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Frontiers in Oncology 2020(alternately referred to as v-raf murine sarcoma viral oncogene homolog B1) is a proto-oncogene involved in the mitogen-activated protein kinase () pathway.... (Review)
Review
(alternately referred to as v-raf murine sarcoma viral oncogene homolog B1) is a proto-oncogene involved in the mitogen-activated protein kinase () pathway. alterations are most commonly missense mutations or aberrant fusions. These mutations are observed in numerous primary central nervous system tumors as well as metastases. This review discusses the prevalence of alteration within select notable CNS tumors, and their prognostic associations. Included are some novel entities such as diffuse leptomeningeal glioneuronal tumor (DLGNT), polymorphous low grade neuroepithelial tumor of the young (PLNTY), and multinodular and vacuolating neuronal tumor (MVNT). Knowledge of this gene's integrity in CNS and PNS tumors can have profound diagnostic and therapeutic implications. Also reviewed are the current state of targeted therapy against aberrant as it pertains mostly to the CNS and to a lesser extent in PNS, and certain diagnostic aspects.
PubMed: 33042847
DOI: 10.3389/fonc.2020.574974 -
BMC Cancer Dec 2022Postoperative stereotactic radiosurgery (SRS) is a standard management option for patients with resected brain metastases. Preoperative SRS may have certain advantages... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase III, multicenter, randomized controlled trial of preoperative versus postoperative stereotactic radiosurgery for patients with surgically resectable brain metastases.
BACKGROUND
Postoperative stereotactic radiosurgery (SRS) is a standard management option for patients with resected brain metastases. Preoperative SRS may have certain advantages compared to postoperative SRS, including less uncertainty in delineation of the intact tumor compared to the postoperative resection cavity, reduced rate of leptomeningeal dissemination postoperatively, and a lower risk of radiation necrosis. The recently published ASCO-SNO-ASTRO consensus statement provides no recommendation for the preferred sequencing of radiotherapy and surgery for patients receiving both treatments for their brain metastases.
METHODS
This multicenter, randomized controlled trial aims to recruit 88 patients with resectable brain metastases over an estimated three-year period. Patients with ten or fewer brain metastases with at least one resectable, fulfilling inclusion criteria will be randomized to postoperative SRS (standard arm) or preoperative SRS (investigational arm) in a 1:1 ratio. Randomization will be stratified by age (< 60 versus ≥60 years), histology (melanoma/renal cell carcinoma/sarcoma versus other), and number of metastases (one versus 2-10). In the standard arm, postoperative SRS will be delivered within 3 weeks of surgery, and all unresected metastases will receive primary SRS. In the investigational arm, enrolled patients will receive SRS of all brain metastases followed by surgery of resectable metastases within one week of SRS. In either arm, single fraction or hypofractionated SRS in three or five fractions is permitted. The primary endpoint is to assess local control at 12 months in both arms. Secondary endpoints include local control at other time points, regional/distant brain recurrence rates, leptomeningeal recurrence rates, overall survival, neurocognitive outcomes, and adverse radiation events including radiation necrosis rates in both arms.
DISCUSSION
This trial addresses the unanswered question of the optimal sequencing of surgery and SRS in the management of patients with resectable brain metastases. No randomized data comparing preoperative and postoperative SRS for patients with brain metastases has been published to date.
TRIAL REGISTRATION
Clinicaltrials.gov , NCT04474925; registered on July 17, 2020. Protocol version 1.0 (January 31, 2020).
SPONSOR
Alberta Health Services, Edmonton, Canada (Samir Patel, MD).
Topics: Humans; Middle Aged; Radiosurgery; Brain Neoplasms; Brain; Necrosis; Alberta; Treatment Outcome
PubMed: 36585629
DOI: 10.1186/s12885-022-10480-z -
Cureus Jan 2022Myeloid sarcoma (MS)/granulocytic sarcoma/myeloblastoma/chloroma is a rare extramedullary proliferation of blast cells of one or more myeloid lineages along with the...
