Doubling down on the future of gynecologic oncology: The SGO future of the profession summit report.

The original vision of the field of gynecologic oncology was to establish a multidisciplinary approach to the management of patients with gynecologic cancers. Fifty years later, scientific advances have markedly changed the overall practice of gynecologic oncology, but the profession continues to struggle to define its value-financial and otherwise. These issues were examined in full at the Society of Gynecologic Oncology (SGO) Future of the Profession Summit and the purpose of this document is to summarize the discussion, share the group's perceived strengths, weaknesses, opportunities, and threats (SWOT) for gynecologic oncologists, further educate members and others within the patient care team about the unique role of gynecologic oncologists, and plan future steps in the short- and long- term to preserve the subspecialty's critical mission of providing comprehensive, longitudinal care for people with gynecologic cancers.

Patient-reported outcome changes at the end of life in recurrent platinum-resistant ovarian cancer: An NRG oncology/GOG study.

OBJECTIVES: In a prospective study of platinum-resistant ovarian cancer patients, we examined whether the Disease-related Symptoms-Physical (DRS--P) scale of the NCCN/FACT-Ovarian Cancer Symptom Index-18 (NFOSI-18) is responsive to clinical change in patients estimated by their provider to survive at least six months. METHODS: The NFOSI-18, and other FACT measures, was collected at study entry and 3 and 6 months post-enrollment. Measures were compared for those who died or dropped off study prior to 3 months or prior to 6 months (assumed as health deterioration over time), or those who stayed on study through 6 months (presumed as stable disease over time). Statistical analyses included a fitted linear mixed model for estimating the group differences over time, Cox regression to assess the probability of survival with patient-reported outcomes, and effect size. RESULTS: DRS-P scores of patients who completed only one assessment were significantly lower compared to patients who were able to complete two assessments [5.9 points lower (2.0-9.8); p < 0.01], or three assessments [8.1 points lower (4.8-11.5); p < 0.01]. Measures of abdominal discomfort, functional well-being, emotional well-being, and quality of life were also significant, but treatment side effects were not. Further, in every scale except for neurotoxicity, higher (better) baseline scores were associated with a decreased likelihood of death, after adjusting for age, performance and disease status. CONCLUSION: The NFOSI-18 DRS-P scale is responsive to clinical change. It has potential as an indicator of changing health status with ovarian cancer disease progression, distinct from treatment side effects.

Cause or Effect? The Role of Prognostic Uncertainty in the Fear of Cancer Recurrence.

BACKGROUND: Fear of cancer recurrence (FCR) is an important cause of suffering for cancer survivors, and both empirical evidence and theoretical models suggest that prognostic uncertainty plays a causal role in its development. However, the relationship between prognostic uncertainty and FCR is incompletely understood. OBJECTIVE: To explore the relationship between prognostic uncertainty and FCR among patients with ovarian cancer (OC). DESIGN: A qualitative study was conducted utilizing individual in-depth interviews with a convenience sample of patients with epithelial ovarian cancer who had completed first-line treatment with surgery and/or chemotherapy. Semi-structured interviews explored participants' (1) understanding of their prognosis; (2) experiences, preferences, and attitudes regarding prognostic information; and (3) strategies for coping with prognostic uncertainty. Inductive qualitative analysis and line-by-line software-assisted coding of interview transcripts was conducted to identify key themes and generate theoretical insights on the relationship between prognostic uncertainty and FCR. RESULTS: The study sample consisted of 21 participants, nearly all of whom reported experiencing significant FCR, which they traced to an awareness of the possibility of a bad outcome. Some participants valued and pursued prognostic information as a means of coping with this awareness, suggesting that prognostic uncertainty causes FCR. However, most participants acknowledged fundamental limits to both the certainty and value of prognostic information, and engaged in various strategies aimed not at reducing but constructing and maintaining prognostic uncertainty as a means of sustaining hope in the possibility of a good outcome. Participants' comments suggested that prognostic uncertainty, fear, and hope are connected by complex, bi-directional causal pathways mediated by processes that allow patients to cope with, construct, and maintain their uncertainty. A provisional dual-process theoretical model was developed to capture these pathways. CONCLUSION: Among patients with OC, prognostic uncertainty is both a cause and an effect of FCR-a fear-inducing stimulus and a hope-sustaining response constructed and maintained through various strategies. More work is needed to elucidate the relationships between prognostic uncertainty, fear, and hope, to validate and refine our theoretical model, and to develop interventions to help patients with OC and other serious illnesses to achieve an optimal balance between these states.

