Greetings from chilly Washington, DC, on a quiet Sunday evening. My weekend has been occupied by completion of an R01 (Antibody-Targeted Cancer Immunotherapy) that is due on March 5; I want to give a shout-out to Erin Fogarty, Carol Herod and Debi Gales for helping me push this project out the electronic door. I’m also grateful to the folks in my lab and my collaborators who made it possible for the project to develop. Now the waiting begins! This is an R01 I have held since 1989, so it feels like part of the family.
The weekend did include a bit of real family, as Elana and Ben came down from Baltimore with Isaac. We met them at the Museum of Natural History so he could take his second (of what I believe will be many for this dinosaur-obsesssed little boy) tours of the dinosaur exhibit. He is a big fan of Tyrannosaurus Rex; I later learned that its life expectancy is estimated to have been about 30 years (in contrast to 100 years for the apatosaurus). The eating must have been pretty good in those days… After about an hour we drove back to our place for some food fit for humans (we were joined briefly by my son David), and a nap for a tired but happy little boy.
I have had no time for naps. On Friday, Hackensack University Medical Center announced the agreement between its BMT physicians and MedStar Georgetown University Hospital to jointly operate a Hematopoietic Stem Cell Transplantation Program at MGUH; this is the first step in developing a closer relationship between the respective cancer centers. Our patients now will have access to world-class bone marrow transplant options, offered by internationally recognized leaders such as Scott Rowley, Andrew Pecora and Andre Goy. I am very excited that we now have a chance to strengthen our scientific connection with this outstanding group of clinicians and investigators. It is nice to know that even in this very challenging fiscal climate (I would say more, but all the good phrases have been sequestered by Congress!) for this country, this region and this University, we still can move forward and do work that makes an impact.
Speaking of impact, the weekend’s work has included the CCSG, of course, and also the preparation of a report for another cancer center that is beginning to gear up for its first CCSG submission; I am a member of its external advisory board, and was there on Wednesday and Thursday to review preparations. As always, reviewing the work of others has certainly sharpened my focus on what we need to do as we gear up our competitive submission. Continuing my series of posts about our CCSG, here is more of the Director’s Overview section of our draft, focusing on some of the other major accomplishments we have had over the past four years. This week’s entry highlights the work done by Georgetown Lombardi’s population scientists.
Population Research with Translational Implications or Applications
- New Guidelines For Mammography Screening Frequency Influence Practice. Simulation modeling estimated the impact of 20 mammography screening strategies identifying efficiency of biennial screening interval and clarifying that decisions about the best starting and stopping ages depend on tolerance for false-positive results and rates of over-diagnosis, work led by Mandelblatt (CPC) and published in Ann Int Med 2009. Subsequently, Mandelblatt has obtained further CISNET funding for a multi-project, multi-PI grant on which she is the contact PI and PI of the Coordinating Center (U01CA152958). As part of this award, she and her CISNET colleagues evaluated the threshold of risk needed for younger women to reach the balance of harms and benefits similar to those seen for routine screening starting at age 50 (vanRavestyn, Ann Intern Med 2012). Recently this CISNET model was applied directly to the Lombardi catchment area to inform screening policies for the District of Columbia (DC) (Near et al., 2012). Impact: This work provides an evidence base for policy regarding mammography screening.
- Strategically Located Community-Based Sites Move Research Into the LCCC Catchment Area. LCCC’s catchment area of 3.9 million individuals includes the District of Columbia (DC) and its surrounding counties—Montgomery and Prince George’s in Maryland and Arlington/Alexandria City and Fairfax in Virginia. Located in wards of DC with a high proportion of disadvantaged individuals, the Office of Minorities and Health Disparities Research and Capital Breast Care Center (CBCC) now provide enhanced research capabilities to LCCC. Adams-Campbell, member of Cancer Prevention and Control Program, received an NIMHD P60 grant in 2012 to establish a Center of Excellence for Health Disparities Research (P60MD006920). Since our catchment area has very high rates of obesity, LCCC has invested in a state-of-the-art exercise physiology laboratory at this site so that CPC researchers can translate discoveries linking obesity to cancer risk into clinical trials testing cancer risk reduction interventions. Other trials open at the site focus on HPV and cervical cancer, nutrition, healthy lifestyles, biospecimen knowledge awareness, and breast cancer. The CBCC, providing free mammography screening to about 1,800 uninsured and low-income women yearly since 2004, now serves as a site for health disparities research. It was the Lombardi site for the collaborative DC Patient Navigation Research Program, a national, multisite, NCI-funded initiative (2005-2010) designed to evaluate cancer patient navigation outcomes (site PIs: Mandelblatt [CPC], Eng-Wong [BC];Ramsey, Cancer 2009; Bensick, under review). An ongoing trial by O’Neill (BC) and Willey (BC) funded by the Prevent Cancer Foundation is assessing awareness of mammographic breast density as a risk factor for breast cancer (Hoffman, Cancer Epidemiol Biomarkers Prev 2012). Impact: This work better places LCCC in the underserved minority community to study and favorably influence cancer risk-associated health behaviors.