Myeloid sarcoma (MS)/granulocytic sarcoma/myeloblastoma/chloroma is a rare extramedullary proliferation of blast cells of one or more myeloid lineages along with the destruction of the normal architecture of adjacent tissue. Isolated MS is a rare entity with an incidence of 0.7 out of 1 million children and 2 out of 1 million adults. Varied clinical presentation, the rarity of the diagnosis, inadequate immunophenotyping, and lack of available literature makes the disease difficult to manage. Here, we report a case of MS in a 44-year-old male with an initial presentation of testicular mass without bone marrow involvement, causing diagnostic challenges. In this case report, we discuss the pathogenesis, diagnostic challenges, and therapeutic options of MS.
PubMed: 35165636
DOI: 10.7759/cureus.21200 -
Radiology Case Reports Jun 2024Ewing sarcoma is the second most frequent primary bone tumour of childhood and adolescence. The aim of this report is to describe the imaging, pathology, clinical...
Ewing sarcoma is the second most frequent primary bone tumour of childhood and adolescence. The aim of this report is to describe the imaging, pathology, clinical findings, and treatment of a primary intradural extramedullary Ewing sarcoma with a unique intracranial metastatic component in a pediatric patient. A 14-year-old girl with a history of mood disorders presented to the emergency department with a 3-week history of neck torticollis, cervical pain, paresis, and paresthesia of the upper and lower extremities on the left side. Initially, non-organic causes such as somatization or conversion disorder were suspected. She returned 3 months later when her symptoms worsened. MRI of the head and spine was performed, and demonstrated the presence of a suprasellar, retro-chiasmatic mass lesion. There was also diffuse leptomeningeal enhancement, another well-defined intradural extramedullary lesion the sacral region and several multifocal cauda equina soft tissue nodules. The patient first underwent surgery. The patient was also treated with a combination of chemotherapy (vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide (VDC/IE)) and radiation as per the Children's Oncology Group AEWS1221 protocol. Most recent imaging conducted 22 months after the initial mass discovery revealed improvement of the suprasellar mass lesion with residual stable appearance of the prominence and enhancement of the pituitary stalk and tuber cinereum. There was interval improvement of the spinal lesions with no convincing residual. Clinically, at almost three years since initial imaging findings, and 25 months since completing treatment, she is stable from an oncology perspective.
PubMed: 38572274
DOI: 10.1016/j.radcr.2024.02.101 -
Cancers Jun 2021Development of brain metastases can occur in up to 30-50% of patients with breast cancer, representing a significant impact on an individual patient in terms of survival... (Review)
Review
Development of brain metastases can occur in up to 30-50% of patients with breast cancer, representing a significant impact on an individual patient in terms of survival and quality of life. Patients with HER2-positive breast cancer have an increased risk of developing brain metastases; however, screening for brain metastases is not currently recommended due to the lack of robust evidence to support survival benefit. In recent years, several novel anti-HER2 agents have led to significant improvements in the outcomes of HER2-positive metastatic breast cancer. Despite these advances, brain and leptomeningeal metastases from HER2-positive breast cancer remain a significant cause of morbidity and mortality, and their optimal management remains an unmet need. This review presents an update on the current and novel treatment strategies for patients with brain metastases from HER2-positive breast cancer and discusses the open questions in the field.
PubMed: 34208287
DOI: 10.3390/cancers13122927 -
BMJ Case Reports Jul 2021This is the case of a parameningeal alveolar rhabdomyosarcoma (ARMS) in a 13-year-old boy who presented with painless loss of vision in the right eye, but very few other...
This is the case of a parameningeal alveolar rhabdomyosarcoma (ARMS) in a 13-year-old boy who presented with painless loss of vision in the right eye, but very few other physical signs. The ARMS diagnosis was confirmed with imaging and molecular characterisation of the tumour. Despite tolerating the initial chemotherapy and radiotherapy regimens, there was leptomeningeal recurrence and the patient unfortunately passed away. Parameningeal ARMS occurs in an area of the body, which leads to a wide variety of possible presenting symptoms, creating a long list of differentials that can delay treatment. This tumour subtype has a poor prognosis, and due to the location of the tumour around vital structures in the head, treatment toxicities must be taken into account. This highlights the necessity for having a strong index of suspicion for this tumour in atypical presentations in children, and the necessity for prompt treatment to prevent leptomeningeal disease from occurring.