Quality of life, symptoms and care needs in patients with persistent or recurrent platinum-resistant ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study.

OBJECTIVES: The goals of treating recurrent platinum-resistant ovarian cancer are palliative, aimed at reducing symptoms and improving progression free survival. A prospective trial was conducted to determine the prevalence and severity of symptoms, and associated care needs. METHODS: Eligible women included those with persistent or recurrent platinum-resistant ovarian cancer with an estimated life expectancy of at least 6 months. The Needs at the End-of-Life Screening Tool (NEST), FACIT-Fatigue (FACIT-F), NCCN-FACT Ovarian Symptom Index [NFOSI-18]; Disease Related Symptoms (DRS), Treatment Side Effects (TSE), and Function/Well Being (F/WB) were collected at study entry, 3 and 6 months. RESULTS: We enrolled 102 evaluable patients. Initiation of Do Not Resuscitate (DNR) discussions increased over time from 28% at study entry to 37% at 6 months. At study entry, the most common disease-related symptoms were fatigue (92%), worry (89%), and trouble sleeping (76%); 73% reported being "bothered by treatment side effects", which included nausea (41%) and hair loss (51%) neither of which changed over time. The most common NEST unmet needs were in the symptom dimension. The social dimension was associated with F/WB (p = 0.002) and FACIT-F (p = 0.006); symptoms were associated with DRS (p = 0.04), TSE (p = 0.03), and FACIT-F (p = 0.04); existential was not associated with any of the patient-reported symptoms; therapeutic was associated with F/WB (p = 0.02). CONCLUSIONS: In patients nearing the end of life, there are significant associations between disease and treatment related symptoms and unmet patient needs, which do not change substantially over time. Careful exploration of specific end-of-life care needs can improve patient-centered care and QOL.

Society of Gynecologic Oncology Clinical Outcomes Registry: From small beginnings come great things.

OBJECTIVE: Clinical registries within medical societies have demonstrated the capacity to promote quality improvement. Opportunities for well-designed data repositories could yield reliable national standards for informing reimbursement, determining adherence to care guidelines, maintaining board certification, and developing bundled payment models. Looking to the future, we set out to develop a gynecologic cancer registry serving the members of the Society of Gynecologic Oncology (SGO). METHODS: The SGO Clinical Outcomes Registry (COR) initiated a web-based data entry platform as a foray into developing a functional registry, compiling data elements specific to gynecologic oncology. Endometrial and ovarian cancer patients began enrollment in early 2014. Within one year, 19 sites were participating with the addition of cervical cancer patients in January 2015. RESULTS: To date, >6500 patients are currently entered from 29 sites, and the COR is being queried to address topics of quality improvement, disparities, and cancer outcomes. CONCLUSIONS: The SGO COR has proven the feasibility of developing a functional gynecologic cancer registry, with high uptake, rapid accrual, and ability to investigate topics of quality and outcome using the COR.

Biomarkers p16, Human Papillomavirus and p53 Predict Recurrence and Survival in Early Stage Squamous Cell Carcinoma of the Vulva.

