Brain metastasis from melanoma: the prognostic value of varying sites of extracranial disease.

Patients with brain metastasis from melanoma have poor outcomes. Radiation is used both for prognostic and symptomatic value. We aimed to further clarify the role of stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) as well as the prognostic implication of various sites of extracranial disease. The records of 73 consecutive patients treated at the University of Rochester Medical Center for brain-metastatic melanoma from January 2004 to October 2013 were reviewed. The median overall survival (OS) was 3.0 months. Patients treated with WBRT alone had decreased OS compared to those treated with SRS alone (HR = 0.38, p = 0.001) or WBRT and SRS (HR = 0.51, p = 0.039). The mean number of brain metastasis differed (p = 0.002) in patients in patients who received WBRT (4.0) compared to those who did not (2.0). Among patients with extracranial disease (n = 63), bone metastasis (HR = 1.86, p = 0.047, n = 15) was a negative prognostic factor; liver (HR = 1.59, p = 0.113, n = 17), lung (HR = 1.51, p = 0.23, n = 51) and adrenal metastasis (HR = 1.70, p = 0.15, n = 10) were not. In patients with concurrent brain and lung metastasis, those with disease limited to those two sites (OS = 8.7 mo, n = 13) had improved OS (HR = 0.44, p = 0.014) compared to those with additional disease (OS = 1.8 mo, n = 50). Based on this hypothesis-generating retrospective analysis, SRS may offer survival benefit compared to WBRT alone in patients with brain metastatic melanoma. Bone metastasis appears to confer a particularly poor prognosis. Those with disease confined to the lung and brain may represent a population with improved prognosis.

Long-term cause-specific mortality in survivors of adolescent and young adult bone and soft tissue sarcoma: a population-based study of 28,844 patients.

BACKGROUND: Despite improved cure rates for bone and soft tissue sarcomas, to the authors' knowledge, no large population-based study to date has evaluated long-term cause-specific mortality in patients diagnosed in the adolescent and young adult (AYA) age range (15 years-39 years). METHODS: A total of 28,844 survivors of AYA bone and soft tissue sarcoma, who accrued 113,206 person-years of follow-up, were identified in the population-based Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMR) and absolute excess risks (AER) (per 10,000 person-years) were calculated to evaluate associations with histology (chemotherapy-sensitive subtypes: Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma vs all other subtypes), age, and initial therapy. RESULTS: All-cause mortality in survivors of AYA sarcoma was found to be significantly increased compared with that of the general population (SMR, 1.76; 95% confidence interval [95% CI], 1.60-1.92 [AER of 19]), and persisted for > 20 years (SMR, 1.39; 95% CI, 1.04-1.82 [AER of 20]). Significant excess mortality was observed for both second malignant neoplasms (SMR, 2.05; 95% CI, 1.71-2.43 [AER of 7]) and noncancer causes (SMR, 1.66; 95% CI, 1.49-1.85 [AER of 19]). Significant excess deaths occurred among patients with chemotherapy-sensitive (SMR, 2.76; 95% CI, 2.20-3.41 [AER of 32]) and nonchemosensitive (SMR, 1.63; 95% CI, 1.47-1.80 [AER of 17]) subtypes. Significantly elevated noncancer mortality in the former group included cardiovascular disease (SMR, 2.33) and infections (SMR, 15.6), whereas significant excess deaths in the latter group included diabetes (SMR, 2.40) and infections (SMR, 2.77). CONCLUSIONS: Survivors of AYA bone and soft tissue sarcoma experience significant long-term mortality due to second malignant neoplasms and noncancer causes. Further research is needed to develop preventive and surveillance guidelines in this understudied population to prevent and reduce long-term excess mortality.

Subcutaneous sarcoidosis (Darier-Roussy sarcoidosis) with extensive disease on positron emission tomography: A case report and review of the literature.

Cutaneous manifestations of sarcoidosis are common, but subcutaneous nodules are rare, originally described in 1904 by Darier and Roussy and thought to represent isolated skin disease. We present a 61-year-old male who presented with 3 months of subcutaneous nodules on the forearms and knees. Biopsy confirmed sarcoidosis. An [F-18] fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showed confluent uptake in the skin of forearms and knees, along with thighs and buttocks, mediastinal, hilar and upper abdominal lymph nodes, and multiple bones. He was well and treated with hydroxychloroquine 400 mg/day. The nodules resolved and a repeat FDG PET/CT at 5 months showed a significant decrease in the uptake at all involved sites. Although a PET scan can demonstrate extensive disease in a patient presenting with subcutaneous nodules, the literature suggests prognosis is good and treatment should start simply with the least toxic approach, such as with hydroxychloroquine therapy.

Spiders and mushrooms: Reporting bowel endometriosis shape on preoperative MRI to flag surgical complexity.

