bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in screening rates in a multi-ethnic population-based study in Chicago.
Authors: Aschebrook-Kilfoy Brisa , Kibriya Muhammad Ghulam , Chiu Brian C-H , Huo Dezheng , List Marcy A , Stepniak Elizabeth , Sarwar Golam , Al Shams Rabab , Gopalakrishnan Rajan , Le Beau Michelle M. , Ahsan Habibul 
Published: September 2018

1509 Background: We initiated the Chicago Multiethnic Prevention and Surveillance Study (COMPASS) in 2013. Here, we present screening rates for key cancers with known disparities in risk/and or outcomes in Chicago, considering the effect health care access and race/ethnicity, and we compare the findings in COMPASS to rates reported by the CDC. Methods: COMPASS participant responses to a health interview were analyzed. The analysis of colorectal cancer screening (CRCS) was limited to persons 50-75, mammography screening (MS) was restricted to women ages 50-74, and cervical screening (CS) by pap smear testing was restricted to women ages 21-65. Frequency statistics and linear regression models were run to evaluate associations. Results: A total of 2,967 COMPASS participants were included in the analysis from 18 communities. We found ever CRCS rates in Chicago are lower than the national average (52.3% vs. 58.6%; p < .01) and that CRCS is lower in blacks (50.3%) and Hispanics (52.1%) compared to whites (65.8%), and that those with health insurance (HI) report a CRCS rate of 56.8% compared to 25.5% without insurance. Mammography within the last 2 years was 70.8% in COMPASS women compared to 72.4% nationally, with black women reporting higher rates of MS in the past 2 years (73.0%) compared to white women (65.4%) and Hispanic women (62.9%); and higher MS among women with HI (74.2%) compared to women without HI (47.2%). Pap screening within the last 5 years was 84.3% in COMPASS women compared to 83.0% nationally (last 3 years), with both black (85.3%) and Hispanic (83.2%) women reporting non-significantly higher CS compared to white women (80.9%) in COMPASS, and significantly higher CS among women with HI (86.2%) compared to women without HI (77.7%). Conclusions: Our results reinforce the fact that differences in cancer screening reflect the larger problem of access to care. We further found racial disparities in CRC screening in COMPASS to be consistent with disparities in incidence. However, our results do not support the notion that the disproportionate burden of breast and cervical cancer in black and Hispanic women in Chicago are primarily due to a lack of screening.
Identification of putative germline mutations in 10,288 patients undergoing circulating tumor DNA testing.
Authors: Slavin Thomas Paul , Banks Kimberly , Chudova Darya , Oxnard Geoffrey R. , Odegaard Justin I. , Nagy Rebecca J , Neuhausen Susan L. , Gray Stacy W. , Cristofanilli Massimo , Rodriguez Angel Augusto , Bardia Aditya , Leyland-Jones Brian , Janicek Mike , Lilly Michael B. , Sonpavde Guru , Lee Christine E. , Lanman Richard B. , Meric-Bernstam Funda , Kurzrock Razelle , Weitzel Jeffrey N. 
Published: September 2018

1514 Background: No studies have yet described incidental detection of germline cancer predisposition mutations using circulating cell-free DNA (cfDNA). Methods: Deidentified cfDNA sequencing data from 10288 advanced cancer patients (pts) undergoing clinical circulating tumor DNA testing (Guardant360, 73 genes) were included in this study. CfDNA was extracted from plasma and quantified. A DNA library was prepared and sequenced to 15,000X average read depth. Using Ingenuity Variant Analysis, point mutations and small indels suspicious for germline origin (allele fraction 40-60%) were classified following American College of Medical Genetics and Genomics guidelines. Results: More than 50 cancer types were studied, including lung (40%), breast (20%), CRC (8%), prostate (6%), and pancreas (3%). Average age was 63.6 years (range:18-95), 42% were male. Of 34,873 putative germline variants identified, 520 (1.5%) were pathogenic or likely pathogenic (PV), 16,939 (49%) were of uncertain significance, and 17,414 (50%) were benign or likely benign. Of the 250 pts (2.4%) with hereditary cancer syndrome gene PVs, 83 were excluded due to high level of somatic tumor burden leaving 167 (1.6%) with putative germline PVs; rates were higher in pts <50 vs >50 overall (3.3% vs 1.4%, p=0.02) and in breast cancer pts (4.3% vs 1.5%, p=0.03). Conclusions: The observed frequency of incidentally identified putative germline PVs is expectedly lower than the true germline rate; however, these findings illustrate that detection from cfDNA is clinically feasible. Importantly, incidental germline findings could impact oncology treatment planning (e.g. PARP inhibitors for BRCA1/2 mutations) and could benefit families via increased surveillance/primary prevention. Further research is needed to explore how to report potential germline results to clinicians using a systems-based approach. [Table: see text]
Germline mutations of PALB2 gene in a sequential series of Chinese patients with breast cancer.
Authors: Zhou Jiaojiao , Zhang Kun , Zhu Xuan , Deng Mei , Luo Meng , Xu Chunjing , Yu Jie-Kai , Chen Yiding 
Published: September 2018

