BackgroundHistiocytic 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 presentationOur 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.ConclusionsThis 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.
Efaproxiral (Efaproxynt, RSR13), a synthetic allosteric modifier of haemoglobin (Hb), decreases Hb-oxygen (O 2 ) binding affinity and enhances oxygenation of hypoxic tumours during radiation therapy. This analysis evaluated the Phase 3, Radiation Enhancing Allosteric Compound for Hypoxic Brain Metastases; RT-009 (REACH) study efficacy results in relation to efaproxiral exposure (efaproxiral red blood cell concentration (E-RBC) and number of doses). Recursive partitioning analysis Class I or II patients with brain metastases from solid tumours received standard whole-brain radiation therapy (3 Gy/fraction  10 days), plus supplemental O 2 (4 l/min), either with efaproxiral (75 or 100 mg/kg daily) or without (control). Efaproxiral red blood cell concentrations were linearly extrapolated to all efaproxiral doses received. Three patient populations were analysed: (1) all eligible, (2) non-small-cell lung cancer (NSCLC) as primary cancer, and (3) breast cancer primary. Efficacy endpoints were survival and response rate. Brain metastases patients achieving sufficient E-RBC (X483 mg/ml) and receiving at least seven of 10 efaproxiral doses were most likely to experience survival and response benefits. Patients with breast cancer primary tumours generally achieved the target efaproxiral exposure and therefore gained greater benefit from efaproxiral treatment than NSCLC patients. This analysis defined the efaproxiral concentration-dependence in survival and response rate improvement, and provided a clearer understanding of efaproxiral dosing requirements.
126 Background: Palliative radiation treatment (pRT) is a common and effective treatment for patients with symptomatic bone metastases. However, patients receiving RT for bone metastases often may have a poor performance status and are more likely to experience toxicity during or after treatment. This study aims to investigate the number and type of toxicity event occurring during or after pRT for bone metastases. Methods: Patients treated with RT for bone metastases at Mayo Clinic from 2007 to 2016 were included in this study. Demographic, disease, treatment, and toxicity information were collected. Specifically, toxicity events were identified as emergency department (ED) visits and inpatient hospitalization (IH) within 90 days, breaks in treatment >4 days, and excessive 30 day financial toxicity defined as standardized Medicare costs >1 standard deviation above the mean. RT treatment was compared by dose and fractionation via descriptive statistics. Results: A total of 538 patients treated with pRT were identified, 124 receiving 8Gy x1, 204 receiving 4Gy x5, and 210 receiving 3Gy x10. Patients with breast and prostate cancer were most likely to be treated with 3Gy x10 and patients with GI and Lung cancer were most likely to be treated with 8Gy x1. A description of the patient characteristics and toxicities are shown in Table 1. For 8Gy x1, 4Gy x5, and 3Gy x10 breaks in treatment were rare (0%, 2%, and 3.3%), ED visits (15%, 24%, & 28%), IH (12%, 23%, & 19%), and financial toxicity (13%, 18%, & 21%) were common. A total of 22.6%, 27.5%, and 38.6% of patients were alive two years following pRT from each group. Conclusions: Toxicity during or shortly after pRT of bone metastases is common. This study confirms that additional steps should be taken to monitor and mitigate toxicity in this vulnerable patient group. [Table: see text]
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