bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing access to genetic cancer risk assessment (GCRA) in Monterrey, Mexico: The beginning of a prevention program.
Authors: Aguilar y Méndez Dione , Weitzel Jeffrey N. , Blazer Kathleen Reilly , Castillo Danielle , Herzog Josef , Marrufo Juan Carlos A. , García-García Marisol , Mesa-Chavez Fernanda , Miaja Melina , Cardona-Huerta Servando , Villarreal-Garza Cynthia 
Published: May 2019

e13150 Background: In limited-resource countries like Mexico, GCRA is not routinely provided due to elevated costs, lack of public coverage for testing and prophylactic surgeries, and limited GCRA expertise or awareness among providers and patients. Thus, GCRA services in Mexico are 20 years behind higher income countries, resulting in suboptimal care and limited opportunity for prevention. The Breast Cancer Center TecSalud established formal GCRA services for underserved patients by recruiting a cancer geneticist who provides care at no added expense to patients, building academic collaborations for training and research with City of Hope, and enabling free genetic testing through the Clinical Cancer Genomics Community Research Network, supported in part by the Breast Cancer Research Foundation. Aim: To report the uptake of the GCRA program by patients and relatives at TecSalud from January 2016 - December 2018. Methods: Eligibility includes Mexican women who meet hereditary breast cancer testing criteria and family members of mutation carriers. Risk reduction procedures are covered by Seguro Popular and/or the NGO Fundación Santos y de la Garza Evia. Results: GCRA was offered to 255 patients and 74 at risk relatives, with an increasing reach (proportion of those eligible who access the program). A significant growth of cascade testing and access to risk reduction surgery over time are noted. Conclusions: A growing number of referrals and GCRA visits shows improving reach, possibly due to engagement of the multidisciplinary team and increased patient awareness. The expansion of cascade testing and performance of risk-appropriate surgeries reflects a maturing prevention program. Key determinants of our progress are collaborations that provided us with crucial mentorship, access to genetic assays, as well as the increasing involvement of local leaders, administrators and benefactors for the establishment of vital clinical and research capacity. Multilevel efforts should continue to enhance the delivery of standard of medical care for the most vulnerable and underserved high-risk patients and families. [Table: see text]
Psychosocial and clinical factors of probands impacting intrafamilial disclosure and uptake of genetic testing in families with BRCA1/2 or MMR gene mutations.
Authors: Pujol Pascal , Alegre Nathalie , vande Perre Pierre , Bignon Yves-Jean , Chiesa Jean , Picot Marie Christine , Galibert Virginie , Bertet Helena , Corsini Carole 
Published: May 2019

e13151 Background: Intrafamilial disclosure of hereditary cancer predisposition in BRCA1/2 and mismatch repair gene (MMR) syndromes allows appropriate prevention strategies in at-risk relatives. We previously showed in a nationwide study that the uptake of genetic targeted testing (GTT) in these families by relatives was only 30%. We aimed to identify the medical and psychosocial factors affecting the proband’s intrafamilial disclosure and relatives’ uptake of GTT in BRCA1/2 or MMR syndromes. Methods: We assessed clinical variables, family history and several psychological variables of probands (depression, anxiety, alexithymia, optimism, coping, family relationship, perception of cancer risks and of hereditary transmission risks), together with disclosure and verified uptake of GTT in BRCA1/2 or MMR families. Results: Among relatives eligible for GTT, 68% were informed of the predisposition and 37% underwent GTT, according to proband reports. Intrafamilial disclosure was inversely associated with the degree of kinship (P < 0.01). In multivariable analysis, disclosure increased with time since proband’s genetic diagnosis (P < 0.01) and proband’s feeling of family cohesion (P = 0.01). GTT uptake increased with proband’s depression score (P = 0.02) and decreased with proband’s perception of cancer risks (P = 0.03). BRCA1/2 and MMR groups did not differ in findings concerning family information and GTT uptake. Conclusions: This study identified factors affecting disclosure to relatives and GTT uptake in BRCA1/2 and MMR syndromes and gives new insights to improve probands’ follow-up and intrafamilial sharing of genetic information.
