How Does the Number of Brain Metastases Correlate With Normal Brain Exposure in Single-Isocenter Multitarget Multifraction Stereotactic Radiosurgery.

Purpose: To investigate the relationship between normal brain exposure in LINAC-based single-isocenter multitarget multifraction stereotactic radiosurgery or stereotactic radiation therapy (SRT) and the number or volume of treated brain metastases, especially for high numbers of metastases. Methods and Materials: A cohort of 44 SRT patients with 709 brain metastases was studied. Renormalizing to a uniform prescription of 27 Gy in 3 fractions, normal brain dose volume indices, including V23 Gy (volume receiving >23 Gy), V18 Gy (volume receiving >18 Gy), and mean dose, were evaluated on these plans against the number and the total volume of targets for each plan. To compare with exposures from whole-brain radiation therapy (WBRT), the SRT dose distributions were converted to equivalent dose in 3 Gy fractions (EQD3) using an alpha-beta ratio of 2 Gy. Results: With increasing number of targets and increasing total target volume, normal brain exposures to dose ≥18 Gy increases, and so does the mean normal brain dose. The factors of the number of targets and the total target volume are both significant, although the number of targets has a larger effect on the mean normal brain dose and the total target volume has a larger effect on V23 Gy and V18 Gy. The EQD3 mean normal brain dose with SRT planning is lower than conventional WBRT. On the other hand, SRT results in higher hot spot (ie, maximum dose outside of tumor) EQD3 dose than WBRT. Conclusions: Based on clinical SRT plans, our study provides information on correlations between normal brain exposure and the number and total volume of targets. As SRT becomes more greatly used for patients with increasingly extensive brain metastases, more clinical data on outcomes and toxicities is necessary to better define the normal brain dose constraints for high-exposure cases and to optimize the SRT management for those patients.

Dosimetric evaluation of LINAC-based single-isocenter multi-target multi-fraction stereotactic radiosurgery with more than 20 targets: comparing MME, HyperArc, and RapidArc.

BACKGROUND: To compare the dosimetric quality of three widely used techniques for LINAC-based single-isocenter multi-target multi-fraction stereotactic radiosurgery (fSRS) with more than 20 targets: dynamic conformal arc (DCA) in BrainLAB Multiple Metastases Elements (MME) module and volumetric modulated arc therapy (VMAT) using RapidArc (RA) and HyperArc (HA) in Varian Eclipse. METHODS: Ten patients who received single-isocenter fSRS with 20-37 targets were retrospectively replanned using MME, RA, and HA. Various dosimetric parameters, such as conformity index (CI), Paddick CI, gradient index (GI), normal brain dose exposures, maximum organ-at-risk (OAR) doses, and beam-on times were extracted and compared among the three techniques. Wilcoxon signed-rank test was used for statistical analysis. RESULTS: All plans achieved the prescribed dose coverage goal of at least 95% of the planning target volume (PTV). HA plans showed superior conformity compared to RA and MME plans. MME plans showed superior GI compared to RA and HA plans. RA plans resulted in significantly higher low and intermediate dose exposure to normal brain compared to HA and MME plans, especially for lower doses of ≥ 8Gy and ≥ 5Gy. No significant differences were observed in the maximum dose to OARs among the three techniques. The beam-on time of MME plans was about two times longer than RA and HA plans. CONCLUSIONS: HA plans achieved the best conformity, while MME plans achieved the best dose fall-off for LINAC-based single-isocenter multi-target multi-fraction SRS with more than 20 targets. The choice of the optimal technique should consider the trade-offs between dosimetric quality, beam-on time, and planning effort.

Association of Radiation Dose to the Amygdala-Orbitofrontal Network with Emotion Recognition Task Performance in Patients with Low-Grade and Benign Brain Tumors.

