Search

OBJECTIVE: Progression-free survival (PFS) is an important early efficacy endpoint in ovarian cancer (OC) and its relevance to patients should be assessed. PRIMA, a phase III trial, assessed niraparib in patients with OC; this post hoc analysis examined the relationship between disease progression in OC and health-related quality of life (HRQoL). METHODS: The PRIMA trial randomized patients with advanced OC responsive to first-line platinum-based chemotherapy to once daily maintenance oral niraparib or placebo. This post hoc analysis evaluated the impact of disease progression on HRQoL by comparing HRQoL at the last visit pre-progression to end of treatment (EoT), and after 4, 8, 12, and 24 weeks. Assessments included the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), the European Quality of Life Five Dimension Five Level questionnaire (EQ-5D-5L) and EQ Visual Analogue Scale (EQ-VAS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC-QLQ-C30), and the EORTC Quality of Life Questionnaire Ovarian Cancer module (EORTC-QLQ-OV28). RESULTS: This post hoc analysis included 733 patients. Mean FOSI, EQ-5D-5L, and EQ-VAS scores deteriorated from last visit pre-progression to EoT and remained low up to 24-week follow-up. Least squares mean changes from last visit pre-progression to EoT were -2.1 (95% confidence interval -2.4, -1.7) for FOSI, -4.6 (-5.6, -3.5) for the EQ-5D-5L index, and -7.9 (-9.6, -6.3) for EQ-VAS. CONCLUSIONS: Disease progression negatively impacted HRQoL in patients with OC. PFS is clinically relevant, and prolonging PFS may preserve HRQoL. ispartof: GYNECOLOGIC ONCOLOGY vol:166 issue:3 pages:494-502 ispartof: location:United States status: published

To determine whether gastrointestinal (GI) disorder insurance claims in the year preceding a diagnosis of ovarian cancer (OC) lead to differing treatment allocations. The hypothesis is that GI disorders may be indicative of advanced OC.This retrospective study identified patients with newly diagnosed OC from January 2015 to January 2019 in the IBM® MarketScan® US commercial insurance and Medicare databases. Analysis was limited to patients with primary or interval debulking surgery or chemotherapy, with or without GI claims in the year prior to diagnosis, with commercial or Medicare coverage for ≥12 months prior and ≥1 month after the index date. Patients were compared in terms of the odds of treatment with neoadjuvant chemotherapy (NCT) or primary debulking surgery (PDS) (logistic regression analysis). Median treatment-free interval in the subset of patients with antineoplastic treatment was compared (Kaplan-Meier analysis).Of the 6286 patients, 22% had a diagnosis of ≥1 GI disorder before their OC diagnosis. Of these patients, 39% were diagnosed with a GI disorder between 6 and 12 months before OC diagnosis and 61% were diagnosed6 months prior. Women with a GI diagnosis were more likely to undergo NCT than PDS (odds ratio [OR], 1.37; P0.0001); this remained significant even when controlling for age, region, insurance plan type, and index year (OR, 1.24; P = 0.001).In this database, ≈25% of women with OC had a GI claim within the past year and were more likely treated with NCT, an indicator of more advanced disease with a worse prognosis. This suggests that OC should be considered in the differential diagnosis among women with GI complaints, which could alter treatment allocation.

Poly(ADP-ribose) polymerase (PARP) inhibitors have rapidly emerged as a new class of daily oral chemotherapeutic agents that have the potential to dramatically alter the way in which primary peritoneal, fallopian tube and ovarian cancers are treated. However, the management of nausea and vomiting, the most common toxicities incurred by these agents, remains poorly understood. The purpose of this review is to provide an overview of current guidelines, antiemetic agents and management steps for patients experiencing nausea and vomiting associated with the use of PARP inhibitors.

Objective This study aims to describe the real-world experience, including the clinical and financial burden, associated with PARP inhibitors in a large community oncology practice. Methods Retrospective chart review identified patients prescribed olaparib, niraparib or rucaparib for maintenance therapy or treatment of recurrent ovarian, primary peritoneal or fallopian tube cancer across twelve gynecologic oncologists between December 2016 and November 2018. Demographic, financial and clinical data were extracted. One PARP cycle was defined as a single 28-day period. For patients treated with more than one PARPi, each course was described separately. Results A total of 47 patients and 506 PARP cycles were identified (122 olaparib, 24%; 89 rucaparib, 18%; 294 niraparib, 58%). Incidence of grade ≥ 3 adverse events were similar to previously reported. Toxicity resulted in dose interruption, reduction and discontinuation in 69%, 63% and 29% respectively. Dose interruptions were most frequent for niraparib but resulted in fewer discontinuations (p-value 0.01). Mean duration of use was 7.46 cycles (olaparib 10.52, rucaparib 4.68, niraparib 7.34). Average cost of PARPi therapy was $8018 per cycle. A total of 711 phone calls were documented (call rate 1.4 calls/cycle) with the highest call volume required for care coordination, lab results and toxicity management. Conclusions Although the toxicity profile was similar to randomized clinical trials, this real-world experience demonstrated more dose modifications and discontinuations for toxicity management than previously reported. Furthermore, the clinical and financial burden of PARP inhibitors may be significant and future studies should assess the impact on patient outcomes.

Health disparities have been found among patients with gynecologic cancers, with the greatest differences arising among groups based on racial, ethnic, and socioeconomic factors. Although there may be multiple social barriers that can influence health disparities, another potential influence may stem from healthcare system factors that unconsciously perpetuate bias toward patients who are racially and socioeconomically disadvantaged. More recent research suggested that providers hold these implicit biases (automatic and unconscious attitudes) for stigmatized populations with cancer, with emerging evidence for patients with gynecologic cancer. These implicit biases may guide providers' communication and medical judgments, which, in turn, may influence the patient's satisfaction with and trust in the provider. This narrative review consolidated the current research on implicit bias in healthcare, with a specific emphasis on oncology professionals, and identified future areas of research for examining and changing implicit biases in the field of gynecologic oncology.

