Sarah M. Temkin

Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: A NCI clinical trials planning meeting report

The incidence of endometrial cancer (EC) in the U.S. has been rising, from an estimated annual incidence of 49,560 in 2013 to 61,380 in 2017. Meanwhile, the SEER-based relative survival of women with EC in the U.S. has remained flat [82.3% from 1987 to 1989, 82.8% from 2007 to 2013] and our recent increased understanding of EC biology and subtypes has not been translated into therapeutic advances. The U.S. National Cancer Institute (NCI) therefore convened a Uterine Clinical Trials Planning Meeting in January 2016 to initiate and accelerate design of molecularly-targeted EC trials. Prior to the meeting a group of experts in this field summarized available data, emphasizing data on human samples, to identify potentially actionable alterations in EC, and the results of their work has been separately published. The Clinical Trials Meeting planners focused on discussion of (1) novel trial designs, including window-of opportunity trials and appropriate control groups for randomized trials, (2) targets specific to serous carcinoma and promises and pitfalls of separate trials for women with tumors of this histology (3) specific recommendations for future randomized trials.

A contemporary framework of health equity applied to gynecologic cancer care: A Society of Gynecologic Oncology evidenced-based review

Health disparities are defined as the preventable difference in the burden of disease, injury, and violence, or opportunity to achieve optimal health that socially disadvantaged populations experience compared to the population as a whole. Disparities in incidence and cancer outcomes for women with gynecologic malignancies have been well described particularly for American women of Black race. The etiology of these disparities has been tied to socio-economics, cultural, educational and genetic factors. While access to high quality treatment has been primarily linked to survival from cervical and ovarian cancer, innate biologic distinctions have been principally cited as reasons for differences in incidence and mortality in cancers of the uterine corpus. This article will update the framework of disparities to incorporate a broader understanding of the social determinants of health and how they affect health equity by addressing the root causes of disparities within the health care system. Special populations are identified who are at risk for health inequities which include but are not limited to Black race, underserved racial and ethnic minorities (e.g. indigenous peoples, low English fluency), trans/gender nonconforming people and rural populations. Each of these populations at risk have unique structural barriers within the healthcare system impacting gynecologic cancer outcomes. The authors provide practical recommendations for practitioners aimed at eliminating cancer related outcome disparities.

Narcotics reduction, quality and safety in gynecologic oncology surgery in the first year of enhanced recovery after surgery protocol implementation

OBJECTIVES Enhanced Recovery After Surgery (ERAS) programs are mechanisms for achieving value-based improvements in surgery. This report provides a detailed analysis of the impact of an ERAS program on patient outcomes as well as quality and safety measures during implementation on a gynecologic oncology service at a major academic medical center. METHODS A retrospective review of gynecologic oncology patients undergoing elective laparotomy during the implementation phase of an ERAS program (January 2016 through December 2016) was performed. Patient demographics, surgical variables, postoperative outcomes, and adherence to core safety measures, including antimicrobial and venous thromboembolism (VTE) prophylaxis, were compared to a historical patient cohort (January 2015 through December 2015). Statistical analyses were performed using t-tests, Wilcoxon rank sum tests, and Chi squared tests. RESULTS The inaugural 109 ERAS program participants were compared to a historical patient cohort (n=158). There was no difference in BMI, race, malignancy, or complexity of procedure between cohorts. ERAS patients required less narcotics (70.7 vs 127.4, p=0.007, oral morphine equivalents) and PCA use (32.1% vs. 50.6%, p=0.002). Despite this substantial reduction in narcotics, ERAS patients did not report more pain and in fact reported significantly less pain by postoperative day 3. There were no differences in length of stay (5days), complication rates (13.8% vs. 20.3%, p=0.17) or 30-day readmission rates (9.5 vs 11.9%, p=0.54) between ERAS and historical patients, respectively. Compliance with antimicrobial prophylaxis was 97.2%. However, 33.9% of ERAS patients received substandard preoperative VTE prophylaxis. CONCLUSIONS ERAS program implementation resulted in reductions in narcotic requirements and PCA use without changes in length of stay or readmission rates. Compliance should be diligently audited during the implementation phase of ERAS programs, with special attention to adherence to pre-existing core safety measures.

Radiation Treatment in Women with Ovarian Cancer: Past, Present, and Future

Ovarian cancer is the most lethal of the gynecologic cancers, with 5-year survival rates less than 50%. Most women present with advanced stage disease as the pattern of spread is typically with dissemination of malignancy throughout the peritoneal cavity prior to development of any symptoms. Prior to the advent of platinum-based chemotherapy, radiotherapy was used as adjuvant therapy to sterilize micrometastatic disease. The evolution of radiotherapy is detailed in this review, which establishes radiotherapy as an effective therapy for women with micrometastatic disease in the peritoneal cavity after surgery, ovarian clear cell carcinoma, focal metastatic disease, and for palliation of advanced disease. However, with older techniques, the toxicity of whole abdominal radiotherapy and the advancement of systemic therapies have limited the use of radiotherapy in this disease. With newer radiotherapy techniques, including intensity-modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and low-dose hyperfractionation in combination with targeted agents, radiotherapy could be reconsidered as part of the standard management for this deadly disease.

