Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 85
Filter
1.
Gynecol Oncol ; 189: 1-8, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38971004

ABSTRACT

OBJECTIVES: Tissue banking procedures have evolved to keep pace with precision medicine, technology, emerging understanding of racial disparities, and regulatory requirements. However, there is little published guidance regarding strategies to create and maintain a successful biorepository. Our objective is to describe the infrastructure and protocols used by our Gynecologic Oncology Tissue Bank. METHODS: Our Tissue Bank was founded in 1992. In August 2022, internal funding was used to modernize the Tissue Bank. We hired three full-time employees, implemented universal screening of patients treated by gynecologic oncology faculty, updated consenting protocols, and standardized communication with providers. Tumor tissue, blood derivatives, ascites, and pleural fluid were collected from eligible, consenting patients and processed. Patient-derived cell lines and organoids were generated. For quality control purposes, one formalin-fixed, paraffin-embedded (FFPE) sample per tissue site was analyzed by a board-certified pathologist. All samples were labeled and tracked in an OpenSpecimen collection protocol and clinically annotated in a secure database. RESULTS: From August 2022 to October 2023, 227 patients (83% white, 15% Black, 1% Asian) were enrolled and 4249 specimens were collected. Adherent cell lines were generated from 15 patients with ovarian cancer and cell suspensions for organoid generation were collected from 46 patients with ovarian cancer. A recharge center was established to self-sustain the Tissue Bank. Samples have been shared with academic and commercial collaborators. CONCLUSIONS: Our Tissue Bank has enrolled a large number of diverse patients, collected numerous specimen types, and collaborated widely. The procedures described here provide guidance for other institutions establishing similar resources.

2.
J Natl Compr Canc Netw ; 21(10): 1000-1010, 2023 10.
Article in English | MEDLINE | ID: mdl-37856201

ABSTRACT

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.


Subject(s)
Breast Neoplasms , Ovarian Neoplasms , Male , Female , Humans , Germ-Line Mutation , Genetic Testing , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Genetic Predisposition to Disease , Risk Factors , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics
3.
N Engl J Med ; 381(25): 2403-2415, 2019 12 19.
Article in English | MEDLINE | ID: mdl-31562800

ABSTRACT

BACKGROUND: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS: In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA-mutation cohort), and the intention-to-treat population. RESULTS: A total of 1140 patients underwent randomization. In the BRCA-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall. CONCLUSIONS: Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ClinicalTrials.gov number, NCT02470585.).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzimidazoles/therapeutic use , Cystadenocarcinoma, Serous/drug therapy , Ovarian Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Administration, Oral , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzimidazoles/adverse effects , Carboplatin/administration & dosage , Combined Modality Therapy , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/surgery , Double-Blind Method , Female , Genes, BRCA1 , Genes, BRCA2 , Humans , Intention to Treat Analysis , Maintenance Chemotherapy , Middle Aged , Mutation , Ovarian Neoplasms/genetics , Ovarian Neoplasms/surgery , Paclitaxel/administration & dosage , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Progression-Free Survival , Quality of Life
4.
Gynecol Oncol ; 167(3): 496-501, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36180305

ABSTRACT

OBJECTIVES: Visceral adiposity has been established as a predictor of outcomes in various cancers. We aimed to determine the association of radiographic measurements of visceral fat with clinical outcomes in patients with endometrial cancer. METHODS: A retrospective review of patients with stage III-IV endometrial cancer who underwent surgery between 2004 and 2014 was performed. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT;VAT+SAT) were assessed on preoperative computed tomography (CT) scans. Exploratory analysis was performed to establish the optimal cut-off values for VAT, SAT, and TAT to identify patients with poor prognostic body composition. Survival rates were analyzed using Kaplan-Meier analysis, log-rank tests, and cox-regression. RESULTS: Eighty-three patients were included. Forty-two (51%) patients had a low VAT/SAT ratio (<0.45) and 41 (49.4%) had a high VAT/SAT ratio (>0.45). There were no significant differences in demographics between the groups. The mean VAT, SAT, and TAT were 176.3 cm2, 379.3 cm2, and 555.3 cm2 respectively. Compared to patients with low VAT/SAT ratios, patients with high VAT/SAT ratios had a shorter recurrence-free survival (median 29.6 vs 32.3 months, P = 0.01) and shorter overall survival (median 56 vs 93.7 months, P = 0.03). CONCLUSIONS: Visceral fat measurements are predictive of outcomes in patients with advanced stage endometrial cancer. Specifically, VAT to SAT ratios are predictive of overall survival. Future studies should be pursued to identify potential therapeutic targets and biological mechanisms that underlie obesity's relationship with endometrial cancer.


