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Treatment of arteriovenous malformations (AVM) with stereotactic radiosurgery (SRS) has been shown to lead to complete response in short-interval time series. The long-term outcomes for these patients have remained a clinical question. Here we present the long-term outcomes of LINAC-based SRS treatments at a high-volume single institution academic center. Consecutive patients treated with LINAC-based SRS treatments with a diagnosis of AVM between 1989 and 2023 were identified. Clinical and dosimetric data were retrospectively collected. Kaplan Meier analysis was utilized to calculate time to complete response (CR). Multivariate linear regression was performed to identify prognostics indicators for disease response. One-hundred and forty patients were identified. Seven patients did not have adequate follow-up imaging to assess disease response, leaving 133 patients evaluable for this study. 70 patients had a reported CR to SRS treatment. An additional 48 patients had a partial response (PR), 11 had stable disease (SD), and 4 had progressive disease (PD). The Kaplan Meier plot estimate probability for CR at 10 years was 56.5% (95% CI = 0.47, 0.68). Median Kaplan Meier estimate of CR achievement was 13.2 years. Of the patients who did not achieve CR (n = 63), median follow-up imaging was 7.2 years. Nineteen patients (14%) of patients did experience a bleed after SRS treatment, with median time reported of 30 months. Multivariate analysis demonstrated the Spetzler-Martin grade (p = 0.01), treatment dose (p = 0.009) and target volume (p = 0.026) were significantly associated with CR rates. LINAC-based stereotactic radiosurgery in the setting of arteriovenous malformations appears to maintain long-term efficacy and safety. Spetzler-Martin grade, dose and treatment volumes are strong predictors for long-term efficacy of SRS for CR in these patients. [ABSTRACT FROM AUTHOR]

Purpose: Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study., Methods: In Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3., Results: Response rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease., Conclusions: This Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matthew Evison – Declarations of interest: none; Gregory Videtic – Declarations of interest: none; Corinne Faivre-Finn –Declarations of interest: none; Kevin Franks –Declarations of interest: none; Suresh Senan – Varian Medical Systems: Advisory board, Departmental research support; AstraZeneca: Advisory board, Institutional research support; BMS: Institutional research support; MSD: Advisory board, consultancy; Iain Phillips –Declarations of interest: none; Jacqueline Kruser –Dr. Kruser has received support for unrelated work from the National Institutes of Health/National Heart, Lung, and Blood Institute under grant numbers F32HL140824 and K23HL146890. Dr. Kruser’s spouse receives honoraria for lectures and speakers bureaus from Astra Zeneca. (Found online); David Palma – Dr Palma reports a Clinician-Scientist Grant from the Ontario Institute for Cancer Research, royalties from Uptodate.com, and a consultant role with equity from Need Inc, all unrelated to the current work; Timothy Kruser –Dr. Kruser sits on the speakers bureau and advisory board for AstraZeneca and serves as a Consultant for Radiologica LLC; Clive Peedell – Disclosures: Speaker fees Elekta, Varian; Clifford Robinson – Radialogica: Leadership, Stock and Other Ownership Interests; Quantaras: Stock and Other Ownership Interests, Consulting or Advisory Role; Varian Medical Systems: Consulting or Advisory Role, Research Funding; AstraZeneca: Consulting or Advisory Role; MED Serono: Consulting or Advisory Role; EmpNia: Consulting or Advisory Role; Merck: Research Funding; Noninvasive imaging and treatment system for cardiac arrhythmias WO 2017078757 A1 U.S. Provisional Application No. 62/598,162 Entitled SYSTEM AND METHOD FOR DETERMINING SEGMENTS FOR ABLATION: Patents, Royalties, Other Intellectual Property; Angela Wright – Declarations of interest: none; Lorraine McCleod – Declarations of interest: none; Percy Lee –Declarations: Varian, Viewray, AstraZeneca, Genentech, Johnson & Johnson: Consulting Fees; AstraZeneca, UK: Manuscript support for a different manuscript (“All