Prognosis and risk of suicide after cancer diagnosis.

INTRODUCTION: Suicide rates are elevated after cancer diagnosis. Existential distress caused by awareness of one's impending death is well-described in patients with cancer. The authors hypothesized that suicide risk is associated with cancer prognosis, and the impact of prognosis on suicide risk is greatest for populations with higher baseline suicide risk. METHODS: The authors identified patients (≥16 years old) with newly diagnosed cancers from 2000 to 2019 in the Surveillance, Epidemiology, and End Results database, representing 27% of US cancers. Multiple primary-standardized mortality ratios (SMR) were used to estimate the relative risk of suicide within 6 months of diagnosis compared to the general US population, adjusted for age, sex, race, and year of follow-up. Suicide rates by 20 most common cancer sites were compared with respective 2-year overall survival rates (i.e., prognosis) using a weighted linear regression model. RESULTS: Among 6,754,704 persons diagnosed with cancer, there were 1610 suicide deaths within 6 months of diagnosis, three times higher than the general population (SMR = 3.1; 95% confidence interval, 3.0-3.3). Suicide risk by cancer site was closely associated with overall prognosis (9.5%/percent survival deficit, R2  = 0.88, p < .0001). The association of prognosis with suicide risk became attenuated over time. For men, the risk of suicide increased by 2.8 suicide deaths per 100,000 person-years (p < .0001) versus 0.3 in women (p < .0001). The risk was also higher for persons ≥60 old and for the White (vs. Black) race. CONCLUSIONS: Poorer prognosis was closely associated with suicide risk early after cancer diagnosis and had a greater effect on populations with higher baseline risks of suicide. This model highlights the need for enhanced psychiatric surveillance and continued research in this patient population.

MGMT promoter methylation in 1p19q-intact gliomas.

OBJECTIVE: Standard-of-care for 1p19q-intact anaplastic gliomas is defined by the international randomized phase III CATNON trial, which found an overall survival (OS) benefit for adjuvant temozolomide (TMZ) when added to radiotherapy. Paradoxically, TMZ did not appear to benefit patients with IDH-wildtype gliomas, regardless of MGMT promoter status. The authors concluded that well-powered prospective study on the clinical efficacy of TMZ for patients with IDH-wildtype anaplastic gliomas (meeting criteria for glioblastoma) is warranted. Given that the prognostic and predictive role of MGMT status for grade 2-3 gliomas is unresolved, we determined the effect of MGMT status on OS in patients with 1p19q-intact gliomas in the National Cancer Database (NCDB). METHODS: We queried the NCDB from 2018 to 2019 for patients with diffuse (grade 2) and anaplastic (grade 3) IDH-wildtype or -mutant astrocytomas who received chemotherapy with follow-up through 2022. The Kaplan-Meier method and Cox proportional hazards regressions models were used to determine the association of MGMT with OS. RESULTS: We identified 1514 patients who were newly diagnosed with IDH-wildtype (n = 802, 33% methylated) or -mutant astrocytomas (n = 712, 48% methylated) and received chemotherapy during initial management. An unmethylated promoter was associated with poorer survival in patients with IDH-wildtype (3-year OS 34% [95%CI 29-39%] vs. 46% [95%CI 39-54%], p < .001, adjusted HR 1.53 [95%CI 1.24-1.89]) but not IDH-mutant astrocytomas (3-year OS 79% [95%CI 74-84%] vs. 80% [95%CI 75-86%], p =0 .81, HR 1.04 [95%CI 0.73-1.50]). CONCLUSIONS: This ancillary analysis supports conclusions from the CATNON trial for adjuvant TMZ as standard-of-care for anaplastic astrocytomas (IDH-mutant and 1p19q-intact), irrespective of MGMT status. Determining the optimal strategy for diffuse gliomas that are IDH-wildtype will be particularly important. MGMT promoter methylation should be considered as a stratification factor in future clinical trials for these patients.

