bluuebunny/crossref_metadata_2025_split huggingface dataset:
Counseling and care: A Breast Cancer Awareness Training to improve participation and adherence to screening recommendations in women with a family history of breast cancer
Authors: Artmann A. , Gottschalk N. , Jacobs V. R. , Meindl A. , Kiechle M. , Rummeny E. J. , Harbeck N. 
Published: August 2020

1530 Background: BRCA1 or BRCA2 mutation carriers are at an increased lifetime risk to develop breast and ovarian cancer. In a substantial number of families with affected members the known susceptibility genes cannot be identified. According to the recommendations of the German Consortium for Hereditary Breast and Ovarian Cancer, women with a hereditary predisposition for breast cancer should participate at an intensified surveillance program (ISP) including genetic counseling, risk estimation, BSE, CBE, BreastUS, MX, and MRI. Nonadherence might be influenced by cancer worryness, anxiety, health beliefs, and a lack of information about screening benefits.The aim of this investigation was to evaluate the impact of an indivualized Breast Cancer Awareness Training to improve the participation and adherence towards an ISP. Methods: Since 2005, an at-risk sample of 46 non-participating women (mean age 29 y; range 19–43 y) got an intensive breast cancer awareness training, including structured BSE, specific information about regular follow-up, screening advice, and radiological diagnostic procedures. To establish invidualized counseling and training particular needs (e.g., reasons for non-adherence, health beliefs and behaviours), risk perception, anxiety, and sociodemographic factors were evaluated by interviews and self-report questionnaires. The control group consisted of 38 participants of the ISP. Results: Breast cancer worry, anxiety, and lack of information about the benefits of screening programs were the main reasons for non-adherence. Within 3 months after the base counseling participation rates in MX (>30J), BUS, MRI, and CBE reached 98%. The numbers remain consistent in a 2-year follow up. 80% of participants practice BSE monthly, and 46% reported changes in lifestyle regarding nutrition, obesity, and health beliefs. Conclusions: Our approach emphasizes importance of self confidence and awareness for participation at the ISP for women at high breast cancer risk. Individualized counseling, BSE, re-evaluation, and reinforcement sessions are correlated with changes in health beliefs and behaviours for enhancing participation and adherence in women with a family history of breast cancer. No significant financial relationships to disclose.
Ethnic/racial barriers to cervical cancer prevention with the HPV vaccine
Authors: Gorin S. , Westhoff C. 
Published: August 2020

1546 Background: High risk types of the human papilloma virus (HPV) are necessary though not sufficient causes of the vast majority of cervical cancers. Black women have the highest prevalence of HPV (20.6%, 95% CI, 19.8–21.5%), followed by Latinas (14.1%, 95% CI, 13.9, 14.4%). Black women have the highest rates of mortality from cervical cancer, followed by Latinas. Recent population-based data reveal low uptake of the HPV vaccine (∼25%), particularly among Black women and Latinas. Objectives: The aim of this systematic review is to describe the supports and barriers to HPV vaccine inoculation among Black and Hispanic U.S. women. Methods: We conducted a systematic literature review of studies with more than one observation point or a comparison group that were published over the past 10 years, using a standardized extraction protocol. Inter-rater reliability rates were high (> 0.98). Of 64 English-language articles from peer-reviewed journals, we selected 16 for review. Results: We found barriers at the policy, provider, and patient levels. Barriers at the policy level include access to health care, cost, insurance coverage, vaccine availability, limited knowledge of the HPV vaccine, and media coverage that stigmatizes inoculation. At the provider level, knowledge about HPV incidence and transmission as well as physician recommendation are important factors that influence parental and patient acceptability of the HPV vaccine. Providers report difficulty in discussing STIs with parents, preadolescents, and adolescents. Providers are hesitant to store a vaccine that will be less widely used. Office-based procedures present structural impediments to dissemination of the vaccine. At the patient level, barriers include limited awareness of the vaccine, socioeconomic status, perception of risk based on sexual history, fear of vaccine safety, socio-cultural, economic, and religious factors. Conclusions: Policy, provider, and patient-focused intervention approaches to increasing dissemination of the HPV vaccine are proposed to increase uptake among Black women and Latinas. No significant financial relationships to disclose.
Lessons learned engaging Hispanic communities in cancer research
Authors: Mika V. , Hurd T. C. , Sunil T. , Morning Star L. , Moore F. , Garcia O. , Lopez L. , Martinez M. , Rios R. , Welsh R. 
Published: August 2020

