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INTRODUCTION: Treatment for glioblastomas, aggressive and nearly uniformly fatal brain tumors, provide limited long-term success. Immunosuppression by myeloid cells in both the tumor microenvironment and systemic circulation are believed to contribute to this treatment resistance. Standard multi-modality therapy includes conventionally fractionated radiotherapy over 6 weeks; however, hypofractionated radiotherapy over 3 weeks or less may be appropriate for older patients or populations with poor performance status. Lymphocyte concentration changes have been reported in patients with glioblastoma; however, monocytes are likely a key cell type contributing to immunosuppression in glioblastoma. Peripheral monocyte concentration changes in patients receiving commonly employed radiation fractionation schemes are unknown. METHODS: To determine the effect of conventionally fractionated and hypofractionated radiotherapy on complete blood cell leukocyte parameters, retrospective longitudinal concentrations were compared prior to, during, and following standard chemoradiation treatment. RESULTS: This study is the first to report increased monocyte concentrations and decreased lymphocyte concentrations in patients treated with conventionally fractionated radiotherapy compared to hypofractionated radiotherapy. DISCUSSION: Understanding the impact of fractionation on peripheral blood leukocytes is important to inform selection of dose fractionation schemes for patients receiving radiotherapy.

PURPOSE: Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly. METHODS AND MATERIALS: A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA. RESULTS: Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P < .01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies. CONCLUSIONS: Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at brainmetgpa.com, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials.

BackgroundBreast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM).MethodsA retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the BCBM.ResultsThe overall receptor discordance rate was 132/316 (42%), and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors-nonetheless, median survival (MS) improved but did not reach statistical significance (HR, 17-28 mo, P = 0.12; HER2, 15-19 mo, P = 0.39). MS for patients who lost receptors was worse (HR, 27-18 mo, P = 0.02; HER2, 30-18 mo, P = 0.08).ConclusionsReceptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost, and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly.Key points1. Receptor discordance alters subtype in 32% of BCBM patients.2. The frequency of receptor gain for HR and HER2 was 25% and 13%, respectively.3. If receptors are lost, survival suffers. If receptors are gained, consider targeted treatment.

PurposeBrain 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 materialsA 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.ResultsMedian 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).ConclusionsMS 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.

BackgroundBrain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985-2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors.MethodsA multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively.ResultsThe 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0-1.0, 1.5-2.0, 2.5-3, and 3.5-4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively.ConclusionThe updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com.

PurposeTo identify prognostic factors, define evolving patterns of care, and the effect of targeted therapies in a larger contemporary cohort of renal cell carcinoma (RCC) patients with new brain metastases (BM).Methods and materialsA multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new BM diagnosed from January 1, 2006, to December 31, 2015, was created. Clinical parameters and treatment were correlated with median survival and time from primary diagnosis to BM. Multivariable analyses were performed.ResultsThe median survival for the prior/present cohorts was 9.6/12 months, respectively (P

PurposeBrain metastases are a common problem in patients with melanoma, but little is known about the effect of gene mutations on survival in these patients.Methods and materialsWe created a retrospective multi-institutional database of 823 patients with melanoma and brain metastases diagnosed between 2006 and 2015. Clinical parameters, gene mutation status (BRAF, C-KIT, NRAS), and treatment were correlated with survival. Treatment patterns and outcomes were compared with a prior era (1985-2005).ResultsBRAF status was known in 584 of 823 patients (71%). BRAF, NRAS, and C-KIT mutations were present in 51%, 22%, and 11% of tested patients, respectively. The median time from primary diagnosis to brain metastasis was 32 months, and overall median survival (MS) from the time of initial treatment of brain metastases was 10 months. MS for BRAF-positive and BRAF-negative patients was 13 months and 9 months, respectively (P=.02). There was no significant difference in MS in patients with or without NRAS or C-KIT mutations. The time from primary diagnosis to brain metastasis did not vary by mutation and was not associated with survival after the diagnosis of brain metastases. MS for the 1985 to 2005 and 2006 to 2015 cohorts was 6.7 months and 10.0 months, respectively (P

