Treatment Of Metastatic Brain Tumors Research Articles

10022-MET-2 CLINICAL FEATURES OF RENAL CELL CARCINOMA BRAIN METASTASES COMPARED WITH OTHER CARCINOMAS

Abstract INTRODUCTION In recent years, the positioning of surgical treatment for metastatic brain tumors has changed. To extract conditions suitable for surgical treatment, the background factors for each primary lesion were verified by retrospective analysis of our case. SUBJECTS AND METHODS From 2014 to 2022, 425 patients with metastatic brain tumors diagnosed and treated at our university were included. There were 219 lung cancers, 46 breast cancers, 64 gastrointestinal cancers, 26 renal cell carcinomas, and 70 others. First, the tumor volume and edema volume were measured, and the ROC curve was drawn for the presence or absence of symptoms to determine the cutoff value. After that, statistical analysis was performed on the following items for each primary lesion. The items were tumor volume (T), edema volume (E), tumor edema ratio (E/T), age, KPS, hemorrhage, cyst formation, meningitis, metastasis to other organs, posterior fossa, simultaneous detection, and single tumor. RESULTS The symptomatic cutoff was 1514mm3 for tumor volume (sensitivity 0.86 specificity 0.74) and 15616 mm3 for edema volume (sensitivity 0.85 specificity 0.85). The tumor edema ratio was significantly higher in renal cell carcinoma. Factors with significant differences were older age and multiple lesions in lung cancer, younger age and posterior fossa in breast cancer, lower KPS in gastrointestinal cancer, and solitary cases and bleeding in renal cell carcinoma. DISCUSSION/CONCLUSION In this analysis, many cases of brain metastasis from renal cell carcinoma are solitary, and because they exhibit extensive edema that seems to be affected by VEGF, they tend to develop symptoms while they are small, and they are characterized by hemorrhage easily during the course. These findings suggest that patients with brain metastases from renal cell carcinoma should be given priority for surgical treatment.

10195-MET-11 THE PREDICTIVE FACTORS OF EFFICACY OF PEMBROLIZUMAB IN BRAIN METASTASES OF LUNG CANER

Abstract The main treatment for metastatic brain tumors is radiation therapy or surgical removal. Since the pembrolizumab, an anti-PD1 monoclonal antibody, was revealed to be effective for brain metastases of lung cancer, it has been used as a therapeutic option. However, the predictive factors of its efficacy have been unclear. If the efficacy of pembrolizumab can be predicted prior to the treatment of metastatic brain tumors, it will have a significant impact on subsequent treatment strategies. In this study, we performed a retrospective analysis of patients with metastatic brain tumors from lung cancer treated with pembrolizumab to investigate predictive factors of pembrolizumab efficacy. From January 2018 to July 2023, 73 patients were treated with pembrolizumab for brain metastases of lung cancer at our institution. Among them, 16 patients who had received pembrolizumab for at least 1 year were included. Median age was 68 years (45-86), 10 were male (63%), and median period of pembrolizumab treatment was 105 months (49-319). Patients with brain metastasis which was well controlled for at least 2 years after starting pembrolizumab were defined as effective, and those who required new treatment were defined as invalid. There were 11 effective cases and 5 invalid cases. We compared clinical characteristics, genetic characteristics of the primary tumor, and imaging characteristics of metastatic brain tumors between the effective and ineffective cases, and identified predictive factors for efficacy of pembrolizumab.

Anti-Cancer Effect of Neural Stem Cells Transfected with Carboxylesterase and sTRAIL Genes in Animals with Brain Lesions of Lung Cancer.

