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In this retrospective series out in @JCOPO_ASCO @GLambertiMD et al reported on intracranial activity of sotorasib in patients with #KRAS G12C mut #NSCLC @Oncoalert @DrMarkAwad #LCSM #JCOPO. [ABSTRACT FROM AUTHOR]

Objective: To identify systemic treatment in the real-world following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDKi) among post-menopausal women with hormone receptor positive, human epidermal growth factor receptor 2 Negative (HR+/HER2-) metastatic breast cancer (mBC).Methods: Post-menopausal women with HR+/HER2- mBC were identified from MarketScan claims databases between January 1, 2012 and October 31, 2017. Eligible mBC patients who received a CDKi-based line of therapy following metastasis diagnosis were selected. A line of therapy ended at the earlier of systemic therapy discontinuation, switch to new treatment, or censoring.Results: In total, 525 patients that received systemic therapy after a CDKi-based line were included (39.6% transitioned from use of a CDKi-based regimen in first line following metastasis diagnosis to any second line, and 60.4% shifted from a CDKi-based [second, third, or fourth line] to a subsequent line). Of post-CDKi second line regimens (n = 208), 38.0% were endocrine only, 35.6% were chemotherapy-based, 14.4% were everolimus-based, 9.6% were also CDKi-based line, and 2.4% were others. After adjusting for demographic and clinical characteristics, patients transitioning from a CDKi-based line to chemotherapy (vs others) had a trend of being more likely to have recurrent rapidly progressing disease, and were significantly less likely to have the prior CDKi-based line in combination with an AI (both p < .05).Conclusions: This population-based study suggests that rapidly progressing disease, metastatic site location, age, and endocrine therapy partner may be predictive of subsequent systemic therapy regimen selection after progression on a CDKi-based line therapy in patients with HR+/HER2- mBC. [ABSTRACT FROM AUTHOR]

Background: Prior studies have only considered the association between static marital status and cancer-specific outcomes. We aim to measure the effect of recent divorce on cancer-specific outcomes.Methods: There were 83,804 patients with 2 malignancies, diagnosed 12 to 60 months apart, from 1973-2006 from the Surveillance, Epidemiology, and End Results database. Patients were identified as newly divorced if married at their first diagnosis and single/divorced at their second. Multivariable logistic regression and competing-risks regression were used to analyze the association of becoming newly divorced or newly married with cancer-specific outcomes from the second malignancy, including advanced diagnosis (T4 or N1 or M1), receipt of treatment, and cancer-specific survival.Results: Four percent became newly divorced and 3.4% became newly married. Compared with long-term married, newly divorced patients were most likely to be diagnosed with advanced disease (adjusted odds ratio [AOR] 1.31; 95% confidence interval [CI], 1.19-1.43), followed by long-term divorced (AOR 1.18; 95% CI, 1.11-1.25), and were least likely to receive curative treatment (AOR 0.74; 95% CI, 0.67-0.81). Newly divorced patients had the worst cancer-specific survival (adjusted hazard ratio [AHR] 1.17; 95% CI, 1.05-1.30, P = .005), followed by long-term divorced (AHR 1.08; 95% CI, 1.01-1.16, P = .032), while newly married patients had similar cancer-specific survival to long-term married (AHR 0.96; 95% CI, 0.85-1.08, P = .46).Conclusion: Recent divorce, which represents an acute disruption of a patient's social support network, was associated with the worst cancer outcomes, followed by long-term divorce. Clinicians should consider recent divorce as a risk factor for worse cancer outcomes, and encourage appropriate screening, treatment, and access to social and financial supports for recently divorced patients. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to determine whether a very low presenting prostate-specific antigen (PSA) level was associated with greater prostate cancer-specific mortality (PCSM) among men with a Gleason score (GS) of 8 to 10.Methods: The Surveillance, Epidemiology, and End Results program was used to identify 328,904 men diagnosed with clinicalT1 (cT1)-4N0M0 prostate cancer between 2004 and 2010. A multivariate Fine-Gray competing risks regression analysis was used to determine PCSM as a function of the PSA level (≤ 2.5, 2.6-4, 4.1-10, 10.1-20, 20.1-40, or > 40 ng/mL) and GS (8-10 vs ≤ 7).Results: The median follow-up was 38 months. Among men with GS 8-10 disease, with a PSA level of 4.1 to 10 ng/mL as the referent, the adjusted hazard ratio for PCSM for men was 2.15 with a PSA level ≤ 2.5 ng/mL (95% confidence interval [CI], 1.65-2.79; P < .001), 1.60 with a PSA level of 2.6 to 4 ng/mL (95% CI, 1.22-2.10; P = .001), 1.60 with a PSA level of 10.1 to 20 ng/mL (95% CI, 1.41-1.82; P < .001), 2.08 with a PSA level of 20.1 to 40 ng/mL (95% CI, 1.81-2.38; P < .001), and 3.23 with a PSA level > 40 ng/mL (95% CI, 2.85-3.65; P < .001). This suggested a U-shaped distribution. There was a significant interaction between the PSA level and GS (P(interaction)  < .001) such that only a PSA level ≤ 2.5 ng/mL significantly predicted poorer PCSM among patients with GS 8-10 disease.Conclusions: Among patients with high-grade disease, patients with PSA levels ≤ 2.5 ng/mL or PSA levels of 2.6 to 4 ng/mL appear to have a higher risk for cancer-specific death in comparison with patients with PSA levels of 10.1 to 20 ng/mL, and this supports the notion that low PSA levels in GS 8-10 disease may be a sign of aggressive and very poorly differentiated or anaplastic low PSA-producing tumors. Patients with low-PSA, GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents for very high-risk prostate cancers. [ABSTRACT FROM AUTHOR]

Background: The prognosis for patients with atypical and malignant meningioma is guarded; whether the extent of resection is associated with survival-based outcomes in this population remains poorly defined. This study investigated the association between gross total resection (GTR) and all-cause mortality in patients with atypical and malignant meningioma.Methods: The Surveillance, Epidemiology, and End Results program was used to identify 575 and 64 patients betweens the ages of 18 and 70 years who were diagnosed with atypical and malignant meningioma, respectively, between 2004 and 2009. Multivariate Cox proportional hazards regression was used to assess the adjusted impact of GTR versus subtotal resection on all-cause mortality.Results: Baseline patient characteristics were similar for patients who did undergo GTR and patients who did not undergo GTR. The 5-year overall survival rates were 91.3% (95% confidence interval [CI], 86.2%-94.5%) and 78.2% (95% CI, 70.0%-84.3%) for patients with atypical meningioma who did and did not undergo GTR, respectively, and 64.5% (95% CI, 45.9%-78.1%) and 41.1% (95% CI, 17.9%-63.1%) for patients with malignant meningioma who did and did not undergo GTR, respectively. After adjustments for available, pertinent confounding variables, GTR was associated with lower all-cause mortality in patients with atypical (hazard ratio, 0.39; 95% CI, 0.23-0.67; P < .001) and malignant meningioma (hazard ratio, 0.35; 95% CI, 0.15-0.81; P = .01).Conclusions: The extent of resection is a powerful predictor of outcome for patients with atypical and malignant meningioma. These data highlight the hazard associated with the presence of gross tumor bulk after surgery and suggest a value for more extensive resections that should be balanced against the additional potential morbidity. [ABSTRACT FROM AUTHOR]

Objective To determine whether African Americans (AAs) with intermediate- to high-risk prostate cancer (PCa) receive similar treatment as white patients and whether any observed disparities are narrowing with time. Methods We used Surveillance, Epidemiology, and End Results to identify 128,189 men with localized intermediate- to high-risk PCa (prostate-specific antigen ≥10 ng/mL, Gleason score ≥7, or T stage ≥T2b) diagnosed from 2004 to 2010. We used multivariate logistic regression analyses to determine the impact of race on the receipt of definitive treatment. Results AA men were significantly less likely to receive curative-intent treatment than white men (adjusted odds ratio [AOR], 0.82; 95% confidence interval [CI], 0.79-0.86; P <.001). There was no evidence of this disparity narrowing over time (Pinteraction 2010 vs 2004 = .490). Disparities in the receipt of treatment between AA and white men were significantly larger in high-risk (AOR, 0.60; 95% CI, 0.56-0.64; P <.001) than in intermediate-risk disease (AOR, 0.92; 95% CI, 0.88-0.97; P = .04; Pinteraction <.001). After adjusting for treatment, demographics, and prognostic factors, AA men had a higher risk of prostate cancer-specific mortality (adjusted hazard ratio, 1.12; 95% CI, 1.01-1.25; P = .03). Conclusion AA men with intermediate- to high-risk PCa are less likely to be treated with curative intent than white men. This disparity is worse in high-risk disease and is not improving over time. Factors underlying this treatment disparity should be urgently studied as it is a potentially correctable contributor to excess PCa mortality among AA patients. [ABSTRACT FROM AUTHOR]