OBJECTIVE: Vulvar squamous cell carcinoma (VSCC) develops through 2 distinct molecular pathways, one involving high-risk human papillomavirus (HPV) infection and the other through early p53 suppressor gene mutation. We sought to evaluate the influence of p53 mutation, HPV status, and p16 expression on local recurrence and disease-specific mortality in early stage VSCC. MATERIALS AND METHODS: We performed a retrospective chart review of all patients with stage I VSCC at the Maine Medical Center from 1998 to 2007 (n = 92). Tumor size, depth of invasion, lymphatic/vascular space invasion, and growth pattern were recorded. Paraffin-embedded tissue blocks were stained by immunohistochemistry for p16 and p53; high-risk HPV was detected by polymerase chain reaction assay. Margin distance was determined by a gynecologic pathologist. Survival analyses were conducted to examine predictors of VSCC recurrence and disease-specific mortality. RESULTS: Age, depth of invasion, lymphatic/vascular space invasion, growth pattern, and margin status were not significant predictors of recurrence or disease-specific mortality. Tumor size of greater than 4.0 cm indicated a 4-fold increase in disease-specific mortality but did not significantly increase recurrence. p16-Positive patients were less likely to recur and had no VSCC-related deaths. Human papillomavirus-positive patients were less likely to recur and had no VSCC-related deaths. p53-positive patients were 3 times more likely to recur and nearly 7 times more likely to die from vulvar cancer. CONCLUSIONS: Our findings suggest that HPV and the surrogate biomarker p16 indicate a less aggressive type of vulvar cancer. p53 positivity was associated with poor prognosis and significantly increased both recurrence and disease-specific mortality.

Electronic Records, Registries, and the Development of "Big Data": Crowd-Sourcing Quality toward Knowledge.

Despite many perceived advances in treatment over the past few decades, cancer continues to present a significant health burden, particularly to the aging US population. Forces including shrinking funding mechanisms, cost and quality concerns, as well as disappointing clinical outcomes have driven a surge of recent efforts into utilizing the technological innovation that has permeated other industries by leveraging large and complex data sets, so called "big data." In this review, we will review some of the history of oncology data collection, including the earliest data registries, as well as explore the future directions of this new brand of research while highlighting some of the more recent and promising efforts to harness the power of the electronic health record and the multitude of data co-located there, in an effort to improve individualized cancer-related outcomes in rapid real time.

Intraperitoneal chemotherapy among women in the Medicare population with epithelial ovarian cancer.

BACKGROUND: Intraperitoneal combined with intravenous chemotherapy (IV/IP) for primary treatment of epithelial ovarian cancer results in a substantial survival advantage for women who are optimally debulked surgically, compared with standard IV only therapy (IV). Little is known about the use of this therapy in the Medicare population. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 4665 women aged 66 and older with epithelial ovarian cancer diagnosed between 2005-2009, with their Medicare claims. We defined receipt of any IV/IP chemotherapy when there was claims evidence of any receipt of such treatment within 12 months of the date of diagnosis. We used descriptive statistics to examine factors associated with treatment and health services use. RESULTS: Among 3561 women with Stage III or IV epithelial ovarian cancer who received any chemotherapy, only 124 (3.5%) received IV/IP chemotherapy. The use of IV/IP chemotherapy did not increase over the period of the study. In this cohort, younger women, those with fewer comorbidities, whites, and those living in Census tracts with higher income were more likely to receive IV/IP chemotherapy. Among women who received any IV/IP chemotherapy, we did not find an increase in acute care services (hospitalizations, emergency department visits, or ICU stays). CONCLUSION: During the period between 2005 and 2009, few women in the Medicare population living within observed SEER areas received IV/IP chemotherapy, and the use of this therapy did not increase. We observed marked racial and sociodemographic differences in access to this therapy.

Correlation between smoking status and cervical cancer screening: a cross-sectional study.

OBJECTIVES: Tobacco use is a risk factor for the development and progression of cervical cancer. The purpose of this study was to determine the correlation between smoking status among women and their compliance with cervical cancer screening guidelines. MATERIALS AND METHODS: A cross-sectional analysis of the Behavioral Risk Factor Surveillance System was performed using the 2006 survey data. Women with no history of hysterectomy who answered the questions regarding smoking status, age, and last Pap smear were included (n = 150,786). Data were weighted for survey design. RESULTS: The overall prevalence of compliance with cervical cancer screening guidelines was 83.9%. The rate of compliance was highest among former smokers (86.7%) compared with never smokers (83.7%) and current smokers (81.7%; p < .001). Among women aged 21 to 65 years, the odds of current smokers having had a Pap test in the past 3 years was 0.70 compared with women who never smoked (95% confidence interval = 0.63-0.77), when controlled for marital status, income, and access to health care. The odds of former smokers complying with screening guidelines were similar to women who never smoked. CONCLUSIONS: Women who smoke are at higher risk for developing cervical cancer but have a lower rate of screening for the disease. Efforts to increase prevalence of Pap test compliance should target current smokers.