1530 Background: PALB2 (Partner and Localizer of BRCA2) is recently recognized as a breast cancer predisposition gene, which plays a critical role in genome maintenance via interacting with BRCA1/2 and RAD51 when DNA break. Germline loss-of-function mutations in PALB2 lead to increased breast cancer risk. Since the germline mutation frequency of PALB2 is much less than BRCA1/2, the distinct mutation spectrum of PALB2 is still obscure. Therefore, we assessed the mutational frequency, spectrum and predictors of the PALB2 gene in a sequential series of Chinese breast cancer patients from our Research DNA Bank, to verify the utility of PALB2 genetic testing in Chinese population. Methods: We examined Chinese breast cancer cases (n = 2279) who agreed to participate in research DNA banking, recruited from 1990 through 2016. To identify the mutations, complete coding sequence and intron–exon boundaries of PALB2 were screened with Next Generation Sequencing. Personal and family histories were synchronously collected for mutation identification. Results: Among the 2279 breast cancer patients, 307 patients were familial breast cancer cases and the rest 1972 patients were sporadic breast cancer cases. PALB2 mutation carriers accounted for 7.8% (n = 24) and 4.8% (n = 95) in familial and sporadic breast cancer cohort separately. In total, 31 missense, 4 nonsense, 3 frameshift, 3 splicing and 1 codon mutations of PALB2 were identified in this study. Among the pathologic variants, PALB2 c.1744C > T, c.2748+1G > A, c.2749-1G > C, c.3114-1G > A were newly identified in sporadic breast cancer, and c.3271delC newly found in familial breast cancer. Based on in silico analysis, a total of 6 potential damaging missense variants were novelly found in this study, among which the PALB2 c.3035C > T was detected in both sporadic and familial breast cancer. Conclusions: Our data presents the germline mutation status of PALB2 in Chinese patients with breast cancer, suggesting that loss-of-function germline mutations of PALB2 are important in both familial and sporadic breast cancer. Clinically, this information may be helpful in genetic counseling of breast cancer patients with PALB2 germline mutation.
Soft palatal melanosis as a predictor for neoplasia in the upper aerodigestive tract.
Authors: Hirata Kenro , Yokoyama Akira , Nakamura Rieko , Omori Tai , Kawakubo Hirofumi , Mizukami Takeshi , Maruyama Katsuya , Kanai Takanori , Yokoyama Tetsuji 
Published: September 2018

