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1.
Surg Neurol Int ; 15: 147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741995

RESUMO

Background: Intramedullary spinal cord abscesses (ISCA) can result in high morbidity and mortality if not treated in a timely manner. The incidence and outcomes of postsurgical ISCA are unknown. We present a case of a 52-year-old male patient with neurofibromatosis type 1 who developed an intramedullary spinal cord abscess after a previous resection of a cervical intradural, extramedullary neurofibroma. Case Description: A 52-year-old male with a history of neurofibromatosis type 1 had previously undergone multiple resections of cervical intradural, extramedullary neurofibromas with internal stabilization. Sixteen months after his initial surgery, he developed acute-onset interscapular pain with bilateral lower extremity pain and left hemi-body weakness. Magnetic resonance imaging (MRI) of the cervical spine demonstrated an enlarging contrast-enhancing intramedullary lesion. Surgical exploration and evacuation of the lesion were completed. Intramedullary cultures confirmed a Serratia marcescens abscess. After abscess evacuation and intravenous antibiotics, the patient's symptoms resolved. Conclusion: Given the potential for permanent neurologic damage and loss of independence with intramedullary spinal cord abscess, we advocate that clinicians maintain a high index of suspicion in the postsurgical patient. Diagnostic imaging through contrasted MRI or computed tomography myelogram should be obtained, and prompt intervention, including evacuation and/or antibiotics, should be implemented for the best chance of a favorable outcome.

2.
J Neurooncol ; 165(3): 449-458, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38015375

RESUMO

PURPOSE: There is a growing body of literature documenting glioma heterogeneity in terms of radiographic, histologic, molecular, and genetic characteristics. Incomplete spatial specification of intraoperative tumor samples may contribute to variability in the results of pathological and biological investigations. We have developed a system, termed geo-tagging, for routine intraoperative linkage of each tumor sample to its location via neuronavigation. METHODS: This is a single-institution, IRB approved, prospective database of undergoing clinically indicated surgery. We evaluated relevant factors affecting data collection by this registry, including tumor and surgical factors (e.g. tumor volume, location, grade and surgeon). RESULTS: Over a 2-year period, 487 patients underwent craniotomy for an intra-axial tumor. Of those, 214 underwent surgery for a newly diagnosed or recurrent glioma. There was significant variation in the average number of samples collected per registered case, with a range of samples from 2.53 to 4.75 per tumor type. Histology and grade impacted on sampling with a range of 2.0 samples per tumor in Grade four, IDH-WT gliomas to 4.5 samples in grade four, IDH-mutant gliomas. The range of cases with sampling per surgeon was 6 to 99 with a mean of 47.6 cases and there was a statistically significant differences between surgeons. Tumor grade did not have a statistically significant impact on number of samples per case. No significant correlation was found between the number of samples collected and enhancing tumor volume, EOR, or volume of tumor resected. CONCLUSION: We are using the results of this analysis to develop a prospective sample collection protocol.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Recidiva Local de Neoplasia , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/cirurgia , Imageamento por Ressonância Magnética/métodos , Sistema de Registros
3.
Eur J Cancer ; 192: 113287, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37657227

RESUMO

BACKGROUND: Immunotherapy and targeted BRAF/MEK inhibitors (i) have revolutionised the systemic management of advanced melanoma. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate clinical outcomes in patients with melanoma brain metastases (MBM) treated with SRS and various systemic therapies. METHODS: Patients were included if MBM were diagnosed and treated with SRS within 3 months of receiving anti-PD-1+CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, or conventional chemotherapy. Comparisons between groups were made for overall survival (OS), distant MBM control, local MBM, systemic progression-free survival (sPFS), and neurotoxicity. RESULTS: In total, 257 patients with 1048 MBM treated over 368 SRS sessions between 2011 and 2020 were identified. On MVA, treatment with anti-PD1+anti-CTLA-4, anti-PD-1, and BRAF/MEK-i improved distant intracranial control over conventional chemotherapy. No significant differences were noted in local control (LC) between groups (p = 0.78). Kaplan-Meier OS at 12 months for anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, and conventional chemotherapy was 68%, 59%, 45%, 62%, 21%, and 15%, respectively (p = <0.0001). The sPFS rates at 12 months were 57%, 53%, 42%, 45%, 14%, and 6% (p = <0.0001). No significant differences were noted in rates of radiation necrosis (p = 0.93). CONCLUSIONS: This is among the largest series evaluating MBM treated with SRS and various systemic therapy regimens. Our analysis noted significant differences in OS, distant MBM control, and sPFS by systemic therapy. No differences in LC or radiation necrosis risk were noted.


