Cancer Treatment-Related Cardiovascular Toxicity in Gynecologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Improvements in early detection and treatment of gynecologic malignancies have led to an increasing number of survivors who are at risk of long-term cardiac complications from cancer treatment. Multimodality therapies for gynecologic malignancies, including conventional chemotherapy, targeted therapeutics, and hormonal agents, place patients at risk of cancer therapy-related cardiovascular toxicity during and following treatment. Although the cardiotoxicity associated with some female predominant cancers (eg, breast cancer) have been well recognized, there has been less recognition of the potential adverse cardiovascular effects of anticancer therapies used to treat gynecologic malignancies. In this review, the authors provide a comprehensive overview of the cancer therapeutic agents used in gynecologic malignancies, associated cardiovascular toxicities, risk factors for cardiotoxicity, cardiac imaging, and prevention strategies.

Causal effect of obesity on gynecologic malignancies.

INTRODUCTION: Gynecologic malignancies are estimated to affect 110,070 women and will be the cause of death in approximately 32,120 in 2018. Endometrial cancer is among the most prevalent with 63,320 estimated new cases and approximately 11,350 deaths, followed by ovarian cancer with an estimate of 22,000 new cases and 14,000 deaths annually. Obesity is one of the most modifiable risk factors. Providers should engage in a multifaceted approach to patient education and healthcare to decrease the projected cases of obesity-related cancers. BACKGROUND: The literature demonstrates a significant link between obesity and the development of certain malignancies such as endometrial, pancreatic, and renal cancer. Specific mechanisms found to play a role in the development of these malignancies include alterations of the metabolic pathway attributed to lipid accumulation as well as a chronic inflammatory process. Obesity also predisposes patients to other medical comorbidities as well as a poorer prognosis once a diagnosis of cancer is established. Factors contributing to poorer prognosis include challenges with treatment planning, specifically pertaining to inappropriate chemotherapy dosing and delivery of radiation therapy. Surgical approach and perioperative management are similarly challenging in obese patients and are associated with increased risk of complications. CONCLUSION: Obesity is a modifiable factor which is associated with an increased risk of cancer and poorer outcomes. Providers should educate patients on all health hazards of obesity, including increased risk of cancer, and encourage them to participate in a structured weight loss plan.

Society of Gynecologic Oncology Future of Physician Payment Reform Task Force report: The Endometrial Cancer Alternative Payment Model (ECAP).

Health care in the United States is in the midst of a significant transformation from a "fee for service" to a "fee for value" based model. The Medicare Access and CHIP Reauthorization Act of 2015 has only accelerated this transition. Anticipating these reforms, the Society of Gynecologic Oncology developed the Future of Physician Payment Reform Task Force (PPRTF) in 2015 to develop strategies to ensure fair value based reimbursement policies for gynecologic cancer care. The PPRTF elected as a first task to develop an Alternative Payment Model for thesurgical management of low risk endometrial cancer. The history, rationale, and conceptual framework for the development of an Endometrial Cancer Alternative Payment Model are described in this white paper, as well as directions forfuture efforts.

Evaluation of a Streamlined Oncologist-Led BRCA Mutation Testing and Counseling Model for Patients With Ovarian Cancer.

Purpose There is a growing demand for BRCA1/ 2 mutation ( BRCAm) testing in patients with ovarian cancer; however, the limited number of genetic counselors presents a potential barrier. To facilitate more widespread BRCAm testing in ovarian cancer, pretest counseling by the oncology team could shorten testing turnaround times and ease the pressure on genetic counselors. Patients and Methods The prospective, observational Evaluating a Streamlined Onco-genetic BRCA Testing and Counseling Model Among Patients With Ovarian Cancer (ENGAGE) study evaluated a streamlined, oncologist-led BRCAm testing pathway. The analysis population comprised 700 patients with ovarian cancer at 26 sites in the United States, Italy, and Spain. The primary objectives were to assess turnaround time and, using questionnaires, to evaluate stakeholder satisfaction (patients, oncologists, and geneticists or genetic counselors) with the oncologist-led BRCAm testing pathway. Results The median overall turnaround time was 9.1 weeks (range, 0.9 to 37.1 weeks), with median turnaround times in the United States, Italy, and Spain of 4.1 weeks (range, 0.9 to 37.1 weeks), 20.4 weeks (range, 2.9 to 35.4 weeks), and 12.0 weeks (range, 2.0 to 36.7 weeks), respectively. Patient satisfaction with the oncologist-led BRCAm testing pathway was high, with > 99% of patients expressing satisfaction with pre- and post- BRCAm test counseling. Oncologist satisfaction with the BRCAm testing pathway was also high, with > 80% agreeing that the process for performing BRCAm testing worked well and that counseling patients on BRCAm testing was an efficient use of their time. Oncologists expressed higher levels of satisfaction with the BRCAm testing pathway than did geneticists or genetic counselors. Conclusion The results of the ENGAGE study demonstrate that an oncologist-led BRCAm testing process is feasible in ovarian cancer. Development of local BRCAm testing guidelines similar to the one used in this study could allow faster treatment decisions and better use of resources in the management of patients with ovarian cancer.