Objective Implicit prejudice and stereotyping may exist in health care providers automatically without their awareness. These biases can correlate with outcomes that are consequential for the patient. This study examined gynecologic oncology care providers' implicit prejudice and stereotyping toward cervical cancer. Methods Members of professional gynecologic oncology organizations were asked to complete two Implicit Association Tests to determine if they implicitly associate cervical cancer with feelings of anger (prejudice) and beliefs about culpability for the disease (stereotypes), compared to ovarian cancer. Linear models and Student t-tests examined average levels of implicit bias and moderators of the implicit bias effects. Results One-hundred seventy-six (132 female, 43 male, 1 nonresponse; X ¯ age = 39.18 years, SDage = 10.58 years) providers were recruited and the final sample included 151 participants (93 physicians and 58 nurses, X ¯ age = 38.93, SDage = 10.59). Gynecologic oncology providers showed significant levels of implicit prejudice, X ¯ = 0.17, SD = 0.47, 95% CI: (0.10, 0.25), toward cervical cancer patients. They also showed significant levels of implicit stereotyping of cervical cancer patients, X ¯ = 0.15, SD = 0.42, 95% CI: (0.08, 0.21). Whereas physicians did not demonstrate significant levels of implicit bias, nurses demonstrated greater levels of implicit prejudice and implicit stereotyping. Providers without cultural competency/implicit bias training demonstrated greater bias than those who had completed such training (p Conclusions This study provides the first evidence that gynecologic oncology providers hold implicit biases related to cervical cancer. Interventions may be designed to target specific groups in gynecologic oncology to improve interactions with patients.

IntroductionTo describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab.MethodsSummarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240.ResultsOf the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain.DiscussionPatients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.

Inflammatory myofibroblastic tumors (IMTs) are spindle cell neoplasms of intermediate (borderline) biologic potential with tendency for local recurrence but low risk of metastasis. They affect children more than adults. The most common sites of involvement are the lung, soft tissue, peritoneum, bladder, and less commonly the gynecologic tract. IMTs are characterized by spindle to epithelioid cells with myofibroblastic differentiation, some degree of smooth muscle differentiation, myxoid stroma and usually associated with brisk lymphoplasmacytic infiltrates. In about half of the cases, IMTs are associated with rearrangements of the anaplastic lymphoma kinase (ALK) gene located at chromosome 2p23. The ALK rearrangement can be detected by immunohistochemistry for ALK protein expression (mostly cytoplasmic with or without perinuclear accentuation) or by fluorescent in situ hybridization (FISH) using dual-color break-apart probes for which the typical pattern is seen as split 3' end (red) and 5' end (green) probe signals in addition to single normal, unsplit red-green signal pair (yellow). Herein we describe a case of uterine IMT initially misdiagnosed intraoperatively as leiomyoma which showed sparse lymphocytic infiltrates, positive ALK expression by immunohistochemistry, a predominantly atypical FISH signal pattern (1 yellow and 1 red signal only) and few typical signal patterns (1 yellow, 1 red, and 1 green signal) in a smaller population of tumor cells. The RNA sequencing showed a recently described DES-ALK fusion transcript in the tumor cells, suggesting an intrachromosomal inversion and deletion as the likely underlying mechanism for the atypical FISH pattern. Familiarity with the unusual morphology and atypical FISH pattern is crucial given that this tumor has an activating ALK rearrangement and may benefit from targeted tyrosine kinase inhibitors in the future.

Olaparib is a poly(ADP-ribose) polymerase inhibitor that received accelerated approval from the US Food and Drug Administration as monotherapy for patients with germline BRCA mutations and ovarian cancer treated with three or more prior lines of chemotherapy. This article summarizes the mechanism of poly(ADP-ribose) polymerase inhibition, therapeutic profile and uses of olaparib, and current and ongoing literature pertaining to olaparib in advanced ovarian cancer.

OBJECTIVE To assess whether there is an association of patient sociodemographic factors with stage at diagnosis, treatment, and overall survival in patients with vulvar cancer in the National Cancer Database. METHODS This was a retrospective cohort study of patients with primary squamous vulvar carcinoma identified from the National Cancer Database (1998-2004). Multivariate logistic regression was conducted to examine risk factors associated with advanced-stage (stage III or IV) disease at diagnosis. Multivariable Cox regression models were performed to explore risk factors associated with 5-year all-cause mortality. RESULTS Of 11,153 patients, 42.3% (n=4,713) were diagnosed with stage I disease, 24.6% (n=2,745) stage II, 22.9% (n=2,556) stage III, and 10.2% (n=1,139) stage IV. Advanced stage was significantly associated with older age, nonprivate insurance, and treatment at a lower case volume center (P

Objective Genetic predisposition to ovarian cancer is well documented. With the advent of next generation sequencing, hereditary panel testing provides an efficient method for evaluating multiple genes simultaneously. Therefore, we sought to investigate the contribution of 19 genes identified in the literature as increasing the risk of hereditary breast and ovarian cancer (HBOC) in a BRCA1 and BRCA2 negative population of patients with a personal history of breast and/or ovarian cancer by means of a hereditary cancer panel. Methods Subjects were referred for multi-gene panel testing between February 2012 and March 2014. Clinical data was ascertained from requisition forms. The incidence of pathogenic mutations (including likely pathogenic), and variant of unknown significance were then calculated for each gene and/or patient cohort. Results In this cohort of 911 subjects, panel testing identified 67 mutations. With 7.4% of subjects harboring a mutation on this multi-gene panel, the diagnostic yield was increased, compared to testing for BRCA1 and BRCA2 mutations alone. In the ovarian cancer probands, the most frequently mutated genes were BRIP1 (n=8; 1.72%) and MSH6 (n=6; 1.29%). In the breast cancer probands, mutations were most commonly observed in CHEK2 (n=9; 2.54%), ATM (n=3; 0.85%), and TP53 (n=3; 0.85%). Conclusions Although further studies are needed to clarify the exact management of patients with a mutation in each gene, this study highlights information that can be captured with panel testing and provides support for incorporation of panel testing into clinical practice.