Assuntos
Neoplasias Encefálicas , Melanoma , Lesões por Radiação , Radiocirurgia , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Radiocirurgia/efeitos adversos , Neoplasias Encefálicas/terapia , Melanoma/terapia , Inibidores de Proteínas Quinases/efeitos adversos , Necrose , Quinases de Proteína Quinase Ativadas por Mitógeno
4.
Cardiovasc Intervent Radiol ; 46(5): 600-609, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37012392

RESUMO

PURPOSE: The OsteoCool Tumor Ablation Post-Market Study (OPuS One) was a prospective, multi-national, single-arm study to investigate safety and effectiveness of radiofrequency ablation (RFA) for palliation of painful lytic bone metastases with 12 months of follow-up. RFA has demonstrated effective palliation of osseous metastases in small clinical studies with short-term follow-up; however, a long-term assessment with robust subject numbers is lacking. MATERIALS AND METHODS: Prospective assessments were conducted at Baseline, 3 days, 1 week, and 1, 3, 6, and 12-months. Pain and quality of life were measured prior to RFA and postoperatively using the Brief Pain Inventory, European Quality of Life-5 Dimension, and European Organization for Research and Treatment of Cancer Care Quality of Life Questionnaire for palliative care. Radiation, chemotherapy and opioid usage, and related adverse events were collected. RESULTS: 206 subjects were treated with RFA at 15 institutions in OPuS One. Worst pain, average pain, pain interference and quality of life significantly improved at all visits starting 3 days post-RFA and sustained to 12 months (P < 0.0001). Post hoc analysis found neither systemic chemotherapy nor local radiation therapy at the index site of RFA influenced worst pain, average pain, or pain interference. Six subjects had device/procedure-related adverse events. CONCLUSION: RFA for lytic metastases provides rapid (within 3 days) and statistically significant pain and quality of life improvements with sustained long-term relief through 12 months and a high degree of safety, independent of radiation. LEVEL OF EVIDENCE: 2B, PROSPECTIVE, NON-RANDOMIZED, POST-MARKET STUDY: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Neoplasias Ósseas , Ablação por Cateter , Ablação por Radiofrequência , Humanos , Cuidados Paliativos/métodos , Qualidade de Vida , Estudos Prospectivos , Resultado do Tratamento , Dor/cirurgia , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Ablação por Radiofrequência/métodos , Ablação por Cateter/métodos
5.
Oper Neurosurg (Hagerstown) ; 23(6): 457-463, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36103359

RESUMO

BACKGROUND: Malignant lesions involving the C2 vertebral body (axis) may be challenging to treat, and not all patients with cancer are good candidates for posterior cervical or occipitocervical instrumentation. OBJECTIVE: To describe a modified technique of the direct anterolateral C2 kyphoplasty using a steerable osteotome, commonly used for the treatment of thoracolumbar spinal lesions. We also report a case series of 11 patients treated with this technique at our institution. METHODS: The authors performed a retrospective review of all patients who underwent a C2 kyphoplasty using the anterior midline approach from 2010 to 2020. Patient demographics, tumor characteristics, pain severity (visual analog scale), Karnofsky performance status , perioperative complications, and postoperative spinal stability were assessed. RESULTS: The main indication for a C2 kyphoplasty was refractory neck pain. All patients tolerated the procedure well. There were no intraoperative complications. One patient developed transient dysphagia. Visual analog scale scores were 9.00 ± 1.10 preoperative and 3.73 ± 1.85 at 2 weeks and 1.67 ± 1.66 at 3 months after the procedure and continued to stay low during the remainder of the follow-up (4-60 months). The Karnofsky performance status improved from 72.73 ± 11.04 preoperatively to 82.22 ± 8.33 at 2 weeks and 86.67 ± 5.00 at 3 months after the procedure. There was no evidence of new occurrence or progression of C2 fractures. CONCLUSION: The anterior kyphoplasty using a steerable osteotome for tumors of the axis can result in lasting pain reduction and improved cervical stability while demonstrating a low complication rate.