Reproductive health care across the lifecourse of the female cancer patient

Reproductive health is a key component of cancer care and survivorship, encompassing gynecologic issues ranging from contraception and fertility to treatment of sexual dysfunction and menopause. Yet, oncology providers are often unfamiliar with the management of gynecologic issues. In order to address the unmet needs of female cancer patients, reproductive health should be addressed at the time of cancer diagnosis and continue through survivorship. Universal screening for pregnancy intention can guide counseling on contraception and fertility preservation. Safe and efficacious contraceptive options for both patients undergoing active treatment and cancer survivors are available and can often offer non-contraceptive benefits such as regulation of menses. Prompt referral to reproductive endocrinology specialists allows patients to explore options for fertility preservation prior to the receipt of cancer-directed therapies. Due to a rapid drop in hormone levels, treatment-induced menopause often results in severe symptoms. In patients with induced menopause, balancing the risks of hormone therapy compared to the decreased quality of life and health concerns associated with early menopause may help patients with difficult decisions regarding symptom control. Cancer treatment impacts sexual function with both physical changes to the vulvovaginal tissues and altered relationship dynamics. Open discussions on the impact to sexual health are paramount to quality of life after cancer. While more data is needed in many areas, proactive management of reproductive health issues is crucial to quality of life in cancer survivorship. In this article, we review contemporary management of the reproductive health of the female cancer patient.

Hysterectomy-corrected rates of endometrial cancer among women younger than age 50 in the United States

PurposeThis analysis describes the impact of hysterectomy on incidence rates and trends in endometrioid endometrial cancer in the United States among women of reproductive age.MethodsHysterectomy prevalence for states containing Surveillance, Epidemiology, and End Results (SEER) registry was estimated using data from the Behavioral Risk Factor Surveillance System (BRFSS) between 1992 and 2010. The population was adjusted for age, race, and calendar year strata. Age-adjusted incidence rates and trends of endometrial cancer among women age 20–49 corrected for hysterectomy were estimated.ResultsHysterectomy prevalence varied by age, race, and ethnicity. Increasing incidence trends were observed, and were attenuated after correcting for hysterectomy. Among all women, the incidence was increasing 1.6% annually (95% CI 0.9, 2.3) and this increase was no longer significant after correction for hysterectomy (+ 0.7; 95% CI − 0.1, 1.5). Stage at diagnosis was similar with and without correction for hysterectomy. The largest increase in incidence over time was among Hispanic women; even after correction for hysterectomy, incidence was increasing (1.8%; 95% CI 0.2, 3.4) annually.ConclusionOverall, endometrioid endometrial cancer incidence rates in the US remain stable among women of reproductive age. Routine reporting of endometrial cancer incidence does not accurately measure incidence among racial and ethnic minorities.

The “value” of value in gynecologic oncology practice in the United States: Society of Gynecologic Oncology evidence-based review and recommendations

a Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, United States b Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Pennsylvania Health System, Pennsylvania Hospital, Philadelphia, PA, United States c Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States d Division of Gynecologic Oncology, Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, NY, United States e Virginia Commonwealth University, Richmond, VA, United States f Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University, Durham, NC, United States

Uterine Sarcoma: Modern Treatment Paradigms

Purpose of ReviewThe purpose of this review is to inform readers of the most current management strategies for women with uterine sarcoma.Recent FindingsSurgery is the standard of care in the management of all soft-tissue sarcomas, including uterine sarcoma. However, there are malignancies that can be challenging to diagnose preoperatively and can mimic the appearance of benign uterine leiomyomas. Because of aggressive tumor biology and relative chemotherapy and radiotherapy resistance, efficacious therapies to achieve prolonged survival or cure in those with both early- and advanced-stage uterine sarcomas have been elusive. The strongest determinant of survival remains the stage at diagnosis, though prediction models may provide a more accurate prognosis. An increase in the use of both adjuvant chemotherapy and radiation therapy more recently has led to a small survival advantage in these tumors.SummaryUterine sarcomas are a rare form of uterine cancer; however, they contribute disproportionately to a large number of uterine cancer deaths. Both the rarity of this disease and the inability to confirm a preoperative diagnosis make it difficult to study women with uterine sarcoma. Randomized controlled trials have demonstrated a limited response to traditional cytotoxic therapy, highlighting the importance of novel treatment strategies. This review provides a critical appraisal of the literature regarding the contemporary management of uterine sarcoma, the role of targeted therapies, and potential future directions for research.