1551 Background: Community involvement is critical to advance cancer education and prevention in minority communities. Researchers must be knowledgeable of the target community's basic cultural beliefs and linguistic needs. This study sought to identify the best approach for conducting community based cancer research in South Texas Hispanic communities. We report our experiences and lessons learned with participants and site recruitment and retention. Methods: We introduced a community based, culturally relevant breast and cervical cancer screening and early detection program, Esperanza y Vida, to address barriers and disparities in four border communities (urban, rural, colonia, and small border town). These areas represent the diverse South Texas Mexican American population in terms of language use, immigration status, and length of time in the US. Within these communities we recruited a grassroots community organization, faith-based health center, rural hospital district, and federally qualified health center. Results: Focus groups were conducted with women and men to assess knowledge, attitudes, and beliefs about women's cancers. To successfully recruit participants, we implemented various techniques to engage the community and establish sustainable relationships. These included community health worker recruitment of community members, traditional recruitment (flyers, posters, word of mouth), key community and cultural leader support, and discussions with local groups and health organizations. We and our community partners identified and overcame investigator/community barriers (lack of community knowledge, community integration into the research process, community understanding of research methods, reluctance to develop innovative approaches). Consequently, participants are eager to remain with the program and are individually and collectively mobilizing others to create a sustainable and durable program. Conclusions: 1. Cultural leader engagement worked best for participant recruitment in the small border town and colonia settings, while key community leader engagement was most effective in the small city urban and rural settings. 2. Research/community partners must identify and discuss project barriers regardless of the fear of creating discordance to reach solutions. No significant financial relationships to disclose.
Current survival statistics for patients with newly diagnosed glioblastoma treated with radiation and temozolomide on research studies in the United States
Authors: Grossman S. A. , Ye X. , Piantadosi S. , Desideri S. , Nabors L. B. , Rosenfeld M. , Fisher J. 
Published: August 2020

2003 Background: Many novel agents are being studied in combination with radiation and temozolomide (RT+TMZ) in newly diagnosed glioblastoma using survival as the primary endpoint. These single arm phase II studies generally plan to compare their results with those reported from the phase III EORTC RT+TMZ study (Stupp, NEJM, 2005). Methods: The NABTT CNS Consortium has completed accrual to three RT+TMZ+ novel agent studies using the same eligibility criteria. A total of 281 patients with newly diagnosed glioblastoma were enrolled. The novel agents included talampanel (72 pts), poly ICLC (97 pts), and cilengitide (112 pts). The survival data emerging from these three single arm phase II studies was compared with the published EORTC data. Results: The median age, KPS, and percent undergoing debulking surgery for EORTC patients was 56, 86% (WHO 0–1), and 84% and for NABTT patients receiving talampanel 60, 90, and 77%, poly ICLC 56, 90, 86%, and cilengitide 55, 90, and 76%. A total of 247 patients (88%) were ages 18–70 making them comparable to the EORTC patient population. Currently available survival data for these NABTT and EORTC studies are provided below. MGMT methylation status and survival based on dose levels are not currently available. Conclusions: Survival of newly diagnosed glioblastoma patients treated with RT+TMZ + novel agents at 9 NABTT institutions accruing from 2005 to 2008 appears increased compared to RT+TMZ at 85 EORTC institutions accruing from 2000 to 2002. These results do not appear related to a specific effective agent. As a result, caution should be exercised when comparing outcomes from recently conducted Phase II studies in this patient population to published EORTC data. [Table: see text] No significant financial relationships to disclose.
Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas (MG) (NABTC 04–02)
Authors: Chang S. M. , Kuhn J. , Lamborn K. , Cloughesy T. , Robins I. , Lieberman F. , Yung A. , Dancey J. , Prados M. , Wen P. 
Published: August 2020

