scholarly journals Medical management of brain metastases

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Adam Lauko ◽  
Yasmeen Rauf ◽  
Manmeet S Ahluwalia
Keyword(s):  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Tumor Biology ◽  
Therapeutic Benefit ◽  
Treatment Modalities ◽  
Primary Tumors ◽  
Mortality And Morbidity ◽  
Novel Approaches ◽  
Neurocognitive Decline

Absrtract The development of brain metastases occurs in 10–20% of all patients with cancer. Brain metastases portend poor survival and contribute to increased cancer mortality and morbidity. Despite multimodal treatment options, which include surgery, radiotherapy, and chemotherapy, 5-year survival remains low. Besides, our current treatment modalities can have significant neurological comorbidities, which result in neurocognitive decline and a decrease in a patient’s quality of life. However, innovations in technology, improved understanding of tumor biology, and new therapeutic options have led to improved patient care. Novel approaches in radiotherapy are minimizing the neurocognitive decline while providing the same therapeutic benefit. In addition, advances in targeted therapies and immune checkpoint inhibitors are redefining the management of lung and melanoma brain metastases. Similar approaches to brain metastases from other primary tumors promise to lead to new and effective therapies. We are beginning to understand the appropriate combination of these novel approaches with our traditional treatment options. As advances in basic and translational science and innovative technologies enter clinical practice, the prognosis of patients with brain metastases will continue to improve.

The brain metastasis journey: Experience from patient, caregiver, and physician surveys on diagnosis and treatment of brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14004-e14004
Author(s):  
Albert Eusik Kim ◽  
GI-Ming WANG ◽  
Kristin A Waite ◽  
Scott Elder ◽  
Avery Fine ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Whole Brain Radiotherapy ◽  
Well Being ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Brain Radiotherapy

e14004 Background: Brain metastases (BM) is one of the most feared complications of cancer due to substantial neurologic sequalae, neuro-cognitive morbidity and grim prognosis. In the past decade, targeted therapies and checkpoint inhibitors have resulted in meaningfully improved overall survival for a minority of these patients. Accordingly, there is a growing need to identify issues surrounding patient survivorship and to standardize physician practice patterns for these patients. To date, there has not been a well-conducted formal study to specifically explore these questions of survivorship and practice standardization for BM patients. Methods: Here, we present results from a cross-sectional survey in which we analyzed responses from 237 BM patients, 209 caregivers, and 239 physicians. Surveys contained questions about BM symptoms, discussion of BM diagnosis by the clinician, psychosocial concerns, available treatment options for BM, BM patient advocacy resources, and BM-specific clinical trials. Results: Our survey revealed compelling findings about current care of BM patients. There were discrepancies in the perceived discussion of the implications of the diagnosis of BM, from the patient/caregiver and physician perspective. Important topics, such as prognosis and worrisome symptoms, were felt to have been discussed more frequently by physicians than by patients or caregivers. In our physician survey, private practice physicians, compared to academic physicians, were significantly more likely to recommend whole brain radiotherapy (61.1 vs 39.7%; p = 0.009). Participation in a clinical trial was one of the least recommended treatment options. Many physicians (59.1% private; 71.9% academic) stated that BM patients in their care are denied participation in a clinical trial, specifically due to the presence of BM. The consensus among physicians, patients and caregivers was that the highest yield area for federal assistance is increased treatment and research funding for BM. Conclusions: Our hope is that these findings will serve as a basis for future quality improvement measures to enhance patient-physician communication and patient well-being, continuing medical education activities detailing latest advances in BM for oncologists, and lobbying efforts to the federal government in prioritizing BM research, clinical trials, and patient survivorship.

Human leukocyte antigen expression in paired primary lung lesions and brain metastases in non-small cell lung cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 43-43
Author(s):  
Jarrett Failing ◽  
Marie-Christine Aubry ◽  
Aaron Scott Mansfield
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Human Leukocyte ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Primary Nsclc