Purpose: Surgery and radiation therapy represent the only curative options for many patients with solid malignancies. However, despite the recommendations of their physicians, some patients refuse these therapies. This study characterized factors associated with refusal of surgical or radiation therapy as well as the impact of refusal of recommended therapy on patients with localized malignancies. Methods and Materials: We used the Surveillance, Epidemiology, and End Results program to identify a population-based sample of 925,127 patients who had diagnoses of 1 of 8 common malignancies for which surgery and/or radiation are believed to confer a survival benefit between 1995 and 2008. Refusal of oncologic therapy, as documented in the SEER database, was the primary outcome measure. Multivariable logistic regression was used to investigate factors associated with refusal. The impact of refusal of therapy on cancer-specific mortality was assessed with Fine and Gray's competing risks regression. Results: In total, 2441 of 692,938 patients (0.4%) refused surgery, and 2113 of 232,189 patients (0.9%) refused radiation, despite the recommendations of their physicians. On multivariable analysis, advancing age, decreasing annual income, nonwhite race, and unmarried status were associated with refusal of surgery, whereas advancing age, decreasing annual income, Asian American race, and unmarried status were associated with refusal of radiation (P<.001 in all cases). Refusal of surgery and radiation were associated with increased estimates of cancer-specific mortality for all malignancies evaluated (hazard ratio [HR], 2.80, 95% confidence interval [CI], 2.59-3.03; P<.001 and HR 1.97 [95% CI, 1.78-2.18]; P<.001, respectively). Conclusions: Nonwhite, less affluent, and unmarried patients are more likely to refuse curative surgical and/or radiation-based oncologic therapy, raising concern that socioeconomic factors may drive some patients to forego potentially life-saving care. [Copyright &y& Elsevier]

BACKGROUND To the authors' knowledge, it remains unknown whether race-based differences in cancer outcomes have changed with time. In the current study, the authors assessed whether racial disparities in cancer-specific mortality have improved over the last 20 years. METHODS The Surveillance, Epidemiology, and End Results program was used to identify 2,713,474 patients diagnosed between 1988 and 2007 with either lung, breast, prostate, or colorectal cancer (the leading 3 causes of cancer-related mortality among each sex). After exclusions, 1,001,978 patients remained eligible for analysis. The impact of race on cancer-specific mortality was assessed using the regression model of Fine and Gray; an interaction model evaluated trends over time. RESULTS African Americans presented with a more advanced stage of disease ( P < .001) and underwent definitive therapy less often ( P < .001) than whites. After adjustment for demographics and year of diagnosis, African Americans were found to have higher estimates of cancer-specific mortality than whites for all cancers combined (hazards ratio, 1.28; 95% confidence interval, 1.26-1.30 [ P < .001]) and within each individual cancer (each P < .05). These differences did not change significantly between 1988 through 1997 and 1998 through 2007, except among patients with breast cancer, in whom survival disparities increased. These findings remained significant after adjustment for stage of disease at presentation and receipt of definitive therapy (hazards ratio for breast cancer mortality in African Americans vs whites: 1.37 from 1988-1997 and 1.53 from 1998-2007; P for interaction, < .001). CONCLUSIONS The survival gap for African Americans has not closed over time. Race-based differences in outcome persist independent of stage of disease and treatment, suggesting that additional strategies beyond screening and improving access to care, such as further research into tumor biologies disproportionately affecting African Americans, are needed to improve survival for African American patients with cancer. Cancer 2014;120:1532-1539. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective To determine whether patients with metastatic non-clear-cell renal cell carcinoma ( RCC) benefit from cytoreductive nephrectomy ( CN)., Patients and Methods We used the Surveillance, Epidemiology, and End Results ( SEER) programme to identify a population-based sample of 4914 patients diagnosed with metastatic RCC between 2000 and 2009., Of the 4914 patients, 591 had non-clear-cell histology., The median follow-up was 20 months., The primary outcome measure was RCC-specific mortality., Results Approximately 64% of patients underwent CN., Patients with non-clear-cell histology who underwent CN had lower RCC-specific and all-cause mortality than those who did not ( P < 0.001 in both cases)., After adjustment for age, gender, race, marital status, year of diagnosis, geographical location and histology, the associations between CN and lower RCC-specific mortality (hazard ratio [ HR] 0.62, 95% confidence interval [ CI] 0.48-0.80, P < 0.001) and between CN and all-cause mortality ( HR 0.45, 95% CI 0.37-0.55, P < 0.001) remained highly significant., Among patients diagnosed between 2006 and 2009 (targeted therapy era), the results remained unchanged ( HR 0.50, 95% CI 0.34-0.72, P < 0.001 and HR 0.43, 95% CI 0.31-0.59, P < 0.001, respectively)., An interaction model found lower all-cause mortality for all histologies after CN., Conclusions Patients from the SEER programme with metastatic non-clear-cell RCC, including those treated in the targeted therapy era, appear to derive a survival benefit from CN, an association which remained significant regardless of histological subtype., This observation suggests that CN should remain standard in patients with advanced RCC who are deemed to be surgical candidates. [ABSTRACT FROM AUTHOR]

Purpose: Specialist bias, in which specialists recommend the therapy that they are capable of delivering, is thought to influence the treatment of patients with localized prostate cancer and to contribute to overtreatment of men with limited life expectancy. Consequently, rates of active surveillance, the preferred management modality per the National Comprehensive Cancer Network (NCCN) for patients with low- and very low-risk disease and a life expectancy of less than 10 and less than 20 years, respectively, are low. We sought to determine whether consultation with a medical oncologist is associated with increased rates of active surveillance in men with low-risk prostate cancer. Methods: We identified 188 patients with low-risk prostate cancer undergoing active surveillance at one of three referral centers in Boston, MA in 2009. Multivariable logistic regression was used to determine whether consultation with a medical oncologist was associated with selection of active surveillance. The data were reanalyzed for patients with low- and very low-risk disease and a life expectancy of less than 10 and less than 20 years, respectively. Results: Consultation with a medical oncologist was associated with increased rates of active surveillance (37% v 21%, P = .01), an association that remained significant on multivariable logistic regression (odds ratio [OR] = 2.70; 95% CI, 1.27 to 5.75; P = .01). When applied to patients with limited life expectancy, this finding remained significant (OR = 4.74; 95% CI, 1.17 to 19.25; P = .03). Conclusion: Consultation with a medical oncologist is associated with increased rates of active surveillance, adherence to NCCN guidelines, and minimization of overtreatment in men with early prostate cancer and limited life expectancy. [ABSTRACT FROM AUTHOR]

BACKGROUND Randomized trials have demonstrated that radiation improves survival in patients with glioblastoma. The purpose of this study was to characterize the risk factors and impact of omission of radiation therapy in such patients. METHODS The Surveillance, Epidemiology, and End Results (SEER) program was used to identify 22,777 patients diagnosed with glioblastoma between 1988 and 2007. Multivariable logistic regression was employed to identify predictors associated with omission of radiation. Cox regression was used to characterize the impact of omitting radiation on all-cause mortality. RESULTS Among the entire cohort, 16,863 of 22,777 patients (74%) received radiation, whereas 5914 of 22,777 patients (26%) did not. Factors associated with omission of radiation included older age (OR = 1.048 per year increase, 95% CI = 1.046-1.051, P < .001), lower annual income (OR = 0.93 per $10,000 increase, 95% CI = 0.90-0.96, P < .001), African American race (reference = white, OR = 1.19, 95% CI = 1.03-1.37, P = .02), Hispanic race (OR = 1.34, 95% CI = 1.19-1.50, P < .001), Asian American race (OR = 1.24, 95% CI = 1.04-1.48, P < .001), unmarried status (OR = 1.71, 95% CI = 1.60-1.83, P < .001), and subtotal resection/biopsy (OR = 1.82, 95% CI = 1.69-1.96, P < .001). The use of radiation was significantly associated with improved overall survival (2-year survival: 14.6% versus 4.2%, P < .001; adjusted HR = 2.09, 95% CI = 2.02-2.16, P < .001). When the population was restricted to patients < 50 years old, these findings remained largely unchanged. CONCLUSIONS Radiation therapy is associated with survival benefit in patients with glioblastoma, and sociodemographic factors play a significant role in the underutilization of radiation. The underlying causes for these disparities in care require further research. Cancer 2014;120:238-243. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? The recently published Prostate Cancer Intervention versus Observation Trial ( PIVOT) did not identify differences in prostate cancer-specific mortality or all-cause mortality among patients with low-risk disease managed conservatively vs those managed definitively; however, recently published data suggest that older men may harbour more aggressive disease than is identified at biopsy owing to sampling error and undergrading. Whether older men with apparent low-risk disease are placed at risk of prostate cancer-specific mortality when managed conservatively remains unknown., The study used population-level data to show that non-curative approaches for older men with low-risk prostate cancer do result in an increased risk of prostate cancer-specific mortality. Differences between our study and the PIVOT trial include the fact that we included a larger sample size, analysed the data using an 'as-treated' approach, and included a healthier cohort of men as evinced by lower 4-year all-cause mortality estimates in our study than in the PIVOT. Our results suggest that older men with apparent low-risk prostate cancer are at risk of undergrading, which probably explains the differences in prostate cancer-specific mortality observed between men managed conservatively vs those managed definitively. Our study suggests that alternative approaches to excluding occult, high grade prostate cancer are needed in such men., Objective To evaluate whether older age in men with low-risk prostate cancer increases the risk of prostate cancer-specific mortality ( PCSM) when non-curative approaches are selected as initial management., Patients and Methods The study cohort consisted of 27 969 men, with a median age of 67 years, with prostate-specific antigen ( PSA)-detected, low-risk prostate cancer (clinical category T1c, Gleason score ≤6, and PSA ≤10) identified by the Surveillance, Epidemiology and End Results programme between 2004 and 2007., Fine and Gray's competing risk regression analysis was used to evaluate whether management with non-curative vs curative therapy was associated with an increased risk of PCSM after adjusting for PSA level, age at diagnosis and year of diagnosis., Results After a median follow-up of 2.75 years, 1121 men died, 60 (5.4%) from prostate cancer., Both older age (adjusted hazard ratio [ AHR] 1.05; 95% confidence interval ( CI) 1.02-1.08; P < 0.001) and non-curative treatment ( AHR 3.34; 95% CI 1.97-5.67; P < 0.001) were significantly associated with an increased risk of PCSM., Men > the median age experienced increased estimates of PCSM when treated with non-curative as opposed to curative intent ( P < 0.001); this finding was not seen in men ≤ the median age ( P = 0.17)., Conclusion Pending prospective validation, our study suggests that non-curative approaches for older men with 'low-risk' prostate cancer result in an increased risk of PCSM, suggesting the need for alternative approaches to exclude occult, high grade prostate cancer in these men. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm3, respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher''s exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Results: Patients with large prostates (>50 cm3) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm3 increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Conclusions: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer. [Copyright &y& Elsevier]

