bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A43: EGFR-targeted therapy in African Americans with advanced non-small cell lung cancer: A prospective clinical, pharmacogenetic, and pharmacokinetic study.
Authors: Phelps Mitch , Stinchcombe Thomas , Blachly James S. , Zhao Weiqiang , Schaaf Larry J. , Starrett Sherri L. , Otterson Gregory , Hicks William , Socinski Mark , Villalona-Calero Miguel
Published: August 2014

Context: Focused evaluation of the efficacy and pharmacokinetics of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and the potential influence of pharmacogenetics and tumor genetics, has not been previously performed in African American patients with Non-Small Cell lung cancer (NSCLC).

Objective: To evaluate disease control rate (DCR) in African American patients with NSCLC produced by erlotinib, the effect of its titration to rash occurrence, and to characterize pharmacokinetics of parent drug and metabolite, tumor genetics, and pharmacogenetics of erlotinib metabolizing enzymes and transporter genes.

Design, Setting and Patients: 55 African Americans with NSCLC on a 2-stage-minimax randomized phase II study.

Intervention: Patients received erlotinib 150 mg daily or a dose based on body weight with subsequent escalations to 200 mg to achieve skin rash.

Main Outcome Measures: The primary endpoint was DCR (CR+PR+SD) at 3 months. Time to progression and 1-year survival were also evaluated.

Results: 12 of 52 evaluable patients had disease control at 3 months; 6 per arm. Absence of skin rash on therapy was associated with early PD (10/11), exposures for erlotinib and OSI-420 were lower compared to previous reports, and pharmacogenetic factors were consistent with high erlotinib clearance in most patients. Tumor genetics showed one EGFR exon 19 mutation, a novel EGFR exon 20 missense mutation, EGFR amplification in 17/47 samples, 8 KRAS mutations and 5 EML4-ALK translocations.

Conclusions: Results from this trial support the serial linkage of cytochrome P450 pharmacogenetics, erlotinib pharmacokinetics, rash, and response. Factors consistent with high erlotinib metabolism are predominantly present in African Americans. However, the dose-to-rash strategy failed to increase clinical benefit within the dose-range tested, and a relatively high incidence of tumor genetics associated with erlotinib resistance was found. As with other ethnicities, assessment of tumor genetics is recommended. The high clearance data suggests that the concept of standard erlotinib dosing in African American patients should be reconsidered

Citation Format: Mitch Phelps, Thomas Stinchcombe, James S. Blachly, Weiqiang Zhao, Larry J. Schaaf, Sherri L. Starrett, Gregory Otterson, William Hicks, Mark Socinski, Miguel Villalona-Calero. EGFR-targeted therapy in African Americans with advanced non-small cell lung cancer: A prospective clinical, pharmacogenetic, and pharmacokinetic study. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A43.
Abstract A47: Evaluating therapeutic care delay among Latina and European American cervical cancer survivors.
Authors: Rosales Monica , Ashing-Giwa Kimlin
Published: August 2014

Purpose: Severe delays, in cancer diagnostic or therapeutic care, approaching ≥60 days negatively affect survival and survivorship outcomes. The purpose of this study was to investigate socioeconomic and healthcare system factors influencing therapeutic care delays among European- and Latina-American cervical cancer survivors (CCS).

Methods: 291 CCS (132 European-, 50 English-proficient (EP) Latina-, and 109 limited English-proficient (LEP) Latina-Americans) were recruited from the California Cancer Registry and hospital registries. CCS completed a self-report questionnaire assessing demographic and cancer-related factors. CCS retrospectively noted the days of delay in obtaining therapeutic care and reasons for delays.

Results: CCS who were LEP Latina-Americans, had lower income and education reported severe therapeutic delays (≥60 days). LEP Latina-Americans experienced more comorbidities (i.e., diabetes) and delays due to financial issues, doctor's delay, and healthcare system issues (p<0.001). Doctor and healthcare system delays were significant predictors of delayed therapeutic care in the logistic regression model.

Conclusions: It is well documented that timely access to therapeutic care for cancers results in better prognosis and less costly treatments; thus reducing the human and economic cost of CCA. Healthcare system delays, patient health status, income, and education significantly influenced access to appropriately-timed care. Yet, the interaction of provider-actions and patient factors remains largely unexplained and needs further comprehensive investigation with larger samples. Our findings indicate that healthcare system administrators, providers, and researchers need to develop a fuller appreciation of the multilevel factors that contribute to health care barriers to better inform effective interventions to increase access to life saving care.