Combination vascular-targeted therapies (VTTs) represent a promising approach for patients with platinum-resistant recurrent ovarian cancer (OC). VTTs include two mechanistically distinct classes of agents: anti-angiogenic agents (AAs) and vascular-disrupting agents (VDAs). AAs suppress growth of new tumor vasculature through inhibition of vascular endothelial growth factor (VEGF) and other pro-angiogenic molecules. Bevacizumab, a monoclonal antibody that binds to VEGF, has improved progression-free survival (PFS) when given with chemotherapy in patients with advanced OC. VDAs target the established tumor vascular network, inducing vessel occlusion, shutdown of circulation, and widespread necrosis within the tumor interior - a region often resistant to conventional chemotherapy and radiation. Tubulin-binding VDAs such as BNC105P, ombrabulin, and combretastatin A4-phosphate (CA4P) have been studied for the treatment of OC. These agents act by binding tubulin in the endothelial cells of tumor vessels, triggering cytoskeletal disruption, altering cellular shape, and destabilizing cell-cell junctions, which lead to increased vascular leakage and, ultimately, to disruption of blood flow. Fundamental differences between the vascular networks of tumors and those of normal tissues allow these agents to selectively reduce tumor circulation while having little effect on non-malignant tissues. Animal studies and clinical trials show enhanced efficacy when VDAs are combined with chemotherapy as well as AAs. The latter combination allows targeting of different aspects of the tumor vasculature, a strong rationale for combining these two drug classes into a single regimen. CA4P is the only VDA in active development for OC. In a phase II trial of patients with recurrent OC, CA4P added to bevacizumab improved PFS compared with bevacizumab alone. The phase II, placebo-controlled PAZOFOS trial (NCT02055690) is evaluating the effects of CA4P plus the anti-angiogenic agent pazopanib in recurrent OC. FOCUS, a phase II/III, placebo-controlled trial (NCT02641639), is currently evaluating CA4P plus bevacizumab and chemotherapy in platinum-resistant OC.

Objectives To present responses to sexual function items contained within the quality of life (QOL) survey of the Gynecologic Oncology Group LAP2 study, to investigate associations between sexual function and other factors (such as relationship quality and body image), and to explore patterns of response in patients with endometrial cancer. Methods Participants enrolled in the LAP2 QOL study arm completed a self-report QOL survey, which contained sexual function items, before surgery, and at 1, 3, and 6 weeks and 6 months after surgery. Responses to sexual function questions were classified into 3 patterns—responder, intermittent responder, and nonresponder—based on whether the sexual function items were answered when the QOL survey was completed. Results Of 752 patients who completed the QOL survey, 225 completed the sexual function items within the QOL survey, 224 responded intermittently, and 303 did not respond at all. No significant differences of sexual function were found between the patients randomized to laparoscopy compared to laparotomy. Among those who responded completely or intermittently, sexual function scores declined after surgery and recovered to presurgery levels at 6 months. Sexual function was positively associated with better quality of relationship (P Conclusion Our findings suggest that younger patients, those who were married, and those who had quality relationships were more likely to answer the sexual function items and have better quality of sexual function. Factors such as age, relationship quality, body image, and pain may place women with endometrial cancer at risk for sexual difficulties in the immediate recovery period; however, sexual function improved by 6 months postoperatively in our cohort of patients with early-stage endometrial cancer.

Background After platinum and taxane chemotherapy, with or without bevacizumab, active regimens for advanced or recurrent cervical cancer are lacking. Our objective was to review a single institution experience in treating recurrent, refractory cervical cancer with nano-particle albumin bound (NAB) paclitaxel with or without bevacizumab. Methods This retrospective case series was conducted in accordance with the regulations set forth by the Institutional Review Board at St. Joseph’s Hospital and Medical center. The chemotherapy log at the outpatient infusion center at the University of Arizona Cancer Center was reviewed to identify all advanced cervical cancer patients treated with NAB-paclitaxel from November 2011 until February 2015. The following data points were extracted from patient charts: demographic information, number of cycles, progression free survival (PFS), overall survival (OS), dose reductions and dose-limiting toxicities. In addition the average number of treatment cycles and age at recurrence were calculated. Results A total of 12 subjects were identified as receiving treatment with NAB-paclitaxel. Mean age at time of recurrence was 47.2 years (36–55). Nine subjects had squamous cell histology and three subjects had adenocarcinoma histology. All subjects had failed treatment with platinum and taxane, or platinum and topotecan chemotherapy. Two subjects were lost to follow up. The Median number of cycles of NAB-paclitaxel was 6.5 (2–19). The total number of cycles of NAB-paclitaxel in the study population was 65. Seven subjects were treated in combination with bevacizumab. Of these, three subjects are still alive and one subject is currently receiving active treatment with NAB-paclitaxel. The median PFS and OS for all subjects that met mortality endpoint was 4.8 months and 8.9 months (n = 7), respectively. One subject discontinued NAB-paclitaxel secondary to peripheral neuropathy, and one subject developed a vesicovaginal fistula while obtaining combination NAB-paclitaxel and bevacizumab therapy. Conclusions NAB-paclitaxel with or without bevacizumab is tolerable and potentially active in treating recurrent cervical cancer after failing platinum-taxane or topotecan chemotherapy. This small case series deserves confirmation through prospective clinical trials.