A metastatic brain tumor is the most common type of malignancy in the central nervous system, which is one of the leading causes of death in patients with lung cancer. The purpose of this study is to evaluate the efficacy of a novel treatment for metastatic brain tumors with lung cancer using neural stem cells (NSCs), which encode rabbit carboxylesterase (rCE) and the secretion form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). rCE and/or sTRAIL were transduced in immortalized human fetal NSCs, HB1.F3. The cytotoxic effects of the therapeutic cells on human lung cancer cells were evaluated in vitro with the ligands and decoy receptor expression for sTRAIL in the presence of CPT-11. Human NSCs encoding rCE (F3.CE and F3.CE.sTRAIL) significantly inhibited the growth of lung cancer cells in the presence of CPT-11 in vitro. Lung cancer cells were inoculated in immune-deficient mice, and therapeutic cells were transplanted systematically through intracardiac arterial injection and then treated with CPT-11. In resting state, DR4 expression in lung cancer cells and DcR1 in NSCs increased to 70% and 90% after CPT-11 addition, respectively. The volumes of the tumors in immune-deficient mice were reduced significantly in mice with F3.CE.sTRAIL transplantation and CPT-11 treatment. The survival was also significantly prolonged with treatment with F3.sTRAIL and F3.CE plus CPT-11 as well as F3.CE.sTRAIL plus CPT-11. NSCs transduced with rCE and sTRAIL genes showed a significant anti-cancer effect on brain metastatic lung cancer in vivo and in vitro, and the effect may be synergistic when rCE/CPT-11 and sTRAIL are combined. This stem-cell-based study using two therapeutic genes of different biological effects can be translatable to clinical application.

The Symptomatic Improvement of Metastatic Brain Tumor Patients Based on Clinical and Distress Thermometer in Adjunctive Psychotherapy

Background: Along with the increasing incidence of primary cancer, metastatic brain tumors are becoming more common. Metastatic brain tumor patients go through a great deal of distress. Therefore, providing adequate standard therapy can alleviate patients’ clinical symptoms and improve their overall quality of life. This study aimed to investigate the role of symptomatic treatments and adjunctive psychotherapy in patients with metastatic brain tumors. Methods: We conducted a randomized, single-blind, parallel design without matching and pragmatic clinical trial at Cipto Mangunkusumo Hospital from August 2019 – June 2020. A total of 30 metastatic brain tumor patients were divided into 2 groups: (1) The treatment group which received a combination of symptomatic and adjunctive psychotherapy, and (2) The control group which was given symptomatic therapy only. The patients’ distress level was evaluated using a distress thermometer (DT). Data analysis was carried out using the Chi-square test, Fisher exact’s, and binominal test.Results: All patients in the treatment group experienced a significant improvement in overall DT scores before and after adjunctive psychotherapy (p=0.01). Symptomatic therapy alleviates headaches and seizures significantly by 100% with or without psychotherapy. Conclusions: The standard symptomatic treatment of metastatic brain tumors can alleviate clinical symptoms in both groups, especially for headaches and seizures. An adjunctive psychotherapy may significantly improve the overall DT.

Abstract 837: Preclinical development of ELU001: A folate receptor alpha (FRα)-targeted C’Dot drug conjugate (CDC) for the treatment of brain metastases

