Resection Of Brain Metastases Research Articles

Survival and Treatment Outcomes in Gastric Cancer Patients with Brain Metastases: A Systematic Review and Meta-Analysis.

Brain metastases (BM) from gastric cancer (GC) are rare but associated with poor prognosis, significantly impacting patient survival and quality of life. The objective of this systematic review and meta-analysis is to consolidate existing research on BM from GC, evaluate the incidence and clinical outcomes, and explore the effectiveness of treatment options. A systematic search was conducted across the Medline, Web of Science, and Scopus databases, following PRISMA guidelines. Eighteen high-quality studies, as per the Newcastle-Ottawa Quality Assessment Scale, were included, encompassing 70,237 GC patients, of whom 621 developed BM. Data on progression-free survival (PFS), overall survival (OS), neurological symptoms, and HER2 status were analyzed using a random-effects model. The incidence of BM in GC patients was found to be 2.29% (95% CI: 1.06-3.53%), with the range extending from 0.47% to 7.79% across studies. HER2-positive status was significantly associated with a higher likelihood of developing BM, with an odds ratio of 43.24 (95% CI: 2.05-913.39; p = 0.02), although this finding was based on limited data. The surgical resection of BM was linked to significantly improved survival outcomes, with a mean difference in OS of 12.39 months (95% CI: 2.03-22.75; p = 0.02) compared to non-surgical approaches. The surgical resection of brain metastases in GC patients significantly enhances overall survival, while HER2-positive patients may show a higher risk for developing BM. These findings underscore the importance of tailored therapeutic approaches for GC patients with BM.

SURG-54. RECURRENT BRAIN METASTASES (RBM) TREATED WITH SURGICALLY TARGETED RADIATION THERAPY (START): PRELIMINARY SAFETY EVALUATION FROM A MULTI-INSTITUTIONAL PROSPECTIVE REGISTRY

Abstract BACKGROUND Resection and intraoperative brachytherapy for operable recurrent brain metastasis allows for pathologic confirmation of recurrent disease, mass effect relief, and immediate initiation of radiotherapy (RT). In this analysis, we report patterns-of-use and treatment-related adverse events (AEs) for rBM patients treated with Cs-131 collagen tiles, an FDA-cleared intracranial brachytherapy device. METHODS Patients with rBM who underwent resection and surgically-targeted radiation therapy (GammaTile, GT Medical Technologies Inc., Tempe, AZ USA) on a prospectively enrolling phase 4 registry study (NCT04427384) were analyzed. AEs were graded per CTCAE v5.0. RESULTS Between 11/2020 and 2/2024, 56 rBM in 51 consecutive patients underwent STaRT at 19 centers, with 5 patients having 2 metastases implanted concurrently. 44 patients (86%) had prior same-site RT (median interval 14.5 mo, range 3-56). Primary tumor histologies were lung (27), melanoma (8), breast (7), renal (4), colon (2), and “other” (3). Median pre-operative maximum diameter was 3.0 cm (range 1.4-5.7); age 63 (range 28-81); 53% females; KPS median 90 (range 40-100); and median implantation time 3 minutes. 26 patients were implanted at a 1st, 15 at a 2nd, and 10 at ≥ 3rd same-site recurrence (range 1-9). At a median follow-up of 6.2 months (range <1-35.1), 6/51 patients (11.8%) experienced ≥Gr 3 AEs at a median of 12 (range 1-69) days postoperatively (POD). No radiation necrosis (RN) events were observed, and no AEs occurred in multi-implant cases or where STaRT was the initial form of RT. CONCLUSIONS In this prospective multi-institutional study, STaRT demonstrated an excellent safety profile in a cohort of larger rBM, even in the setting of multi-recurrent disease. Accrual and follow-up are on-going and will provide data on tumor control and long-term RN rates.