Subject(s)
Endometrial Neoplasms , Intra-Abdominal Fat , Humans , Female , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/metabolism , Subcutaneous Fat/diagnostic imaging , Body Composition , Tomography, X-Ray Computed , Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/surgery , Endometrial Neoplasms/metabolism
5.
Gynecol Oncol ; 161(2): 477-482, 2021 05.
Article in English | MEDLINE | ID: mdl-33546868

ABSTRACT

OBJECTIVES: To study associations among employment, insurance status, and distress in gynecologic oncology patients; and to evaluate the impact of being unemployed or having no/Medicaid insurance on different distress problem areas. METHODS: In this single institution, cross-sectional analysis of gynecologic oncology patients, we screened for distress and problem areas using the National Comprehensive Cancer Network distress thermometer and problem list at outpatient appointments between 6/2017-9/2017. Primary outcome was self-reported high distress (score ≥ 5). The distress problem list included 5 categories-practical, family, emotional, physical, and other. Employment status included employed, unemployed, homemaker, and retired. Logistic regression was used to predict high distress from employment and insurance statuses, adjusting for relevant covariates. RESULTS: Of 885 women, 101 (11.4%) were unemployed, and 53 (6.0%) uninsured or had Medicaid coverage. One in five patients (n = 191, 21.6%) indicated high distress. Unemployed patients were more likely than employed to endorse high distress [adjusted odds ratio (aOR) = 3.5, 95% confidence interval (CI) 2.2-5.7, p < 0.001]. Compared to employed patients, a greater proportion of unemployed patients endorsed distress related to practical (p < 0.05), emotional (p < 0.001), physical (p < 0.01), and other (p < 0.05) problems. Uninsured/Medicaid patients were more likely to endorse high distress (aOR = 2.8, 95% CI 1.5-5.1, p < 0.001) and report family (p < 0.001), emotional (p < 0.001), and other (p < 0.01) problems than patients who had Medicare/commercial insurance. CONCLUSIONS: Gynecologic oncology patients who are unemployed or have no/Medicaid insurance face high distress that appears to arise from issues beyond practical problems, including financial and/or insurance insecurities.


Subject(s)
Employment/psychology , Employment/statistics & numerical data , Genital Neoplasms, Female/economics , Genital Neoplasms, Female/psychology , Insurance Coverage/statistics & numerical data , Cross-Sectional Studies , Female , Humans , Insurance, Health/statistics & numerical data , Logistic Models , Medicaid/statistics & numerical data , Middle Aged , Psychological Distress , Socioeconomic Factors , Unemployment/psychology , Unemployment/statistics & numerical data , United States
6.
Gynecol Oncol ; 162(3): 770-777, 2021 09.
Article in English | MEDLINE | ID: mdl-34140179

ABSTRACT

OBJECTIVE: To evaluate the ability of a personalized text-message-based intervention to increase weight loss among endometrial cancer survivors with obesity. METHODS: In this randomized, controlled trial, endometrial cancer survivors with obesity (BMI ≥30 kg/m2) were randomized to a personalized SMS text-message-based weight loss intervention or enhanced usual care. Primary outcome was weight loss at 6 months; secondary outcomes were weight loss at 12 months and changes in psychosocial measures. We also compared clinical characteristics and weight change between trial participants and non-participants. RESULTS: Between May 18 and December 31, 2017, 80 endometrial cancer survivors with obesity consented to participate in the randomized trial. There were no differences in clinical characteristics between the two arms. Weight changes were similar in the two arms (P = 0.08). At 6 months, no differences in quality of life, physical activity, or body image were noted. Of 358 eligible patients, 80 became trial participants and 278, non-participants. Trial participants were younger (59.3 vs. 63.4 years, P < 0.001), more likely non-white (P = 0.02), on fewer medications (4 vs. 7, P < 0.001), and had a higher median BMI (38.7 vs. 37.6 kg/m2, P = 0.01) than non-participants. Weight change was similar between participants and non-participants (P = 0.85). At 6 months, similar percentages of participants and non-participants (47.7% vs. 44.4%) had gained weight, and similar percentages (9.2% vs. 11.2%) had lost at least 5% of their body weight. CONCLUSIONS: This text-message-based intervention did not increase weight loss among endometrial cancer survivors with obesity, nor did participation in the trial. Other weight management interventions should be promoted to increase weight loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT03169023.


