed overview of the detection, prognostication, and multidisciplinary, management of BM arising from non-small cell lung cancer and small cell lung cancer. We discuss contemporary evidence and active clinical trials supporting a wide array of treatment options, including surgery, radiosurgery, memory-avoidance whole brain radiation, craniospinal irradiation, chemotherapy, targeted agents and immunotherapy. Multidisciplinary paradigms will continue to evolve as currently accruing randomized trials evaluating these promising treatments options mature.

PURPOSE:The central nervous system World Health Organization (WHO) grade 4 adult-type diffuse glioma represents one of the most aggressive and challenging primary brain tumors. This guideline aims to provide evidence-based recommendations for the multidisciplinary management of these tumors, focusing on diagnosis, initial treatment, reirradiation, and health disparities, while acknowledging that present literature primarily represents historical histologic grade 4 glioblastoma. METHODS:The American Society for Radiation Oncology convened a task force to address 4 key questions focused on indications for radiation therapy (RT) and/or adjunctive therapies (eg, systemic therapy, alternating electric field therapy), appropriate regimens for external beam RT after initial biopsy/resection including variables such as pretreatment characteristics, target volumes, technique, dose, reirradiation indications and techniques, and health disparities. Recommendations are based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS:Following maximum safe resection, molecular and pathologic diagnosis, and prognostic stratification of WHO grade 4 adult-type diffuse glioma, concurrent RT with temozolomide followed by adjuvant temozolomide is recommended for eligible patients and incorporation of alternating electric field therapy is conditionally recommended. In elderly patients, hypofractionated RT with concurrent and adjuvant temozolomide is conditionally recommended. In frail patients, supportive and palliative care is conditionally recommended following multidisciplinary, patient-centered discussion. Appropriate reirradiation techniques, with or without additional systemic therapies, can be considered and are conditionally recommended in patients following pathologic or advanced imaging confirmation of WHO grade 4 diffuse glioma recurrence. Health disparities exist in patients with WHO grade 4 adult-type diffuse glioma and attention is necessary to improve outcomes and increase clinical trial enrollment for underserved populations. CONCLUSIONS:These evidence-based recommendations and current practice adoption patterns inform best clinical practices on the management of WHO grade 4 adult-type diffuse glioma. Future advancements in personalized medicine, biomarker discovery, and novel therapies are essential to improving outcomes. The integration of multidisciplinary care and participation in future clinical trials, especially in underserved populations, is crucial in addressing the poor outcomes among WHO grade 4 adult-type diffuse glioma.

The ARS brain committee recommends that vorasidenib may be appropriate for recurrent or residual IDH-mutant grade 2 oligodendroglioma or astrocytoma. Vorasidenib is usually not appropriate for completely resected grade 2 oligodendroglioma or astrocytoma, any grade 3 oligodendroglioma or astrocytoma, or combined with radiotherapy and/or chemotherapy for any grade 2-3 glioma.

BACKGROUND:This practice parameter was revised collaboratively by the American College of Radiology (ACR), and the American Radium Society. This practice parameter provides updated reference literature regarding radiation oncology practice and its key personnel. METHODS:This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the American Radium Society. RESULTS:This practice parameter provides a comprehensive update to the reference literature regarding radiation oncology practice in general. The overall roles of the radiation oncologist, the Qualified Medical Physicist, and other specialized personnel involved in the delivery of external-beam radiation therapy are discussed. The use of radiation therapy requires detailed attention to equipment, patient and personnel safety, equipment maintenance and quality assurance, and continuing staff education. Because the practice of radiation oncology occurs in a variety of clinical environments, the judgment of a qualified radiation oncologist should be used to apply these practice parameters to individual practices. Radiation oncologists should follow the guiding principle of limiting radiation exposure to patients and personnel while accomplishing therapeutic goals. CONCLUSION:This practice parameter can be used as an effective tool to guide radiation oncology practice by successfully incorporating the close interaction and coordination among radiation oncologists, medical physicists, dosimetrists, nurses, and radiation therapists.