SURG-06. IMPACT OF LASER INTERSTITIAL THERMAL THERAPY VERSUS RESECTION FOR METASTASES ASSOCIATED WITH THE MOTOR CORTEX

Abstract BACKGROUND For brain metastases (BM), resection remains a mainstay for the upfront management of large, symptomatic lesions, while laser interstitial thermal therapy (LITT) has become a key treatment for radiographically progressive BM following stereotactic radiosurgery (SRS). Compared to LITT, resection-associated morbidity may delay systemic therapies. We evaluated functional outcomes for resection versus LITT to primary motor cortex (PMC)-associated metastases. METHODS Patients receiving resection or LITT for BM radiographically associated with the PMC from 2015-2023 were retrospectively reviewed. Demographic and survival data were collected, with patient Karnofsky Performance Status (KPS) or modified Rankin Scale (mRS) scores assessed out to 1-year by independent raters. RESULTS Forty-one patients underwent resection and 30 underwent LITT to a PMC-associated lesion. Median age was 67 (range 38 – 80) vs 65 (44 – 80) for resection vs LITT; median pre-operative KPS (70 vs 80, P = 0.1) or mRS (2 vs 2, P = 0.66) did not differ between groups. Lung was the most common primary (56.1% resections vs 56.7% LITTs). Resected lesions were of larger median diameter than LITT, 2.8 vs 1.9 cm, P = 0.0001. For resections, length of stay was longer, median 2 vs 1 day, P = 0.0002, and ICU use more frequent (75.6% versus 20.0%, P < 0.0001). At 1-month post-op, 66.7% of resection patients and 51.7% of LITT patients had stable or improved symptoms from pre-op, P = 0.21, with parity at 3-months (65.7% vs 62.9%) and therafter. Further, there was no significant decrement in KPS or mRS score out to a year for either intervention. CONCLUSIONS While there is a short-term increased risk of post-operative neurologic worsening due to LITT-associated edema, our data shows that, relative to resection, this is a transient and clinically limited phenomenon. With careful patient selection, LITT to lesions involving the PMC is feasible.

SURG-01. INTRAOPERATIVE FLUORESCENCE ACTIVITY OF 5-AMINOLEVULINIC ACID IN BRAIN METASTASIS OF LUNG CANCER IS ASSOCIATED WITH THE GENETIC ALTERATION OF CELL CYCLE REGULATION

Abstract With advancement of technology in brain tumor surgery, fluorescence image, such as 5-Aminolevulinic Acid (5-ALA), can help detect the residual tumor during surgery. Recently, genetic alteration of cancer is additionally considered as prognostic factor with being added into traditional prognostic system, such as Graded Prognostic Assessment (GPA) scoring system. The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-ALA in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM of lung adenocarcinoma at our institute for five years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). Total 72 patients were eligible for analysis. Strong fluorescence was obtained in 56 (77.8%) patient during surgery. The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. In the NGS data of BM, genetic alteration of cell cycle regulation, DNA repair, tumorigenesis, proliferation, epigenetic regulation, and cancer immunology were detected in 73.6%, 44.4%, 56.9%, 66.7%, 30.6%, and 2.8%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. Additionally, age, KPS, status of NSCLC, RPA class, GPA score, modality of adjuvant treatment were associated with PFS and OS.The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.

SURG-35. NEURONAVIGATED INTRAOPERATIVE ULTRASSOUND X SODIUM FLUORESCEIN FOR BRAIN METASTASIS: WHICH IS BETTER?

Abstract BACKGROUND Improve quality of life with a maximum surgical resection is the main goal of neurosurgeons. Brain metastasis are even more prevalent because of patients are living more. The grade of resection and the maintenance of a good performance are fundamental for these patients perform adjuvant radiotherapy. There are several technologies that may help. Considering two of them that have an easier access and are cheaper, we compared a high definition ultrasound (BK 3000) coupled to neuronavigation system (Brainlab) and sodium fluorescein (SF). METHODS Adult patients with main radiological hypothesis of brain metastasis were included in a PhD study previously approved by ethics committee. 3-5mg/kg of SF was administered by intravenous infusion during anesthetic induction. An specific craniotomy transducer was used in all cases with shift correction in real time by neuronavigator. All procedures were guided by the same neurosurgeon. RESULTS High definition ultrasound allows an excellent tumor delimitation. SF helped to increase grade of resection however made confusion about what is infiltration and what is tumor and for this ultrasound were superior. Increased fluorescence is easily detected when compared to ultrasound information’s.. For both technologies, when the surgical site had blood, the evaluation about grade of resection is not accurate because in ultrasound appears a posterior shadow and considering SF it seems that there are not further tumor because blood does not have increased fluorescence. CONCLUSIONS US and SF are different tools which improve brain metastasis resection. In each moment of surgery one technology was superior or not. We used an specific probe for neurosurgery that has high quality and allowed detailed evaluations. These technologies helps surgeons take quick decision and optimized brain tumor removal. The neurosurgeon should be more familiar to US images because provide a real time evaluation with low cost.