Citation Format: Monica Rosales, Kimlin Ashing-Giwa. Evaluating therapeutic care delay among Latina and European American cervical cancer survivors. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A47.
Abstract A53: Proximity to clinic and time to diagnostic resolution after abnormal cancer screening in an urban safety net setting.
Authors: Han Ann M. , Battaglia Tracy , Vieira Veronica M. , Bak Sharon , Heeren Tim , Chen Clara , Freund Karen M.
Published: August 2014

Objectives: To evaluate the effect of proximity from subjects' residence to their clinic on the time to diagnostic resolution for subjects with a breast or cervical cancer screening abnormality in an urban safety net setting.

Methods: Boston Patient Navigation Research Program collected data (2007- 2008) for women who had a breast or cervical cancer screening abnormality at six community health centers. Kaplan-Meier survival curves and proportional hazards regression models examined the effect of distance to clinic on time to resolution, adjusting for community health center, age, race, language, and insurance.

Results: We geocoded addresses for 1512 of 1544 subjects (98%). Among those with a breast screening abnormality (36% Black, 33% Hispanic; 44% non-English), there was no significant difference in adjusted hazard ratios between the distance quartiles, 0.08 to >6.12 miles, (p-values 0.50-0.98). Among those with a cervical screening abnormality (22% Black, 21% Hispanic; 15% non-English) those in the closest distance quartile (<0.6 miles) were less likely to resolve than the next closest quartile (0.6-1.47 miles) (adjusted Hazard Ratio 0.756, 95% CI 0.574 -0.995). Cervical screening subjects living closest to their clinic were slower to resolve.

Conclusions: Increased distance between residence and clinic is not a barrier to diagnostic resolution for this vulnerable urban population

Citation Format: Ann M. Han, Tracy Battaglia, Veronica M. Vieira, Sharon Bak, Tim Heeren, Clara Chen, Karen M. Freund. Proximity to clinic and time to diagnostic resolution after abnormal cancer screening in an urban safety net setting. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A53.
Abstract A91: Healthcare reform: Closing the health disparities gap. Where does patient navigation belong?
Authors: Preston Michael A. , Glover-Collins Katherine , Gray Dale , Smith Sharla , Henry-Tillman Ronda
Published: August 2014

Background: Prostate cancer is the most commonly diagnosed cancer and second leading cause of cancer death in the US among men. Although overall incidence and mortality has decreased over time, disparities still exist among racial/ethnic groups. Strategies to reduce disparities in cancer detection, treatment, and outcomes among racial/ethnic minorities and low-income patients have been gathering momentum with the introduction of patient navigation (PN) initiatives. The current advancement of medical knowledge and technology spurs a widening gap in healthcare delivery for racial/ethnical minorities and medically underserved populations for certain emerging state-of-the-art treatments. The controversy around the effectiveness of prostate-specific antigen (PSA) and digital rectal exam (DRE) as screening tools was cited as a possible reason for this information void, but research suggests that African American males rely on their physicians to recommend all needed tests/screenings. The study examined the current and potential roles of PN in the improvement of prostate cancer screenings among disadvantaged populations.

Methods: A Longitudinal study design was conducted on males over 35 years of age to examine the role of patient navigation on equity of access to prostate cancer screening among disadvantaged populations since 2008 (n=1602). Patient's demographics, geographical location, PSA scores, and DRE scores, and the array of event types in which community engagement occurred were collected. Data were analyzed using comparison analyses.

Results: Patient navigation allowed for greater utilization of health services among populations of rural origins (Urban: n=747; Rural: n=833). Mean PSA scores were within normal range, although mean PSA scores for non-whites residing in rural areas (1.45ng/mL) was slightly higher than non-whites in urban areas of the state (1.36ng/mL; p=0.03). The mean age was 54 years (Urban: 51 years; Rural: 56 years; p=0.001).

Conclusions: Equity of access to cancer screenings among disadvantaged populations may be achieved with the utilization of patient navigation programs. Access to the health care system is a strong barrier which fosters disparities among disadvantaged populations. PN allows rural disadvantaged populations entry into the health care system at earlier stages, considering PSA as a proxy for disease. Health care reform lays the foundation for preventative programs such as patient navigation.