Abstract Antibody-drug conjugates (ADCs) exhibit limited efficacy against brain malignancies due to their inability to cross the blood-brain barrier (BBB) and penetrate into solid tumors. In clinical imaging studies C’Dots readily crossed tumor-disrupted BBB and penetrated across/localized in tumors in the brain avoiding healthy brain. CDCs are ultra-small (6-7 nm) nanoparticles with a silica core coated by short polyethylene glycol chains conjugated to up to 80 small payload and targeting moieties, creating highly potent and avid agents. CDCs’ small size mediates rapid renal clearance leading to limited exposure to healthy tissues. ELU001 is a potent anti-FRα CDC with an average of 21 exatecan topoisomerase-1 inhibitor payload molecules and 13 folic acid targeting molecules on its surface. ELU001 is currently in a dose escalation trial in patients with systemic solid tumor indications that have the potential to overexpress FRα. Early signs of activity with a manageable safety profile have been seen across antigen expression levels. ELU001 exhibits in vitro potency in the sub/low nanomolar range against cancer cell lines that express 3+, 2+ or 1+ levels of FRα. In studies performed in immunodeficient mice bearing intracranial NCI-H2228-luc bioluminescent non-small cell lung cancer tumors, ELU001 was observed to penetrate across disrupted BBB and localize in tumors. Microscopic analysis revealed that ELU001 distributed throughout the tumors but not into the healthy brain. Treatment with a single cycle of ELU001 Q3Dx3 in mice bearing either early (Day 7) or late (Day 14) brain tumors was well tolerated and resulted in significant reduction in tumor burden measured by bioluminescence as well as a prolonged survival benefit. Retreatment of these animals resulted in an additional decrease in tumor burden. These results suggest that ELU001 may have promise for the treatment of metastatic brain tumors that are difficult to treat with currently available agents. Citation Format: Gregory P. Adams, Tin Khor, Feng Chen, Kai Ma, Marion Scocca, Aranapakam Venkatesan, Cathy Reddick, Mary Hilgart, Thomas Gardinier, Fei Wu, Melik Turker, Peiming Chen, Vaibhav Patel, Eliel Bayever. Preclinical development of ELU001: A folate receptor alpha (FRα)-targeted C’Dot drug conjugate (CDC) for the treatment of brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 837.

Abstract 2472: Interdisciplinary method to elucidate the interaction between brain microenvironment and cancer cells

Abstract Cancer cells may escape from host immunity to form distant metastases. We have made an original imaging model of brain metastasis (IBrM) to show a heterogeneous interaction between microglia, the tissue macrophages in the brain, and cancer cells in the brain niche. Here we report that enhanced microglial elimination of cancer cells is a new potential treatment for metastatic brain tumors by inhibiting their engraftment. First, to explore factors that favor survival of cancer cells in the brain microenvironment, mouse lung cancer cells (CMT167) were injected through the internal carotid artery, and after 4, 7, 10, and 13 days, surviving cancer cells in the mouse brain were collected and RNAseq was performed. In particular, we focused on CD24/CD7/PD-L1, a known factor that escapes phagocytosis by macrophages. The expression of CD24/CD47 in cancer cells gradually increased, while that of PD-L1 decreased. Next, we injected adenocarcinoma lung cancer cells (LUCs, CMT167) or breast cancer cells (BCCs, E0711) expressing mCherry via the internal carotid artery of the CX3CR1-EGFP mice, whose microglia had been specifically labeled with EGFP. The microglia and LUCs/BCCs were visualized in vivo simultaneously by two-photon microscopy for 14 days. The tumor fate and microglial response against cancer cells were evaluated at single cell resolution in the IBrM. Microglial phagocytosis was significantly increased by single deletion of CD47 or CD24 compared with WT cells. Combined deletion of CD47 and CD24 also synergically increased microglial phagocytosis, resulting in reduced IBrM and prolonged mouse survival. By contrast, deletion of PD-L1 did not enhance microglial phagocytosis or prolong survival. The pharmacological (PLX3397) or genetic conditional (Siglechdtr het/CX3CR1GFP het) conditional depletion of microglia canceled both the increased phagocytosis and the extended survival time, suggesting that the effect of “don't eat me” signals was microglia dependent. The extended survival time was also observed in IBrM using BALB-c nu/nu, that suggest the effect is not dependent on matured T-lymphocytes.These results indicate that novel function of microglia against cancer cells, and suppression of both CD24 and CD47 in cancer cells and enhances microglial phagocytic activity and suppresses the metastatic formation. We are further developing a method for isolating LUCs fluorescently labeled in vivo using holographic 2-photon microscopy for evaluating single cell gene expression profiles. Using the novel techniques, the spatio-temporal information can be integrated across the molecular, cellular and tissue levels that allow us to further investigate the dynamic behavior of not only tumors, but also microglia and neurons. Citation Format: Takahiro Tsuji, Hiroaki Wake, Mariko Shindo, Rahadian Y. Hartantio, Misuzu Horikoshi, Daisuke Kato, Hiroaki Ozasa, Toyohiro Hirai. Interdisciplinary method to elucidate the interaction between brain microenvironment and cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2472.