Malignant central nervous system (CNS) cancers include a group of heterogeneous dis-eases characterized by a relative resistance to treatments and distinguished as either primary tumors arising in the CNS or secondary tumors that spread from other organs into the brain. Despite therapeutic efforts, they often cause significant mortality and morbidity across all ages. Radiotherapy (RT) remains the main treatment for brain cancers, improving associated symptoms, improving tumor control, and inducing a cure in some. However, the ultimate goal of cancer treatment, to improve a patient’s survival, remains elusive for many CNS cancers, especially primary tumors. Over the years, there have thus been many preclinical studies and clinical trials designed to identify and overcome mechanisms of resistance to improve outcomes after RT and other therapies. For example, immunotherapy delivered concurrent with RT, especially hypo-fractionated stereotactic RT, is synergistic and has revolutionized the clinical management and outcome of some brain tumors, in particular brain metastases (secondary brain tumors). However, its impact on gliomas, the most common primary malignant CNS tumors, remains limited. In this review, we provide an overview of radioresistance mechanisms, the emerging strategies to overcome radioresistance, the role of the tumor microenviroment (TME), and the selection of the most significant results of radiation–immuno–oncological investigations. We also identify novel therapeutic opportunities in primary and secondary brain tumors with the purpose of elucidating current knowledge and stimulating further research to improve tumor control and patients’ survival.

Background: Vestibular schwannomas are benign tumors arising from the Schwann cells of vestibulocochlear nerve. Surgical resection as well stereotactic radiosurgery (SRS) which provides highly conformal delivery of high-dose radiation, both are effective treatment modalities for vestibular schwannoma (VS). MRI is the gold standard for diagnosis and also critical for precise target delineation for SRS planning. Prostate Specific Membrane Antigen (PSMA) PET has established clinical utility for diagnosis and monitoring of prostate cancer. However, despite the name, PSMA is overexpressed in many other benign and malignant neoplasms. Few previous reports have reported avidity of VS on PSMA-PET. Currently, there are no functional imaging biomarkers available to determine VS viability and growth for treatment planning and response assessment. We present the first clinical use of PSMA-PET as an adjunct imaging modality in VS management.

Background Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. Methods Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post-radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and progression-free survival (PFS) was evaluated using Cox regression. Results Twenty-seven patients with 64 tumors (26% World Health Organization [WHO]-1, 41% WHO-2, 26% WHO-3, and 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT; mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (P < .0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort. Conclusions DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post-radiosurgery. Lesion size decrease was statistically significant; however, it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery.

BACKGROUND AND PURPOSE: WHO grade 3 meningiomas are rare and poorly understood and have a higher propensity for recurrence, metastasis, and worsened clinical outcomes compared with lower-grade meningiomas. The purpose of our study was to prospectively evaluate the molecular profile, PET characteristics, and outcomes of patients with World Health Organization grade 3 meningiomas who were imaged with gallium 68 (Ga-68) DOTATATE PET/MR imaging. MATERIALS AND METHODS: Patients with World Health Organization grade 3 meningiomas enrolled in our prospective observational cohort evaluating the utility of (Ga-68) DOTATATE PET/MR imaging in somatostatin receptor positive brain tumors were included. We stratified patients by de novo-versus-secondary-progressive status and evaluated the differences in the PET standard uptake value, molecular profiles, and clinical outcomes. RESULTS: Patients met the inclusion criteria (secondary-progressive: 7/14; de novo: 7/14). The secondary-progressive cohort had a significantly higher per-patient number of surgeries (4.1 versus 1.6; P = .011) and trended toward a higher number of radiation therapy courses (2.4 versus 1.6; P = .23) and cumulative radiation therapy doses (106Gy versus 68.3Gy; P = .31). The secondary-progressive cohort had a significantly lower progression-free survival compared with the de novo cohort (4.8 versus 37.7 months; P = .004). Secondary-progressive tumors had distinct molecular pathology profiles with higher numbers of mutations (3.5 versus 1.2; P = .024). Secondary-progressive tumors demonstrated higher PET standard uptake values (17.1 versus 12.4; P = .0021). CONCLUSIONS: Our study confirms prior work illustrating distinct clinical outcomes in secondary-progressive and de novo World Health Organization grade 3 meningiomas. Furthermore, our findings support (Ga-68) DOTATATE PET/MR imaging as a useful management strategy in World Health Organization grade 3 meningiomas and provide insight into meningioma biology, as well as clinical management implications.

