Identification of incidental brain tumors in prostate cancer patients via PSMA PET/CT.

PURPOSE: Brain metastases are rare in patients with prostate cancer and portend poor outcome. Prostate-specific membrane antigen positron emission tomography (PSMA PET)/CT scans including the brain have identified incidental tumors. We sought to identify the incidental brain tumor detection rate of PSMA PET/CT performed at initial diagnosis or in the setting of biochemical recurrence. METHODS: An institutional database was queried for patients who underwent 68Ga-PSMA-11 or 18F-DCFPyL (18F-piflufolastat) PET/CT imaging at an NCI-designated Comprehensive Cancer Center from 1/2018 to 12/2022. Imaging reports and clinical courses were reviewed to identify brain lesions and describe clinical and pathologic features. RESULTS: Two-thousand seven hundred and sixty-three patients underwent 3363 PSMA PET/CT scans in the absence of neurologic symptoms. Forty-four brain lesions were identified, including 33 PSMA-avid lesions: 10 intraparenchymal metastases (30%), 4 dural-based metastases (12%), 16 meningiomas (48%), 2 pituitary macroadenomas (6%), and 1 epidermal inclusion cyst (3%) (incidences of 0.36, 0.14, 0.58, 0.07, and 0.04%). The mean parenchymal metastasis diameter and mean SUVmax were 1.99 cm (95%CI:1.25-2.73) and 4.49 (95%CI:2.41-6.57), respectively. At the time of parenchymal brain metastasis detection, 57% of patients had no concurrent extracranial disease, 14% had localized prostate disease only, and 29% had extracranial metastases. Seven of 8 patients with parenchymal brain metastases remain alive at a median 8.8 months follow-up. CONCLUSION: Prostate cancer brain metastases are rare, especially in the absence of widespread metastatic disease. Nevertheless, incidentally detected brain foci of PSMA uptake may represent previously unknown prostate cancer metastases, even in small lesions and in the absence of systemic disease.

Fast, light, and scalable: harnessing data-mined line annotations for automated tumor segmentation on brain MRI.

OBJECTIVES: While fully supervised learning can yield high-performing segmentation models, the effort required to manually segment large training sets limits practical utility. We investigate whether data mined line annotations can facilitate brain MRI tumor segmentation model development without requiring manually segmented training data. METHODS: In this retrospective study, a tumor detection model trained using clinical line annotations mined from PACS was leveraged with unsupervised segmentation to generate pseudo-masks of enhancing tumors on T1-weighted post-contrast images (9911 image slices; 3449 adult patients). Baseline segmentation models were trained and employed within a semi-supervised learning (SSL) framework to refine the pseudo-masks. Following each self-refinement cycle, a new model was trained and tested on a held-out set of 319 manually segmented image slices (93 adult patients), with the SSL cycles continuing until Dice score coefficient (DSC) peaked. DSCs were compared using bootstrap resampling. Utilizing the best-performing models, two inference methods were compared: (1) conventional full-image segmentation, and (2) a hybrid method augmenting full-image segmentation with detection plus image patch segmentation. RESULTS: Baseline segmentation models achieved DSC of 0.768 (U-Net), 0.831 (Mask R-CNN), and 0.838 (HRNet), improving with self-refinement to 0.798, 0.871, and 0.873 (each p < 0.001), respectively. Hybrid inference outperformed full image segmentation alone: DSC 0.884 (Mask R-CNN) vs. 0.873 (HRNet), p < 0.001. CONCLUSIONS: Line annotations mined from PACS can be harnessed within an automated pipeline to produce accurate brain MRI tumor segmentation models without manually segmented training data, providing a mechanism to rapidly establish tumor segmentation capabilities across radiology modalities. KEY POINTS: • A brain MRI tumor detection model trained using clinical line measurement annotations mined from PACS was leveraged to automatically generate tumor segmentation pseudo-masks. • An iterative self-refinement process automatically improved pseudo-mask quality, with the best-performing segmentation pipeline achieving a Dice score of 0.884 on a held-out test set. • Tumor line measurement annotations generated in routine clinical radiology practice can be harnessed to develop high-performing segmentation models without manually segmented training data, providing a mechanism to rapidly establish tumor segmentation capabilities across radiology modalities.