Despite improvements in our understanding of the progression of cervical intraepithelial neoplasia (CIN) to invasive cancer, cervical cancer is the leading cause of cancer deaths in women of developing nations [1–3]. Although the overall incidence in the United States has decreased dramatically over the years, patients who belong to a certain minority and/or low-income populations remain at high risk for cervical cancer. This may be due to a lack of access to health care and/or a lack of compliance once access has been granted. Disparities are known to exist among the US population in relation to incidence rates of cervical cancer, including racial and ethnic disparities [1, 4], especially in African American and Latina women [5]; age [6]; and socioeconomic status such as income, health care access, and education level [7, 8]. There are also discrepancies in prevention, screening, and treatment [1, 9]. Thus, an effort should be made to design and implement effective intervention strategies to improve compliance among high-risk patients. Originating from a high-risk human papillomavirus (HPV) infection, invasive cervical cancer may take years to tens of years to progress, with potential opportunities to identify and treat CIN accordingly [10]. For women with persistently abnormal Pap test results, follow-up is based on the American Society for Colposcopy and Cervical Pathology (ASCCP) 2006 Consensus Guidelines, including screening via Pap test, then colposcopy-directed biopsy and/or elimination of cancer precursors through excisional procedures and continued surveillance and follow-up of care [11, 12]. This requires multiple visits to the doctor to avoid missed disease. Thus, noncompliance with any of these procedures may increase the risk of advanced CIN and/or the development of invasive cervical cancer [13–15]. Although research has revealed that progression to invasive cervical cancer or even the most severe CIN (CIN 3) does not occur in most HPV-infected women owing to regression of the infection [16–18], visits to the gynecologist are still necessary to detect advanced CIN and/or changes in cervical cells. It is likely that uninsured patients who do go on to develop a preventable disease like cervical cancer cause significant drain of public resources. This could include such expenses as radical surgery/chemoradiation (if curable) or possibly multiple emergency room visits, imaging, and palliative therapies (if incurable). Funding colposcopy clinics in areas of high-risk patients (i.e., areas of patients with low socioeconomic status) may help to offset the cost of caring for even one patient that develops advanced disease that would otherwise have been preventable. Furthermore, even though one may argue that most cases of CIN 1 and CIN 2 regress spontaneously, ultimately, some develop a worse preinvasive disease necessitating excisional procedures that may affect a patient's fertility and pregnancy outcomes, which are also likely impacting cost [19]. Thus, the objective of this study was to describe non-compliance with triage of abnormal Pap smear results and colposcopy in an inner-city, primarily government-funded program. Through exploration of risk factors associated with better follow-up, the goal was to be able to better define the patients at highest risk for noncompliance.

Objective To explore feasibility of measuring tumor blood flow as marker for antiangiogenic activity using DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging) in women with recurrent EOC/PPC treated with bevacizumab. Methods In a phase II study, 62 patients with recurrent/persistent EOC/PPC were treated with bevacizumab (15mg/kg IV q21days) until disease progression. DCE-MRI was performed pre-cycle 1 and 4 of bevacizumab. Images were analyzed retrospectively by a single experienced blinded radiologist. Tumor and muscle contrast enhancement was measured by region of interest signal intensity within the same DCE-MRI images. Flow rates were obtained with concentration of dye as a function of time. Relative blood flow (RBF) was calculated as a ratio of average blood flow into tumor to muscle tissue. Associations between RBF and characteristics/outcomes were explored. Results Sixty-two patients were eligible for study. Unfortunately, only 14 (23%) patients had imaging data available for analysis at baseline and 13 of those same patients (21%) had imaging data available for analysis pre-cycle 4. The RBF distribution was similar from pre-cycle 1 to 4. RBF remained stable for the majority of the cases (median change -0.21). Baseline RBF was not significantly associated with being progression-free at 6months, microvessel density, 17month overall survival, tumor response, or platinum sensitivity. However, increases in blood flow rates were associated with likelihood to be progression-free at 6months. Conclusion Functional imaging of tumor blood flow is a potential research endpoint that may be explored further. Consideration should be given to timing of endpoint and standardizing the technique.

article i nfo Purpose. To determine associations between pretreatment health-related quality of life subscales with progression-free (PFS) and overall survival (OS) in advanced and recurrent cervical cancer. Patients and Methods. Patients included those participating in Gynecologic Oncology Group advanced or recurrent cervical cancer phase III treatment trials who completed the Functional Assessment of Cancer Ther- apy for patients with cervical cancer (FACT-Cx) and a single-item pain scale at study entry. The FACT-Cx in- cludes five domains: physical (PWB), emotional (EWB), social (SWB), functional well being (FWB), and cervix cancer subscale (CCS). A high quality of life (QoL) score reflects better QoL. After stratifying by protocol and adjusting for patient and disease characteristics, a Cox proportional hazards model was fitted for each subscale as a continuous variable. If statistically significant, (pb0.05), an analysis on mean item scores (MIS) was performed. Results. Nine-hundred-ninety-one patients were enrolled from 1997 to 2007. The majority (87%) had re- current disease. After adjustment for covariates and predictors, only the PWB domain (better physical QoL) was associated with improved OS (HR 0.96 95% CI 0.95-0.98; pb0.001). When classifying patients based on the MIS of each subscale, the patients with the lowest risk of death were likely to report less compromised QoL (MIS>3) for PWB (HR 0.44 (0.33-0.58) Pb0.001), FWB (0.49 (0.38-0.62) Pb0.001), and CCS (0.48 (0.38-0.61) Pb0.001). Conclusion. The pretreatment patient-reported PWB as measured by the PWB subscale of the FACT-Cx, is significantly associated with survival in advanced cervical cancer trials, even after controlling for known prognostic factors.

