bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of second primary malignancies (SPM) in men with castration-resistant prostate cancer (CRPC) in SEER-Medicare database.
Authors: Kaye James A. , Saltus Catherine W , Calingaert Brian , Harris David H , Hunter Shannon , Zong Jihong , Brobert Gunnar Persson , Soriano-Gabarro Montse , Andrews Elizabeth B 
Published: September 2018

e13080 Background: A number of population-based epidemiological studies have been conducted to estimate incidence rates of SPM (newly detected malignancies) among cancer survivors, including those with prostate cancer. However, such data in patients with CRPC are limited. This study was conducted to estimate the incidence of SPM and overall survival (OS) in men with CRPC in the US. Methods: In the SEER-Medicare database, men aged > 65 years with prostate cancer diagnosed in 2000 through 2011 were eligible for the study if they had no other prior malignancy, had surgical or medical castration, and met the protocol-defined criteria for ascertaining castration resistance based on subsequent treatment with any of these therapies: abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, or sipuleucel-T. First SPM were identified in Medicare data as 1 inpatient claim, 2 outpatient claims, or 2 physician claims; or in SEER data as 1 diagnosis. Follow-up data ended in 2013. We estimated incidence of SPM as events per 100 person-years (py) with 95% confidence intervals (CI) and survival by the Kaplan-Meier method. Results: Among 2,234 men with CRPC (83.6% white; mean age, 76.6 years; 80.4% with bone metastases), we identified 172 with SPM, of which 20 (11.6%) were in SEER data. The incidence of all first SPM was 5.9 per 100 py (95% CI, 5.0-6.8). The most common of these were lung (n = 29), bladder (n = 22), colorectal (n = 21), other genitourinary cancers (n = 18), and non-colorectal gastrointestinal cancers (n = 17). Mean (SD) time from CRPC ascertainment to SPM was 1.0 (1.1) year. Median OS for the entire study population was 1.2 years (95% CI, 1.1-1.3) after CRPC ascertainment; estimated survival probabilities (95% CI) at 1, 3, and 5 years were 56% (54%-58%), 17% (15%-18%), and 9% (7%-11%), respectively. Conclusions: Most CRPC patients had claims for a diagnosis of bone metastasis when CRPC was ascertained. SPM were common among the study population and occurred relatively soon after CRPC. Most SPM were identified in Medicare rather than SEER data. These results provided context for the incidence of SPM in men with CRPC up to 2013.
Characterization of germline and tumor genomic profile in unselected young black breast cancer patients.
Authors: Pal Tuya , Cragun Deborah , Wang Xuefeng , Yoder Sean J. , MESA Tania , Rosa Marilin , Tezak Ann , Weidner Anne , Vadaparampil Susan Thomas , Phelan Catherine 
Published: September 2018

e13090 Background: Young black women bear a disproportionate burden of breast cancer (BC), yet there is limited characterization of these cancers based on BRCA1 and BRCA2 ( BRCA) status and tumor genomics. In this pilot study, we characterized: tumor and clinical characteristics based on BRCA carrier status and overlap of basal-like (BL) and triple negative (TN) BC. Methods: A population-based sample of 481 black women diagnosed with invasive BC < age 50 were recruited through the Florida Cancer Registry (FCR). BRCA status was determined based on germline testing. TN status was determined based on pathology reports and FCR data. Among a subset of 90 participants, gene expression profiling (GEP) was conducted on tumor samples through PAM50 analyses to classify intrinsic subtypes and risk of recurrence (ROR) scores. Results: Mean age at BC diagnosis was 41.9 (range: 25-50) and mean ROR score was 49.6 (range: 8.7-80.7). Participants included 7 BRCA1 carriers, 5 BRCA2 carriers, 67 non-carriers (NC), and 11 with no confirmed testing. Of 46 BL tumors, 33 were TN (71.7%) constituting 94.3% of TN tumors (the remaining 5.7% were Luminal A). All BRCA1 carriers had BL tumors, of which 5 were TN. Sensitivity, positive predictive value, and negative predictive value in identifying BRCA1 carrier was higher based on BL compared to TN status (Table 1). BRCA2-associated tumors included 3 Luminal A, 1 Luminal B, and 1 BL. Mean ROR score was highest among BRCA1 carriers (57.7), followed by NC (50.5) and BRCA2 carriers (41.5). Conclusions: Study findings suggest BL status predicted BRCA1 positivity better than TN status. BRCA2- (compared to BRCA1-) associated tumors were more heterogeneous with over half being Luminal A, which may explain the lower ROR among BRCA2 carriers. Additional follow-up and expansion of this cohort with collection of clinical outcomes will be useful in assessing the predictive utility of ROR scores among young black women with BC. [Table: see text]
Ancestry-based differences in hereditary cancer genetic testing.
Authors: Olopade Olufunmilayo I. , Nielsen Sarah , Wang Shengfeng , Bernhisel Ryan , Brown Krystal , Cox Hannah C , Cummings Shelly , Rosenthal Eric Thomas , Saam Jennifer , Lancaster Johnathan M. , Huo Dezheng 
Published: September 2018