Citation Format: Michael A. Preston, Katherine Glover-Collins, Dale Gray, Sharla Smith, Ronda Henry-Tillman. Healthcare reform: Closing the health disparities gap. Where does patient navigation belong? [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A91.
Abstract B14: Community health workers support CBPR ethics: Lessons learned along the research-to-practice-to-community continuum.
Authors: Smith Selina A. , Blumenthal Daniel S.
Published: August 2014

Ethical principles of community-based participatory research (CBPR)'specifically, community engagement, mutual learning, action-reflection, and commitment to sustainability' stem from the work of Kurt Lewin and Paulo Freire. These are particularly relevant in cancer disparities research because vulnerable populations are often construed to be powerless, supposedly benefiting from programs over which they have no control. The long history of exploiting minority individuals and communities for research purposes (the U.S. Public Health Service Tuskegee Syphilis Study being the most notorious) has left a legacy of mistrust of research and researchers. The purpose of this abstract is to examine experiences and lessons learned from community health workers (CHWs) in the 10-year translation of an educational intervention in the research-to-practice-to-community continuum, with a focus on colorectal cancer screening. We conclude that the central role played by CHWs enabled the community to gain some degree of control over the intervention and its delivery, thus operationalizing the ethical principles of CBPR. GRANT SUPPORT: U54 CA118638.

Citation Format: Selina A. Smith, Daniel S. Blumenthal. Community health workers support CBPR ethics: Lessons learned along the research-to-practice-to-community continuum. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B14.
Abstract B50: Concordance between self-reported and medical record breast cancer treatment data by income and education.
Authors: McDougall Jean A. , Malone Kathleen E. , Tang Mei-Tzu C. , Li Christopher I.
Published: August 2014

While the use of self-reported treatment data is common in cancer disparities research, it is unknown whether their accuracy varies by study participant's income or education. Using data collected from a population-based case-control study of contralateral breast cancer, we compared the concordance between participant responses to a telephone questionnaire and medical record data obtained from all facilities where a participant received breast cancer treatment. This analysis included women age 40 – 79 diagnosed with contralateral breast cancer (n=256) or only a single breast cancer (n = 533) between 1990 and 2005. Concordance was evaluated by calculating the percent agreement, Kappa statistic and its 95% confidence interval (CI) for the agreement between self-report and medical record data for the type of breast cancer surgery received, receipt and start date (month and year) of chemotherapy and radiation, and type of hormonal therapy received of all 789 participants stratified by highest level of education received (≤ high school, some college, ≥ college graduate) and annual household income (<$35,000, $35,000-$69,000, ≥$70,000) at the time of diagnosis. Concordance between self-reported and medical record data for receipt of mastectomy, chemotherapy, and radiation therapy was high and did not vary according to education or income strata (all κ > .90). However, some variation with respect to treatment start date was observed. For radiation start date, concordance was lower among women reporting an income of <$35,000 compared to those with an income ≥$70,000 (κ = 0.47, 95% CI 0.45–0.48 vs. κ = 0.60, 95% CI 0.58–0.62, respectively), and lower among women with ≤ high school education compared to college graduates (κ = 0.51, 95% CI 0.50'0.53 vs. κ = 0.60, 95% CI 0.58'0.61 respectively). These same patterns were seen with chemotherapy start dates. These findings suggest a high degree of accuracy regardless of income or education for self-reported receipt of various forms of breast cancer treatment. There was overall less concordance with respect to start dates of radiation and chemotherapy with evidence that concordance was the poorest among women with less income and less education. Studies of socioeconomic disparities in breast cancer treatment that require accurate dates of treatment initiation may require ascertainment of medical record data to avoid potential bias.

Citation Format: Jean A. McDougall, Kathleen E. Malone, Mei-Tzu C. Tang, Christopher I. Li. Concordance between self-reported and medical record breast cancer treatment data by income and education. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B50.
Abstract B78: Referral delay after community diagnosis of non-small cell lung cancer impairs survival.
Authors: Kanarek Norma F. , Hooker Craig M. , Mathieu Luckson , Tsai Hua-Ling , Rudin Charles M. , Herman James G. , Brock Malcolm V.
Published: August 2014

Context: “Rush to surgery” among patients with worse symptoms, delays related to morbidity, and inclusion of patients with advanced disease have produced a mixed picture of importance of time to treatment to survival of non-small cell lung cancer (NSCLC).

Objective: To assess the contribution of diagnosis to first surgery interval to survival among patients diagnosed in the community with early stage NSCLC.

Methods: Patients (N=174) diagnosed between 2003 and 2009 and treated at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins were followed for vital status through 2011.

Diagnosis to first surgery interval was examined overall; as two segments: referral interval and treatment interval; as short and longer intervals (<22, <31, and <43 days); and as a continuous variable. Our primary end point was survival since first surgery.

