scholarly journals Characterization of plasma circulating small extracellular vesicles in patients with metastatic solid tumors and newly diagnosed brain metastasis.

2021 ◽  
Author(s):  
Alberto Carretero-Gonzalez ◽  
Sara Sanchez-Redondo ◽  
Luis Manso Sanchez ◽  
Eva Ciruelos Gil ◽  
Daniel Castellano ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Solid Tumors ◽  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Dynamic Monitoring ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Advanced Cancer Patients ◽  
Melanoma Patients

Purpose: Nearly 40% of the advanced cancer patients will present brain metastases during the course of their disease, with a 2-year life expectancy of less than 10%. Immune system impairment, including the modulation of both STAT3 and PD-L1, is one of the hallmarks of brain metastases. Liquid biopsy could offer several advantages in brain metastases management, such as the possibility of non-invasive dynamic monitoring. Extracellular vesicles (EVs) have been recently proposed as novel biomarkers especially useful in liquid biopsy due to their secretion in biofluids and their role in cell communication during tumor progression. Materials and Methods: The main aim of this work was to characterize the size and protein cargo of plasma circulating EVs in patients with solid tumors and their correlation with newly diagnosed brain metastases, in addition to their association with other relevant clinical variables. Results: We analyzed circulating EVs in the plasma of 123 patients: 42 patients with brain metastases, 50 without brain metastases and 31 healthy controls. Patients with newly diagnosed brain metastases had a lower number of circulating EVs in the plasma and a higher protein concentration in small EVs (sEVs) compared to patients without brain metastases and healthy controls. Interestingly, melanoma patients with brain metastases presented decreased STAT3 activation and increased PD-L1 levels in circulating sEVs compared to patients without central nervous system metastases. Conclusions: Decreased STAT3 activation and increased PD-L1 in plasma circulating sEVs identify melanoma patients with brain metastasis.

196 Checkpoint blockade therapy for brain-metastatic non-small cell lung cancer: a comparative effectiveness analysis of national data

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A211-A211
Author(s):  
Nayan Lamba ◽  
Bryan Iorgulescu
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Second Line ◽  
Newly Diagnosed ◽  
Small Cell Lung ◽  
Survival Analyses ◽  
Stage 4 ◽  
Insured Patients

BackgroundManagement of advanced non-small cell lung carcinoma (NSCLC) has been transformed by PD-1/PD-L1 immune checkpoint inhibitors (ICI), with FDA approvals in 2015 (second-line) and 2016 (first-line). Despite ~40% of NSCLC patients developing brain metastases, these patients were disproportionately excluded from the pioneering ICI trials. Thus herein we evaluate the overall survival (OS) associated with ICI in NSCLC brain metastases nationally.MethodsPatients newly-diagnosed with stage 4 NSCLC, including brain metastases, from 2010–2016 were identified from the National Cancer Database (comprising >70% of all newly-diagnosed cancers in the U.S.) Landmark survival analysis was used to address immortal time bias. Post-approval, median time from diagnosis to ICI was 58 days, and this timepoint was selected for all landmark survival analyses (OS estimated by Kaplan-Meier technique, and compared by logrank test and multivariable Cox regression) and for multivariable logistic regression to identify predictors of ICI utilization.Results50,858 patients presented with advanced NSCLC that involved the brain: representing 27.6% of all newly-diagnosed stage 4 cases. Following initial FDA approvals in 2015, ICI use in brain metastasis patients rose from 7.2% in 2015 to 12.7% in 2016. OS for NSCLC brain metastasis patients diagnosed post-approval (i.e. 2015, median 6.3 months, 95% [confidence interval] CI: 6.0–6.6) was substantially better than those diagnosed pre-approval (median 5.5 months, 95%CI: 5.4–5.7, p<0.001) and, in fact, than those diagnosed in 2014 (median 5.9 months, 95%CI: 5.6–6.1, p=0.002). Among patients diagnosed post-approval (in 2015, n=7,431), ICI receipt demonstrated substantially improved OS in landmark survival analyses (median 13.8 months, 95%CI: 12.2–15.1; vs. 8.5 months, 95%CI: 8.3–8.9, p<0.001) – benefits which persisted in multivariable landmark survival analyses (hazard ratio [HR] 0.83, 95%CI: 0.71–0.96, p=0.02), independent of patient characteristics, other therapies, and extracranial disease. For patients diagnosed post-approval, who reached the landmark timepoint, ICI receipt was independent of patient demographics, socioeconomic status, and hospital type—with the exception of Medicaid-insured patients, who were less likely than privately insured patients to receive ICI (OR 0.77, 95%CI: 0.60–0.97, p=0.03).ConclusionsNationally, the use of ICI for NSCLC brain metastasis patients is increasing, generally without significant socioeconomic barriers. Brain metastasis patients diagnosed in the post-approval second-line ICI era (2015) demonstrated significantly better OS than patients diagnosed pre-approval and even than patients diagnosed only in 2014. ICI was associated with a >60% relative increase in median OS. Together our findings from a real-world population demonstrate that the dramatic OS benefits of ICIs for advanced NSCLC also extended to brain metastasis patients.

