Postoperative stereotactic radiosurgery for patients with resected brain metastases: a volumetric analysis.

PURPOSE: Postoperative stereotactic radiosurgery (SRS) is increasingly utilized following resection of brain metastases (BM); however, there are no volumetric data guiding dose selection. We performed a volumetric analysis to guide cavity SRS dosing for resected BM. METHODS: 83 consecutive patients with gross total resection who underwent postoperative SRS to 90 cavities were identified. The 12 Gy isodose lines (V12total) along with the volume of brain parenchyma receiving 12 Gy excluding cavity fluid, ventricular fluid, and calvarium (V12parenchyma) were contoured. Local recurrence (LR) and radionecrosis (RN) were calculated using cumulative incidence rates. Multivariate analysis (MVA) and cutpoint analysis were conducted. RESULTS: Median follow-up was 12.3 months; median dose was 16 Gy. 1- and 2-year cumulative incidence rates of LR were 7.9% and 11.0%. Radiation dose [hazard ratio (HR) 2.04, p = 0.002] was significantly associated with time to LR on MVA. 1- and 2-year cumulative incidence rates of RN were 2.6% and 5.5% respectively. MVA demonstrated increased risk of RN with a larger V12parenchyma (HR 1.46, p = 0.0496). Cavities ≤ 10 cc showed a low 2-year RN risk (4.3%), but had a modest LR risk (13.9%). A radiation dose ≥ 18 Gy significantly improved LC (HR 4.79, p = 0.01). CONCLUSIONS: V12parenchyma should be examined in postoperative SRS to assess RN risk. Cavities > 10 cc treated with 16 Gy achieved excellent LC and minimal RN at 2 years. Cavities ≤ 10 cc may be better treated with a dose ≥ 18 Gy to significantly improve LC given the low RN rate observed with 16 Gy.

Postsurgical Cavity Evolution After Brain Metastasis Resection: How Soon Should Postoperative Radiosurgery Follow?

BACKGROUND: Postoperative stereotactic radiosurgery (SRS) to the cavity after resection of brain metastases improves local control. We hypothesized that significant cavity constriction would occur from the immediate postoperative period to the time of SRS and aimed to elucidate optimal treatment timing. METHODS: We retrospectively reviewed 79 consecutive patients with 85 resection cavities treated with SRS after gross total resection of a brain metastasis. Preoperative lesion, immediate postoperative cavity, and cavity at the time of SRS were contoured for each patient. Factors influencing cavity size and interval cavity change were analyzed. RESULTS: Median immediate postoperative cavity volume was 7.5 cm3, and median SRS cavity volume was 8.7 cm3. Median time from surgery to SRS was 20 days. Median volumetric cavity change was an increase of 28%. Of cavities, 34 (40%) increased in size >2 cm3, whereas only 8 cavities (9%) decreased in size >2 cm3; 43 cavities (51%) had ≤2 cm3 change. The largest postoperative cavities experienced the smallest percentage cavity change in the time interval to SRS (Spearman correlation -0.32, P = 0.003). CONCLUSIONS: Cavity size after brain metastasis resection increased a median of 28% from immediate postoperative scan to time of SRS. Greater than 90% of postoperative cavities either increased >2 cm3 or remained within 2 cm3 of their immediate postoperative cavity volume. Early postoperative SRS within 2-3 weeks may be appropriate to minimize cavity growth. Delaying postoperative SRS beyond 3 weeks in hopes of significant cavity contraction is not warranted.

Dejerine-Roussy syndrome from thalamic metastasis treated with stereotactic radiosurgery.

Dejerine-Roussy syndrome (central thalamic pain) is associated with damage to the ventral posterior sensory nuclei of the thalamus. We report a patient with breast cancer who developed contralateral hemibody paresthesias and dysesthesias. MR imaging revealed limited volume intracranial metastatic disease including a right posterior thalamic lesion. Stereotactic radiosurgery was utilized to selectively treat the lesion while preserving the remaining thalamus. Two months following treatment, the patient reported vastly improved to complete resolution of her sensory symptoms. This is the first reported case of thalamic tumor directed radiosurgical treatment leading to resolution of central neuropathic pain.

Single Fraction Stereotactic Radiosurgery for Retreatment of Skull Base Recurrent Head and Neck Malignancies.