support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.) No time limit for this item.”); Varian, Viewray, AstraZeneca: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Radiosurgery Society: Support for attending meeting/travel; Genentech, Viewray, AstraZeneca: Participation on a Data Safety Monitoring Board or Advisory Board; Radiosurgery Society board of director: Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid; Houda Bahig –Declarations: Research grants from Varian Medical Systems; Research grant from Astra Zeneca; Advisory boards - Sanofi & Astra Zeneca; Kevin Chua – Declarations: Advisory boards: AstraZeneca, Regeneron, Roche, Seagen, MSD, Takeda; Speaker honoraria: Varian, PeerVoice; Travel: Varian; Shakar Shiva – Declarations of interest: none; Melody Qu – Declarations of interest: none; Nazia Chaudhuri –Declarations of interest: none; Susan Harden –Declarations of interest: none; Cicely Cunningham –Declarations of interest: none; Indu S. Voruganti Maddali – Declarations of interest: none; Alexander V. Louie – Dr. Louie has received honoraria from AstraZeneca, unrelated to this review; Stephen Harrow – Declarations of interest: none., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background: Tumor Treating Fields (TTFields) Therapy is an FDA-approved therapy in the first line and recurrent setting for glioblastoma. Despite Phase 3 evidence showing improved survival with TTFields, it is not uniformly utilized. We aimed to examine patient and clinician views of TTFields and factors shaping utilization of TTFields through a unique research partnership with medical neuro oncology and medical social sciences., Methods: Adult glioblastoma patients who were offered TTFields at a tertiary care academic hospital were invited to participate in a semi-structured interview about their decision to use or not use TTFields. Clinicians who prescribe TTFields were invited to participate in a semi-structured interview about TTFields., Results: Interviews were completed with 40 patients with a mean age of 53 years; 92.5% were white and 60% were male. Participants who decided against TTFields stated that head shaving, appearing sick, and inconvenience of wearing/carrying the device most influenced their decision. The most influential factors for use of TTFields were the efficacy of the device and their clinician's opinion. Clinicians (N = 9) stated that TTFields was a good option for glioblastoma patients, but some noted that their patients should consider the burdens and benefits of TTFields as it may not be the desired choice for all patients., Conclusions: This is the first study to examine patient decision making for TTFields. Findings suggest that clinician support and efficacy data are among the key decision-making factors. Properly understanding the path to patients' decision making is crucial in optimizing the use of TTFields and other therapeutic decisions for glioblastoma patients., (© 2024. The Author(s).)

Background: The role for radiotherapy or surgery in the upfront management of brain metastases (BrM) in epidermal growth factor receptor mutant ( EGFR m) or anaplastic lymphoma kinase translocation positive ( ALK +) non-small cell lung cancer (NSCLC) is uncertain because of a lack of prospective evidence supporting tyrosine kinase inhibitor (TKI) monotherapy. Further understanding of practice heterogeneity is necessary to guide collaborative efforts in establishing guideline recommendations., Methods: We conducted an international survey among medical (MO), clinical (CO), and radiation oncologists (RO), as well as neurosurgeons (NS), of treatment recommendations for asymptomatic BrM (in non-eloquent regions) EGFRm or ALK+ NSCLC patients according to specific clinical scenarios. We grouped and compared treatment recommendations according to specialty. Responses were summarized using counts and percentages and analyzed using the Fisher exact test., Results: A total of 449 surveys were included in the final analysis: 48 CO, 85 MO, 60 NS, and 256 RO. MO and CO were significantly more likely than RO and NS to recommend first-line TKI monotherapy, regardless of the number and/or size of asymptomatic BrM (in non-eloquent regions). Radiotherapy in addition to TKI as first-line management was preferred by all specialties for patients with ≥4 BrM. NS recommended surgical