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John Suh

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Papers by John Suh

CMET-11. Impact of Tumor Size and Molecular Profile on Local Control in Patients with Breast Cancer Brain Metastases: Understanding Tumor Biology and Radiosurgery Dosing

Neuro-Oncology

NEURO-ONCOLOGY • NOVEMBER 2017 to melanoma brain metastases was increased cMET expression frequen... more NEURO-ONCOLOGY • NOVEMBER 2017 to melanoma brain metastases was increased cMET expression frequency relative to the primary (36.4% versus 7.9%, P=0.0003). CONCLUSION: We report enriched expression of markers associated with DNA synthesis, replication, and repair in brain metastases compared with primary cancer specimens. This trend occurred across all tumor histologies, supporting the prioritization of therapies that target these pathways.

Is there a volume threshold of brain metastases for Linac-based stereotactic radiotherapy?

Purpose To investigate whether there is a volume threshold in target volume of brain metastases b... more Purpose To investigate whether there is a volume threshold in target volume of brain metastases below which a small cone size and sharp penumbra in Gamma Knife (GK) may provide improved plan quality when compared to Volumetric Modulated Arc Therapy (VMAT)-based stereotactic radiosurgery (SRS). Methods For patients treated on GK SRS for brain metastases in 2018-2019 in our institution, 121 patients with two and three targets were identified. Twenty-six patients with two or three brain metastases (total of 76 lesions) were selected for this study. Two VMAT plans, SmartArc (Pinnacle) and HyperArc (Eclipse), were generated retrospectively for each patient. Plan quality was evaluated based on RTOG conformity index (CI), Paddick gradient index (GI), normal tissue (NT) V12Gy and V4.5Gy. By using the receiver operating characteristic (ROC) curve for both VMAT plans (SmartArc and HyperArc) and metrics of RTOG CI and NT V12Gy, we compared GK plans to SmartArc and HyperArc plans separately to ...

NIMG-02. 18F-FLUCICLOVINE Positron Emission Tomography to Distinguish Tumor Progression from Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastasis: A Qualitative Analysis

Neuro-Oncology

PURPOSE/OBJECTIVE(S) To assess the ability of 18F-Fluciclovine PET/CT to distinguish radiation ne... more PURPOSE/OBJECTIVE(S) To assess the ability of 18F-Fluciclovine PET/CT to distinguish radiation necrosis (RN) from tumor progression (TP) among patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) in a prospective pilot study. MATERIALS/METHODS Adults with post-SRS BM presenting with follow-up brain MRI equivocal for RN versus TP underwent 18F-Fluciclovine PET/CT within 30 days of equivocal MRI. PET images were reconstructed using a point-spread-function algorithm. Three physician reviewers independently performed qualitative analyses of each lesion using a three-point visual score relative to PET-avidity of blood pool and parotid. Quantitative metrics for each lesion were documented. Reference standard was clinical follow-up with brain MRI until tumor board consensus or tissue confirmation. Nonparametric estimates of area under the receiver operating characteristic curve (AUC) for clustered data were estimated, with diagnostic performance based on visual ...

Stereotactic Radiosurgery for Postoperative Spine Malignancy: A Systematic Review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines

Practical Radiation Oncology

PURPOSE To determine safety and efficacy of postoperative spine stereotactic body radiation thera... more PURPOSE To determine safety and efficacy of postoperative spine stereotactic body radiation therapy (SBRT) in the published literature, and to present practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). MATERIALS AND METHODS A systematic review of the literature was performed, specific to postoperative spine SBRT, using PubMed and Embase databases. A meta-analysis for 1-year local control (LC), overall survival (OS) and vertebral compression fracture (VCF) probability was conducted. RESULTS The literature search revealed 251 potentially relevant articles after duplicates were removed. Of these 56 were reviewed in-depth for eligibility and 12 met all the inclusion criteria for analysis. 7 studies were retrospective, 2 prospective observational and 3 were prospective phase I/II clinical trials. Outcomes for a total of 461 patients and 499 spinal segments were reported. 10 studies used an MRI fused to CT-simulation for treatment planning, 2 investigations reported on all patients receiving a CT-myelogram at the time of planning. Meta-analysis for 1 year LC and OS was 88.9% and 57%, respectively. The crude reported VCF rate was 5.6%. One case of myelopathy was described in a patient with a previously irradiated spinal segment. One patient developed an esophageal fistula requiring surgical repair. CONCLUSIONS Postoperative spine SBRT delivers a high 1-year LC with acceptably low toxicity. Patients that may benefit from this include those with oligometastatic disease, radioresistant histology, paraspinal masses and/or those with a history of prior irradiation to the affected spinal segment. The ISRS recommends a minimum interval of 8 to 14 days after invasive surgery prior to simulation for SBRT, with initiation of radiotherapy within 4 weeks of surgery. An MRI fused to the planning CT, and/or the use of a CT-myelogram, are necessary for target and organ-at-risk delineation. A planning organ-at-risk volume (PRV) of 1.5 to 2mm for the spinal cord is advised.

$Research paper thumbnail of The Judicious Use of Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy in the Management of Large Brain Metastases$

The Judicious Use of Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy in the Management of Large Brain Metastases

Cancers

Brain metastases are the most common intracranial malignant tumor in adults and are a cause of si... more Brain metastases are the most common intracranial malignant tumor in adults and are a cause of significant morbidity and mortality for cancer patients. Large brain metastases, defined as tumors with a maximum dimension >2 cm, present a unique clinical challenge for the delivery of stereotactic radiosurgery (SRS) as patients often present with neurologic symptoms that require expeditious treatment that must also be balanced against the potential consequences of surgery and radiation therapy—namely, leptomeningeal disease (LMD) and radionecrosis (RN). Hypofractionated stereotactic radiotherapy (HSRT) and pre-operative SRS have emerged as novel treatment techniques to help improve local control rates and reduce rates of RN and LMD for this patient population commonly managed with post-operative SRS. Recent literature suggests that pre-operative SRS can potentially half the risk of LMD compared to post-operative SRS and that HSRT can improve risk of RN to less than 10% while improvin...