BACKGROUND: Although data are limited, difficulty in social cognition occurs in up to 83% of patients with brain tumors. It is unknown whether cranial radiation therapy (RT) dose to the amygdala-orbitofrontal network can impact social cognition. METHODS: We prospectively enrolled 51 patients with low-grade and benign brain tumors planned for cranial RT. We assessed longitudinal changes on an emotion recognition task (ERT) that measures the ability to recognize emotional states by displaying faces expressing six basic emotions and their association with the RT dose to the amygdala-orbitofrontal network. ERT outcomes included the median time to choose a response (ERTOMDRT) or correct response (ERTOMDCRT) and total correct responses (ERTHH). RESULTS: The RT dose to the amygdala-orbitofrontal network was significantly associated with longer median response times on the ERT. Increases in median response times occurred at lower doses than decreases in total correct responses. The medial orbitofrontal cortex was the most important variable on regression trees predicting change in the ERTOMDCRT. DISCUSSION: This is, to our knowledge, the first study to show that off-target RT dose to the amygdala-orbitofrontal network is associated with performance on a social cognition task, a facet of cognition that has previously not been mechanistically studied after cranial RT.

A comprehensive evaluation of advanced dose calculation algorithms for brain stereotactic radiosurgery.

PURPOSE: Accurate dose calculation is important in both target and low dose normal tissue regions for brain stereotactic radiosurgery (SRS). In this study, we aim to evaluate the dosimetric accuracy of the two advanced dose calculation algorithms for brain SRS. METHODS: Retrospective clinical case study and phantom study were performed. For the clinical study, 138 SRS patient plans (443 targets) were generated using BrainLab Elements Voxel Monte Carlo (VMC). To evaluate the dose calculation accuracy, the plans were exported into Eclipse and recalculated with Acuros XB (AXB) algorithm with identical beam parameters. The calculated dose at the target center (Dref), dose to 95% target volume (D95), and the average dose to target (Dmean) were compared. Also, the distance from the skull was analyzed. For the phantom study, a cylindrical phantom and a head phantom were used, and the delivered dose was measured by an ion chamber and EBT3 film, respectively, at various locations. The measurement was compared with the calculated doses from VMC and AXB. RESULTS: In clinical cases, VMC dose calculations tended to be higher than AXB. It was found that the difference in Dref showed > 5% in some cases for smaller volumes < 0.3 cm3 . Dmean and D95 differences were also higher for small targets. No obvious trend was found between the dose difference and the distance from the skull. In phantom studies, VMC dose was also higher than AXB for smaller targets, and VMC showed better agreement with the measurements than AXB for both point dose and high dose spread. CONCLUSION: The two advanced calculation algorithms were extensively compared. For brain SRS, AXB sometimes calculates a noticeable lower target dose for small targets than VMC, and VMC tends to have a slightly closer agreement with measurements than AXB.

Sustained Preservation of Cognition and Prevention of Patient-Reported Symptoms With Hippocampal Avoidance During Whole-Brain Radiation Therapy for Brain Metastases: Final Results of NRG Oncology CC001.

PURPOSE: Initial report of NRG Oncology CC001, a phase 3 trial of whole-brain radiation therapy plus memantine (WBRT + memantine) with or without hippocampal avoidance (HA), demonstrated neuroprotective effects of HA with a median follow-up of fewer than 8 months. Herein, we report the final results with complete cognition, patient-reported outcomes, and longer-term follow-up exceeding 1 year. METHODS AND MATERIALS: Adult patients with brain metastases were randomized to HA-WBRT + memantine or WBRT + memantine. The primary endpoint was time to cognitive function failure, defined as decline using the reliable change index on the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association, or the Trail Making Tests (TMT) A and B. Patient-reported symptom burden was assessed using the MD Anderson Symptom Inventory with Brain Tumor Module and EQ-5D-5L. RESULTS: Between July 2015 and March 2018, 518 patients were randomized. The median follow-up for living patients was 12.1 months. The addition of HA to WBRT + memantine prevented cognitive failure (adjusted hazard ratio, 0.74, P = .016) and was associated with less deterioration in TMT-B at 4 months (P = .012) and HVLT-R recognition at 4 (P = .055) and 6 months (P = .011). Longitudinal modeling of imputed data showed better preservation of all HVLT-R domains (P < .005). Patients who received HA-WBRT + Memantine reported less symptom burden at 6 (P < .001 using imputed data) and 12 months (P = .026 using complete-case data; P < .001 using imputed data), less symptom interference at 6 (P = .003 using complete-case data; P = .0016 using imputed data) and 12 months (P = .0027 using complete-case data; P = .0014 using imputed data), and fewer cognitive symptoms over time (P = .043 using imputed data). Treatment arms did not differ significantly in overall survival, intracranial progression-free survival, or toxicity. CONCLUSIONS: With median follow-up exceeding 1 year, HA during WBRT + memantine for brain metastases leads to sustained preservation of cognitive function and continued prevention of patient-reported neurologic symptoms, symptom interference, and cognitive symptoms with no difference in survival or toxicity.