43 Background: Human leukocyte antigens (HLA) are crucial for cytotoxic T cell responses to cancer. Loss of HLA expression is a mechanism of tumor immune escape and may contribute to resistance to immunotherapy. In patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors we have observed discordant responses between brain metastases and extracranial disease and reported on differential PD-L1 expression and clonal T cell infiltration between paired primary lung lesions and brain metastases. In this project we sought to evaluate whether HLA expression was retained in metastatic NSCLC. Methods: Adult patients with paired primary NSCLC and brain metastases were identified from our institution’s tissue registry. HLA-A cell membrane expression on tumor cells was determined by immunohistochemistry with an anti-HLA-A antibody. Tumors with greater than 10% HLA expression were considered positive. Agreement statistics (κ) and Fisher’s exact test were used for analysis. Results: 51 patients with paired primary NSCLC and brain lesions were identified. The median HLA expression was 20% in the primary tumors (IQR 0-65%) and 10% in the brain metastases (IQR 5-40%). 27 primary tumors and 24 brain metastases were positive for HLA expression. There was disagreement in HLA positivity between paired lesions in 11 patients (22%, 95% CI 12-35%)(κ = 0.57, 95% CI 0.35-0.79)(p = 0.0001). There was no significant difference in the time between the primary tumor and brain metastasis resections in patients with HLA expression disagreement compared to those with HLA expression agreement. None of the patients received immune checkpoint inhibitors for treatment of these lesions. Conclusions: We found significant differences in HLA-A expression on tumor cells in nearly one quarter of paired primary lung cancers and brain metastases. Differences in HLA expression may help explain the discrepancies in response to immune checkpoint inhibitors at different sites of disease and warrants further study.

scholarly journals Differential expression of the G0/G1 switch gene 2, G0S2, in the brain metastases of patients with breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Differential Expression ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Breast Cancer Brain Metastasis ◽  
Microarray Datasets ◽  
The Brain

In patients with breast cancer, brain metastasis provides limited treatment options (1-3). To discover genes associated with brain metastases in patients with metastatic breast cancer, we mined published microarray datasets, comparing global transcription in brain metastases and primary tumors of the breast (4, 5). Using this methodology, we identified significant differential expression of the G0/G1 switch gene 2, encoded by G0S2, in the brain metastases of patients with breast cancer as compared to primary tumors of the breast. The G0S2 gene product could be of relevance to any one of the numerous processes by which tumor cells in breast cancer metastasize, including exit of the breast, entry into the periphery, breach of the blood brain barrier or colonization of and survival in the brain.

Clinical and pathologic factors associated with survival in BRAFV600E colorectal cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4047-4047
Author(s):  
Van K. Morris ◽  
Bryan K. Kee ◽  
Michael J. Overman ◽  
David R. Fogelman ◽  
Arvind Dasari ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Treatment Options ◽  
Tumor Biology ◽  
Mapk Signaling ◽  
Hepatic Flexure ◽  
Locoregional Therapy ◽  
Cancer Center ◽  
Term Survival ◽  
Primary Tumors ◽  
Pathologic Features

4047 Background: BRAFV600E mutations occur in fewer than 10% of all patients (pts) with metastatic colorectal cancer (mCRC) and arise from sessile serrated adenomas. Despite efficacy with targeted therapies against MAPK signaling and with immunotherapies in this population, survival outcomes for pts with BRAFV600E mCRC in general are poor. Characteristics distinguishing pts with BRAFV600E mCRC with favorable versus unfavorable outcomes have not been well annotated. Methods: Records of 188 pts with BRAFV600E mCRC evaluated at MD Anderson Cancer Center between 3/2010-1/2020 were reviewed. Pts with the shortest and longest metastatic survival (N = 25 for each group) were compared. Associations between prognostic group and clinical/pathologic features were measured by odds ratio and for median survival by log-rank testing. Results: Median metastatic survival differed between the 2 BRAFV600E mCRC populations (8.6 vs 84 months, p < .0001). Pts with poor survival more commonly had primary tumors arising from the hepatic flexure/proximal transverse colon (44% vs 16%, p = .04) and more frequent hepatic involvement (75% vs 28%, p = .001). Pts with favorable survival were more likely to develop metachronous metastases (52% vs 16%, p = .01), have fewer distant organ involvement (median 1 vs 2, p = .02), and undergo definitive locoregional therapy to metastatic disease (44% vs 0%, p = .01). Microsatellite instability (36% vs 4%, p = .008) and a history of tobacco use (44% vs 16%, p = .04) were associated with a favorable prognosis. Durable responses to MAPK-targeted therapies (5/25) and immunotherapy (3/25) were noted in the favorable group. Conclusions: Pts with BRAFV600E mCRC can achieve excellent long-term survival which belies conventional context and is driven by locoregional and systemic treatment options alike. Anatomic localization of the primary tumor and prior exposures may highlight environmental influences on tumor biology which account for the clinical heterogeneity of pts with BRAFV600E mCRC.