SINGLE INSTITUTION RETROSPECTIVE ANALYSIS OF COMPLICATIONS ASSOCIATED WITH SURGICAL DEBULKING OF BRAIN METASTASIS

Abstract AIMS Surgical resection of brain metastasis is associated with complications, which worsen patient’s quality of life, results in oncological treatment delays and death. Surgical complication data aids decision making, leads to objective risk benefit analysis and informed consent. The aim of this study is to quantify rates, types and risk factors for complications related to surgical debulking of brain metastasis. METHOD Retrospective analysis on adult patients with brain metastasis, who underwent surgical debulking between 2017 and 2023 at Royal Preston Hospital. Data collected included demographics, diagnosis, 30-days post-operative complications, 30-days mortality, 30-days post-operative palliation, primary tumour, Karnofsky-Performance Score (KPS), first vs. repeat resection, use of drain and type of suture materials etc. Univariate analysis was carried out using Graphpad software. RESULTS Two-hundred and twenty-seven patients qualified. The most common primaries were lung (n=93, 41%), breast (n=43, 18.9%), and skin (n=31, 13.7%). The most common complications were Hospital-acquired pneumonia (HAP) (n=27, 11.9%), surgical site infection (SSI) (n=19, 8.4%), wound dehiscence (n=14, 6.2%), thromboembolic events (n=12, 5.3%) and CSF leak (n=8, 3.5%). Thirty days mortality and post-operative palliation (due to surgical complications) were both 3.5% each (n=8). Two-hundred and six (93.2%) had KPS ³70 whilst 15 (6.8%) had KPS < 70 [range 30-60 pre-operatively (median 60)). KPS < 70 was statistically significant for post-operative palliation (p=0.01), HAP (0=0.02) and urine infection (p=0.002), but not for 30-day mortality. Twenty-five (11.1%) patients undergoing repeat resections, experienced higher wound infections (p=0.002). CONCLUSION Surgical debulking is associated with significant post-operative complications, with 7% either dying or not receiving any further treatment, 18.1% percent developing serious wound complications (SSI, CSF leak, Wound dehiscence) and 19.4% experiencing significant medical complications (HAP/UTI/Thromboembolism). Pre- operative KPS < 70 and repeat resections are associated with statistically increased risk of complications.

Patterns of Care for Brain Metastases in Asia: A Real-World Survey Conducted by the Federation of Asian Organizations for Radiation Oncology.

To report the patterns of care for brain metastases (BMs) in the Federation of Asian Organizations for Radiation Oncology (FARO). Overall, 37 questions were prepared. The survey was conducted online using Google Forms, and the URL was distributed to members of the FARO research committee. Radiation oncologists associated with FARO responded to the questionnaire between May 2023 and June 2023, and their answers were analyzed. Responses were received from 32 radiation oncologists in 13 countries participating in FARO. Twenty-six physicians (81.3%) were affiliated with academic centers, and 22 (68.8%) were able to perform stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (fSRT) for BMs at their institution. The most typically used prognostic index for BM was the recursive partitioning analysis classification (17 physicians, 53.1%). The maximum number of BMs indicated for SRT/SRS was ≤three (11 physicians, 34.4%), whereas eight (25.0%) physicians answered for 6-10 BMs. The maximum size of BMs considered for SRS/fSRT was ≤3 cm (14 physicians, 43.8%), whereas nine (28.1%) answered that SRS/fSRT was preferred if the maximum size was >4 cm. When whole-brain radiotherapy (RT) was indicated, hippocampal avoidance and memantine usage were limited to 50.0% and 25.0% of patients, respectively. The most typical RT modality after BM resection was SRS/fSRT alone, regardless of whether the margin was positive (19 physicians, 59.4%) or negative (13 physicians, 40.6%). We report the survey results of the patterns of care for BMs in the FARO. This survey was conducted only among a limited number of FARO members. Since many respondents were affiliated with relatively large-scale academic centers, large-scale surveys, including community hospitals, are warranted for future initiatives.