Topics: Adolescent; Child; Family; Head and Neck Neoplasms; Humans; Male; Meningeal Neoplasms; Neoplasm Recurrence, Local; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal
PubMed: 34266827
DOI: 10.1136/bcr-2021-243267 -
Journal of Medical Case Reports May 2013Histiocytic sarcoma is a rare neoplasm with few cases reported in the literature of which some were diagnosed in animals. This neoplasm arises from abnormal...
INTRODUCTION
Histiocytic sarcoma is a rare neoplasm with few cases reported in the literature of which some were diagnosed in animals. This neoplasm arises from abnormal reticuloendothelial system cell proliferation of histiocytes and has an aggressive behavior especially if located in the central nervous system. We present the first case of a patient with histiocytic sarcoma that involved the meninges and had a good course after multidisciplinary treatment.
CASE PRESENTATION
Our patient was a 41-year-old Caucasian woman with no previous history of disease who started with systemic symptoms such as headache and chills. Magnetic resonance imaging with gadolinium contrast of the brain suggested a mass 1.5×2cm in diameter in the temporal lobe with a non-uniform vasogenic edema. This lesion was implanted in the meninges and surgery was the first treatment. The histological findings revealed a histiocytic sarcoma. The patient received concomitant chemoradiotherapy after surgery with good tolerance and currently lives without disease.
CONCLUSION
Although histiocytic sarcomas in the brain present an unusual location and have a poorer prognosis, we have identified the first primary leptomeningeal histiocytic sarcoma with a disease-free survival greater than 3 years following multidisciplinary treatment with surgery and chemotherapy and radiotherapy.
PubMed: 23668836
DOI: 10.1186/1752-1947-7-127 -
Journal of Cancer Research and... 2022Parameningeal rhabdomyosarcomas (PM RMSs) are rarely seen childhood tumors. Their treatment might be challenging and prognosis is poor compared to other head and neck... (Review)
Review
Parameningeal rhabdomyosarcomas (PM RMSs) are rarely seen childhood tumors. Their treatment might be challenging and prognosis is poor compared to other head and neck RMS. Here we report a PM RMS presenting with leptomeningeal seeding metastasis a year after diagnosis. A five-year-old girl presented with an enlarging mass protruding from the right ear and right facial paralysis. Magnetic resonance imaging (MRI) revealed a large mass extending from right external auditory canal to the temporal lobe, pterygoid fossa and nasopharynx with an intracranial component indenting the right temporal lobe and extending into the right cavernous sinus. Trucut biopsy revealed embryonal rhabdomyosarcoma. Cerebrospinal fluid (CSF) cytology was negative for malignant cells. Chemotherapy was started since it was found unresectable. At second week of chemotherapy, radiotherapy was applied to primary tumor location with intensity-modulated radiation therapy (IMRT) technique in 1.8 Gy fractions to total dose of 50.4 Gy. At week 27, MRI showed significant response. At week 36, the patient presented with vomiting and tendency to sleep. MRI was found to be compatible with meningitis and antibacterial therapy was started. At week 39, chemotherapy was stopped. But MRI performed one month later revealed linear contrast enhancements around the spinal cord compatible with leptomeningeal metastases. Chemotherapy and craniospinal irradiation were applied. But the patient did not improve and received palliative treatment. Six months after the completion of radiotherapy the patient died. Treatment of parameningeal rhabdomyosarcomas require multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Prognosis is poor for patients with leptomeningeal spread.