scholarly journals CTIM-02. TWO OUNCES OF PREVENTION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF VEGF AND IMMUNE CHECK POINT INHIBITION FOR PRIMARY AND SECONDARY PREVENTION OF BRAIN METASTASES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii32-ii33
Author(s):  
Alireza Mansouri ◽  
Alireza Mansouri ◽  
Timothy Brown ◽  
Dawit Aregawi ◽  
Brad Zacharia ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Secondary Prevention ◽  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Treatment Options ◽  
Sensitivity Analyses ◽  
Primary And Secondary Prevention ◽  
Predictors Of Response ◽  
Inverse Variance

Abstract INTRODUCTION As treatments for cancer outside of the central nervous system improve, brain metastases (BMs) are becoming increasingly frequent. Despite novel treatment options, BMs remain a frequent cause of death for many advanced malignancies, and both the metastases and their treatments are associated with profound cognitive, quality of life, and economic costs. METHODS We conducted exhaustive, PRISMA-compliant systematic reviews of the literature from January 2000 to June 2020 for studies comparing the frequency of new BM in patients treated with chemotherapy regimens including and not including bevacizumab (“primary prevention”), and for studies comparing the frequency of new outside-of-treatment-field metastases in patients treated with stereotactic radiosurgery (SRS) with or without immune checkpoint inhibitors (“secondary prevention”). Pre-specified data was extracted and summary statistics were calculated using the inverse variance method and random effects model. RESULTS Seven studies (n=6,212) reported on BMs in breast, lung, and colon cancer patients treated with chemotherapy with or without bevacizumab. The relative risk (RR) and 95% confidence intervals [95% CI] for the development of new brain metastases was 0.71 [0.55–0.91, p=0.001]. A sensitivity analysis performed on the 3 breast cancer trials (n=2,350) showed a RR of 0.57 [0.34–0.94, p=0.027]. Seven studies (n=609) reported on patients with melanoma BM receiving SRS without or without an ICI. The RR for the development of new out-of-treatment field brain metastases was 0.70 [0.51–0.94, p=0.017]. Results were similar in sensitivity analyses examining only class I and class II trials. CONCLUSION This analysis suggests that the addition of bevacizumab to chemotherapy or ICI SRS+/- chemotherapy can reduce the development of first-ever or new BM by 30% in patients with advanced stage breast, lung, or colon cancer. Prospective trials of primary and secondary prevention in patient groups at high risk of developing BMs, and examining additional predictors of response, are currently underway.

scholarly journals Multimodal Strategy in Localized Merkel Cell Carcinoma: Where Are We and Where Are We Heading?

2021 ◽  
Vol 22 (19) ◽  
pp. 10629
Author(s):  
Gianluca Ricco ◽  
Elisa Andrini ◽  
Giambattista Siepe ◽  
Cristina Mosconi ◽  
Valentina Ambrosini ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Checkpoint Inhibitors ◽  
Tumor Biology ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Merkel Cell ◽  
Advantages And Disadvantages ◽  
Improved Outcomes ◽  
Metastatic Setting

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin whose incidence is rising. Multimodal treatment is crucial in the non-metastatic, potentially curable setting. However, the optimal management of patients with non-metastatic MCC is still unclear. In addition, novel insights into tumor biology and newly developed treatments (e.g., immune checkpoint inhibitors) that dramatically improved outcomes in the advanced setting are being investigated in earlier stages with promising results. Nevertheless, the combination of new strategies with consolidated ones needs to be clarified. We reviewed available evidence supporting the current treatment recommendations of localized MCC with a focus on potentially ground-breaking future strategies. Advantages and disadvantages of the different treatment modalities, including surgery, radiotherapy, chemotherapy, and immunotherapy in the non-metastatic setting, are analyzed, as well as those of different treatment modalities (adjuvant as opposed to neoadjuvant). Lastly, we provide an outlook of remarkable ongoing studies and of promising agents and strategies in the treatment of patients with non-metastatic MCC.