Synergistic effects of radiotherapy with JNK inhibitor-incorporated nanoparticle in an intracranial Lewis Lung Carcinoma Mouse Models.

Radiosurgery has been recognized as a reasonable treatment for metastatic brain tumors. Increasing the radiosensitivity and synergistic effects are possible ways to improve the therapeutic efficacy of specific regions of tumors. c-Jun-N-terminal kinase (JNK) signaling regulates H2AX phosphorylation to repair radiation-induced DNA breakage. We previously showed that blocking JNK signaling influenced radiosensitivity in vitro and in an in vivo mouse tumor model. Drugs can be incorporated into nanoparticles to produce a slow-release effect. This study assessed JNK radiosensitivity following the slow release of the JNK inhibitor SP600125 from a poly (DL-lactide-co-glycolide) (LGEsese) block copolymer in a brain tumor model. A LGEsese block copolymer was synthesized to fabricate SP600125-incorporated nanoparticles by nanoprecipitation and dialysis methods. The chemical structure of the LGEsese block copolymer was confirmed by 1H nuclear magnetic resonance (NMR) spectroscopy. The physicochemical and morphological properties were observed by transmission electron microscopy (TEM) imaging and measured with particle size analyzer. The blood-brain barrier (BBB) permeability to the JNK inhibitor was estimated by BBBflammaTM 440-dye-labeled SP600125. The effects of the JNK inhibitor were investigated using SP600125-incorporated nanoparticles and by optical bioluminescence, magnetic resonance imaging (MRI), and a survival assay in a mouse brain tumor model for Lewis lung cancer (LLC)-Fluc cells. DNA damage was estimated by histone γH2AX expression and apoptosis was assessed by the immunohistochemical examination of cleaved caspase 3. The SP600125-incorporated nanoparticles of the LGEsese block copolymer were spherical and released SP600125 continuously for 24h. The use of BBBflammaTM 440-dye-labeled SP600125 demonstrated the ability of SP600125 to cross the BBB. The blockade of JNK signaling with SP600125-incorporated nanoparticles significantly delayed mouse brain tumor growth and prolonged mouse survival after radiotherapy. γH2AX, which mediates DNA repair protein, was reduced and the apoptotic protein cleaved-caspase 3 was increased by the combination of radiation and SP600125-incorporated nanoparticles.

Surgical Management and Postoperative Outcome in patients with Brain Metastases: Our Surgical Experience

Aims: Metastatic brain tumors are the most commonly seen intracranial lesion in adults and an important cause of morbidity and mortality in patients with cancer. This study aimed to evaluate the postoperative mortality, morbidity, and survival rates of patients who underwent surgery in our clinic for metastatic brain tumorsMethod: Clinical data of 131 patients, including age, sex, symptoms, localization, primer site, surgical methods, resection, complications and recurrence were collected.Results: Fifty patients (38.1%) were female, and 81 (61.8%) patients were male. The average age of the patients was 54,9. The most common reason for hospital admission was headache (68.7%). Lesions were detected in the cerebral hemisphere in 108 (82.4%) patients and the posterior fossa in 23 (17.5%) patients, and 16 (12.2%) patients had multiple lesions. All patients (n=131) underwent surgery with neuronavigation. Total resection was performed in 25 (19%) patients, gross total resection in 83 (63.3%), subtotal resection in 18 (13.7%), and biopsy in 5 (3.8%). The most commonly seen tumor originated from the lungs (n=63, 48%), according to the histopathological examination. The mean overall survival was 5.3 (range, 1–36) months during the follow-up period. Twelve (9.1%) patients had recurrence and underwent surgery again.Conclusion: Multidisciplinary treatment methods are used in the treatment of metastatic brain tumors. Effective surgical intervention to eliminate peritumoral edema and increased intracranial pressure improves postoperative survival rates. In addition, post-surgical whole-brain radiotherapy reduces recurrence and improves survival.

