Ann Marie Beddoe

Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers

Background High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools. Methods and Findings Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival. Conclusions Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic dilemma and a potential critical inflection point in precision medicine. This study suggests that the use of personalized ctDNA biomarkers in gynecologic cancers can identify the presence of residual tumor while also more dynamically predicting response to treatment relative to currently used serum and imaging studies. Of particular interest, ctDNA was an independent predictor of survival in patients with ovarian and endometrial cancers. Earlier recognition of disease persistence and/or recurrence and the ability to stratify into better and worse outcome groups through ctDNA surveillance may open the window for improved survival and quality and life in these cancers.

Challenges to Cancer Program Development in Low- and Middle-Income Countries

The Millennium Development Goals (MDGs) were established in 2000 to address the inequities in health, education, gender, environment, and economics of the poorest nations in the world. Absent from the targets set by the MDGs, however, was the devastating health impact that noncommunicable diseases have on both developing and developed nations. A high-level meeting of the United Nation’s General Assembly in 2011 addressed this omission and presented a unique and historic opportunity for international leaders to commit to prevention and control of noncommunicable diseases. Cancer is one of the leading noncommunicable diseases that must be viewed as a major public health threat to life and economic survival, particularly in low-resource countries. The World Cancer Declaration was proposed in 2013 by the Union for International Cancer Control to call on government leaders and stakeholders to work together to decrease the cancer burden worldwide. Between 1990 and 2013, global deaths from cancer rose from 5.7 million to 8.2 million, and this number is expected to rise even further. Of the 14.9 million new cancer cases that occurred in 2012, 8 million occurred in developing countries. The increase in morbidity and mortality as a result of cancer is fueled by population growth, aging, and less mortality from infectious diseases as well as the adoption of western diets and lifestyles, particularly in lowand middle-income countries (LMICs). Most developing countries are not positioned to meet this rapidly rising cancer burden. The infrastructure needed to launch a cancer treatment program in low-resource countries that

The impact of nativity on cervical cancer survival in the public hospital system of Queens, New York

OBJECTIVE We studied cervical cancer patients who presented to the Public Hospital System in ethnically-diverse Queens, New York from 2000 to 2010 with the purpose of examining the relationship between nativity (birthplace) and survival. METHODS A retrospective review of tumor registries was used to identify patients diagnosed with cervical cancer between January 1, 2000 and December 31, 2010. Using electronic medical records, data from 317 patients were available for this analysis. RESULTS The majority of patients were born outside the United States (US) (85.5% versus 14.5%). One hundred patients (31.5%) were born in Latin America, 105 in the Caribbean Islands (33.1%), 48 in Asia (15.1%), 8 in the South Asia (2.5%), 10 in Russia/Eastern Europe (3.2%) and 46 (14.5%) in the United States. Patients presented at varying stages of disease: 51.4% at stage I, 19.6% at stage II, 19.6% at stage III, and 8.5% at stage IV. Kaplan-Meier estimated survival curves stratified by birthplace demonstrated significant differences in survival distributions among the groups using the log-rank test (P<0.0001). The most favorable survival curves were observed among patients born in Latin America and Asia whereas the least favorable was demonstrated in US-born patients. Time to death was analyzed using the Cox proportional hazards model. Adjusting for age at diagnosis, insurance status, stage and treatment modality, nodal metastases and hydronephrosis, birthplace was significantly associated with survival time (P<0.0001). CONCLUSION An immigrant health paradox was defined for foreign-born Latino and Asian patients presenting with cervical cancer to the Public Hospital System of Queens, New York as patients born in Latin America and Asia were less likely to die at any given time compared to those born in the United States.

Challenges to development of cervical and breast cancer program development in post conflict Liberia: Presentation prepared for African First Ladies' Conference, 10th SCCA Conference, Addis Ababa, Ethiopia 2016

Highlights • Integrating cancer care in post-conflict settings.• Building health worker and infrastructure for cancer care in low resource setting.• Foreword by Her Excellency President Sirleaf, Republic of Liberia.

Cervical cancer screening in rural South Africa among HIV-infected migrant farm workers and sex workers

At an HIV clinic in the Limpopo province of South Africa, chart reviews revealed long delays in addressing abnormal Pap smears, difficulty in referrals, poor quality and lost results, and increasing cases of cervical cancer. To address these barriers, a “see and treat” approach to screening was proposed. The objective was to integrate this method into current HIV care offered by local providers and to obtain demographic and risk factor data for use in future educational and intervention programs in the region. A cross sectional study of HIV farm workers and at-risk sex workers attending an HIV clinic was performed with visual inspection with acetic acid (VIA). Those with positive screens were offered cryotherapy. Clinic charts were reviewed retrospectively for Pap smear results for the previous year at the time of program initiation and at 12 and 18 months post-program. A total of 403 participants consented and underwent screening with VIA (306 Farm workers and 97 sex workers participated). 83.9% of participants (32.9% sex workers and 100% farm workers) were HIV +. VIA was positive in 30.5% of participants, necessitating cryotherapy. There was no significant difference in VIA positivity between HIV + farm workers and sex workers. There was a positive correlation between Pap smears and VIAs results. We demonstrate successful integration of cervical cancer screening using VIA for HIV + farm workers and sex workers into an existing HIV treatment and prevention clinic in rural South Africa, addressing and treating abnormal results promptly.