Purpose: To determine whether whole pelvic radiotherapy (WPRT) or prostate-only radiotherapy (PORT) yields improved biochemical disease-free survival (BDFS) in patients with advanced or aggressive prostate adenocarcinoma. Methods and Materials: Between 2000 and 2007, a consecutive sample of 277 patients with prostate adenocarcinoma and at least a 15% likelihood of lymph node involvement who had undergone WPRT (n = 68) or PORT (n = 209) at two referral centers was analyzed. The median radiation dose in both arms was 75.6 Gy. The outcome measure was BDFS, as determined using the prostate-specific antigen nadir + 2 ng/mL definition of failure. BDFS was calculated using the Kaplan-Meier method and compared with the log–rank test. A multivariate analysis was performed to assess for confounding. Treatment-related toxicity was assessed using the National Cancer Institute''s Common Terminology Criteria for Adverse Events guidelines. The median follow-up was 30 months. Results: WPRT patients had more advanced and aggressive disease at baseline (p < .001). The 4-year BDFS rate was 69.4% in the PORT cohort and 86.3% in the WPRT cohort (p = .02). Within the entire cohort, after adjustment for confounding variables, the pretreatment prostate-specific antigen (p < .001), Gleason score (p < .001), use of hormonal therapy (p = .002), and use of WPRT (vs. PORT, p = .006) predicted for BDFS. Patients undergoing WPRT had increased acute gastrointestinal toxicity (p = .048), but no significant difference in acute genitourinary toxicity was seen (p = .09). No difference in late toxicity was found. Conclusion: WPRT may yield improved BDFS in patients with advanced or aggressive prostate adenocarcinoma, but results in a greater incidence of acute toxicity. [Copyright &y& Elsevier]

Abstract: Background and purpose: To determine whether radical prostatectomy (RP) or intensity-modulated radiation therapy (IMRT) to ⩾72Gy, plus hormonal therapy if indicated, results in improved biochemical disease-free survival (BDFS) in localized prostate adenocarcinoma. Materials and methods: Between 1997 and 2005, a consecutive sample of 556 patients who underwent RP (n =204) or IMRT (n =352) at two referral centers was analyzed. The patients were stratified into prognostic groups based on clinical stage, Gleason score, and pretreatment prostate-specific antigen (PSA). The outcome measure was BDFS. Results: IMRT patients had more advanced disease at baseline (p <.001). There was no difference in five-year BDFS rates between RP and IMRT in the favorable (92.8% vs. 85.3%, p =.20) or intermediate prognosis (86.7% vs. 82.2%, p =.46) subsets. A difference favoring IMRT plus hormonal therapy was seen in the poor prognosis (38.4% vs. 62.2%, p <.001) subset. Within the entire cohort, after adjustment for confounding variables, Gleason score (p <.001) and clinical stage (p <.001) predicted BDFS, but treatment modality (p =.06) did not. Within the poor prognosis subset, treatment modality (p =.006) predicted BDFS. Conclusions: BDFS is similar between RP and IMRT for patients with a favorable or intermediate prognosis. Patients with a poor prognosis display higher BDFS when treated with IMRT to ⩾72Gy plus hormonal therapy. [Copyright &y& Elsevier]

Abstract: While axonal regeneration is more successful in peripheral nerve than in the central nervous system, it is by no means complete and research to enhance peripheral nerve regeneration is clinically important. Olfactory ensheathing cells (OECs) are known to enhance axonal regeneration and to produce myelin after transplantation. In contrast to Schwann cells their migratory potential and ability to penetrate glial scars is higher. This study evaluated the effect of OEC transplantation on microsurgically repaired sciatic nerves. Rat sciatic nerves were transected followed by microsurgical repair and transplantation of OECs or injection of medium without cells. Twenty-one days later the nerves were removed and prepared for either histology or electrophysiological analysis. Footprint analysis was carried out at 7, 14 and 21 days. The OECs survived and integrated into the repaired nerves as indicated by eGFP-expressing cells aligned with neurofilament identified axons bridging the repair site. Moreover, regenerated axons were myelinated by the transplanted OECs and nodes of Ranvier were formed. Conduction velocity in the OEC transplant group was increased in comparison to the microsurgical repair alone, and improved stepping was observed in the transplant group. These results suggest that presentation of OECs at the time of nerve injury enhances regeneration and improves functional outcome. Even a modest improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery. [Copyright &y& Elsevier]

Background and introduction: Increasing evidence suggests that a subgroup of patients with oligometastatic cancer might achieve a prolonged disease-free survival through local therapy for all active cancer lesions. Our aims are to investigate the impact of brain metastases on the classification, treatment, and outcome in these patients. Materials and methods: We analyzed a total of 7,000 oncological positron emission tomography scans to identify patients with extracranial oligometastatic disease (defined as ≤ 5 intra- or extra-cranial metastases). Concurrent magnetic resonance imaging brain was assessed to quantify intracranial tumor burden. We investigated the impact of brain metastases on oligometastatic disease state, therapeutic approaches, and outcome. Predictors for transitioning from oligo- to polymetastatic states were evaluated using regression analysis. Results: A total of 106 patients with extracranial oligometastases and simultaneous brain metastases were identified, primarily originating from skin or lung/pleura cancers (90%, n = 96). Brain metastases caused a transition from an extracranial oligometastatic to a whole-body polymetastatic state in 45% (n = 48) of patients. While oligometastatic patients received systemic therapy (55% vs. 35%) more frequently and radiotherapy for brain metastases was more often prescribed to polymetastatic patients (44% vs. 26%), the therapeutic approach did not differ systematically between both sub-groups. The oligometastatic sub-group had a median overall survival of 28 months compared to 10 months in the polymetastatic sub-group (p < 0.01). Conclusion: In patients with brain metastases, a low total tumor burden with an oligometastatic disease state remained a significant prognostic factor for overall survival. Presence of brain metastases should therefore not serve as exclusion criterion for clinical trials in the field of oligometastatic disease. Moreover, it underscores the importance of considering a multimodality treatment strategy in oligometastatic cancer patients. [ABSTRACT FROM AUTHOR]

The syntheses of three C2 symmetric triptycenes containing two pendant groups are described. The pendant groups are designed to promote oriented adsorption to graphite or gold electrodes such that the unfunctionalized aryl group extends perpendicular to the surface. Initial STM studies are consistent with oriented adsorption on graphite. [Copyright &y& Elsevier]

The effect of adjuvant radiotherapy in management for high‐grade meningiomas, especially atypical meningiomas, remains controversial. We aimed to explore the role of adjuvant radiotherapy in this population. A total of 162 adults with high‐grade meningiomas (99 atypical meningiomas and 63 anaplastic meningiomas) were treated from 2003 to 2008 at Huashan Hospital. One hundred and seventeen patients presented with primary and 45 with recurrent disease. One hundred and fifteen patients (70.9%) were treated with adjuvant radiotherapy after surgical resection. The median follow‐up was 76.5 months (range 1‐142 months). Kaplan‐Meier survival curve and Cox proportional hazards modeling were used for analyses. Adjuvant radiotherapy was associated with prolonged progression‐free survival (PFS) and overall survival (OS) in patients with newly diagnosed anaplastic meningiomas irrespective of extent of resection (PFS, P = .001; OS, P = .003). Gross total resection was the only independent prognostic factor for those with newly diagnosed atypical meningiomas (PFS, P < .001; OS, P = .012). A survival benefit for adjuvant radiation was also found in subgroup analysis of patients with high‐grade meningiomas who underwent subtotal resection (PFS, P = .023; OS, P = .013). Among recurrent high‐grade meningiomas, radiotherapy offered no statistically significant improvement in either PFS or OS. Adjuvant radiotherapy is associated with improved survival in patients with newly diagnosed anaplastic meningiomas and those high‐grade meningiomas following subtotal resection. However, there was no significant correlation identified between postoperative radiation and outcome for recurrent high‐grade meningiomas. Future prospective randomized trials may help clarify the optimal tailored treatment for patients with high‐grade meningioma. The article focuses on the prognostic value of postoperative radiation in patients with atypical or anaplastic meningioma. We demonstrate that adjuvant radiotherapy is associated with improved survival in patients with high‐grade meningiomas following subtotal resection. However, postoperative radiation was not associated with significant improvement in outcome for patients with recurrent high‐grade meningiomas. The article focuses on the prognostic value of postoperative radiation in patients with atypical or anaplastic meningioma. We demonstrate that adjuvant radiotherapy is associated with improved survival in patients with high‐grade meningiomas following subtotal resection. However, postoperative radiation was not associated with significant improvement in outcome for patients with recurrent high‐grade meningiomas. [ABSTRACT FROM AUTHOR]