Current approaches to the treatment of metastatic brain tumors

Background/Aim. About 10% of patients diagnosed with systemic cancer leads to the appearance of brain metastases in the central nervous system. Diseased lungs, breasts, urinary and digestive tract as well as melanoma of the skin, are increasingly treated by neurosurgeons due to their dissemination and creation of secondary deposits in the brain. Methods. The retrospective study was performed at the Clinic for Neurosurgery and the Clinic for Oncology in the period from 2018 to 2020. 111 patients with solitary changes in the brain and 122 patients with multiple changes were examined. Results. It was found that multiple metastases are more common in primary lung cancer, while single metastases are more common in adenocarcinoma, but patients with primary adenocarcinoma died in a significantly higher number. Conclusion. Surgery and radiation remain the cornerstone of therapy for symptomatic lesions; We should strive to improve surgical techniques in the direction of less damage to the surrounding healthy tissue. Radiosurgery, as well as VBRT radiation, remain the basic form in the treatment of multiple metastases.

Treating Metastatic Brain Cancers With Stem Cells.

Stem cell therapy may present an effective treatment for metastatic brain cancer and glioblastoma. Here we posit the critical role of a leaky blood-brain barrier (BBB) as a key element for the development of brain metastases, specifically melanoma. By reviewing the immunological and inflammatory responses associated with BBB damage secondary to tumoral activity, we identify the involvement of this pathological process in the growth and formation of metastatic brain cancers. Likewise, we evaluate the hypothesis of regenerating impaired endothelial cells of the BBB and alleviating the damaged neurovascular unit to attenuate brain metastasis, using the endothelial progenitor cell (EPC) phenotype of bone marrow-derived mesenchymal stem cells. Specifically, there is a need to evaluate the efficacy for stem cell therapy to repair disruptions in the BBB and reduce inflammation in the brain, thereby causing attenuation of metastatic brain cancers. To establish the viability of stem cell therapy for the prevention and treatment of metastatic brain tumors, it is crucial to demonstrate BBB repair through augmentation of vasculogenesis and angiogenesis. BBB disruption is strongly linked to metastatic melanoma, worsens neuroinflammation during metastasis, and negatively influences the prognosis of metastatic brain cancer. Using stem cell therapy to interrupt inflammation secondary to this leaky BBB represents a paradigm-shifting approach for brain cancer treatment. In this review article, we critically assess the advantages and disadvantages of using stem cell therapy for brain metastases and glioblastoma.

Single-fraction versus hypofractionated gamma knife radiosurgery for small metastatic brain tumors.

Stereotactic radiosurgery (SRS) has become a standard of care for the treatment of metastatic brain tumors (METs). Although a better balance of tumor control and toxicity of hypofractionated SRS (hfSRS) compared with single-fraction SRS (sfSRS) was demonstrated in large METs, there is no data comparing two approaches for small METs (< 4 cm3). It was aimed to compare clinical outcomes between sfSRS versus hfSRS Gamma Knife radiosurgery (GKRS) in a series of patients with unresected, small METs. Patients (n = 208) treated with sfGKRS or hfGKRS between June 2017 and May 2020 were retrospectively examined in a single center. The co-primary endpoints of local control (LC) and toxicity were estimated by applying the Kaplan-Meier method. Multivariate analysis using Cox proportional hazards (HR) modeling was used to assess the effect of independent variables on the outcomes. The actuarial LC rate was 99.7% at six months and 98.8% at 18months in the sfGKRS group, and 99.4% and 94.3% in the hfGKRS group (p = 0.089), respectively. In multivariate analysis, MET volume (p = 0.023, HR 2.064) and biologically effective dose (BED10) (p < 0.0001, HR 0.753) was associated with LC. In total, treatment-related toxicity was observed in 13 (8.7%) patients during a median period of 10weeks (range 1-31). Radiation necrosis was observed in four patients (1.9%), and all patients were in the sfGKRS group (p = 0.042). Only the maximum dose was associated with toxicity (p = 0.032, HR 1.047). Our current results suggest that hfGKRS is advantageous and beneficial also in patients with unresected, small METs.