Assuntos
Fraturas Espontâneas , Cifoplastia , Fraturas da Coluna Vertebral , Humanos , Cifoplastia/efeitos adversos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/etiologia , Resultado do Tratamento , Coluna Vertebral/cirurgia
6.
Onco Targets Ther ; 15: 953-962, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36097632

RESUMO

Leukoencephalopathy in the setting of multiple myeloma (MM) is a rare demyelinating condition, with few reported cases in literature. Daratumumab is a CD38 targeted monoclonal antibody that has been widely used for the management of MM. In the absence of central nervous system (CNS) disease, many medication-induced leukoencephalopathy cases reported with MM, including daratumumab-induced, are associated with progressive multifocal leukoencephalopathy (PML) and John Cunningham (JC) virus. Currently, there are no reported cases of daratumumab-induced leukoencephalopathy among patients without CNS involvement or PML. We discuss 2 patients who developed leukoencephalopathy while receiving daratumumab-based therapy without evidence of PML or CNS disease. Both patients had baseline MRIs without significant white matter changes before daratumumab-based therapy. Patients began experiencing neurological deficits about 6 to 8 months after daratumumab-based therapy initiation. One patient passed away before being assessed for improvement of symptoms with daratumumab cessation. The second patient had some stabilization of symptoms after cessation; however, the leukoencephalopathy remained irreversible. As the class of anti-CD38 monoclonal antibodies expands in MM therapy, we highlight a potential treatment complication and the importance of detecting leukoencephalopathy early among patients receiving anti-CD38 therapy. We recommend vigilant monitoring of any new or worsening neurological symptoms to avoid serious complications of irreversible leukoencephalopathy.

7.
Front Oncol ; 12: 962702, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033542

RESUMO

Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive. Recent advances in genetics and epigenetics have uncovered molecular alterations that drive tumor meningioma biology with prognostic and therapeutic implications. In this review, we will discuss the advances on molecular determinants of therapeutic response in meningiomas to date and discuss findings of targeted therapies in meningiomas.

8.
J Neurosurg Case Lessons ; 3(24): CASE21683, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35733635

RESUMO

BACKGROUND: Maximal safe resection is the paramount objective in the surgical management of malignant brain tumors. It is facilitated through use of image-guided neuronavigation. Intraoperative image guidance systems use preoperative magnetic resonance imaging (MRI) as the navigational map. The accuracy of neuronavigation is limited by intraoperative brain shift and can become less accurate over the course of the procedure. Intraoperative MRI can compensate for dynamic brain shift but requires significant space and capital investment, often unavailable at many centers. OBSERVATIONS: The authors described a case in which an image fusion algorithm was used in conjunction with an intraoperative computed tomography (CT) system to compensate for brain shift during resection of a brainstem hemorrhagic melanoma metastasis. Following initial debulking of the hemorrhagic metastasis, intraoperative CT was performed to ascertain extent of resection. An elastic image fusion (EIF) algorithm was used to create virtual MRI relative to both the intraoperative CT scan and preoperative MRI, which facilitated complete resection of the tumor while preserving critical brainstem anatomy. LESSONS: EIF algorithms can be used with multimodal images (preoperative MRI and intraoperative CT) and create an updated virtual MRI data set to compensate for brain shift in neurosurgery and aid in maximum safe resection of malignant brain tumors.

9.
Front Oncol ; 12: 854402, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35311078

RESUMO

Brain metastases are the most common form of brain cancer. Increasing knowledge of primary tumor biology, actionable molecular targets and continued improvements in systemic and radiotherapy regimens have helped improve survival but necessitate multidisciplinary collaboration between neurosurgical, medical and radiation oncologists. In this review, we will discuss the advances of targeted therapies to date and discuss findings of studies investigating the synergy between these therapies and stereotactic radiosurgery for non-small cell lung cancer, breast cancer, melanoma, and renal cell carcinoma brain metastases.