Association of Lack of Speech Arrest During Cortical Stimulation With Interhemispheric Reorganization of the Functional Language Network in Patients With Brain Tumors.

BACKGROUND. Brain tumors induce language reorganization, which may influence the extent of resection in surgical planning. Direct cortical stimulation (DCS) allows definitive language mapping during awake surgery by locating areas of speech arrest (SA) surrounding the tumor. Although functional MRI (fMRI) combined with graph theory analysis can illustrate whole-brain network reorganization, few studies have corroborated these findings with DCS intraoperative mapping and clinical language performance. OBJECTIVE. We evaluated whether patients with low-grade gliomas (LGGs) without SA during DCS show increased right-hemispheric connections and better speech performance compared with patients with SA. METHODS. We retrospectively recruited 44 consecutive patients with left perisylvian LGG, preoperative language task-based fMRI, speech performance evaluation, and awake surgery with DCS. We generated language networks from ROIs corresponding to known language areas (i.e., language core) on fMRI using optimal percolation. Language core connectivity in the left and right hemispheres was quantified as fMRI laterality index (LI) and connectivity LI on the basis of fMRI activation maps and connectivity matrices. We compared fMRI LI and connectivity LI between patients with SA and without SA and used multivariable logistic regression (p < .05) to assess associations between DCS and connectivity LI, fMRI LI, tumor location, Broca area and Wernicke area involvement, prior treatments, age, handedness, sex, tumor size, and speech deficit before surgery, within 1 week after surgery, and 3-6 months after surgery. RESULTS. Patients with SA showed left-dominant connectivity; patients without SA lateralized more to the right hemisphere (p < .001). Between patients with SA and those without, fMRI LI was not significantly different. Patients without SA showed right-greater-than-left connectivity of Broca area and premotor area compared with patients with SA. Regression analysis showed significant association between no SA and right-lateralized connectivity LI (p < .001) and fewer speech deficits before (p < .001) and 1 week after (p = .02) surgery. CONCLUSION. Patients without SA had increased right-hemispheric connections and right translocation of the language core, suggesting language reorganization. Lack of interoperative SA was associated with fewer speech deficits both before and immediately after surgery. CLINICAL IMPACT. These findings support tumor-induced language plasticity as a compensatory mechanism, which may lead to fewer postsurgical deficits and allow extended resection.

Semisupervised Training of a Brain MRI Tumor Detection Model Using Mined Annotations.

Background Artificial intelligence (AI) applications for cancer imaging conceptually begin with automated tumor detection, which can provide the foundation for downstream AI tasks. However, supervised training requires many image annotations, and performing dedicated post hoc image labeling is burdensome and costly. Purpose To investigate whether clinically generated image annotations can be data mined from the picture archiving and communication system (PACS), automatically curated, and used for semisupervised training of a brain MRI tumor detection model. Materials and Methods In this retrospective study, the cancer center PACS was mined for brain MRI scans acquired between January 2012 and December 2017 and included all annotated axial T1 postcontrast images. Line annotations were converted to boxes, excluding boxes shorter than 1 cm or longer than 7 cm. The resulting boxes were used for supervised training of object detection models using RetinaNet and Mask region-based convolutional neural network (R-CNN) architectures. The best-performing model trained from the mined data set was used to detect unannotated tumors on training images themselves (self-labeling), automatically correcting many of the missing labels. After self-labeling, new models were trained using this expanded data set. Models were scored for precision, recall, and F1 using a held-out test data set comprising 754 manually labeled images from 100 patients (403 intra-axial and 56 extra-axial enhancing tumors). Model F1 scores were compared using bootstrap resampling. Results The PACS query extracted 31 150 line annotations, yielding 11 880 boxes that met inclusion criteria. This mined data set was used to train models, yielding F1 scores of 0.886 for RetinaNet and 0.908 for Mask R-CNN. Self-labeling added 18 562 training boxes, improving model F1 scores to 0.935 (P < .001) and 0.954 (P < .001), respectively. Conclusion The application of semisupervised learning to mined image annotations significantly improved tumor detection performance, achieving an excellent F1 score of 0.954. This development pipeline can be extended for other imaging modalities, repurposing unused data silos to potentially enable automated tumor detection across radiologic modalities. © RSNA, 2022 Online supplemental material is available for this article.