Feasibility of fractionated gamma knife radiosurgery in the management of newly diagnosed Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with overall survival remaining poor despite ongoing efforts to explore new treatment paradigms. Given these outcomes, efforts have been made to shorten treatment time. Recent data report on the safety of CyberKnife (CK) fractionated stereotactic radiosurgery (SRS) in the management of GBM using a five-fraction regimen. The latest Gamma Knife (GK) model also supports frameless SRS, and outcomes using GK SRS in the management of primary GBM have not yet been reported. OBJECTIVE: To report on the feasibility of five-fraction SRS with the GammaKnife ICON in the management of newly diagnosed GBM. METHODS: In this single institutional study, we retrospectively reviewed all patients from our medical center from January 2017 through December 2021 who received fractionated SRS with Gamma Knife ICON for newly diagnosed GBM. Patient demographics, upfront surgical margins, molecular subtyping, radiation treatment volumes, systemic therapies, and follow-up imaging findings were extracted to report on oncologic outcomes. RESULTS: We identified six patients treated within the above time frame. Median age at diagnosis was 73.5 years, 66% were male, and had a median Karnofsky Performance Status (KPS) of 70. All tumors were IDH wild-type, and all but one were MGMT methylated and received concurrent temozolomide (TMZ). Within this group, progression free survival was comparable to that of historical data without significant radiation-induced toxicities. CONCLUSION: Gamma Knife ICON may be discussed as a potential treatment option for select GBM patients and warrants further investigation in the prospective setting.

Stereotactic radiosurgery for management of vestibular schwannoma: a short review.

Management options for newly diagnosed vestibular schwannoma (VS) include observation, surgery, or radiation. There are no randomized trials to guide management of patients with VS. This article is a short review of the role of stereotactic radiosurgery in management of newly diagnosed VS.

A multi-institutional analysis of clinical outcomes and patterns of care of 1p/19q codeleted oligodendrogliomas treated with adjuvant or salvage radiation therapy.

PURPOSE: Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage radiation therapy (sRT) in a multi-institutional cohort. METHODS: Oligodendroglioma patients with confirmed 1p/19q codeletion who were treated with RT with or without chemotherapy from 2000 to 2017 at four tertiary centers were retrospectively reviewed. Overall survival (OS), post-RT progression-free survival (PFS), freedom-from-RT (FFRT), and radiation necrosis (RN) rates were determined using Kaplan-Meier analyses. OS1/PFS1 were defined from the initial surgery. OS2/PFS2 were defined from the RT start-date. Multivariable analyses (MVAs) of prognostic factors for OS and PFS were performed with Cox regression. RESULTS: One hundred eighty-six patients were identified: 124(67%) received aRT and 62(33%) received sRT; of sRT patients, 58% were observed after surgery while 42% received chemotherapy without aRT. The median time from initial diagnosis to sRT was 61 months, and 74% had reoperations before sRT. sRT had longer OS1 than aRT (94% vs. 69% at 10 years, p = 0.03) and PFS1 (10-year PFS of 80% vs. 68%, p = 0.03), though sRT was not associated with significantly different OS1/PFS1 on MVAs. Chemotherapy did not delay sRT compared to observation and had worse PFS2 (42% vs. 79% at 5 years, p = 0.08). Higher RT dose was not associated with improved clinical outcomes but was associated with higher symptomatic RN rate (15% vs. 0% at 2 years, p = 0.003). CONCLUSIONS: Delaying RT for selected oligodendroglioma patients appears safe. Adjuvant chemotherapy does not delay sRT longer than observation and may be associated with worse PFS after RT.

Surgery plus adjuvant radiotherapy for primary central nervous system lymphoma.

Objective: Recent studies of primary central nervous system lymphoma (PCNSL) have found a positive association between cytoreductive surgery and survival, challenging the traditional notion that surgery is not beneficial and potentially harmful. However, no studies have examined the potential added benefits of adjuvant treatment in the post-operative setting. Here, we investigate survival in PCNSL patients treated with surgery plus radiation therapy (RT).Methods: The Surveillance, Epidemiology, and End-Results Program was used to identify patients with PCNSL from 1995-2013. We retrospectively analyzed the relationship between treatment, prognostic factors, and survival using case-control design. Treatment categories were compared to biopsy alone.Results: We identified 5417 cases. Median survival times for biopsy alone (n = 1824, 34%), biopsy + RT (n = 1460, 27%), surgery alone (n = 1222, 27%), and surgery + RT (n = 911, 17%) were 7, 8, 20, and 27 months, respectively. On multivariable analysis, surgery + RT was associated with improved survival over surgery alone (hazard ratio [HR] = 0.58 [95% confidence interval = 0.53-0.64] vs. HR = 0.71 [0.65-0.77]). Adjuvant RT was associated with improved survival, regardless of the extent of resection. HR's for subtotal resection, gross-total resection, subtotal resection + RT, and gross-total resection + RT were 0.77 (0.66-0.89), 0.66 (0.57-0.76), 0.62 (0.52-0.72), and 0.54 (0.46-0.63), respectively. Survival improved after adjuvant RT in patients under and over 60 years old. All findings were confirmed by multivariable analysis of cause-specific survival.Conclusion: Adjuvant RT was associated with improved survival in PCNSL patients who underwent surgery. Although these data are hypothesis-generating, additional information on neurotoxicity, dosing, and concurrent chemotherapy will be necessary to validate these findings. Cytoreductive surgery for PCNSL is common in the general population, and more studies are needed to assess optimal treatment in the post-operative setting.