Subject(s)
Endometrial Neoplasms/psychology , Exercise , Obesity/diet therapy , Text Messaging , Adult , Aged , Aged, 80 and over , Body Mass Index , Cancer Survivors/psychology , Endometrial Neoplasms/complications , Female , Humans , Middle Aged , Obesity/complications , Obesity/psychology , Prospective Studies , Quality of Life , Surveys and Questionnaires
7.
Gynecol Oncol ; 161(2): 512-515, 2021 05.
Article in English | MEDLINE | ID: mdl-33610319

ABSTRACT

OBJECTIVE: To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651). METHODS: This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates. RESULTS: Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes. CONCLUSIONS: Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Clinical Trials, Phase I as Topic , Female , Genes, BRCA1 , Genes, BRCA2 , Hematologic Diseases/chemically induced , Hematologic Diseases/genetics , Humans , Middle Aged , Multicenter Studies as Topic , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Prospective Studies
8.
Gynecol Oncol ; 161(3): 700-704, 2021 06.
Article in English | MEDLINE | ID: mdl-33648746

ABSTRACT

OBJECTIVE: To determine the association between scores from a 25-item patient-reported Rockwood Accumulation of Deficits Frailty Index (DAFI) and survival outcomes in gynecologic cancer patients. METHODS: A frailty index was constructed from the SEER-MHOS database. The DAFI was applied to women age ≥ 65 diagnosed with all types of gynecologic cancers between 1998 and 2015. The impact of frailty status at cancer diagnosis on overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: In this cohort (n = 1336) the median age at diagnosis was 74 (range 65-97). Nine hundred sixty-two (72%) women were Caucasian and 132 (10%) were African-American. Overall, 651(49%) of patients were considered frail. On multivariate analysis, frail patients had a 48% increased risk for death (aHR 1.48; 95% CI 1.29-1.69; P < 0.0001). Each 10% increase in frailty index was associated with a 16% increased risk of death (aHR, 1.16; 95% CI, 1.11 to 1.21; P < 0.0001). In subgroup analyses of the varying cancer types, the association of frailty status with prognosis was fairly consistent (aHR 1.15-2.24). The DAFI was more prognostic in endometrial (aHR 1.76; 95% CI 1.41-2.18, P < 0.0001) and vaginal/vulvar (aHR 1.94; 95% CI 1.34-2.81, P = 0.0005) cancers as well as patients with loco-regional disease (aHR 1.94; 95% CI 1.62-2.33, P < 0.0001). CONCLUSIONS: Frailty appears to be a significant predictor of mortality in gynecologic cancer patients regardless of chronological age. This measure of functional age may be of particular utility in women with loco-regional disease only who otherwise would have a favorable prognosis.


Subject(s)
Frail Elderly , Frailty , Genital Neoplasms, Female/mortality , Aged , Aged, 80 and over , Cohort Studies , Databases, Factual , Ethnicity , Female , Genital Neoplasms, Female/ethnology , Humans , Medicare , Predictive Value of Tests , Proportional Hazards Models , Retrospective Studies , SEER Program , Survival Analysis , United States
9.
Gynecol Oncol ; 159(1): 209-213, 2020 10.
Article in English | MEDLINE | ID: mdl-32694061

ABSTRACT

OBJECTIVES: Fellow involvement in patient care is important for education, but effect on patient care is unclear. Our aim was to compare patient outcomes in gynecologic oncology attending clinics versus a fellow training clinic at a large academic medical center. METHODS: A retrospective review of consecutive gynecologic oncology patients from six attending clinics and one faculty-supervised fellow clinic was used to analyze differences based on patient demographics, cancer characteristics, and practice patterns. Primary outcome was overall survival (OS); secondary outcomes included recurrence-free survival (RFS), postoperative complications and chemotherapy within the last 30 days of life. Survival analyses were performed using Kaplan-Meier curves with log-rank tests. RESULTS: Of 159 patients, 76 received care in the attending clinic and 83 in the fellow clinic. Patients in the fellow clinic were younger, less likely to be Caucasian, and more overweight, but cancer site and proportion of advanced stage disease were similar. Both clinics had similar rates of moderate to severe adverse events related to surgery (15% vs. 8%, p = .76), chemotherapy (21% vs. 23%, p = .40), and radiation (14% vs. 17%, p = .73). There was no difference in median RFS in the fellow compared to attending clinic (38 vs. 47 months, p = .78). OS on both univariate (49 months-fellow clinic, 60 months-attending clinic vs. p = .40) and multivariate analysis [hazard ratio 1.3 (0.57, 2.75), P = .58] was not significantly different between groups. CONCLUSIONS: A fellow-run gynecologic oncology clinic designed to provide learning opportunities does not compromise patient outcomes and is a safe and feasible option for fellow education.