scholarly journals Temporal muscle thickness is an independent prognostic marker in melanoma patients with newly diagnosed brain metastases

2018 ◽  
Vol 140 (1) ◽  
pp. 173-178 ◽  
Author(s):  
Julia Furtner ◽  
Anna S. Berghoff ◽  
Veronika Schöpf ◽  
Robert Reumann ◽  
Benjamin Pascher ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Prognostic Marker ◽  
Muscle Thickness ◽  
Newly Diagnosed ◽  
Temporal Muscle ◽  
Independent Prognostic Marker ◽  
Melanoma Patients

scholarly journals Estimating population-based incidence of brain metastases – a comprehensive incident cohort study

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv21-iv21
Author(s):  
Hamish Sinclair ◽  
Kerlann Le Calvez ◽  
Jiarong Chen ◽  
Lillie Pakzad-Shahabi ◽  
Luke Dixon ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Registration ◽  
Intracranial Tumour ◽  
Newly Diagnosed ◽  
Single Centre ◽  
Registration System ◽  
True Incidence ◽  
Radiology Reports ◽  
Number Of Patients

Abstract Aims Brain metastases are the most common intracranial tumour and affect approximately 20% of adult cancer patients, most commonly from lung, breast, melanoma, and kidney cancer. However, the true incidence of brain metastasis is unknown. England’s cancer registration system only reliably captures brain metastases present at diagnosis (rather than those that develop later), and the same is true for US-based data. Although it is relatively easy to identify patients receiving some treatments for brain metastases (surgery, stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT)), identifying those receiving chemotherapy or no treatment is much harder. As a result, the existing literature is heavily biased towards reporting treated populations. This study attempts to find an unbiased estimate of the true number of patients developing brain metastases, based on data from a single centre. Method Cases of brain metastasis were retrospectively identified from the radiology information system database (SolitonTM). We performed a Boolean search for specific keywords in the radiology reports of all CT and MRI head scans performed at the trust between 1st January 2018 and 31st December 2019. The following keywords were searched for “metastases”, “metastatic“, “metastasis”, “mets”, “deposit”, “deposits”, “secondaries”, “secondary” and “disseminated”. Duplicate cases were then removed and the subsequent list was manually reviewed We identified all patients who received any treatment for brain metastases who were diagnosed at our centre. We only included patients with newly diagnosed brain metastases (included: leptomeningeal; excluded: skull-based metastases). We excluded patients who were diagnosed in other centres and treated here or diagnosed outside the study period. We then extracted data on primary diagnosis, admissions, and survival. Results 1192 patients had a CT or MRI of the head with a mention of “brain metastases” in the report; of these 305 were newly diagnosed with brain metastases during the study period (432 had metastases; 127 diagnosed earlier). Of these 305 patients, 217 (71.1%) were treated locally (SRS = 88; WBRT = 74; surgery = 88; systemic therapy = 16; multiple treatments = 45) and 10 (3.3%) were referred elsewhere. 78 (25.6%) patients received no treatment. Of the 217 treated patients, 124 were female, and the median age was 61. Of the 78 untreated patients, 38 were females, and the median age was 70 years old. The commonest primary diagnoses in both groups were lung (39%) and breast (21%) cancer. 16 (21%) of the untreated patients had an unbiopsied primary tumour. Median survival for patients having (any) treatment was 52 weeks compared to 5 weeks for those not having treatment. Conclusion We have presented an unbiased single-centre estimate of brain metastases occurrence. Unlike previous work, we manually reviewed all imaging reports that suggested metastasis, and included all patients diagnosed with brain metastases at any timepoint. We reduced the bias associated with being a tertiary centre by only including patients who were diagnosed here, rather than referred from other centres. 25% of our cohort received no treatment, and survival in this group is poor. This is broadly in line with the only other study on this topic (Bentley, 2019) that reported a large minority (39%) of untreated patients. Our key conclusions are: When assessing the incidence of brain metastases, studies that do not account for untreated patients are likely to significantly underestimate incidence, and over-estimate survival. Improving outcomes in patients with brain metastases might be best achieved by addressing earlier identification and intervention in those who currently receive no treatment