Genetic testing for hereditary breast and ovarian cancer in Indian population: A single institutional study.
Authors: Selvakumar Veda Padma Priya , Garg Shubha , Kaur Jatinder , Kadayaprath Geeta , Rohatgi Nitesh , Walia Meenu , Rangaraju Ranga Rao , Julka Pramod Kumar , Chaturvedi Harit Kumar , Verma Amit 
Published: May 2019

e13153 Background: Women with Hereditary breast ovarian cancer have an increased lifetime risk of developing breast, ovarian and other second primary cancers . A number of genes including BRCA 1 & 2 have been implicated in Hereditary Breast Ovarian Cancer. In this background we sought to analyze the genetic pattern of patients who underwent genetic testing as per the NCCN criteria for hereditary breast ovarian cancer syndrome. Methods: All consecutive patients who fit into the NCCN criteria for genetic testing for Hereditary Breast Ovarian Cancer from 2016 to 2018 were referred to our genetic clinic. The data of all the patients who underwent further genetic testing after counselling were collected and analyzed. Results: Out of 155 patients who underwent genetic testing ,131 patients were found eligible for the study.127 were female and 4 were male. There were 27 pathogenic mutations identified while 32 were variants of unknown significance . The remaining 72 were negative for any of the known mutations. 22 were pathogenic for BRCA 1 Mutation , two pathogenic for BRCA 2 and one for TP53 ,PALB2 and ATM each. Out of the 32 VUS, 9 were BRCA 2, 4 in CDH 1, 2 in BRCA1, CHEK2 ,MSH2 and BRIP1 and one each in MLH1, MLH3, ATM, APC, RAD51D, XRCC3, NBN, TP53.Three patients had double VUS reported. BRCA 1 is the most common pathogenic mutation ( 16.79% ) found while BRCA 2 is the most common VUS reported ( 28 %). Conclusions: 20.6 % of eligible patients had pathogenic mutations which is much higher than the western literature. However the VUS rates in Indian population are high 22% owing to a paucity of genetic data of Indian population. Multigene testing helps in identifying other genes asscociated with the Hereditary breast ovarian cancer criteria in addition to BRCA 1 & 2.
BRCA1/2 and multigene panel testing among metastatic breast, pancreas, prostate, and ovarian cancer patients.
Authors: Trivedi Meghna S. , Vo VanAnh L , Jones Tarsha , Silverman Thomas , Chung Wendy , Kukafka Rita , Crew Katherine D. 
Published: May 2019

e13160 Background: Given the availability of targeted therapies such as PARP inhibitors, patients with metastatic breast, pancreas, prostate, and ovarian cancer are recommended to have germline genetic testing for hereditary cancer syndromes. Completion of genetic testing among this population is understudied. Methods: We performed a retrospective study of 548 patients with stage 4 breast, pancreas, prostate, and ovarian cancer at diagnosis from January 2013-December 2017 identified in the New York Presbyterian Hospital Tumor Registry at Columbia University Irving Medical Center. Data on socio-demographics, clinical factors, and genetic testing completion and results were collected from the medical record. We conducted descriptive statistics. Results: Our study population had a median age of 66 years (range, 23-97) at diagnosis; 61% female; 50% non-Hispanic white/22% Hispanic/15% non-Hispanic black/5% Asian/7% other; 33% private insurance/16% Medicaid/44% Medicare/7% unknown insurance. Primary cancer was 24% breast, 8% ovary, 61% pancreas, and 7% prostate. Only 38 patients were seen by a genetic counselor (7%) and only 50 (9%) had genetic testing performed. Among those who underwent germline testing, 92% had multigene panel testing (median number of genes tested 13.5, range 2-74). Pathogenic variants were detected in 6 patients (12%), of which 4 had a BRCA1/2 mutation, and 26% had a variant of uncertain significance (VUS). Conclusions: We found that only a small percentage of metastatic breast, pancreas, prostate, and ovarian cancer patients underwent genetic testing. Further research is necessary to identify the barriers to genetic testing uptake in metastatic cancer patients. BRCA1/2 and multigene panel testing has important implications in this patient population not only for treatment decisions, but also to increase cascade testing in unaffected family members who may be at risk for malignancy in the future.