INTRODUCTION: Recurrent head and neck carcinomas are notoriously difficult to treat. Salvage surgery, brachytherapy, and repeat external beam radiotherapy have all been utilized, achieving modest local control at the expense of elevated toxicity. We performed a retrospective review to evaluate the efficacy of single fraction stereotactic radiosurgery (SRS) for the treatment of recurrent head and neck carcinomas. METHODS: Eighteen previously irradiated patients diagnosed with a locoregionally recurrent head and neck malignancy and treated with single fraction SRS from 2000 to 2016 were analyzed. Actuarial rates for local control (LC) and overall survival (OS) were calculated with Kaplan-Meier estimates. RESULTS: Median follow-up was 16.1 months and SRS dose was 13.3 Gy. One-year rate of LC was 52.7% (95% confidence interval [CI] 29%-72%). Median OS was 25.4 months. Parotid gland primary had an increased risk of progressive disease (PD) following SRS (hazard ratio [HR] 4.24, p=0.02). Squamous cell histology was negatively associated with OS (HR 3.85, p=0.03). One patient experienced grade 2 radionecrosis. CONCLUSIONS: Single fraction SRS is an acceptable treatment for previously irradiated patients with recurrent head and neck primary malignancies. Dose escalation to optimize LC should be examined.

Multi-institutional external validation of a novel glioblastoma prognostic nomogram incorporating MGMT methylation.

A recent nomogram for glioblastoma (GBM) was designed to incorporate methylguanine-DNA methyltransferase (MGMT) methylation status in trial patients receiving temozolomide. Since clinical trial patients are strictly selected, compared to the general population, we performed a multi-institutional, external, independent assessment of the nomogram. Consecutive adult patients with supratentorial GBM diagnosed between June 2007 and December 2014 who initiated TMZ-based concurrent chemoradiotherapy (CRT) and were not enrolled on RTOG 0525 or 0825 were eligible. We collected age, gender, MGMT status, performance status, resection extent, race, and tumor site and Cox regression analysis of overall survival (OS) was conducted with the 1-year nomogram-predicted survival (NPS). The predictive accuracy was quantified by the concordance index (c-index) as well as by separating patients into quintile-groups of the population distribution of NPS and comparing mean NPS and observed OS. Of 514 patients with GBM, 309 had all nomogram factors. Median OS was 18.7 months. NPS and observed OS demonstrated a c-index of 0.695. On univariate analysis, the NPS and all included factors except gender were significant. On multivariable analysis (MVA) the only significant factor for worse survival was lower NPS. When separated into quintile-groups of NPS, the observed survival was slightly better than the predicted survival for all but the worst prognostic group. Our multi-institutional cohort provides independent external validation of a novel GBM nomogram incorporating MGMT methylation status. No individual factor included in the nomogram retained significance on MVA after adjusting for NPS.

Stereotactic radiosurgery for brain metastases from primary head and neck carcinomas: a retrospective analysis.

Patients with head and neck malignancies commonly develop metastatic disease, yet rarely do these carcinomas metastasize to the brain. Stereotactic radiosurgery (SRS) is routinely employed to treat brain metastases (BM). This study was undertaken to examine the efficacy of SRS for BM from primary head and neck carcinomas. From 2000 to 2016, a total of 19 patients with 38 lesions were retrospectively identified. All patients presented with a primary head and neck malignancy and subsequently developed metastatic disease to the brain treated with SRS at our institution. Actuarial rates for overall survival (OS), local control (LC) and distant brain metastases (DBM) were calculated using Kaplan-Meier estimates. Median follow up was 6.8 months and median survival was 15.8 months. Eleven lesions received post-operative SRS to a surgical cavity and 27 lesions received definitive SRS to a metastasis. The median dose prescribed was 18 Gy. One-year actuarial rate for LC was 77.3% (95% confidence interval [CI] 44-92%) while 1 year and 2 year rates of OS were 52.9% (CI 28-73%) and 31.7% (CI 11-55%) respectively. The median time to develop DBM was 8.4 months. Three patients (16%) underwent repeat SRS following development of new BM and three patients (16%) underwent salvage whole brain radiotherapy (WBRT). SRS may be utilized in the treatment of patients with primary head and neck malignancies metastasized to the brain with high efficacy. Patients with well-controlled systemic disease and good performance status may benefit the most from definitive SRS while avoiding WBRT.

Do changes in interfraction organ at risk volume and cylinder insertion geometry impact delivered dose in high-dose-rate vaginal cuff brachytherapy?