scholarly journals Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1635
Author(s):  
Loredana Guglielmi ◽  
Marta Nardella ◽  
Carla Musa ◽  
Ingrid Cifola ◽  
Manuela Porru ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Extracellular Vesicles ◽  
Xenograft Model ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Circulating Mirnas ◽  
Human Melanoma Xenograft ◽  
Melanoma Xenograft ◽  
Melanoma Patients ◽  
The Brain

The identification of liquid biomarkers remains a major challenge to improve the diagnosis of melanoma patients with brain metastases. Circulating miRNAs packaged into tumor-secreted small extracellular vesicles (sEVs) contribute to tumor progression. To investigate the release of tumor-secreted miRNAs by brain metastasis, we developed a xenograft model where human metastatic melanoma cells were injected intracranially in nude mice. The comprehensive profiles of both free miRNAs and those packaged in sEVs secreted by the melanoma cells in the plasma demonstrated that most (80%) of the sEV-associated miRNAs were also present in serum EVs from a cohort of metastatic melanomas, included in a publicly available dataset. Remarkably, among them, we found three miRNAs (miR-224-5p, miR-130a-3p and miR-21-5p) in sEVs showing a trend of upregulation during melanoma progression. Our model is proven to be valuable for identifying miRNAs in EVs that are unequivocally secreted by melanoma cells in the brain and could be associated to disease progression.

scholarly journals Salvage Surgical Resection after Linac-Based Stereotactic Radiosurgery for Newly Diagnosed Brain Metastasis

2021 ◽  
Vol 28 (6) ◽  
pp. 5255-5265
Author(s):  
Ryosuke Matsuda ◽  
Takayuki Morimoto ◽  
Tetsuro Tamamoto ◽  
Nobuyoshi Inooka ◽  
Tomoko Ochi ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Survival Time ◽  
Stereotactic Radiosurgery ◽  
Surgical Resection ◽  
Statistical Significance ◽  
Cyst Formation ◽  
Histopathological Diagnosis ◽  
Newly Diagnosed

Background: This study aimed to assess the clinical outcomes of salvage surgical resection (SSR) after stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) for newly diagnosed brain metastasis. Methods: Between November 2009 and May 2020, 318 consecutive patients with 1114 brain metastases were treated with SRS/fSRT for newly diagnosed brain metastasis at our hospital. During this study period, 21 of 318 patients (6.6%) and 21 of 1114 brain metastases (1.9%) went on to receive SSR after SRS/fSRT. Three patients underwent multiple surgical resections. Twenty-one consecutive patients underwent twenty-four SSRs. Results: The median time from initial SRS/fSRT to SSR was 14 months (range: 2–96 months). The median follow-up after SSR was 17 months (range: 2–78 months). The range of tumor volume at initial SRS/fSRT was 0.12–21.46 cm3 (median: 1.02 cm3). Histopathological diagnosis after SSR was recurrence in 15 cases, and radiation necrosis (RN) or cyst formation in 6 cases. The time from SRS/fSRT to SSR was shorter in the recurrence than in the RNs and cyst formation, but these differences did not reach statistical significance (p = 0.067). The median survival time from SSR and from initial SRS/fSRT was 17 and 74 months, respectively. The cases with recurrence had a shorter survival time from initial SRS/fSRT than those without recurrence (p = 0.061). Conclusions: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.