PURPOSE: RET rearrangements and RET activating point mutations represent targetable genomic alterations in advanced solid tumors. However, the frequency and clinicopathologic characteristics of wild-type RET amplification in cancer and its potential role as a targetable oncogenic driver are not well-characterized. METHODS: In two institutional cohorts of patients with solid cancers from the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC) whose tumors underwent next-generation sequencing (NGS), the frequency and clinicopathologic features of wild-type RET amplification in the absence of RET rearrangements or activating mutations was assessed. The findings were validated using merged data from The Cancer Genome Atlas (TCGA), Genomics Evidence Neoplasia Information Exchange (GENIE), and China Pan-Cancer data sets. RESULTS: The frequency of wild-type RET amplification across all solid cancers was 0.08% (26 of 32,505) in the DFCI cohort, 0.05% (26 of 53,152) in the MSKCC cohort, and 0.25% (71 of 28,623) in the cohort from TCGA, GENIE, and China Pan-Cancer. Cancer types with RET amplification included non–small-cell lung cancer (NSCLC), hepatobiliary cancer, prostate cancer, breast cancer, and others. The median RET copy number in RET -amplified cases was 7.5 (range, 6-36) in the DFCI cohort and 5.7 (range, 4-27.7) in the MSKCC cohort. Among 11 RET -amplified NSCLCs, eight had no other concurrent driver mutations. Finally, we report on a 69-year-old man with recurrent NSCLC harboring high-level wild-type RET amplification (22-28 copies) as the only identified putative genomic driver who experienced both a systemic and intracranial confirmed response to the RET inhibitor selpercatinib. CONCLUSION: Amplification of wild-type RET represents a novel, targetable molecular subset of cancer. This study establishes wild-type RET amplification as a novel, actionable genomic subset of cancer. [ABSTRACT FROM AUTHOR]

Objectives: The clinical management of meningioma is guided by tumor grade and biological behavior. Currently, the assessment of tumor grade follows surgical resection and histopathologic review. Reliable techniques for pre-operative determination of tumor grade may enhance clinical decision-making. Methods: A total of 175 meningioma patients (103 low-grade and 72 high-grade) with pre-operative contrast-enhanced T1-MRI were included. Fifteen radiomic (quantitative) and 10 semantic (qualitative) features were applied to quantify the imaging phenotype. Area under the curve (AUC) and odd ratios (OR) were computed with multiple-hypothesis correction. Random-forest classifiers were developed and validated on an independent dataset (n = 44). Results: Twelve radiographic features (eight radiomic and four semantic) were significantly associated with meningioma grade. High-grade tumors exhibited necrosis/hemorrhage (ORsem = 6.6, AUCrad = 0.62–0.68), intratumoral heterogeneity (ORsem = 7.9, AUCrad = 0.65), non-spherical shape (AUCrad = 0.61), and larger volumes (AUCrad = 0.69) compared to low-grade tumors. Radiomic and sematic classifiers could significantly predict meningioma grade (AUCsem = 0.76 and AUCrad = 0.78). Furthermore, combining them increased the classification power (AUCradio = 0.86). Clinical variables alone did not effectively predict tumor grade (AUCclin = 0.65) or show complementary value with imaging data (AUCcomb = 0.84). Conclusions: We found a strong association between imaging features of meningioma and histopathologic grade, with ready application to clinical management. Combining qualitative and quantitative radiographic features significantly improved classification power. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory breast cancer (IBC) have a high risk of central nervous system metastasis (mCNS). The purpose of this study was to quantify the incidence of and identify risk factors for mCNS in patients with IBC. Methods: The authors retrospectively reviewed patients diagnosed with IBC between 1997 and 2019. mCNS‐free survival time was defined as the date from the diagnosis of IBC to the date of diagnosis of mCNS or the date of death, whichever occurred first. A competing risks hazard model was used to evaluate risk factors for mCNS. Results: A total of 531 patients were identified; 372 patients with stage III and 159 patients with de novo stage IV disease. During the study, there were a total of 124 patients who had mCNS. The 1‐, 2‐, and 5‐year incidence of mCNS was 5%, 9%, and 18% in stage III patients (median follow‐up: 5.6 years) and 17%, 30%, and 42% in stage IV patients (1.8 years). Multivariate analysis identified triple‐negative tumor subtype as a significant risk factor for mCNS for stage III patients. For patients diagnosed with metastatic disease, visceral metastasis as first metastatic site, triple‐negative subtype, and younger age at diagnosis of metastases were risk factors for mCNS. Conclusions: Patients with IBC, particularly those with triple‐negative IBC, visceral metastasis, and those at a younger age at diagnosis of metastatic disease, are at significant risk of developing mCNS. Further investigation into prevention of mCNS and whether early detection of mCNS is associated with improved IBC patient outcomes is warranted. Patients with inflammatory breast cancer (IBC), particularly those with triple negative IBC, visceral metastasis, and those at a younger age at diagnosis of metastatic disease, are at significant risk of developing central nervous system metastasis (mCNS). Further investigation into prevention of mCNS and whether early detection of mCNS is associated with improved IBC patient outcomes is warranted. [ABSTRACT FROM AUTHOR]

Aim No evidence-based approach to the evaluation of CKD has been established. We sought to identify clinical criteria to guide a rational diagnostic approach for the initial evaluation of CKD. Methods We conducted a retrospective cohort study of 1487 patients presenting for initial evaluation of CKD over 3 years (1/2010-1/2013) to academic nephrology clinics. We utilized the electronic medical record to determine tests ordered, abnormal results and testing that affected diagnosis and/or management. Diagnostic and management yield of testing was defined as the percentage of tests that affected diagnosis and/or management. High yield for a given test was defined as an increased likelihood of the test affecting diagnosis and/or management. Results We identified clinical criteria predictive of high yield for paraprotein-related testing (one of the following: history of monoclonal disease, high risk of CKD progression, hypercalcemia or haemoglobin < 10.6), and clinical criteria predictive of high yield for glomerulonephritis testing (one of the following: abnormal urine sediment, 3+ or greater hematuria or proteinuria > 500 mg/gm). A prior history of hydronephrosis and renal artery stenosis was predictive of high yield of abnormal renal ultrasound. Higher yield of testing was associated with higher risk progression categories for ANA, SPEP, urine sediment, calcium, PTH, haemoglobin, iron and ferritin. We estimate that initial CKD evaluation costs range from $28 to $109 million/year in US-Medicare expenditure. Conclusion Numerous tests without significant clinical utility are obtained in initial CKD evaluation. Identifying criteria that can guide diagnostic testing may lead to a more informed and cost-effective approach to evaluation. [ABSTRACT FROM AUTHOR]

Purpose: We retrospectively evaluated outcomes after radiation therapy for patients with oligoprogression on immune checkpoint inhibitors (ICI).Methods and Materials: We identified patients irradiated to ≤5 progressive lesions while receiving ICI between 2010 and 2020. We excluded patients whose systemic therapy was switched after radiation but before progression. We evaluated predictors of local control (LC), progression-free survival (PFS) and overall survival (OS).Results: We screened 1423 patients and identified 120 who were eligible; the most common histologies were lung cancer (n = 59) and melanoma (n = 36). The median number of oligoprogressive lesions was 1. For the median LC of irradiated oligoprogressive lesions, PFS and OS were not reached at 6.41 (4.67-7.66) and 29.80 (22.54-43.33) months, respectively. Tumor histology, radiated site, or radiation modality were not associated with LC, PFS, or OS. Local response to radiation (P < .0001) and radiation of newly developed lesions (P = .02) were associated with LC. Predictors of PFS on univariate and multivariate analyses were best response to radiation (P = .006) and high programmed death ligand 1 tumor proportion score (P = .02). On multivariate analyses, OS was associated with cumulative oligoprogressive lesion volumes (P = .02) and duration of ICI before oligoprogression (P = .03).Conclusions: Promising outcomes were observed among patients irradiated for oligoprogression on ICI, especially those with a favorable local response, high tumor programmed death ligand 1 expression, and those receiving ICI for longer periods before oligoprogression. These data can help identify patients well suited for radiation therapy versus those who should switch systemic treatment. [ABSTRACT FROM AUTHOR]