Objective. Minority and low-income cancer patients are underrepresented in clinical trials, contributing to diminished access to state-of-the-art care and disparities in cancer outcomes including survivorship issues. In cervical cancer, there is a disproportionate disease burden among minority and underserved women and persistent quality of life disruption. We encountered significant challenges in both recruitment and retention in a randomized biobehavioral clinical trial for cervical cancer survivors, identified through California Cancer Registries, leading to this investigation. Methods. To determine differential rates of accrual and retention, data from our trial are analyzed using descriptive statistics, logistic regression and multivariate analysis of variance. Ethnic differences in associations between covariables and attrition rates were tested by interaction factors. Process evaluation and focus group data were obtained to inform improvement strategies. Results. Of eligible subjects with viable phone numbers, 29% enrolled and 71% actively or passively refused. Enrolled Hispanic women were more likely to have less education ( p p =0.003), and more children ( p =0.028). The dropout rate was associated with less education ( p =0.012), foreign-birth ( p =0.061), speaking Spanish in the home ( p =0.012). Reported reasons for active refusal were ‘too busy' for all women, ‘too emotional' for non-Hispanic women, ‘too ill' and phlebotomy for Hispanic women. Subsequent focus groups identified specific strategies to improve study materials. Conclusion. Although population-based recruitment of minority and underserved cancer patients continues to be a challenge, specific sociodemographic and disease variables can predict accrual difficulties. The information herein, taken together with disease and culturally relevant strategies, can be useful when recruiting underserved cancer survivors.

Objective.: To identify patient characteristics which predict receipt of neoadjuvant chemotherapy (NCT) versus standard therapy (ST) in metastatic ovarian cancer. Methods.: A retrospective matched case control study was conducted of 52 women treated with NCT compared to 104 women who received standard treatment from 1996 to 2007. The t test was used for comparison of means between the groups, and the χ2test was used for categorical data. Multivariable analysis was performed with logistic regression models and only two-tailed analyses with a P value < 0.05 were considered statistically significant. Results.: Age, employment and marital status, and insurance alone did not affect treatment allocation (P = NS). However, non-Hispanic White (NHW) patients were more as likely to receive ST (P < 0.05). When insurance was stratified by ethnicity, NHW patients were twice as likely to have private insurance (OR = 2.29, CI = 1.16-4.53). Furthermore, medically compromised (MC) patients who were NHW were almost three times more likely to receive ST (OR = 2.72, CI = 1.02-5.00). In multivariate analysis, only MC and publically funded women were more likely to receive NCT (OR 3.83 CI = 1.35-11.11); P = 0.01). During surgery, patients receiving NCT were found to have smaller tumors and less ascites, and were more likely to be optimally debulked with lower estimated blood loss and shorter hospital stays. The median survival for ST was 55.8 months versus 26 months for NCT (P < 0.001). Conclusions.: Non-clinical factors such as publically funded status and non-Hispanic White race may influence the allocation of NCT for women with metastatic ovarian cancer. © 2009 Elsevier Inc. All rights reserved.

The rates of cervical cancer in the United States are low in comparison with developing nations. Whereas the Papanicolaou smear has performed well in terms of dectecting both precursors of squamous cell carcinoma and squamous cell carcinoma of the cervix, this test has been less successful at identifying those women with the highest-risk premalignant disease. The use of human papillomavirus testing has also contributed to the improved sensitivity of screening for cervical cancer. In light of this, the colposcopy clinic retains high referral rates yet has poor diagnostic accuracy. Unfortunately, patients are triaged to follow-up for abnormal Papanicolaou smears based on algorithms that rely on the less evidence-based techniques of colposcopy. Therefore, the need to improve the specificity of colposcopic-guided biopsy remains. The colposcopic procedure is highlighted in this review and evaluated in terms of current literature on technique, the colposcopic impression, cervical biopsy, and methods proposed to enhance appreciation of the highest-risk lesions. By outlining certain flaws in technique and discussing the proposal of new tests to supplement the current standard of care, this review aimed to highlight the need for future research to maintain sensitivity but improve the specificity of colposcopy.

ObjectiveThis study aimed to describe pretreatment patient characteristics and baseline quality-of-life scores as they relate to the development of grade 3 or 4 toxicity in patients receiving chemotherapy for advanced/recurrent cervical cancer.MethodsThe study sample was drawn from Gynecologic Oncology Group protocols 179 and 204. Grade 3 or 4 toxicities were considered in 4 specified categories as follows: peripheral neuropathy, fatigue, hematological, and gastrointestinal (GI). The data variables explored included age, stage, pretreatment radiation, performance status (PS) at treatment initiation, and baseline Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) score. A logistic regression model was developed with various adverse events as binary (0/1) outcomes.ResultsSix hundred seventy-three patient-reported questionnaires were used in the analyses. At baseline, pain was the most severe patient-reported symptom. Baseline line-item patient concerns did demonstrate specific correlations with the development of individual toxicities. In 401 patients who were enrolled on Gynecologic Oncology Group 204 (fatigue not measured on 179), a worse PS predicted the development of grade 3 or 4 fatigue (odds ratio, 2.78; 95% confidence interval, 1.66–4.68). Exposure to previous radiation, treatment regimen, and a worse FACT-Cx score were associated with the reporting of both grade 3 or 4 leukopenia (P< 0.05) and anemia (P< 0.0005). Performance status and treatment regimen (P< 0.05) were associated with the development of grade 3 or 4 thrombocytopenia. Age and treatment regimen (P< 0.05) were associated with the development of grade 3 or 4 neutropenia. The FACT-Cx score (P= 0.0016) predicted grade 3 or 4 GI toxicity.ConclusionsThe development of fatigue, hematological, and GI toxicity might be predictable based on factors other than treatment assignment such as age, PS, and patient-reported quality-of-life measurement.

article i nfo The human microbiome is the collection of microorganisms in the body that exist in a mutualistic relationship with the host. Recent studies indicate that perturbations in the microbiome may be implicated in a number of diseases, including cancer. More specifically, changes in the gut and vaginal microbiomes may be associated with a variety of gynecologic cancers, including cervical cancer, uterine cancer, and ovarian cancer. Current re- search and gaps in knowledge regarding the association between the gut and vaginal microbiomes and the de- velopment, progression, and treatment of gynecologic cancers are reviewed here. In addition, the potential use of probiotics to manage symptoms of these gynecologic cancers is discussed. A better understanding of how the microbiome composition is altered at these sites and its interaction with the host may aid in prevention, op- timization of current therapies, development of new therapeutic agents and/or dosing regimens, and possibly limit the side effects associated with cancer treatment.