Spinal location is prognostic of survival for solitary-fibrous tumor/hemangiopericytoma of the central nervous system.

BACKGROUND: Prior studies have highlighted infratentorial tumor location as a prognostic factor for solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) of the central nervous system (CNS), and spinal location is considered a positive prognostic factor for other tumors of the CNS. While SFT/HPC of the CNS is known to frequently arise from the spinal meninges, there are no case series that report outcomes for spinally located CNS tumors, and their prognosis in relation to intracranial and other CNS-located tumors is unknown. OBJECTIVE: To investigate outcomes for patients with SFT/HPC of the spinal meninges. METHODS: The Surveillance, Epidemiology, and End-Results Program was used to identify patients with SFT/HPC within the CNS from 1993-2015. We retrospectively analyzed the relationship between tumor location (spinal vs. Brain and other CNS) and survival. RESULTS: We identified 551 cases of CNS SFT/HPC, 64 (11.6%) of which were primary tumors of the spinal meninges. Spinal tumors were more likely than brain and other CNS tumors to be SFT vs. HPC (37.5 vs. 12%, p < 0.001), benign (42.2 vs. 20.3%, p < 0.001), and less than 5 cm (53.1 vs. 35.7%, p < 0.001). The 10-year survival rates for spinal and brain/other CNS tumors were 85 and 58%, respectively. Median survival time was significantly longer for spinal tumors (median survival not reached vs. 138 months, p = 0.03, HR = 0.41 [95% CI 0.18-0.94]). On multivariable analysis, spinal tumor location was associated with improved survival over tumors located in the brain and other CNS (HR = 0.36 [95% CI 0.15-0.89], p = 0.03). CONCLUSION: Spinal tumor location is associated with improved survival in patients with SFT/HPC of the CNS. Larger institutional studies are necessary to characterize the relationship between tumor location and other relevant factors such as presentation and amenability to gross-total resection and adjuvant radiotherapy. Future studies exploring optimal management of spinally located tumors are also needed.

Natural history, clinical course and predictors of interval time from initial diagnosis to development of subsequent NSCLC brain metastases.

PURPOSE: Non-small cell lung cancer (NSCLC) brain metastases are associated with substantial morbidity and mortality. During recent years, accompanying dramatic improvements in systemic disease control, NSCLC brain metastases have emerged as an increasingly relevant clinical problem. However, optimal surveillance practices remain poorly defined. This purpose of this study was to further characterize the natural history, clinical course and risk factors associated with earlier development of subsequent NSCLC brain metastases to better inform clinical practice and help guide survivorship care. METHODS: We retrospectively reviewed all institutional NSCLC brain metastasis cases treated with radiotherapy between 1997 and 2015. Exclusion criteria included presence of brain metastases at initial NSCLC diagnosis and incomplete staging information. Interval time to brain metastases and subsequent survival were characterized using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: Among 105 patients within this cohort, median interval time to development of brain metastases was 16 months. Median interval times were 29, 19, 16 and 13 months for Stage I-IV patients, respectively (P = 0.016). Additional independent predictors for earlier development of NSCLC brain metastases included non-adenocarcinomatous histopathology (HR 3.036, P < 0.001), no prior surgical resection (HR 1.609, P = 0.036) and no prior systemic therapy (HR 3.560, P = 0.004). Median survival following intracranial progression was 16 months. Delayed development of brain metastases was associated with better prognosis (HR 0.970, P < 0.001) but not survival following intracranial disease onset. CONCLUSIONS: Collectively, our results provide valuable insights into the natural history of NSCLC brain metastases. NSCLC stage, histology, prior surgical resection and prior systemic therapy emerged as independent predictors for interval time to brain metastases.

NRG brain tumor specialists consensus guidelines for glioblastoma contouring.