Results: Cox method hazard analysis revealed older age at diagnosis (OR=1.02 per year 95% confidence intervals:1.00-1.05), stage IIB (OR=2.17, 95% confidence intervals:1.12-4.21), large, >4 cm (OR=3.68, 95% confidence intervals: 1.05-12.93) or unknown tumor size (OR+4.45, 95% confidence intervals: 1.21-16.38), and longer length of diagnosis to first surgery interval predicted worse survival (OR= 1.04 per week delay, 95% confidence intervals: 1.00-1.09). Factors of race, place of residence, marital status, morbidity and insurance coverage were not predictive of survival or interval length. No threshold effect of time to surgery was observed.

Conclusions: Surgery is not only the best treatment for early stage NSCLC but it is urgent once a diagnosis is made. Patients benefit from universal consideration of lung cancer as a time sensitive condition that merits rapid response to reduce tumor burden, especially among patients with small tumors. We will need to know more about referral delays encountered by patients, because particularly small tumors found upon low dose computed tomography scan will increase. Referral delay experienced in the community is unduly long (61 days). In addition to patient choices, an unconscious physician bias that lung cancer is untreatable or an inevitable consequence of smoking may be operating.

Citation Format: Norma F. Kanarek, Craig M. Hooker, Luckson Mathieu, Hua-Ling Tsai, Charles M. Rudin, James G. Herman, Malcolm V. Brock. Referral delay after community diagnosis of non-small cell lung cancer impairs survival. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B78.
Abstract B91: Addressing the growing confidence gap in public acceptance of vaccines in the United States.
Authors: Ellis Glenn
Published: August 2014

The public health community has gotten markedly better at distributing effective vaccines to the children who need them. But researchers are noticing an increase in mistrust of vaccines around the world, and they're concerned that unfounded suspicions could derail immunization programs essential to saving lives.

One in eight American parents has refused at least one vaccine recommended for their children by their family doctor, according to a study published in Journal of Pediatrics. Therefore, even if only ten of 100 people refuse vaccines but most of them live in the same neighborhood, the likelihood of outbreaks increases due to local breakdown of herd immunity.

Fears and suspicions around vaccine safety have already contributed to a slight decline in vaccination rates in the U.S.

Vaccine distrust can evolve out of cultural, religious, ethical or sometimes economic or political reasons.

Suspicion and apprehension about vaccination is fairly common, particularly among several specific disenfranchised communities in the United States and internationally. For these communities, the suspicion is best understood in a social and historical context of inequality and mistrust. For example, several studies have found that the legacy of racism in medicine and the Tuskegee Syphilis Study, a clinical trial conducted with African Americans who were denied appropriate treatment opportunities, are key factors underlying African Americans' distrust of medical and public health interventions, including vaccination.

Through a historical and cultural overview, the focus of this presentation will be on solutions to building and sustaining trust with those who accept and support vaccines, while working to understand and address the growing confidence gap.

Addressing mothers' concerns about immunization is important both from an ethical perspective, in assuring that they are fully informed of the risks and benefits of immunizations, as well as from a practical one, in reducing the possibility that people will decide not to immunize themselves or their child. Changes, particularly, in the childhood immunization process should be made to reduce parental concern about vaccine safety. Some changes that may be considered include improved provider communication about immunizations and additional tailored information about the necessity and safety of vaccines.

Note: This abstract was not presented at the conference.

Citation Format: Glenn Ellis, Sr. Addressing the growing confidence gap in public acceptance of vaccines in the United States. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B91.
Abstract ED01-02: Employing a community partnership approach to recruit African American men to a cancer prevention trial.
Authors: Cook Elise D.
Published: August 2014

Background: Many large chemoprevention studies have not recruited significant numbers of minorities. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), a large phase III study, evaluated the impact of selenium and vitamin E on the clinical incidence of prostate cancer. Over 400 SELECT study sites in the United States, Canada, and Puerto Rico recruited men to this trial. The SELECT recruitment goal was 24% minorities, with 20% blacks, 3% Hispanics, and 1% Asians. The goal for blacks was set at 20% because of their proportion in the United States population and their prevalence of prostate cancer.

Methods: The minority recruitment strategies in SELECT were to: (1) consider minority recruitment during site selection, (2) expand the eligibility criteria by lowering the age criterion for black men and including men with controlled co-morbid illnesses, (3) develop a national infrastructure, (4) give additional funds to sites with the potential to increase black enrollment, and (5) provide resources to maximize free media opportunities to promote SELECT.

Results: SELECT recruitment was intended to last five years but concluded two years ahead of schedule. Of the 35,534 participants enrolled, 21% were minorities with 15% blacks, 5% Hispanics, and 1% Asians.

