Management Of Brain Metastases Research Articles

Management of Brain Metastasis in Patients With Breast Cancer

Management of Brain Metastasis in Patients With Breast Cancer

168: Utilization Trends of Stereotactic Radiosurgery and Whole Brain Radiotherapy in the Management of Brain Metastases at a Regional Cancer Centre

168: Utilization Trends of Stereotactic Radiosurgery and Whole Brain Radiotherapy in the Management of Brain Metastases at a Regional Cancer Centre

Second window ICG predicts gross-total resection and progression-free survival during brain metastasis surgery.

Metastases are the most common intracranial malignancies and complete resection can provide relief of neurological symptoms and reduce recurrence. The authors' prospective pilot study in 2017 demonstrated promising results for the application of high-dose, delayed imaging of indocyanine green (ICG), known as second window ICG (SWIG), in patients undergoing surgery for brain metastases. In this prospective cohort study, the authors evaluated intraoperative imaging and clinical outcomes of treatment using SWIG. Patients were prospectively enrolled in an approved study of high-dose, delayed ICG (SWIG) and received 5 mg/kg (2014-2018) or 2.5 mg/kg (2018-2019) ICG 24 hours preoperatively. Intraoperatively, near-infrared (NIR) imaging was performed using a dedicated NIR exoscope. NIR images were analyzed and the signal-to-background ratio (SBR) was calculated to quantify fluorescence. Residual fluorescence on the postresection NIR view was compared and correlated to the residual gadolinium enhancement on postoperative MRI. Patient survival and predictive factors were analyzed. In total, 51 intracranial metastases were surgically treated in 47 patients in this cohort. All 51 metastatic tumors demonstrated strong NIR fluorescence (mean SBR 4.9). In tumors ≤ 10 mm from the cortical surface, SWIG with 5 mg/kg ICG produced enhanced transdural tumor visibility (91.3%) compared to 2.5 mg/kg (52.9%; p = 0.0047). Neoplastic margin detection using NIR fluorescence compared to white light improved sensitivity, albeit lowered specificity; however, increasing the SBR cutoff for positive fluorescence significantly improved specificity without sacrificing sensitivity, increasing the overall accuracy from 57.5% to 72.5%. A lack of residual NIR fluorescence after resection was closely correlated with a lack of residual enhancement on postoperative MRI (p = 0.007). Among the 16 patients in whom tumor recurred at the site of surgery, postoperative MRI successfully predicted 8 cases, whereas the postresection NIR view predicted 12 cases. Progression-free survival rate at 12 months was greater for patients without residual NIR fluorescence (38%) than for those without residual enhancement on postoperative MRI (29%). The current study demonstrates the clinical benefits of the SWIG technique in surgery for patients with brain metastases. Specifically, this technique allows for dose-dependent, transdural localization of neoplasms and improved sensitivity in neoplastic margin detection. Postresection residual fluorescence can be a powerful tool to evaluate extent of resection in conjunction with MRI, and it may guide decisions on brain metastasis management.

NEIM-04. PROSPECTIVE STUDY OF SCREENING MRI OF THE BRAIN IN PATIENTS WITH METASTATIC OR INFLAMMATORY BREAST CANCER

Abstract BACKGROUND The management of brain metastases is often dictated by the size and number of lesions present, with more invasive/aggressive therapies such as resection and whole brain radiation utilized for more extensive intracranial disease. Consensus guidelines for patients with advanced lung cancer or melanoma recommend magnetic resonance imaging (MRI) of the brain to screen for brain metastases. Due to a lack of prospective studies demonstrating benefit, screening brain imaging is currently not recommended by consensus guidelines in breast cancer. APPROACH Eligible patients are those with breast cancer initiating first-fourth line chemotherapy for extracranial metastatic disease or unresectable local recurrence devoid of prior intracranial involvement. A study-specific MRI (3D T1 pre-contrast + 3D T1 post-contrast acquisition) was developed to limit scan time to approximately 10-12 minutes. Patients with HR+/HER2- and HER2+ positive disease are randomized to screening brain MRIs vs not (primary outcome: neurologic quality of life, target N=156) while all patients with triple negative breast cancer (TNBC) receive brain MRIs (primary outcome: rate of symptomatic brain metastases relative to historical controls, target N=33). Screened patients undergo one MRI at enrollment and, if negative, a second MRI at first systemic progression. In addition, an exploratory cohort of patients with inflammatory breast cancer (IBC) managed with curative intent is included, in which patients undergo brain MRIs at baseline and, if negative, every six months for two years (primary endpoint: cumulative incidence of brain metastases, target N=25). In all cohorts, a multidisciplinary discussion is convened to determine optimal management in cases where brain metastases are identified. STUDY PROGRESS The study activated in 2019. As of 7/9/21, 28 patients have been enrolled. Enrollment has been more robust in single arm cohorts (TNBC: 13/33 enrolled; IBC 8/25 enrolled) than in the randomized subset (7/156 enrolled). Updated accrual will be presented at the meeting.