CMET-18. Impact of Kras Mutation Status on the Efficacy of Immunotherapy in Lung Cancer Brain Metastases

Neuro-Oncology

BACKGROUND Immunotherapy is increasingly used in patients with non-small cell lung cancer brain m... more BACKGROUND Immunotherapy is increasingly used in patients with non-small cell lung cancer brain metastases (NSCLCBM). KRAS mutations are associated with worse prognosis and there is no FDA approved targeted therapy. KRAS mutations are associated with increased expression of PD-L1. We evaluated the outcomes of NSCLCBM with KRAS mutations treated with immune checkpoint inhibitors (ICI). METHODS We reviewed 800 patients with NSCLCBM treated at our tertiary care center. 226 had known KRAS mutational status, 121 of which received immunotherapy. Overall survival (OS) was calculated from either the start of immunotherapy (when both groups received immunotherapy) or from the date of diagnosis of brain metastasis. Kaplan-Meier method and Cox Proportional hazard model were utilized to determine differences in OS and the Chi-square test was utilized to determine differences in PD-L1 expression. RESULTS In 109 patients where both KRAS and PD-L1 status were known, KRAS mutations had greater PD-L...

Risk Factors for Malignant Transformation of Low-Grade Glioma

International journal of radiation oncology, biology, physics, Jan 15, 2018

The incidence, risk factors, and outcomes of low-grade glioma patients who undergo malignant tran... more The incidence, risk factors, and outcomes of low-grade glioma patients who undergo malignant transformation (MT) in the era of temozolomide are not well known. This study evaluates these factors in a large group of World Health Organization grade 2 glioma patients treated at a tertiary-care institution. Patient, tumor, and treatment factors were analyzed using an institutional review board-approved low-grade glioma database. Characteristics were compared using χand Wilcoxon signed rank tests. Time to event was summarized using proportional hazards models. Univariate and multivariate survival analyses were performed. Of a total of 599 patients, 124 underwent MT; 76 (61.3%) had biopsy-proven MT. The MT incidence was 21%, and the median time to MT was 56.4 months. The 5- and 10-year progression-free survival rates were 30.6% ± 4.2% and 4.8% ± 1.9%, respectively, for MT patients and 60% ± 2.4% and 38% ± 2.7%, respectively, for non-MT patients. The 5- and 10-year overall survival rates w...

Clinical trial design for local therapies for brain metastases: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group

The Lancet. Oncology, 2018

The goals of therapeutic and biomarker development form the foundation of clinical trial design, ... more The goals of therapeutic and biomarker development form the foundation of clinical trial design, and change considerably from early-phase to late-phase trials. From these goals, decisions on specific clinical trial design elements, such as endpoint selection and statistical approaches, are formed. Whereas early-phase trials might focus on finding a therapeutic signal to make decisions on further development, late-phase trials focus on the confirmation of therapeutic impact by considering clinically meaningful endpoints. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we highlight issues related to, and provide recommendations for, the design of clinical trials on local therapies for CNS metastases from solid tumours. We discuss endpoint selection criteria, the analysis appropriate for early-phase and late-phase trials, the association between tumour-specific and clinically meaningful endpoints, and possible issues related to...

Long-Term Outcome Following Stereotactic Radiosurgery for Glomus Jugulare Tumors: A Single Institution Experience of 20 Years

Neurosurgery, Jan 4, 2017

Glomus jugulare tumors (GJTs) are rare benign tumors, which pose significant treatment challenges... more Glomus jugulare tumors (GJTs) are rare benign tumors, which pose significant treatment challenges due to proximity to critical structures. To evaluate the long-term clinical and radiological outcome in patients undergoing stereotactic radiosurgery (SRS) for GJTs through retrospective study. Forty-two patients with 43 GJTs were treated using Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden) at our institute from 1997 to 2016. Clinical, imaging, and radiosurgery data were collected from an institutional review board approved database. Most patients were females (n = 35, 83.3%) and median age was 61 yr (range 23-88 yr). Median tumor volume and diameter were 5 cc and 3 cm, respectively, with a median follow-up of 62.3 mo (3.4-218.6 mo). Overall, 20 patients (47.6%) improved clinically and 14 (33.3%) remained unchanged at last follow-up. New onset or worsening of hearing loss was noted in 6 patients (17.2%) after SRS. The median prescription dose to the tumor margin was 15 Gy...