e13107 Background: Ancestry-based disparities in genetic testing for the hereditary breast and ovarian cancer (HBOC) genes BRCA1/2 have been well documented, but it is unclear whether this extends to other cancer-risk genes. Given reduced costs and broader access to multi-gene panels, we evaluated ancestry-based differences in the utilization and outcomes of HBOC and pan-cancer panel testing. Methods: Individuals who had genetic testing for BRCA1/2only (2006-2016) or with a multi-gene pan-cancer panel (2013-2016) were assessed. Clinical information was obtained from provider-completed test request forms. The most commonly reported ancestries [European (EU), Latin American/Caribbean (LA/C), African (AF), Asian (AS)] were evaluated. Individuals of Ashkenazi Jewish ancestry were not included in the EU group. Results: The relative utilization of HBOC testing in 2013-2016 increased in AF and LA/C individuals (vs 2006-2013) and was similar to panel testing in all ancestries (Table). The positive mutation rate for panel testing was 6.7%; AF (6.4%), LA/C (6.6%), AS (7.1%), EU (7.1%). The positive rate for HBOC testing from 2006-2013 was 5.7%. Of significance, the HBOC positive rate from 2013-2016 dropped to 4.1% and ancestry-specific positive rates were much lower relative to panel testing (Table). Gene-specific mutation prevalence differed by ancestry, but mutations were identified in a wide range of genes for all ancestries. Possible founder mutations were identified in BRCA1/2 and other genes. Conclusions: In this cohort, broader access to genetic testing has reduced disparities in recent years and panel testing shows improved clinical utility relative to HBOC testing in all ancestries. [Table: see text]
Understanding barriers to receiving genetic testing after referral.
Authors: Murray Drew , Mandadi Mounika 
Published: September 2018

e13108 Background: About 5-10% of breast cancers are hereditary. Identifying women with hereditary breast and ovarian cancer syndromes helps implement screening strategies, chemoprevention regimens, preventative surgeries and identify family members at risk. Little is known about reasons for non-compliance with genetic testing after referral by an oncologist. To gain insight we investigated these barriers in a population of patients in Louisville, Kentucky. Methods: The study design was a IRB approved single institution retrospective analysis of all newly diagnosed breast cancer patients in the year 2014. Data on age, gender, race, education, insurance status, family history, referral orders and genetic testing results were analyzed for 204 patients. Characteristics of patients who received genetic testing after referral was made were compared to patients who did not receive genetic testing, despite referral. The categorical variables were compared using the Pearson Chi-square test for contingency tables while the t-test was used for continuous variables. Significance level was set at p≤0.05. All calculations are performed with SAS statistical software (SAS Institute Inc., Cary, NC). Results: Of 204 newly diagnosed breast cancer patients seen in 2014, 109 met NCCN guidelines for genetic testing. 89 total patients were referred for genetic testing. 67 patients received genetic testing after referral, while 22 patients did not receive the testing despite being referred. 29 patients met criteria for testing but were never referred. Statistical significance existed (P = 0.019) for the insurance status variable, those with private insurance being more likely to receive testing after being referred, and those without insurance being less likely to show up for genetic testing after being referred. There was no statistical significance for age(P = 0.787), race(P = 0.555), or education (P = 0.322). Conclusions: Being covered by private insurance was associated with increased completion of genetic testing after being referred by an oncologist. Age, race, and education did not impact the likelihood of receiving testing if referred. Further investigations will be made into reasons for non-referral in patients who met NCCN guidelines for testing.
Frequency of germline patghogenic mutation in breast cancer patients at high risk hereditary cancer.
Authors: Shin Hee-Chul , Han Wonshik , Lee Han-Byoel , Moon Hyeong-Gon , Lee Eunshin , Noh Dong Young 
Published: September 2018