A PILOT STUDY OF NEUROCOGNITIVE FUNCTION IN PATIENTS WITH ONE TO THREE NEW BRAIN METASTASES INITIALLY TREATED WITH STEREOTACTIC RADIOSURGERY ALONE

Neurosurgery ◽  
2007 ◽  
Vol 60 (2) ◽  
pp. 277-284 ◽  
Author(s):  
Eric L. Chang ◽  
Jeffrey S. Wefel ◽  
Moshe H. Maor ◽  
Samuel J. Hassenbusch ◽  
Anita Mahajan ◽  
...  
Keyword(s):  
Executive Function ◽  
Pilot Study ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Neurocognitive Function ◽  
Newly Diagnosed ◽  
Whole Brain Radiation ◽  
Motor Dexterity ◽  
Improved Learning

Abstract OBJECTIVE Whether to administer or omit adjuvant whole-brain radiation therapy in conjunction with stereotactic radiosurgery (SRS) in the initial management of patients with one to three newly diagnosed brain metastases is the subject of debate. This report provides data from a pilot study in which neurocognitive function (NCF) was prospectively measured for patients with one to three newly diagnosed brain metastases treated with initial SRS alone. METHODS Fifteen patients were prospectively treated with initial SRS alone. Assessment of NCF and magnetic resonance imaging scans were performed. RESULTS At baseline, 67% of the patients had impairment on one or more tests of NCF. The domains most frequently impaired at baseline were executive function, motor dexterity, and learning/memory with an incidence of 50, 40, and 27% respectively. Brain metastasis volume (.3 cm3) measured at the time of initial SRS treatment was associated with worse performance on a measure of attention (P &lt; 0.05). At 1 month, declines in the learning/memory and motor dexterity domains were most common. In a subgroup of five patients still alive 200 days after enrollment, four patients (80%) demonstrated stable or improved learning/memory, three (60%) demonstrated stable or improved executive function, and three (60%) demonstrated stable or improved motor dexterity relative to their baseline evaluation. CONCLUSION Although two-thirds of the brain metastasis patients had impaired NCF at baseline, the majority of five long-term survivors had stable or improved NCF performance across executive function, learning/memory, and motor dexterity.

scholarly journals Immunotherapy is associated with improved survival and decreased neurologic death after SRS for brain metastases from lung and melanoma primaries

2019 ◽  
Vol 6 (5) ◽  
pp. 402-409 ◽  
Author(s):  
Claire M Lanier ◽  
Ryan Hughes ◽  
Tamjeed Ahmed ◽  
Michael LeCompte ◽  
Adrianna H Masters ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Median Overall Survival ◽  
Patterns Of Failure ◽  
Whole Brain Radiation ◽  
Kaplan Meier ◽  
Brain Failure ◽  
Melanoma Patients ◽  
Brain Radiation ◽  
The Brain

Abstract Background The effect of immunotherapy on brain metastasis patients remains incompletely understood. Our goal was to evaluate its effect on survival, neurologic death, and patterns of failure after stereotactic radiosurgery (SRS) without prior whole-brain radiation therapy (WBRT) in patients with lung and melanoma primaries metastatic to the brain. Methods We performed a retrospective analysis of 271 consecutive lung or melanoma patients treated with upfront SRS for brain metastases between 2013 and 2018. Of these patients, 101 (37%) received immunotherapy and 170 (63%) did not. Forty-three percent were treated with nivolumab. Thirty-seven percent were treated with pembrolizumab. Fifteen percent were treated with ipilimumab. One percent were treated with a combination of nivolumab and ipilimumab. One percent were treated with atezolizumab. Three percent were treated with another immunotherapy regimen. Survival was estimated by the Kaplan–Meier method and cumulative incidences of neurologic death, and local and distant brain failure were estimated using death as a competing risk. Results The median overall survival (OS) of patients treated with immunotherapy vs without was 15.9 (95% CI: 13.3 to 24.8) vs 6.1 (95% CI: 5.1 to 8.8) months (P < .01). The 1-year cumulative incidence of neurologic death was 9% in patients treated with immunotherapy vs 23% in those treated without (P = .01), while nonneurologic death was not significantly different (29% vs 41%, P = .51). Median brain metastasis velocity (BMV) did not differ between groups, and rates of salvage SRS and WBRT were similar. Conclusions The use of immunotherapy in patients with lung cancer or melanoma metastatic to the brain treated with SRS is associated with improved OS and decreased incidence of neurologic death.