Subject(s)
Faculty/statistics & numerical data , Genital Neoplasms, Female/therapy , Internship and Residency/statistics & numerical data , Neoplasm Recurrence, Local/epidemiology , Practice Patterns, Physicians'/statistics & numerical data , Student Run Clinic/statistics & numerical data , Academic Medical Centers/organization & administration , Academic Medical Centers/statistics & numerical data , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant/statistics & numerical data , Disease-Free Survival , Drug Prescriptions/statistics & numerical data , Faculty/organization & administration , Feasibility Studies , Female , Follow-Up Studies , Genital Neoplasms, Female/mortality , Gynecologic Surgical Procedures/adverse effects , Gynecologic Surgical Procedures/education , Gynecologic Surgical Procedures/statistics & numerical data , Gynecology/education , Gynecology/organization & administration , Gynecology/statistics & numerical data , Humans , Incidence , Internship and Residency/methods , Internship and Residency/organization & administration , Medical Oncology/education , Medical Oncology/organization & administration , Medical Oncology/statistics & numerical data , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Patient Safety/statistics & numerical data , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Practice Patterns, Physicians'/organization & administration , Retrospective Studies , Student Run Clinic/organization & administration
10.
Gynecol Oncol ; 157(3): 639-643, 2020 06.
Article in English | MEDLINE | ID: mdl-32248993

ABSTRACT

OBJECTIVE: To compare FIGO 2009 and FIGO 2018 cervical cancer staging criteria with a focus on stage migration and treatment outcomes. METHODS: This study is based on a database cohort of 1282 patients newly diagnosed with cervical cancer from 1997 to 2019. All underwent standard clinical examination and whole-body FDG-PET. Tumor stage was recorded using the FIGO 2009 system, which excluded surgical pathologic, FDG-PET and other advanced imaging findings, and then re-classified to the FIGO 2018 system, including surgical pathologic and imaging findings. Patient management was based on clinical, surgical, and imaging findings. Stage migration and prognosis were evaluated. RESULTS: The distribution per the 2009 staging system was stage I in 593 (46%), stage II in 342 (27%), stage III in 263 (21%), and stage IV in 84 (7%) and the 2018 staging system was stage I in 354 (28%), stage II in 156 (12%), stage III in 601 (47%), and stage IV in 171 (13%). No patients were down-staged. Stage migration occurred in 53% (676/1282) and was attributable to detection of occult lymph node metastasis in 520 (41%), occult distant metastasis in 90 (7%), and tumor size and extent in 66 (5%). The 5-year progression-free survivals (PFS) by FIGO 2009 versus FIGO 2018 were as follows: stage I, 80% vs. 87% (p = 0.02); stage II, 59% vs. 71% (p = 0.002); stage III, 35% vs. 55% (p < 0.001), and stage IV, 20% vs. 16% (p = 0.41). CONCLUSION: Inclusion of surgical pathologic and imaging findings resulted in upward stage migration in the majority, mostly related to nodal and distant metastasis. While FIGO 2018 improves survival discriminatory ability for stages I and IV patients, survival remains heterogeneous among stage III substages.


Subject(s)
Uterine Cervical Neoplasms/classification , Cell Movement , Female , History, 21st Century , Humans , Neoplasm Staging , Prognosis , Survival Analysis
11.
Gynecol Oncol ; 156(1): 13-22, 2020 01.
Article in English | MEDLINE | ID: mdl-31708167

ABSTRACT

BACKGROUND: Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC. METHODS: A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles. FINDINGS: Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID. INTERPRETATION: The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651). FUNDING: National Cancer Institute.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Ovarian Epithelial/drug therapy , Fallopian Tube Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Ovarian Epithelial/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cohort Studies , Dose-Response Relationship, Drug , Fallopian Tube Neoplasms/pathology , Female , Humans , Injections, Intraperitoneal , Injections, Intravenous , Middle Aged , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Peritoneal Neoplasms/pathology , Progression-Free Survival
12.
Gynecol Oncol ; 156(1): 140-146, 2020 01.
Article in English | MEDLINE | ID: mdl-31780235