Malignant eccrine spiradenoma is a rare skin tumor of sweat gland origin. We present the first reported case of this tumor in the female genitalia. Due to the rarity of this tumor, there has yet to be an established standard of care. The present case is that of a 41-year-old woman with malignant eccrine spiradenoma of the periclitoral region. She had an 18-month history of a recurrent, painful mass adjacent to the clitoris. Her diagnosis was made after excision of the cystic tumor. The patient then underwent a partial radical vulvectomy with bilateral sentinel lymph node sampling. As malignant eccrine spiradenoma is a rare tumor, no standard care exists for treatment and postoperative management. Based on our review of the literature, wide local excision appears to be the preferred initial treatment. Furthermore, adjuvant chemotherapy and/or radiation does not seem to improve survival in patients with advanced or recurrent cancer. Although lymph node sampling and/or lymphadenectomy is frequently reported in the treatment of this tumor, hematogenous metastasis can also occur. Therefore, these patients require close postoperative follow-up for recurrent disease.

To describe characteristics associated with neurotoxicity (NT) in advanced ovarian cancer patients treated on Gynecologic Oncology Group 218 and examine effect of substituting docetaxel for paclitaxel in these patients.The development of NT was defined as Common Toxicity Criteria grade (G)≥1. The association between substitution with docetaxel and NT improvement was explored with generalized estimating equations adjusting for treatment cycle and NT grading at previous cycle.Of 1864 evaluable patients, 1329 (71%) developed G≥1 NT during the study. Nearly half appeared within the first two cycles of chemotherapy, with 31% experiencing G≥2. Older patients or those with worse quality of life (QoL) scores at baseline (p0.05) were more likely to experience NT. One-hundred-six patients received docetaxel as substitute for paclitaxel. Of them, 47 patients started with docetaxel at cycle one due to reaction to paclitaxel (n=32), fear of NT (n=4), and other reasons (n=11), whereas 59 patients switched to docetaxel during cycle 2-6 due to NT (n=32), reaction to paclitaxel (n=19), and other reasons (n=8). Although the protocol instructed otherwise, the majority continued paclitaxel despite G≥2 NT symptoms. There was no evidence that substitution with docetaxel improved NT (Odds Ratio: 1.57; 95% CI 0.98-2.54; p0.05). Of 59 patients who switched to docetaxel, only seven (12%) discontinued taxane prior to chemotherapy completion. A roughly equal chance of worsening NT was reported on paclitaxel (6%) as on docetaxel (5%).Age and worse QoL at baseline are associated with NT. Substitution of docetaxel did not improve NT symptoms.

Background To determine the protein expression profile (PEP) of primary and recurrent ovarian cancer patients in order to predict therapeutic targets for chemotherapy. Methods Tissue samples were submitted for PEP in two formats, including formalin-fixed paraffin-embedded tissue for immunohistochemistry (IHC) and fresh frozen tissue for oligonucleotide microarray (MA) gene expression assays. Specimens were analyzed for 18 protein markers and 88 MA genes. A series of Generalized Linear Models (GLM) was used to predict the proportion of positive results by histology for each biomarker. Results Four hundred and twenty-eight specimens were analyzed for IHC and 67 specimens for MA analysis. The majority of specimens, 82%, were serous histology and 35.3% of specimens were poorly differentiated. Sixty percent of specimens were advanced stage, 62% were from a primary diagnosis, and 53% were obtained from a metastatic site. BCRP, ER, MGMT, and RRM1 proteins were overexpressed in 85%, 47%, 93%, and 47% of serous carcinomas, respectively. The MGMT and RRM1 biomarkers were significantly overexpressed in serous (p

© 2014 Elsevier Inc. All rights reserved. Introduction The purpose of this study is to identify factors that are associated with poor quality of life (QOL) among cervical cancer survivors.Methods Patients identified through the California Cancer Registry were recruited to participate in a randomized counseling intervention. Patient-reported outcomes (PROs) were collected at study baseline (9-30 months post-diagnosis) and subsequent to the intervention. Multivariable linear models were used to identify independent factors associated with poor baseline QOL.Results Non-Hispanic (N = 121) and Hispanic (N = 83) women aged 22-73 completed baseline measures. Approximately 50% of participants received radiation therapy with or without chemotherapy. Compared to the US population, cervical cancer patients reported lower QOL and significantly higher levels of depression and anxiety (26% and 28% > 1 SD above the general population means, respectively). Among those in the lowest quartile for QOL, 63% had depression levels > 1 SD above the mean. In addition, treatment with radiation ± chemotherapy (p = 0.014), and self-reported comorbidities predating the cancer diagnosis (p < 0.001) were associated with lower QOL. Sociodemographic characteristics explained only a small portion of variance in QOL (r2= 0.23). Persistent gynecologic problems, low social support, depression, somatization, less adaptive coping, comorbidities, sleep problems and low education were all independently associated with low QOL in multivariate analysis (r2= 0.74).Conclusion We have identified key psychological and physical health factors that contribute significantly to poor quality of life subsequent to definitive cancer treatment. The majority of these factors are amenable to supportive care interventions and should be evaluated at the time of primary treatment.