Purpose Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ). Methods and Materials We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013. The distribution of clinical covariates across various radiation regimens was analyzed for possible selection bias. Survival was calculated using the Kaplan-Meier method. Comparison of hypofractionated radiation (typically, 40 Gy/15 fractions) versus standard fractionation (typically, 60 Gy/30 fractions) in the setting of temozolomide was conducted using Cox regression and propensity score analysis. Results Patients received SRT + TMZ (n=57), SRT (n=35), HRT + TMZ (n=34), or HRT (n=9). Patients receiving HRT were significantly older (median: 79 vs 69 years of age; P <.001) and had worse baseline performance status ( P <.001) than those receiving SRT. On multivariate analysis, older age (adjusted hazard ratio [AHR]: 1.06; 95% confidence interval [CI]: 1.01-1.10, P =.01), lower Karnofsky performance status (AHR: 1.02; 95% CI: 1.01-1.03; P =.01), multifocal disease (AHR: 2.11; 95% CI: 1.23-3.61, P =.007), and radiation alone (vs SRT + TMZ; SRT: AHR: 1.72; 95% CI: 1.06-2.79; P =.03; HRT: AHR: 3.92; 95% CI: 1.44-10.60, P =.007) were associated with decreased overall survival. After propensity score adjustment, patients receiving HRT with TMZ had similar overall survival compared with those receiving SRT with TMZ (AHR: 1.10, 95% CI: 0.50-2.4, P =.82). Conclusions With no randomized data demonstrating equivalence between HRT and SRT in the setting of TMZ for glioblastoma, significant selection bias exists in the implementation of HRT. Controlling for this bias, we observed similar overall survival for HRT and SRT with concurrent TMZ among elderly patients, suggesting the need for a randomized trial to compare these regimens directly. [ABSTRACT FROM AUTHOR]

Purpose The long-term prostate cancer-specific survival for patients initially managed with active surveillance for low-risk prostate cancer ranges from 97% to 100%. We characterized factors that are associated with aggressive treatment with radical prostatectomy or radiation for indolent prostate cancer (defined as screening-detected, low-risk disease). Methods The Surveillance, Epidemiology, and End Results Program was used to extract a cohort of 39,803 men diagnosed with prostate-specific antigen–detected, low-risk prostate cancer (clinical category T1c, Gleason score ≤6, and prostate-specific antigen <10) from 2004 to 2010. After socioeconomic profiles were generated from county-linked education and income data, multivariable logistic regression was used to determine whether there were any factors associated with high rates of aggressive treatment. Results The rate of aggressive treatment among all men with indolent prostate cancer was 64.3%. Greater rates of aggressive treatment were experienced by men with high socioeconomic status, Caucasian men, and married men ( P < .001 for all cases). The increased adjusted odds for receipt of aggressive therapy were 1.25 (95% confidence interval [CI], 1.17-1.32; P < .001), 1.26 (95% CI, 1.21-1.32; P < .001), and 1.88 (95% CI, 1.80-1.97; P < .001) for men with high socioeconomic status, Caucasian men, and married men, respectively, compared with men with low socioeconomic status, non-Caucasian men, and unmarried men, respectively. Conclusions Although men with high socioeconomic status, Caucasian men, and married men often receive the highest quality health care and have the best outcomes for many cancers, it seems that they are most at risk for the avoidable potential harms of aggressive treatment of indolent prostate cancer. Future policy should encourage more stringent guidelines for deferred treatment and culturally and sociodemographically competent counseling of active surveillance. [ABSTRACT FROM AUTHOR]

BACKGROUND The objective of this study was to examine the effects of marital status on stage at presentation, receipt of treatment, and survival in patients with head and neck cancer (HNC). METHODS The Surveillance, Epidemiology, and End Results database was used to analyze 51,272 patients who were diagnosed with HNC from 2007 to 2010. The impact of marital status on cancer stage at presentation, receipt of definitive treatment, and HNC-specific mortality (HNCSM) was determined using multivariable logistic and Fine and Gray competing-risks regression models, as appropriate. RESULTS Marriage had a protective effect against metastatic presentation of oral and laryngeal cancers (oral cancer: adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.60-0.87; P < .001; laryngeal cancer: AOR, 0.53; 95% CI, 0.42-0.67; P < .001) but not against oropharyngeal, hypopharyngeal, or nasopharyngeal cancers. Among patients with nonmetastatic disease, married patients were more likely to receive definitive treatment (overall AOR, 1.77; 95% CI, 1.60-1.95; P < .001) and had a lower risk of HNCSM (overall adjusted hazard ratio, 0.72; 95% CI, 0.68-0.77; P < .001); these associations remained significant across all HNC sites. CONCLUSIONS Among patients with oral and laryngeal cancers, those who are married are less likely to present with metastatic disease. In addition, married patients are more likely to receive definitive treatment and less likely to die from HNC across all HNC sites. This suggests that spousal support may have a role in the surveillance of visual and symptomatic HNC types and leads to higher rates of treatment and better survival across all HNC sites. Cancer 2015;121:1273-1278. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the associations between African American race and stage at diagnosis, receipt of definitive therapy, and cancer-specific mortality among patients with head and neck cancer. MATERIALS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to conduct a retrospective study on 34,437 patients diagnosed with head and neck cancer from 2007 to 2010. Multivariable logistic regression analyses were applied to determine the impact of race on cancer stage at presentation (metastatic vs. non-metastatic) and receipt of definitive treatment. Fine and Gray competing-risks regression modeled the association between race and head and neck cancer-specific mortality. RESULTS: African Americans were more likely to present with metastatic cancer compared to non-African Americans (Adjusted Odds Ratio [AOR] 1.76; CI 1.50-2.07; P<0.001). Among patients with non-metastatic disease, African Americans were less likely to receive definitive treatment (AOR 0.63; CI 0.55-0.72; P<0.001). After a median follow-up of 19months, African Americans with non-metastatic disease were found to have a higher risk of head and neck cancer specific mortality (AHR 1.19; 95% CI 1.09-1.29; P<0.001). CONCLUSION: African Americans with head and neck cancer are more likely to present with metastatic disease, less likely to be treated definitively, and are more likely to die from head and neck cancer. The unacceptably high rates of disparity found in this study should serve as immediate targets for urgent healthcare policy intervention. [ABSTRACT FROM AUTHOR]

Summary Objectives To determine the associations between African American race and stage at diagnosis, receipt of definitive therapy, and cancer-specific mortality among patients with head and neck cancer. Materials and methods The Surveillance, Epidemiology and End Results (SEER) database was used to conduct a retrospective study on 34,437 patients diagnosed with head and neck cancer from 2007 to 2010. Multivariable logistic regression analyses were applied to determine the impact of race on cancer stage at presentation (metastatic vs. non-metastatic) and receipt of definitive treatment. Fine and Gray competing-risks regression modeled the association between race and head and neck cancer-specific mortality. Results African Americans were more likely to present with metastatic cancer compared to non-African Americans (Adjusted Odds Ratio [AOR] 1.76; CI 1.50–2.07; P < 0.001). Among patients with non-metastatic disease, African Americans were less likely to receive definitive treatment (AOR 0.63; CI 0.55–0.72; P < 0.001). After a median follow-up of 19 months, African Americans with non-metastatic disease were found to have a higher risk of head and neck cancer specific mortality (AHR 1.19; 95% CI 1.09–1.29; P < 0.001). Conclusion African Americans with head and neck cancer are more likely to present with metastatic disease, less likely to be treated definitively, and are more likely to die from head and neck cancer. The unacceptably high rates of disparity found in this study should serve as immediate targets for urgent healthcare policy intervention. [ABSTRACT FROM AUTHOR]

Neurologic death is the most serious consequence of intracranial disease among patients with brain metastases. Identifying patients with brain metastases at increased risk of neurologic death can improve care and guide further research. We sought to delineate factors predictive of neurologic death among patients with brain metastases. We identified 1218 patients with newly diagnosed brain metastases managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute from 2008–2015. Factors predictive of neurologic death were assessed via univariable and multivariable Fine and Gray competing risks regression. On multivariable analysis, neurologic death was associated with number of brain metastases (hazard ratio [HR] 1.01 per 1 metastasis increase, 95% confidence interval [CI] 1.01–1.02, P < 0.001) and 3 primary tumor sites (reference=non-small cell lung cancer): melanoma (HR 4.67, 95% CI 3.27–6.68, P < 0.001), small cell lung cancer (HR 2.33, 95% CI 1.47–3.68, P < 0.001), and gastrointestinal cancer (HR 2.21, 95% CI 1.28–3.82, P = 0.005). Conversely, a reduction in neurologic death was found in patients with good Karnofsky performance status (90–100 vs. 30-80, HR 0.67, 95% CI 0.48–0.95, P = 0.03) and progressive extracranial metastases at diagnosis of intracranial disease (HR 0.50, 95% CI 0.38–0.67, P = 0.001). Among patients with breast primaries, HER2+ patients displayed increased neurologic death relative to the reference of HR+/HER2– (univariable analysis only: HR 2.41, 95% CI 1.00–5.84, P = 0.05). Patients with melanoma, small cell lung cancer, gastrointestinal cancer, and HER2+ breast cancer primaries, as well as greater intracranial versus extracranial disease burden, harbor significant risk of neurologic death. Future research investigating novel intracranial approaches should focus on these populations. [ABSTRACT FROM AUTHOR]

