Stereotactic radiosurgery for brain metastasis from cholangiocarcinoma.

OBJECTIVE: Accounting for approximately 15% of primary liver cancers and 3% of gastrointestinal malignancies, cholangiocarcinoma (CCA) poses a serious health concern given its high mortality rate. Managing brain metastases (BMs) from CCA is challenging because of their rarity and poor prognosis, with little guidance on treatment from the literature. In this study, the authors aimed to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in managing BMs from CCA. METHODS: This multicenter retrospective study included 13 CCA patients with 41 BMs treated with SRS from October 2006 to April 2022 at eight institutions affiliated with the International Radiosurgery Research Foundation. Inclusion criteria were a CCA diagnosis, an age over 18 years, no other malignancies, single-fraction SRS treatment for BMs, and at least one follow-up image. Data on demographics, tumor characteristics, treatment details, and outcomes were collected. The primary endpoints were local control (LC), intracranial progression-free survival (PFS), and overall survival (OS). The secondary endpoint was the development of adverse radiation effects (AREs). RESULTS: The median radiological follow-up was 5 months (range 1-18 months). At the last follow-up, LC was achieved in 39 (95.1%) of 41 BMs. New distant metastases were observed in 3 patients (23.1%), and the mean intracranial PFS was 9.4 months (95% CI 6.5-12.3 months). Six-month and 1-year OS rates were 38.5% and 11.5%, respectively, and the median OS was 6 months (95% CI 4.9-7.2 months). Concurrent immunotherapy was associated with a high risk of local failure (HR 29.665, 95% CI 1.799-489.206, p = 0.018), and the absence of systemic chemotherapy before SRS was linked to reduced OS (HR 6.658, 95% CI 1.173-37.776, p = 0.032). Regarding AREs, only 1 patient (7.7%) experienced right hemiparesis and was treated with corticosteroid therapy. CONCLUSIONS: SRS is an effective option for managing BMs in CCA patients, showing promise in LC and a high safety profile.

Characterization of Pediatric Infratentorial Arteriovenous Malformations: A Retrospective, Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Infratentorial arteriovenous malformations (AVMs) harbor different characteristics compared with supratentorial AVMs. This study aims to explore the unique characteristics of pediatric infratentorial AVMs and their response to single session stereotactic radiosurgery (SRS). METHODS: The International Radiosurgery Research Foundation database of pediatric patients with AVM (age <18 years) who underwent SRS was retrospectively reviewed. Baseline demographics, AVM characteristics, outcomes, and complications post-SRS were compared between infratentorial and supratentorial pediatric AVMs. Unfavorable outcome was defined as the absence of AVM obliteration, post-SRS hemorrhage, or permanent radiation-induced changes at last follow-up. RESULTS: A total of 535 pediatric AVMs managed with SRS with a median follow-up of 67 months (IQR 29.0-130.6) were included, with 69 being infratentorial and 466 supratentorial. The infratentorial group had a higher proportion of deep location (58.4% vs 30.3%, P = <.001), deep venous drainage (79.8% vs 61.8%, P = .004), and prior embolization (26.1% vs 15.7%, P = .032). There was a higher proportion of hemorrhagic presentation in the infratentorial group (79.7% vs 71.3%, P = .146). There was no statistically significant difference in the odds of an unfavorable outcome (odds ratio [OR] = 1.36 [0.82-2.28]), AVM obliteration (OR = 0.85 [0.5-1.43]), post-SRS hemorrhage (OR = 0.83 [0.31-2.18]), or radiologic radiation-induced changes (OR = 1.08 [0.63-1.84]) between both cohorts. No statistically significant difference on the rates of outcomes of interest and complications were found in the adjusted model. CONCLUSION: Despite baseline differences between infratentorial and supratentorial pediatric AVMs, SRS outcomes, including AVM obliteration and post-SRS hemorrhage rates, were comparable amongst both groups. SRS appears to have a similar risk profile and therapeutic benefit to infratentorial pediatric AVMs as it does for those with a supratentorial location.

Repeat single-session stereotactic radiosurgery for arteriovenous malformation: a systematic review and meta-analysis.