[Metastatic Brain Tumors].

Metastatic brain tumors are malignant lesions that spread to the brain from a primary neoplasm such as cancer or sarcoma located in other body organs. Brain metastases tend to cause deterioration of neurological function and negatively affect patients quality of life. Control of brain metastases is important, following improved outcomes that are being observed in patients with cancer. Recent advances in radiotherapy and drug therapy have led to a paradigm shift in the treatment of metastatic brain tumors. In this article, we review the clinical characterization of metastatic brain tumors that has reached a turning point in oncology.

Intraoperative real-time near-infrared optical imaging for the identification of metastatic brain tumors via microscope and exoscope.

As chemotherapy and radiotherapy have developed, the role of a neurosurgeon in the treatment of metastatic brain tumors is gradually changing. Real-time intraoperative visualization of brain tumors by near-infrared spectroscopy (NIRS) is feasible. The authors aimed to perform real-time intraoperative visualization of the metastatic tumor in brain surgery using second-window indocyanine green (SWIG) with microscope and exoscope systems. Ten patients with intraparenchymal brain metastatic tumors were administered 5 mg/kg indocyanine green (ICG) 1 day before the surgery. In some patients, a microscope was used to help identify the metastases, whereas in the others, an exoscope was used. NIRS with the exoscope and microscope revealed the tumor location from the brain surface and the tumor itself in all 10 patients. The NIR signal could be detected though the normal brain parenchyma up to 20 mm. While the mean signal-to-background ratio (SBR) from the brain surface was 1.82 ± 1.30, it was 3.35 ± 1.76 from the tumor. The SBR of the tumor (p = 0.030) and the ratio of Gd-enhanced T1 tumor signal to normal brain (T1BR) (p = 0.0040) were significantly correlated with the tumor diameter. The SBR of the tumor was also correlated with the T1BR (p = 0.0020). The tumor was completely removed in 9 of the 10 patients, as confirmed by postoperative Gd-enhanced MRI. This was concomitant with the absence of NIR fluorescence at the end of surgery. SWIG reveals the metastatic tumor location from the brain surface with both the microscope and exoscope systems. The Gd-enhanced T1 tumor signal may predict the NIR signal of the metastatic tumor, thus facilitating tumor resection.

Stereotactic cyst aspiration directly followed by Gamma Knife radiosurgery for large cystic brain metastases.

Gamma Knife radiosurgery (GKRS) has been proven to be a successful primary treatment for metastatic brain tumors (BM). BM can come in cystic lesions and are often too large for GKRS. An alternative approach to treat cystic BM is stereotactic cyst aspiration (SCA) for volume reduction, making it suitable for GKRS afterwards. Our objective is evaluation of volumetric reduction after SCA, tumor control, and complications after SCA directly followed by GKRS. We performed a retrospective analysis of all patients who underwent SCA directly followed by GKRS at the Gamma Knife Center of the Elisabeth-Tweesteden Hospital in Tilburg between 2002 and 2015. In total, 54 patients had undergone this combined approach. Two patients were excluded because of prior intracranial treatment. The other 52 patients were included for analysis. SCA resulted in a mean volumetric reduction of 56.5% (range 5.50-87.00%). In 83.6% of the tumors (46 tumors), SCA led to sufficient volumetric reduction making GKRS possible. The overall local tumor control (OLTC) of the aspirated lesions post-GKRS was 60.9% (28 out of 46 tumors). Median progression-free survival (PFS) and overall survival (OS) for all patients were 3 (range 5days-14months) and 12months (range 5days-58months), respectively. Leptomeningeal disease was reported in 5 (9.6%) cases. SCA directly followed by GKRS is an effective and time-efficient treatment for large cystic BM in selected patients in which surgery is contraindicated and those with deeply located lesions.