Objectives Treating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP. Materials and methods The Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level >20 ng/ml or Gleason score 8–10 or stage>cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy. Results Compared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95% CI: 0.56–0.64; P <0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status ( P interaction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27–0.54, P <0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57–0.66, P <0.001) among insured men. Conclusions AA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers. [ABSTRACT FROM AUTHOR]

Background Falls in patients with cancer harbor potential for serious sequelae. Patients with brain metastases (BrM) may be especially susceptible to falls but supporting investigations are lacking. We assessed the frequency, etiologies, risk factors, and sequelae of falls in patients with BrM using 2 data sources. Methods We identified 42 648 and 111 patients with BrM utilizing Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2008-2016) and Brigham and Women's Hospital/Dana-Farber Cancer Institute (BWH/DFCI) institutional data (2015), respectively, and characterized falls in these populations. Results Among SEER-Medicare patients, 10 267 (24.1%) experienced a fall that prompted medical evaluation, with cumulative incidences at 3, 6, and 12 months of 18.0%, 24.3%, and 34.1%, respectively. On multivariable Fine/Gray's regression, older age (≥81 or 76-80 vs 66-70 years, hazard ratio [HR] 1.18 [95% CI, 1.11-1.25], P <.001 and HR 1.10 [95% CI, 1.04-1.17], P <.001, respectively), Charlson comorbidity score of >2 vs 0-2 (HR 1.08 [95% CI, 1.03-1.13], P =.002) and urban residence (HR 1.08 [95% CI, 1.01-1.16], P =.03) were associated with falls. Married status (HR 0.94 [95% CI, 0.90-0.98], P =.004) and Asian vs white race (HR 0.90 [95% CI, 0.81-0.99], P =.03) were associated with reduced fall risk. Identified falls were more common among BWH/DFCI patients (N = 56, 50.4% of cohort), resulting in emergency department visits, hospitalizations, fractures, and intracranial hemorrhage in 33%, 23%, 11%, and 4% of patients, respectively. Conclusions Falls are common among patients with BrM, especially older/sicker patients, and can have deleterious consequences. Risk-reduction measures, such as home safety checks, physical therapy, and medication optimization, should be considered in this population. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? There is limited data that suggests that men aged >70 years have a higher proportion of Gleason 8-10 prostate cancer than men aged <70 years, as well as a higher risk of PSA recurrence, distant metastases, and disease-specific death on univariate analysis. The present study shows that older as compared with younger men with Gleason score 6 and 7 prostate cancer have an increased risk of prostate cancer-specific mortality. This may be due to the presence of occult high-grade disease and suggests further diagnostic studies, e.g. multiparametric MRI, may be indicated in these men to reduce biopsy sampling error. OBJECTIVE To determine if advancing age is a risk factor for high-grade prostate cancer due to occult high-grade disease in elderly men with Gleason score 6 or 7 prostate cancer. We investigated whether advancing age is associated with the risk of prostate cancer-specific mortality (PCSM) within established Gleason score categories adjusting for known predictors of PCSM., PATIENTS AND METHODS Using data from the Surveillance, Epidemiology and End Results database between 1 January 2004 to 31 December 2007, 166 104 men with non-metastatic prostate cancer were identified and formed the study cohort., Within established Gleason score categories, Fine and Gray's multivariable competing risk regressions were used to evaluate whether increasing age at diagnosis was significantly associated with an increased risk of PCSM, adjusting for prostate-specific antigen level and T-category at diagnosis and whether treatment was curative or non-curative., RESULTS After adjusting for treatment and prognostic factors, Gleason score 8-10 and 7 as compared with ≤6 was associated with an increased risk of PCSM ( P < 0.001)., Increasing age was associated with an increased risk of PCSM only in Gleason score 6 (adjusted hazard ratio [AHR] 1.06, 95% confidence interval [CI] 1.04-1.08, P < 0.001) and 7 (AHR 1.02, 95% CI 1.01-1.03, P < 0.001), but not with Gleason score 8-10 (AHR 0.999, 95% CI 0.995-1.003, P= 0.61)., These risks were highest in men aged >70 years having Gleason score 6 (AHR 1.10, 95% CI 1.07-1.13, P < 0.001) and Gleason score 7 prostate cancer (AHR 1.04, 95% CI 1.02-1.06, P < 0.001)., CONCLUSIONS PCSM increases with advancing age in men with Gleason score 6 and 7 but not 8-10 prostate cancer., Techniques to reduce biopsy sampling error in men, particularly those aged >70 years and healthy with Gleason score 6 and 7 disease deserve further study. [ABSTRACT FROM AUTHOR]

Background Older patients with brain metastases (BrM) commonly experience symptoms that prompt acute medical evaluation. We characterized emergency department (ED) visits and inpatient hospitalizations in this population. Methods We identified 17 789 and 361 Medicare enrollees diagnosed with BrM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2010-2016) and an institutional database (2007-2016), respectively. Predictors of ED visits and hospitalizations were assessed using Poisson regression. Results The institutional cohort averaged 3.3 ED visits/1.9 hospitalizations per person-year, with intracranial disease being the most common reason for presentation/admission. SEER-Medicare patients averaged 2.8 ED visits/2.0 hospitalizations per person-year. For patients with synchronous BrM (N = 7834), adjusted risk factors for ED utilization and hospitalization, respectively, included: male sex (rate ratio [RR] = 1.15 [95% CI = 1.09-1.22], P <.001; RR = 1.21 [95% CI = 1.13-1.29], P <.001); African American vs white race (RR = 1.30 [95% CI = 1.18-1.42], P <.001; RR = 1.25 [95% CI = 1.13-1.39], P <.001); unmarried status (RR = 1.07 [95% CI = 1.01-1.14], P =.02; RR = 1.09 [95% CI = 1.02-1.17], P =.01); Charlson comorbidity score >2 (RR = 1.27 [95% CI = 1.17-1.37], P <.001; RR = 1.36 [95% CI = 1.24-1.49], P <.001); and receipt of non-stereotactic vs stereotactic radiation (RR = 1.44 [95% CI = 1.34-1.55, P <.001; RR = 1.49 [95% CI = 1.37-1.62, P <.001). For patients with metachronous BrM (N = 9955), ED visits and hospitalizations were more common after vs before BrM diagnosis (2.6 vs 1.2 ED visits per person-year; 1.8 vs 0.9 hospitalizations per person-year, respectively; RR = 2.24 [95% CI = 2.15-2.33], P <.001; RR = 2.06 [95% CI = 1.98-2.15], P <.001, respectively). Conclusions Older patients with BrM commonly receive hospital-level care secondary to intracranial disease, especially in select subpopulations. Enhanced care coordination, closer outpatient follow-up, and patient navigator programs seem warranted for this population. [ABSTRACT FROM AUTHOR]

Objectives: To compare the incidence of treatment-related necrosis between combination SRS+ICI therapy and SRS therapy alone in patients with brain metastases from melanoma and non-small cell lung cancer (NSCLC). Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to August 10, 2020. The difference in the pooled incidence of treatment-related necrosis after SRS+ICI or SRS alone was evaluated. The cumulative incidence of treatment-related necrosis at the specific time point after the treatment was calculated and plotted. Subgroup and meta-regression analyses were additionally performed. Results: Sixteen studies (14 on melanoma, 2 on NSCLC) were included. In NSCLC brain metastasis, the reported incidences of treatment-related necrosis in SRS+ICI and SRS alone ranged 2.9–3.4% and 0–2.9%, respectively. Meta-analysis was conducted including 14 studies on melanoma brain metastasis. The incidence of treatment-related necrosis was higher in SRS+ICI than SRS alone (16.0% vs. 6.5%; p = 0.065; OR, 2.35). The incidence showed rapid increase until 12 months after the SRS when combined with ICI therapy (14%; 95% CI, 8–22%) and its pace of increase slowed thereafter. Histopathologic diagnosis as the reference standard for treatment-related necrosis and inclusion of only symptomatic cases were the source of heterogeneity in SRS+ICI. Conclusions: Treatment-related necrosis tended to occur 2.4 times more frequently in the setting of combination SRS+ICI therapy compared with SRS alone in melanoma brain metastasis showing high cumulative incidence within the first year. Treatment-related necrosis should be considered when SRS+ICI combination therapy is used for melanoma brain metastasis, especially in the first year. Key Points: • Treatment-related necrosis occurred 2.4 times more frequently in the setting of combination SRS+ICI therapy compared with SRS alone in melanoma brain metastasis. • Treatment-related necrosis more frequently occurred in brain metastases from melanoma than NSCLC. • Reference standard for treatment-related necrosis and inclusion of only symptomatic treatment-related necrosis were a significant source of heterogeneity, indicating varying definitions of treatment-related necrosis in the literature need to be unified. [ABSTRACT FROM AUTHOR]