Salvage resection plus cesium-131 brachytherapy durably controls post-SRS recurrent brain metastases.

BACKGROUND: Salvage of recurrent previously irradiated brain metastases (rBrM) is a significant challenge. Resection without adjuvant re-irradiation is associated with a high local failure rate, while reirradiation only partially reduces failure but is associated with greater radiation necrosis risk. Salvage resection plus Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced normal brain dose versus re-irradiation, however data are limited. METHODS: A prospective registry of consecutive patients with post-stereotactic radiosurgery (SRS) rBrM undergoing resection plus implantation of collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60 Gy at 5 mm from the cavity was analyzed. RESULTS: Twenty patients underwent 24 operations with Cs131 implantation in 25 tumor cavities. Median maximum preoperative diameter was 3.0 cm (range 1.1-6.3). Gross- or near-total resection was achieved in 80% of lesions. A median of 16 Cs131 seeds (range 6-30), with a median air-kerma strength of 3.5 U/seed were implanted. There was one postoperative wound dehiscence. With median follow-up of 1.6 years for survivors, two tumors recurred (one in-field, one marginal) resulting in 8.4% 1-year progression incidence (95%CI = 0.0-19.9). Radiographic seed settling was identified in 7/25 cavities (28%) 1.9-11.7 months post-implantation, with 1 case of distant migration (4%), without clinical sequelae. There were 8 cases of radiation necrosis, of which 4 were symptomatic. CONCLUSIONS: With > 1.5 years of follow-up, intraoperative brachytherapy with commercially available Cs131 implants was associated with favorable local control and toxicity profiles. Weak correlation between preoperative tumor geometry and implanted tiles highlights a need to optimize planning criteria.

Patient-specific radiological protection precautions following Cs collagen embedded Cs-131 implantation in the brain.

OBJECTIVE: Cesium-131 brachytherapy is an adjunct for brain tumor treatment, offering potential clinical and radiation protection advantages over other isotopes including iodine-125. We present evidence-based radiation safety recommendations from an initial experience with Cs-131 brachytherapy in the resection cavities of recurrent, previously irradiated brain metastases. METHODS: Twenty-two recurrent brain metastases in 18 patients were resected and treated with permanent Cs-131 brachytherapy implantation using commercially procured seed-impregnated collagen tiles (GammaTile, GT Medical Technologies). Exposure to intraoperative staff was monitored with NVLAP-accredited ring dosimeters. For patient release considerations, NCRP guidelines were used to develop an algorithm for modeling lifetime exposure to family and ancillary staff caring for patients based on measured dose rates. RESULTS: A median of 16 Cs-131 seeds were implanted (range 6-46) with median cumulative strength of 58.72U (20.64-150.42). Resulting dose rates were 1.19 mSv/h (0.28-3.3) on contact, 0.08 mSv/h (0.01-0.35) at 30 cm, and 0.01 mSv/h (0.001-0.03) at 100 cm from the patient. Modeled total caregiver exposure was 0.91 mSv (0.16-3.26), and occupational exposure was 0.06 mSv (0.02-0.23) accounting for patient self-shielding via skull and soft tissue attenuation. Real-time dose rate measurements were grouped into brackets to provide close contact precautions for caregivers ranging from 1-3 weeks for adults and longer for pregnant women and children, including cases with multiple implantations. CONCLUSIONS: Radiological protection precautions were developed based on patient-specific emissions and accounted for multiple implantations of Cs-131, to maintain exposure to staff and the public in accordance with relevant regulatory dose constraints.

Melanoma brain metastasis presentation, treatment, and outcomes in the age of targeted and immunotherapies.