e13110 Background: Next-generation sequencing technology allows the simultaneous sequencing of multiple target genes. We developed a gene panel containing 64 genes which were associated with various hereditary cancers. This study was performed to evaluate the frequency of pathogenic mutations associated with hereditary cancer among Korean patients at high risk hereditary breast cancer using multi-gene sequencing panel. Methods: A total of 252 breast cancer patients with high-risk hereditary cancer were included. Among them, 179 patients (71.0%) had multiple primary cancers including breast cancer, 27 patients (10.7%) were diagnosed with bilateral breast cancer at age 40 or younger. Thirty-five patients (13.9%) had breast cancer family history of more than 2 relatives. With the 64 gene panel, sequence variants were detected by next-generation sequencing technology. Results: Sixty seven patients (26.8%) were found to have 77 germline pathogenic mutations, 12 in BRCA1, 13 in BRCA2, 9 in CDH1, 3 in FH, 5 in MSH2, 2 in MSH6, 4 in NAT1, 6 in PTCH1, 3 in RAD51, 7 in RET, 4 in SPINK1, 3 in TP53 and one each in ALK, BRIP1, CHEK2, MLH2, MUTYH, and PTEN. In 20 patients (4.0%), 2 (n = 9) or 3 (n = 1) pathogenic mutations were detected. In 227 patients with BRCA1/2 negative, CDH1 (n = 7), RET (n = 7), PTCH1 (n = 5), and MSH2 (n = 5) were the most prevalent pathogenic mutations. Conclusions: The 64 gene panel detected germline pathogenic mutations in 26.8% of Korean breast cancer patients with feature of hereditary cancer. Mutations of BRCA1, BRCA2, CDH1, RET, and PTCH1 were the most prevalent variants.Mutation carriers were considered as high risk to develop malignancy and recommended to receive genetic counseling and intensive cancer screening.
Management of germline findings revealed throughout the course of tumor-normal whole genome sequencing in oncology.
Authors: Lim Howard John , Schrader Kasmintan A , Young Sean , Nelson Jessica , Fok Alexandra , Pleasance Erin , Jones Martin , Shen Yaoqing , Armstrong Linlea , Virani Alice , Rassekh Shahrad Rod , Deyell Rebecca , Yip Stephen , Roscoe Robyn , Karsan Aly , Marra Marco , Laskin Janessa J. 
Published: September 2018

e13113 Background: The Personalized OncoGenomics (POG) project at the BC Cancer Agency utilizes tumor-normal whole genome sequencing (WGS) to understand key driver pathways and guide personalized treatment decisions. Analysis of the germline data can reveal variants; these may be presumed pathogenic, presumed benign or of unknown significance (VUS). We have developed a process for evaluating and returning presumed pathogenic variants in known cancer susceptibility genes to patients, for counseling and validation in a clinical-accredited laboratory. Methods: Patients receive germline cancer related information as part of the consent process for participation in the POG program. A sub-committee comprised of medical geneticists, bioinformaticians, pathologists, oncologists and an ethicist review the germline results. Any variants suspicious of being an artifact undergo a technical validation step. Presumed pathogenic findings of known cancer susceptibility genes are returned to the patient by their treating oncologist and patients are referred to the Hereditary Cancer Program (HCP), for genetic counseling and clinical confirmation. Results: From June 2012 - January 2017 – 466 patients have consented to the project. To date, 39 cases (8.4%) had at least one variant that was deemed pathogenic, 86 cases had at least one VUS in a known cancer susceptibility gene. 11 out of 23 cases (47.8%) with high penetrance mutations were already known to HCP. All VUS were reviewed by the sub-committee taking in to consideration the VUS and clinical context. 8 of the subjects with pathogenic results and 3 with VUS were known to HCP before POG data was generated. A VUS in 7 cases (1.5%) was returned after review. Conclusions: The number of pathogenic variants in known cancer susceptibility genes is consistent with published oncology results. We created a process to manage clinically relevant germline findings discovered during the course of genomic research to ensure appropriate care for patients. Genetic counseling within HCP and validation of variants in the clinically accredited Cancer Genetics Laboratory enables seamless return of research generated clinically relevant germline results to affected subjects. Clinical trial information: NCT02155621.
Prognostic implication of GATA3 gene mutation on survival in invasive ductal carcinoma of the breast.
Authors: Kailasam Karthik , Omaira Mohammad , Chhatrala Hardik Satish , Ravichandar Marie 
Published: September 2018