10.
Nat Med ; 28(3): 513-516, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35314819

RESUMO

Preimplantation genetic testing (PGT) of in-vitro-fertilized embryos has been proposed as a method to reduce transmission of common disease; however, more comprehensive embryo genetic assessment, combining the effects of common variants and rare variants, remains unavailable. Here, we used a combination of molecular and statistical techniques to reliably infer inherited genome sequence in 110 embryos and model susceptibility across 12 common conditions. We observed a genotype accuracy of 99.0-99.4% at sites relevant to polygenic risk scoring in cases from day-5 embryo biopsies and 97.2-99.1% in cases from day-3 embryo biopsies. Combining rare variants with polygenic risk score (PRS) magnifies predicted differences across sibling embryos. For example, in a couple with a pathogenic BRCA1 variant, we predicted a 15-fold difference in odds ratio (OR) across siblings when combining versus a 4.5-fold or 3-fold difference with BRCA1 or PRS alone. Our findings may inform the discussion of utility and implementation of genome-based PGT in clinical practice.


Assuntos
Diagnóstico Pré-Implantação , Blastocisto , Embrião de Mamíferos , Feminino , Fertilização in vitro , Testes Genéticos/métodos , Humanos , Gravidez , Diagnóstico Pré-Implantação/métodos
11.
Clin Neurol Neurosurg ; 215: 107206, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35290789

RESUMO

BACKGROUND: Craniotomies for resection of neoplastic lesions are at increased risk for surgical site infections (SSIs) as compared to non-neoplastic pathologies. SSIs can be detrimental due to delay in pivotal adjuvant therapies. OBJECTIVE: The purpose of this study was to determine the rate of SSI in primary brain tumors, to analyze risk factors, and to evaluate effectiveness of topical vancomycin in reducing SSIs. METHODS: A retrospective cohort study was conducted at a National Cancer Institutedesignated Comprehensive Cancer Center. Patients with primary brain tumors (n = 799) who were subjected to craniotomy from 2004 to 2014 were included. Patient demographics, tumor characteristics, use of topical vancomycin and clinical outcomes were analyzed. RESULTS: Topical vancomycin was associated with a significantly lower rate of SSI (0.8%) compared to standard care (5%), ( p = 0.00071; OR = 0.15; 95% CI = 0.02 - 0.5). Narcotic use ( p = 0.043; OR = 2.24; 95% CI = 0.96 - 4.81), previous brain radiation ( p = 0.043; OR = 2.08; 95% CI = 1.02 - 4.29), length of hospitalization ( p = 0.01; OR= 1.04; 95% CI = 1.01 - 1.08), and 30 day re-operation ( p = 1.58 ×10 -10; OR = 15.23; 95% CI = 7.06 - 32.71) were associated with increased risk for SSI. CONCLUSION: Topical vancomycin effectively reduced the rate of SSI in patients subjected to craniotomy for primary brain tumor resection. Furthermore, preoperative narcotic use, previous head/brain radiation, length of hospitalization, and 30-day reoperation were associated with increased risk of SSI.


Assuntos
Neoplasias Encefálicas , Vancomicina , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Neoplasias Encefálicas/complicações , Craniotomia/efeitos adversos , Humanos , Entorpecentes , Pós/uso terapêutico , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Vancomicina/uso terapêutico
12.
Adv Radiat Oncol ; 6(6): 100798, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34934864

RESUMO

PURPOSE: We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated, and may improve intracranial tumor control rates compared with SRS alone. METHODS AND MATERIALS: The study was designed as a prospective, single-arm, nonrandomized, open-label, phase 1b 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, Eastern Cooperative Oncology Group Performance Status ≤2 with ≤10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg intravenously) 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. No dose limiting toxicities were noted in our patient population. The most common neurologic adverse events included grade 1 to 2 headaches and dizziness occurring in 5 (42%) of patients. Median intracranial control was 6.2 months (95% confidence interval, 3-14 months) 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 progression free survival 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 data reveals activity in certain breast cancer patients to study therapy.