BACKGROUND: Stereotactic radiosurgery is the preferred option for treating brain arteriovenous malformation (AVM) when the risks associated with surgery outweigh the potential benefits. However, some patients require repeat radiosurgery due to residual AVM after the first procedure. This systematic review and meta-analysis aimed to investigate the safety and efficacy of repeated procedure of radiosurgery for AVM. METHOD: A systematic review was conducted according to the PRISMA guideline. The search was conducted on PubMed, Scopus, Embase, and Web of Science, using a pre-designed search string. Studies investigating the efficacy of repeat radiosurgery for residual AVM following initial single session radiosurgery were included. The risk of bias was assessed using the JBI tool. Meta-analysis and met-regression were performed to pool and inspect data. RESULTS: Our meta-analysis, with a mean follow-up of 45.57 months, reveals repeat radiosurgery as a viable option for arteriovenous malformations (AVMs), achieving a 60.82% obliteration rate with a mean time to obliteration of 33.18 months. Meta-regression identifies AVM volume and Spetzler-Martin (SM) grade as factors influencing obliteration, with smaller volume and lower SM grades associated with higher rates. Complications include 10.33% radiation-induced changes, 5.26% post-radiosurgery hemorrhage, 2.56% neurologic deficits, and 0.67% cyst formation. Heterogeneity in complications is primarily attributed to male proportion and SM grade, while factors influencing post-radiosurgery hemorrhage remain unclear. The type of radiosurgery, whether Gamma Knife Radiosurgery (GKRS) or LINAC, does not significantly impact outcomes. CONCLUSION: Repeat radiosurgery is a feasible, effective, and safe treatment for AVMs following failure of initial radiosurgery. When utilized in appropriate patient subgroups, it provides an acceptable risk-to-benefit profile. Feature studies are required to clarify its clear indications.

Long-term Outcomes of Surgery and Radiation Treatment for Adult Patients with Craniopharyngioma.

OBJECTIVE: Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in the adult population undergoing GTR versus STR-RT. METHODS: A total of 115 patients in 5 institutions were enrolled in this retrospective study on adult craniopharyngiomas. Patients with STR received postoperative RT with stereotactic radiosurgery (SRS) or fractionated radiation therapy (FRT) per institutional preference and ability to spare optic structures. RESULTS: Median age was 44 years (19 - 79 years). GTR was achieved in 34 patients and STR-RT in 81 patients with median follow up of 78.9 months (1 - 268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection there was no difference in local control (p = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in STR-RT patients that were underdosed with FRT (p = 0.03) or SRS (p = 0.04). CONCLUSIONS: There is good long-term control for adult craniopharyngioma that underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long term morbidity.

Stereotactic radiosurgery in the management of skull base chordomas: a comprehensive systematic review and meta-analysis.

OBJECTIVE: Chordoma is a primary bone tumor with limited literature on its management because of its rarity. Resection, while considered the first-line treatment, does not always provide adequate tumor control. In this systematic review, the authors aimed to provide comprehensive insights by managing these tumors with stereotactic radiosurgery (SRS). METHODS: A systematic review was conducted according to PRISMA guidelines using the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases. Search terms included chordoma and radiosurgery and their equivalent terms. Data on baseline characteristics, SRS details, and outcomes were extracted. The Joanna Briggs Institute checklist was used to assess risk of bias. A meta-analysis was performed on relevant variables. RESULTS: A total of 33 eligible studies encompassing 714 patients with skull base chordomas were included. Most studies had a low risk of bias. Patients, predominantly male (57.37%) with a mean age of 46.54 years, exhibited a conventional chordoma subtype (74.77%) and primary lesions (77.91%), mainly in the clivus (98.04%). The mean lesion volume was 13.49 cm3, and 96.68% of patients had undergone prior surgical attempts. Gamma Knife radiosurgery (88.76%) was the predominant SRS method. Radiologically, 27.19% of patients experienced tumor regression, while 55.02% showed no signs of disease progression at the latest follow-up. Progression occurred after a mean of 48.02 months. Symptom improvement was noted in 27.98% of patients. Radiosurgery was associated with a relatively low overall adverse event rate (11.94%), mainly cranial nerve deficits (8.72%). Meta-regression revealed that age and primary lesion type influenced symptom improvement, while factors like extent of resection, radiotherapy, and SRS type affected adverse event rates. CONCLUSIONS: This systematic review provides evidence on the safety and effectiveness of radiosurgery in the management of skull base chordomas. Local tumor control was achieved in the majority of patients treated with SRS. Various baseline characteristics and SRS features have been analyzed to identify modifying factors for each outcome to provide a framework for informed decision-making when managing these patients.

Vestibular Schwannoma International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS Study.

PURPOSE: The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function. METHODS AND MATERIALS: This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes. RESULTS: In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001). CONCLUSIONS: SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.

Stereotactic radiosurgery for intracranial cavernous malformations of the deep-seated locations: systematic review and meta-analysis.