- Chromosome-Specific Telomere Length Variations Are Potential Markers for Local Breast Cancer Recurrence (Zheng, Hum Mol Genet 2011; Zhou, Carcinogenesis 2012). Women who were diagnosed with breast cancer at LCCC were included in this nested case-control study initiated by Zheng in the Cancer Prevention and Control Program. Patients who had large vs. small telomere length variation had significantly better 10-year recurrence free survival rate, and telomere length variation in normal epithelial cells adjacent to tumor may be a promising biomarker for predicting breast cancer local recurrence after breast conserving surgery. Building on this study, Zheng was funded (R01CA132996) to study the impact of chromosome-specific telomere length variations on bladder cancer risk in collaboration with Loffredo (CPC), who is providing the research infrastructure to enroll the cases and controls and obtain biological specimens. In collaboration with Schlegel (MO), Zheng is also evaluating the use of immortalized patient tumor cells to determine their telomere health profile, which may predict response to therapy, survival, and recurrence risk. Impact: This work identifies molecular features in populations to identify high risks for cancer recurrence.
- An Expansion of Health Services and Outcomes Research Builds on Strengths in Population-Based Research (Potosky [CPC], NIH U01AR057971). Since 2009, the Cancer Prevention and Control Program has greatly expanded its efforts in health services and patient outcomes research. For example, Potosky, with CPC member Wang and junior faculty in CPC (Jensen, Davis), has been conducting research as part of the national Patient Reported Outcomes Measurement Information Systems (PROMIS®) Network Initiative funded by the NIH in 12 academic centers across the US. This initiative aims to provide clinicians and researchers access to efficient, precise, valid, and responsive adult- and child-reported measures of health and well being. The U01 led by Potosky aims to validate PROMIS measures by recruiting 5,000 cancer survivors (diagnosed with either breast, uterine, cervical, colorectal, prostate, lung cancer, or non-Hodgkin’s lymphoma) in 4 states. The primary objective is to evaluate the equivalency of measures across racial-ethnic and age groups in a diverse community-based sample of patients comprised equally of non-Hispanic whites and blacks, Hispanics, and Asians. More than 4,500 study subjects ages 21-84 have been enrolled to date. Impact: This methodological work contributes to the National Cancer Program’s capacity to conduct clinical trials and comparative effectiveness studies that incorporate patient-reported outcomes in more diverse and representative patient populations. This research can thus inform practice and policy evaluations of care that include patient-reported outcomes for those cancers that are prevalent in the LCCC catchment area.
- Multiple Tobacco Modeling Studies Document the Impact of National Tobacco Control Policies in the U.S. and Internationally (Levy; Moolgavkar, J Natl Cancer Inst 2012; Levy, PLoS Med 2012). New CPC recruit David Levy uses his Cancer Intervention and Surveillance Modeling Network (CISNET) model to extend observational and trial data along with national data to examine smoking, tobacco control policies, and lung cancer outcomes. He used his CISNET model to estimate that 625,000 lung cancer deaths were averted from 1975 to 2000, as a result of tobacco control policies implemented since 1964, and an additional 2,110,000 lung cancer deaths could have been averted if all smoking was stopped in 1965. Prediction models for tobacco relapse and ongoing tobacco use in the context of lung cancer screening (Taylor et al., J Natl Cancer Inst 2012) have also been analyzed. Impact: In keeping with the LCCC vision of “global impact”, this work examines the impact of tobacco control policies on lung cancer deaths in diverse locations around the world.
- First U.S. Study Prospectively Evaluates the Long-Term Outcomes of Genetic Testing for Breast-Ovarian Cancer Susceptibility (Schwartz [CPC], Cancer 2012; Graves [CPC], Cancer Epidemiol Biomarkers Prev 2012). Funded by DOD, Schwartz and collaborators from CPC and BC evaluated long-term outcomes of 464 women who underwent BRCA1/2 testing documenting higher rates of risk reducing surgery than previously assumed. Carriers who opted for risk reducing surgery reported better quality of life than those who opted against surgery (Hooker, under review). Building on these and earlier observational studies, Schwartz and other NCI R01 funded colleagues at LCCC are developing interactive decision support tools to guide risk management decisions in BRCA1/2 carriers. Impact: This work defines how to best use genetic testing to guide collaborative therapeutic decision-making.
More to follow! Have a great week, and keep your winter gear handy for a little while longer.