A nomogram for estimating the probability of ovarian cancer.

OBJECTIVE: Accurate preoperative estimates of the probability of malignancy in women with adnexal masses are essential for ensuring optimal care. This study presents a new statistical model for combining predictive information and a graphic decision support tool for calculating risk of malignancy. METHODS: The study included 153 women treated with definitive surgery for adnexal mass between 2001 and 2007 with preoperative ultrasound testing and a serum CA125. Multivariable logistic regression was used to develop a statistical model for estimating the probability of ovarian cancer as a function of age, ultrasound score, and CA125 value, with adjustments for nonlinear and interactive relationships. RESULTS: A total of 20 cases of pathologically confirmed cancer (13 invasive malignancies, and 7 tumors of low malignant potential) were identified (20/153=13%). The model obtained excellent discrimination (ROC area=0.87), explained nearly half of the observed variation in the risk of malignancy (R²=0.43), and was well calibrated across the full range of malignancy probabilities. The model equation is represented in the form of a nomogram, which can be used to calculate preoperative probability of malignancy. At a 5% risk of malignancy threshold, the model has a sensitivity of 90% and a specificity of 73%. CONCLUSIONS: Statistical models for estimating the probability of adnexal mass malignancy are substantially improved by including adjustments for non-linear relationships among key variables. A clinically relevant nomogram provides an objective tool to further aid clinicians in counseling patients and ensuring proper referral to surgical sub-specialists when indicated.

A phase II study of gemcitabine (gemzar, LY188011) in the treatment of recurrent or persistent endometrial carcinoma: a gynecologic oncology group study.

OBJECTIVE: The study aims to evaluate the anti-tumor activity and toxicity of gemcitabine in patients with persistent or recurrent endometrial carcinoma. METHODS: Patients with advanced or recurrent carcinoma of the endometrium previously treated with one chemotherapy regimen were treated on a phase II trial conducted by the Gynecologic Oncology Group (GOG). Gemcitabine was administered as an intravenous infusion at a dose of 800 mg/m² over 30 min on days 1 and 8 every 21 days. RESULTS: Twenty-four patients were entered by 11 GOG member institutions. One patient was ineligible due to wrong primary tumor. A total of ninety 21-day cycles of therapy were administered with 35% of patients receiving four or more cycles. All patients had been previously treated with a platinum-based regimen. One patient had a partial response (4%), nine had stable disease (39%), and twelve had increasing disease (52%). The median progression-free survival was 1.7 months. Treatment was generally well tolerated with only 22% of patients experiencing grade 3 or grade 4 hematologic toxicity. There was one treated-related death due to pulmonary toxicity. CONCLUSION: Gemcitabine has minimal activity in the treatment of recurrent or persistent endometrial carcinoma at the dose and schedule tested.

Appendiceal pathology at the time of oophorectomy for ovarian neoplasms.