Supplemental digital content is available in the text., Objective Integration of carcinogenic human papillomaviruses (HPVs) into the host genome is a significant tumorigenic factor in specific cancers including cervical carcinoma. Although major strides have been made with respect to HPV diagnosis and prevention, identification and development of efficacious treatments for cervical cancer patients remains a goal and thus requires additional detailed characterization of both somatic events and HPV integration. Given this need, the goal of this study was to use the next generation sequencing to simultaneously evaluate somatic alterations and expression changes in a patient’s cervical squamous carcinoma lesion metastatic to the lung and to detect and analyze HPV infection in the same sample. Materials and Methods We performed tumor and normal exome, tumor and normal shallow whole-genome sequencing, and RNA sequencing of the patient’s lung metastasis. Results We generated over 1.2 billion mapped reads and identified 130 somatic point mutations and indels, 21 genic translocations, 16 coding regions demonstrating copy number changes, and over 36 genes demonstrating altered expression in the tumor (corrected P < 0.05). Sequencing also revealed the HPV type 18 (HPV-18) integration in the metastasis. Using both DNA and RNA reads, we pinpointed 3 major events indicating HPV-18 integration into an intronic region of chromosome 6p25.1 in the patient’s tumor and validated these events with Sanger sequencing. This integration site has not been reported for HPV-18. Conclusions We demonstrate that DNA and RNA sequencing can be used to concurrently characterize somatic alterations and expression changes in a biopsy and delineate HPV integration at base resolution in cervical cancer. Further sequencing will allow us to better understand the molecular basis of cervical cancer pathogenesis.

To explore data from the National Cancer Database to identify pretreatment patient characteristics associated with receipt of nonstandard treatment for advanced ovarian cancer.Between 2003 and 2006, there were 47,390 patients with ovarian cancer registered with the National Cancer Database. Variables included demographics, insurance, Charlson comorbidity score, zip income, and facility characteristics. Multivariable log binomial regression analyses were performed to assess factors associated with nonstandard care.Among the 47,390 patients, 27,045 (81%) were stage IIIC or IV. After excluding patients with missing treatment information (n=1,129 [2.38%]), 13,789 (53.21%) had received standard treatment. In multivariable analyses, uninsured and Medicaid-insured patients were less likely to receive standard treatment as compared with privately insured patients (relative risk 0.88, 95% confidence interval [CI] 0.83-0.93 and relative risk 0.91, 95% CI 0.86-0.95, respectively). African Americans and Hispanics were also less likely to receive standard treatment (relative risk 0.87, 95% CI 0.83-0.92 and relative risk 0.89, 95% CI 0.84-0.94, respectively). Patients with a Charlson comorbidity score of 2+ were less likely to receive standard care (relative risk 0.74, 95% CI 0.68-0.80). Treatment at a community cancer hospital compared with a teaching hospital was also less likely to be associated with standard treatment (relative risk 0.83, 95% CI 0.80-0.87).In this large multi-institutional cohort, approximately 47% of patients with stage IIIC and IV ovarian cancer did not receive standard treatment. Pretreatment patient characteristics such as race, insurance status, age, Charlson comorbidity score, and facility type were associated with nonstandard treatment.

Objective. To examine the impact of race and insurance on survival among a large cohort of uterine cancer patients from the National Cancer Database (NCDB). Methods. Women diagnosed with stages I–III uterine cancer between 2000 and 2001 were selected from the NCDB. Kaplan–Meier (KM) and multivariate Cox proportional hazards were used to estimate 4year survival rates and hazard ratios (HR) and 95% confidence intervals (CIs), respectively. Results. Among the 39,510 evaluable patients, African Americans had a higher risk of death compared to whites (HR=1.43 95% CI 1.31–1.56) after adjusting for age, clinical and facility factors and zip code level education. After additional adjustment for treatment, the risk death decreased among African Americans (HR=1.33 95%CI 1.21–1.46) and subsequent adjustment for insurance further reduced the hazard of death (HR=1.28 95% CI 1.17–1.40). Patients with insurance other than private had an increased risk of death (uninsured HR=1.44 95% CI 1.20–1.72, Medicaid HR=1.70, 95% CI 1.46–1.99, Medicare among patients aged 18–64 HR=2.49, 95% CI 2.10–2.95, Medicare among patients aged 65–99 HR=1.22, 95% 1.11–1.34). Conclusions. The largest contributors to African American/white survival disparities in this study were clinical factors, including stage at diagnosis, grade and histopathology. Patients without private health insurance had worse uterine cancer survival that may be improved through future health care reform aimed at improving access to preventive services and adequate treatment.

Objective. Primary cytoreductive surgery is well accepted in the initial management of ovarian cancer with a goal of maximal tumor reduction. The role of cytoreductive surgery at disease recurrence is controversial and guidelines are not standardized. We aimed to review cases of women with recurrent ovarian cancer who were collaboratively managed by two teams of oncologic surgeons with different areas of surgical expertise. Methods. A list of 616 patients with recurrent ovarian cancer from 1995 to 2009 was generated at a single institution. 20 cases of recurrent ovarian cancer were identified that were managed collaboratively. Data collected included date of diagnosis, initial treatment, recurrence date, location and number of sites of recurrence, secondary cytoreductive procedure performed, residual disease after surgery, pre-operative status, post-operative course, and pathologic findings. Results. Of the 20 cases that fit eligibility criteria, 11 were completely resected, 5 were incompletely resected, and 4 were biopsied only. Median disease-free interval following primary surgery was 18months (6–147). Median interval from diagnosis to collaborative cytoreduction was 63months (13–170). Our patients had metastatic disease to the liver (11), lymph nodes (8), the diaphragm (7), other locations including colon, pancreas, lung, adrenal, kidney (9). Two patients had additional miliary disease. All patients underwent joint surgical management by gynecologic and surgical oncologists. There were no deaths in the immediate post-operative period. The 5year survival rate was 45% following the joint surgical effort, with a median post-collaborative surgery survival duration of 42months. Conclusions. Previous studies document survival benefit of surgery for women with recurrent ovarian cancer when there has been a long disease-free interval, localized pelvic or intra-abdominal recurrences and an optimal performance status. Most gynecologic oncologists do not perform extensive liver or diaphragm resections or lymph node excision above the renal vessels; thus, collaboration with a surgical oncologist is a viable option. In this small descriptive study, the feasibility of this reasonably well-tolerated approach, with possible survival benefit, is documented.