Validation of the Disease-Specific GPA for Patients With 1 to 3 Synchronous Brain Metastases in Newly Diagnosed NSCLC

Clinical Lung Cancer

The disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful pro... more The disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful prognostic tool but has not been validated for patients with synchronous brain metastases (SBM) in newly diagnosed non-small-cell lung cancer (NSCLC). We identified patients with newly diagnosed NSCLC with 1 to 3 SBM treated with stereotactic radiosurgery (SRS) between 1997 and 2012. We included patients whose brain metastases were treated with SRS alone or combined SRS and whole-brain radiotherapy (WBRT). Patients were stratified according to NSCLC DS-GPA to evaluate the accuracy of survival estimates. One hundred sixty-four patients were treated with either SRS alone (n = 85; 52%) or SRS and WBRT (n = 79; 48%). Median overall survival (OS) stratified according to DS-GPA of 0 to 1, 1.5 to 2, 2.5 to 3, and 3.5 to 4 were 2.8, 6.7, 9.8, and 13.2 months, respectively, consistent with OS reported for brain metastases in NSCLC DS-GPA (3.0, 6.5, 11.3, and 14.8 months, respectively). No difference in median progression-free survival or OS was noted with combined use of SRS and WBRT: 6.0 versus 6.1 months (P = .81) and 8.5 versus 9.1 months (P = .093), respectively. In multivariable analysis, Karnofsky performance status (hazard ratio [HR], 0.98; P = .008), extracranial metastases (HR, 0.498; P = .0003), squamous histology (HR, 1.81; P = .02), and number of brain metastases (2 vs. 1; HR, 1.504; P = .04, and 3 vs. 1; HR, 1.66; P = .05) were significant predictors of OS. The DS-GPA accurately estimates the prognosis of patients with SBM in newly diagnosed NSCLC. Patients with synchronous brain metastasis in newly diagnosed NSCLC should be carefully stratified for consideration of aggressive therapy.

Stereotactic Radiosurgery for Trigeminal Neuralgia Improves Patient-Reported Quality of Life and Reduces Depression

International Journal of Radiation Oncology*Biology*Physics

To characterize quality-of-life (QOL) outcomes after stereotactic radiosurgery (SRS) for trigemin... more To characterize quality-of-life (QOL) outcomes after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). The EuroQOL 5 Dimensions (EQ-5D) and Patient Health Questionnaire 9 (PHQ-9) were prospectively collected before and after SRS for 50 patients with TN. Pain response and treatment-related facial numbness were classified by Barrow Neurological Institute (BNI) scales. Differences in pooled QOL outcomes were tested with paired t tests and sign tests. The Kaplan-Meier method was used to estimate time-dependent improvements in the EQ-5D index, EQ-5D perceived health status (PHS), PHQ-9 score, and freedom from pain failure (BNI class IV-V) or facial numbness (BNI class III-IV). Following SRS, the 12-month rate of freedom from pain failure was 92% (95% confidence interval [CI], 77%-97%) while the 12-month rate of freedom from facial numbness was 89% (95% CI, 66%-97%). Significant improvements in the EQ-5D index (P&amp;amp;amp;amp;lt;.01), PHS (P=.01), and PHQ-9 (P=.03) were observed, driven by the EQ-5D subscores for self-care and for pain and/or discomfort (P=.02 and P&amp;amp;amp;amp;lt;.01, respectively). At 12 months after SRS, the actuarial rates of improvement in the EQ-5D, PHS, and PHQ-9 were 55% (95% CI, 40%-70%), 59% (95% CI, 40%-76%), and 59% (95% CI, 39%-76%), respectively. The median time to improvement in each of the QOL measures was 9 months (95% CI, 3-36 months) for the EQ-5D index, 5 months (95% CI, 3-36 months) for PHS, and 9 months (95% CI, 3-18 months) for the PHQ-9. On multivariate analysis, only higher prescription dose (86 Gy vs ≤82 Gy) was associated with improvement in the EQ-5D index (hazard ratio, 5.73; 95% CI, 1.85-22.33; P&amp;amp;amp;amp;lt;.01). Patients with TN treated with SRS reported significant improvements in multiple QOL measures, with the therapeutic benefit strongly driven by improvements in pain and/or discomfort and in self-care, along with lower rates of depression. In this analysis, there appears to be a correlation between prescription dose and treatment response as measured by the EQ-5D.

Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

Journal of Neurosurgery

OBJECTIVEStereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. H... more OBJECTIVEStereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%–62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy.METHODSFifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board–approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study ev...

Melanoma brain metastasis: the impact of stereotactic radiosurgery, BRAF mutational status, and targeted and/or immune-based therapies on treatment outcome

Journal of Neurosurgery

OBJECTIVEThe goal of this study was to investigate the impact of stereotactic radiosurgery (SRS),... more OBJECTIVEThe goal of this study was to investigate the impact of stereotactic radiosurgery (SRS), BRAF status, and targeted and immune-based therapies on the recurrence patterns and factors associated with overall survival (OS) among patients with melanoma brain metastasis (MBM).METHODSA total of 366 patients were treated for 1336 MBMs; a lesion-based analysis was performed on 793 SRS lesions. The BRAF status was available for 78 patients: 35 had BRAFmut and 43 had BRAF wild-type (BRAF-WT) lesions. The Kaplan-Meier method evaluated unadjusted OS; cumulative incidence analysis determined the incidences of local failure (LF), distant failure, and radiation necrosis (RN), with death as a competing risk.RESULTSThe 12-month OS was 24% (95% CI 20%–29%). On multivariate analysis, younger age, lack of extracranial metastases, better Karnofsky Performance Status score, and fewer MBMs, as well as treatment with BRAF inhibitors (BRAFi), anti–PD-1/CTLA-4 therapy, or cytokine therapy were signif...