The Surgical Management of Brain Metastases in Non-Small Cell Lung Cancer (NSCLC): Identification of the Early Laboratory and Clinical Determinants of Survival.

Background: Brain metastases (BM) indicate advanced states of cancer disease and cranial surgery represents a common treatment modality. In the present study, we aimed to identify the risk factors for a reduced survival in patients receiving a surgical treatment of BM derived from non-small cell lung cancer (NSCLC). Methods: A total of 154 patients with NSCLC that had been surgically treated for BM at the authors’ institution between 2013 and 2018 were included for a further analysis. A multivariate analysis was performed to identify the predictors of a poor overall survival (OS). Results: The median overall survival (mOS) was 11 months (95% CI 8.2–13.8). An age > 65 years, the infratentorial location of BM, elevated preoperative C-reactive protein levels, a perioperative red blood cell transfusion, postoperative prolonged mechanical ventilation (>48 h) and the occurrence of postoperative adverse events were identified as independent factors of a poor OS. Conclusions: The present study identified several predictors for a worsened OS in patients that underwent surgery for BM of NSCLC. These findings might guide a better risk/benefit assessment in the course of metastatic NSCLC therapy and might help to more sufficiently cope with the challenges of cancer therapy in these advanced stages of disease.

SURG-01. Management of solitary brain metastasis less than 4 cm in diameter. Surgical resection versus stereotactic radiotherapy: a meta-analysis

IntroductionTo treat a solitary metastasis in the brain, surgical resection and/or radiotherapy are the standard treatments of care. However, the clinical scenarios in which to use these techniques alone or in combination are controversial. While a course of stereotactic radiotherapy is often administered to a patient who presents with multiple metastases, surgical resection is often directed against a larger solitary brain metastasis before irradiating the resection bed. The management of a smaller solitary tumor (diameter less than 4 cm) is less clear. Accordingly, our meta-analysis assembled studies that focused on patients with a solitary tumor less than 4 cm in diameter.MethodsFollowing PRISMA guidelines (PROSPERO ID: CRD42021242434), we searched PubMed, Web of Knowledge, and Cochrane Library databases for randomized controlled trials (RCT) and observational studies comparing surgery to radiotherapy for solitary metastatic brain tumors less than 4 cm in diameter. From 498 total records, we included 9 studies for meta-analysis. Analysis was performed on R.Results2 RCTs and 7 observational studies were identified. 431 patients underwent surgical intervention, and 349 patients exclusively underwent radiotherapy. The surgical treatment cohort did not exhibit a difference in 1-year (OR [95% CI] = 0.866 [0.609–1.289]), 2-year (1.7 [0.843–3.428]), or overall survival (1.18 [0.598–2.327]). However, the surgical treatment group demonstrated greater local tumor recurrence after 1-year (3.975 [1.979–7.987]) and overall local recurrence (3.045 [1.276 - 7.268]). There was no difference between the overall rates of distant recurrence (0.565 [0.218 - 1.466]).ConclusionsOur analysis opens more discussion about the management of solitary brain metastasis. Patient selection is paramount in achieving better local control. Stereotactic radiotherapy should be considered for treatment of solitary brain metastasis less than 4 cm in diameter in selected patients. Future randomized control trials for small solitary masses are recommended.