13.
SAGE Open Med Case Rep ; 9: 2050313X211042215, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457306

RESUMO

The use of immune checkpoint inhibitors including ipilimumab and nivolumab has expanded for several tumors including melanoma brain metastasis. These have resulted in a growing spectrum of neurologic immune-related adverse events, including ones that are rare and difficult to diagnose and treat. Here, we present a patient with melanoma brain metastasis who was treated with immune checkpoint inhibitors and developed an Acute Motor Axonal Neuropathy. To our knowledge, this is the first case of Acute Motor Axonal Neuropathy as an immune-related adverse event associated with combination treatment of ipilimumab and nivolumab, who was successfully treated. A 28-year-old woman with metastatic BRAF V600E melanoma developed melanoma brain metastasis and was enrolled on Checkmate 204, a Phase 2 clinical trial using ipilimumab (3 mg/kg intravenous) and nivolumab (1 mg/kg intravenous) every 3 weeks for four cycles, followed by monotherapy with nivolumab (240 mg intravenous) every 2 weeks. A few days after Cycle 2 of ipilimumab and nivolumab, she developed a pure motor axonal neuropathy consistent with Acute Motor Axonal Neuropathy. She was treated with several immunosuppressive treatments including high dose methylprednisolone, immune globulin, and infliximab, and her motor neuropathy eventually improved several months after onset of symptoms. Unfortunately, she had progression of her systemic disease and died several months later. This is the first case reported of Acute Motor Axonal Neuropathy associated with ipilimumab and nivolumab, successfully treated with immune-suppressive therapy. As the field of immunotherapy expands with the increasing use of the immune checkpoint inhibitors, it is critical to increase our knowledge and understanding of the neurologic immune-related adverse events associated with immune checkpoint inhibitors. This includes the spectrum of rare neurologic immune-related adverse events, which can be quite difficult to recognize and treat. Early consultations with neurology may expedite a diagnosis and treatment plan in patients with unexplained weakness receiving immune checkpoint inhibitor therapy.

14.
Clin Neurol Neurosurg ; 203: 106593, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33706061

RESUMO

OBJECTIVE: Sacroiliac joint (SIJ) arthropathy is an increasingly recognized problem in adult spinal deformity patients undergoing long construct surgery. S2-alar-iliac (S2AI) screw instrumentation is thought to reduce morbidity from pelvic fixation in these patients. The goal of this study is to assess the overall incidence of SIJ arthropathy in patients with long constructs to the pelvis as well as compare SIJ outcomes of partially threaded (PT) versus fully threaded (FT) S2AI screws. METHODS: Data of eligible patients were collected from a prospectively maintained database with retrospective review of electronic records at an academic institution between 2016 and 2019. RESULTS: 65 consecutive patients who underwent S2AI screw instrumentation (40 in PT group, 25 in FT group) were enrolled. The rate of postoperative SIJ pain was higher in the PT (52.5 %) compared to FT (32 %) group. There was a significantly shorter time-to-pain development in the PT compared to FT group (11.8 versus 20.1 months, respectively). Of those who developed SIJ pain in the PT group, the pain worsened in 80.9 % versus only 25 % of those in the FT group despite conservative treatment. Cox regression found the PT group more likely to develop SIJ pain at any point during follow-up compared to the FT group (Hazard Ratio = 7.308). SIJ fusion was not detected on imaging of any patient during follow-up. CONCLUSION: FT S2AI screws are associated with better SIJ outcomes compared to PT screws. However, our data suggest that S2AI screw instrumentation is not sufficient to achieve fusion or prevent development of SIJ pain. Concurrent SIJ fusion may be necessary in patients with long constructs to prevent SIJ arthropathy.


Assuntos
Parafusos Ósseos/efeitos adversos , Artropatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Articulação Sacroilíaca , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/instrumentação , Feminino , Humanos , Incidência , Artropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Doenças da Coluna Vertebral/diagnóstico por imagem
15.
Neuro Oncol ; 23(4): 677-686, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33173935

RESUMO

BACKGROUND: Radiotherapy may synergize with programmed cell death 1 (PD1)/PD1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high-grade gliomas (HGGs). METHODS: Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W. RESULTS: Thirty-two patients were enrolled (bevacizumab-naïve, n = 24; bevacizumab-resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab-naïve cohort, 20 patients (83%) had a complete response or partial response. The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab-resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (n = 20/26; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression <1%. CONCLUSIONS: The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.