1542 Background: Squamous cell dysplasia and carcinoma in the upper aerodigestive tract (UAT) was frequently accompanied by melanosis in the UAT. Soft palatal melanosis can be detected by visual inspection during routine physical examination or even personally in a mirror. Methods: We reviewed digitalized records of high-quality endoscopic images of the soft palate of 1786 Japanese alcoholic men who underwent endoscopic screening combined with esophageal iodine staining and evaluated to what extent the presence of soft palatal melanosis combined with other risk factors can predict the risk of UAT neoplasia. Results: Soft palatal melanosis was observed in 381 (21·3%) of the subjects (mild, 15·0%; distinct, 6·3%). An older age, an inactive heterozygous aldehyde dehydrogenase-2 genotype, smoking, and a high mean corpuscular volume (MCV) were positively associated with the presence of soft palatal melanosis. The age-adjusted odds ratio (OR [95% CI]) for neoplasia in the UAT was 1·92 [1·40–2·64] in the group with melanosis and 2·51 (1·55–4·06) in the group with distinct melanosis, compared with the melanosis-free group. A multiple logistic analysis including the alcohol and aldehyde dehydrogenases genotypes and non-genetic risk factors showed that the presence of soft palatal melanosis was independently associated with a high risk of neoplasia in the UAT. We calculated the individual number of risk factors out of four easily identifiable and significant factors: age ≥55 years, current/former alcohol flushing, MCV ≥106 fl, and distinct soft palatal melanosis. Compared with the risk-factor-free condition, the OR (95% CI) values of UAT neoplasia for one, two, three and four risk factors were 1·49 (0·97–2·30), 3·14 (2·02–4·88), 4·80 (2·71–8·51) and 7·80 (2·17–28·1), respectively. Conclusions: Soft palatal melanosis combined with other simple risk assessments provides a simple new strategy for identifying heavy drinkers with a high risk for UAT neoplasia.
Safety of multiplex gene testing for inherited cancer risk in a fully accrued prospective trial.
Authors: Kurian Allison W. , Idos Gregory , Ricker Charite Nicolette , Culver Julie , Sturgeon Duveen , Kingham Kerry , Koff Rachel , Lowstuter Katrina , Chun Nicolette M. , Rowe-Teeter Courtney , Partynski Katlyn , Hartman Anne-Renee , Allen Brian , Kidd John , Mills Meredith , Hong Christine , McDonnell Kevin , Ladabaum Uri , Ford James M. , Gruber Stephen B. 
Published: September 2018

1576 Background: Sequencing more genes increases the chance of finding a pathogenic mutation and/or a variant of uncertain significance (VUS). Little is known about potential harms of multiplex testing for cancer risk, such as unwarranted surgery or adverse psychological effects. Methods: We conducted a prospective trial of sequencing 25 genes : APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were eligible if they met standard testing guidelines or predictive models estimated ≥2.5% mutation probability. Participants were surveyed 3 months post-test: the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale measured distress, uncertainty and positive experiences. We report on the fully accrued trial (N = 2000). Results: 1998/2000 (99.9%) participants currently have reported results: 12.1% tested positive for a pathogenic mutation (Pos), 34.5% had VUS only and 53.5% tested negative (Neg). Median age was 51, 81% were female, 40% Hispanic, and 72% had a cancer history. Self-reported preventive surgery rates were low (mastectomy 9.3%, hysterectomy 1.5%, oophorectomy 1.6%), with no difference between VUS and Neg patients (p = 0.346). Most patients never or rarely had thoughts of cancer affecting daily activities (Pos 59.5%, VUS 66.9%, Neg 71.0%), never regretted testing (Pos 84.1%, VUS 90.0%, Neg 93.6%), and wanted to know all results, even those that doctors do not fully understand (Pos 81.7%, VUS 78.8%, Neg 77.1%). Pos patients had higher MICRA distress and uncertainty scores than VUS and Neg patients, whose distress and uncertainty scores did not differ significantly (p = 0.165, p = 0.129). Relatives of Pos patients completed genetic testing (30.4%) more often than VUS (5.8%) or Neg patients (5.1%, p < 0.001). Conclusions: After multiplex testing of 2000 diverse patients, few reported preventive surgery at 3 months; VUS patients had no more distress, regret or uncertainty than Neg patients. Pos patients most often advised relatives to test, suggesting that participants understood the implications of test results. Longer-term follow-up of test-related outcomes is underway. Clinical trial information: NCT02324062.
Remote genomic consultation to support uptake of a multi-gene genomic tumor panel (MGTP) by community oncologists (COs): Results of a pilot study.
Authors: Hall Michael J. , Chertock Yana , Handorf Elizabeth , Kaczmar John M. , Innocent Julie , Wong Yu-Ning , Daly Mary Beryl 
Published: September 2018