Conclusions: Careful planning, recruitment of large numbers of clinical centers and adequate resources accomplished by the combined efforts of the National Cancer Institute (NCI), Southwest Oncology Group (SWOG), SELECT Recruitment and Adherence Committee (RAC), SELECT Minority and Medically Underserved Subcommittee (MMUS), and the local SELECT sites resulted in attainment of the estimated sample size ahead of schedule and recruitment of the largest percentage of black participants ever randomized to a cancer prevention trial.

Citation Format: Elise D. Cook. Employing a community partnership approach to recruit African American men to a cancer prevention trial. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr ED01-02.
Abstract ED03-01: Minority and rural population views and consent preferences for biospecimen and biobank donation.
Authors: Baquet Claudia R.
Published: August 2014

Advances in medicine and public health require diverse population participation in biospecimen donation as well as clinical trials where biospecimen collection is included. This is increasingly related to improving our understanding of the factors related to cancer and other disease outcomes and etiology. Barriers to biospecimen and biobank donation for underserved communities are poorly understood especially for minority and rural communities who experience delays in translation of research results, lower participation in clinical trials and delays in technology transfer.

On Maryland's rural Eastern Shore, formative research and evaluation of educational programs and materials on biospecimen donation was undertaken. Supported by an NCI grant, this presentation will describe research results, biospecimen educational programs targeting the public and health professionals and donation barriers in a rural and diverse community on Maryland's Eastern Shore. Recommendations for planned quantitative studies as well as educational modules for community physicians and nurses will be discussed.

Citation Format: Claudia R. Baquet. Minority and rural population views and consent preferences for biospecimen and biobank donation. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr ED03-01.
Abstract PL07-02: Genome sequencing of triple-negative breast cancer in African American women.
Authors: Carpten John D.
Published: August 2014

It is universally accepted that somatic alterations (i.e., point mutations, small insertions and deletions, rearrangements, gains and losses) occur at the DNA level in cancer. These somatic events can drive tumorigenesis, metastatic progression, and/or drug resistance. More importantly, specific somatic alterations are intimately tied to companion targeted therapeutics. Recent technological advances in the form of Next Generation Sequencing technologies now provide us with platforms to interrogate entire human genomes at a fraction of the time and cost compared to more traditional sequencing technologies. These technologies are already being used to survey the global somatic landscape of tumors across large cohorts. As many cancer types disproportionately affect underrepresented populations, this session will highlight new findings from deep genomic profiling of tumors from individuals from diverse populations. Ultimately it is our hope to glean new insights into the possible role of somatic events.

Citation Format: John D. Carpten. Genome sequencing of triple-negative breast cancer in African American women. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr PL07-02.
Abstract SS02-02: Increasing diversity in the cancer research workforce: Funding opportunities.
Authors: Aguila H. Nelson
Published: August 2014

Ethnic and racial groups and the socioeconomically disadvantaged continue to suffer higher rates of cancer incidence and mortality than the general population. This disparity is compounded by a dearth of researchers and physicians from these populations entering a career in cancer science.

In 1999, the NCI launched the Continuing Umbrella of Research Experiences (CURE) training program, which today remains a major part of the Center to Reduce Cancer Health Disparities (CRCHD) approach to addressing cancer health disparities. CURE is a holistic program that provides funding opportunities to underrepresented students and investigators interested in pursuing basic, translational, clinical, population or behavioral cancer research. The CURE approach is to develop a pipeline of students and investigators that will apply for the various funding mechanisms offered by the NCI at different levels of training and education. As such, CURE offers funding from high school to early stage investigators interested in acquiring training and career development experiences in cancer research.

The goals of the CURE program are to: 1) increase the size of the talent pool, 2) emphasize strategic and scientific areas of greatest needs, and 3) expand and extend the period of training. The long-term goal of the CURE program is to increase the number of competitive investigators from underserved populations conducting cancer research and cancer health disparities research.

The CURE program is based on a pipeline approach that includes mentorship as a key component at all levels of education and training. It provides trainees and mentors with programmatic support that helps them to navigate the NCI/NIH system, decide on the next steps in career development of the trainees, emphasize training in peer review through a mock review and ensure protected time for the trainees' research efforts.

The purpose of this presentation is to provide you with a general view of the CURE program, its approach, the various funding mechanisms offered at different levels of education and training and finally inform you of some outcomes of the CURE program in the last ten years.