2004 Background: Glioblastomas (GBM) frequently have EGFR amplification/mutations and inactivation of PTEN. Although single agent EGFR and mTOR inhibitors have limited activity, combinations of these agents may be more effective. Methods: The North American Brain Tumor Consortium conducted a phase I/II study of the EGFR inhibitor erlotinib in combination with the mTOR inhibitor temsirolimus in recurrent MG. Eligibility criteria were histologically proven GBM and anaplastic gliomas (AG), radiologic progression, >18 years old, KPS >60, adequate bone marrow and organ function. There was no limit on the number of prior relapses for phase I and no more than two prior relapses for phase II. Patients must not be receiving enzyme-inducing antiepileptic drugs. The dose of erlotinib was 150 mg/d in phase I and titrated up to maximum of 200mg/d in phase II depending on tolerability. Patients initially received temsirolimus 50 mg i.v. once weekly and the dose adjusted based on toxicities. Escalation was performed in groups of three. MTD was defined as the dose with 1/6 or fewer patients with dose-limiting toxicities (DLTs). Primary endpoint for the phase II component was PFS6. Results: In phase I, 22 patients were enrolled (15 GBM; 7 AG). Median age was 54 years (26–74); median KPS 90 (70–100); median prior relapses 1 (0–3). The MTD was determined to be 150 mg of erlotinib daily combined with 15 mg of temsirolimus weekly. DLTs were rash, mucositis, and liver function abnormalities. Pharmacokinetic data were similar to that for single agent erlotinib and temsirolimus; there was no interaction between the two drugs. AUC accumulation ratios between cycle 1 and 2 for erlotinib and OSI-420 were 3.6 and 4.6, respectively. In phase II, there were 56 patients (including 12 phase I patients treated at the MTD): 40 GBM; 16 AG, median age 47 years (20–72); median KPS 90 (range 60–100), median prior relapses 1 (range 1–3). Six patients discontinued therapy as a result of toxicities. For GBM patients, there was no PR, 30% SD, and PFS6 was 12.5%. For AG patients there was 12.5% PR, 12.5% SD, and PFS6 was 6.25%. Conclusions: The combination of erlotinib and temsirolimus was associated with a higher than expected incidence of toxicities and had minimal activity in recurrent MG. [Table: see text]
Phase I/II study of sorefenib and erlotinib for patients with recurrent glioblastoma (GBM) (NABTC 05–02)
Authors: Prados M. , Gilbert M. , Kuhn J. , Lamborn K. , Cloughesy T. , Lieberman F. , Puduvalli V. , Robins H. I. , Lassman A. , Wen P. Y. 
Published: August 2020

2005 Background: Single agent targeted therapy has been disappointing in GBM. Combination therapy simultaneously targeting both EGFR and the MAP kinase pathway may be more effective. Methods: The NABTC conducted a phase I/II study of sorafenib (VEGFR/PDGFR/Raf inhibitor) in combination with erlotinib (EGFR inhibitor) in recurrent GBM. Eligibility criteria included histologically proven GBM, radiologic progression, > 18 yrs old, KPS > 60, adequate bone marrow reserve, and organ function. There was no limit on the number of prior therapies for phase I and no more than two prior relapses for phase II. No enzyme-inducing antiepileptic drugs were allowed. Dose-finding used a standard 3 + 3 design and the MTD was defined as the dose with DLTs in 1/6 or fewer patients. The primary endpoint for the phase II component was PFS6 (p0 = 15%; p1 = 35%). A 2-stage design was used. If > 4 of the initial 19 patients achieved PFS6, an additional 14 patients would be accrued for a total of 33 patients. Results: In phase I, 17 patients were enrolled. Median age 50 years (35–69); median prior chemotherapy 1 (1–3). The initial doses were sorafenib 200 mg bid and erlotinib 100mg qd. MTD was 400 mg bid of sorafenib daily combined with 100 mg of erlotinib daily. At this dose 1/6 evaluable patients had a DLT (grade 4 lipase). Other grade 3 or 4 toxicities included transaminitis, hypertension, hypophosphatemia, and increased lipase. Pharmacokinetic studies showed no alterations in sorafenib PK, but no accumulation of erlotinib, suggesting a drug-drug interaction with sorafenib altering erlotinib metabolism or clearance. In phase II, 19 patients were accrued to stage I. Median age 51 years (30–75); median prior chemotherapy 2 (range 1–3). Phase II toxicity and outcome data are not yet mature but will be available at the time of presentation. Conclusions: This combination was moderately well-tolerated. MTD was below other combination phase I studies. Sorafenib affected the PK of erlotinib preventing drug accumulation. Phase II toxicity and outcome data will be reported. [Table: see text]
RTOG 0625: A phase II study of bevacizumab with irinotecan in recurrent glioblastoma (GBM)
Authors: Gilbert M. R. , Wang M. , Aldape K. , Lassman A. , Sorensen A. G. , Mikkelson T. , Groves M. , Werner-Wasik M. , Regine W. , Mehta M. 
Published: August 2020