scholarly journals Sudden Onset of Brain Metastasis despite the Use of Vemurafenib for Another Metastatic Lesion in Malignant Melanoma Patients

2017 ◽  
Vol 10 (1) ◽  
pp. 290-295 ◽  
Author(s):  
Keisuke Imafuku ◽  
Koji Yoshino ◽  
Kei Yamaguchi ◽  
Satoshi Tsuboi ◽  
Kuniaki Ohara ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Acquired Resistance ◽  
Metastatic Lesion ◽  
Sudden Onset ◽  
Brain Lesions ◽  
Metastatic Lesions ◽  
Melanoma Patients ◽  
The Brain

Vemurafenib is an inhibitor of the BRAF mutation and has been approved by the Food and Drug Administration as a treatment option for patients with unresectable melanoma without brain metastasis. In the literature, vemurafenib has been reported to be also effective against brain metastasis. We encountered 3 cases with brain metastasis on vemurafenib therapy. In these cases, vemurafenib was clinically effective against metastatic lesions other than those in the brain. The brain lesions developed after the metastatic lesion had occurred. Therefore, we assume that the melanomas of the patients acquired resistance against vemurafenib. The brain metastases were treated with the cyberknife. Patients 1 and 2 without LDH elevation are still alive, but patient 3 with abnormal LDH elevation died despite the treatment. We need to carefully follow patients on vemurafenib therapy because brain metastasis can suddenly occur even if the metastatic lesion has decreased clinically. The therapeutic effect of vemurafenib against brain metastasis is poor in cases with LDH elevation.

Gamma Knife surgery for multiple brain metastases from a malignant schwannoma of the penis

2006 ◽  
Vol 105 (Supplement) ◽  
pp. 238-240 ◽  
Author(s):  
Albertus T. C. J. van Eck ◽  
Gerhard A. Horstmann
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Gamma Knife ◽  
De Novo ◽  
Tumor Resection ◽  
Gamma Knife Surgery ◽  
Malignant Schwannoma ◽  
Efficacy And Safety ◽  
Single Brain Metastasis ◽  
Therapy Option

✓The occurrence of brain metastases from a malignant schwannoma of the penis is extremely rare. In patients with a single brain metastasis, microsurgical extirpation is the treatment of choice and verifies the diagnosis. In cases of multiple or recurrent metastases, radiosurgery is an effective and safe therapy option. Gamma Knife surgery was performed in a patient who had previously undergone tumor resection and who presented with recurrence of the lesion and three de novo brain metastases. This first report on brain metastasis from a malignant penile schwannoma illustrates the efficacy and safety of radiosurgical treatment for these tumors.

Tumor recurrence and survival following gamma knife surgery for brain metastases

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 287-288 ◽  
Author(s):  
Thomas Mindermann
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Gamma Knife ◽  
Tumor Recurrence ◽  
Patient Survival ◽  
Gamma Knife Surgery ◽  
Recurrence Rates ◽  
Term Survival ◽  
Content Type ◽  
Fine Print

Object. The authors evaluated prognostic factors for tumor recurrence and patient survival following gamma knife surgery (GKS) for brain metastasis. Methods. A retrospective review of 101 patient charts was undertaken for those patients treated with GKS for brain metastases from 1994 to 2001. Recurrence rates of brain metastasis following GKS depended on the duration of patient survival. Long-term survival was associated with a higher risk of tumor recurrence and shorter-term survival was associated with a lower risk. The duration of survival following GKS for brain metastases seems to be characteristic of the primary disease rather than the cerebral disease. Conclusions. Recurrence rates of brain metastasis following GKS are related to duration of survival, which is in turn mostly dependent on the nature and course of the primary tumor.

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