Background and Purpose: Leptomeningeal metastases (LMs) carry a poor prognosis. Existing LM scoring systems show limited reproducibility. We assessed the contribution of education level on the reproducibility of LM scoring using structured planning and implementation of new experiments (SPINE), a novel web-based platform.Methods: Stringent radiological definitions of LM and a customized interactive scoring system were implemented in SPINE. Five patients with brain LM and 3 patients with spine, but no brain LM, were selected. Each patient's baseline post-contrast T1-weighted brain MRI was analyzed by three attending neuroradiologists, two neuroradiology fellows, and two radiology residents. Raters identified and characterized all LMs based on: (1) location (cerebrum, cerebellum, brainstem, ventricle, and/or cranial nerves); (2) shape (nodular and/or linear/curvilinear); (3) size (≥ or <5mm in two orthogonal diameters); (4) spatial extension (focal or diffuse). Inter-rater agreement and association of LM with patient survival were investigated.Results: On average, 6.5 LMs per case were detected. Forty-nine percent of LMs were cerebral, 77.7% were nodular, 86.6% were focal, and 66% were <5 × 5 mm. Agreement on the total number of LMs and the above-mentioned common LM characteristics was higher between attendings (intra-class correlation [ICC] = 0.8-0.94) than fellows (ICC = 0.6-0.82) or residents (ICC = 0.43-0.73). Agreement on ventricular, cranial nerve, and nodular + linear LM was low even between attendings. The number of brainstem LMs showed significant correlation with survival.Conclusion: Structured education using SPINE may improve consistency in LM reporting. Future work should address the impact of the presented approach on the reproducibility of longitudinal analyses directly relevant to the assessment of treatment-response. [ABSTRACT FROM AUTHOR]

Among patients with brain metastases, hippocampal avoidance whole brain radiation (HA-WBRT) preserves neurocognitive function relative to conventional WBRT but the feasibility of hippocampal sparing in patients with metastases in/near the hippocampus is unknown. We identified the incidence of hippocampal/perihippocampal metastases and evaluated the feasibility of HA-WBRT in such patients. Dosimetric data from 34 patients randomized to HA-WBRT (30 Gy/10 fractions) in a phase III trial (NCT03075072) comparing HA-WBRT to stereotactic radiation in patients with 5 to 20 brain metastases were analyzed. Patients with metastases in/near the hippocampi received HA-WBRT with prioritization of tumor coverage over hippocampal avoidance. Target coverage and hippocampal sparing metrics were compared between patients with targets in/near the hippocampus versus not. In total, 9 of 34 (26%) patients had targets in the hippocampus and an additional 5 of 34 (15%) patients had targets in the hippocampal avoidance zone (HAZ, hippocampus plus 5 mm expansion) but outside the hippocampus. Patients with targets within the hippocampus and those with targets in the HAZ but outside the hippocampus were spared 34% and 73% of the ipsilateral mean biologically equivalent prescription dose, respectively. Of the latter cohort, 88% and 25% met conventional hippocampal sparing metrics of Dmin ≤ 9 Gy and Dmax ≤ 16 Gy, respectively. Among 11 patients with unilateral hippocampal/perihippocampal involvement, the uninvolved/contralateral hippocampus was limited to Dmin ≤ 9 Gy and Dmax ≤ 17 Gy in all cases. In this study, a substantial percentage of patients with 5 to 20 brain metastases harbored metastases in/near the hippocampus. In such cases, minimizing hippocampal dose while providing tumor coverage was feasible and may translate to neurocognitive protection. [ABSTRACT FROM AUTHOR]

Background: Prior literature has suggested synergy between immune checkpoint therapy (ICT) and radiotherapy (RT) for the treatment of brain metastases (BrM), but to the authors' knowledge the optimal timing of therapy to maximize this synergy is unclear. Methods: A total of 199 patients with melanoma and non–small cell lung cancer with BrM received ICT and RT between 2007 and 2016 at the study institution. To reduce selection biases, individual metastases were included only if they were treated with RT within 90 days of ICT. Concurrent treatment was defined as RT delivered on the same day as or in between doses of an ICT course; all other treatment was considered to be nonconcurrent. Multivariable Cox proportional hazards models were used to assess time to response and local disease recurrence on a per‐metastasis basis, using a sandwich estimator to account for intrapatient correlation. Results: The final cohort included 110 patients with 340 BrM, with 102 BrM treated concurrently and 238 BrM treated nonconcurrently. Response rates were higher with the use of concurrent treatment (70% vs 47%; P <.001), with correspondingly lower rates of progressive disease (5% vs 26%; P <.001). On multivariable analysis, concurrent treatment was found to be associated with improved time to response (hazard ratio, 1.76; 95% CI, 1.18‐2.63 [P =.006]) and decreased local recurrence (hazard ratio, 0.42; 95% CI, 0.23‐0.78 [P =.006]). This effect appeared to be greater for melanoma than for non–small cell lung cancer, although interaction tests were not statistically significant. Only 1 of 103 metastases which had a complete response later developed disease progression. Conclusions: Concurrent RT and ICT may improve response rates and decrease local recurrence of brain metastases compared with treatment that was nonconcurrent but delivered within 90 days. Further study of this combination in prospective, randomized trials is warranted. There is significant interest in potential synergy between radiotherapy and immune checkpoint therapy, but the optimal timing of each therapy remains unclear. The current study examines a cohort of patients with melanoma and non–small cell lung cancer with brain metastases who were managed with immune checkpoint therapy and brain‐directed radiotherapy within a 90‐day period. Compared with nonconcurrent therapy, concurrent therapy is associated with an improved brain metastasis response rate and decreased local recurrence. [ABSTRACT FROM AUTHOR]

Background: Brain metastases are associated with considerable morbidity and mortality. Integration of hospice at the end of life offers patients symptom relief and improves quality of life, particularly for elderly patients who are less able to tolerate brain-directed therapy. Population-level investigations of hospice utilization among elderly patients with brain metastases are limited.Methods: Using the Surveillance, Epidemiology and End Results-Medicare database for primary cancer sites that commonly metastasize to the brain, we identified 50 148 patients (aged 66 years and older) diagnosed with brain metastases between 2005 and 2016. We calculated the incidence, timing, and predictors of hospice enrollment using descriptive techniques and multivariable logistic regression. All statistical tests were 2-sided.Results: The incidence of hospice enrollment was 71.4% (95% confidence interval [CI] = 71.0 to 71.9; P < .001), a rate that increased over the study period (P < .001). The odds of enrollment for black (odds ratio [OR] = 0.76, 95% CI = 0.71 to 0.82; P < .001), Hispanic (OR = 0.80, 95% CI = 0.72 to 0.87; P < .001), and Asian patients (OR = 0.52, 95% CI = 0.48 to 0.57; P < .001) were substantially lower than white patients; men were less likely to be enrolled in hospice than women (OR = 0.78, 95% CI = 0.74 to 0.81; P < .001). Among patients enrolled in hospice, 32.6% (95% CI = 32.1 to 33.1; P < .001) were enrolled less than 7 days prior to death, a rate that was stable over the study period.Conclusions: Hospice is used for a majority of elderly patients with brain metastases although a considerable percentage of patients die without hospice services. Many patients enroll in hospice late and, concerningly, statistically significant sociodemographic disparities exist in hospice utilization. Further investigations to facilitate targeted interventions addressing such disparities are warranted. [ABSTRACT FROM AUTHOR]

The use of targeted therapies and immune checkpoint inhibitors has drastically changed the management of patients with melanoma and brain metastases. Specifically, combination therapy with ipilimumab, a cytotoxic T-lymphocyte antigen 4 inhibitor, and nivolumab, a programmed cell death protein 1 inhibitor, has become a preferred systemic therapy option for patients with melanoma and asymptomatic brain metastases. However, the efficacy and toxicity profile of these agents in combination with brain-directed radiation therapy is not well described. In this case series, we highlight a series of patients with melanoma demonstrating severe radiation necrosis immediately refractory to surgical resection following brain-directed stereotactic radiation therapy with concurrent ipilimumab and nivolumab. Three patients described in this series each received stereotactic radiation therapy to a dose of 30 Gy in 5 fractions to a melanoma brain metastasis. These areas developed radiographic evidence of necrosis, which was managed surgically and progressed immediately and rapidly after resection. Re-resection, bevacizumab, steroids, and/or discontinuation of nivolumab was used to mitigate further necrosis with varying efficacy. Patients with metastatic melanoma receiving brain-directed radiation therapy with concurrent ipilimumab and nivolumab are at risk for developing severe, surgically refractory radiation necrosis and should be closely followed clinically and with imaging. The exact mechanism for such severe necrosis is unknown, and future studies are needed to better understand this pathophysiology and identify optimal treatment strategies. [ABSTRACT FROM AUTHOR]