2011 Background: Angiogenesis is a hallmark of GBM, making the tumor vasculature an attractive therapeutic target. In gliomas, vascular endothelial growth factor (VEGF) promotes both angiogenesis and invasion of tumor cells. Bevacizumab is a humanized monoclonal antibody against VEGF-A that rapidly reduces the concentration of VEGF in the circulation. Irinotecan may enhance efficacy by synergistic tumor endothelial cell death or improved tumor delivery of the chemotherapy via “normalized” tumor vasculature. Prior studies of this combination demonstrated high radiographic response and 6-month progression free (6-mPFS) rates. This study was designed to determine the efficacy and safety of this regimen in the cooperative group setting. Methods: Eligibility included age ≥ 18, centrally confirmed GBM or gliosarcoma, progressive or recurrent disease. Enzyme-inducing anticonvulsants were not allowed. Treatment was intravenous bevacizumab 10 mg/kg and irinotecan 200 mg/m2 every 2 weeks. Accrual goal was 57 eligible patients. Primary endpoint was 6-mPFS rate where an estimate of ≥ 35% would define efficacy (15% improvement over historical data). Results: Full enrollment (57) was achieved, median age was 57, median KPS was 80; all had prior radiation and temozolomide treatment. The 6m-PFS rate was 37% (95% CI: 24–50%), with 21 of 57 patients progression-free at 6 months. Moderate toxicity was noted with 21(37%) grade 3, seven (12%) grade 4, and one (<2%) treatment-related death (intracranial hemorrhage). There were six episodes of venous thrombosis, 14 episodes of grade 3 or 4 hematologic toxicity, predominantly lymphopenia (7), and neutropenia (4), no opportunistic infections or febrile neutropenia were noted. Other toxicities included fatigue (9), diarrhea (2), and hypertension (2). Conclusions: These results, in the cooperative group context, corroborate the efficacy of the bevacizumab and irinotecan combination for recurrent GBM with the 6m-PFS surpassing the predetermined efficacy threshold. Previously described toxicities were confirmed with a moderately high rate of venous thrombosis, one intracranial hemorrhage, and moderate hypertension. Studies to determine the contribution of the cytotoxic agent to efficacy and the role of bevacizumab in newly diagnosed GBM are planned. [Table: see text]
The paradoxical effect of targeted antivascular agents in the therapy of CNS malignancies
Authors: Neuwelt E. A. , Frenkel E. 
Published: August 2020

2013 Background: The rationale of vascular targeted agents (i.e., inhibitors of vascular endothelial growth factors [VEGF] or endothelial intergrins) in the therapy of central nervous system (CNS) malignancies is based upon the concept that normalization of tumor vasculature, with a decrease in tumor interstitial pressure, will improve access of cytoreductive drugs. However, previous studies in our laboratory have raised the serious concern that these agents rapidly normalize the blood-brain barrier (BBB) and therefore may result in restoration of the low permeability characteristics of the BBB. Methods: To evaluate this, we studied the effects of bevacizumab, an anti-VEGF agent on tumor vasculature by MRI, using gadolinium-enhanced T1 weighted sequences to assess permeability and the blood pool agent ferumoxytol to assess blood volume. Patient imaging studies were done on IRB approved protocols. Results: Utilizing two rat brain tumor models, we documented that bevacizumab rapidly decreases tumor enhancement, a pattern equivalent to administration of high dose steroid therapy. Correlative studies in rats and humans exploiting T2 weighted imaging, demonstrated resolution of tumor enhancement with occasional concomitant increase in tumor volume. In a parallel evaluation, pseudo-progression was seen in 9 of 14 glioblastoma patients treated with combined chemo-radiation. These inflammatory responses to treatment, when examined by dynamic MRI, were associated with a transient increase in tumor permeability and decreased cerebral blood volume. This increase could be blocked or reduced by decreasing vascular permeability with bevacizumab. Conclusions: These animal and human studies provide evidence that anti-vascular agents have a steroid-like effect; and in the CNS, may result in reduced delivery of cytoreductive agents to the tumor, thereby compromising standard chemo-radiotherapy. [Table: see text]
Safety and efficacy of the addition of bevacizumab (BV) to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM)
Authors: Vredenburgh J. J. , Desjardins A. , Reardon D. A. , Peters K. , Herndon J. E. , Kirkpatrick J. , Gururangan S. , Bailey L. , Friedman A. H. , Friedman H. S. 
Published: August 2020