Citation Format: H. Nelson Aguila. Increasing diversity in the cancer research workforce: Funding opportunities. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr SS02-02.
Abstract B05: Tissue-compatible EGFR genotyping in tumor-derived extracellular vesicles from malignant pleural effusions.
Authors: Hur Jae Young , Choi Do-Young , Kim Hee Joung , Cho Kyung-Cho , Kim Kwang Pyo , Lee Kye Young
Published: August 2014

Purpose: Tumor cells shed extracellular vesicles (TEV) into body fluids. These TEV are a potential source for biomarkers that could be used for non-invasive molecular diagnosis. We investigated whether TEV contain cell-specific mutant EGFR DNA using PC9 cells harboring an exon 19 deletion (E19 del) and PC9/GR cells harboring T790M mutations. In addition, we investigated whether the TEV from malignant pleural effusions can be used for EGFR mutation testing.

Materials and Methods: TEV were isolated from the culture medium of PC9 and PC9/GR cells or pleural effusions by serial centrifugations. Isolated TEV were inspected by electron microscopy to determine their size and intact structure. EGFR mutation testing was performed using PNA-mediated clamping PCR. The DNA contents of the TEV from the PC9 and PC9/GR cells were analyzed by array comparative genome hybridization analysis.

Results: EGFR genotyping of TEV DNA revealed exactly the same EGFR mutations with cellular DNA in the PC9 and PC9/GR cells. These findings suggest that TEV contain cell-specific mutant DNA that may contain an oncogenic molecular signature such as mutations in EGFR. Testing of the TEV from malignant effusions in eight NSCLC patients yielded the same tissue genotyping results. We observed T790M mutation in addition to the initial E19 del mutation from one patient who developed acquired gefitinib-resistance.

Conclusions: In this study, we demonstrated that TEV contain cell-specific oncogenic DNA, including EGFR mutants in the cell line systems examined and pleural effusions. This is the first report detailing how TEV can be used for EGFR mutation testing.

Citation Format: Jae Young Hur, Do-Young Choi, Hee Joung Kim, Kyung-Cho Cho, Kwang Pyo Kim, Kye Young Lee. Tissue-compatible EGFR genotyping in tumor-derived extracellular vesicles from malignant pleural effusions. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B05.
Abstract B19: Three-dimensional nuclear telomere organization and clinical significance in non-small cell lung cancer patients.
Authors: Sunpaweravong Patrapim , Sathitruangsak Chirawadee , Thu Kelsie , Lam Wan L. , Mai Sabine
Published: August 2014

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related death worldwide. Survival of NSCLC patients remains unfavorable prompting a better understanding of its molecular biology and causality, along with advances in diagnostic methods and multidisciplinary therapeutic approaches. Aberrant three-dimensional (3D) nuclear telomere organization can identify patient subgroups in various cancers and its correlation with tumor and patient characteristics may play a major role as a predictive and prognostic factor in NSCLC of different subgroups. This study aimed to explore the clinical application of 3D nuclear telomeric organization in NSCLC patients of different EGFR mutational status and smoking backgrounds. Paraffin-embedded NSCLC tissue specimens from non-smoking (N=6) and smoking (N=4) patients who underwent surgical resections at the British Columbia Cancer Research Centre of Canada were examined using the 3D fluorescent in situ hybridization (FISH). 3D nuclear-telomeric architecture analyses were performed using the TeloView program (Vermolen et al., 2005). The 3D nuclear telomere organization of 100 interphase nuclei per specimen was quantified by telomere numbers, telomere signal intensities, and frequencies of telomeric aggregates. Comparisons of 3D nuclear telomere organization between patient subgroups are shown below. In the smoking group, more telomeres, higher signal intensities, and greater numbers of aggregates were observed, compared to the non-smokers. The same pattern of 3D nuclear telomere organization was observed in the EGFR-negative/unknown group, compared to the EGFR-positive patients. This study provides a better understanding of 3D telomeric organization in NSCLC patients with different smoking backgrounds and EGFR mutational status, leading to a rationale of further exploration of this molecular profile in this cancer.