SURG-03. The effect of surgery on radiation necrosis in irradiated brain metastases: extent of resection and long-term clinical and radiographic outcomes

ObjectiveRadiation 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.MethodsA 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 2003–2018. 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.ResultsForty-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). There was a trend towards decreased steroid use, from 8mg daily dexamethasone-equivalent (range 2–36) preoperatively to 3mg 12-months postoperatively (range 1–8; p=0.063).ConclusionsRN resection conferred both durable T2-FLAIR reduction, which correlated with EOR, and reduced steroid dependency.

Breast cancer brain metastasis: insight into molecular mechanisms and therapeutic strategies

Breast cancer is one of the most prevalent malignancies in women worldwide. Early-stage breast cancer is considered a curable disease; however, once distant metastasis occurs, the 5-year overall survival rate of patients becomes significantly reduced. There are four distinct metastatic patterns in breast cancer: bone, lung, liver and brain. Among these, breast cancer brain metastasis (BCBM) is the leading cause of death; it is highly associated with impaired quality of life and poor prognosis due to the limited permeability of the blood-brain barrier and consequent lack of effective treatments. Although the sequence of events in BCBM is universally accepted, the underlying mechanisms have not yet been fully elucidated. In this review, we outline progress surrounding the molecular mechanisms involved in BCBM as well as experimental methods and research models to better understand the process. We further discuss the challenges in the management of brain metastases, as well as providing an overview of current therapies and highlighting innovative research towards developing novel efficacious targeted therapies.

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

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. 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. 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 6months 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 12months postoperatively (p = 0.001). RN resection conferred both durable T2-FLAIR reduction, which correlated with EOR; and reduced steroid dependency.

Nonsurgical Management of Melanoma Brain Metastasis: Current Therapeutics, Challenges, and Strategies for Progress.

This review aims to provide an overview of nonsurgical treatment strategies for central nervous system metastases in melanoma as well as discuss treatment challenges and future directions. Recent strategies for melanoma brain metastases have involved proving the intracranial activity of approved therapies as well as identifying novel drug targets. BRAF/MEK combination therapy has intracranial activity in those with BRAF V600 mutations, though disease control is shorter for intracranial than extracranial metastases. Immunotherapy and combination immunotherapies have emerged as providing durable responses in melanoma, and newer studies combining immunotherapy with targeted therapies are emerging. Continued challenges include penetration through the blood-brain barrier and development of resistance mechanisms. Novel therapeutic targets and methods to improve central nervous system penetrance are being identified through the application of deep DNA- and RNA-sequencing analyses. Radiation therapy approaches, especially stereotactic radiosurgery in combination or in sequence with systemic therapies, are also being investigated. Both targeted therapies and immunotherapies have revolutionized the field of melanoma treatment. Multimodality approaches with multidisciplinary teams will pave the way for the future of central nervous system disease treatment in melanoma.

Nivolumab and stereotactic radiosurgery for patients with breast cancer brain metastases: A non-randomized, open-label phase Ib study.

e14010 Background: There may be a potential synergy intracranially between stereotactic radiation and immune checkpoint inhibition in brain metastases management. We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated and may improve intracranial tumor control rates compared to SRS alone in the management of breast cancer brain metastases. Methods: The study was designed as a prospective, single-arm, nonrandomized, open-label, phase Ib trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Key eligibility criteria included patients with breast cancer brain metastases of all subtypes, age ≥ 18, ECOG ≤ 2 with ≤ 10 brain metastases. The primary objective was to evaluate the safety and feasibility of study therapy. Secondary objectives included evaluation of local brain metastasis control, distant brain metastasis control, progression free survival (PFS), and overall survival following study therapy. Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) and immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria were used to assess intracranial and extracranial disease, respectively. Treatment was initiated with a dose of nivolumab (480 mg IV) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT03807765. Results: Between February 2019 and July 2020, a total of 12 patients were treated to 17 lesions. Median follow-up from start of protocol therapy is currently 9.6 months (range: 2.8-18.7 months). No dose limiting toxicities (DLTs) were noted in our patient population. The most common neurologic adverse events included grade 1-2 headaches and dizziness occurring in 5 (42%) of patients. Median intracranial control was 6.2 months (95% CI 3.0 -14) with 6 and 12 month control rates of 55% and 22%, respectively. A total of 4 patients had systemic progression during the study. Median time to systemic PFS has not been reached with 6 and 12 month rates of 63% and 51%, respectively. Conclusions: Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. Preliminary studies reveal activity in certain breast cancer patients to study therapy. Clinical trial information: NCT03807765.