First follow-up radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastases

Cancer Medicine

Local progression (LP) and radiation necrosis (RN) occur in >20% of cases following stereotactic ... more Local progression (LP) and radiation necrosis (RN) occur in >20% of cases following stereotactic radiosurgery (SRS) for brain metastases (BM). Expected outcomes following SRS for BM include tumor control/shrinkage, local progression and radiation necrosis. 1427 patients with 4283 BM lesions were treated using SRS at Cleveland Clinic from 2000 to 2012. Clinical, imaging and radiosurgery data were collected from the database. Local tumor progression and RN were the primary end points and correlated with patient and tumor-related variables. 5.7% of lesions developed radiographic RN and 3.6% showed local progression at 6 months. Absence of new extracranial metastasis (P < 0.001), response to SRS at first follow-up scan (local progression versus stable size (P < 0.001), partial resolution versus complete resolution at first follow up [P = 0.009]), prior SRS to the same lesion (P < 0.001), IDL% (≤55; P < 0.001), maximum tumor diameter (>0.9 cm; P < 0.001) and MD/PD gradient index (≤1.8, P < 0.001) were independent predictors of high risk of local tumor progression. Absence of systemic metastases (P = 0.029), good neurological function at 1st follow-up (P ≤ 0.001), no prior SRS to other lesion (P = 0.024), low conformity index (≤1.9) (P = 0.009), large maximum target diameter (>0.9 cm) (P = 0.003) and response to SRS (tumor progression vs. stable size following SRS [P < 0.001]) were independent predictors of high risk of radiographic RN. Complete tumor response at first follow-up, maximum tumor diameter <0.9 cm, tumor volume <2.4 cc and no prior SRS to the index lesion are good prognostic factors with reduced risk of LP following SRS. Complete tumor response to SRS, poor neurological function at first follow-up, prior SRS to other lesions and high conformity index are favorable factors for not developing RN. Stable or partial response at first follow-up after SRS have same impact on local progression and RN compared to those with complete resolution or progression.

Evaluation of Prognostic Factors for Early Mortality After Stereotactic Radiosurgery for Brain Metastases: a Single Institutional Retrospective Review

Neurosurgery, Jan 29, 2017

Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to impro... more Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival. To evaluate prognostic factors, which may predict early death (within 90 d) after SRS. A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices. Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatme...

Quality of Life following Stereotactic Radiosurgery for Single and Multiple Brain Metastases

Neurosurgery, Jan 23, 2017

Given the neurological morbidity and poor prognosis associated with brain metastases, it is criti... more Given the neurological morbidity and poor prognosis associated with brain metastases, it is critical to deliver appropriate therapy while remaining mindful of patient quality of life (QOL). For many patients, stereotactic radiosurgery (SRS) effectively controls intracranial disease, but QOL outcomes have not been characterized. To determine the effect of number of brain metastases upon QOL preservation following SRS. The EuroQol 5 Dimensions questionnaire (EQ-5D) and Patient Health Questionnaire 9 instruments were prospectively collected from a cohort of patients undergoing SRS for brain metastasis between 2008 and 2015. These instruments served as measures of overall QOL and depression. QOL deterioration exceeding the minimum clinically important difference was considered failure. Freedom from 12-month EQ-5D index failure was the primary outcome. One hundred and twenty-two SRS treatments (67 patients, 421 lesions) were eligible for inclusion. Intracranial failure (local or distant)...

Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies

Cancer, Jan 13, 2017

The current study was conducted to investigate survival and the response to radiotherapy among pa... more The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 mo...

The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies

Journal of neuro-oncology, Jan 22, 2017

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing ster... more To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 a...

Episcleral brachytherapy of uveal melanoma: role of intraoperative echographic confirmation

The British journal of ophthalmology, Jun 29, 2016

To compare the rates of tumour recurrence following episcleral brachytherapy for uveal melanoma b... more To compare the rates of tumour recurrence following episcleral brachytherapy for uveal melanoma before and after implementation of intraoperative echographic confirmation of plaque placement. All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between 1 January 2004 and 30 December 2013 were included. Exclusion criteria were patients with previous radiation treatment and patients who received adjuvant transpupillary thermotherapy. Since February 2007, intraoperative echographic confirmation was initiated to ensure that the plaque was centred on the tumour base and/or all tumour margins were covered by the plaque. 252 patients were included in the study. Local tumour control after primary brachytherapy was achieved in 242/252 (96.0%). Of the 10 patients with treatment failure, 8 patients had local recurrence and 2 patients had failure to response. With the incorporation of the intraoperative echographic con...

A cure is possible: a study of 10-year survivors of brain metastases

Journal of Neuro-Oncology, 2016

Little is known on the natural history, recurrence patterns, neurocognitive outcomes and prognost... more Little is known on the natural history, recurrence patterns, neurocognitive outcomes and prognostic factors associated with survival in long-term survivors (≥10 years) from brain metastasis (BM). In this study, the records of 1953 patients who underwent treatment for BM with a potential for ≥10 years of follow-up were reviewed. Cox regression analysis identified factors predictive for overall survival (OS). The median age at brain metastasis diagnosis was 60 years and the median OS was 6.4 months. The 1-year OS rate was 29.9, 12.1 % at 2 years, 3.0 % at 5 years, and 1.3 % at 10 years. On multivariable analysis, factors associated with worse OS included gender (males, HR 1.2), multiple brain metastases (HR 1.3), no surgery (HR 1.8), and no stereotactic radiosurgery (HR 1.8) (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001 each). Fifty-six patients (2.9 %) survived ≥5 years; 23 patients (1.2 %) survived ≥10 years and the median survival for ≥10 year survivors was 18.5 years. Six of the 10-year survivors had an intracranial recurrence, five occurred within 11 years from the first treatment. Presence of a solitary lesion or single lesion at the time of brain metastasis diagnosis was associated with improved survival. Eight of the ≥10 year survivors (34.8 %) had no neurological symptoms at last follow-up; none of the 10-year survivors were documented to have a neurologic death. Our study demonstrates that patients with favorable prognostic features should undergo multimodality treatment. Albeit rare, patients who are alive 10 years after treatment for their brain metastases may be considered cured from their intracranial disease.