1587 Background: MGTP use in routine cancer (CA) care is likely to increase w/lower costs for NGS-based testing and growing numbers of actionable targets coupled with targeted therapeutics. Early MGPT uptake has been slow among community oncologists (COs) due to their lower confidence to order, interpret, and act upon results of MGTP. This study evaluated the provision of telephone genomic consultation (GC) via an academic clinician link to an institutional genomic tumor board to support MGTP testing of CA patients (PTs) by COs. Methods: 4 practices of COs participated: 9 COs recruited 25 PTs w/metastatic CA. All PTs/COs completed baseline and follow-up (FU) assessments. Tumor blocks were evaluated at Fox Chase Cancer Center (FCCC) and tested w/a 50-gene MGTP. 12% blocks were inadequate. MGTP results were presented when appropriate at FCCC’s Genomic Tumor Board. All MGTP yielded > 1 variant (Var) [range 1-6]: 13/22 (59%) pts tested had a clinically relevant V; 6 other Vars were potentially actionable w/ approved therapy, while 3 Vars have novel therapies in Phase I/II studies. MGTP were called out to COs (by MJH) < 2 wks of resulting. A tailored summary was provided to COs. Results: At baseline, COs (n = 9) had limited experience w/MGTP (78%, < 5 ordered). Barriers for COs were: poor understanding of MGTPs (67%), cost (89%), uncertain benefit (44%), and poor access to targeted therapies (67%). At FU, 4/8 (50%) COs found GC “very useful”, and 63% reported MGPT paired w/GC would “probably/definitely” increase their use of MGTPs. Most (88%) felt MGPTs should be offered to PTs w/incurable CA. Among PTs at baseline (n = 25), awareness of MGTP was moderate (50%), but 79% reported it would help doctors take better care of their PTs. Valuation of MGTP was mixed—30% would pay $0 out of pocket, yet 30% also said they would travel “any distance” for an MGT-targeted experimental therapy. At FU (n = 14), 86% PTs felt MGPT was valuable, yet only 46% would “definitely” retest, and only 31% would pay > $100 to retest, even for 500+ genes. Conclusions: GC can be effective to support COs to use MGTPs. PTs w/CA have high expectations of MGTPs to improve their care, and yet attribute modest value to retest or to have a larger MGTP.
Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: Efficacy and imaging analyses of the ARTE trial.
Authors: Wirsching Hans-Georg , Tabatabai Ghazaleh , Roelcke Ulrich , Hottinger Andreas Felix , Schmid Andrea , Plasswilm Ludwig , Conen Katrin Lisa , Hundsberger Thomas , Caparrotti Francesca , Von Moos Roger , Riklin Christian Alexander , Remonda Luca , Roth Patrick , Held Leonhard , Rushing Elisabeth Jane , Ochsenbein Adrian , Weller Michael 
Published: September 2018

2014 Background: The addition of bevacizumab (BEV) to first-line temozolomide chemoradiotherapy prolonged progression-free survival (PFS), but not overall survival (OS) in newly diagnosed glioblastoma in two phase III trials. Elderly and frail patients are underrepresented in most clinical trials, but early uncontrolled reports of BEV treatment of glioblastoma suggested preferential benefit in this patient population. Methods: ARTE was a 2:1 randomized, multi-center, open-label trial of hypofractionated radiotherapy (RT) in combination with intravenous BEV every 2 weeks (Arm A, N = 50) versus RT alone (Arm B, N = 25) in patients with newly diagnosed glioblastoma aged 65 years or older. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Response was assessed using Response Assessment in Neuro-Oncology (RANO) criteria. Exploratory imaging studies included apparent diffusion coefficient (ADC) mapping and 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET). Results: Established prognostic factors including age, Karnofsky performance score (KPS), O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation and steroid intake at study entry were balanced between arms. Median PFS was longer in Arm A vs. Arm B (7.6 vs. 4.8 months, p = 0.003), but OS was similar (12.1 vs 12.2 months, p = 0.8). Prior to progression, no differences in QoL were noted, but clinical deterioration was deferred in Arm A vs. Arm B. In a Cox model that controlled for established prognostic factors, an association with prolonged PFS was detected for Arm A versus Arm B (hazard ratio [HR] 0.36, p = 0.001) and for KPS 90-100% versus 60-80% (HR 0.50, p = 0.02). Applying a similar Cox model to OS detected an association with age 65-69 vs 70+ (HR 0.52, p = 0.02) and KPS 90-100% versus 60-80% (HR 0.53, p = 0.03). Exploration of imaging predictors of OS for Arm A identified response by RANO (HR 0.52, p = 0.02), but detected no prognostic role for T2, ADC or FET signal intensity. Conclusions: Efficacy outcomes and exploratory imaging analyses of the ARTE trial do not support the notion that benefit from BEV is more pronounced in elderly glioblastoma patients. Clinical trial information: NCT01443676.
Final results from the dose-escalation stage of a phase 1/2 trial of TPI 287, a brain penetrable microtubule inhibitor, plus bevacizumab in patients with recurrent glioblastoma.
Authors: Goldlust Samuel Aaron , Nabors Louis B. , Mohile Nimish , Benkers Tara L. , Hsu Sigmund H. , Silberman Sandra , Singer Samuel , Rao Mayank , Cappello Lori , Farmer George 
Published: September 2018