Use of brain radiotherapy as part of first course of treatment for NSCLC with de novo brain metastasis.

9118 Background: Loco-regional management of brain metastases from non-small cell lung cancer (NSCLC) are surgery and/or brain radiotherapy, either whole brain (WBRT) or stereotactic (SRS). We used a national registry to evaluate trends in the use of brain radiotherapy as part of the first course of management in patients diagnosed with de novo brain metastasis. Methods: We retrospectively analyzed the National Cancer Database (NCDB) to identify patients with NSCLC and de novo brain metastasis diagnosed from 2004-2016. We described the socio-demographic and clinical characteristics of this population, then used chi-squared testing to evaluate for an association between these variables and the use of brain radiotherapy (either SRS or WBRT). Significant variables (p &lt; 0.05) were included in a multiple logistic regression model. Results: Of n = 41,454 patients with NSCLC and de novo brain metastasis, n = 27,949 (67.4%) received either SRS or WBRT as part of their first course of treatment, while n = 13,505 (32.6%) did not receive primary brain radiation. Of those that did not receive radiation: n = 9,927 (73.5%) were &lt; 70 years old while n = 3,578 (26.5%) were ≥70. N = 11,081 (82.7%) were White, n = 1,550 (11.6%) were Black and n = 768 (5.7%) were Asian. Variables significantly associated with the use of primary brain radiotherapy at the multivariate level were: treatment facility type (p = 0.004), tumor histology (p &lt; 0.001), clinical T-staging (p &lt; 0.001), and clinical N-staging (p &lt; 0.001). Age, sex, race, comorbidity, grade, insurance status, and setting (metro vs. rural vs. urban) were not significantly associated with the use of radiotherapy. Compared to patients treated at community cancer programs (CPs), those treated at comprehensive community CPs (OR 1.152, 95% CI 1.027-1.291, p = 0.015) and academic CPs (OR 1.242, 95% CI 1.104-1.398, p &lt; 0.001) were more likely to receive primary brain radiotherapy. Patients with squamous NSCLC were less likely (OR 0.680, 95% CI 0.619-0.747, p &lt; 0.001) to receive brain radiotherapy compared to those with adenocarcinoma. Finally, patients with advanced T-staging (p &lt; 0.001) and N-staging (p &lt; 0.001) were less likely (OR &lt; 1) to receive brain radiotherapy as part of the first course of treatment. Conclusions: While insurance status and setting were not significantly associated with the use of brain radiotherapy, facility type was. Further research is needed to evaluate whether this is a true disparity in medical practice, or the differences can be explained by characteristics of the patient population undocumented by the NCDB (e.g. severity of brain metastasis). Additionally, patients with larger primary tumors were less likely to receive brain radiation as part of the first course of treatment, which may reflect the need for local therapy prior to treating metastatic sites.

Management of brain metastases in elderly patients with lung cancer.

The incidence of brain metastases (BM) is continuing to grow in the elderly population with lung cancer, but these patients are seriously under-represented in clinical trials. Thus, their treatment is not based on the evidence from randomized prospective studies. Age is a well recognized poor prognostic factor for survival in patients with BM from lung cancer, which is reflected in prognostic scales, but its impact on the patients' prognosis reflected by its value in gradually updated grading indices seems to decrease. The reason for poorer outcomes in the elderly is unknown—it may result from the influence of the age per se, simplified staging work-up and suboptimal treatment in this patient subgroup or the excess toxicity of the aggressive anticancer treatment secondary to the impaired physiological regulation mechanisms and comorbidities. The main goal of treatment of BM is to ameliorate neurological symptoms and delay neurological progression, with the focus on the improvement and maintenance of the patients’ quality of life. The possible treatment options for BM from lung cancer are whole-brain radiotherapy, stereotactic radiosurgery, surgery, chemotherapy, targeted therapies and best supportive care. The aim of this review is to summarize the problems related to the management of BM in elderly patients with lung cancer, to analyze the value of the above mentioned treatment options, and to provide an insight into the influence of age-related clinical factors on the patients’ outcomes.