2015 Background: Standard GBM treatment includes TMZ and RT, and results in a median progression-free survival and median survival of 6.9 and 15.8 months, respectively. GBM have high concentrations of vascular endothelial growth factor (VEGF), higher levels are associated with poorer prognosis. BV is a humanized antibody to VEGF with activity in recurrent GBMs. This study aims to improve the survival of newly diagnosed GBM patients by incorporating an anti-angiogenic agent with RT and TMZ, and adding a topoisomerase I inhibitor, and an anti-angiogenic agent to TMZ post-RT therapy. Methods: Patients received standard RT and TMZ at 75 mg/m2/day, with BV at 10 mg/kg every 14 days beginning a minimum of 28 days post-operatively. Following the completion of RT, patients received 6 cycles of BV, TMZ and CPT-11. Each cycle was 28 days. BV was given at a dose of 10 mg/kg on days 1 and 15, TMZ at 200 mg/m2 on days 1–5 and CPT-11 on days 1 and 15 at 125 mg/m2 for patients not on an enzyme inducing anti-epileptic drug (EIAED) and 340 mg/m2 for patients on an EIAED. The study was designed to differentiate between a 16-month survival rate of 45% and 60% with type I and II error rates of 0.05. Results: 75 patients were enrolled between 8/07 and 9/08. All the patients have completed RT; 40 patients continue to receive BV, TMZ, and CPT-11. Twenty-two patients have completed 6 cycles of BV, TMZ, and CPT-11; 17 of them had a cold PET One patient developed a CNS hemorrhage (grade 2) necessitating stopping BV. Five patients developed thrombocytopenia for which TMZ was held (grade 3, n = 1; grade 4, n = 4). There were no other ≥ grade 3 toxicities, including no wound dehiscence during RT. Twelve patients had tumor progression, and 14 stopped because of toxicity, including: 6 with fatigue; 3 with PEs; 2 with grade 4 thrombocytopenia; the patient with CNS hemorrhage, and one each with a rectal abscess and sepsis. There have been 7 deaths: 5 from tumor progression; one each from sepsis and PEs. At a median follow-up of 9 months, 81% remain alive and progression-free. Conclusions: Adding BV to TMZ and RT followed by BV, TMZ with CPT-11 is tolerable and efficacious. No significant financial relationships to disclose.
Role of IκBα as a negative regulator of EGFR and a molecular determinant of prognosis in glioblastoma multiforme
Authors: Bredel M. , Renfrow J. , Yadav A. , Alvarez A. , Lin D. , Scholtens D. , He X. , Chandler J. , Scheck A. , Harsh G. 
Published: August 2020

2028 Background: Glioblastoma multiforme is a complex disease that involves the deregulation of overlapping signaling pathways. Constitutive activation of the transcription factor nuclear factor-κB (NF-κB) has been broadly associated with various human cancers, including glioblastomas, and their therapy resistance and may be due to cross-coupling with other oncogenic pathways, such as epidermal growth factor signaling. Methods: Multidimensional analysis involving gene and transcript data for the endogenous NF-κB modulator IκBα/NFKBIA and clinical patient profiles of 482 glioblastomas/high-grade gliomas from multiple institutions in the United States and The Cancer Genome Atlas Pilot Project. Functional analyses using LN229, U87, and U118 glioblastoma cells, and human embryonic kidney 293T cells with transgene phenotypes for IκBα. IκBα promoter and coding sequence and promoter methylation analyses in a resistance model of 15 glioblastomas cell lines with in vitro and/or in vivo resistance to O6-alkylating agents. Results: We have identified a regulatory circuit between NF-κB and EGFR signaling in glioblastomas, where IκBα binds to EGFR and attenuates EGFR signaling by immobilizing its kinase domain into an inactive conformation. We found the NFKBIA gene at 14q13.2 deleted in 25% of glioblastomas and its occurrence mutually exclusive with EGFR amplification. Loss of NFKBIA associates independently with patient survival. Functional analyses uncover a bona fide tumor suppressor role for IκBα in glioblastoma cells, where it functions to constrain tumorigenic and migratory potential, and induce spontaneous cellular senescence, and apoptosis in response to treatment. IκBα expression is an independent predictor of patient prognosis in multiple glioblastoma populations. Glioblastomas with initially high IκBα expression significantly repress IκBα upon tumor recurrence, suggesting an acquired mechanism to evade its tumor-suppressive and/or chemo-sensitizing effects during tumor progression. Conclusions: IκBα is a molecular determinant of biological tumor behavior and patient survival in glioblastoma multiforme. Deletion of NFKBIA could present an alternate mechanism to activate EGFR signaling in EGFR non-amplified glioblastomas. No significant financial relationships to disclose.