INTRODUCTION: NRG protocols for glioblastoma allow for clinical target volume (CTV) reductions at natural barriers; however, literature examining CTV contouring and the relevant white matter pathways is lacking. This study proposes consensus CTV guidelines, with a focus on areas of controversy while highlighting common errors in glioblastoma target delineation. METHODS: Ten academic radiation oncologists specializing in brain tumor treatment contoured CTVs on four glioblastoma cases. CTV expansions were based on NRG trial guidelines. Contour consensus was assessed and summarized by kappa statistics. A meeting was held to discuss the mathematically averaged contours and form consensus contours and recommendations. RESULTS: Contours of the cavity plus enhancement (mean kappa 0.69) and T2-FLAIR signal (mean kappa 0.74) showed moderate to substantial agreement. Experts were asked to trim off anatomic barriers while respecting pathways of spread to develop their CTVs. Submitted CTV_4600 (mean kappa 0.80) and CTV_6000 (mean kappa 0.81) contours showed substantial to near perfect agreement. Simultaneous truth and performance level estimation (STAPLE) contours were then reviewed and modified by group consensus. Anatomic trimming reduced the amount of total brain tissue planned for radiation targeting by a 13.6% (range 8.7-17.9%) mean proportional reduction. Areas for close scrutiny of target delineation were described, with accompanying recommendations. CONCLUSIONS: Consensus contouring guidelines were established based on expert contours. Careful delineation of anatomic pathways and barriers to spread can spare radiation to uninvolved tissue without compromising target coverage. Further study is necessary to accurately define optimal target volumes beyond isometric expansion techniques for individual patients.

Extent of resection and survival for oligodendroglioma: a U.S. population-based study.

BACKGROUND: National guidelines recommend maximal safe resection of low-grade and high-grade oligodendrogliomas. However, there is no level 1 evidence to support these guidelines, and recent retrospective studies on the topic have yielded mixed results. OBJECTIVE: To assess the association between extent of resection (EOR) and survival for oligodendrogliomas in the general U.S. METHODS: Cases diagnosed between 2004 and 2013 were selected from the Surveillance, Epidemiology, and End-Results (SEER) Program and retrospectively analyzed for treatment, prognostic factors, and survival times. Cases that did not undergo tumor de-bulking surgery (e.g. no surgery or biopsy alone) were compared to subtotal resection (resection) and gross-total resection (GTR). The primary end-points were overall survival (OS) and cause-specific survival (CSS). An external validation cohort with 1p/19q-codeleted tumors was creating using the TCGA and GSE16011 datasets. RESULTS: 3135 Cases were included in the final analysis. The 75% survival time (75ST) and 5-year survival rates were 47 months and 70.8%, respectively. Subtotal resection (STR, 75ST = 50 months) and GTR (75ST = 61 months) were associated with improved survival times compared to cases that did not undergo surgical debulking (75ST = 20 months, P < 0.001 for both), with reduced hazard ratios (HRs) after controlling for other factors (HR 0.81 [0.68-0.97] and HR 0.65 [0.54-0.79], respectively). GTR was associated with improved OS in both low-grade and anaplastic oligodendroglioma subgroups (HR 0.74 [0.58-0.95], HR 0.60 [0.44-0.82], respectively) while STR fell short of significance in the subgroup analysis. All findings were corroborated by multivariable analysis of CSS and externally validated in a cohort of patients with 1p19q-codeleted tumors. CONCLUSION: Greater EOR is associated with improved survival in oligodendrogliomas. Our findings in this U.S. population-based cohort support national guidelines.

Epidermal growth factor receptor (EGFR) amplification rates observed in screening patients for randomized trials in glioblastoma.

PURPOSE: Epidermal growth factor receptor (EGFR) amplification has been reported to occur in ~ 50% of glioblastomas (GBMs). We are conducting several global studies that require central testing for EGFR amplification during screening, representing an opportunity to confirm the frequency of amplification in GBM in a large cohort and to evaluate whether EGFR amplification differs by region of the world. METHODS: EGFR amplification was measured by fluorescence in situ hybridization during screening for therapeutic trials of an EGFR antibody-drug conjugate: two Phase 2/3 global trials (INTELLANCE-1, INTELLANCE-2), and a Japanese Phase 1/2 trial (INTELLANCE-J). We evaluated the proportion of tumor tissue samples harboring EGFR amplification among those tested and differences in amplification frequency by geography. RESULTS: EGFR was amplified in 54% of 3150 informative cases screened for INTELLANCE-1 and -2, consistent with historic controls, but was significantly lower in patients from Asia versus the rest of the world (35% vs. 56%, P < 0.0030). The independent INTELLANCE-J trial validated this finding (33% amplified of 153 informative cases). CONCLUSIONS: EGFR amplification occurs less frequently in patients from Asia than elsewhere. Further study is required to understand biological differences to optimize treatment in glioblastoma.

