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Meningioma classification and treatment have evolved over the past eight decades. Since Bailey, Cushing, and Eisenhart's description of meningiomas in the 1920s and 1930s, there have been continual advances in clinical stratification by histopathology, radiography and, most recently, molecular profiling, to improve prognostication and predict response to therapy. Precise and accurate classification is essential to optimizing management for patients with meningioma, which involves surveillance imaging, surgery, primary or adjuvant radiotherapy, and consideration for clinical trials. Currently, the World Health Organization (WHO) grade, extent of resection (EOR), and patient characteristics are used to guide management. While these have demonstrated reliability, a substantial number of seemingly benign lesions recur, suggesting opportunities for improvement of risk stratification. Furthermore, the role of adjuvant radiotherapy for grade 1 and 2 meningioma remains controversial. Over the last decade, numerous studies investigating the molecular drivers of clinical aggressiveness have been reported, with the identification of molecular markers that carry clinical implications as well as biomarkers of radiotherapy response. Here, we review the historical context of current practices, highlight recent molecular discoveries, and discuss the challenges of translating these findings into clinical practice.

Glioblastoma (GBM) continues to be one of the most lethal malignancies and is almost always fatal. In this review article, the role of radiation therapy, systemic therapy, as well as the molecular basis of classifying GBM is described. Technological advances in the treatment of GBM are outlined as well as the diagnostic imaging characteristics of this tumor. In addition, factors that affect prognosis such as differentiating progression from treatment effect is discussed. The role of MRI guided radiation therapy and how this technology may provide a mechanism to improve the care of patients with this disease are described.

Purpose: We investigated why three patient-derived xenograft (PDX) childhood BRAFV600E-mutant brain tumor models are highly sensitive to trametinib. Mechanisms of acquired resistance selected in situ, and approaches to prevent resistance were also examined, which may translate to both low-grade glioma (LGG) molecular subtypes., Experimental Design: Sensitivity to trametinib [MEK inhibitor (MEKi)] alone or in combination with rapamycin (TORC1 inhibitor), was evaluated in pediatric PDX models. The effect of combined treatment of trametinib with rapamycin on development of trametinib resistance in vivo was examined. PDX tissue and tumor cells from trametinib-resistant xenografts were characterized., Results: In pediatric models TORC1 is activated through ERK-mediated inactivation of the tuberous sclerosis complex (TSC): consequently inhibition of MEK also suppressed TORC1 signaling. Trametinib-induced tumor regression correlated with dual inhibition of MAPK/TORC1 signaling, and decoupling TORC1 regulation from BRAF/MAPK control conferred trametinib resistance. In mice, acquired resistance to trametinib developed within three cycles of therapy in all three PDX models. Resistance to trametinib developed in situ is tumor-cell-intrinsic and the mechanism was tumor line specific. Rapamycin retarded or blocked development of resistance., Conclusions: In these three pediatric BRAF-mutant brain tumors, TORC1 signaling is controlled by the MAPK cascade. Trametinib suppressed both MAPK/TORC1 pathways leading to tumor regression. While low-dose intermittent rapamycin to enhance inhibition of TORC1 only modestly enhanced the antitumor activity of trametinib, it prevented or retarded development of trametinib resistance, suggesting future therapeutic approaches using rapamycin analogs in combination with MEKis that may be therapeutically beneficial in both KIAA1549::BRAF- and BRAFV600E-driven gliomas., (©2022 American Association for Cancer Research.)

Background: Meningiomas are the most common tumor arising within the cranium of adults. Despite surgical resection and radiotherapy, many meningiomas invade the brain, and many recur, often repeatedly. To date, no chemotherapy has proven effective against such tumors. Thus, there is an urgent need for chemotherapeutic options for treating meningiomas, especially those that enhance radiotherapy. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 that has been shown to enhance radiotherapy in preclinical models of other cancers, is well-tolerated in patients, and is used to treat malignancies elsewhere in the body. We, therefore, sought to determine its therapeutic potential in preclinical models of meningioma., Methods: Patient-derived meningioma cells were tested in vitro and in vivo with combinations of palbociclib and radiation. Outputs included cell viability, apoptosis, clonogenicity, engrafted mouse survival, and analysis of engrafted tumor tissues after therapy., Results: We found that palbociclib was highly potent against p16-deficient, Rb-intact CH157 and IOMM-Lee meningioma cells in vitro , but was ineffective against p16-intact, Rb-deficient SF8295 meningioma cells. Palbociclib also enhanced the in vitro efficacy of radiotherapy when used against p16-deficient meningioma, as indicated by cell viability and clonogenic assays. In vivo , the combination of palbociclib and radiation extended the survival of mice bearing orthotopic p16 deficient meningioma xenografts, relative to each as a monotherapy., Conclusions: These data suggest that palbociclib could be repurposed to treat patients with p16-deficient, Rb-intact meningiomas, and that a clinical trial in combination with radiation therapy merits consideration., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: A comprehensive response to the unprecedented SARS-CoV-2 (COVID-19) challenges for public health and its impact on radiation oncology patients and personnel for resilience and adaptability is presented., Methods: The general recommendations included working remotely when feasible, implementation of screening/safety and personal protective equipment (PPE) guidelines, social distancing, regular cleaning of treatment environment, and testing for high-risk patients/procedures. All teaching conferences, tumor boards, and weekly chart rounds were conducted using a virtual platform. Additionally, specific recommendations were given to each section to ensure proper patient treatments. The impact of these measures, especially adaptability and resilience, were evaluated through specific questionnaire surveys., Results: These comprehensive COVID-19-related measures resulted in most staff expressing a consistent level of satisfaction in regard to personal safety, maintaining a safe work environment, continuing quality patient care, and continuing educational activities during the pandemic. There was a significant reduction in patient treatments and on-site patient visits with an appreciable increase in the number of telemedicine e-visits., Conclusions: Survey results demonstrated substantial adaptability and resilience, including in the rapid recovery of departmental activities during the reactivation phase. In the event of a future public health emergency, the measures implemented may be adopted with good outcomes by radiation oncology departments across the globe.