Prioritizing Radiation and Targeted Systemic Therapies in Patients with Resected Brain Metastases from Lung Cancer Primaries with Targetable Mutations: A Report from a Multi-Site Single Institution.

Background/Objectives: Brain metastases (BrMs) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While the treatment of BrMs requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, the advances in molecular sequencing have improved outcomes in patients with targetable mutations. With a push towards the molecular characterization of cancers, we evaluated the outcomes by treatment modality at our institution with respect to prioritizing RT and targeted therapies. Methods: We identified the patients with NSCLC BrMs treated with surgical resection. The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). The secondary endpoint included index lesion recurrence. The tumor molecular profiles were reviewed. The outcomes were evaluated by treatment modality: surgery followed by adjuvant RT and/or adjuvant systemic therapy. Results: In total, 155/272 (57%) patients who received adjuvant therapy with adequate follow-up were included in this analysis. The patients treated with combination therapy vs. monotherapy had a median FFP time of 10.72 months vs. 5.38 months, respectively (p = 0.072). The patients of Hispanic/Latino vs. non-Hispanic/Latino descent had a statistically significant worse OS of 12.75 months vs. 53.15 months, respectively (p = 0.015). The patients who received multimodality therapy had a trend towards a reduction in index lesion recurrences (χ2 test, p = 0.063) with a statistically significant improvement in the patients receiving immunotherapy (χ2 test, p = 0.0018). Conclusions: We found that systemic therapy combined with RT may have an increasing role in delaying the time to progression; however, there was no statistically significant relationship between OS and treatment modality.

Performance status improvement and advances in systemic treatment after brain metastases resection: a retrospective single-center cohort study of non-small cell lung cancer patients

BackgroundBrain metastasis (BrM) is prevalent among patients with NSCLC, and surgical resection of BrM constitutes a promising treatment strategy for local management and histopathological diagnosis, although it is offered for a select group of patients. Limited information exists concerning the improvement in performance status (PS) following BrM resection or the outcomes stratified by subsequent systemic therapy.MethodsWe conducted a retrospective single-center cohort study including NSCLC patients with surgically resected BrM and focused on the improvement in PS and subsequent therapy after BrM resection.Results71 patients were included, and the median overall survival was 18.3 months (95% confidence interval [95% CI]: 8.7, not reached). Patients with NSCLC who underwent surgical resection of BrM showed significant improvement in PS (18% and 39% showed ECOG PS of 0–1, before and after BrM resection, respectively [p = 0.006]), and patients with PS improvement were younger than those with PS unimprovement (median, 62 years versus 66 years; p = 0.041). Regarding subsequent systemic therapy after BrM resection, 21 patients (30%) received cytotoxic chemotherapy, 14 patients (20%) received tyrosine kinase inhibitors (TKIs), 3 patients (4%) received immune checkpoint inhibitors (ICIs), and 21 patients (30%) received no subsequent therapy. The survival outcomes of patients stratified by subsequent systemic treatments suggested the tendency that those who received TKI or ICI showed better survival outcomes, although a small number of patients hindered statistical comparisons.ConclusionsWe describe the outcomes of patients with NSCLC who underwent surgical resection of BrM, revealing that younger patients were more likely to anticipate improvement in PS, and patients who received TKI or ICI after BrM resection tended to exhibit a more preferable prognosis.

Gastric cancer and brain metastasis: A systematic review and meta‑analysis.

Gastric cancer (GC) constitutes one of the most wide-ranging cancers, with brain metastasis (BM) being a markedly uncommon and unfavorable outcome. The present meta-analysis evaluated the relationship between no-surgical treatment vs. additional surgical BM resection on the patient's quality of life and potential survival using electronic databases, including PubMed (1980-April 2024), Medline (1980-April 2024), Cochrane Library, and EMBASE (1980-April 2024). After a literature search, six articles were included in the final study pool. The number of patients with BM and conservative treatment was 289 (80.05%) compared with those that underwent an additional surgical resection 72 (19.95%). The mean age was 59.2 years, and the males were 195 (73.8%) of 264 available from five studies. The findings of the present meta-analysis revealed that the curative effect of BM tumor resection on patients with GC undergoing additional treatment with stereotactic radiosurgery, whole-brain radiotherapy or chemotherapy was favorable for their survival.