scholarly journals Differential expression of growth-arrest specific 1, GAS1, in the brain metastases of patients with breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Differential Expression ◽  
Microarray Data ◽  
Treatment Options ◽  
Growth Arrest ◽  
Metastatic Breast ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a complication of breast cancer (1, 2) with limited treatment options (3). We mined published microarray data (4, 5) to discover genes associated with brain metastases in patients with metastatic breast cancer. We identified significant differential expression of GAS1 in the brain metastases of patients with breast cancer as compared to primary tumors of the breast. GAS1 may be relevant to the underlying biology by which tumor cells of the breast spread to the brain.

scholarly journals PPM1H is differentially expressed in brain metastases in breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Treatment Options ◽  
Normal Breast ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Gene Encoding ◽  
Primary Tumors ◽  
Microarray Datasets ◽  
The Brain

Breast cancer patients with metastasis to the brain are faced with limited treatment options (1). To facilitate enhanced understanding of the transcriptional makeup of brain metastasis in human breast cancer and to support discovery of novel therapeutic targets, we mined published microarray datasets (2, 3) to identify genes whose expression was most markedly different when comparing brain metastases to primary tumors from patients with breast cancer and to the normal breast. We identified the gene encoding the protein phosphatase PPM1H as among the genes whose expression was most significantly different in metastases to the brain as compared to primary tumors of the breast. Increased expression of PPM1H in brain metastases in patients with breast cancer may be important for any number of steps involved in metastasis, including colonization of the brain.

scholarly journals An easily adopted murine model of distal pancreatectomy for investigating immunotherapy efficacy in resectable pancreatic adenocarcinoma

2020 ◽  
Author(s):  
Katherine E Baxter ◽  
Christiano Tanese de Souza ◽  
Lee-Hwa Tai ◽  
Pasha Yaghini ◽  
Manijeh Daneshmand ◽  
...  
Keyword(s):  
Murine Model ◽  
Immune Cell ◽  
Therapeutic Benefit ◽  
Treatment Modalities ◽  
Ductal Adenocarcinoma ◽  
Primary Tumors ◽  
Immune Phenotyping ◽  
Immunocompetent Mice ◽  
And Function ◽  
Post Implantation

AbstractBackgroundAlthough surgery provides the greatest therapeutic benefit to eligible pancreatic ductal adenocarcinoma (PDAC) patients it does not significantly improve survival for the majority of patients. Unfortunately our understanding of the therapeutic benefit of combining surgery with different treatment modalities including promising immunotherapeutics is limited by the current lack of easily adopted surgical models. The purpose of this study was to develop a surgically resectable model of PDAC in immunocompetent mice for use in preclinical investigations.Materials and MethodsSurgically resectable orthotopic tumors were generated by injecting Pan02 cells into the tail of the pancreas. Fifteen days post implantation the primary tumors and tail of the pancreas were resected by laparotomy while preserving the spleen. Splenic function, tumor growth, immune phenotyping and survival were assessed following surgical resection of the primary tumor mass.ResultsAs expected orthotopic tumor implants recapitulated many of the major histological hallmarks of PDAC including disrupted lobular structure and vascular invasion. Preservation of splenic immune cell viability and function was not associated with improved survival following surgery alone. However, pre-operative vaccination with GVAX was associated with improved survival which was not impacted by surgery.ConclusionThis represents the first murine model of surgically resectable murine model of PDAC which recapitulates known pathological hallmarks of human disease in an immune competent model while allowing spleen preservation. This relatively simple and easily adopted approach provides an ideal platform to examine the efficacy of potential immunotherapy combinations for PDAC surgery patients.

scholarly journals The Management of Brain Metastases—Systematic Review of Neurosurgical Aspects

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1616
Author(s):  
Martin A. Proescholdt ◽  
Petra Schödel ◽  
Christian Doenitz ◽  
Tobias Pukrop ◽  
Julius Höhne ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Radiation Treatment ◽  
Systemic Treatment ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Cytotoxic Chemotherapy ◽  
Treatment Modalities ◽  
Multidisciplinary Management ◽  
Current State ◽  
Treatment Paradigm

The multidisciplinary management of patients with brain metastases (BM) consists of surgical resection, different radiation treatment modalities, cytotoxic chemotherapy, and targeted molecular treatment. This review presents the current state of neurosurgical technology applied to achieve maximal resection with minimal morbidity as a treatment paradigm in patients with BM. In addition, we discuss the contribution of neurosurgical resection on functional outcome, advanced systemic treatment strategies, and enhanced understanding of the tumor biology.

Sign in / Sign up

Export Citation Format

Share Document