Cognitive and neuroimaging outcomes in individuals with benign and low-grade brain tumours receiving radiotherapy: a protocol for a prospective cohort study.

INTRODUCTION: Radiation-induced cognitive decline (RICD) occurs in 50%-90% of adult patients 6 months post-treatment. In patients with low-grade and benign tumours with long expected survival, this is of paramount importance. Despite advances in radiation therapy (RT) treatment delivery, better understanding of structures important for RICD is necessary to improve cognitive outcomes. We hypothesise that RT may affect network topology and microstructural integrity on MRI prior to any gross anatomical or apparent cognitive changes. In this longitudinal cohort study, we aim to determine the effects of RT on brain structural and functional integrity and cognition. METHODS AND ANALYSIS: This study will enroll patients with benign and low-grade brain tumours receiving partial brain radiotherapy. Patients will receive either hypofractionated (>2 Gy/fraction) or conventionally fractionated (1.8-2 Gy/fraction) RT. All participants will be followed for 12 months, with MRIs conducted pre-RT and 6-month and 12 month post-RT, along with a battery of neurocognitive tests and questionnaires. The study was initiated in late 2018 and will continue enrolling through 2024 with final follow-ups completing in 2025. The neurocognitive battery assesses visual and verbal memory, attention, executive function, processing speed and emotional cognition. MRI protocols incorporate diffusion tensor imaging and resting state fMRI to assess structural connectivity and functional connectivity, respectively. We will estimate the association between radiation dose, imaging metrics and cognitive outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Research Subjects Review Board at the University of Rochester (STUDY00001512: Cognitive changes in patients receiving partial brain radiation). All results will be published in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04390906.

Patterns of recurrence after intracranial stereotactic radiosurgery for brain-only metastases from non-small cell lung cancer and the impact of upfront thoracic therapy with synchronous presentation.

Background: We characterized long-term organ-specific patterns of recurrence, time to progression (TTP) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) with brain-only metastases treated with single-fraction stereotactic radiosurgery (SRS) and analyzed the impact of upfront thoracic therapy (UTT) in those with synchronous presentation of primary NSCLC and brain metastases. Methods: The clinical records of 137 patients with brain metastases from NSCLC treated with intracranial SRS, and no other metastatic sites, were retrospectively reviewed. Patients with available follow-up imaging (n=124) were analyzed for patterns of recurrence; all were analyzed for OS. Results: The majority of first distant recurrences were in brain and thoracic sites, while extra-thoracic sites were relatively uncommon. After median follow-up of 16.0 months, 24.8% did not develop recurrence outside of brain and/or thoracic sites and 43.5% were free of distant extracranial recurrence. Whole brain radiotherapy (WBRT) and UTT, but not systemic therapy, altered patterns of recurrence and intracranial or extracranial TTP. Multivariable analysis revealed UTT, but not systemic therapy or WBRT, was associated with more favorable OS [hazard ratio (HR) 0.515, P=0.029] among 88 patients with synchronous presentation. Within the subgroup of thoracic stage III patients (n=69), those treated with UTT experienced remarkable median extracranial TTP and OS of 19.3 and 22.7 months, respectively. Conclusions: First and cumulative recurrences in patients treated with intracranial SRS for NSCLC metastases limited to brain are most often in the brain and thorax. Long-term survival is possible, regardless of thoracic stage, and is dependent on UTT among other factors.