BACKGROUND: Historically, the prognosis for patients who have melanoma brain metastasis (MBM) has been dismal. However, breakthroughs in targeted and immunotherapies have improved long-term survival in those with advanced melanoma. Therefore, MBM presentation, prognosis, and the use of multimodality central nervous system (CNS)-directed treatment were reassessed. METHODS: In this retrospective study, the authors evaluated patients with MBM who received treatment at Memorial Sloan Kettering Cancer Center between 2010 and 2019. Kaplan-Meier methodology was used to describe overall survival (OS). Recursive partitioning analysis and time-dependent multivariable Cox modeling were used to assess prognostic variables and to associate CNS-directed treatments with OS. RESULTS: Four hundred twenty-five patients with 2488 brain metastases were included. The median OS after an MBM diagnosis was 8.9 months (95% CI, 7.9-11.3 months). Patients who were diagnosed with MBM between 2015 and 2019 experienced longer OS compared to those who were diagnosed between 2010 and 2014 (OS, 13.0 months [95% CI, 10.47-17.06 months] vs 7.0 months [95% CI, 6.1-8.3 months]; P = .0003). Prognostic multivariable modeling significantly associated shortened OS independently with leptomeningeal dissemination (P < .0001), increasing numbers of brain metastases at diagnosis (P < .0001), earlier MBM diagnosis year (P = .0008), higher serum levels of lactate dehydrogenase (P < .0001), receipt of immunotherapy before MBM diagnosis (P = .003), and the presence of extracranial disease (P = .02). The use of different CNS-directed treatment modalities was associated with presenting symptoms, diagnosis year, number and size of brain metastases, and the presence of extracranial disease. Multivariable analysis demonstrated improved survival for patients who underwent craniotomy (P = .01). CONCLUSIONS: The prognosis for patients with MBM has improved within the last 5 years, coinciding with the approval of PD-1 immune checkpoint blockade and combined BRAF/MEK targeting. Improving survival reflects and may influence the willingness to use aggressive multimodality treatment for MBM. LAY SUMMARY: Historically, melanoma brain metastases (MBM) have carried a poor survival prognosis of 4 to 6 months; however, the introduction of immunotherapy and targeted precision medicines has altered the survival curve for advanced melanoma. In this large, single-institution, contemporary cohort, the authors demonstrate a significant increase in survival of patients with MBM to 13 months within the last 5 years of the study. A worse prognosis for patients with MBM was significantly associated with the number of metastases at diagnosis, previous exposure to immunotherapy, spread of disease to the leptomeningeal compartment, serum lactate dehydrogenase elevation, and the presence of extracranial disease. The current age of systemic treatments has also been accompanied by shifts in the use of central nervous system-directed therapies.

The effect of surgery on radiation necrosis in irradiated brain metastases: extent of resection and long-term clinical and radiographic outcomes.

OBJECTIVE: Radiation therapy is a cornerstone of brain metastasis (BrM) management but carries the risk of radiation necrosis (RN), which can require resection for palliation or diagnosis. We sought to determine the relationship between extent of resection (EOR) of pathologically-confirmed RN and postoperative radiographic and symptomatic outcomes. METHODS: A single-center retrospective review was performed at an NCI-designated Comprehensive Cancer Center to identify all surgically-resected, previously-irradiated necrotic BrM without admixed recurrent malignancy from 2003 to 2018. Clinical, pathologic and radiographic parameters were collected. Volumetric analysis determined EOR and longitudinally evaluated perilesional T2-FLAIR signal preoperatively, postoperatively, and at 3-, 6-, 12-, and 24-months postoperatively when available. Rates of time to 50% T2-FLAIR reduction was calculated using cumulative incidence in the competing risks setting with last follow-up and death as competing events. The Spearman method was used to calculate correlation coefficients, and continuous variables for T2-FLAIR signal change, including EOR, were compared across groups. RESULTS: Forty-six patients were included. Most underwent prior stereotactic radiosurgery with or without whole-brain irradiation (N = 42, 91%). Twenty-seven operations resulted in gross-total resection (59%; GTR). For the full cohort, T2-FLAIR edema decreased by a mean of 78% by 6 months postoperatively that was durable to last follow-up (p < 0.05). EOR correlated with edema reduction at last follow-up, with significantly greater T2-FLAIR reduction with GTR versus subtotal resection (p < 0.05). Among surviving patients, a significant proportion were able to decrease their steroid use: steroid-dependency decreased from 54% preoperatively to 15% at 12 months postoperatively (p = 0.001). CONCLUSIONS: RN resection conferred both durable T2-FLAIR reduction, which correlated with EOR; and reduced steroid dependency.

Cerebrospinal fluid diversion for leptomeningeal metastasis: palliative, procedural and oncologic outcomes.