Assuntos
Neoplasias Encefálicas , Glioma , Reirradiação , Anticorpos Monoclonais Humanizados , Bevacizumab , Neoplasias Encefálicas/terapia , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Microambiente Tumoral
16.
J Vasc Interv Radiol ; 31(11): 1745-1752, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33129427

RESUMO

PURPOSE: To evaluate the effectiveness of radiofrequency (RF) ablation as measured by change in worst pain score from baseline to 3 mo after RF ablation for the palliative treatment of painful bone metastases. MATERIALS AND METHODS: One hundred patients (mean age, 64.6 y) underwent RF ablation for metastatic bone disease and were followed up to 6 mo. Subjects' pain and quality of life were measured before RF ablation and postoperatively by using the Brief Pain Index and European Quality of Life questionnaires. Opioid agent use and device-, procedure-, and/or therapy-related adverse events (AEs) were collected. RESULTS: Eighty-seven patients were treated for tumors involving the thoracolumbar spine and 13 for tumors located in the pelvis and/or sacrum. All ablations were technically successful, and 97% were followed by cementoplasty. Mean worst pain score decreased from 8.2 ± 1.7 at baseline to 3.5 ± 3.2 at 6 mo (n = 22; P < 0.0001 for all visits). Subjects experienced significant improvement for all visits in average pain (P < .0001), pain interference (P < .0001), and quality of life (P < .003). Four AEs were reported, of which 2 resulted in hospitalization for pneumonia and respiratory failure. All 30 deaths reported during the study were attributed to the underlying malignancy and not related to the study procedure. CONCLUSIONS: Results from this study show rapid (within 3 d) and statistically significant pain improvement with sustained long-term relief through 6 mo in patients treated with RF ablation for metastatic bone disease.


Assuntos
Neoplasias Ósseas/cirurgia , Dor/prevenção & controle , Cuidados Paliativos , Ablação por Radiofrequência , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/complicações , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Cementoplastia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/etiologia , Dor/mortalidade , Medição da Dor , Estudos Prospectivos , Qualidade de Vida , Ablação por Radiofrequência/efeitos adversos , Ablação por Radiofrequência/mortalidade , Fatores de Tempo , Resultado do Tratamento
17.
J Med Case Rep ; 14(1): 189, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33059729

RESUMO

BACKGROUND: Extramedullary disease in multiple myeloma often portends a worse diagnosis. In approximately 1% of cases, multiple myeloma may metastasize to the central nervous system as either leptomeningeal involvement or an intracranial, intraparenchymal lesion. Spinal cord metastases, however, are exceedingly rare. We present a case of spinal cord multiple myeloma as well as a literature review of reported cases. CASE PRESENTATION: A 66-year-old African American man with multiple myeloma presented with acute midthoracic pain and lower extremity paresis and paresthesia. Magnetic resonance imaging of the spine revealed two contrast-enhancing intramedullary enhancing lesions in the T1-T2 and T6-T7 cord. Resection with biopsy yielded a diagnosis of metastatic multiple myeloma. CONCLUSION: To date, only six cases of extramedullary disease to the spinal cord in patients with multiple myeloma have been reported, including our patient's case. In all cases, neurologic deficit was observed at presentation, and magnetic resonance imaging of the spine revealed an intramedullary, homogeneously enhancing lesion. Current evidence suggests worse prognosis in patients with extramedullary disease to the central nervous system, and treatment paradigms remain debatable.