3D Telomeric parameters

Average number of telomere per cell : Non-smokers 77.71, Smokers 80.37

Average number of aggregates per cell : Non-smokers 21.36, Smokers 27.59

Percentage of cells with aggregates : Non-smokers 2.16, Smokers 3.03

Average number of telomere per cell : Pos. EGFR 73.69, Neg./Unknown EGFR 80.95

Average number of aggregates per cell : Pos. EGFR 19.97, Neg./Unknown EGFR 25.52

Percentage of cells with aggregates : Pos. EGFR 1.96, Neg./Unknown EGFR 2.75

Citation Format: Patrapim Sunpaweravong, Chirawadee Sathitruangsak, Kelsie Thu, Wan L. Lam, Sabine Mai. Three-dimensional nuclear telomere organization and clinical significance in non-small cell lung cancer patients. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B19.
Abstract B35: The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts.
Authors: Okayama Hirokazu , Schetter Aaron J. , Ishigame Teruhide , Robles Ana I. , Kohno Takashi , Yokota Jun , Takenoshita Seiichi , Harris Curtis C.
Published: August 2014

We previously developed and validated a prognostic classifier using the mRNA expression levels of BRCA1, HIF1A, DLC1, and XPO1. This 4-gene classifier aimed to identify stage I lung adenocarcinoma patients with a high risk of relapse. Our initial study evaluated patients in five independent cohorts from various regions of the world, suggesting that the 4-gene classifier was robust and representative of most lung adenocarcinomas. In an attempt to further validate this classifier, we have used a meta-analysis based approach to study 12 cohorts consisting of 1069 TNM stage I lung adenocarcinoma patients. These cohorts were obtained through a systematic search of public gene expression datasets and all suitable datasets were analyzed. Kaplan-Meier analysis of each cohort showed that the classifier was significantly associated with prognosis in ten of the twelve cohorts (p<0.05). The association was highly consistent across all cohorts regardless of the ethnic diversity or microarray platform and there was no evidence of heterogeneity across all cohorts (I2 = 0.0%, p=0.98). The pooled estimate demonstrated that patients classified as high risk had worse overall survival for all stage I (Hazard Ratio [HR], 2.66; 95% Confidence Interval [CI], 1.93-3.67; P<0.0001) patients and in stratified analyses of stage IA (HR, 2.69; 95%CI, 1.66-4.35; P<0.0001) and stage IB (HR, 2.69; 95%CI, 1.74-4.16; P<0.0001) patients. These results suggest that the 4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors and may assist clinicians in decisions regarding postoperative management of early stage patients.

Citation Format: Hirokazu Okayama, Aaron J. Schetter, Teruhide Ishigame, Ana I. Robles, Takashi Kohno, Jun Yokota, Seiichi Takenoshita, Curtis C. Harris. The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B35.
Abstract IA06: Adaptive designs and adaptive learning for biomarker-based clinical trials for targeted therapies.
Authors: Lee J. Jack
Published: August 2014

Rapid advancements in genomics have changed the landscape of target identification and drug development for targeted therapies. Targeted agents work well when drugs are given to patients with the actionable targets. For example, TKI works well for lung cancer patients with EGFR mutation and crizotinib is highly effective for patients with EML4-ALK translocation. Targeted agents, however, do not work for everyone and may not work at all. Hence, the goals for developing target agents include (1) testing the treatment efficacy, (2) identifying prognostic and predictive markers, and (3) providing better treatments to patients enrolled in the trial. Several novel designs have been introduced to achieve these objectives. For example, Bayesian adaptive designs can assign more patients to the more effective treatments based on the available data at the time via the outcome-adaptive randomization. More frequent interim monitoring can drop the ineffective treatments early for futility. New treatments can be added, and effective treatments can graduate for further evaluation. The concepts of the basket design and the N-of-1 design have also been proposed to study the targeted agents based on patients' genomic profiles across different disease sites. Information collected from such trials can be put together to form a continuously updated knowledge database for adaptive learning. Statistical methods such as the hierarchical model and Individual level meta-analysis can be applied to model data collected in the knowledge database to estimate the treatment effect, the marker effect, and their interactions. A platform of a clinical trial infrastructure can be established to facilitate the conduct of such trials. In the talk, pros and cons of various designs will be discussed. Examples and lessons learned from the recently completed BATTLE trial and the on-going BATTLE-2 trial in non-small cell lung cancer will be given.

Citation Format: J. Jack Lee. Adaptive designs and adaptive learning for biomarker-based clinical trials for targeted therapies. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA06.
Abstract IA10: Molecular testing to personalized EGFR and ALK inhibitor therapies in lung cancer.
Authors: Tsao Ming Sound
Published: August 2014