Solitary-fibrous tumor/hemangiopericytoma of the central nervous system: a population-based study.

The World Health Organization (WHO) classification of tumors of the central nervous system (CNS) was recently updated, restructuring solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) into one combined entity. This is the first population-based study to examine outcomes of SFT/HPC based on the new WHO guidelines. The Surveillance, Epidemiology, and End Results (SEER) database (1998-2013) was queried to examine age-adjusted incidence and prognostic factors associated with overall survival in 416 surgically resected cases. Age-adjusted incidence was calculated to be 3.77 per 10,000,000 and was rising. Median survival was 155 months, with 5- and 10-year survival rates of 78 and 61%, respectively. Younger age, Asian/Pacific Islander versus white race, benign histology, tumor location, gross-total resection (GTR), and GTR plus radiation (RT) versus subtotal resection were significantly associated with survival. In multivariable analysis, older age (HR = 1.038, p < 0.0001), infratentorial location (HR = 2.019, p = 0.038), GTR (HR = 0.313, p = 0.041), and GTR + RT (HR = 0.215, p = 0.008) were independent prognostic factors. In the HPC and borderline/malignant subgroups, GTR + RT was associated with significantly increased survival compared with GTR alone (HR = 0.537, p = 0.039 and HR = 0.525, p = 0.038). After eliminating patients that died within 3 months of diagnosis, GTR + RT was still associated with an incremental increase in survival (HR = 0.238, p = 0.031) over GTR alone (HR = 0.280, p = 0.054). GTR + RT may be optimal in the management CNS HPC and SFT/HPC tumors with borderline/malignant features. This study, in combination with existing literature, warrants further investigation of adjuvant radiation through a prospective clinical trial.

Local control and overall survival for adjuvant stereotactic radiosurgery in patients with residual or recurrent disease.

Prior studies of post-operative stereotactic radiosurgery (SRS) have not distinguished between Adjuvant SRS (ARS) versus Adjuvant SRS to residual/recurrent disease (ARD). In this study, we defined ARS and ARD and investigated local control (LC), overall survival (OS), distant development of brain metastases (DBF), and leptomeningeal disease (LMD). We retrospectively identified BM patients who received surgical resection and SRS for BM from an IRB approved database between Jan 2009-Aug 2015. Patients were stratified into two groups: ARS and ARD. LC was determined by follow-up MRI studies and OS was measured from the date of surgery. LC and OS were assessed using the Kaplan-Meier method. 70 cavities underwent surgical resection of BM and received SRS to the post-operative bed. 41 cavities were classified as ARS and 29 as ARD. There was no significant difference in 12-month LC between the ARS and ARD group (71.4 vs. 80.8%, respectively; p = 0.135) from the time point of SRS. The overall 1-year survival for ARS and ARD was 79.9 and 86.1%, respectively (p = 0.339). Mean time to progression was 6.45 and 8.0 months and median follow-up was 10 and 15 months for ARS and ARD, respectively. 11.8% of ARS patients and 15.4% of ARD patients developed LMD, p = 0.72. 29.4% of ARS and 48.0% of ARD patients developed DBF, p = 0.145. Our findings suggest that observation after surgical resection, with subsequent treatment with SRS after the development of local failure, may not compromise treatment efficacy. If validated, this would spare patients who do not recur post-surgically from additional treatment.

Clinical and molecular characteristics of gliosarcoma and modern prognostic significance relative to conventional glioblastoma.