Examining molecular landscape and drug sensitivity profiles of patient-derived xenografts from resected brain metastases.

28 Background: Brain metastases (BrMet) remain an unmet need. Preclinical models of BrMet are rare but can be a valuable tool to interrogate pathology and develop novel therapeutic approaches. We previously published molecular profiles and drug sensitivity screening using novel BrMet patient-derived xenograft (PDX) models established from resected BrMet from patients with breast cancer. We further expanded our study to include BrMet from other solid tumors. Methods: We ascertained the genomic profiles of thirteen novel non-breast BrMet PDX models from patients undergoing clinically indicated surgical resection of BrMet. We then conducted drug sensitivity screening on ex vivo organoids with a panel of over 350 drugs to interrogate drug responses. We also collected information on molecular alterations and clinical treatment history from matched source patient material to correlate molecular alterations between tissue and matched PDXs when available, as well as with drug response in PDXs. Results: The PDXs included tumors that commonly (lung and melanoma) and less commonly (ovarian and sarcoma) metastasize to the brain. We observed potentially targetable DNA alterations in the DNA damaging repair pathway ( ATM, BRCA, CHEK2) and ERBB2. Using the drug sensitivity score 3 (DSS3), we assessed the sensitivity of the drugs tested. While the panel did not include the recently approved anti-HER2 targeted drugs, lapatinib (anti-HER2 TKI), and PARP inhibitors, e.g. olaparib and niraparib, were inactive against these PDXs. The three most active drugs among the BrMet PDXs were romidepsin, bortezomib, and triptolide, similar to what we observed previously for breast BrMet PDXs. When available, we correlated the DSS3 from the PDX testing with the drug exposure history and potentially actionable alterations reported in the matched source patient clinical samples. Interestingly, one case with CDKN2A/1B homozygous deletion had differential sensitivity against CDK inhibitors (highly active to dinaciclib but inactive to abemaciclib and palbociclib). Conclusions: We observed prevalent gene alterations associated with homologous recombination deficiency and HER2 among these non-breast BrMet PDX models, opening an opportunity for novel cross cancer approaches as these alterations are also reportedly linked to BrMet from breast cancer, these mechanisms may contribute to the propensity for BrMet. We also found that there are common drugs that are active across BrMet from different solid tumor types. To further explore the shared molecular features of BrMet across various solid tumors, we have established additional PDX models (near 100) from multiple solid tumors and plan to report on the molecular features.

Navigating Brain Metastases: Unveiling the Potential of 3-Tesla Intraoperative Magnetic Resonance Imaging.

Intraoperative magnetic resonance imaging (iMRI) has witnessed significant growth in the field of neurosurgery, particularly in glioma surgery, enhancing image-guided neuronavigation and optimizing the extent of resection (EOR). Despite its extensive use in the treatment of gliomas, its utility in brain metastases (BMs) remains unexplored. This study examined the effect of iMRI on BM resection. This retrospective study was conducted at the neurosurgical center of the University Hospital of the Technical University of Munich and involved 25 patients with BM who underwent resection using 3-Tesla iMRI between 2018 and 2022. Volumetric measurements of the resected contrast-enhancing metastases were performed using preoperative, intraoperative, and postoperative MRI images. The Karnofsky Performance Score (KPS) and neurological status of the patients were assessed pre- and postoperatively. Local recurrence and in-brain progression were reported in patients who underwent follow-up MRI at 3 and 6 months postoperatively. In this cohort (n = 25, mean age 63.6 years), non-small-cell lung cancer (NSCLC) was the most common origin (28%). The mean surgical duration was 219.9 min, and that of iMRI was 61.7 min. Indications for iMRI were primarily associated with preoperative imaging, suggesting an unclear entity that is often suspicious for glioma. Gross total resection (GTR) was achieved in 21 patients (84%). Continued resection was pursued after iMRI in six cases (24%), resulting in an improved EOR of 100% in five cases and 97.6% in one case. Neurological status postoperatively remained stable in 60%, improved in 24%, and worsened in 16% of patients. No wound healing or postoperative complications were observed. Among the thirteen patients who underwent follow-up MRI 3 months postoperatively, one patient showed local recurrence at the site of resection, and seven patients showed in-brain progression. Of the eight patients who underwent a 6-month follow-up MRI, two showed local recurrence, while three exhibited in-brain progression. The observed favorable profiles of GTR, coupled with the notable absence of wound-healing problems and acute postoperative complications, affirm the safety and feasibility of incorporating iMRI into the neurosurgical workflow for resecting BM with specific indications. The real-time imaging capabilities of iMRI offer unparalleled precision, aiding meticulous tumor delineation and informed decision-making, ultimately contributing to improved patient outcomes. Although our experience suggests the potential benefits of iMRI as a safe tool for enhancing EOR, we acknowledge the need for larger prospective clinical trials. Comprehensive investigations on a broader scale are imperative to further elucidate the specific indications for iMRI in the context of BMs and to study its impact on survival. Rigorous prospective studies will refine our understanding of the clinical scenarios in which iMRI can maximize its impact, guiding neurosurgeons toward more informed and tailored decision-making.