OBJECTIVE: To determine the outcomes of stereotactic radiosurgery (SRS) for deep-seated (brainstem, basal ganglia, thalamus, cerebellar peduncle) intracranial cavernous malformations (ICMs). METHODS: A systematic review and meta-analysis was performed according to PRISMA and MOOSE guidelines. The main outcomes were comparing pre- and post-SRS hemorrhage rates, using the pooled risk ratios (RR) as the measure of effect. Additionally, the study assessed lesion volume changes and radiation-injury incidence. RESULTS: Data of 850 patients across 14 studies were included in the meta-analysis. The pooled RR of all deep-seated ICMs show a decrease in hemorrhage rate after SRS compared to pre-SRS over the total follow-up period (RR =0.13), initial 2 years (RR =0.22), and after 2 years (RR =0.07). For 9 studies that reported hemorrhage rate of the brainstem only, the pooled RR shows a decrease of hemorrhage rate after SRS compared to pre-SRS over the total follow-up period (RR =0.13), initial 2 years (RR =0.19), and after 2 years (RR =0.07). Volumetric regression was achieved in 44.25% and stability in 56.1%. The pooled incidence of symptomatic and permanent radiation injury was 9% (95% CI, 7-11) and 3% (95% CI, 0-1.9%), respectively. CONCLUSION: SRS appears effective in reducing hemorrhage rates for deep-seated ICMs. The risk of symptomatic radiation injury is low. Given the high risk of surgical morbidity, SRS is a reasonable treatment option for patients with deep-seated ICMs with at least one prior hemorrhage.

Stereotactic radiosurgery with versus without embolization for intracranial dural arteriovenous fistulas: a systematic review and meta-analysis.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been established as a safe and alternative treatment for dural arteriovenous fistulas (dAVFs). While embolization alone is the most commonly used modality for the treatment of dAVFs, the adjunctive use of embolization with SRS, with the growing use of SRS, has gained increasing interest in the past few years. However, the relative efficacy and safety of SRS combined with embolization versus SRS alone for dAVFs remains uncertain. Hence, this systematic review aimed to evaluate the efficacy of SRS with adjunctive embolization for intracranial dAVFs. METHODS: A systematic review and meta-analysis was conducted by searching electronic databases, including PubMed, Embase, and the Cochrane Library, up to August 2023. All studies evaluating the utilization of adjunctive embolization and SRS for dAVFs were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on the suitable outcomes. RESULTS: Eighteen studies involving 715 patients were included. The mean age of the participants in the study was 64.30 years in the adjunctive embolization group and 60.51 years in the SRS-alone group. In the adjunctive embolization group 41.3% of patients were female, compared with 47.1% in the SRS-only group. The dAVF obliteration rates were 64.7% and 65.7% in the adjunctive embolization and SRS-alone groups, respectively. These obliteration rates were comparable between the two groups (p = 0.96), as were the symptom improvement rates (p = 0.35). Adverse events were rare, and were more commonly associated with the adjunctive embolization procedure, although further causal analysis was not possible. CONCLUSIONS: This study provides evidence that adjunctive embolization plus SRS provides similar obliteration and symptom improvement rates compared with SRS alone, with both having very limited SRS-related adverse events. Considering the added burden and adverse events of additional endovascular treatment, the authors recommend embolization be reserved for more complex dAVFs or when embolization can potentially be curative alone or provide more rapid symptomatic relief or protection during the radiosurgical latency period.

Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization.

OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

OBJECTIVE: Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS: There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS: SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

Hypofractionated Stereotactic Radiosurgery in the Management of Brain Metastases.

Stereotactic radiosurgery (SRS) is an important weapon in the management of brain metastases. Single-fraction SRS is associated with local control rates ranging from approximately 70% to 100%, which are largely dependent on lesion and postoperative cavity size. The rates of local control and improved neurocognitive outcomes compared with conventional whole-brain radiation therapy have led to increased adoption of SRS in these settings. However, when treating larger targets and/or targets located in eloquent locations, the risk of normal tissue toxicity and adverse radiation effects within healthy brain tissue becomes significantly higher. Thus, hypofractionated SRS has become a widely adopted approach, which allows for the delivery of ablative doses of radiation while also minimizing the risk of toxicity. This approach has been studied in multiple retrospective reports in both the postoperative and intact settings. While there are no reported randomized data to date, there are trials underway evaluating this paradigm. In this article, we review the role of hypofractionated SRS in the management of brain metastases and emerging data that will serve to validate this treatment approach. Pertinent articles and references were obtained from a comprehensive search of PubMed/MEDLINE and clinicaltrials.gov.

The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Focused Ultrasound Blood-Brain Barrier Opening Arrests the Growth and Formation of Cerebral Cavernous Malformations.