Correlation of negative PD-L1 expression with TMB-H and MSI-H rates.
Authors: Dong Jun , Zhang Xiaoni , Qu Hongyue , Chen Shifu , Zhu Ziyang , Huang Tanxiao , Ye Da-Wei , Bai Long , Cai Xiuyu 
Published: May 2019

e13162 Background: PD-L1 protein expression, tumor mutation burden (TMB) and microsatellite instability (MSI) are majorbiomarkers for PD-1/PD-L1 blockade therapy for solid tumors. We designed a study to evaluate the relevance of these biomarkers. Methods: From April 2018 to December 2018, 197 patients with lung cancer, colorectal cancer, andgastric cancer wereprospectivelyenrolled.Foreachpatient, afreshfrozentissuesampleor FFPE sample wascollected. Each sample was dividedinto3parts for next-generation sequencing (NGS), PD-L1 protein expression evaluation and MSI evaluation. The sequencing library was captured using a 605-gene panel and sequenced at~5,000×coverage.Mutationsinthe NGS datawereidentified,andTMB was then calculated. The PD-L1 protein expression was analyzedby immunohistochemistry, and the MSI was evaluated using a multiplex PCR comprising 5 loci(NR27, NR21, NR24, BAT25, and BAT26). Results: 18.78% (37/197) were detected with high PD-L1 expression (positive tumor cells ≥50%); 5.08% (10/197) ofpatientswere diagnosed as MSI-H; 4.06% (8/197) of patients had a TMB-H (TMB > 20 mutations/Mb). Among the 37 PD-L1 positive patients, only one patientwith TMB-Hwas detected, and 3patients were MSI-H. In contrast, among the 14 patients with PD-L1 expression less than 1%, 8patients (57.14%) were detected with TMB-H or MSI-H (3 with TMB-H only, 3 with MSI-H only, and 2 with both). In addition, among all the 10patients with MSI-H, 4patients had TMB-H, indicating that MSI-H may be partly associatedwith high TMB. Conclusions: From our preliminary result, PD-L1 protein expression negative patients tend to have higher rates of TMB-H and MSI-H. For patients with negative PD-L1 expression, it issuggested to evaluate its TMB level and MSI status. This study is ongoing, and more data will be collected to verify these findings.
Treatment of cancer-associated thrombosis after craniotomy.
Authors: Katelnitskaya Oksana V. , Kit Oleg I. , Rostorguev Eduard Evgenevich , Kuznetsova Natalya S. , Porksheyan David H. , Atmachidi Dmitriy P. , Kavitskiy Sergey E. , Guskova Nailya K. , Zakharchenko Viktoria R. , Nozdricheva Anastasia S. , Abakumova Svetlana V. , Selyutina Olesya N. , Tselishcheva Irina V. , Belgova Svetlana V. 
