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. 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. 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.

Background: Mast Cell Activation Syndrome (MCAS) is classified as an idiopathic mast cell disorder where inconsistent or unknown triggers release inflammatory mediators and cause a constellation of symptoms. Studies demonstrate mast cells increase histamine, tryptase, and inflammatory cytokine expression following ionizing radiation. Additionally, there are cases of cutaneous mastocytosis developing within the initial radiation field suggesting mast cells play a role in local tissue reactions. Literature is sparse on radiation induced toxicity in patients with mast cell disorders. Case presentation: A 62 year old female patient with a history of MCAS received breast conservation therapy for invasive lobular carcinoma of the left breast initially AJCC 7th Stage IIB, pT3 pN0 M0. The patient underwent external beam radiotherapy (EBRT) and received 4500 cGy to the left whole breast, followed by a 1000 cGy boost to the lumpectomy cavity. She developed grade 1 radiation dermatitis. Two years later she progressed distantly and received stereotactic body radiation therapy to a lumbar vertebrae lesion to a dose of 2400 cGy in a single fraction. She developed no in-field dermatologic or systemic flare in her MCAS symptoms during radiation therapy. Conclusions: To our knowledge there are no reported cases in the literature of patients diagnosed with MCAS or other idiopathic mast cell disorders undergoing radiation therapy. Idiopathic mast cell disorders such as MCAS and primary mast cell disorders alike should not be considered a contraindication to treatment with EBRT. This patient population appears to tolerate treatment without systemic flares in symptoms.

The United States Veterans Affairs (VA) Health Care System has a strong history of conducting impactful oncology randomized clinical trials (RCTs). We developed a phase II/III RCT to test the use of metastasis-directed therapy in Veterans with oligometastatic prostate cancer (OMPC)—the first VA RCT in OMPC that leverages novel imaging and advanced radiotherapy techniques. To accomplish this, we developed a clinical trial network to conduct the study. In this manuscript, we describe several challenges we encountered in study development/conduct and our strategies to address them, with the goal of helping investigators establish robust study networks to conduct clinical trials. In the study start-up, we encountered challenges in timely site activation, and leveraged project management to maximize efficiency. Additionally, there were several changes in the clinical paradigms in imaging and treatment that led to protocol amendments to ensure maximum equipoise, recruitment, and impact of the study. Specifically, we amended the trial to add de novo OMPC patients (from initially only recurrent OMPC) and expanded the study to allow up to 10 metastases (from initially five). Finally, in order to maintain local study team engagement, we developed initiatives to maximize collaboration and add value to the overall clinical program through study participation.