Introduction: Metastatic uveal melanoma (mUM) is a difficult to treat disease. The liver is the primary site of metastasis in most patients, though uveal melanoma spreads widely in advanced disease. The only FDA approved immunotherapy medication for metastatic uveal melanoma is the HLA-A02:01 restricted bispecific T cell engager drug, Tebentafusp. Checkpoint inhibitor strategies and combination approaches have been tried with some limited success. We describe our experience treating patients at the University of Minnesota. Methods: Patients were included if they had biopsy-confirmed mUM. Twenty)five (25) patients meeting the criteria were identified. Medical records were reviewed and data extracted for patient baseline characteristics and response to treatments. Results: Median time to metastasis from the time of local therapy to the eye was 14.2 months (IQR; 9.3-22.0), and first site of metastasis was liver in 92% of patients. Two patients (8%) did not receive systemic therapy or radiation therapy for metastatic disease. Twenty-three (92%) patients received systemic therapy, 13 patients (52%) received ipilimumab-nivolumab as the first-line, while 4 patients (16%) received pembrolizumab. Landmark survival analysis by receipt of systemic therapy and radiation therapy treatments within 6 months of biopsy confirmed diagnosis is shown. Twenty patients (80%) received systemic therapy within 6 months of mUM diagnosis. Thirteen patients (52%) received liver directed radiation therapy within 6 months of mUM diagnosis. Discussion: Within our cohort, there was no overall survival benefit for patients receiving treatment of metastatic disease within 6 months of mUM diagnosis, versus those electing later or no treatment at all. There was remarkable clinical activity of ipilimumab and nivolumab in a subset of patients with mUM, in agreement with prior studies, and metastatic PD-L1 positive tumors were associated with a prolonged survival. [ABSTRACT FROM AUTHOR]

Dog bite injuries often present to Emergency Departments (ED), and between 2001 and 2003, approximately 4.5 million adults and children were injured. Injuries may range from puncture wounds to deep tissue lacerations or avulsions. Deaths have been described. Our objective was to describe dog bite injuries, the overall location of injuries, and need for vaccination among children who presented to a Pediatric ED designated as a level III trauma center with a robust facial surgical infrastructure. This was a 6-year retrospective study. Charts were identified by International Classification of Diseases, Tenth Revision (ICD-10) codes for lacerations or injuries secondary to animal bites and accessing the hospital's trauma database. Variables abstracted were age, sex, type of injury, location, need for antibiotics, immunization states and requirement of tetanus or rabies vaccine, disposition from ED to the operating room, home, or any in-patient unit. We excluded children older than 17 years of age and children who had a post-bite injury infection or injury not initially managed in our facility or medical system. The final cohort consisted of 152 children. The median age was 52 months and age ranged from 2 to 215 months. Children with a single bite injury were older when compared with those with numerous injuries, 81 and 62 months of age, respectively. Among young children, 75% of injuries occurred above the neck and 15.1% were managed in the operating room. Twenty-four percent of children required either a tetanus or rabies vaccination. Most dog bite injuries occurred to facial structures. Comprehensive care of dog victims included awareness of both dog and injured child vaccination status. [ABSTRACT FROM AUTHOR]

Objective: To determine whether pediatric emergency medicine physicians are compliant with the 9-year-old simple febrile seizure guideline created by the American Academy of Pediatrics (AAP). Methods: A retrospective chart review of patients, ages 6 to 60 months, who presented to the emergency department between May 2011 and December 2019. Key variables abstracted were urine, blood, nasal viral swab, and radiographic results. Results: The retrospective cohort of 285 children met inclusion criteria. Among 285 children, 342 studies were performed with a median of 1.2 studies per patient. There were 77 urine cultures obtained with 6 bacterial pathogens. Nasal viral swabs were performed on 65 children with 9 positive results. Blood cultures were obtained for 28 children and none were positive. Chest radiographs were performed on 37 children with 4 showing pneumonia. Conclusion: The study results reflect areas of opportunity to update guidelines with a focus to consider obtaining urine studies, viral sampling, and chest x-rays. [ABSTRACT FROM AUTHOR]

PurposeLung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno).MethodsA multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials.ResultsOf 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR-/+ was 10/15 months (P=.02) and for ALK-/+ was 10/20 months (P