Published: May 2019

e13510 Background: The high rates of mortality from venous thromboembolism (VTE) in neurooncological patients determine the relevance of the topic. The risk of VTE in patients with glioma reaches 36% during the treatment period, 16.1% during the first 6 months and increases by 3 times after tumor biopsy. The aim of this study was to evaluate the efficacy and safety of VTE treatment with fondaparinux after surgical interventions for brain tumors. Methods: The study included 32 cancer patients aged from 27 to 76 years (mean 56.5 years) in the acute period of VTE, the first month after craniotomy. Creatinine clearance below 30 ml/min, active bleeding, thrombocytopenia below 50x109/l were exclusion criteria. Glioma was diagnosed in 15 patients (46.9%), metastasis - 9 (28.1%), and meningioma - 8 patients (25%). Radical interventions were performed in 12 (37.5%) cases, palliative - 20 (62.5%). In 81.2% of cases (26 patients) deep vein thrombosis of lower extremities (DVT) was detected, 3 patients (9.4%) had combination with pulmonary embolism. VTE developed in the postoperative period with radiotherapy in 9 cases (32%), dexamethasone - 13 (40.6%). Surgical treatment of DVT was performed in 8 patients (thrombectomy, plication of the femoral vein). Segmental deep vein thrombosis of the lower leg was detected in 14 (43.8%) cases. Results: The efficiency of anticoagulant therapy was assessed by a decrease of thrombinemia markers (fibrinogen, SFMC and D-dimer). After a week of anticoagulant therapy, a significant reduction in the level of D-dimer was observed. However, the decline in fibrinogen and SFMC was statistically insignificant. VTE therapy was performed with fondaparinux in a therapeutic dose from 10 days to 1 month, followed by a transition to oral anticoagulants. There was no hospital mortality. Hematuria developed in one case (3.1%), and was managed conservatively. There were no hemorrhagic complications in the operative intervention zone. Two patients (6.25%) had a recurrence of VTE during the period of radiation therapy. Conclusions: An integrated approach to the treatment of VTE in patients undergoing craniotomy provides a low incidence of recurrent VTE and major bleeding.
High-grade gliomas (HGGs) and immunotherapeutic early-phase clinical trials (ieCTs): A single-center experience.
Authors: Simonelli Matteo , Persico Pasquale , Dipasquale Angelo , Lorenzi Elena , Giordano Laura , Pessina Federico , Navarria Pierina , Scorsetti Marta , Bello Lorenzo , Santoro Armando 
Published: May 2019

e13512 Background: Patients with HGGs have historically been excluded from ieCTs due to unavailability of serial bioptic sampling, frequent need of corticosteroids, concerns on activity of immunotherapy in central nervous system, and rapid clinical deterioration. Methods: We retrospectively reviewed data of all recurrent HGG patients enrolled in ieCTs at Humanitas Cancer Center Phase I Unit between 2014 and 2018. Disease control rate (DCR) according to RANO criteria, six-months progression-free and overall survival (PFS-6; OS-6), and treatment-related adverse events (TRAEs), were evaluated. A control-cohort (CC) of patients treated with standard treatments (temozolomide, fotemustine, lomustine and procarbazine, bevacizumab) matched (1:1) for age, line of treatment, MGMT methylation and IDH mutational status, was selected for comparison. Clinical parameters including use of steroids, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, albumin, total protein, were correlated with survival through an univariate analysis. Results: 5 among 21 ieCTs allowed inclusion of HGG patients. 20 patients were enrolled in our experimental cohort (EC); 17 (85%) glioblastoma, 3 (15%) anaplastic astrocytoma. Median age was 53 years (range 30-71); 12 patients (60%) were men, 8 (40%) women; 13 pts (65%) required steroid therapy, with a median dexamethasone dose of 2 mg (range 1-6). The median number of prior systemic therapies was 1 (range 1-2). 11 patients (55%) received monotherapies (anti PD-1, anti CSFR-1, anti TGF-ß, anti cereblon), 9 (45%) combination regimens (anti PD-L1 + anti CD38, anti PD-1 + anti CSFR-1). DCR was 45% (1 CR + 2 PR + 6 SD) and 30% (1 RP +5 SD), in EC and CC, respectively. 4 patients (20%) in EC had grade ≥3 TRAEs (1 neutropenia, 1 pneumonia, 2 hepatitis). With a median follow-up of 22 months PFS-6 and OS-6 were 53% and 11% (p < .0001), 80% and 42% (p < 0.0001) in EC and CC, respectively. In our small series, none of clinical factors resulted prognostic. Conclusions: Survival outcomes of our HGG patients treated into ieCTs compared very favorably with a matched CC. Inclusion of HGGs patients into ieCTs should be strongly encouraged. Identification of clinical selection factors remains crucial.