New dosimetric guidelines for linear Boltzmann transport equations through comparative evaluation of stereotactic body radiation therapy for lung treatment planning.

PURPOSE: To propose guidelines for lung stereotactic body radiation therapy (SBRT) when using Acuros XB (AXB) equivalent to the existing ones developed for convolution algorithms such as analytic anisotropic algorithm (AAA), considering the difference between the algorithms. METHODS: A retrospective analysis was performed on 30 lung patients previously treated with SBRT. The original AAA plans, which were developed using dynamic conformal arcs, were recalculated and then renormalized for planning target volume (PTV) coverage using AXB. The recalculated and renormalized plans were compared to the original plans based on V100% and V90% PTV coverage, as well as V105%, conformality index, D2cm , Rx/Dmax , R50, and Dmin . These metrics were analyzed nominally and on variations according to RTOG and NRG guidelines. Based on the relative difference between each metric in the AAA and AXB plans, new guidelines were developed. The relative differences in our cohort were compared to previously documented AAA to AXB comparisons found in the literature. RESULTS: AAA plans recalculated in AXB had a significant reduction in most dosimetric metrics. The most notable changes were in V100% (4%) and the conformality index (7.5%). To achieve equal PTV coverage, AXB required an average of 1.8% more monitor units (MU). This fits well with previously published data. Applying the new guidelines to the AXB plans significantly increased the number of minor violations with no change in major violations, making them comparable to those of the original AAA plans. CONCLUSION: The relative difference found between AAA and AXB for SBRT lung plans has been shown to be consistent with previous works. Based on these findings, new guidelines for lung SBRT are recommended when planning with AXB.

Risk of brain metastases in T1-3N0 NSCLC: a population-based analysis.

AIM: Several consensus guidelines recommend against routine brain imaging at diagnosis of T1-3N0 non-small cell lung cancer (NSCLC). METHODS: From the Surveillance, Epidemiology and End Results registry, patients with pathologically confirmed T1-3N0 NSCLC were identified. Risks of brain metastases at time of initial diagnosis were analyzed. RESULTS: Patients selected to not undergo primary NSCLC resection had approximately tenfold greater incidence of brain metastases versus those who did. Younger age, adenocarcinoma histology, higher tumor stage and higher histologic grade were all significantly (p < 0.0001) associated with greater likelihood of presenting with brain metastases. CONCLUSION: Given the morbidity and mortality of brain metastases, routine brain screening after NSCLC diagnosis (particularly adenocarcinoma) may be justifiable, though more refined cost-benefit analyses are warranted.

Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001.

PURPOSE: Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS: This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS: Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [P = .049] and 16.4% v 33.3% [P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue (P = .04), less difficulty with remembering things (P = .01), and less difficulty with speaking (P = .049) and using imputed data, less interference of neurologic symptoms in daily activities (P = .008) and fewer cognitive symptoms (P = .01). CONCLUSION: HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.

Short course radiation therapy for rectal cancer in the elderly: can radical surgery be avoided?