Hospital frailty risk score predicts high-value care outcomes following brain metastasis resection

ObjectiveBrain metastases (BM) are the most common adult intracranial tumors, representing a significant source of morbidity in patients with systemic malignancy. Frailty indices, including 11- and 5-factor modified frailty indices (mFI-11 and mFI-5), American Society of Anesthesiologists (ASA) physical status classification, and Charlson Comorbidity Index (CCI), have recently demonstrated an important role in predicting high-value care outcomes in neurosurgery. This study aims to investigate the efficacy of the newly developed Hospital Frailty Risk Score (HFRS) on postoperative outcomes in BM patients. MethodsAdult patients with BM treated surgically at a single institution were identified (2017–2019). HFRS was calculated using ICD-10 codes, and patients were subsequently separated into low (<5), intermediate (5−15), and high (>15) HFRS cohorts. Multivariate logistic regressions were utilized to identify associations between HFRS and complications, length of stay (LOS), hospital charges, and discharge disposition. Model discrimination was assessed using receiver operating characteristic (ROC) curves. ResultsA total of 356 patients (mean age: 61.81±11.63 years; 50.6 % female) were included. The mean±SD for HFRS, mFI-11, mFI-5, ASA, and CCI were 6.46±5.73, 1.31±1.24, 0.95±0.86, 2.94±0.48, and 8.69±2.07, respectively. On multivariate analysis, higher HFRS was significantly associated with greater complication rate (OR=1.10, p<0.001), extended LOS (OR=1.13, p<0.001), high hospital charges (OR=1.14, p<0.001), and nonroutine discharge disposition (OR=1.12, p<0.001), and comparing the ROC curves of mFI-11, mFI-5, ASA,and CCI, the predictive accuracy of HFRS was the most superior for all four outcomes assessed. ConclusionThe predictive ability of HFRS on BM resection outcomes may be superior than other frailty indices, offering a new avenue for routine preoperative frailty assessment and for managing postoperative expectations.

Surgically targeted radiation therapy versus stereotactic radiation therapy: A dosimetric comparison for brain metastasis resection cavities

BackgroundSurgically targeted radiation therapy (STaRT) with Cesium-131 seeds embedded in a collagen tile is a promising treatment for recurrent brain metastasis. In this study, the biological effective doses (BED) for normal and target tissues from STaRT plans were compared with those of external beam radiotherapy (EBRT) modalities. MethodsNine patients (n=9) with 12 resection cavities (RCs) who underwent STaRT (cumulative physical dose of 60 Gy to a depth of 5 mm from the RC edge) were replanned with CyberKnife® (CK), Gamma Knife® (GK), and intensity modulated proton therapy (IMPT) using an SRT approach (30 Gy in 5 fractions). Statistical significance comparing D95% and D90% in BED10Gy (BED10Gy95% and BED10Gy90%) and to RC + 0 to + 5 mm expansion margins, and parameters associated with radiation necrosis risk (V83Gy, V103Gy, V123Gy and V243Gy) to the normal brain were evaluated by a Wilcoxon-signed rank test. ResultsFor RC+0 mm, median BED10Gy90% for STaRT (90.1 Gy10, range: 64.1-140.9 Gy10) was significantly higher than CK (74.3 Gy10, range:59.3-80.4 Gy10, p=0.04), GK (69.4 Gy10, range: 59.8-77.1 Gy10, p=0.005), and IMPT (49.3 Gy10, range: 49.0-49.7 Gy10, p=0.003), respectively. However, for the RC+5 mm, the median BED10Gy90% for STaRT (34.1 Gy10, range: 22.2-59.7 Gy10) was significantly lower than CK (44.3 Gy10, range: 37.8-52.4 Gy10), and IMPT (46.6 Gy10, range: 45.1-48.5 Gy10), respectively but not significantly different from GK (34.1 Gy10, range: 22.8-47.0 Gy10). The median V243Gy was significantly higher in CK (11.7 cc, range: 4.7-20.1 cc), GK(6.2 cc, range: 2.3-11.9 cc) and IMPT (19.9 cc, range: 11.1-36.6 cc) compared to STaRT (1.1 cc, range: 0.0-7.8 cc) (p<0.01). ConclusionThis comparative analysis suggests the STaRT approach may treat recurrent brain tumors effectively via delivery of higher radiation doses with equivalent or greater BED up to at least 3 mm from the RC edge as compared to EBRT approaches.