Assuntos
Mieloma Múltiplo , Neoplasias da Medula Espinal , Idoso , Biópsia , Humanos , Imageamento por Ressonância Magnética , Masculino , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/diagnóstico por imagem , Medula Espinal , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia
18.
J Neurooncol ; 144(3): 583-589, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399935

RESUMO

PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors are becoming increasingly utilized in the setting of advanced, hormone receptor (HR+) positive breast cancer. Pre-clinical data suggests a potential synergy between radiation therapy (RT) and CDK4/6 inhibitors. We assessed clinical outcomes of patients treated at our institution with the use of CDK4/6 inhibitors and stereotactic radiation in the management of HR+ breast brain metastases. METHODS: A retrospective analysis of patients who received stereotactic radiotherapy for HR+ brain metastases within 6 months of CDK4/6 inhibitor administration was performed. The primary endpoint was neurotoxicity during or after stereotactic radiation. Secondary endpoints were local brain control, distant brain control, and overall survival (OS). RESULTS: A total of 42 lesions treated with stereotactic radiation in 15 patients were identified. Patients received either palbociclib (n = 10; 67%) or abemaciclib (n = 5; 33%). RT was delivered concurrently, before, or after CDK4/6 inhibitors in 18 (43%), 9 (21%), and 15 (36%) lesions, respectively. Median follow-up following stereotactic radiation was 9 months. Two lesions (5%) developed radionecrosis, both of which received four prior RT courses to the affected lesion prior to onset of radionecrosis and subsequently managed with steroids and bevacizumab. Six- and 12-month local control of treated lesions was 88% and 88%, while 6- and 12-month distant brain control was 61% and 39%, respectively. Median OS was 36.7 months from the date of brain metastases diagnosis. CONCLUSIONS: Stereotactic radiation to breast brain metastases was well tolerated alongside CDK4/6 inhibitors. Compared to historical data, brain metastases control rates are similar whereas survival appears prolonged.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/terapia , Neoplasias da Mama/terapia , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Radiocirurgia/mortalidade , Adulto , Idoso , Aminopiridinas/administração & dosagem , Benzimidazóis/administração & dosagem , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Prognóstico , Piridinas/administração & dosagem , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida
20.
Breast Cancer Res Treat ; 175(3): 781-788, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30859348

RESUMO

PURPOSE: Leptomeningeal disease is a rare presentation of advanced metastatic breast cancer. The purpose of this study was to evaluate craniospinal progression between intrathecal (IT) trastuzumab, IT chemotherapy, and whole brain radiation therapy (WBRT) in leptomeningeal disease. METHODS: A total of 56 patients were identified with breast cancer leptomeningeal disease at our institution treated with IT trastuzumab (n = 18; 32%), single-agent IT chemotherapy (methotrexate n = 14 or thiotepa n = 1; 27%), or WBRT alone (n = 23; 41%). Patients were treated beginning November 2012 and followed until November 2018. RESULTS: Median time from breast cancer diagnosis to development of leptomeningeal disease was 4.3 years. There were no significant differences noted between IT trastuzumab, IT chemotherapy, or WBRT groups in age (p = 0.4), Karnofsky Performance Status (KPS) (p = 0.07), or receipt of systemic therapy at time of leptomeningeal disease treatment (p = 0.47). Median follow-up of patients from leptomeningeal diagnosis was 5 months (range 0.2-81.1 months). Significant differences were noted in Kaplan-Meier (KM) craniospinal progression-free survival (CS-PFS) with 6-month rates of 44%, 18%, and 26% (p = 0.04) between IT trastuzumab, IT chemotherapy, and WBRT, respectively. Craniospinal control > 10 months was achieved in four patients treated with IT trastuzumab. Twelve-month KM OS rates were 54%, 10%, and 19% (p = 0.01) between IT trastuzumab, IT chemotherapy, and WBRT groups, respectively. IT therapy was adequately tolerated with three patients undergoing treatment-related hospitalizations. CONCLUSIONS: In our institutional series, significant differences were noted in CS-PFS and OS by treatment modality. IT trastuzumab should be considered in the management HER2+ breast leptomeningeal disease.


Assuntos
Neoplasias da Mama/terapia , Irradiação Craniana/métodos , Tratamento Farmacológico/métodos , Neoplasias Meníngeas/secundário , Neoplasias Meníngeas/terapia , Trastuzumab/administração & dosagem , Adulto , Idoso , Feminino , Hospitalização , Humanos , Injeções Espinhais , Avaliação de Estado de Karnofsky , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Tiotepa/administração & dosagem , Tiotepa/uso terapêutico , Trastuzumab/uso terapêutico , Resultado do Tratamento
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