CMET-11. Impact of Tumor Size and Molecular Profile on Local Control in Patients with Breast Cancer Brain Metastases: Understanding Tumor Biology and Radiosurgery Dosing

Neuro-Oncology

NEURO-ONCOLOGY • NOVEMBER 2017 to melanoma brain metastases was increased cMET expression frequen... more NEURO-ONCOLOGY • NOVEMBER 2017 to melanoma brain metastases was increased cMET expression frequency relative to the primary (36.4% versus 7.9%, P=0.0003). CONCLUSION: We report enriched expression of markers associated with DNA synthesis, replication, and repair in brain metastases compared with primary cancer specimens. This trend occurred across all tumor histologies, supporting the prioritization of therapies that target these pathways.

Is there a volume threshold of brain metastases for Linac-based stereotactic radiotherapy?

Purpose To investigate whether there is a volume threshold in target volume of brain metastases b... more Purpose To investigate whether there is a volume threshold in target volume of brain metastases below which a small cone size and sharp penumbra in Gamma Knife (GK) may provide improved plan quality when compared to Volumetric Modulated Arc Therapy (VMAT)-based stereotactic radiosurgery (SRS). Methods For patients treated on GK SRS for brain metastases in 2018-2019 in our institution, 121 patients with two and three targets were identified. Twenty-six patients with two or three brain metastases (total of 76 lesions) were selected for this study. Two VMAT plans, SmartArc (Pinnacle) and HyperArc (Eclipse), were generated retrospectively for each patient. Plan quality was evaluated based on RTOG conformity index (CI), Paddick gradient index (GI), normal tissue (NT) V12Gy and V4.5Gy. By using the receiver operating characteristic (ROC) curve for both VMAT plans (SmartArc and HyperArc) and metrics of RTOG CI and NT V12Gy, we compared GK plans to SmartArc and HyperArc plans separately to ...

NIMG-02. 18F-FLUCICLOVINE Positron Emission Tomography to Distinguish Tumor Progression from Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastasis: A Qualitative Analysis

Neuro-Oncology

PURPOSE/OBJECTIVE(S) To assess the ability of 18F-Fluciclovine PET/CT to distinguish radiation ne... more PURPOSE/OBJECTIVE(S) To assess the ability of 18F-Fluciclovine PET/CT to distinguish radiation necrosis (RN) from tumor progression (TP) among patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) in a prospective pilot study. MATERIALS/METHODS Adults with post-SRS BM presenting with follow-up brain MRI equivocal for RN versus TP underwent 18F-Fluciclovine PET/CT within 30 days of equivocal MRI. PET images were reconstructed using a point-spread-function algorithm. Three physician reviewers independently performed qualitative analyses of each lesion using a three-point visual score relative to PET-avidity of blood pool and parotid. Quantitative metrics for each lesion were documented. Reference standard was clinical follow-up with brain MRI until tumor board consensus or tissue confirmation. Nonparametric estimates of area under the receiver operating characteristic curve (AUC) for clustered data were estimated, with diagnostic performance based on visual ...

Stereotactic Radiosurgery for Postoperative Spine Malignancy: A Systematic Review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines

Practical Radiation Oncology

PURPOSE To determine safety and efficacy of postoperative spine stereotactic body radiation thera... more PURPOSE To determine safety and efficacy of postoperative spine stereotactic body radiation therapy (SBRT) in the published literature, and to present practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). MATERIALS AND METHODS A systematic review of the literature was performed, specific to postoperative spine SBRT, using PubMed and Embase databases. A meta-analysis for 1-year local control (LC), overall survival (OS) and vertebral compression fracture (VCF) probability was conducted. RESULTS The literature search revealed 251 potentially relevant articles after duplicates were removed. Of these 56 were reviewed in-depth for eligibility and 12 met all the inclusion criteria for analysis. 7 studies were retrospective, 2 prospective observational and 3 were prospective phase I/II clinical trials. Outcomes for a total of 461 patients and 499 spinal segments were reported. 10 studies used an MRI fused to CT-simulation for treatment planning, 2 investigations reported on all patients receiving a CT-myelogram at the time of planning. Meta-analysis for 1 year LC and OS was 88.9% and 57%, respectively. The crude reported VCF rate was 5.6%. One case of myelopathy was described in a patient with a previously irradiated spinal segment. One patient developed an esophageal fistula requiring surgical repair. CONCLUSIONS Postoperative spine SBRT delivers a high 1-year LC with acceptably low toxicity. Patients that may benefit from this include those with oligometastatic disease, radioresistant histology, paraspinal masses and/or those with a history of prior irradiation to the affected spinal segment. The ISRS recommends a minimum interval of 8 to 14 days after invasive surgery prior to simulation for SBRT, with initiation of radiotherapy within 4 weeks of surgery. An MRI fused to the planning CT, and/or the use of a CT-myelogram, are necessary for target and organ-at-risk delineation. A planning organ-at-risk volume (PRV) of 1.5 to 2mm for the spinal cord is advised.

$Research paper thumbnail of The Judicious Use of Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy in the Management of Large Brain Metastases$

The Judicious Use of Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy in the Management of Large Brain Metastases

Cancers

Brain metastases are the most common intracranial malignant tumor in adults and are a cause of si... more Brain metastases are the most common intracranial malignant tumor in adults and are a cause of significant morbidity and mortality for cancer patients. Large brain metastases, defined as tumors with a maximum dimension >2 cm, present a unique clinical challenge for the delivery of stereotactic radiosurgery (SRS) as patients often present with neurologic symptoms that require expeditious treatment that must also be balanced against the potential consequences of surgery and radiation therapy—namely, leptomeningeal disease (LMD) and radionecrosis (RN). Hypofractionated stereotactic radiotherapy (HSRT) and pre-operative SRS have emerged as novel treatment techniques to help improve local control rates and reduce rates of RN and LMD for this patient population commonly managed with post-operative SRS. Recent literature suggests that pre-operative SRS can potentially half the risk of LMD compared to post-operative SRS and that HSRT can improve risk of RN to less than 10% while improvin...