BACKGROUND: Cerebral cavernous malformations (CCM) are vascular lesions within the central nervous system, consisting of dilated and hemorrhage-prone capillaries. CCMs can cause debilitating neurological symptoms, and surgical excision or stereotactic radiosurgery are the only current treatment options. Meanwhile, transient blood-brain barrier opening (BBBO) with focused ultrasound (FUS) and microbubbles is now understood to exert potentially beneficial bioeffects, such as stimulation of neurogenesis and clearance of amyloid-ß. Here, we tested whether FUS BBBO could be deployed therapeutically to control CCM formation and progression in a clinically-representative murine model. METHODS: CCMs were induced in mice by postnatal, endothelial-specific Krit1 ablation. FUS was applied for BBBO with fixed peak-negative pressures (PNPs; 0.2-0.6 MPa) or passive cavitation detection-modulated PNPs. Magnetic resonance imaging (MRI) was used to target FUS treatments, evaluate safety, and measure longitudinal changes in CCM growth after BBBO. RESULTS: FUS BBBO elicited gadolinium accumulation primarily at the perilesional boundaries of CCMs, rather than lesion cores. Passive cavitation detection and gadolinium contrast enhancement were comparable in CCM and wild-type mice, indicating that Krit1 ablation does not confer differential sensitivity to FUS BBBO. Acutely, CCMs exposed to FUS BBBO remained structurally stable, with no signs of hemorrhage. Longitudinal MRI revealed that FUS BBBO halted the growth of 94% of CCMs treated in the study. At 1 month, FUS BBBO-treated lesions lost, on average, 9% of their pre-sonication volume. In contrast, non-sonicated control lesions grew to 670% of their initial volume. Lesion control with FUS BBBO was accompanied by a marked reduction in the area and mesenchymal appearance of Krit mutant endothelium. Strikingly, in mice receiving multiple BBBO treatments with fixed PNPs, de novo CCM formation was significantly reduced by 81%. Mock treatment plans on MRIs of patients with surgically inaccessible lesions revealed their lesions are amenable to FUS BBBO with current clinical technology. CONCLUSIONS: Our results establish FUS BBBO as a novel, non-invasive modality that can safely arrest murine CCM growth and prevent their de novo formation. As an incisionless, MR image-guided therapy with the ability to target eloquent brain locations, FUS BBBO offers an unparalleled potential to revolutionize the therapeutic experience and enhance the accessibility of treatments for CCM patients.

Estimating the risk of brain metastasis for patients newly diagnosed with cancer.

BACKGROUND: Brain metastases (BM) affect clinical management and prognosis but limited resources exist to estimate BM risk in newly diagnosed cancer patients. Additionally, guidelines for brain MRI screening are limited. We aimed to develop and validate models to predict risk of BM at diagnosis for the most common cancer types that spread to the brain. METHODS: Breast cancer, melanoma, kidney cancer, colorectal cancer (CRC), small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC) data were extracted from the National Cancer Database to evaluate for the variables associated with the presence of BM at diagnosis. Multivariable logistic regression (LR) models were developed and performance was evaluated with Area Under the Receiver Operating Characteristic Curve (AUC) and random-split training and testing datasets. Nomograms and a Webtool were created for each cancer type. RESULTS: We identify 4,828,305 patients from 2010-2018 (2,095,339 breast cancer, 472,611 melanoma, 407,627 kidney cancer, 627,090 CRC, 164,864 SCLC, and 1,060,774 NSCLC). The proportion of patients with BM at diagnosis is 0.3%, 1.5%, 1.3%, 0.3%, 16.0%, and 10.3% for breast cancer, melanoma, kidney cancer, CRC, SCLC, and NSCLC, respectively. The average AUC over 100 random splitting for the LR models is 0.9534 for breast cancer, 0.9420 for melanoma, 0.8785 for CRC, 0.9054 for kidney cancer, 0.7759 for NSCLC, and 0.6180 for SCLC. CONCLUSIONS: We develop accurate models that predict the BM risk at diagnosis for multiple cancer types. The nomograms and Webtool may aid clinicians in considering brain MRI at the time of initial cancer diagnosis.

When patients are diagnosed with cancer, it is unknown which patients have a significant risk of cancer spread to the brain. Cancer spread to the brain is important to diagnose since it changes how patients are treated and affects their prognosis. This study used a large national database of patients diagnosed with cancer and studied the characteristics that were associated with cancer spread to the brain. The results can be used by doctors to assess the risk of cancer spread to the brain and determine which patients with cancer may benefit most from brain imaging.

Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients. METHODS: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded. RESULTS: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic. CONCLUSIONS: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients.

OBJECTIVE: The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients. METHODS: Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation. RESULTS: The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%-7.8%) at 1 year to 44% (95% CI 32%-55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%-62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%-16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed. CONCLUSIONS: The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.