Gliosarcoma is a rare histopathologic variant of glioblastoma traditionally associated with a poor prognosis. While gliosarcoma may represent a distinct clinical entity given its unique histologic composition and molecular features, its relative prognostic significance remains uncertain. While treatment of gliosarcoma generally encompasses the same standardized approach used in glioblastoma, supporting evidence is limited given its rarity. Here, we characterized 32 cases of gliosarcoma and retrospectively evaluated survival relative to 451 glioblastoma patients diagnosed during the same era within the same institution. Overall, we identified 22 primary gliosarcomas, representing 4.7% of WHO Grade IV primary glioblastomas, and 10 secondary gliosarcomas. With median age of 62, patients were predominately Caucasian (87.5%) and male (65.6%). Tumors with available molecular profiling were primarily MGMT-unmethylated (87.5%), IDH-1-preserved (100%) and EGFR wild-type (100%). Interestingly, while no significant median survival difference between primary gliosarcoma and glioblastoma was observed across the entire cohort (11.0 vs. 14.8 months, p = 0.269), median survival was worse for gliosarcoma specifically among patients who received modern temozolomide-based (TMZ) chemoradiotherapy (11.0 vs. 17.3 months, p = 0.006). Matched-pair analysis also trended toward worse median survival among gliosarcomas (11.0 vs. 19.6 months, log-rank p = 0.177, Breslow p = 0.010). While adjuvant radiotherapy (HR 0.206, p = 0.035) and TMZ-based chemotherapy (HR 0.531, p = 0.000) appeared protective, gliosarcoma emerged as a significantly poor prognostic factor on multivariate analysis (HR 3.27, p = 0.012). Collectively, our results suggest that gliosarcoma may still portend worse prognosis even with modern trimodality therapy.

Invasiveness is associated with metastasis and decreased survival in hemangiopericytoma of the central nervous system.

Meningeal hemangiopericytoma (m-HPC) is a rare tumor of the central nervous system (CNS), which is distinguished clinically from meningioma by its tendency to recur and metastasize. The histological classification and grading scheme for m-HPC is still evolving and few studies have identified tumor features that are associated with metastasis. All patients at our institution with m-HPC were assessed for patient, tumor, and treatment characteristics associated with survival, recurrence, and metastasis. New findings were validated using the SEER database. Twenty-seven patients were identified in our institutional records with m-HPC with a median follow-up time of 85 months. Invasiveness was the strongest predictor of decreased overall survival (OS) and decreased metastasis-free survival (MFS) (p = 0.004 and 0.001). On subgroup analysis, bone invasion trended towards decreased OS (p = 0.056). Bone invasion and soft tissue invasion were significantly associated with decreased MFS (p = 0.001 and 0.012). An additional 315 patients with m-HPC were identified in the SEER database that had information on tumor invasion and 263 with information on distant metastasis. Invasion was significantly associated with decreased survival (HR = 5.769, p = 0.007) and metastasis (OR 134, p = 0.000) in the SEER data. In this study, the authors identified a previously unreported tumor characteristic, invasiveness, as the strongest factor associated with decreased survival and metastasis. The association of invasion with decreased survival and metastasis was confirmed in a separate, larger, publicly available database. Invasion may be a useful parameter in the histological grading and clinical management of hemangiopericytoma of the CNS.

Breast cancer subtype and stage are prognostic of time from breast cancer diagnosis to brain metastasis development.

Breast cancer brain metastasis (BCBM) is associated with high morbidity and mortality. Patients with breast cancer risk factors associated with rapid development of BCBM could potentially benefit from early brain metastasis screening. We retrospectively reviewed all BCBM patients treated with brain radiotherapy at our institution from 1997 to 2015. Interval time to BCBM was defined as date of pathologic breast cancer diagnosis to date of radiographic evidence of brain metastasis. Patients were stratified by breast cancer molecular subtype and stage at diagnosis. Kaplan Meier analysis was conducted on time to development of BCBM. Breast cancer risk factors were correlated with time to BCBM on Cox proportion hazard analysis. The study cohort comprised 121 BCBM patients, with median interval time to BCBM of 46 months. Times to BCBM for Her2+/2HR+, Her2+, Her2-/HR+, and triple-negative (TNBC) subtypes were 70, 44, 42, and 28 months respectively (p = 0.002). Time to BCBM for stages I, II, III, and IV were 70, 54, 29, and 24 months, respectively (p = 0.000). BCBM patients were further stratified by both molecular subtype (TNBC vs. non-TNBC) and stage (I, II vs. III, IV). Median times to BCBM for non-TNBC/stage I-II, TNBC/stage I-II, non-TNBC stage III-IV, and TNBC/stage III-IV were 68, 47, 29, and 6 months respectively (p = 0.000). Subtype and stage were associated with shorter time to BCBM on multivariate analysis. Subtype and initial stage are independently correlated with decreased time to development of BCBM. Patients with advanced high stage and triple negative breast cancer develop brain metastases significantly earlier.