PIK3CA mutation frequency varies among breast cancer (BC) subtypes. Recent evidence suggests combination therapy with the PI3K inhibitor (PI3Ki) alpelisib and endocrine therapy (ET) improves response rates and progression-free survival (PFS) in PIK3CA-mutant, hormone receptor positive (HR+) BC versus ET alone; thus, better understanding the clinical and epidemiologic elements of these mutations is warranted. This systematic review characterizes the PIK3CA mutation epidemiology, type of testing approaches (e.g., liquid or tissue tumor biopsy), and stability/concordance (e.g., consistency in results by liquid versus solid tumor sample, by the same method over time) in patients with HR+/HER2– advanced (locally unresectable) or metastatic disease (HR+/HER2– mBC) and explores performance (e.g., pairwise concordance, sensitivity, specificity, or predictive value) of respective mutation findings. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts (i.e., AACR, ASCO, SABCS, ECCO, and ESMO conferences between 2014 and 2017) identified 39 studies of patients with HR+, HER2– mBC. The median prevalence of PIK3CA mutation was 36% (range: 13.3% to 61.5%); identified testing approaches more commonly used tissue over liquid biopsies and primarily utilized next-generation sequencing (NGS), polymerase chain reaction (PCR), or Sanger sequencing. There was concordance and stability between tissues (range: 70.4% to 94%) based on limited data. Given the clinical benefit of the PI3Ki alpelisib in patients with PIK3CA mutant HR+/HER2– mBC, determination of tumor PIK3CA mutation status is of importance in managing patients with HR+/HER2– mBC. Prevalence of this mutation and utility of test methodologies likely warrants PIK3CA mutation testing in all patients with this breast cancer subtype via definitive assessment of PIK3CA mutational status. [ABSTRACT FROM AUTHOR]

Purpose: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts.Methods and Materials: A multi-institutional (19), multinational (3), retrospective database of 2473 patients with breast cancer with newly diagnosed brain metastases (BCBM) diagnosed from January 1, 2006, to December 31, 2017, was created and compared with prior cohorts. Associations of PF and treatment with survival were analyzed. Kaplan-Meier survival estimates were compared with log-rank tests. PF were weighted and the Breast GPA was updated such that a GPA of 0 and 4.0 correlate with the worst and best prognoses, respectively.Results: Median survival (MS) for cohorts A, B, and C improved over time (from 11, to 14 to 16 months, respectively; P < .01), despite the subtype distribution becoming less favorable. PF significant for survival were tumor subtype, Karnofsky Performance Status, age, number of BCBMs, and extracranial metastases (all P < .01). MS for GPA 0 to 1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 was 6, 13, 24, and 36 months, respectively. Between cohorts B and C, the proportion of human epidermal receptor 2 + subtype decreased from 31% to 18% (P < .01) and MS in this subtype increased from 18 to 25 months (P < .01).Conclusions: MS has improved modestly but varies widely by diagnosis-specific PF. New PF are identified and incorporated into an updated Breast GPA (free online calculator available at brainmetgpa.com). The Breast GPA facilitates clinical decision-making and will be useful for stratification of future clinical trials. Furthermore, these data suggest human epidermal receptor 2-targeted therapies improve clinical outcomes in some patients with BCBM. [ABSTRACT FROM AUTHOR]

Histopathological grading of meningiomas is insufficient for optimal risk stratification. The purpose of the present study was to determine the prognostic value of atypical histopathological features across all nonmalignant meningiomas (World Health Organization [WHO] grade I-II). The data from 334 patients with WHO grade I (n = 275) and grade II (n = 59) meningiomas who had undergone surgical resection from 2001 to 2015 at 2 academic centers were pooled. Progression/recurrence (P/R) was determined radiographically and measured from the date of surgery. The median follow-up was 52 months. The patients were stratified by the number of atypical features: 0 (n = 151), 1 (n = 71), 2 (n = 66), 3 (n = 22), and 4 or 5 (n = 24). The risk of P/R increased with an increasing number of atypical features (log-rank test, P = 0.001). The 5-year actuarial rates of P/R stratified by the number of atypical features were as follows: 0, 16.3% (95% confidence interval [CI], 10.7–24.4); 1, 21.7% (95% CI, 12.8–35.2); 2, 28.2% (95% CI, 18.4–41.7); 3, 30.4% (95% CI, 13.8–58.7); and 4 or 5, 51.4% (95% CI, 31.7–74.5). On univariate analysis, the presence of high nuclear/cytoplasmic ratio (P = 0.007), prominent nucleoli (P = 0.007), and necrosis (P < 0.00005) were associated with an increased risk of P/R. On multivariate analysis, the number of atypical features (hazard ratio [HR], 1.30; 95% CI, 1.03–1.63; P = 0.03), ≥4 mitoses per high-power fields (HR, 2.45; 95% CI, 1.17–5.15; P = 0.02), subtotal resection (HR, 3.9; 95% CI, 2.5–6.3; P < 0.0005), and the lack of adjuvant radiotherapy (HR, 2.40; 95% CI, 1.19–4.80; P = 0.01) were associated with an increased risk of P/R. An increased number of atypical features, ≥4 mitoses per 10 high-power fields, subtotal resection, and the lack of adjuvant radiotherapy were independently associated with P/R of WHO grade I-II meningiomas. Patients with these features might benefit from intensified therapy. [ABSTRACT FROM AUTHOR]

Background: There are a growing number of cancer survivors in the United States who are at risk for chronic pain due to cancer disease and treatments. The prevalence of chronic pain among cancer survivors has not been comprehensively reported.Methods: This study used data from the National Health Interview Survey (2010-2017) to compare the prevalence of chronic pain between participants with a cancer diagnosis and participants without one. Adjusted odds ratios (AORs) of having chronic pain were assessed by multivariable logistic regression, which included an age (less than the median age vs greater than or equal to the median age) × cancer diagnosis (yes vs no) interaction term. Among cancer survivors, multivariable logistic regression defined the odds of feeling depressed, feeling worried/nervous/anxious, being unable to work, and needing assistance for activities of daily living (ADLs) and instrumental activities of daily living (IADLs).Results: Among 115,091 participants, a cancer diagnosis was associated with an increased AOR of chronic pain in comparison with the general population (30.8% vs 15.7%; AOR, 1.48; 95% confidence interval, 1.38-1.59). Older age was associated with higher odds of chronic pain (P < .001 across all increasing age categories); however, the positive association between older age and chronic pain was seen only in participants without cancer and was not seen in those with a cancer diagnosis (Page×cancer  < .001). Among patients reporting a cancer diagnosis, chronic pain was associated with greater odds of feeling depressed, feeling worried/nervous/anxious, being unable to work, and needing assistance with ADLs or IADLs (P < .001 for all).Conclusions: Cancer survivors appear to have a high prevalence of chronic pain, which is associated with worse mental, functional, and employment outcomes. Screening and management of chronic pain should be addressed by policymakers to improve cancer survivorship care. [ABSTRACT FROM AUTHOR]

• BMV is a novel prognostic score for OS in patients with BMs from solid cancers. • To date, three versions of the BMV have been proposed: Classic , initial and volume-based. • This is the first study to attempt to externally validate all three BMV scores in a large cohort. • cBMV and iBMV were successfully validated, while validation of vBMV was not achieved. • External validation and easy transferability suggest clinical potential for cBMV and iBMV. Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores. Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS. For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, "classic" BMV was validated as categorical (p < 0.0001) and continuous variable (HR 1.02; 95% CI 1.02–1.03; p < 0.0001). In a sub-group of 284 patients, "initial" BMV was validated as categorical variable (high-risk vs. low-risk; p < 0.01), but not as continuous variable (HR 1.02; 95% CI 0.99–1.04; p = 0.224). "Volume-based" BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01–3.38; p < 0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p < 0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30–6.91; p < 0.05). This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved. [ABSTRACT FROM AUTHOR]

The article discusses a study published in the October 22, 2016 issue of the periodical by Paula Mulvenna and colleagues related to assessment of whole brain radiotherapy (WBRT) in comparison with optimal supportive care among brain metastases and non-small cell lung cancer (NSCLC) patients. Topics discussed include no potential survival benefit with WBRT, less patients with brain metastases dying of neurological disease and substantial benefit from radiation if used appropriately.

Introduction: Stereotactic radiosurgery (SRS) is a promising treatment option for patients with multiple brain metastases (BM). Recent technical advances have made LINAC based SRS a patient friendly technique, allowing for accurate patient positioning and a short treatment time. Since SRS is increasingly being used for patients with multiple BM, it remains essential that SRS be performed with the highest achievable quality in order to prevent unnecessary complications such as radionecrosis. The purpose of this article is to provide guidance for high-quality LINAC based SRS for patients with BM, with a focus on single isocenter non-coplanar volumetric modulated arc therapy (VMAT). Methods: The article is based on a consensus statement by the study coordinators and medical physicists of four trials which investigated whether patients with multiple BM are better palliated with SRS instead of whole brain radiotherapy (WBRT): A European trial (NCT02353000), two American trials and a Canadian CCTG lead intergroup trial (CE.7). This manuscript summarizes the quality assurance measures concerning imaging, planning and delivery. Results: To optimize the treatment, the interval between the planning-MRI (gadolinium contrast-enhanced, maximum slice thickness of 1.5 mm) and treatment should be kept as short as possible (< two weeks). The BM are contoured based on the planning-MRI, fused with the planning-CT. GTV-PTV margins are minimized or even avoided when possible. To maximize efficiency, the preferable technique is single isocenter (non-)coplanar VMAT, which delivers high doses to the target with maximal sparing of the organs at risk. The use of flattening filter free photon beams ensures a lower peripheral dose and shortens the treatment time. To bench mark SRS treatment plan quality, it is advisable to compare treatment plans between hospitals. Conclusion: This paper provides guidance for quality assurance and optimization of treatment delivery for LINAC-based radiosurgery for patients with multiple BM. [ABSTRACT FROM AUTHOR]