INTRODUCTION: Preoperative imaging of patients with endometriosis allows adequate counselling, referral to appropriate centres of expertise and workforce planning. The objective of this study was to assess the feasibility of simplified three-category preoperative endometriosis MRI morphological descriptors to predict subsequent surgical management. METHODS: A single-centre observational study in 76 patients (median age 38 years, range 18-55) with preoperative endometriosis mapping MRI between 1 Jan 2015 and 31 Dec 2019. MRI studies were prospectively re-read blind-to-surgical outcome to categorise rectosigmoid morphology as normal, spider-shaped (linear T2-dark fibrotic bands) superficial endometriosis or typical crescentic or mushroom-shaped deep infiltrating endometriosis (DIE). Bowel motility was similarly categorised as normal, tethered or distorted/fixed. The reference standard was subsequent surgery within 3 years of MRI, categorised as no bowel surgery, adhesiolysis only or more complex surgeries. RESULTS: Despite three-quarters of surgical cases having normal bowel morphology on preoperative MRI (72%, 55/76; 12% linear superficial endometriosis, 10% crescentic and 5% mushroom-shaped DIE) more than half showed bowel tethering (54%, 41/76) or distortion/fixation (10%, 8/76) and most patients underwent adhesiolysis (79%, 60/76). Complex surgery such as bowel resection, laparotomy conversion or complex adhesiolysis is predicted by morphology (crescentic or mushroom-shaped DIE, P < 0.001) and motility (tethered or distorted bowel, P = 0.002) descriptors. CONCLUSIONS: Comprehensive and clinically relevant diagnostic reporting does not have to be convoluted to have clinical impact: in our study population, categorising bowel morphology as normal, spider-shaped (superficial) or crescentic/mushroom-(DIE) shaped and motility as normal, tethered (superficial) or distorted/fixed (deep endometriosis) correlates to subsequent surgical complexity.

Single-Fraction Radiosurgery Using Conservative Doses for Brain Metastases: Durable Responses in Select Primaries With Limited Toxicity.

BACKGROUND: Optimal doses for single-fraction stereotactic radiosurgery (SRS) in the treatment of brain metastases are not well established. Our institution utilized conservative dosing compared to maximum-tolerated doses from the Radiation Therapy Oncology Group 90-05 Phase I study. OBJECTIVE: To report individual lesion control (LC) from conservative single-fraction doses and determine factors affecting LC. METHODS: From 2003 to 2015, patients who underwent linear accelerator-based single-fraction SRS for cerebral/cerebellar metastases and receiving at least 1 follow-up magnetic resonance imaging (MRI) were identified. Lesion response was assessed by a size-based rating system and modified "Response Assessment in Neuro-Oncology Brain Metastases" (RANO-BM) criteria. RESULTS: Among 188 patients with 519 lesions, median survival was 13.1 mo; median follow-up time with MRI was 9.6 mo per course. Median tumor-periphery dose was 15 Gy (range: 7.5-20.7). Median lesion volume was 0.5 cc and diameter was 9 mm (range: 2-45). Concordance between RANO-BM and size-based system was 93%. Crude 1-yr LC was 80%, 73%, 56%, and 38% for lesions 1 to 10, 11 to 20, 21 to 30, >31 mm, respectively. On multivariate analysis, increased size, melanoma and colorectal histology, and progression after whole brain radiation therapy predicted worse LC. When excluding lesions treated as a boost, dose was a significant predictor of LC in multivariate models (hazard ratio 0.89, P = .01). Symptomatic radiation necrosis occurred in 10 lesions in 10 patients. CONCLUSION: Histology predicts LC after conservative SRS doses with evidence of a dose-response relationship. Conservative single-fraction SRS doses confer minimal toxicity and acceptable control in certain subgroups (breast cancer, <5 mm), with suboptimal control in larger lesions and in combination with whole brain radiation therapy.

Radiotherapy for Brain Metastases From Renal Cell Carcinoma in the Targeted Therapy Era: The University of Rochester Experience.

OBJECTIVES: Radiotherapy remains the standard approach for brain metastases from renal cell carcinoma (RCC). Kinase inhibitors (KI) have become standard of care for metastatic RCC. They also increase the radiosensitivity of various tumor types in preclinical models. Data are lacking regarding the effect of KIs among RCC patients undergoing radiotherapy for brain metastases. We report our experience of radiotherapy for brain metastatic RCC in the era of targeted therapy and analyzed effects of concurrent KI therapy. METHODS: We retrospectively analyzed 25 consecutive patients who received radiotherapy for brain metastases from RCC with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Kaplan-Meier rates of overall survival (OS) and brain progression-free survival (BPFS) were calculated and univariate analyses performed. RESULTS: Lower diagnosis-specific graded prognostic assessment (DS-GPA) score and multiple intracranial metastases were associated with decreased OS and BPFS on univariate analysis; DS-GPA is also a prognostic factor on multivariate analysis. There was no significant difference in OS or BPFS for SRS compared with WBRT or WBRT and SRS combined. The concurrent use of KI was not associated with any change in OS or BPFS. CONCLUSIONS: This hypothesis-generating analysis suggests among patients with brain metastatic RCC treated with the most current therapies, those selected to undergo SRS did not experience significantly different survival or control outcomes than those selected to undergo WBRT. From our experience to date, limited in patient numbers, there seems to be neither harm nor benefit in using concurrent KI therapy during radiotherapy. Given that most patients progress systemically, we would recommend considering KI use during brain radiotherapy in these patients.

Repeat courses of SRS in patients initially treated with SRS alone for brain-metastatic melanoma.

AIM: Stereotactic radiosurgery (SRS) is often used in the treatment of brain metastatic melanoma. Little data exist regarding outcomes of repeat course of SRS in this population. We aimed to identify treatment outcomes and toxicities in melanoma patients treated with repeat SRS after upfront SRS. PATIENTS & METHODS: We reviewed ten consecutive patients treated with repeat SRS following upfront SRS alone for brain metastatic melanoma. RESULTS: The median overall survival from initial treatment was 17.5 months. The median overall survival from repeat SRS was 6.7 months with a 6-month local control rate of 80%. The majority of patients progressed systemically before death. Four patients reported six adverse events, all grade 1. CONCLUSION: Prospective study regarding the safety and efficacy of repeat courses of SRS in patients with brain-metastatic melanoma, especially in combination with novel immunotherapies, is warranted.