CMET-18. Impact of Kras Mutation Status on the Efficacy of Immunotherapy in Lung Cancer Brain Metastases

Neuro-Oncology

BACKGROUND Immunotherapy is increasingly used in patients with non-small cell lung cancer brain m... more BACKGROUND Immunotherapy is increasingly used in patients with non-small cell lung cancer brain metastases (NSCLCBM). KRAS mutations are associated with worse prognosis and there is no FDA approved targeted therapy. KRAS mutations are associated with increased expression of PD-L1. We evaluated the outcomes of NSCLCBM with KRAS mutations treated with immune checkpoint inhibitors (ICI). METHODS We reviewed 800 patients with NSCLCBM treated at our tertiary care center. 226 had known KRAS mutational status, 121 of which received immunotherapy. Overall survival (OS) was calculated from either the start of immunotherapy (when both groups received immunotherapy) or from the date of diagnosis of brain metastasis. Kaplan-Meier method and Cox Proportional hazard model were utilized to determine differences in OS and the Chi-square test was utilized to determine differences in PD-L1 expression. RESULTS In 109 patients where both KRAS and PD-L1 status were known, KRAS mutations had greater PD-L...

Risk Factors for Malignant Transformation of Low-Grade Glioma

International journal of radiation oncology, biology, physics, Jan 15, 2018

The incidence, risk factors, and outcomes of low-grade glioma patients who undergo malignant tran... more The incidence, risk factors, and outcomes of low-grade glioma patients who undergo malignant transformation (MT) in the era of temozolomide are not well known. This study evaluates these factors in a large group of World Health Organization grade 2 glioma patients treated at a tertiary-care institution. Patient, tumor, and treatment factors were analyzed using an institutional review board-approved low-grade glioma database. Characteristics were compared using χand Wilcoxon signed rank tests. Time to event was summarized using proportional hazards models. Univariate and multivariate survival analyses were performed. Of a total of 599 patients, 124 underwent MT; 76 (61.3%) had biopsy-proven MT. The MT incidence was 21%, and the median time to MT was 56.4 months. The 5- and 10-year progression-free survival rates were 30.6% ± 4.2% and 4.8% ± 1.9%, respectively, for MT patients and 60% ± 2.4% and 38% ± 2.7%, respectively, for non-MT patients. The 5- and 10-year overall survival rates w...

Clinical trial design for local therapies for brain metastases: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group

The Lancet. Oncology, 2018

The goals of therapeutic and biomarker development form the foundation of clinical trial design, ... more The goals of therapeutic and biomarker development form the foundation of clinical trial design, and change considerably from early-phase to late-phase trials. From these goals, decisions on specific clinical trial design elements, such as endpoint selection and statistical approaches, are formed. Whereas early-phase trials might focus on finding a therapeutic signal to make decisions on further development, late-phase trials focus on the confirmation of therapeutic impact by considering clinically meaningful endpoints. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we highlight issues related to, and provide recommendations for, the design of clinical trials on local therapies for CNS metastases from solid tumours. We discuss endpoint selection criteria, the analysis appropriate for early-phase and late-phase trials, the association between tumour-specific and clinically meaningful endpoints, and possible issues related to...

Long-Term Outcome Following Stereotactic Radiosurgery for Glomus Jugulare Tumors: A Single Institution Experience of 20 Years

Neurosurgery, Jan 4, 2017

Glomus jugulare tumors (GJTs) are rare benign tumors, which pose significant treatment challenges... more Glomus jugulare tumors (GJTs) are rare benign tumors, which pose significant treatment challenges due to proximity to critical structures. To evaluate the long-term clinical and radiological outcome in patients undergoing stereotactic radiosurgery (SRS) for GJTs through retrospective study. Forty-two patients with 43 GJTs were treated using Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden) at our institute from 1997 to 2016. Clinical, imaging, and radiosurgery data were collected from an institutional review board approved database. Most patients were females (n = 35, 83.3%) and median age was 61 yr (range 23-88 yr). Median tumor volume and diameter were 5 cc and 3 cm, respectively, with a median follow-up of 62.3 mo (3.4-218.6 mo). Overall, 20 patients (47.6%) improved clinically and 14 (33.3%) remained unchanged at last follow-up. New onset or worsening of hearing loss was noted in 6 patients (17.2%) after SRS. The median prescription dose to the tumor margin was 15 Gy...