BACKGROUND: Leptomeningeal metastasis (LM) occurs in 3-5% of patients with solid metastatic tumors and often portends a severe prognosis including symptomatic hydrocephalus and intracranial hypertension. Cerebrospinal fluid (CSF) shunting can provide symptomatic relief in this patient subset; however, few studies have examined the role of shunting in the palliation, prognosis and overall oncologic care of these patients. OBJECTIVE: To identify and evaluate risk factors associated with prognosis after CSF diversion and assess surgical, symptomatic and oncologic outcomes in this population. METHODS: A retrospective study was conducted on patients with solid-malignancy LM treated with a shunt at a NCI-designated Comprehensive Cancer Center between 2010 and 2019. RESULTS: One hundred and ninety patients with metastatic LM underwent CSF diversion. Overall survival was 4.14 months from LM diagnosis (95% CI: 3.29-4.70) and 2.43 months (95% CI: 2.01-3.09) from shunting. Karnofsky performance status (KPS) at time of shunting and brain metastases (BrM) number at LM diagnosis demonstrated significant associations with survival (HR = 0.66; 95% CI [0.51-0.86], p = 0.002; HR = 1.40; 95% CI [1.01-1.93] per 10 BrM, p = 0.04, respectively). Eighty-three percent of patients experienced symptomatic relief, and 79% were discharged home or to rehabilitation facilities post-shunting. Post-shunt, 56% of patients received additional systemic therapy or started or completed WBRT. Complications included infection (5%), symptomatic subdural hygroma/hematoma (6.3%), and shunt externalization/removal/repair (8%). Abdominal seeding was not identified. CONCLUSIONS: CSF diversion for LM with hydrocephalus and intracranial hypertension secondary to metastasis can achieve symptomatic relief, hospital discharge, and return to further oncologic therapy, with a complication profile unique to this pathophysiology. However, decision-making in this population must incorporate end-of-life goals of care given limited prognosis.

Thalamic gliomas in adults: a systematic review of clinical characteristics, treatment strategies, and survival outcomes.

PURPOSE: Thalamic gliomas are rare neoplasms that pose significant surgical challenges. The literature is limited to single-institution retrospective case series. We systematically review the literature and describe the clinical characteristics, treatment strategies, and survival outcomes of adult thalamic gliomas. METHODS: Relevant articles were identified on PubMed, Scopus, and Cochrane databases. Papers containing cases of adult thalamic gliomas with clinical outcome data were included. A comprehensive review of clinical characteristics and survival analysis was conducted. RESULTS: We included 25 studies comprising 617 patients. The median age was 45 years (male = 58.6%). Glioblastoma was the most frequent histological type (47.2%), and 82 tumors were H3 K27M-mutant. Motor deficit was the most common presenting symptom (51.8%). Surgical resection was performed in 69.1% of cases while adjuvant chemotherapy and radiotherapy were administered in 56.3% and 72.6%, respectively. Other treatments included laser interstitial thermal therapy, which was performed in 15 patients (2.4%). The lesion laterality (P = 0.754) and the surgical approach (P = 0.111) did not correlate with overall survival. The median progression-free survival was 9 months, and the overall two-year survival rate was 19.7%. The two-year survival rates of low-grade and high-grade thalamic gliomas were 31.0% and 16.5%, respectively. H3 K27M-mutant gliomas showed worse overall survival (P = 0.017). CONCLUSION: Adult thalamic gliomas are associated with poor survival. Complete surgical resection is associated with improved survival rates but is not always feasible. H3 K27M mutation is associated with worse survival and a more aggressive approach should be considered for mutant neoplasms.

Salvage resection of recurrent previously irradiated brain metastases: tumor control and radiation necrosis dependency on adjuvant re-irradiation.