resection more often than other specialties for BrM measuring >2 cm., Conclusions: Recommendations for the management of BrM from EGFRm or ALK+ NSCLC vary significantly according to oncology sub-specialties. Development of multidisciplinary guidelines and further research on establishing optimal treatment strategies is warranted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-697/coif). NM serves on the advisory boards of Pfizer, Novartis, and Seagen. NM reports honoraria from Takeda Oncology and Astra Zeneca. FYM reports consulting fees from Elekta, and honoraria from Astra Zeneca and IASLC; grants and contracts from CTAQ Queen’s University. JCHY reports participation in advisory board with Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Ono Pharmaceuticals, Pfizer, Roche/Genentech, Takeda, Yuhan Pharmaceuticals, JNJ, Puma Technology, Gilead, and GSK; grant support with Astra Zeneca. JHL reports participation in advisory boards with Novartis, Takeda, Eli Lilly, and Astra Zeneca; consulting fees from Pfizer, and payments or honoraria from Bayer, Pfizer, Daiichi-Sankyo, Novartis and Boehringer Ingelheim. NP reports research support from Pfizer, Bayer, and Roche; Honoraria from Boehringer Ingelheim, Pfizer, Roche, Takeda, Pieere-Faber; Advisory board participation from Boehringer Ingelheim, MSD, Astra Zeneca, Merck, Bristol Meyers Squibb, Pfizer, Roche, Takeda, AllVascular, Beigene, Novartis. PK reports financial compensation from Medexus Pharmaceuticals Canada. MD reports consulting fees from Roche, Astra Zeneca, Takeda, Eisai, and Merck; honoraria from Roche and Astra Zeneca. NBL reports research support from Amgen, Array, Astra Zeneca, Bayer, Eli Lilly, EMD Serono, Pfizer, Roche, Guardant Health, Takeda; Honoraria from Amgen, Astra Zeneca, BMS, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and Takeda. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Radiotherapy (RT) and surgery (Sx) are effective in treating brain metastases. However, immune checkpoint inhibitors (ICI) have shown activity against asymptomatic melanoma brain metastases (MBM). BRAF/MEK inhibitors can be used to treat BRAF V600 mutation positive (BRAF+) MBM., Method: We conducted an international survey among experts from medical oncology (MO), clinical oncology (CO), radiation oncology (RO), and neurosurgery (NS) about treatment recommendations for patients with asymptomatic BRAF+ or BRAF mutation negative (BRAF-) MBM. Eighteen specific clinical scenarios were presented and a total of 267 responses were collected. Answers were grouped and compared using Fisher's exact test., Results: In most MBM scenarios, survey respondents, regardless of specialty, favored RT in addition to systemic therapy. However, for patients with BRAF+ MBM, MO and CO were significantly more likely than RO and NS to recommend BRAF/MEK inhibitors alone, without the addition of RT, including the majority of MO (51%) for patients with 1-3 MBM, all <2 cm. Likewise, for BRAF- MBM, MO and CO more commonly recommended single or dual agent ICI only and dual agent ICI therapy alone was the most common recommendation from MO or CO for MBM <2 cm. When at least 1 of 3 MBM (BRAF+ or BRAF-) was >2 cm, upfront Sx was recommended by all groups with the exception that MO and RO recommended RT for BRAF- MBM., Conclusions: In most clinical settings involving asymptomatic MBM, experts recommended RT in addition to systemic therapy. However, recommendations varied significantly according to specialty, with MO and CO more commonly recommending dual systemic therapy alone for up to 9 BRAF- MBM <2 cm., Competing Interests: Conflicts of interest statement The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: STK11 mutation ( STK11 m ) in patients (pts) with stage IV non-small cell lung cancer (NSCLC) is associated with inferior survival and poor response to immune checkpoint inhibitors (ICI). The significance of STK11 m in stage III NSCLC pts treated with concurrent chemoradiation (CCRT) with or without consolidation ICI is unknown., Methods: Stage III NSCLC patients who received CCRT and had known STK11 mutational status were included in this retrospective study. The data on the STK11 m pts were collected from 4 cancer institutions. A cohort of pts with wild type STK11 ( STK11 w ) from the University of Iowa served as a comparison group. Patient demographics and clinical characteristics were collected. Cox regression models were used to explore the effect of STK11 mutation on survival., Results: 75 pts with stage III NSCLC who had known STK11 mutational status were identified. 