Topics: Female; Humans; Child; Child, Preschool; Rhabdomyosarcoma, Embryonal; Rhabdomyosarcoma; Meningeal Carcinomatosis; Meninges; Magnetic Resonance Imaging
PubMed: 36412455
DOI: 10.4103/jcrt.JCRT_1491_20 -
Radiation Oncology (London, England) Sep 2018Histiocytic sarcoma (HS) is an aggressive malignant neoplasm. HS in the central nervous system is exceptionally rare and associated with a poor prognosis. This report... (Review)
Review
Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review.
BACKGROUND
Histiocytic sarcoma (HS) is an aggressive malignant neoplasm. HS in the central nervous system is exceptionally rare and associated with a poor prognosis. This report documents a case of primary HS of the central nervous system with treatment including surgery, radiotherapy, and chemotherapy.
CASE PRESENTATION
Our patient was a 47 year old female presenting with progressive ataxia, headaches, imbalance, nausea, vomiting, and diplopia. MRI showed a heterogeneously enhancing lesion approximately 2.9 × 3.0 × 2.3 cm centered upon the cerebellar vermis with mild surrounding vasogenic edema and abnormal enhancement of multiple cranial nerves. The patient underwent surgical debulking, which revealed histiocytic sarcoma with grossly purulent drainage. Staging revealed diffuse leptomeningeal involvement, primarily involving the brain and lower thoracic and lumbar spine. She underwent adjuvant radiotherapy to the brain and lower spine and was started on high dose methotrexate. However, she experienced progressive disease in the cervical and thoracic spine as well as pulmonary involvement. Genomic sequencing of her tumor showed a mutation in the platelet-derived growth factor receptor A (p.V0681) which could be targeted with Dasatinib. However, she did not tolerate Dasatinib and she succumbed to progressive disseminated disease eight months from original diagnosis. Our pathologic evaluation also revealed expression of PD-L1 and PD-L2 by tumor cells raising the potential therapeutic role for immune checkpoint inhibition.
CONCLUSIONS
This case provides an example of effective CNS control with resection and moderate doses of radiation therapy. A review of the literature confirms aggressive multidisciplinary treatment is the most effective treatment against this disease. In addition, genomic sequencing may play an important role in determining new therapeutic options. However, CNS histiocytic sarcoma remains an aggressive disease with a propensity for early widespread dissemination and few long term survivors.
Topics: B7-H1 Antigen; Brain Neoplasms; Fatal Outcome; Female; Histiocytic Sarcoma; Humans; Middle Aged; Mutation; Programmed Cell Death 1 Ligand 2 Protein; Receptor, Platelet-Derived Growth Factor alpha; Spinal Neoplasms; Terminal Care
PubMed: 30185195
DOI: 10.1186/s13014-018-1115-x -
Journal of Neurosurgery. Case Lessons Mar 2021Ewing sarcoma is a neoplasm within the family of small round blue cell tumors and most frequently arises from skeletal bone. Primary involvement of the central nervous...
BACKGROUND
Ewing sarcoma is a neoplasm within the family of small round blue cell tumors and most frequently arises from skeletal bone. Primary involvement of the central nervous system in these lesions is extremely rare, with an incidence of 1%.
OBSERVATIONS
A case is presented of a 34-year-old man who presented with left facial numbness, multiple intracranial lesions, a lumbar intradural lesion, and diffuse spinal leptomeningeal involvement. A lumbar laminectomy and biopsy were performed, which revealed the diagnosis of extraskeletal Ewing sarcoma/primitive neuroectodermal tumor. The patient had a rapidly progressive clinical decline despite total neuroaxis radiation and multiple lines of chemotherapeutic treatments, eventually dying from his disease and its sequelae 6 months after diagnosis.
LESSONS
The authors' review of 40 cases in the literature revealed only 2 patients with isolated intraaxial cranial lesions, 4 patients with cranial and spine involvement, and an additional 34 patients with spine lesions. The unique characteristics of this patient's case, including his presentation with diffuse disease and pathology that included a rare V600E mutation, are discussed in the context of the available literature.
PubMed: 35855436
DOI: 10.3171/CASE2042