Radiotherapy for brain metastases from small-cell lung cancer in distinct clinical indications and scenarios.

Management of brain metastases (BM) from small-cell lung cancer (SCLC) is complex and not supported by a strong evidence from prospective clinical trials. Owing to the different clinical and pathological characteristics of SCLC, patients with this histology were not included in the prospective studies on the value of whole-brain radiotherapy (WBRT) and local surgical or ablative radiation treatment like stereotactic radiosurgery (SRS). Chemotherapy also represents a major part of the armamentarium against BM from SCLC due to the well-recognized chemoresponsiveness of this cancer and the frequent presentation of BM with extracranial progression. WBRT in combination with chemotherapy has long been a standard approach in this setting. However, data on the neurocognitive toxicity and the lack of documented impact on overall survival of WBRT in the management of BM from other solid tumors, as well as the increasing availability of the stereotactic radiotherapy technologies, has led to the increasing use of SRS with omission of WBRT also in SCLC. In the current review the use of different modalities of radiotherapy and ways of combining radiotherapy with chemotherapy for BM from SCLC will be presented for distinct clinical situations: presentation of BM synchronous with primary, metachronous presentation of BM—without previous prophylactic cranial irradiation (PCI) vs. after PCI, and asymptomatic BM found at the staging before PCI.

Differentiation of brain metastases from small and non-small lung cancers using apparent diffusion coefficient (ADC) maps

BackgroundBrain metastases are particularly common in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC showing a less aggressive clinical course and lower chemo- and radio sensitivity compared to SCLC. Early adequate therapy is highly desirable and depends on a reliable classification of tumor type. The apparent diffusion coefficient is a noninvasive neuroimaging marker with the potential to differentiate between major histological subtypes. Here we determine the sensitivity and specificity of the apparent diffusion coefficient to distinguish between NSCLC and SCLC.MethodsWe enrolled all NSCLC and SCLC patients diagnosed between 2008 and 2019 at the University Medical Center Göttingen. Cranial MR scans were visually inspected for brain metastases and the ratio of the apparent diffusion coefficient (ADC) was calculated by dividing the ADC measured within the solid part of a metastasis by a reference ADC extracted from an equivalent region in unaffected tissue on the contralateral hemisphere.ResultsOut of 411 enrolled patients, we detected 129 patients (83 NSCLC, 46 SCLC) with sufficiently large brain metastases with histologically classified lung cancer and no hemorrhage. We analyzed 185 brain metastases, 84 of SCLC and 101 of NSCLC. SCLC brain metastases showed an ADC ratio of 0.68 ± 0.12 SD, and NSCLC brain metastases showed an ADC ratio of 1.47 ± 0.31 SD. Receiver operating curve statistics differentiated brain metastases of NSCLC from SCLC with an area under the curve of 0.99 and a 95% CI of 0.98 to 1, p < 0.001. Youden's J cut-point is 0.97 at a sensitivity of 0.989 and a specificity of 0.988.ConclusionsIn patients with lung cancer and brain metastases with solid tumor parts, ADC ratio enables an ad hoc differentiation of SCLC and NSCLC, easily achieved during routine neuroradiological examination. Non-invasive MR imaging enables an early-individualized management of brain metastases from lung cancer.Trial registration: The study was registered in the German Clinical Trials Register (DRKS00023016).

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021.

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.2020), and Brain Metastases Management (added in v3.2020). The v1.2021 update included additional modifications of these sections and notable revisions to Principles of: Pathology, Surgical Margins for Wide Excision of Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic Lymph Node Dissection, and Radiation Therapy. These NCCN Guidelines Insights discuss the important changes to pathology and surgery recommendations, as well as additions to systemic therapy options for patients with advanced disease.