16/75 (21%) had STK11 m . 5/16 with STK11 m did not receive CCRT so they were excluded from the analysis. The clinical and demographic characteristics for the 11 STK11 m and 59 STK11 w pts were not statistically different ( STK11 m vs. STK11 w ): mean age: 57 vs. 64 yrs, non-squamous histology: 8/11 (73%) vs. 37/59 (63%), KRAS mutation: 3/11 (27%) vs. 11/59 (19%), TP53 mutation: 6/11 (55%) vs. 15/59 (25%), PD-L1 ≥50%: 1/8 (13%) vs. 10/32 (31%), and consolidation ICI 6/11 (55%) vs. 17/59 (29%). Regarding the 6 STK11 m pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3-17) vs. 6 (range, 1-25) in the 17 pts with STK11 w who received ICI (durvalumab). After adjusting for performance status and cancer stage, multivariable analysis showed that progression free survival (PFS) for the STK11 m pts was significantly worse than STK11 w pts (HR =2.25; 95% CI, 1.03-4.88, P=0.04), whereas overall survival (OS) showed no significant difference for STK11 m vs. STK11 w patients (HR 1.47, 95% CI, 0.49-4.38, P=0.49)., Conclusions: In stage III NSCLC patients who received CCRT, STK11 m was associated with worse PFS compared to STK11 w . Larger studies are needed to further explore the prognostic implications of STK11 m in stage III NSCLC and whether ICI impacts survival for this subgroup., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-177). MF serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. TK reports personal fees from AstraZeneca for consulting and advisory board, and personal fees AstraZeneca, OncLive, and Targeted Oncology for speaking. NHH’s institution received grant support from BMS, Genentech, Merck on studies that in which he is the PI, and is the medical writer for UptoDate and served on a DSMB for a study sponsored by Beyond Spring. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Background: Progress in extending the survival of glioblastoma (GBM) patients has been slow. A better understanding of why patient survival remains poor is critical to developing new strategies. Postmortem studies on GBM can shed light on why patients are dying., Methods: The brains of 33 GBM patients were autopsied and examined for gross and microscopic abnormalities. Clinical-pathologic correlations were accomplished through detailed chart reviews. Data were compared with older published autopsy GBM studies that predated newer treatment strategies, such as more extensive surgical resection and adjuvant temozolomide., Results: In older GBM autopsy series, mass effect was observed in 72% of brains, with herniation in 50% of all cases. Infiltration of tumor into the brainstem was noted in only 21% of those older cases. In the current series, only 10 of 33 (30%) GBMs showed mass effect (P = 0.0003), and only 1 (3%) showed herniation (P < 0.0001). However, extensive GBM infiltration of the brainstem was present in 22 cases (67%, P < 0.0001), with accompanying destruction of the pons and white matter tracts. There was a direct correlation between longer median patient survival and the presence of brainstem infiltration (16.1 mo in brainstem-invaded cases vs 9.0 mo in cases lacking extensive brainstem involvement; P = 0.0003)., Conclusions: With improving care, severe mass effect appears to be less common in GBM patients today, whereas dissemination, including life-threatening brainstem invasion, is now more pronounced. This has major implications regarding preclinical GBM models, as well as the design of clinical trials aimed at further improving patient survival., (© The Author(s) 2019. 