Reevaluating stereotactic radiosurgery for glioblastoma: new potential for targeted dose-escalation.

Countless therapeutic strategies have been explored over many decades to prevent or slow the progression of glioblastoma. Despite radical changes in radiation management in other malignancies, there have been no major advances in the radiotherapeutic approach to glioblastoma in over 30 years. Past hopes to overcome inherent radioresistance with escalating doses have been met with frustration. However, prior clinical trials were performed before temozolomide, a radiosensitizer, altered the standard of care and this has renewed interest in dose escalation. Immunotherapy has led to further excitement, given the substantial responses that have been observed in other cancers when combined with high-dose radiation. In addition, advances in molecular profiling and neuroimaging have created new opportunities to improve patient selection for the most appropriate course of treatment. In this review, we outline past attempts to utilize radiosurgery in glioblastoma and focus on the potential to reintroduce this modality of dose escalation in the setting of modern and emerging systemic agents, molecular studies and imaging analyses.

Breast cancer subtype as a predictor for outcomes and control in the setting of brain metastases treated with stereotactic radiosurgery.

We investigated effects of breast cancer subtype on overall survival (OS), local and distant control, and time from initial diagnosis to brain metastases (BM). We also investigated advances in graded prognostic assessment (GPA) scores. A cohort of 72 patients treated for BM from breast cancer with Gamma Knife stereotactic radiosurgery at our institution from 2000 to 2014 had subtyping available and were used for this study. Median follow up for OS was 12 months and for control was 6 months. OS for luminal, HER2, and triple negative subtypes were 26, 20, and 22 months. OS when stratified by Sperduto et al. (J Clin Oncol 30(4):419-425, 2012) and Subbiah et al. (J Clin Oncol 33(20):2239-2245, 2015) GPAs were similar (p = 0.087 and p = 0.063). KPS and treatment modality were significant for OS (p = 0.002; p = 0.034). On univariate analysis, triple negative subtype and >3 BM were trending and significant for decreased OS (p = 0.084; p = 0.047). On multivariable analysis HER2, triple negative, and >3 BM were significant for OS (p = 0.022; p = 0.040; p = 0.009). Subtype was significant for response on a per lesion basis (p = 0.007). Subtype was trending towards significance when analyzing time from initial diagnosis to BM treatment (p = 0.064). Breast cancer subtype is an important prognostic factor when stratifying breast cancer patients with BM. The addition of number of BM to the GPA is a useful addition and should be further investigated. Subtype has an effect on lesion response, and also on rate of development BM after initial diagnosis.

Control of brain metastases from radioresistant tumors treated by stereotactic radiosurgery.

Renal cell carcinoma, sarcoma, and melanoma are considered to be "radioresistant" tumor histologies. Brain metastases (BM) from these tumors are considered unlikely to be controlled using the relatively low doses used in whole brain radiotherapy (WBRT). Our objective was to analyze the efficacy of stereotactic radiosurgery (SRS) on local control and overall survival of BM from radioresistant primary tumors. We reviewed all patients who received Gamma Knife Radiosurgery (GKRS) for BM at Columbia University Medical Center between January 2009 and April 2014. All patients were treated using the Gamma Knife Perfexion System. Dosimetric data was collected from treatment plans and metastases were categorized as radioresistant or not. Response was assessed by reviewing follow-up brain imaging studies and classified according to RECIST. Local control and median overall survival were calculated using the Kaplan-Meier method. In total, 373 tumors were analyzed from 126 patients. Of these tumors, 49 (13.1 %) originated from radioresistant cancers. The overall local control rate in the radioresistant cohort was 89.8 and 90.1 % in the non-radioresistant cohort. Univariate and multivariate analyses demonstrated that radioresistance status of the primary tumor had no statistically significant effect on local control with hazard ratios of 1.0 (p = 1.0, 95 % CI 0.388-2.576) and 0.954 (p = 0.926, 95 % CI 0.349-2.603) respectively. Median overall survival for both radioresistant and non-radioresistant cohorts was 20.0 months, with a p value of 0.926. There was no significant difference in local control of BM from radioresistant and non-radioresistant primary tumors treated with GKRS. Both cohorts showed excellent response and local control, suggesting that SRS upfront or in addition to WBRT may be an appropriate strategy in the treatment of BM from radioresistant cancers. Median overall survival for both cohorts was equal, suggesting that improved local control may be associated with an improvement in long-term survival.