P09.07 Oncologists Practices and Perceptions on Management of Brain Metastases from Non-Small Cell Lung Cancers-: A Nationally Representative Survey

P09.07 Oncologists Practices and Perceptions on Management of Brain Metastases from Non-Small Cell Lung Cancers-: A Nationally Representative Survey

Bevacizumab for radiation necrosis following radiotherapy of brain metastatic disease: a systematic review & meta-analysis

BackgroundRadiotherapy is the mainstay of brain metastasis (BM) management. Radiation necrosis (RN) is a serious complication of radiotherapy. Bevacizumab (BV), an anti-vascular endothelial growth factor monoclonal antibody, has been increasingly used for RN treatment. We systematically reviewed the medical literature for studies reporting the efficacy and safety of bevacizumab for treatment of RN in BM patients.Materials and methodsPubMed, Medline, EMBASE, and Cochrane library were searched with various search keywords such as “bevacizumab” OR “anti-VEGF monoclonal antibody” AND “radiation necrosis” OR “radiation-induced brain necrosis” OR “RN” OR “RBN” AND “Brain metastases” OR “BM” until 1st Aug 2020. Studies reporting the efficacy and safety of BV treatment for BM patients with RN were retrieved. Study selection and data extraction were carried out by independent investigators. Open Meta Analyst software was used as a random effects model for meta-analysis to obtain mean reduction rates.ResultsTwo prospective, seven retrospective, and three case report studies involving 89 patients with RN treated with BV were included in this systematic review and meta-analysis. In total, 83 (93%) patients had a recorded radiographic response to BV therapy, and six (6.7%) had experienced progressive disease. Seven studies (n = 73) reported mean volume reductions on gadolinium-enhanced T1 (mean: 47.03%, +/− 24.4) and T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI images (mean: 61.9%, +/− 23.3). Pooling together the T1 and T2 MRI reduction rates by random effects model revealed a mean of 48.58 (95% CI: 38.32–58.85) for T1 reduction rate and 62.017 (95% CI: 52.235–71.799) for T2W imaging studies. Eighty-five patients presented with neurological symptoms. After BV treatment, nine (10%) had stable symptoms, 39 (48%) had improved, and 34 (40%) patients had complete resolution of their symptoms. Individual patient data was available for 54 patients. Dexamethasone discontinuation or reduction in dosage was observed in 30 (97%) of 31 patients who had recorded dosage before and after BV treatment. Side effects were mild.ConclusionsBevacizumab presents a promising treatment strategy for patients with RN and brain metastatic disease. Radiographic response and clinical improvement was observed without any serious adverse events. Further class I evidence would be required to establish a bevacizumab recommendation in this group of patients.