The concept of “oncogene addiction” led to the realization that not all patients respond equally to each targeted therapy, and best therapeutic results are obtained when the therapy is given to patients whose tumor harbors the “driver mutation” that is sensitive to the drug. In lung cancer, two currently approved new therapies require patient selection based on the presence of sensitizing epidermal growth factor (EGFR) tyrosine kinase domain (TKD) mutation or the anaplastic lymphoma kinase (ALK) gene rearrangement. EGFR mutations occur almost always in lung cancer of adenocarcinoma histology, and uncommonly in other histologies except when they also contain adenocarcinoma component. They are more common in East Asian (~45%) compared to Caucasian (~15-25%) patients, in never/light smokers and in female patients. Ninety percent of EGFR sensitizing mutations involve the 3-5 amino acid deletions on exon 19 and the L858R mutation on exon 21. Although ALK rearrangement also occurs mainly in lung adenocarcinoma and never/light smokers, it is not associated with sex or ethnicity. A great majority of the ALK gene rearrangements that occur in lung cancer involve a fusion between the C-terminal of ALK containing the kinase domain and the N-terminal of echinoderm microtubule-associated protein-like 4 (EML4), which results from an inversion on the short arm of chromosome 2. While EGFR mutations are detected by mainly by sequencing or PCR-based techniques, ALK rearrangement is best detected by the fluorescent in situ hybridization (FISH). However, recent data suggest that the oncogenic ALK fusion proteins can be detected with close to 100% sensitivity and specificity in lung cancer by immunohistochemistry using commercially available ALK specific antibodies, while the native ALK protein is not expressed in normal lung cells. Based on a systematic review of the published literatures, experts representing the International Association for the Study of Lung Cancer (IASLC), in collaboration with the College of American Pathologists (CAP) and the Association of Molecular Pathologists (AMP) recently issued a guideline on Molecular Testing of EGFR and ALK in Lung Cancer. The testing algorithm reported in this guideline will be discussed.

Citation Format: Ming Sound Tsao. Molecular testing to personalized EGFR and ALK inhibitor therapies in lung cancer. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA10.
Abstract IA11: Promises and challenges of applying molecular profiles to lung cancer treatment and early diagnosis.
Authors: Wistuba Ignacio I.
Published: August 2014

The field of lung cancer molecular pathology is rapidly changing due to advances in our understanding of the molecular pathogenesis of tumors. In the past ten years, the identification of new molecular targets has provided unique opportunities to attack cancer with targeted therapies in a personalized manner. Recent advances in expanding the available non-small cell lung carcinoma (NSCLC) targeted therapies require the analysis of a broad panel of molecular abnormalities in tumor specimens, including gene mutations, amplifications, fusions and expression by applying different methodologies to frequently small tumor tissue (biopsy) and cell (cytology) samples. In addition, there is growing consensus that tumor tissue specimens must represent the setting of the disease to be treated, and increasingly, more tissue samples are being obtained for molecular testing of advanced, metastatic and chemo-refractory NSCLC tumors (e.g., MD Anderson BATTLE Lung Cancer Program). Currently available methodologies and technologies, including microarrays and next-generation sequencing, have variable applicability for the molecular and genomic analysis of these small specimens. Thus, the role of the pathologist is becoming increasingly important to adequately integrate routine histopathology assessments and molecular testing with clinical pathology for the most accurate tumor diagnosis and subsequent selection of the most appropriate therapy. In addition, applying high-throughput molecular methodologies currently used in studying established tumors to epithelial cell samples obtained from the airway of high-risk individuals and lung cancer patients is expanding our understanding of the early pathogenesis of lung cancer. Earlier studies have highlighted a field cancerization phenomenon in which histologically normal-appearing tissue adjacent to neoplastic and preneoplastic lesions display molecular abnormalities some of which are in common with those in the tumors. There is consensus that advances in the understanding of this field phenomenon will help to the development of biomarkers for early detection of and personalized chemoprevention of lung cancer.

Citation Format: Ignacio I. Wistuba. Promises and challenges of applying molecular profiles to lung cancer treatment and early diagnosis. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA11.
Abstract IA39: Squamous cell lung cancer 2014.
Authors: Hammerman Peter S.
Published: August 2014

Despite the robust progress in developing molecularly targeted therapies for patients with lung adenocarcinoma, patients with other types of lung cancer have not benefitted much to date from molecularly targeted therapy. While in the past this was due to a lack of knowledge of the molecular underpinnings of other lung cancer types, large-scale genomic surveys have now demonstrated that relevant and targetable genomic alterations can be found in all histologies of lung cancer. Here I discuss recent data from genomic analyses of squamous cell lung cancer, the second most common type of non-small cell lung cancer and describe potential therapeutic targets in this disease with an emphasis on Fibroblast Growth Factor Receptors. I will summarize preclinical and early clinical studies and discuss how further progress in targeted therapy for squamous cell carcinomas can be made.

Citation Format: Peter S. Hammerman. Squamous cell lung cancer 2014. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA39.