Purpose  This study aims to report long-term clinical outcomes after Gamma Knife radiosurgery (GKRS) for intracranial grade 2 meningiomas. Methods  In this Institutional Review Board approved study, we reviewed records of all patients with grade 2 meningiomas treated with GKRS between 1998 and 2014. Results  A total of 97 postoperative histopathologically confirmed grade 2 meningiomas in 75 patients were treated and are included in this study. After a mean follow-up of 41 months, 28 meningiomas had local recurrence (29.79%). Median time to local recurrence was 89 months (mean: 69, range: 47-168). The 3- and 5-year actuarial local control (LC) rates were 68.9 and 55.7%, respectively. The 3- and 5-year overall survival rates were 88.6 and 81.1%, respectively. There was a trend toward worse LC with tumors treated with radiation doses ≤ 13 versus > 13 Gy. There was no radiation necrosis or second malignant tumors noted in our series. Conclusion  This report, one of the largest GKRS series for grade 2 meningiomas, demonstrates that GKRS is a safe and effective treatment modality for patients with grade 2 meningiomas with durable tumor control and minimal toxicity. Adjuvant GKRS could be considered as a reasonable treatment approach for patients with grade 2 meningiomas.

Objectives: This study aims to report tumor control rates and cranial nerve function after low dose (11.0 Gy) Gamma knife radiosurgery (GKRS) in patients with vestibular schwannomas., Methods: A retrospective chart review was performed on 30 consecutive patients with vestibular schwannomas treated from March 2004 to August 2010 with GKRS at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The marginal dose for all patients was 11.0 Gy prescribed to the 50% isodose line. Median follow-up time was 42 months. The median treatment volume was 0.53 cm3. Hearing data were obtained from audiometry reports before and after radiosurgery., Results: The actuarial progression free survival (PFS) based on freedom from surgery was 100% at 5 years. PFS based on freedom from persistent growth was 91% at 5 years. One patient experienced tumor progression requiring resection at 87 months. Serviceable hearing, defined as Gardner-Robertson score of I-II, was preserved in 50% of patients. On univariate and multivariate analyses, only higher mean and maximum dose to the cochlea significantly decreased the proportion of patients with serviceable hearing., Conclusion: Vestibular schwannomas can be treated with low doses (11.0 Gy) of GKRS with good tumor control and cranial nerve preservation.

Purpose: While there are several reports of prostate multisector dosimetry data obtained from CT or MRI scans performed at intervals ranging from 14-70 days after prostate brachytherapy (PB), there are no reports on multisector dosimetry performed in the immediate post-implant period. This study was undertaken to determine the results of prostate multisector dosimetry performed in the immediate post-implant period on day 1 post-implant dosimetry after (125)I PB., Material and Methods: The day 1 post-implant CT-based V100 and D90 were determined for the prostate base (PGB) and compared to doses to the entire gland (PG), mid-gland (PMG), and apex (PA) in 75 patients who underwent (125)I PB to a dose of 144 Gy. Similar multisector dosimetry was also performed on the pre-implant ultrasound volume study scans of these patients., Results: All patients had good quality implants. On day 1 post-implant multisector dosimetry there was significant under dosage of the PGB for both V100 and D90. The average magnitude of under dosage of PGB compared to PMG and PA was 17.2% and 22.7% for V100 and 44.6 Gy and 31.7 Gy for D90, respectively. On pre-implant multisector dosimetry there was no statistically significant under dosage of the PGB for V100, but the PGB D90 was significantly lower compared to PMG and PA, however, the average magnitude of under dosage was small at 12.6 Gy and 4.2 Gy, respectively., Conclusions: This report demonstrates that similar to other reports on more delayed post-implant multisector dosimetry data, there is significant under dosage of the prostate base in the immediate post-implant period based on day 1 post-implant dosimetry. The clinical significance of this under dosage remains to be defined and further studies are warranted.