Intraoperative radiotherapy after neurosurgical resection of brain metastases as institutional standard treatment- update of the oncological outcome form a single center cohort after 117 procedures.

Stereotactic radiotherapy (SRT) is the predominant method for the irradiation of resection cavities after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50kV x-rays is an alternative way to irradiate the resection cavity focally. We have already reported the outcome of our first 40 IORT patients treated until 2020. Since then, IORT has become the predominant cavity treatment in our center due to patients´ choice. We retrospectively analyzed the outcomes of all patients who underwent resection of BM and IORT between 2013 and August 2023 at Augsburg University Medical Center (UKA). We identified 105 patients with 117 resected BM treated with 50kV x-ray IORT. Median diameter of the resected metastases was 3.1cm (range 1.3 - 7.0cm). Median applied dose was 20Gy. All patients received standardized follow-up (FU) including three-monthly MRI of the brain. Mean FU was 14months, with a median MRI FU for patients alive of nine months. Median overall survival (OS) of all treated patients was 18.2months (estimated 1-year OS 57.7%). The observed local control (LC) rate of the resection cavity was 90.5% (estimated 1-year LC 84.2%). Distant brain control (DC) was 61.9% (estimated 1-year DC 47.9%). Only 16.2% of all patients needed WBI in the further course of disease. The observed radio necrosis rate was 2.6%. After 117 procedures IORT still appears to be a safe and appealing way to perform cavity RT after neurosurgical resection of BM with low toxicity and excellent LC.

Bilateral Supplementary Motor Area Syndrome Following Resection Of Parasagittal Large Brain Metastasis – A Case Report and Review of Literature

Bilateral Supplementary Motor Area Syndrome Following Resection Of Parasagittal Large Brain Metastasis – A Case Report and Review of Literature

Neurosurgical resection of multiple brain metastases: outcomes, complications, and survival rates in a retrospective analysis

PurposeThis study investigates the outcomes of microsurgical resection of multiple brain metastasis (BMs).MethodsThis retrospective, monocentric analysis included clinical data from all consecutive BM patients, who underwent simultaneous resection of ≥ 2 BMs between January 2018 and May 2023. Postoperative neurological and functional outcomes, along with perioperative complications, as well as survival data were evaluated.ResultsA total of 47 patients, with a median age of 61 years (IQR 48–69), underwent 73 craniotomies (median 2; range 1–3) for resection of 104 BMs. Among patients, 80.8% presented with symptomatic BMs, causing focal neurological deficits in 53% of cases. Gross total resection was achieved in 87.2% of BMs. Karnofsky Performance Scale (KPS) scores improved in 42.6% of patients, remained unchanged in 46.8%, and worsened in 10.6% after surgery. Perioperative complications were observed in 29.8% of cases, with transient complications occurring in 19.2% and permanent deficits in 10.6%. The 30-days mortality rate was 2.1%. Logistic regression identified eloquent localization (p = 0.036) and infratentorial craniotomy (p = 0.018) as significant predictors of postoperative complications. Concerning overall prognosis, patients with permanent neurological deficits post-surgery (HR 11.34, p = 0.007) or progressive extracranial disease (HR: 4.649; p = 0.006) exhibited inferior survival.ConclusionMicrosurgical resection of multiple BMs leads to clinical stabilization or functional improvement in most patients. Although transient complications do not affect overall survival, the presence of persistent neurological deficits (> 3 months post-surgery) and progressive extracranial disease negatively impact overall survival. This highlights the importance of careful patient selection for resection of multiple BMs.