Safety of nivolumab in combination with dendritic cell vaccines in recurrent high-grade glioma.
Authors: Peters Katherine B. , Archer Gerald E. , Norberg Pamela , Xie Weihua , Threatt Stevie , Lipp Eric S , Herndon James Emmett , Healy Patrick , Congdon Kendra , Sanchez-Perez Luis , Friedman Henry S. , Desjardins Annick , Vlahovic Gordana , Sampson John H. 
Published: May 2019

e13526 Background: Recurrence of high-grade glioma (HGG) (WHO grade III-IV) is a nearly universal phenomenon and necessitates the development of new therapeutic modalities. Two possible immunotherapeutic modalities are checkpoint blockade with agents such as nivolumab, a blocking antibody against the inhibitory checkpoint programmed cell death-1 (PD-1), and dendritic cell (DC) vaccination. We have shown in phase 1 and 2 trials that DC vaccination against the glioblastoma (GBM)-associated antigen human cytomegalovirus pp65-lysosomal-associated membrane protein (CMVpp65) is safe and possesses potential benefit. We hypothesized that nivolumab-induced immune checkpoint blockade could enhance efficacy of DC vaccination. Therefore, we undertook a phase 1 study to evaluate safety of nivolumab in combination with CMVpp65 mRNA pulsed DC vaccination in subjects with first or second recurrence of resectable HGG. Methods: We performed a phase 1, single-center, randomized study of nivolumab alone versus nivolumab + DC vaccination prior to planned surgical resection for both groups. We administered nivolumab 3 mg/kg IV q2weeks for 8 weeks followed by surgery and planned continuation of nivolumab. For the group receiving nivolumab + DC vaccination, we administered 3 vaccines before surgical resection with both groups receiving 5 planned post-resection DC vaccines. Primary endpoint was safety assessment using NCI-CTCAE 4.03. Results: We enrolled 6 subjects (4: GBM, 1: anaplastic astrocytoma, 1: anaplastic oligodendroglioma) with 3 receiving nivolumab alone and 3 receiving nivolumab + DC vaccination. Age range was 45-63 years subjects. We documented similar adverse events in both groups with most common grade 1-2 toxicities being fatigue (2 subjects, nivolumab alone) and thrombocytopenia (2 subjects, nivolumab + DC vaccine). Grade 4 toxicities included wound infection (2 subjects, nivolumab + DC vaccine) and meningitis (1 subject, nivolumab + DC vaccine). While we designed the study to enroll 66 subjects, we terminated the study early in light of CheckMate 143 phase III data showing nivolumab did not improve overall survival in recurrent GBM. Conclusions: Safety of nivolumab + DC vaccination in recurrent HGG is similar to nivolumab alone. Continued evaluation of new therapeutics including immunotherapy is underway for this patient population. Clinical trial information: NCT02529072.
The impact of Epstein-Barr virus status on primary CNS lymphoma survival.