e13114 Background: GATA3 encodes a transcription factor, which is involved in activation and suppression of genes involved in cell maturation. GATA3 is necessary in the adult mammary gland to maintain the integrity and function of the luminal epithelium. Methods: METABRIC project funded by cancer research UK, the British Columbia cancer foundation and the Canadian breast cancer foundation mapped 173 gene mutations and amplifications in 2,433 primary breast tumors. Retrospective analysis was done for patients with invasive ductal carcinoma of the breast in the age group 30-60; to study the effect of GATA3 mutation on survival. Median survival was obtained from Kaplan-Meier plot, and mortality between groups was compared by Odds ratio (OR). Results: A total of 1500 patients across all age groups had invasive ductal carcinoma. 650 were within the age group 30-60; of which 234 died due to the disease, 360 were alive and 55 died due to other causes. 398 patients (61.2%) tested positive for estrogen receptor (ER) and 521 patients (80.2%) were negative for HER2 (human epidermal growth factor receptor 2). TP53 (50%) and PIK3CA (36%) mutations were more prevalent. GATA3 mutation was found in 79 patients (12.34%); among which, all 79 patients tested positive for ER (100%) and 74 patients (94.9%) negative for HER2. 10 patients (12.7%) died due to the disease, 62 patients (78.5%) were alive and 7 patients (8.9%) died due to other causes. Hence, patients with GATA3 mutations were more likely to survive (OR 4.66; CI 2.33-9.29 p < 0.0001) than patients without the mutation. The median survival for patients with GATA3 mutation (300 months) was also greater than patients without the mutation (219 months). In addition, patients with GATA3 mutation were more likely to be ER positive and HER2 negative. Conclusions: In the mammary gland, GATA3 is required for luminal epithelial cell differentiation. Loss of GATA3 results in de-differentiation to stem cell phenotype. It is found that GATA3 mutation correlates with a better prognosis compared to more common TP53 and PIK3CA gene mutations.
Determining the prevalence of germline BAP1 mutations in malignant mesothelioma (MM).
Authors: Zauderer Marjorie Glass , DuBoff Mariel A. , Siegel Beth , Robson Mark E. , Arnold Angela G. , Berliner Janice , Harlan Fleischut Megan , Mandelker Diana , Ladanyi Marc 
Published: September 2018

e13118 Background: Somatic BAP1 mutations are very common in MM tumors (Bueno et al. Nat Genet 2016, Bott et al. Nature Genet 2011) and germline BAP1 mutations have also been shown to segregate in numerous families with clusters of malignancies including MM (Testa et al. Nat Genet 2011). However, the prevalence of germline BAP1 alterations in an unselected population of MM patients remains unknown. Methods: Unselected patients with MM were enrolled on a prospective trial (NCT01773655) to collect germline DNA, detailed family history, exposure questionnaires, and tumor tissue if available. De-identified germline DNA sequencing was performed to evaluate for the presence of BAP1 mutations. Patients with prespecified high-risk criteria (age < 50 yrs, no asbestos exposure, personal/family history of choroidal nevus, uveal melanoma, melanoma, or mesothelioma, or cancer in ≥ two 1st degree relatives) were contacted by Clinical Genetics and offered counseling and identified BAP1 testing. Results: 120 patietns with MM were enrolled. The majority are male (63%) with pleural mesothelioma (78%) and mostly epithelioid histology (75%). Sixty-seven percent met high-risk criteria for identified testing and 27 patients have consented for identified testing. Both deidentified and identified testing is ongoing. To date, among 17 patients tested, 3 have been identified with germline pathogenic BAP1 alterations. Two of those three patients had a personal history of an associated malignancy. Additional testing results will be reported at the meeting. Conclusions: Germline BAP1 mutations may be more common than previously thought among MM patients. Further work is needed to clarify those at high risk for germline mutation so they and their at-risk family members may receive testing and genetic counseling regarding their risk of malignancy. Additionally, ongoing work to define associations between genotype and phenotype should continue so that the full scope of diseases and risks are outlined for this new BAP1 associated cancer predisposition syndrome.
A feasibility study of the Nativis Voyager system in patients with recurrent glioblastoma multiforme (GBM): Interim results of first-in-human study.
Authors: Barkhoudarian Garni 
Published: September 2018