Objective:To estimate the accuracy of 3-dimensional (3D) vascular ultrasound in the preoperative assessment of pelvic masses for malignancy.Methods:We performed a chart review of 66 patients who underwent 3D ultrasound for pelvic masses. Each mass was preoperatively judged to be benign or malignant based upon a study of vascularity within an ovarian mass using 3D ultrasound. Masses with orderly vascular architecture were categorized as probably benign, and masses with chaotic vascular patterns were categorized as malignant. The predictive value of 3D vascular ultrasound was compared with that of 2-dimensional ultrasound and cancer antigen 125 as a predictor of malignancy.Results:Among the 66 patients examined, 34 underwent a documented surgical intervention. Of those 34 patients, 10 had primary malignant neoplasms including 2 with low-malignant potential tumors. Suspicious 3D vascular ultrasound findings predicted malignant neoplasm in 10 patients. Two patients had recurrent cancer; however, only 1 had a suspicious ultrasound finding. There was 1 case of a low-malignant potential tumor without a suspicious ultrasound finding. Excluding the recurrent cancers and the observed patients, the positive predictive value (PPV) and the negative predictive value (NPV) of 3D vascular ultrasound were 100% and 95%, respectively. The PPV and the NPV of 2-dimensional ultrasound in predicting malignancy were 37% and 100%, respectively. An abnormal level of cancer antigen 125 had a PPV and an NPV of 73% and 83%, respectively, in this patient population.Conclusions:In this preliminary and observational study, 3D ultrasound examination of vascular architecture was discriminatory in distinguishing benign ovarian masses from malignancy. Chaotic vascular architecture correlated with malignancy in this group of high-risk patients.

104 Background: Symptoms reported by women with cervical cancer (CCx) include pain, fatigue, lymphedema, sexual dysfunction, proctitis, cystitis, constipation and diarrhea. The objective of this study was to delineate and measure the symptom distress experienced by patients with advanced CCx at the time of palliative care (PC) referral. Methods: A total of 156 advanced CCx patients were referred to PC from 2010 to 2012. Of these, 88 patients had completed the Edmonton Symptom Assessment System (ESAS) and were included in the analysis. Descriptive statistics were used to summarize the data. Results: At the time of presentation mean age was 45 (25-76), 47% were Caucasian, 18% African American, and 33% Hispanic. Fifty-one percent were married; 64% had no advance directives; 75% had recurrent disease. Clinically significant symptoms (defined as ESAS scores ≥ 4) were pain (81%), anorexia (72%), a poor feeling of well-being (70%), fatigue (69%), and insomnia (54%). The chief complaint was pain in 94% of patients. According to the PC specialists’ assessment, pain (96%), emotional distress (77%), and constipation (50%) were predominant symptoms. Various palliative care interventions including opioids, laxatives, and expressive supportive counseling were provided. The median time from advanced cervical diagnosis to PC consultation was 6.0 months (95% CI 5.0-7.8) and the median survival after first PC visit was 4.8 months (95% CI 3.4-6.2). Clinically significant symptoms including nausea, depression, anxiety, and feeling of well-being showed significant improvements at follow-up visits. Conclusions: More than half of patients with advanced CCx were significantly burdened with pain, anorexia, poor feeling of well-being, fatigue, insomnia, and constipation at the time of PC referral. Clinically significant symptoms showed improvements at follow-up visits. In patients with significant symptom distress, early PC involvement may be important to improve quality of life.

Objectives: To explore the incidence and characteristics of pelvic pain in cancer patients attending a single institution cancer center. Methods: A cross-sectional study was undertaken consisting of a sixpage survey distributed to a random sample of patients attending this comprehensive cancer center. The survey contained anonymous self-reported demographic, treatment, lifestyle characteristics, Quality of Life (QOL), and pelvic pain inquiries that were randomly distributed to cancer patients. The QOL data collected was the Functional Assessment of Cancer Therapy — General (FACT-G) in addition to a previously validated female pelvic pain survey. FACT-G and Pain scores, along with subdomains, were compared by patient descriptive variables (exercise, diet, BMI, stage, disease status, treatment) using two-group t-tests or Analysis of Variance. Results: Over the course of 1 year, 124 cancer patients completed this survey of which 105 were female and thus completed the pelvic pain survey. 68% (N= 68) of patients who completed the pelvic pain survey (N= 100) had gynecologic cancers. The non-gynecologic cancers represented included brain, breast, colon, and esophageal cancers. The majority of patientswere in the 61–70 age range,with roughly 80% being English-speaking (N= 83). Approximately half of the patients reported receiving chemotherapy and/or radiation. The stages were distributed as follows however 32% (N= 35) of patients did not report a stage: 23% stage I, 24% stage II, 34% stage III, 19% stage IV. 25% of the patients report never exercising and 50% report eating 1–2 servings of fruits and/or vegetables per day. Of a total possible score of 45 and individual total scores of 23, 10 and 12 for pain, urinary andQOL impact respectively, this group of patients had a mean overall score of 12.30 (±9.48) with 4.75 (±5.66), 2.27 (±2.48) and 5.40 (±3.61) for pain, urinary and QOL impact subscales. In multivariate analysis pelvic pain (P b 0.0005) and less exercise (P = 0.01) were associated with poorer QOL. In this group of patients, pelvic pain was more likely to be associated with the gynecologic cancer patients (P b 0.05) and in patientswith a BMI N 30. In addition the pelvic pain scores were significantly associated with individual quartiles of the FACT-G (P = 0.0001). Conclusions: Data collected in this study demonstrates that pelvic pain scores are poor in this population. Pelvic pain is associated with infrequent exercise, poor QOL, gynecologic cancers, and higher BMI. There is a direct correlation of pelvic pain to the FACT-G total scores.