OBJECTIVE: To investigate the prevalence of appendiceal pathology in women undergoing surgery for a suspected ovarian neoplasm and the predictive value of intraoperative findings to determine the need for appendectomy at the time of surgery. METHODS: Retrospective analysis of patients who underwent oophorectomy and appendectomy during the same surgical procedures at the University of Virginia Health System from 1992 to 2007. Observations were stratified based on the nature (benign, borderline, or malignant) and histology (serous compared with mucinous) of the ovarian neoplasm, frozen compared with final pathological diagnosis, and the gross appearance of the appendix. RESULTS: Among the 191 patients identified, frozen section was consistent with seven mucinous and 35 serous carcinomas, 16 serous and 33 mucinous borderline tumors, 71 mucinous and serous cystadenomas, and 29 cases of suspected metastatic tumor from a gastrointestinal primary. The highest rates of coexisting appendiceal pathology were associated with serous ovarian cancers (94.4% of grossly abnormal and 35.3% of normal appendices) and ovarian tumors suspected to be of primary gastrointestinal origin (83.3% grossly abnormal and 60.0% normal appendices harbored coexisting mucinous neoplasms). Linear regression analysis revealed that appearance of the appendix and frozen section diagnosis of the ovarian pathology were statistically significant predictors of coexisting appendiceal pathology, but the latter was more important. CONCLUSION: The prevalence of coexisting, clinically significant appendiceal pathology is low with a frozen section diagnosis of serous or mucinous cystadenoma. Appendectomy is recommended when frozen section diagnosis is mucinous or serous ovarian carcinoma, borderline tumor or metastatic carcinoma of suspected gastrointestinal origin.

Temozolomide in advanced and recurrent uterine leiomyosarcoma and correlation with o6-methylguanine DNA methyltransferase expression: a case series.

INTRODUCTION: Our objective was to retrospectively review temozolomide in advanced and recurrent uterine leiomyosarcoma and to determine if tumor O-methylguanine DNA methyltransferase (MGMT) expression correlated with clinical response. METHODS: All patients with advanced or recurrent uterine leiomyosarcoma who received temozolomide during treatment were retrospectively identified. Relevant clinical and pathologic data were collected and compared. O-Methylguanine DNA methyltransferase expression was assessed by immunohistochemistry and scored by a gynecologic pathologist blinded to clinical outcomes. RESULTS: From 1999 to 2008, 9 cases of leiomyosarcoma were diagnosed; 6 patients received temozolomide. Median follow-up was 54 months (range, 4-114 months). There was 1 patient with complete response, 1 durable partial response (27+ months), 3 stable disease (range, 3-10 months), and 1 progressive disease. Overall, 5 out of 6 patients derived clinical benefit. The patient with a complete response recurred 18 months after her last cycle. Median progression free interval was 15.4 months (95% confidence interval, 9.4-21.4). Two patients died of disease. Temozolomide was well tolerated with no dose-limiting toxicities, and no dose adjustments were required in 64 prescribed cycles. The MGMT expression was inversely correlated with response to temozolomide. Patients with tumors negative for MGMT expression had a median progression free interval of 18.5 months compared with 3 months for those whose tumors were positive, although not statistically significant. CONCLUSIONS: Temozolomide is an easily administered, well-tolerated chemotherapeutic option in advanced or recurrent uterine leiomyosarcomas with a reasonable response rate. Assessment of MGMT expression may identify a subset of patients that will respond optimally to this therapy.

Surgical management and postoperative treatment of endometrial carcinoma.

Endometrial carcinoma affects over 40,000 American women annually, making it the most common gynecologic malignancy. Over 80% of disease is diagnosed in the early stages, resulting in a generally favorable prognosis for most patients. However, discrepancies still exist with regard to primary surgical management and postoperative adjuvant therapies directed at reducing recurrence rates and improving survival. In this review, we outline the surgical management of newly diagnosed disease and review the risk factors that guide clinicians in the recommendation for postoperative adjuvant therapy.

Utilization of a uniform grading system for interpreting serous ovarian cancer.

OBJECTIVE: The purpose of the study was to implement a uniform system for assigning tumor grade in serous ovarian cancer and evaluate its correlation with response to conventional chemotherapy. STUDY DESIGN: Serous ovarian cancer tumor samples were retrospectively reviewed by 3 pathologists who were blinded to the original report. Samples were scored for architectural pattern, nuclear pleomorphism, and mitotic activity. Sum scores from these 3 indices were used to classify tumors as low grade or high grade. RESULTS: A total of 21 patients were identified as low-grade tumors and 21 were identified as high-grade tumors. Of low-grade tumors, 16 (76%) were found to be platinum resistant, defined as recurrent or persistent disease, 180 days from completion of the final cycle of chemotherapy, Of 21 patients defined as high grade, 9 (43%) were platinum resistant (P = .028). CONCLUSION: Utilization of a uniform grading system retrospectively correlates with platinum sensitivity.