Abstract INTRODUCTION Re-irradiation with stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) may be used for treating recurrent brain metastases. Here, we are reporting on the rate of cranial re-irradiation based on our institutional experience in patients with mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (mEGFR-NSCLC). METHODS This is a retrospective review of patients from three NYP-WCM hospitals with brain metastases treated with radiotherapy and Tyrosine Kinase Inhibitors (TKIs) from December 2012 to May 2023. RESULTS Ninety-eight patients (60.5%) out of 162 with brain metastases from mEGFR-NSCLC were treated with radiation. Twenty-seven patients (27.5%) were treated with WBRT. Among 71 patients treated with SRS, 10 (14.1%) patients underwent surgical resection of the dominant brain lesion followed by fractioned SRS (FSRS) to the surgical bed. Sixty-one (85.9%) patients received SRS for intact brain lesions ranging from single fraction 16-20Gy to FSRT with 24Gy –30Gy in 3-5 fractions based on the size and eloquence of the brain site of the brain metastasis. In the SRS group, fifteen (21.1%) patients required at least one more course of cranial irradiation. The mean duration of local intracranial control between the first and the second course of radiation was 19.6 months [range from 2.0- 56.7 months], while from the start of TKI to the first intracranial failure was 11.3 months [0.8m-45.3 months]. In the WBRT group, two patients (7.4%) were treated with another course of WBRT 20Gy in 5 fractions. These two patients started TKI simultaneously with their first course of WBRT; the mean duration of intracranial local control was 12.8 months [range from 11.6-14.1 months]. Both patients suffered significant cognitive declines. CONCLUSION In the Tyrosine Kinase Inhibitor era, patients with brain metastases from mEGFR-NSCLC have protracted progression-free survival. Multiple courses of cranial re-irradiation may be needed. Stereotactic radiotherapy should be preferred for the best results in preserving cognitive functions.

Purpose: Theranostic approaches combining prostate-specific membrane antigen (PSMA)-PET/CT or PET/MRI with PSMA-targeted radionuclide therapy have improved clinical outcomes in patients with prostate cancer (PCa) especially metastatic castrate resistant prostate cancer. Dural metastases in PCa are rare but can pose a diagnostic challenge, as meningiomas, a more common dural based lesions have been shown to express PSMA. The aim of this study is to compare PSMA PET parameters between brain lesions classified as dural metastases and meningiomas in prostate cancer patients. Methods: A retrospective analysis of PSMA PET/CT scans in patients with PCa and intracranial lesions was conducted. Brain lesions were categorized as dural metastases or meningiomas based on MRI characteristics, longitudinal follow-up, and histopathological characteristics. Standardized uptake values (SUVmax) of each brain lesion were measured, along with SUV ratio referencing parotid gland (SUVR). SUVs between lesions classified as metastases and meningiomas, respectively, were compared using Mann-Whitney-test. Diagnostic accuracy was evaluated using ROC analysis. Results: 26 male patients (median age: 76.5 years, range: 59-96 years) met inclusion criteria. A total of 44 lesions (7 meningiomas and 37 metastases) were analyzed. Median SUVmax and SUVR were significantly lower in meningiomas compared to metastases (SUVmax: 2.7 vs. 11.5, p = 0.001; SUVR: 0.26 vs. 1.05, p < 0.001). ROC analysis demonstrated AUC 0.903; the optimal cut-off value for SUVR was 0.81 with 81.1 % sensitivity and 100 % specificity. Conclusion: PSMA PET has the potential to differentiate meningiomas from dural-based metastases in patients with PCa, which can optimize clinical management and thus improve patient outcomes.

Purpose/Objective(s) Ventricular tachycardia (VT) in patients with structural heart disease is associated with reduced quality of life and poor prognosis. Therapeutic options include medication, anti-tachycardia pacing or shock by implantable cardiac devices and catheter-based ablation of heart arrhythmogenic substrates. STereotactic Arrhythmia Radioablation (STAR) tested in a phase I/II trial by Robinson and colleagues offers a novel approach. Materials/Methods Data from a retrospective series of 5 high-risk patients with VT refractory to catheter ablation and medication, treated with STAR are reported from a single referral center. CTV was defined to encompass the arrhythmogenic substrate by a team of a radiation oncologists and treating electrophysiologists, based on clinical and electro-anatomical information derived from CT scan and catheter ablation maps. ITV was added to CTV to compensate for heart and respiratory movement. PTV was then defined by adding an isotropic margin of 2-3 mm to the ITV. Volumetric Modulated Arc Therapy (VMAT) plans were generated, optimized, and delivered using medical linear accelerator. The prescription dose to the PTV was 25 Gy in 1 fraction. Results Mean CTV, ITV and PTV volumes, were 141.1cc, 187.7cc, 298.1cc, respectively. Mean heart volume was 1740.6 cc. All 5 patients completed STAR procedure and treatment. There were no acute treatment-related adverse events. Clinical and treatment-efficacy data are summarized in Table. STAR significantly reduced or abrogated arrythmia at a median time of 24 weeks (range = 4-48) post-treatment. Patient n.1 and n.3 showed a remarkable reduction of VT episodes at 4- and 8-weeks post-treatment, respectively. Patients n.2, n.4 and n.5 were free of VT episodes at 6-months post-treatment. At a median follow-up time of 11 months (range = 1-19), 2/5 patients are alive (patient n.2 and n.4), both free of VT events at 1-year post-treatment. Patient n.1 died due to complication after cardiac transplantation, patients n.3 due to sepsis and multiorgan failure and patient n.5 due to COVID pneumonia, at 11-, 1- and 5-months post-STAR, respectively. Conclusion These data suggest that LINAC-based STAR is a safe and effective treatment option in high-risk patients with VT refractory to catheter ablation and medication. Results from large perspective studies will define optimal patient selection and inform about long-term outcomes.