PURPOSE: Within a multifraction high-dose-rate vaginal cuff brachytherapy course, we determined if individual variations in organ at risk (OAR) volume and cylinder insertion geometry (CIG) impacted dose and whether planned minus fractional (P - F) differences led to a discrepancy between planned dose and delivered dose. METHODS AND MATERIALS: We analyzed vaginal cuff brachytherapy applications from consecutive patients treated with three fractions of 5 Gy after each undergoing a planning CT and three repeat fractional CTs (fCTs). Rectal and bladder D2ccs and volumes were recorded in addition to the x (in relationship to midplane) and y (in relationship to the table) angles of CIG. Paired t-tests and multiple regression analyses were performed. RESULTS: Twenty-seven patients were identified. In comparing the planning CT vs. mean fCT rectal volumes, bladder volumes, x angles, and y angles, only bladder volume was significantly different (planned volume higher, t = 2.433, p = 0.017). The cumulative mean planned OAR D2cc vs. delivered D2cc was only significantly different for the bladder (planned dose lower, t = -2.025, p = 0.053). Regression analysis revealed planned rectal D2cc (p < 0.0003) and a positive (posterior) y insertion angle (p = 0.015) to significantly impact delivered rectal D2cc. Additionally, P - F rectal volume (p = 0.037) was significant in determining rectal delivered dose. CONCLUSIONS: A more posterior y angle of insertion was found to increase rectal D2cc leading us to believe that angling the vaginal cylinder anteriorly may reduce rectal dose without significantly increasing bladder dose. Although attention should be paid to OAR volume and CIG to minimize OAR dose, the clinical significance of P - F changes remains yet to be shown.

Postoperative radiation therapy for parotid pleomorphic adenoma with close or positive margins: treatment outcomes and toxicities.

AIM: To evaluate the locoregional control and treatment toxicity of patients with pleomorphic adenoma after resection with close or positive margins followed by postoperative radiation therapy (PORT). PATIENTS AND METHODS: Between 2002 and 2011, twenty-one patients underwent PORT at the Mount Sinai Beth Israel Medical Center for pleomorphic adenoma of the parotid with close or positive margins. Four out of the 21 patients (19%) had recurrent lesions. The median dose was 57.6 Gy (range 55.8-69.96) delivered at 1.8-2.12 Gy/fraction. Treatment and follow-up data were retrospectively analyzed for locoregional control as well as acute- and late-treatment toxicities. Actuarial survival analysis was also performed. RESULTS: Twelve women and 9 men with a median age of 46 (26-65) at PORT were included in this study. Eighty-one percent of the cohort had positive resection margins while 19% had close margins. At a median follow-up of 92 months, 19/21 patients (90%) had locoregional control. Two patients who failed had primary lesions which recurred locally, and initially had positive margins. The two recurrences occurred at 8 months and 12 months. Acute Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicities were experienced by 11 (52%) and 4 (19%) patients, respectively, while 2 (10%) experienced late RTOG grade 1 toxicities. No patients experienced any grade 2-4 late toxicities. Actuarial survival was 100%. CONCLUSION: PORT for patients with pleomorphic adenoma of the parotid gland after resection with close or positive margins results in excellent locoregional control and low treatment-related morbidity.

Blue rubber bleb nevus syndrome: novel lymphangiomatosis-like growth pattern within the uterus and immunohistochemical analysis.

Blue Rubber Bleb Nevus Syndrome is a rare, primarily sporadic condition characterized by vascular lesions principally involving the skin and gastrointestinal tract. Although considered a venous malformation, telangiectatic capillaries, arteriovenous malformations, and lymphangiomas have been reported, but a lymphangiomatosis-like growth pattern has not been described. This case of Blue Rubber Bleb Nevus Syndrome demonstrated a labyrinth of variably sized vascular spaces lined by an attenuated layer of bland endothelial cells, dissecting uterine tissues and sequestering remaining myometrium. Immunohistochemical profile of lesional endothelial cells from the myometrium included strong, diffuse CD31; variable CD34; strong, patchy D2-40; weak, patchy factor VIII-related antigen; focal linear subendothelial collagen type IV; Ki-67 in 1% of cells; and no GLUT-1 or WT1 expression. This report expands the morphological spectrum of vascular lesions in Blue Rubber Bleb Nevus Syndrome to include a lymphangiomatosis-like growth pattern and the immunohistochemistry suggests dual vascular and lymphatic differentiation, supporting the current belief that these lesions are malformations.