A cost-effective analysis of adjuvant therapies for the treatment of stage I endometrial adenocarcinoma.

OBJECTIVES: Recent surveys have indicated that four alternatives are employed for adjuvant treatment of stage I endometrial adenocarcinoma: observation (OBS), high dose rate vaginal brachytherapy (VB), whole pelvic external beam radiotherapy (EBRT), or a combination of pelvic external beam with vaginal brachytherapy (COMB). Our goal was to evaluate the cost-effectiveness of these alternatives for management of stage I endometrial adenocarcinoma. METHODS: We designed a decision analysis model comparing the four possible treatments in terms of their utility and cost. We reviewed the existing literature and utilized published data to estimate complication and recurrence rates from each treatment option. We obtained cost data from a chart review of patients treated with each approach at a single institution between 1995 and 2005. RESULTS: OBS yielded the lowest expected cost, $437 million per 100,000 women. COMB yielded the highest cost, at $2.93 billion per 100,000 women. VB yielded the highest 5-year quality adjusted survival, 86%. In a population of 100,000 women, VB would result in an additional 8200 quality adjusted survivors compared to OBS, at a cost of $65,900 per survivor. In contrast, EBRT and COMB result in either fewer survivors and/or greater costs when compared to OBS or VB. CONCLUSION: Routine use of adjuvant EBRT or COMB in the management of surgical stage I endometrial adenocarcinoma is not cost-effective. Compared to OBS, post-operative VB improves survival at a cost of $65,900 per survivor, supporting further investigation of this adjuvant therapy.

Cervical adenocarcinoma in situ: the predictive value of conization margin status.

OBJECTIVE: We evaluated the impact of conization margin status on outcomes of patients diagnosed with cervical adenocarcinoma in situ. STUDY DESIGN: A retrospective chart review identified patients at a University hospital from 1988-2006 with adenocarcinoma in situ (AIS) on conization. RESULTS: Seventy-four patients were included. Median follow-up was 26 months. Twenty-two of 74 patients (30%) had positive margins, 46 patients (62%) had negative margins, and 6 patients had indeterminate margins. Of patients with positive margins, 55% (12/22) were diagnosed with residual or recurrent disease, including 3 patients diagnosed with adenocarcinoma on hysterectomy. Thirteen percent of patients with negative conization margins (6/46) were diagnosed with residual or recurrent disease, including 2 patients diagnosed with adenocarcinoma during follow-up. Cold knife conization resulted in a significantly higher number of negative margins compared to other conization procedures (P = .013). CONCLUSIONS: Even with negative conization margins, women still face a risk of residual, recurrent, or invasive disease.

Use of cisplatin without desensitization after carboplatin hypersensitivity reaction in epithelial ovarian and primary peritoneal cancer.

OBJECTIVE: The purpose of this study was to evaluate the results of substituting cisplatin for carboplatin in women who experienced a carboplatin-associated hypersensitivity reaction while undergoing treatment for gynecologic cancers. STUDY DESIGN: Using a comprehensive data repository, we identified all epithelial ovarian cancer and primary peritoneal cancer patients who experienced a documented significant hypersensitivity reaction to carboplatin and were subsequently treated with cisplatin at our institution from 1995 to the present. We also performed a review of published case reports of similar patient management. RESULTS: We identified a total of 24 patients who met inclusion criteria. Eighteen patients (75%) tolerated cisplatin without any adverse events. Six patients (25%) eventually developed a reaction to cisplatin; none was life threatening, and only 1 required hospitalization. Twenty-three of the 24 patients (96%) tolerated at least 1 cycle of cisplatin. Of the 5 patients who initially tolerated cisplatin but eventually experienced a reaction, the mean number of cycles tolerated was 3.4. CONCLUSION: The use of cisplatin without desensitization is a reasonable approach for continuing platinum-based chemotherapy in patients with a significant carboplatin hypersensitivity reaction. Patients should be advised of risks and closely monitored, given published case reports of anaphylaxis.