Does 5-ALA Fluorescence Microscopy Improve Complete Resectability in Cerebral/Cerebellar Metastatic Surgery? A Retrospective Data Analysis from a Cranial Center.

(1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases.

Genetic profiles of oligometastatic non-small-cell lung cancer and corresponding brain metastases.

In patients with oligometastatic non-small-cell lung cancer (NSCLC), systemic therapy in combination with local ablative treatment of the primary tumour and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary NSCLC and corresponding brain metastases (BM). We retrospectively identified patients with oligometastatic NSCLC and synchronous (<3 months) or metachronous (>3 months) BM who underwent surgical resection of both primary tumour and BM. Mutation profiling of formalin-fixed paraffin-embedded tumour cell blocks was performed by targeted next-generation sequencing using the Oncomine Focus Assay panel. Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumours (67.4%) and 40 BM (86.9%). The alteration of the primary tumours was preserved in the corresponding BM in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumours and BM was a KRAS (Kirsten rat sarcoma viral oncogene) mutation (s = 21). In 16 patients (34.8%), the BM harboured additional oncogenic alterations. The presence of a private genetic alteration in the BM was an independent predictor of shorter overall survival. In oligometastatic NSCLC, BM retain the main genetic alterations of the primary tumours. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the BM are dismal.

Abstract PO5-20-03: Phase I/II study of stereotactic radiosurgery with concurrent olaparib followed by adjuvant durvalumab and physician’s choice systemic therapy in subjects with breast cancer brain metastases

Abstract BACKGROUND: Despite progress in the treatment of brain metastasis for HER2+ breast cancer, outcomes for patients with HER2-negative breast cancer brain metastases remain poor. Current standard of care consists of local therapies, including surgery and radiotherapy, followed by systemic therapy. Preclinical studies show inhibitors of poly(ADP-ribose) polymerase (PARP) are effective in combination with radiation therapy as a DNA damage response inhibitor. Triple-negative breast cancer (TNBC) has higher rates of homologous recombination deficiency compared to other breast cancer subtypes, and together with HER2-negative, BRCA-mutated breast cancer would be particularly sensitive to PARP inhibition. PARP inhibition has also demonstrated promising efficacy combined with immunotherapy in patients with germline BRCA-mutant and metastatic TNBC in clinical trials (MEDIOLA, TOPACIO). In addition, immunotherapy with stereotactic radiosurgery (SRS) is associated with favorable intracranial control and survival in patients with brain metastases. We hypothesize that this biologically-driven combination will enhance local control of SRS-treated brain metastases through synergy with PARP inhibition, while controlling micrometastatic disease in the brain and extracranial sites via potentiation of the immune response. METHODS: We are conducting a multi-institution, Phase I/II trial of SRS plus olaparib, followed by durvalumab (with physician’s choice systemic therapy), for patients with TNBC (any BRCA status) or HER2-negative with BRCA-mutated (germline or somatic) breast cancer brain metastases [NCT04711824]. A total of 41 patients are planned for enrollment at 8 sites. The primary objectives are to evaluate safety and tolerability (Phase I) and determine intracranial disease control at 6 months (Phase II) of this treatment combination. Secondary objectives include determining clinical activity via intracranial and global progression-free survival, overall survival, and intracranial and extracranial response rate. Exploratory objectives will assess potential biomarkers of treatment response, including changes in circulating tumor cells and DNA in blood and cerebrospinal fluid, germline and tumor mutations in DNA repair pathway genes, and PD-L1 expression, as well as quality of life and patient-reported outcomes. A surgical sub-study (n=5) will evaluate olaparib concentration/distribution in resected brain metastases. As of June 2023, cohort 2 of phase I has been completed without dose-limiting toxicity. Citation Format: Colette Shen, Yara Abdou, Linda Chen, Xianming Tan, Gaorav Gupta, Mina Lobbous, Filipa Lynce, Erica Stringer-Reasor, Carey Anders. Phase I/II study of stereotactic radiosurgery with concurrent olaparib followed by adjuvant durvalumab and physician’s choice systemic therapy in subjects with breast cancer brain metastases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-03.