PURPOSE: The efficacy of salvage resection (SR) of recurrent brain metastases (rBrM) following stereotactic radiosurgery (SRS) is undefined. We sought to describe local recurrence (LR) and radiation necrosis (RN) rates in patients undergoing SR, with or without adjuvant post-salvage radiation therapy (PSRT). METHODS: A retrospective cohort study evaluated patients undergoing SR of post-SRS rBrM between 3/2003-2/2020 at an NCI-designated cancer center. Cases with histologically-viable malignancy were stratified by receipt of adjuvant PSRT within 60 days of SR. Clinical outcomes were described using cumulative incidences in the clustered competing-risks setting, competing risks regression, and Kaplan-Meier methodology. RESULTS: One-hundred fifty-five rBrM in 135 patients were evaluated. The overall rate of LR was 40.2% (95% CI 34.3-47.2%) at 12 months. Thirty-nine (25.2%) rBrM treated with SR + PSRT trended towards lower 12-month LR versus SR alone [28.8% (95% CI 17.0-48.8%) versus 43.9% (95% CI 36.2-53.4%), p = .07 by multivariate analysis]. SR as re-operation (p = .03) and subtotal resection (p = .01) were independently associated with higher rates of LR. On univariate analysis, tumor size (p = .48), primary malignancy (p = .35), and PSRT technique (p = .43) bore no influence on LR. SR + PSRT was associated with an increased risk of radiographic RN at 12 months versus SR alone [13.4% (95% CI 5.5-32.7%) versus 3.5% (95% CI 1.5-8.0%), p = .02], though the percentage with symptomatic RN remained low (5.1% versus 0.9%, respectively). Median overall survival from SR was 13.4 months (95% CI 10.5-17.7). CONCLUSION: In this largest-known series evaluating SR outcomes in histopathologically-confirmed rBrM, we identify a significant LR risk that may be reduced with adjuvant PSRT and with minimal symptomatic RN. Prospective analysis is warranted.

Laser interstitial thermal therapy as a radiation-sparing approach for central nervous system tumors in children with cancer predisposition syndromes: report of a child with Li-Fraumeni syndrome. Illustrative case.

BACKGROUND: Ionizing radiation and alkylating chemotherapies increase secondary malignancy risk in patients with cancer predisposition syndromes (CPSs), such as Li-Fraumeni syndrome. Laser interstitial thermal therapy (LITT) is a minimally invasive ablation technique that has not been associated with mutagenic risks. We describe the case of a child with LFS and a history of treated choroid plexus carcinoma (CPC) who developed a second primary glial tumor that was safely treated with magnetic resonance imaging (MRI)-guided LITT. OBSERVATIONS: A 4-year-old male with left parietal World Health Organization grade III CPC associated with a TP53 germline mutation was evaluated. The patient underwent neoadjuvant platinum-based chemotherapy before near-total resection, followed by 131I-8H9 immunotherapy and 30 fractions of 54-Gy proton radiotherapy. He remained without evidence of disease for 2 years before developing a slow-growing mass adjacent to the left frontal ventricular horn. Stereotactic biopsy revealed a glial neoplasm. Given the nonsuperficial location and focality of the lesion, MRI-guided LITT was performed for ablative therapy. There were no complications, and 2 years of surveillance revealed continued retraction of the ablated tumor focus and no subsequent disease. LESSONS: Alternatives to mutagenic therapies for brain tumors should be explored for patients with CPS. LITT paired with imaging surveillance is a logical strategy to ensure durable outcomes and mitigate treatment-related secondary neoplasms.

Prognostic Implications of Small Cell Lung Cancer Transcriptional Subtyping for CNS Metastases.