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: Stereotactic radiosurgery (SRS) can enhance immune activation and improve disease control through stimulation of anti-tumor immunity. However, patients with cancer receiving chemotherapy are often immunosuppressed, which may impact the efficacy of SRS. Here we investigate the relationship between systemic lymphopenia and response to SRS in patients with brain-metastatic lung cancer., Methods: We reviewed 125 patients with lung cancer brain metastases treated with SRS between January 2014 and May 2017. Complete blood counts from the time of SRS were reviewed, and lymphopenia was defined as absolute lymphocyte count < 1×10 9 cells/L. Kaplan-Meier survival analysis and cox proportional-hazards models were used to evaluate risks of progression and death., Results: The median age was 65 years (range 43-86), with 54% female patients. Lymphopenia was present in 60 patients. In univariate analysis, lymphopenic patients had significantly shorter PFS (HR = 2.995, p < 0.0001) and OS (HR = 3.928, p < 0.0001). When accounting for age, gender, smoking history, ECOG score, surgery, and tumor histology in a multivariate model, lymphopenia remained significantly predictive of worse PFS (HR = 1.912, p = 0.002) and OS (HR = 2.257, p < 0.001). Patients who received immunotherapy within 3 months of SRS demonstrated significantly shorter PFS (HR = 3.578, p = 0.006) and OS (HR = 6.409, p = 0.001) if lymphopenic., Conclusions: Brain-metastatic lung cancer patients with lymphopenia treated with SRS had significantly worse PFS and OS. The effect of lymphopenia was even more pronounced in patients receiving immunotherapy. These data demonstrate the significant impact of deficient immunity on disease control and survival. Lymphopenic patients may benefit from interventions to improve immune function prior to SRS for brain metastases.

Meningiomas are the most common primary intracranial tumor. Important advances are occurring in meningioma research. These are expected to accelerate, potentially leading to impactful changes on the management of meningiomas in the near and medium term. This review will cover the histo- and molecular pathology of meningiomas, including recent 2016 updates to the WHO classification of CNS tumors. We will discuss clinical and radiographic presentation and therapeutic management. Surgery and radiotherapy, the two longstanding primary therapeutic modalities, will be discussed at length. In addition, data from prior and ongoing investigations of other treatment modalities, including systemic and targeted therapies, will be covered. This review will quickly update the reader on the contemporary management and future directions in meningiomas. [Formula: see text].

Background: Atypical and malignant meningiomas are far less common than benign meningiomas. As aggressive lesions, they are prone to local recurrence and may lead to decreased survival. Although malignant meningiomas typically are treated with maximal surgical resection and adjuvant radiotherapy (RT), to the authors' knowledge the optimal treatment for atypical lesions remains to be defined. There are limited prospective data in this setting., Methods: The National Cancer Data Base was queried to investigate cases of histologically confirmed meningiomas diagnosed from 2004 to 2014. This included 7811 patients with atypical meningiomas (World Health Organization grade 2) and 1936 patients with malignant meningiomas (World Health Organization grade 3); during the same period, a total of 60,345 patients were diagnosed with benign meningiomas (World Health Organization grade 1). Data collected included patient and tumor characteristics, extent of surgical resection, and use of RT. Survival analysis was performed using Kaplan-Meier estimates with the log-rank test of significance and Cox univariate and multivariate regression. Logistic regression was used to determine factors associated with use of RT., Results: The 5-year overall survival rate was 85.5% in patients with benign meningiomas, 75.9% in patients with atypical meningiomas, and 55.4% in patients with malignant meningiomas (P<.0001). In patients with atypical meningiomas, gross (macroscopic) total resection (GTR) and adjuvant RT were found to be associated with significantly improved survival, independently and especially in unison (GTR plus RT: hazard ratio, 0.47; P = .002). On multivariate analysis, the combination of GTR plus RT was found to be the most important factor for improved survival. However, GTR was associated with significantly lower rates of RT use., Conclusions: GTR and adjuvant RT appear to be highly associated with improved survival, independent of other factors, in patients with atypical meningiomas. Cancer 2018;124:734-42. © 2017 American Cancer Society., (© 2017 American Cancer Society.)