Simple Summary: Despite recent advances in immunotherapy, melanoma remains the deadliest cutaneous malignancy. Immunocompromised patients are at heightened risk of developing melanoma and experience greater levels of morbidity and mortality compared to their non-immunocompromised peers with the disease. We sought to characterize immunocompromised patients with melanoma at our institution in terms of histopathologic parameters, trends in survival analysis, and comparison to the general population using the Surveillance, Epidemiology, and End Results (SEER) database. Analysis of our transplant sub-cohort revealed an overall melanoma standardized incidence ratio of 1.53, though variation was seen based on transplant type, sex, and time since transplantation. Our study reveals important trends in disease among immunocompromised patients with melanoma at an academic tertiary-care center and is valuable for clinicians caring for this unique demographic of patients. Background: Malignant melanoma is the leading cause of death due to cutaneous malignancy. Immunocompromised individuals have an elevated risk of developing melanoma. We aimed to provide histopathologic and statistical characterization of melanoma development in immunocompromised patients. Methods: We reviewed our institution's databases to identify all patients with a confirmed history of immunosuppression who subsequently developed melanoma, focusing on diagnoses during the follow-up period of 2011–2019. A total of 93 patients with a combined 111 melanoma lesions were identified. Results: Common causes of immunosuppression included transplantation and lymphoproliferative disorders. Superficial spreading and lentigo malignant melanoma were the most common malignant melanoma subtypes. Median Breslow depth was 0.7 mm, and the most common primary tumor stage was T1a. Our transplant sub-cohort had an overall melanoma incidence of 0.9 per 1000 person-years (95% CI 0.66 to 1.20) and a standardized incidence ratio (SIR) of 1.53 (95% CI 1.12 to 2.04) relative to a general population cohort from the Surveillance, Epidemiology, and End Results Program (SEER). Conclusions: We report histopathologic characteristics of immunocompromised patients developing melanoma at a large academic tertiary-care center. Differences in age, sex, time since transplantation, and transplant type may play a significant role in melanoma SIR in this patient demographic. [ABSTRACT FROM AUTHOR]

Background: Transfusion of blood products is an essential component of the hematopoietic cell transplantation (HCT) process. Blood transfusion carries several risks including, but not limited to, lung injury. The effect of transfusions on lung complications after HCT has not been previously investigated.Study Design and Methods: We retrospectively studied 215 adult allogeneic HCT recipients at the University of Minnesota and examined the association between transfusion of blood components and development of lung complications after HCT. Patients without lung complications were used as the control group.Results: A total of 113 (58%) of the patients developed lung injury events before Day 180 after HCT. Six-month survival was significantly lower in the lung event group (52%) versus the controls (78%; p = 0.01). Patients who eventually developed lung events received more transfusion episodes per week in the first month after HCT (median, 4.3 vs. 2.7 for controls), platelet units per week (3.5 vs. 2.0), and RBC units per week (1.8 vs. 1.4; p < 0.01) for all. In a multivariable analysis, each additional transfusion before Day +30 was associated with a 2.7% higher risk of lung complication (95% confidence interval, 0.8-4.8; p = 0.01), adjusting for time to engraftment, conditioning intensity, and donor type. Blood utilization increased after the lung event and remained high for several months relative to controls.Conclusion: Our data suggest that transfusion of blood products is associated with and may further complicate lung complications after HCT. Cautious use of blood components in the post HCT period is recommended. [ABSTRACT FROM AUTHOR]

Purpose: To update the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for a markedly heterogeneous patient population, patients with melanoma and brain metastases, using a larger, more current cohort, including molecular markers.Methods: The original Melanoma-GPA is based on data from 483 patients whose conditions were diagnosed between 1985 and 2005. This is a multi-institutional retrospective database analysis of 823 melanoma patients with newly diagnosed brain metastases from January 1, 2006, to December 31, 2015. Multivariable analyses identified significant prognostic factors, which were weighted and included in the updated index (Melanoma-molGPA). Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios to design the updated Melanoma-molGPA in which scores of 4.0 and 0.0 are associated with the best and worst prognoses, as with all of the diagnosis-specific GPA indices. Log-rank tests were used to compare adjacent classes.Results: There were 5 significant prognostic factors for survival (age, Karnofsky performance status [KPS], extracranial metastases [ECM], number of brain metastases, and BRAF status), whereas only KPS and the number of brain metastases were significant in the original Melanoma-GPA. Median survival improved from 6.7 to 9.8 months between the 2 treatment eras, and the median survival times for patients with Melanoma-molGPA of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 4.9, 8.3, 15.8, and 34.1 months (P<.0001 between each adjacent group).Conclusions: Survival and our ability to estimate survival in melanoma patients with brain metastases has improved significantly. The updated Melanoma-molGPA, a user-friendly tool to estimate survival, will facilitate clinical decision making regarding whether and which treatment is appropriate and will also be useful for stratification of future clinical trials. To further simplify use, a free online/smart phone app is available at brainmetgpa.com. [ABSTRACT FROM AUTHOR]

Purpose: The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. Methods and Materials: A multi-institutional retrospective database of 400 breast cancer patients treated for newly diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. Results: Significant prognostic factors by multivariate Cox regression and RPA were Karnofsky performance status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60 to 80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 3.4 (n = 23), 7.7 (n = 104), 15.1 (n = 140), and 25.3 (n = 133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR positive improved MST from 6.4 to 9.7 months, whereas in HER2-positive patients, being ER/PR positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA vs. 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision making and stratification in clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone. [ABSTRACT FROM AUTHOR]