Rectal cancer in elderly patients can be difficult to manage. Short course radiation therapy (SCRT) has shown to be effective when given immediately prior to surgery. Here we report outcomes of elderly patients who underwent SCRT either alone or prior to resection. Between 2010 and 2015, elderly patients with rectal cancer and no distant metastatic disease were identified. Symptoms at diagnosis, therapies, toxicities, and pathologic and clinical response were recorded from patient charts. The SCRT prescription dose was 5 Gy ×5 to the rectal tumor and 4 Gy ×5 to the mesorectum, omitting the iliac nodes. Twenty patients were identified with median age of 85 years (range, 71-93 years). No patient received systemic therapy. Sixty percent of patients were cT3 at diagnosis. Half underwent resection post SCRT and half received SCRT as definitive therapy. The 1- and 2-year overall survival was 75% and 54%. Overall survival did not differ between patients treated with SCRT and surgery compared to SCRT alone (P=0.8). Of the 10 surgical patients, 3 had a complete pathologic response at time of resection and 3 patients died within 2 weeks due to perioperative complications. Of patients treated with SCRT alone, 8 were symptomatic at presentation and 5 had a clinician defined symptomatic response. No patient treated with SCRT monotherapy required additional palliative measures for outflow obstruction, but 2 progressed locally and died. SCRT is well tolerated, results in pathologic complete responses in a small percentage of patients, and achieves 63% symptom improvement rate as monotherapy. A high peri-operative complication rate was observed in this small series. In elderly patients, SCRT as initial treatment with a watch and wait approach for surgery is feasible and should be evaluated prospectively.

Radiation-Induced Edema After Single-Fraction or Multifraction Stereotactic Radiosurgery for Meningioma: A Critical Review.

PURPOSE: Potential dosimetric and clinicopathologic predictors of radiation-induced brain edema after single-fraction or multifraction stereotactic radiosurgery (SRS) for non-base of skull (non-BOS) meningiomas are summarized based on a systematic review of the published literature. METHODS AND MATERIALS: Reviewed studies (PubMed indexed from 1998 through 2017) included all or some non-BOS meningioma patients, reported risks of edema after SRS, and correlated dosimetric and/or nondosimetric measures with the magnitude of risk. RESULTS: Twenty-six studies reporting risks of edema after SRS for meningioma are reviewed. The treatment techniques as well as distribution of tumor locations, target dosing, and target volume varied across studies. Among 13 studies that included only non-BOS tumors or separately grouped non-BOS tumors, symptomatic edema occurred in 5% to 43% of patients and any edema occurred in 28% to 50%. The reported average time to onset of edema ranged from approximately 3 to 9 months in most studies. Factors reported to significantly correlate with increased risks of edema and/or symptomatic edema after SRS for meningioma include the following: greater tumor margin and/or maximum dose, greater tumor size and/or volume, non-BOS (particularly parasagittal) location, no prior resection for meningioma, and presence of pretreatment edema. Nevertheless, the extent and significance of these factors were inconsistent across studies. Potentially important dosimetric factors, such as volume of brain or tissue receiving single-fraction doses > 10 to 12 Gy, are not well studied. CONCLUSIONS: The variability in risks of edema and in factors impacting those risks is likely a result of differences across studies in the clinicopathologic characteristics of the patient populations, as well as differences in treatment modalities and SRS planning and delivery parameters. More studies on pooled populations, grouped by potential prognostic factors such as tumor location and prior therapy, are needed to better understand dosimetric and nondosimetric factors predictive of edema risk after SRS for meningioma.

Impact of Right-sided Primary Tumor Location Among Patients With Oligometastatic Colorectal Cancer Treated With Stereotactic Body Radiotherapy.

INTRODUCTION: Among patients with colorectal cancer, those with right-sided primary tumors have worse outcomes in both the primary and metastatic setting. Patients with oligometastatic colorectal cancer (OMCC) have improved prognosis relative to those with diffusely metastatic disease. We aimed to assess if the trend toward worse outcomes with right-sided tumors remained in the oligometastatic setting. PATIENTS AND METHODS: We analyzed 31 patients treated at a single institution with stereotactic body radiotherapy for OMCC from 2011 to 2014 to assess the impact that primary tumor location had on overall survival (OS) and progression-free survival (PFS). RESULTS: Overall, patient local control was fair (66% at 2 y); however, distant control was only 37.4% at 2 years. The median OS was 2.4 years; the median PFS was 6.5 months. Patients with right-sided primary tumors had numerically worse median OS than those with left-sided or rectal primary tumors (1.4 vs. 3.7 y, P=0.09). Median PFS was significantly worse among those with right-sided primaries (2.9 vs. 10.8 mo, P=0.05). This held on multivariate analysis. CONCLUSIONS: These results affirm that patients with OMCC have extended OS periods and that stereotactic body radiotherapy offers strong local control in these settings. We show that even in the oligometastatic setting those with right-sided primary tumors have worse outcomes relative to those with left-sided or rectal primary tumors. This suggests more aggressive treatment may be needed for those with oligometastatic right-sided colorectal cancer.

