Stereotactic radiosurgery for brain metastases from malignant melanoma and the impact of hemorrhagic metastases.

INTRODUCTION: Stereotactic radiosurgery (SRS) is a common treatment modality among patients with brain metastases, particularly from malignant melanoma. Our objective was to investigate the difference in local control, toxicity, and survival among patients with hemorrhagic and solid melanoma brain metastases. METHODS: We collected demographic, treatment, local control, toxicity, and survival for 134 patients with a total of 936 intracranial melanoma metastases who underwent SRS between 1998 and 2015. Pre-radiosurgical diagnostic imaging was reviewed for evidence of hemorrhage (melanin-containing or clearly hemorrhagic). RESULTS: The cohort consisted of 92 men and 42 women with a mea age of 61.7 years (range 21.2-84.9) at the time of radiosurgery. Overall survival of patients with brain metastases from malignant melanoma was 42, 31, 12% at 12, 24, and 72 months from date of first SRS. At 6 months, 43% of the patients with hemorrhagic metastases had local tumor control compared to 83% of solid melanoma metastases (p < 0.001). No significant difference in toxicity was noted between the two groups. Factors that were significantly associated with time to local tumor progression on multivariate analysis include prior WBRT (HR 1.62, p = 0.003), prior chemotherapy (HR 0.69, p = 0.011), margin dose (HR 0.88, p < 0.001) and radiographic features of melanin deposition (HR 3.73, p < 0.001), or clear hemorrhage (HR 2.20, p < 0.001). CONCLUSIONS: Our findings demonstrate that hemorrhagic intracranial melanoma metastases are associated with inferior local tumor control when treated with SRS, as compared to solid tumors. These results highlight the importance of early radiosurgery among patients with melanoma brain metastases before hemorrhage occurs.

Clinicopathologic Factors and Their Association with Outcomes of Salivary Duct Carcinoma: A Multicenter Experience.

Purpose: This series reports long-term clinical outcomes of patients with salivary duct carcinoma (SDC), which is associated with a poor prognosis. Methods and Materials: Eighty-nine patients with SDC were treated with curative intent from February 5, 1971, through September 15, 2018. Kaplan-Meier and competing risk analyses were used to estimate locoregional control, distant metastasis-free survival (DMFS), progression-free survival, and overall survival (OS). Cox regression analyses of disease and treatment characteristics were performed to discover predictors of locoregional control, DMFS, and OS. Results: Median follow-up was 44.1 months (range, 0.23-356.67). The median age at diagnosis was 66 years (interquartile range, 57-75). Curative surgery followed by adjuvant radiation therapy was performed in 73 patients (82%). Chemotherapy was delivered in 26 patients (29.2%). The 5-year local recurrence and distant metastasis rates were 27% and 44%, respectively, with death as a competing risk. Distant metastasis was associated with lymph node-positive disease (hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.38-7.23; P = .006), stage IV disease (HR, 4.78; 95% CI, 1.14-20.11; P = .033), perineural invasion (HR, 4.56; 95% CI, 1.74-11.97; P = .002), and positive margins (HR, 9.06; 95% CI, 3.88-21.14; P < .001). Median OS was 4.84 years (95% CI, 3.54-7.02). The 5-year OS was 42%. Reduced OS was associated with lymphovascular space invasion (HR, 3.49; 95% CI, 1.2-10.1; P = .022), perineural invasion (HR, 2.05; 95% CI, 1.06-3.97; P = .033), positive margins (HR, 2.7; 95% CI, 1.3-5.6; P = .011), N2 disease (HR, 1.88; 95% CI, 1.03-3.43; P = .04), and N3 disease (HR, 11.76; 95% CI, 3.19-43.3; P < .001). Conclusions: In this single-institution, multicenter retrospective study, the 5-year survival was 42% in patients with SDC. Lymphovascular space invasion, lymph node involvement, and higher staging at diagnosis were associated with lower DMFS and OS.

Pragmatic, Prospective Comparative Effectiveness Trial of Carbon Ion Therapy, Surgery, and Proton Therapy for the Management of Pelvic Sarcomas (Soft Tissue/Bone) Involving the Bone: The PROSPER Study Rationale and Design.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

Current use of stereotactic body radiation therapy for low and intermediate risk prostate cancer: A National Cancer Database Analysis.

BACKGROUND: Recent studies have demonstrated both safety and efficacy of stereotactic body radiation therapy (SBRT) as monotherapy in the treatment of low and intermediate risk prostate cancer. Our study aims to provide an update analyzing the use of SBRT compared with conventional and hypofractionated regimens in the United States from 2004 to 2015. METHODS: This retrospective review was conducted using the National Cancer Database. We identified 114,931 patients with sufficient diagnostic and treatment information treated with definitive radiation therapy in the United States from 2004 to 2015. The relative utilization of conventional fractionation (defined as 180-200 cGy per fraction and >5 fractions), moderate hypofractionation (defined as >200 cGy per fraction and >5 fractions), and SBRT (defined as >200 cGy per fraction and 5 fractions or less) were compared over the same time period. Logistic regression models were used to estimate trends. Demographic factors were collected and analyzed using chi-squared tests and independent t-tests. RESULTS: The proportion of prostate cancer patients receiving SBRT increased substantially from 0.9% in 2004 to 19.5% in 2015. Moderate hypofractionation exhibited some growth, increasing from 2.7% of patients to 4.7% in 2015. Conventional fractionation use declined significantly from 96.3% in 2004 to 75.8% in 2015. Notably, there was a sharp decline in the absolute number of patients receiving conventional fractionation in 2011, from 14,699 patients treated in 2009 to 1492 in 2011. Patients treated with SBRT were more likely to be treated in academic centers, younger, and have higher income than other fractionation groups. The most frequently used fractionation schedule was 3625 cGy in five fractions. CONCLUSIONS: The use of SBRT for low and intermediate risk prostate cancer has increased significantly from 2004 to 2015, coinciding with recently published data supporting the efficacy and favorable toxicity profile of this technique.

Treatment of a glioblastoma multiforme dural metastasis with stereotactic radiosurgery: A case report and select review of the literature.

Glioblastoma multiforme (GBM) is a primary brain neoplasm accounting for approximately 75% of all high grade gliomas. It is diffusely infiltrative and exhibits rapid proliferation with a poor overall prognosis. Maximum surgical resection and postoperative radiotherapy, accompanied by concurrent and adjuvant temozolomide chemotherapy, remain the standard of care without major therapeutic advances over the past 10 years. Herein, we present the case of a 64-year-old Caucasian male with a GBM who subsequently developed a left frontal dural metastasis, subsequently treated with stereotactic radiosurgery (20 Gy in 1 fraction). With six month follow-up, the patient showed near complete resolution of his dural metastases and no overall change in neurological symptoms or side effects following radiosurgery. Due to the paucity of clinical literature regarding dural metastases from GBM, its optimal treatment remains unknown. While the role of SRS has yet to be defined in this setting, here we provide evidence suggesting its overall efficacy in the treatment of select dural GBM metastases.

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.

Recurrent myxoinflammatory fibroblastic sarcoma: a case report.

Myxoinflammatory fibroblastic sarcoma is a rare sarcoma which typically presents in the extremities and is treated by definitive surgery. In recurrent disease, the reported utilization of radiotherapy is increasing, and more modern techniques such as intensity-modulated radiotherapy may be improving long-term outcomes.