2021 Background: Microtubule inhibitors, including taxanes, are active in preclinical models of glioblastoma (GBM), however, clinical benefit is hampered by poor blood-brain barrier (BBB) accumulation. TPI 287, a third-generation taxane designed to evade P-glycoprotein mediated efflux, readily penetrates the BBB and overcomes this limitation. CB-017 is a multi-center phase 1/2 trial designed to determine the optimal dose of TPI 287 and potential efficacy in patients treated with this drug plus bevacizumab (BEV) for treatment of recurrent GBM. Final results of the dose escalation Phase 1 stage of this trial are reported. Methods: GBM patients at first or second relapse after standard therapy and without prior exposure to anti-angiogenic agents were eligible for enrollment. BEV was administered at 10 mg/kg every 2 weeks and TPI 287 every 3 weeks via IV infusion. MRIs were obtained every six weeks with response assessed via RANO criteria. TPI 287 dose escalation was based on a traditional 3+3 design. Results: Twenty-four patients were enrolled in 7 TPI 287 dose-escalation cohorts (140-220 mg/m2) from 6 U.S. centers. Twenty and 23 patients were evaluable for response and survival, respectively. Median follow-up was 28 months. Results are shown in the table below. Of the 9 patients from which biomarker data was available, tumors from 8 patients (89%) harbored an unmethylated MGMT promoter, an established negative prognostic indicator for survival. No DLTs were reported and myelosuppression (n=3) was the only drug-related grade 3/4 adverse event. Conclusions: TPI 287 in combination with BEV is safe and well tolerated at doses up to 220 mg/m2. Final survival results from the Phase 1 portion of this study compare favorably with historical controls and support further investigation of TPI 287 plus BEV for treatment of recurrent GBM. Clinical trial information: NCT01933815. [Table: see text]
Phase I/II study of an implantable device delivering low intensity pulsed ultrasound (LIPU) to disrupt the blood-brain barrier (BBB) followed by intravenous carboplatin chemotherapy in patients with recurrent glioblastoma (GBM).
Authors: Idbaih Ahmed , Canney Michael , Vignot Alexandre , Law-Ye Bruno , Dehais Caroline , Houillier Caroline , Laigle-Donadey Florence , Delattre Jean-Yves , Carpentier Alexandre 
Published: September 2018

2034 Background: The BBB prevents the passage of most drugs from the blood to the brain and may be responsible for the limited efficacy of current chemotherapies in GBM patients. Two to four minutes of LIPU in combination with injection of micron-sized microbubbles has been shown to be a safe method for disrupting the BBB for a duration of 6 hours to increase the passage of drugs such as carboplatin by 5 to 7 fold in normal brain. Methods: Patients with recurrent GBM were implanted with a 1 MHz, 10-mm diameter pulsed ultrasound device in a burr hole during additional debulking surgery or during a dedicated procedure under local anesthesia. Ultrasound dose was escalated using a 3+3 Simon design. The device was activated monthly in combination with injection of a sulfur hexafluoride microbubble to transiently disrupt the BBB in 5 cm3 of the tumor field before IV administration of carboplatin chemotherapy (AUC4-6). Patients received 150-270 seconds of pulsed ultrasound < 1 hour prior to chemotherapy. BBB disruption was visualized using contrast-enhanced T1w MRI, and patients were monitored clinically and with T2, FLAIR, DWI and SWI sequences. Tumor progression was evaluated using the RANO criteria. Results: Nineteen patients were treated by LIPU until tumor progression. In 65 ultrasound sessions, 52 showed BBB disruption. The median number of monthly sonications per patient was 3 and ranged from 1-10. No significant adverse events related to ultrasound sonications were observed. Six patients (31%) had long PFS (19, 20, 35, 38, 40, 52 weeks). When tumor recurrence occurred, it was predominantly outside of the ultrasound sonication field. Conclusions: This trial has demonstrated that LIPU is a safe modality for disrupting the BBB in GBM patients and may increase the effectiveness of drug therapies in the brain. The sonication of larger volumes of brain may further increase the effectiveness of this therapy in patients with GBM. Clinical trial information: NCT02253212.