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.

Stereotactic Body Radiotherapy for Lung Metastases from Colorectal Cancer: Prognostic Factors for Disease Control and Survival.

OBJECTIVES: To evaluate disease control and survival after stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer and to identify prognostic factors after treatment. METHODS: Patients with metastatic colorectal cancer to the lungs treated with SBRT from 2002 to 2013 were identified from a prospectively maintained database. Patients may have received prior systemic therapy, radiotherapy to nonthoracic sites and/or resection of thoracic and/or nonthoracic metastases. Endpoints were timed from end of SBRT and included overall survival (OS), progression-free survival, distant metastases-free survival, and local failure-free survival. Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors. RESULTS: Sixty-five patients were identified. Before SBRT, 69.2% and 33.8% of patients received systemic therapy and lung-directed local therapy, respectively, for metastatic disease. At the time of SBRT, 64.6% had lung-only involvement. Median survivals were: OS of 20.3 months (95% confidence intervals [CI], 15.9-27.0 mo), progression-free survival of 5.7 months (95% CI, 3.2-7.0 mo), distant metastases-free survival of 5.8 months (95% CI, 3.2-7.6 mo), and local failure-free survival of 15.4 months (95% CI, 8.5-21.1 mo). Nearly all (98%) patients developed distant progression. Extra lung and liver involvement at the time of initial metastases (hazard ratios [HR] 2.10) and extra lung involvement at SBRT (HR 2.67) were the only independent predictors of OS. Net gross target volume of >14.1 mL (HR 2.49) was the only independent predictor of local failure-free survival. CONCLUSIONS: Reasonable survival and local control can be achieved with SBRT. We identified several prognostic factors testable in future prospective trials that may help improve patient selection.

SBRT for Hepatocellular Carcinoma: 8-Year Experience from a Regional Transplant Center.

PURPOSE: The study aimed to evaluate stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) in patients not eligible for liver transplant (LT). METHODS: We retrospectively identified transplant-ineligible HCC patients treated with SBRT to the liver between 2004 and 2013. Our primary endpoint was overall survival (OS). We also report treatment toxicities using CTCAE 3.0, radiographic response, and patterns of failure. RESULTS: We identified 93 patients with median age at SBRT of 65.8 years. Forty-six percent were classified as Child-Pugh B or C and 85% had an Eastern Cooperative Oncology Group performance status of 1-2. After SBRT, 86% of patients experienced no or mild treatment-related adverse events. Only 8% of patients experienced grade 3 and 2% of patients experienced grade 4 adverse events. Overall radiographic response was complete in 1.2%, partial in 35.4%, stable in 43.9%, and progressive disease in 19.5%. Median OS was 8.8 months with 1-, 2-, and 3-year OS rates of 38.0, 29.8 and 21.2%, respectively. The Cancer of the Liver Italian Program (CLIP) score was found to strongly correlate with survival. Median OS for patients with CLIP scores of 0, 1, 2, and 3 was 21.1, 8.5, 5.1, and 7.1 months, respectively (p = 0.003). CONCLUSION: Our series demonstrates that SBRT is generally safe for HCC patients, even those with advanced liver failure. Although survival is generally poor, we were able to identify a group of patients with good liver function and early tumor stage who can achieve median OS of close to 2 years with SBRT.

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.

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.