Validation of the Disease-Specific GPA for Patients With 1 to 3 Synchronous Brain Metastases in Newly Diagnosed NSCLC

Clinical Lung Cancer

The disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful pro... more The disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful prognostic tool but has not been validated for patients with synchronous brain metastases (SBM) in newly diagnosed non-small-cell lung cancer (NSCLC). We identified patients with newly diagnosed NSCLC with 1 to 3 SBM treated with stereotactic radiosurgery (SRS) between 1997 and 2012. We included patients whose brain metastases were treated with SRS alone or combined SRS and whole-brain radiotherapy (WBRT). Patients were stratified according to NSCLC DS-GPA to evaluate the accuracy of survival estimates. One hundred sixty-four patients were treated with either SRS alone (n = 85; 52%) or SRS and WBRT (n = 79; 48%). Median overall survival (OS) stratified according to DS-GPA of 0 to 1, 1.5 to 2, 2.5 to 3, and 3.5 to 4 were 2.8, 6.7, 9.8, and 13.2 months, respectively, consistent with OS reported for brain metastases in NSCLC DS-GPA (3.0, 6.5, 11.3, and 14.8 months, respectively). No difference in median progression-free survival or OS was noted with combined use of SRS and WBRT: 6.0 versus 6.1 months (P = .81) and 8.5 versus 9.1 months (P = .093), respectively. In multivariable analysis, Karnofsky performance status (hazard ratio [HR], 0.98; P = .008), extracranial metastases (HR, 0.498; P = .0003), squamous histology (HR, 1.81; P = .02), and number of brain metastases (2 vs. 1; HR, 1.504; P = .04, and 3 vs. 1; HR, 1.66; P = .05) were significant predictors of OS. The DS-GPA accurately estimates the prognosis of patients with SBM in newly diagnosed NSCLC. Patients with synchronous brain metastasis in newly diagnosed NSCLC should be carefully stratified for consideration of aggressive therapy.

Stereotactic Radiosurgery for Trigeminal Neuralgia Improves Patient-Reported Quality of Life and Reduces Depression

International Journal of Radiation Oncology*Biology*Physics

To characterize quality-of-life (QOL) outcomes after stereotactic radiosurgery (SRS) for trigemin... more To characterize quality-of-life (QOL) outcomes after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). The EuroQOL 5 Dimensions (EQ-5D) and Patient Health Questionnaire 9 (PHQ-9) were prospectively collected before and after SRS for 50 patients with TN. Pain response and treatment-related facial numbness were classified by Barrow Neurological Institute (BNI) scales. Differences in pooled QOL outcomes were tested with paired t tests and sign tests. The Kaplan-Meier method was used to estimate time-dependent improvements in the EQ-5D index, EQ-5D perceived health status (PHS), PHQ-9 score, and freedom from pain failure (BNI class IV-V) or facial numbness (BNI class III-IV). Following SRS, the 12-month rate of freedom from pain failure was 92% (95% confidence interval [CI], 77%-97%) while the 12-month rate of freedom from facial numbness was 89% (95% CI, 66%-97%). Significant improvements in the EQ-5D index (P&amp;amp;amp;amp;lt;.01), PHS (P=.01), and PHQ-9 (P=.03) were observed, driven by the EQ-5D subscores for self-care and for pain and/or discomfort (P=.02 and P&amp;amp;amp;amp;lt;.01, respectively). At 12 months after SRS, the actuarial rates of improvement in the EQ-5D, PHS, and PHQ-9 were 55% (95% CI, 40%-70%), 59% (95% CI, 40%-76%), and 59% (95% CI, 39%-76%), respectively. The median time to improvement in each of the QOL measures was 9 months (95% CI, 3-36 months) for the EQ-5D index, 5 months (95% CI, 3-36 months) for PHS, and 9 months (95% CI, 3-18 months) for the PHQ-9. On multivariate analysis, only higher prescription dose (86 Gy vs ≤82 Gy) was associated with improvement in the EQ-5D index (hazard ratio, 5.73; 95% CI, 1.85-22.33; P&amp;amp;amp;amp;lt;.01). Patients with TN treated with SRS reported significant improvements in multiple QOL measures, with the therapeutic benefit strongly driven by improvements in pain and/or discomfort and in self-care, along with lower rates of depression. In this analysis, there appears to be a correlation between prescription dose and treatment response as measured by the EQ-5D.

Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

Journal of Neurosurgery

OBJECTIVEStereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. H... more OBJECTIVEStereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%–62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy.METHODSFifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board–approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study ev...

Melanoma brain metastasis: the impact of stereotactic radiosurgery, BRAF mutational status, and targeted and/or immune-based therapies on treatment outcome

Journal of Neurosurgery

OBJECTIVEThe goal of this study was to investigate the impact of stereotactic radiosurgery (SRS),... more OBJECTIVEThe goal of this study was to investigate the impact of stereotactic radiosurgery (SRS), BRAF status, and targeted and immune-based therapies on the recurrence patterns and factors associated with overall survival (OS) among patients with melanoma brain metastasis (MBM).METHODSA total of 366 patients were treated for 1336 MBMs; a lesion-based analysis was performed on 793 SRS lesions. The BRAF status was available for 78 patients: 35 had BRAFmut and 43 had BRAF wild-type (BRAF-WT) lesions. The Kaplan-Meier method evaluated unadjusted OS; cumulative incidence analysis determined the incidences of local failure (LF), distant failure, and radiation necrosis (RN), with death as a competing risk.RESULTSThe 12-month OS was 24% (95% CI 20%–29%). On multivariate analysis, younger age, lack of extracranial metastases, better Karnofsky Performance Status score, and fewer MBMs, as well as treatment with BRAF inhibitors (BRAFi), anti–PD-1/CTLA-4 therapy, or cytokine therapy were signif...