Abstract 3744: Repurposing the neuroprotective agent dimethyl fumarate against white matter damage and cognitive decline after radiotherapy

Abstract Radiation therapy (RT) is a critical tool for the treatment of metastatic brain tumors, most commonly glioblastoma multiforme (GBM), however, patients can have significant cognitive impairment due to the exposure to ionizing radiation. Up to 50%-90% of adult patients that survive these brain tumors will develop radiation-induced cognitive dysfunction within 3-6 months. Brain injury from IR is characterized by white matter damage from the loss of myelin-producing oligodendrocyte cells, subsequent demyelination, and vascular inflammation. While neuro-oncology outcomes are often concerned with survival, strategies to ameliorate and understand radiation-induced demyelination after IR treatment are needed to preserve and improve patient quality of life (QOL). Here we investigate the ability of dimethyl fumarate (DMF), an established neuroprotective agent, to amend damage and demyelination caused by RT in oligodendrocyte cells versus glioma cells. Our in vitro study confirms that DMF acts opposingly in each cell type at lower doses (10 nM), but proves toxic in both the tumor and normal model at high concentrations (100 µM). DMF also increased survival rates in oligodendrocytes after radiation. Using metabolomics, we also noted that oligodendrocyte cells upregulated TCA cycle intermediates in response to DMF treatment with RT. This work provides a basis for in vivo dosing and timing strategies using DMF to cause cessation of ROS-driven oligodendrocyte loss and inflammation after RT. Ultimately, DMF is a promising therapy that could be used to ameliorate radiation-induced demyelination, promoting patient QOL. Citation Format: Alexandra Taraboletti, Albert J. Fornace. Repurposing the neuroprotective agent dimethyl fumarate against white matter damage and cognitive decline after radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3744.

Postoperative radiosurgery for the treatment of metastatic brain tumor: Evaluation of local failure and leptomeningeal disease

In patients undergoing surgical resection of a metastatic brain tumor, whole brain radiation therapy reduces the risk of recurrence and neurologic death. Focal radiation has the potential to mitigate neurocognitive side effects. We present an institutional experience of postoperative radiosurgery for the treatment of brain metastases. A retrospective review of a prospectively maintained institutional radiosurgery database was performed for the years 2005–2015 identifying all adult patients treated with postoperative radiosurgery to the tumor bed. Primary endpoints include local recurrence and postoperative LMD. Kaplan-Meier curves and Cox regression were used to evaluate time to local recurrence and postoperative LMD. Ninety-one patients received adjuvant focal radiation for a brain metastasis. Median radiographic follow-up among patients who had not developed a local failure was 9 months. Of the 91 patients, 20 (22%) developed local recurrence and 32 (35%) experienced postoperative LMD. Freedom from local recurrence and LMD at 1 year was 84% and 69%, respectively. In multivariable models, predictors of local failure included the presence of more than one brain metastasis (HR = 2.65, p = .04) with a preoperative tumor diameter of >3 cm (HR = 4.16, p = .06) trending toward significance. There was a trend to a higher risk of LMD with >1 tumor (HR 2.07, p = .06) and breast cancer (HR 2.37, p = .07). More than one metastasis is an independent predictor of local and leptomeningeal failure following postoperative radiosurgery. The high rate of LMD was likely related to the liberal definition of LMD to include focal dural recurrences.

Analysis of Evolving Clinicopathological Features of Metastatic Brain Tumors Over 30 Years of Surgical Management.

We reviewed 232 cases, in which patients underwent surgical resection and histopathological diagnosis of metastatic brain tumor between 1985 and 2014. We analyzed trends in clinicopathological changes present over three decades in a single institution. The most frequent site of metastatic tumors was the frontal lobe. The average patient age and the percentage of female patients increased over the 30-year study period. The most frequent primary cancer was lung cancer, followed by breast cancer; these were the top two primary cancer types over the three decades. However, use of chemotherapy and radiotherapy as standard treatments for postoperative treatment of metastatic brain tumors has increased over the past 20 years. Development of novel, targeted treatments for these cancer types have created new tools for use in the clinical care of patients with metastatic brain tumors. Incorporation of these tools in a multimodal approach is critical in contemporary management of metastatic brain tumors.