Abstract PS14-08: Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal disease

Abstract BACKGROUNDImprovements in systemic therapies have led to significantly improved survival in patients with breast cancer and have created a challenge with regards to management of brain metastases (BM) and leptomeningeal disease (LMD). LMD is a highly aggressive condition, resulting in rapid neurological decline and a short survival of weeks to months. The purpose of this study is to identify clinical factors that can predict for LMD when a patient is diagnosed with BM, and to assess outcomes with various treatment modalities.METHODSA retrospective analysis was conducted using a clinical database at a single institution and included 178 patients with breast cancer and treated BM between 2007-2020. Demographic, clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cytology or neuroimaging. Chi-square and t-test were used.RESULTSOut of 178 patients with breast cancer and treated BM, 41 (23%) developed LMD. Median age for the study cohort was 51.3 +-13.4 years; those with LMD was 47.9 +-12.3 (p=0.057) years. One of the 178 patients was a male and all 41 with LMD were females. There were 58.5% Caucasian women in the LMD group followed by African-American being 24.4% (p=0.31). Characteristics like number of brain lesions (p=0.57), median size of the largest brain lesion (p=0.70), hemorrhagic/cystic lesions (p=0.68), systemic disease being progressive in 42.6%, stable in 19.3% and 26.1% with no evidence of systemic disease at the time of diagnosis of BM (p=0.34) did not pose a higher risk in developing LMD. For 29% patients the brain lesions were supratentorial, 23.7% were infratentorial and 47.4% patients had both and had a higher risk for LMD (p=0.025). Patients with liver (p=0.45) and bone (p=0.48) lesions did not have higher risk for LMD which was seen in those without lung metastases (p=0.03). In the LMD group, 39% had HR+, 31.7% HER2+, and 41.4% had triple negative breast cancer (TNBC). The higher incidence of HR+ patients could be attributed to the fact that the more aggressive HER2+ and TNBC patients may have not gotten treatment for their BM as they pursued comfort care status. In the LMD group, 13.1% received prior stereotactic radiation, 39.5% whole brain radiation, 10.5% had surgery alone and 36.8% had surgery with pre/post-op radiation. Patients who had any surgery did not have a higher risk for LMD (p=0.26). Surgery did not pose a higher risk for local recurrence, seen in 28% patients (p=0.42) and occurrence of BM at another site, seen in 36.5% patients (p=0.16). CONCLUSIONSAmong breast cancer patients with brain metastases those who develop LMD tend to be younger, with higher risk in Caucasians and African-American women; however, this was not statistically significant. The number, size, hemorrhagic/cystic character of brain lesions did not pose a higher risk whereas occurrence of synchronous lesions in supratentorial and infratentorial locations increased risk of LMD. There was no statistically significant difference in the rates of LMD, local recurrence, CNS recurrence at another site with surgery and/or radiation. EthnicityBrain metastases (N=178)LMD group (N=41) (p=0.31)Caucasian58.4%58.5%Hispanic12.4%4.9%African-American19.1%24.2%Others10.1%12.2% Clinical characteristicsBrain metastasesLMD groupP valueNumber of brain lesions (Median interquartile range)3 (1-8)2.5 (1-9)P=0.57Median size of the largest brain lesion (cm)2.4 1.42.53 1.69p=0.70Hemorrhagic lesions223P=0.68Cystic lesions163 Citation Format: Akshjot Puri, Charisma Mylavarapu, Jiagiong Xu, Tejal A Patel, Bin S Teh, Ivo Tremont-Lukats, Jenny C Chang, Polly Niravath. Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal disease [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-08.

Prognostic Value of 5-ALA Fluorescence, Tumor Cell Infiltration and Angiogenesis in the Peritumoral Brain Tissue of Brain Metastases.

Simple SummaryIn a recent study, we observed 5-ALA fluorescence not only in brain metastases (BM) but also in the peritumoral brain tissue. However, the histopathological correlate of visible 5-ALA fluorescence in the peritumoral brain tissue is not fully understood. Therefore, we safely collected and analyzed tissue samples from fluorescing and non-fluorescing peritumoral brain tissue. Surprisingly, 5-ALA fluorescence in the peritumoral brain tissue did not correlate with tumor cell infiltration but did show a significant relation with angiogenesis. Moreover, the presence of angiogenesis significantly correlated with shorter time to local progression/recurrence and one-year survival. Consequently, angiogenesis in the peritumoral brain tissue might be a novel prognostic marker in BM. This represents the first study in the literature describing the prognostic impact of angiogenesis in fluorescent peritumoral brain tissue of BM, which might support individualized perioperative treatment concepts in the future.Complete resection is an indispensable treatment option in the management of brain metastases (BM). 5-aminolevulinic acid (5-ALA) fluorescence is used for improved intraoperative visualization of tumor tissue in gliomas and was recently observed in BM. We investigated the potential of 5-ALA fluorescence to visualize the infiltrative growth of BM in the peritumoral brain tissue and its histopathological correlate. Patients with BM resection after 5-ALA administration and collection of tissue samples from peritumoral brain tissue were included. Each tissue sample was histopathologically investigated for tumor cell infiltration and angiogenesis. Altogether, 88 samples were collected from the peritumoral brain tissue in 58 BM of 55 patients. Visible 5-ALA fluorescence was found in 61 (69%) of the samples, tumor infiltration in 19 (22%) and angiogenesis in 13 (15%) of samples. Angiogenesis showed a significant correlation with presence of fluorescence (p = 0.008). Moreover, angiogenesis was related to visible 5-ALA fluorescence and showed an association with patient prognosis since it was significantly correlated to shorter time to local progression/recurrence (p = 0.001) and lower one-year survival (p = 0.031). Consequently, angiogenesis in the peritumoral brain tissue of BM might be a novel prognostic marker for individualized perioperative treatment concepts in the future.