First follow-up radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastases

Cancer Medicine

Local progression (LP) and radiation necrosis (RN) occur in >20% of cases following stereotactic ... more Local progression (LP) and radiation necrosis (RN) occur in >20% of cases following stereotactic radiosurgery (SRS) for brain metastases (BM). Expected outcomes following SRS for BM include tumor control/shrinkage, local progression and radiation necrosis. 1427 patients with 4283 BM lesions were treated using SRS at Cleveland Clinic from 2000 to 2012. Clinical, imaging and radiosurgery data were collected from the database. Local tumor progression and RN were the primary end points and correlated with patient and tumor-related variables. 5.7% of lesions developed radiographic RN and 3.6% showed local progression at 6 months. Absence of new extracranial metastasis (P < 0.001), response to SRS at first follow-up scan (local progression versus stable size (P < 0.001), partial resolution versus complete resolution at first follow up [P = 0.009]), prior SRS to the same lesion (P < 0.001), IDL% (≤55; P < 0.001), maximum tumor diameter (>0.9 cm; P < 0.001) and MD/PD gradient index (≤1.8, P < 0.001) were independent predictors of high risk of local tumor progression. Absence of systemic metastases (P = 0.029), good neurological function at 1st follow-up (P ≤ 0.001), no prior SRS to other lesion (P = 0.024), low conformity index (≤1.9) (P = 0.009), large maximum target diameter (>0.9 cm) (P = 0.003) and response to SRS (tumor progression vs. stable size following SRS [P < 0.001]) were independent predictors of high risk of radiographic RN. Complete tumor response at first follow-up, maximum tumor diameter <0.9 cm, tumor volume <2.4 cc and no prior SRS to the index lesion are good prognostic factors with reduced risk of LP following SRS. Complete tumor response to SRS, poor neurological function at first follow-up, prior SRS to other lesions and high conformity index are favorable factors for not developing RN. Stable or partial response at first follow-up after SRS have same impact on local progression and RN compared to those with complete resolution or progression.

Evaluation of Prognostic Factors for Early Mortality After Stereotactic Radiosurgery for Brain Metastases: a Single Institutional Retrospective Review

Neurosurgery, Jan 29, 2017

Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to impro... more Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival. To evaluate prognostic factors, which may predict early death (within 90 d) after SRS. A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices. Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatme...

Quality of Life following Stereotactic Radiosurgery for Single and Multiple Brain Metastases

Neurosurgery, Jan 23, 2017

Given the neurological morbidity and poor prognosis associated with brain metastases, it is criti... more Given the neurological morbidity and poor prognosis associated with brain metastases, it is critical to deliver appropriate therapy while remaining mindful of patient quality of life (QOL). For many patients, stereotactic radiosurgery (SRS) effectively controls intracranial disease, but QOL outcomes have not been characterized. To determine the effect of number of brain metastases upon QOL preservation following SRS. The EuroQol 5 Dimensions questionnaire (EQ-5D) and Patient Health Questionnaire 9 instruments were prospectively collected from a cohort of patients undergoing SRS for brain metastasis between 2008 and 2015. These instruments served as measures of overall QOL and depression. QOL deterioration exceeding the minimum clinically important difference was considered failure. Freedom from 12-month EQ-5D index failure was the primary outcome. One hundred and twenty-two SRS treatments (67 patients, 421 lesions) were eligible for inclusion. Intracranial failure (local or distant)...

Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies

Cancer, Jan 13, 2017

The current study was conducted to investigate survival and the response to radiotherapy among pa... more The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 mo...

The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies

Journal of neuro-oncology, Jan 22, 2017

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing ster... more To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 a...

Episcleral brachytherapy of uveal melanoma: role of intraoperative echographic confirmation

The British journal of ophthalmology, Jun 29, 2016

To compare the rates of tumour recurrence following episcleral brachytherapy for uveal melanoma b... more To compare the rates of tumour recurrence following episcleral brachytherapy for uveal melanoma before and after implementation of intraoperative echographic confirmation of plaque placement. All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between 1 January 2004 and 30 December 2013 were included. Exclusion criteria were patients with previous radiation treatment and patients who received adjuvant transpupillary thermotherapy. Since February 2007, intraoperative echographic confirmation was initiated to ensure that the plaque was centred on the tumour base and/or all tumour margins were covered by the plaque. 252 patients were included in the study. Local tumour control after primary brachytherapy was achieved in 242/252 (96.0%). Of the 10 patients with treatment failure, 8 patients had local recurrence and 2 patients had failure to response. With the incorporation of the intraoperative echographic con...

A cure is possible: a study of 10-year survivors of brain metastases

Journal of Neuro-Oncology, 2016

Little is known on the natural history, recurrence patterns, neurocognitive outcomes and prognost... more Little is known on the natural history, recurrence patterns, neurocognitive outcomes and prognostic factors associated with survival in long-term survivors (≥10 years) from brain metastasis (BM). In this study, the records of 1953 patients who underwent treatment for BM with a potential for ≥10 years of follow-up were reviewed. Cox regression analysis identified factors predictive for overall survival (OS). The median age at brain metastasis diagnosis was 60 years and the median OS was 6.4 months. The 1-year OS rate was 29.9, 12.1 % at 2 years, 3.0 % at 5 years, and 1.3 % at 10 years. On multivariable analysis, factors associated with worse OS included gender (males, HR 1.2), multiple brain metastases (HR 1.3), no surgery (HR 1.8), and no stereotactic radiosurgery (HR 1.8) (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001 each). Fifty-six patients (2.9 %) survived ≥5 years; 23 patients (1.2 %) survived ≥10 years and the median survival for ≥10 year survivors was 18.5 years. Six of the 10-year survivors had an intracranial recurrence, five occurred within 11 years from the first treatment. Presence of a solitary lesion or single lesion at the time of brain metastasis diagnosis was associated with improved survival. Eight of the ≥10 year survivors (34.8 %) had no neurological symptoms at last follow-up; none of the 10-year survivors were documented to have a neurologic death. Our study demonstrates that patients with favorable prognostic features should undergo multimodality treatment. Albeit rare, patients who are alive 10 years after treatment for their brain metastases may be considered cured from their intracranial disease.