PURPOSE: Small cell lung cancer (SCLC) often metastasizes to the brain and has poor prognosis. SCLC subtypes distinguished by expressing transcriptional factors ASCL1 or NEUROD1 have been identified. This study investigates the impact of transcription factor-defined SCLC subtype on incidence and outcomes of brain metastases (BMs). METHODS: Patients with SCLC with ASCL1 (A) and NEUROD1 (N) immunohistochemical expression status were identified and classified: (1) A+/N-, (2) A+/N+, (3) A-/N+, and (4) A-/N-. Cumulative incidence competing risk analyses were used to assess incidence of CNS progression. Cox proportional hazards models were used for multivariable analyses of overall survival (OS) and CNS progression-free survival (CNS-PFS). RESULTS: Of 164 patients, most were either A+/N- or A+/N+ (n = 62, n = 63, respectively). BMs were present at diagnosis in 24 patients (15%). Among them, the 12-month cumulative incidence of subsequent CNS progression was numerically highest for A+/N- (50% [95% CI, 10.5 to 74.7]; P = .47). Among those BM-free at diagnosis, the 12-month cumulative incidence of CNS progression was numerically the highest for A+/N- (16% [95% CI, 7.5 to 27.9]) and A-/N+ (9.1% [95% CI, 0.0 to 34.8]; P = .20). Both subtypes, A+/N- and A-/N+, had worse OS compared with A+/N+ (A+/N-: hazard ratio [HR], 1.62 [95% CI, 1.01 to 2.51]; P < .05; A-/N+: HR, 3.02 [95% CI, 1.35 to 6.76]; P = .007). Excellent response rates (28, 65% CR/PR) across subtypes were seen in patients who had CNS-directed radiotherapy versus systemic therapy alone (9, 36% CR/PR). CONCLUSION: To our knowledge, this report is the first to investigate CNS-specific outcomes based on transcription factor subtypes in patients with SCLC. BM-free patients at diagnosis with A+/N- or A-/N+ subtypes had worse outcomes compared with those with transcriptional factor coexpression. Further investigation into the mechanisms and implications of SCLC subtyping on CNS-specific outcomes is warranted to ultimately guide personalized care.

Distinct tumor architectures and microenvironments for the initiation of breast cancer metastasis in the brain.

Brain metastasis, a serious complication of cancer, hinges on the initial survival, microenvironment adaptation, and outgrowth of disseminated cancer cells. To understand the early stages of brain colonization, we investigated two prevalent sources of cerebral relapse, triple-negative (TNBC) and HER2+ (HER2BC) breast cancers. Using mouse models and human tissue samples, we found that these tumor types colonize the brain, with a preference for distinctive tumor architectures, stromal interfaces, and autocrine programs. TNBC models tend to form perivascular sheaths with diffusive contact with astrocytes and microglia. In contrast, HER2BC models tend to form compact spheroids driven by autonomous tenascin C production, segregating stromal cells to the periphery. Single-cell transcriptomics of the tumor microenvironment revealed that these architectures evoke differential Alzheimer's disease-associated microglia (DAM) responses and engagement of the GAS6 receptor AXL. The spatial features of the two modes of brain colonization have relevance for leveraging the stroma to treat brain metastasis.

Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery.

BACKGROUND: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS). OBJECTIVE: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021. INTERVENTION: SRS for RCC BMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death. RESULTS AND LIMITATIONS: Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, p = 0.001, q = 0.01), with the majority being PTEN alterations (17% vs 2.7%, p = 0.003, q = 0.041). CONCLUSIONS: To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting. PATIENT SUMMARY: We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis.

Meningioma Presenting with Spontaneous Venous Intraparenchymal Hemorrhage.

A 65-year-old woman with a known right-sided, dural-based lesion and metastatic pancreatic neuroendocrine tumor presented with multiple days of progressive lethargy and left-sided weakness culminating with obtundation and dilated pupils. Computed tomography demonstrated an acute right convexity subdural hematoma and a frontotemporal intraparenchymal hemorrhage with 1.3 cm of midline shift, uncal herniation, and an increase in size of now a hemorrhagic dural-based lesion. She underwent emergency hemicraniectomy for evacuation of subdural hematoma and resection of hemorrhagic meningioma with excellent postoperative result including improvement in midline shift and gross total resection of lesion. Pathology was consistent with a World Health Organization grade II meningioma with a chordoid component. She underwent adjuvant stereotactic radiosurgery and cranioplasty and made a full neurologic recovery. Identification of hemorrhagic meningioma as the underlying pathology causing multicompartmental hemorrhage is crucial. We recommend single-stage decompression with extraaxial clot evacuation and resection of the meningioma when feasible.

Incidence of HER2-expressing brain metastases in patients with HER2-null breast cancer: a matched case analysis.

The HER2-directed antibody-drug conjugate trastuzumab deruxtecan is active against lower levels of HER2 expression than prior-generation therapies. The rate of HER2 expression in brain metastases among patients with initially HER2-null breast cancer is undefined, and receptor discordance in advanced breast cancer with brain metastases may underestimate CNS response potential in the absence of brain metastasis sampling. In this cohort study including 136 patients with 401 samples scored according to ASCO/CAP guidelines, 15/28 patients (54%) with HER2-null primary breast cancer have detectable HER2 expression in subsequently resected brain metastases, a significant discordant population.