Morcellation in gynecologic oncology.

PURPOSE OF REVIEW: Morcellation of uteri with unsuspected malignancies has been the focus of reports for decades. More intensive evaluation of clinical outcomes and evaluation of impact of changes in practice has occurred since the release of FDA statement advising against the use of power morcellators. The review summarizes some of the most relevant publications on this topic. RECENT FINDINGS: The Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists concur that symptomatic women should undergo appropriate evaluation, morcellation should not be performed whenever malignancy is suspected or diagnosed, and acknowledge the limitations of diagnostic testing currently available to detect leiomyosarcoma. Accurate incidence of occult leiomyosarcoma in women undergoing hysterectomy for symptomatic myomas is not known because of poor quality of data. Increased complication rates, including death, with abdominal procedures and increased societal costs have been reported. The FDA safety communication has resulted in decreased laparoscopic hysterectomy rates. SUMMARY: Clinical judgement and practice in accordance to clinical guidelines, based on best current scientific evidence, is recommended. Women should be aware of the limitation of current data regarding the incidence of occult leiomyosarcoma or other malignancies whenever consenting to any form of therapy for symptomatic myomas, including surgical, medical and expectant management. If surgical treatment is selected, morcellation should not be performed if a malignancy diagnosis is known or suspected. A minimally invasive surgical approach is associated with a decreased complication rate and an increased quality of life years. Research efforts should focus on improving diagnostic accuracy and efficacy of therapeutic interventions.

Outcomes and Postoperative Complications After Hysterectomies Performed for Benign Compared With Malignant Indications.

OBJECTIVE: To compare complications and outcomes after hysterectomy for benign compared with malignant indications in the United States. METHODS: Women who underwent hysterectomy in the United States for either benign or malignant indications from January 2008 to December 2012 were retrospectively identified using the National Surgical Quality Improvement Program database. Patients were excluded if the procedure was not performed for primary gynecologic indications. Appropriate procedures were identified using Current Procedural Terminology and International Classification of Diseases, 9th Revision codes. Univariate and multivariable models for complication risk were estimated using logistic regression. RESULTS: We identified 59,525 eligible patients, with 49,331 (82.9%) hysterectomies performed for benign and 10,194 (17.1%) for malignant indications. All complications, including wound complications (2.5% benign compared with 5.5% malignant, P<.001), venous thromboembolism (0.33% compared with 1.7%, P<.001), urinary tract infection (2.7% compared with 3.2%, P=.009), sepsis (0.53% compared with 1.9%, P<.001), blood transfusion (2.6% compared with 11.5%, P<.001), death (0.02% compared with 0.10%, P<.001), unplanned readmission (1.8% compared with 4.5%, P<.001), and returns to the operating room (0.91% compared with 1.4%, P<.001), were significantly more common for malignant hysterectomies. The overall rate of complications for benign cases was 7.9% compared with a rate of 19.4% for malignant hysterectomy. The median operating time for laparoscopy in benign cases was significantly longer than for open or vaginal hysterectomy procedures (127 minutes compared with 105 or 94 minutes, respectively; P<.001). The median operating time in malignant cases was significantly longer than for benign cases (P<.001). CONCLUSION: Hysterectomies performed for gynecologic malignancies are associated with a more than twofold higher complication rate compared with those performed for benign conditions. Minimally invasive surgery is associated with a decreased complication rate compared with open surgery. These data can be used for patient counseling and surgical planning, determining physician and hospital costs of care, and considered when assigning value-based reimbursement.

U.S. Food and Drug Administration's Guidance Regarding Morcellation of Leiomyomas: Well-Intentioned, But Is It Harmful for Women?

The U.S. Food and Drug Administration (FDA) is warning against the use of laparoscopic power morcellators in the majority of women undergoing myomectomy or hysterectomy for the treatment of leiomyomas because of the concern for inadvertent spread of tumor cells if an undiagnosed cancer were present. The authors, representing a 45-member review group, reviewed the current literature to formulate prevalence rates of leiomyosarcoma in women with presumed leiomyomas and to asses reliable data regarding patient survival after morcellation. The authors disagree with the FDA's methodology in reaching their conclusion and provide clinical recommendations for care of women with leiomyomas who are planning surgery.