Prognosis of efficacy of post-operation treatment of metastatic brain tumors.

Background . Metastatic affection of brain by its prevalence, medical and social importance, economical burden represents a topical medical problem in neurosurgery and adjacent medical specialties. Objective – optimization of prognosis for post-operation metastatic brain tumors treatment efficacy. Methods . An active cohort randomized research with retro- and prospective, cross-sectional and longitude components has been conducted in 176 patients, including 96 males and 80 females aged 56 years with adenocarcinoma (152), melanoblastoma (21) and sarcoma (3), derived from lungs (39), breast (34), skin (25) kidneys (9), digestive tract (11), ovary and uterus (by 4 each), thymus (2), nasopharynx, pronaus (by 1 each). Standard basic diagnostic and treatment procedures have been performed. P-level critical value was 0.05. Results . Discriminant models of post-operation tactics choice, prognostic algorithm of unfavorable outcome evaluation after treatment have been developed. The approbation of the algorithm allowed to state its sensitivity (69.2 %), specificity (95.2 %), positive predicting value (75.0 %), negative predicting value (93.7 %). Conclusion . For the purpose of widening of arsenal of available decision-making means for further treatment tactics in metastatic brain tumors after conducted neurosurgical treatment the use of developed discriminant models is recommended. The risk of unfavorable outcome and efficacy of combined treatment prognosis for patients with metastatic brain tumors are recommended to assess using the developed prognostic algorithm.

The effectiveness of the combined treatment of metastatic brain tumors

Цель. Оценка эффективности лучевой терапии (ЛТ) и химиотерапии (ХТ) при метастатических опухолях головного мозга (МОГМ) в послеоперационном периоде. Материалы и методы. Обследованы 49 пациентов, у которых выявлены МОГМ: 4 (12,9%) — в лобной доле, у 2 (6,5%) — в височной, у 8 (25,8%) — в теменной, у 4 (12,9%) — в затылочной, у 7 (22,6%) — в полушарии мозжечка, у 2 (6,5%) — в костях черепа, по 1 (3,2%) — в области мосто-мозжечкового угла, гипофиза, оболочках, лобной пазухе. Результаты. Аденокарцинома диагностирована у 35 (71,4%) больных, меланобластома — у 13 (26,6%), саркома — у 1 (2,0%). Первичная опухоль у 31 пациента локализовалась: в коже — у 13 (41,9%), легких — у 6 (19,4%), грудной железе и почках — по 4 (12,9%) наблюдения, в зобной железе, яичнике, матке, наружных половых органах — по 1 (3,2%). Опухоль удалена радикально у 32 (65,3%) больных, субтотально — у 14 (28,6%), частично — у 2 (4,1%), у 1 — проведена биопсия. В раннем периоде умер 1 (2,0%) больной (тромбоэмболия легочной артерии). У 9 (18,8%) больных (І группа) проведена ХТ, у 6 (12,5%) (ІІ группа) — ЛТ, у 3 (6,3%) (ІІІ группа) — ХТ и ЛТ; у 30 (62,4%) — специальное лечение не проводили. За В сроки наблюдения до 1 года в III группе — живы все пациенты, в I и II группах — 66,7%, без специального лечения — 33,3%. Выводы. При МОГМ после операции сочетанное проведение ЛТ и ХТ является оптимальной тактикой лечения. Дальнейшая перспектива — продолжение исследования с изучением качества жизни пациентов.

Clinical trial update: treatment of metastatic brain tumors using MRgFUS

Metastatic brain tumors are common lesions that are currently treated with multimodal therapy. Surgical resection, focused stereotactic radiosurgery, and whole brain radiation remain traditional therapies. It has been postulated that metastatic brain tumors could be treated effectively with MRgFUS using thermal ablation.