OBJECTIVE:Our purpose was to describe our initial institutional experience using dedicated brain [18F]-Fluoroestradiol (FES) PET/CT or PET/MRI in the management of patients with estrogen-receptor-positive (ER+) breast cancer brain metastases (BCBM), and compare to [18F]-Fluorodeoxyglucose (FDG) PET and MRI. MATERIALS & METHODS:Patients with biopsy-proven ER+ disease and MRI findings of suspected new, progressive, or recurrent BCBM were included in this retrospective study. Clinical and demographic data were collected. Dedicated brain FES PET/CT or PET/MRI was performed for clinical purposes. Maximum standardized uptake value (SUV) in MRI-defined target lesions and SUV ratio (SUVR, referencing normal-appearing parenchyma) were obtained. Pathology and/or clinical and MRI follow-up data were used as gold standard to classify viable neoplasm versus post-radiotherapy (RT) sequelae. Mann-Whitney tests were performed to compare subgroups. RESULTS:Seven patients met inclusion criteria. 15/16 (94 %) lesions classified as neoplasm were FES-positive. 4/4 (100 %) lesions classified as RT sequelae were FES-negative. Median tumor FES-SUVR were higher than median RT-sequelae FES-SUVR (6.0 (2.8-9.1) versus 0.5 (0.3-0.7), p < 0.01), and similarly, median tumor FES-SUV were higher than median RT-sequelae FES-SUV (4.8 (2.8-9.1) versus 0.6 (0.3-0.8), p < 0.01). Lesion-based analysis of FDG-SUV and -SUVR demonstrated a trend for higher FDG avidity in lesions characterized as neoplasm; however, this did not reach statistical significance. CONCLUSION:Dedicated FES brain PET represents a promising adjunct modality, noting limitations of small sample size, retrospective nature of our study, and the possibility of ER expression heterogeneity. Our findings merit future prospective clinical trials incorporating dedicated brain FES PET/CT and PET/MRI in the management of patients with ER-positive disease and BCBM.

PURPOSE:Meningiomas are the most common primary intracranial tumor. Somatostatin receptor 2 is almost universally expressed in meningioma tissue. For patients who require adjuvant radiation, somatostatin receptor based (68)Ga-DOTATATE positron emission tomography (PET) imaging can detect additional or residual disease not discernible on magnetic resonance imaging. PET guided radiation treatments may improve local control, minimize toxicity by allowing for more precise radiation therapy plans, and allow for more precise dose-escalation to maximize local control. The aim of this study was to develop consensus PET guided treatment planning guidelines for common meningioma presentations. METHODS AND MATERIALS:Five postoperative clinically relevant meningioma cases were selected from a prospective single-institutional registry of patients. Each patient had a preoperative and postoperative contrast-enhanced T1-weighted volumetric magnetic resonance imaging, and a postoperative (68)Ga-DOTATATE PET/CT, to assist with target delineation. The full treatment scenario including clinical history, histology, surgical history, and imaging were provided for each patient. Nineteen international experts who have published on the treatment and management of meningiomas, and who use (68)Ga-DOTATATE PET/CT in their practice, evaluated each case. Individual prescription recommendations were created, pooled, and discussed to create consensus recommendations. RESULTS:Consensus recommendations were created for each case. In most cases, PET-based contouring allowed for more precise dose-escalation to 66-70 Gy targeting residual disease. When compared to RTOG 0539 and modern clinical trial contouring guidelines, a smaller clinical target volume expansion from the surgical cavity was recommended using PET guided radiation plans in the absence of radiographic or pathologic evidence of brain or bone invasion. CONCLUSIONS:This report provides consensus target volume delineation guidelines for meningiomas receiving postoperative radiation in common clinical situations. Integration of these guidelines into clinical practice may allow for more precise biomarker guided radiation treatments and standardize radiation therapy on future meningioma clinical trials.