CyberKnife Boost for Patients with Cervical Cancer Unable to Undergo Brachytherapy.

Standard radiation therapy for patients undergoing primary chemosensitized radiation for carcinomas of the cervix usually consists of external beam radiation followed by an intracavitary brachytherapy boost. On occasion, the brachytherapy boost cannot be performed due to unfavorable anatomy or because of coexisting medical conditions. We examined the safety and efficacy of using CyberKnife stereotactic body radiotherapy (SBRT) as a boost to the cervix after external beam radiation in those patients unable to have brachytherapy to give a more effective dose to the cervix than with conventional external beam radiation alone. Six consecutive patients with anatomic or medical conditions precluding a tandem and ovoid boost were treated with combined external beam radiation and CyberKnife boost to the cervix. Five patients received 45 Gy to the pelvis with serial intensity-modulated radiation therapy boost to the uterus and cervix to a dose of 61.2 Gy. These five patients received an SBRT boost to the cervix to a dose of 20 Gy in five fractions of 4 Gy each. One patient was treated to the pelvis to a dose of 45 Gy with an external beam boost to the uterus and cervix to a dose of 50.4 Gy. This patient received an SBRT boost to the cervix to a dose of 19.5 Gy in three fractions of 6.5 Gy. Five percent volumes of the bladder and rectum were kept to ≤75 Gy in all patients (i.e., V75 Gy ≤ 5%). All of the patients remain locally controlled with no evidence of disease following treatment. Grade 1 diarrhea occurred in 4/6 patients during the conventional external beam radiation. There has been no grade 3 or 4 rectal or bladder toxicity. There were no toxicities observed following SBRT boost. At a median follow-up of 14 months, CyberKnife radiosurgical boost is well tolerated and efficacious in providing a boost to patients with cervix cancer who are unable to undergo brachytherapy boost. Further follow-up is required to see if these results remain durable.

Promoting knowledge of cancer prevention and screening in an underserved Hispanic women population: a culturally sensitive education program.

This article aims to measure the baseline knowledge of cancer prevention, screening, and early detection practices, to understand the barriers to cancer screening and sources of health information; and to evaluate the effectiveness of a culturally sensitive education program in an underserved Hispanic women population. A total of 180 women participated. Pre- and postsurveys were administered. Multivariate analysis was used to analyze the impact of program on knowledge and to determine factors affecting learning. Results showed Significant overall improvement in knowledge of cancer symptoms (1.85 baseline vs. 3.67 postintervention, p < .001), knowledge of risk-reducing behaviors (2.71 vs. 4.81, p < .001); and effect on planned behavior (89% planned to follow screening guidelines). Higher incomes and younger age are associated with better learning. Major barriers to cancer screening were financial limitations and lack of knowledge. The intervention was effective in promoting awareness and knowledge of cancer screening and prevention. Programs aimed at reducing cancer incidence and mortality should recognize the importance of cultural sensitivity and facilitating access to screening tests.

Prophylactic and risk-reducing bilateral salpingo-oophorectomy: recommendations based on risk of ovarian cancer.

Women who do not have a documented germline mutation or who do not have a strong family history suspicious for a germline mutation are considered to be at average risk of ovarian cancer. Women who have confirmed deleterious BRCA1 and BRCA2 germline mutations are high risk of ovarian cancer. In addition, women who have a strong family history of either ovarian or breast cancer may carry a deleterious mutation and must be presumed to be at higher-than-average risk, even if they have not been tested, because there could be other mutations that are either untested or yet undiscovered that confirm higher-than-average risk of these diseases. We reviewed studies pertaining to prophylactic bilateral salpingo-oophorectomy in women at average risk of ovarian cancer who are undergoing hysterectomy for benign disease. We also reviewed the role of prophylactic bilateral salpingo-oophorectomy in preventing ovarian cancer based on the level of risk of the patient. For women at average risk of ovarian cancer who are undergoing a hysterectomy for benign conditions, the decision to perform prophylactic bilateral salpingo-oophorectomy should be individualized after appropriate informed consent, including a careful analysis of personal risk factors. Several studies suggest an overall negative health effect when prophylactic bilateral salpingo-oophorectomy is performed before the age of menopause. Ovarian conservation before menopause may be especially important in patients with a personal or strong family history of cardiovascular or neurological disease. Conversely, women at high risk of ovarian cancer should undergo risk-reducing bilateral salpingo-oophorectomy.