e13506 Background: The Nativis Voyager® ulRFE™ system, a non-invasive investigational device, was studied in a first-in-human feasibility study to assess if it is a safe and feasible treatment for recurrent glioblastoma multiforme (GBM). The anti-mitotic therapy delivers ultra-low radio frequency energy ( ulRFE) profiles produced by changes in molecular electrostatic surface potential to the brain. The interim results of the first stage of a 2-stage study are presented here. Methods: In this prospective, multi-center trial, patients with GBM, following recurrence after receiving standard-of-care chemotherapy and/or radiotherapy were considered for the study. Patients were treated with Voyager alone or with Voyager plus concurrent chemotherapy or Avastin at the discretion of the investigator. Safety was assessed by incidence of any adverse events associated with the investigational therapy. Tumor progression at 8 weeks (2 cycles) was assessed by radiological response by local site. Patients were followed at least every 8 weeks during treatment and every 4 months thereafter. Results: Fourteen patients were enrolled and treated at four clinical sites across the United States. Eleven subjects were followed per protocol. Three subjects withdrew consent prior to the first radiological assessment (day 28) for reasons not associated with the study or investigational therapy, and were not included in the analysis. The local sites reported a partial response in the first 2 months of treatment in 2 of the 11 subjects. These subjects were Avastin-naïve. Two were reported to be progression free after 6 cycles (24 weeks) of treatment. No serious adverse events associated with the investigational therapy were reported. Conclusions: The Nativis Voyager appears to be feasible and safe for the treatment of recurrent GBM. Given that therapy is delivered non-invasively, and no serious adverse events attributed to the investigational therapy were reported, further prospective study in an expanded study of the investigational device is warranted. Clinical trial information: NCT02296580.
Primary brain tumor and risk of venous thromboembolism.
Authors: Dwary Ashish Dutta , Gupta Ankita , Burton Gary Von , Peddi Prakash 
Published: September 2018

e13518 Background: Venous thromboembolism (VTE) is frequently associated with primary brain tumors (PBT). Brain tumors have been associated with higher rates of VTE in multiple studies. Studies comparing VTE incidence in meningioma (MEN), astrocytoma (AA), oligodendroglioma (OG) and glioblastoma multiforme (GBM) are lacking. The aim of this retrospective study is to report the VTE outcomes in all of the above brain tumors. Methods: Retrospective data from 476 patients with PBTs diagnosed between 1995-2015 at Louisiana State University Health Sciences Center-Shreveport was analyzed. The incidence of VTE (deep vein thrombosis or pulmonary embolism) was studied in these patients. Results: Out of 476 patients, 298 were females and 179 were male. One hundred and twenty seven (127) patients had GBM, 52 had AA, 33 had OG and 264 had MEN. Only two patients out of 264 with MEN had VTE (one patient had central line catheter associated DVT). VTE incidence did not correlate with the type of primary treatment i.e surgery verses radiation verses observation in this patient group. The incidence of VTE was 7.8 % in GBM patients. The risk of VTE in AA and OG patients were 7.7% and 9.0 % respectively. The VTE event in the OG, AA and GBM occurred during all phases of treatment including inpatient hospitalization for surgical resection, during concurrent chemo-radiation and in maintenance phase. Biopsy versus partial resection versus complete resection of GBM didn’t correlate with VTE occurrence. Conclusions: VTE is prevalent among adult patients with both low and high grade glial tumors. The thrombotic events occur during all phases of therapy indicating hypercoagulable state for many patients. Life-long anticoagulation may be necessary in these patients with thrombotic events. Thrombotic events in patients with MEN, however, are rare ( < 1%). MEN do not appear to be a hypercoagulable and life-long anticoagulation is probably unnecessary in those with VTE.