Authors: Prado Isabel P , Barbiero Frank , Baehring Joachim M. , Becker Kevin , Corbin Zachary 
Published: May 2019

e13528 Background: Primary CNS lymphoma (PCNSL) incidence is increasing among the elderly and immunocompromised. Especially for these vulnerable populations, a deeper understanding of the prognostic value of tumor biomarkers is necessary to recommend more targeted therapies. Our primary objective is to evaluate the predictive strength of immunohistochemical markers on PCNSL overall survival. Secondary objectives include estimating the impact of these biomarkers on event-free survival. Methods: We retrospectively analyzed PCNSL patients treated at Yale between 2000 and 2018. The primary endpoint is overall survival. Event-free survival, measured by time to relapse or death, is the secondary endpoint. Kaplan-Meier survival curves with log-log confidence intervals were used to estimate survival outcomes. Cox proportional hazards regression models were used to evaluate the statistical significance (at alpha = 0.05) of immunohistochemical markers. Results: One hundred ten subjects were analyzed. Not all biomarkers were available for every subject. The median age of the cohort is 64 years. Sixty-three patients died, and seventy-six experienced an event (progression or death). Surviving patients had a median follow-up of 4.36 years. The median overall survival is 2.63 years (95% confidence interval (CI): 1.13 to 5.98 years). Epstein-Barr virus (EBV) status by immunohistochemistry significantly impacted overall survival. Adjusting for age and immunocompromised status, EBV-positive patients had a higher risk of death than EBV-negative patients (n = 13, hazard ratio (HR) = 33.75, 95% CI: 1.61-708.68). Other significant biomarkers include the GFAP and S100 proteins. The median event-free survival is 1.13 years (95% CI: 0.66 to 2.12 years), and EBV-positive patients had an increased risk of event (HR = 38.23, 95% CI: 2.32-630.88). CD10, BCL2, BCL6, and MUM1 were not significant to predict either survival outcome. Conclusions: We describe a large cohort of PCNSL patients treated at a single institution with comparable survival outcomes to similar research yet conflicting evidence of biomarker significance. Multi-institutional studies may further clarify the prognostic role of immunohistochemistry for improved PCNSL patient survival.
The utility of surgery in butterfly glioblastoma: A case-control study.
Authors: Hall Benjamin James , Maleyko Igor , Brodbelt Andrew , Jenkinson Michael D , Chavredakis Emmanuel 
Published: May 2019

e13529 Background: Glioblastoma is the most common primary brain tumour and may rarely infiltrate the corpus callosum. Such ‘butterfly’ glioblastomas (BGBM) are believed to confer a poorer prognosis than their non-callosal counterparts. We aimed to determine the impact of surgery on overall survival (OS) and postoperative morbidity in butterfly glioblastomas. Methods: Retrospective analysis was performed on all case notes of patients histologically diagnosed with GBM from January 2011 to January 2017 at The Walton Centre NHS Foundation Trust, Liverpool. Data was collected under the following headings: demographics, tumour characteristics, surgical data, adjuvant therapy and survival data. A case-matched control group was produced according to age, sex and 1o resection. Univariate analysis was performed. Results: 632 glioblastoma patients were identified. 37 patients were diagnosed with butterfly BGBM, with a median age of 62.7 years and a gender split of 24 males (64.9%) to 13 females (35.1%). Median tumour volume was 31700mm3, with 24 (56%) tumours involving the genu and 13 (22%) the splenium of the callosum. Kaplan-Meier analysis with log-rank testing demonstrated a significant (p = 0.04) decrease in median OS in those with BGBM (100 days (95%CI 57-142)) vs controls (276 days (95%CI 224-327)). Resection of BGBMs resulted in longer median OS than biopsy alone (296 days (95%CI 229-363) vs 81 (66-96)), though this was a non-significant difference (p = 0.36). Multifocal disease occurred significantly more often in BGBM patients (p = 0.01), the exclusion of which from analysis demonstrated a significant survival benefit with resection (427 days (95%CI 207-647)) compared to biopsy (221 days (95%CI 151-291)) (p = 0.04). Postoperative complications did not occur significantly more often in BGBM resections than controls (7/36 (19.4%) vs 5/36 (13.9%) (p = 0.257)). Conclusions: Overall, butterfly glioblastomas confer a worse prognosis than those without callosal involvement. A greater prevalence of multifocal disease is seen in butterfly glioblastoma, warranting further investigation. Resection offers a significant improvement in OS in solitary butterfly glioblastomas without a significant increase in postoperative morbidity, and should therefore be considered an efficacious and safe treatment option.