Use of longitudinal functional MRI to demonstrate translocation of language function in patients with brain tumors.

OBJECTIVE: The ability of functional MRI (fMRI) to localize patient-specific eloquent areas has proved worthwhile in efforts to maximize resection while minimizing risk of iatrogenic damage in patients with brain tumors. Although cortical reorganization has been described, the frequency of its occurrence and the factors that influence incidence are not well understood. The authors investigated changes in language laterality between 2 fMRI studies in patients with brain tumors to elucidate factors contributing to cortical reorganization. METHODS: The authors analyzed 33 patients with brain tumors involving eloquent language areas who underwent 2 separate presurgical, language task-based fMRI examinations (fMRI1 and fMRI2). Pathology consisted of low-grade glioma (LGG) in 15, and high-grade glioma (HGG) in 18. The mean time interval between scans was 35 ± 38 months (mean ± SD). Regions of interest were drawn for Broca's area (BA) and the contralateral BA homolog. The laterality index (LI) was calculated and categorized as follows: > 0.2, left dominance; 0.2 to -0.2, codominance; and < -0.2, right dominance. Translocation of language function was defined as a shift across one of these thresholds between the 2 scans. Comparisons between the 2 groups, translocation of language function (reorganized group) versus no translocation (constant group), were performed using the Mann-Whitney U-test. RESULTS: Nine (27%) of 33 patients demonstrated translocation of language function. Eight of 9 patients with translocation had tumor involvement of BA, compared to 5/24 patients without translocation (p < 0.0001). There was no difference in LI between the 2 groups at fMRI1. However, the reorganized group showed a decreased LI at fMRI2 compared to the constant group (-0.1 vs 0.53, p < 0.01). The reorganized cohort showed a significant difference between LI1 and LI2 (0.50 vs -0.1, p < 0.0001) whereas the constant cohort did not. A longer time interval was found in the reorganized group between fMRI1 and fMRI2 for patients with LGG (34 vs 107 months, p < 0.002). Additionally, the reorganized cohort had a greater proportion of local tumor invasion into eloquent areas at fMRI2 than the constant group. Aphasia was present following fMRI2 in 13/24 (54%) patients who did not exhibit translocation, compared to 2/9 (22%) patients who showed translocation. CONCLUSIONS: Translocation of language function in patients with brain tumor is associated with tumor involvement of BA, longer time intervals between scans, and is seen in both LGG and HGG. The reduced incidence of aphasia in the reorganized group raises the possibility that reorganization supports the conservation of language function. Therefore, longitudinal fMRI is useful because it may point to reorganization and could affect therapeutic planning for patients.

Postradiosurgery cystic degeneration in brain metastases causing delayed and potentially severe sequelae: systematic review and illustrative cases.

BACKGROUND: Cystic postradiation degeneration has previously been described in the literature as a rare but potentially severe complication after central nervous system (CNS) irradiation for vascular malformations. Limited cases have been reported in the setting of brain metastases. OBSERVATIONS: Thirty-six total cases, including three reported here, of cystic postradiation degeneration are identified. Of 35 cases with complete clinical information, 34 (97.25%) of 35 were symptomatic from cystic changes at diagnosis. The average time between initial radiation dose and cyst development was 7.61 years (range 2-31 years). Although most patients were initially treated conservatively with medication, including steroids, 32 (88.9%) of 36 ultimately required surgical intervention. The most common interventions were craniotomy for cyst fenestration or resection (25 of 36; 69.4%) and Ommaya placement (8 of 36). After intervention, clinical improvement was seen in 10 (67%) of 15 cases, with persistent or worsening deficit or death seen in 5 (33%) of 15. Cysts were decompressed or obliterated on postoperative imaging in 20 (83.3%) of 24 cases, and recurrence was seen in 4 (16.7%) of 24. LESSONS: Cystic degeneration is a rare and delayed sequela after radiation for brain metastases. This entity has the potential to cause significant and permanent neurological deficit if not properly recognized and addressed. Durable control can be achieved with a variety of surgical treatments, including cyst fenestration and Ommaya placement.