ABSTRACT

OBJECTIVE: Cascade genetic testing (CGT) of hereditary breast and ovarian cancer (HBOC) or Lynch Syndrome (LS) patients' relatives offers opportunities to prevent cancer, but CGT rates are not well described. We aimed to measure reported disclosure of genetic testing results and CGT rates in these families and evaluate patients' views of educational media. METHODS: Patients with HBOC or LS identified from germline genetic testing at an academic institution between 2011 and 2016 were surveyed regarding disclosure, testing among relatives, and perceptions of educational materials. Medical records and pedigrees provided numbers of total and first-degree relatives. RESULTS: Of 103 mutation carriers consented, 64 (63%) completed the survey an average of 38 months after receiving genetic testing results. Participants' mean age was 53 years, and thirty-one (48%) had a cancer diagnosis. The majority (86%) felt extremely or very comfortable sharing health information. Participants disclosed results to 87% of first-degree relatives, but reported that only 40% of first-degree relatives underwent testing. First-degree female relatives had significantly higher CGT rates than first-degree male relatives (59% versus 21%, P < 0.001). Participants with HBOC reported higher CGT rates than those with LS (49% versus 33%, P = 0.02). Participants did not identify any one educational medium as more helpful than the others for disclosing results. CONCLUSION: Disclosure rates are high among HBOC and LS mutation carriers, but reported CGT rates are low. Gender- and mutation-specific barriers prevent patients' family members from undergoing CGT. Future studies should implement materials to address these barriers and improve CGT rates.


Subject(s)
Genetic Testing/methods , Genital Neoplasms, Female/genetics , Genital Neoplasms, Female/prevention & control , Female , Genetic Testing/statistics & numerical data , Germ-Line Mutation , Humans , Male , Middle Aged , Surveys and Questionnaires
13.
Gynecol Oncol ; 155(1): 105-111, 2019 10.
Article in English | MEDLINE | ID: mdl-31383570

ABSTRACT

BACKGROUND: Ovarian cancer is the deadliest gynecologic malignancy, yet the effects on survival of modifiable pre-diagnosis lifestyle factors, such as obesity and physical activity, remain largely unexplored. Our objective was to evaluate the effect of pre-diagnosis BMI and physical activity on ovarian cancer mortality using prospectively collected data. METHODS: Data on women who developed ovarian cancer after enrollment into the NIH-AARP Diet and Health Study were analyzed. Cancer incidence was ascertained through linkage state cancer registries and consisted of 741 cases of epithelial ovarian cancer. RESULTS: Higher pre-diagnosis BMI was associated with increased overall and ovarian cancer-specific mortality. Comparing women with BMI 25-29.9, 30-34.9 and ≥ 35 to normal weight women, the HRs of overall mortality were 1.18 (95%CI 0.96-1.45), 1.05 (0.82-1.36) and 1.59 (1.14-2.18, p-trend = 0.02). The findings were similar for ovarian cancer-specific mortality comparing women with BMI ≥ 35 to normal weight women (BMI <25) with a HR of 1.47 (95%CI 1.03-2.09, p-trend 0.08). Pre-diagnosis physical activity was not associated with mortality, with HRs for overall mortality of 1.06 (95%CI 0.79-1.43), 0.94 (0.72-1.23), 0.98 (0.76-1.25), and 0.98 (0.75-1.28, p-trend = 0.91), comparing women who engaged in vigorous physical activity 1-3 times/month, 1-2 times/week, 3-4 times/week and 5 times/week, respectively, with those who never/rarely engaged in such activity. CONCLUSIONS: Women who were obese before developing ovarian cancer had increased mortality than those who were normal weight, but physical activity before diagnosis was not associated with mortality in this study population. These results suggest that maintaining a healthy weight is a powerful preventative tool.


Subject(s)
Body Mass Index , Carcinoma, Ovarian Epithelial/mortality , Exercise , Ovarian Neoplasms/mortality , Aged , Female , Humans , Incidence , Middle Aged , Proportional Hazards Models , Registries , United States/epidemiology
14.
Gynecol Oncol ; 153(1): 123-126, 2019 04.
Article in English | MEDLINE | ID: mdl-30651188

ABSTRACT

OBJECTIVES: Premenopausal women may undergo surgical menopause after staging for their endometrial cancer. Our aim was to determine the association between body mass index (BMI) and surgical menopausal symptoms. METHODS: We report a retrospective review of endometrial cancer patients whom underwent menopause secondary to their surgical staging procedure. Symptoms were classified as severe if treatment was prescribed, or mild if treatment was offered, but declined. Univariate analysis was performed with ANOVA and Chi-square tests as appropriate. Relative risks (RR) were generated from Poisson regression models. RESULTS: We identified 166 patients in whom the BMI (kg/m2) distribution was as follows: 33 (19.9%) had BMI <30, 49 (29.5%) had BMI 30-39.9, 50 (30.1%) had BMI 40-49.9, and 34 (20.5%) had BMI ≥50. There were no differences in race, age, or adjuvant treatment among the groups. Overall, 65 (39.2%) women reported symptoms of surgical menopause, including 19 (11.4%) mild and 46 (27.7%) severe. Symptom type did not differ by BMI; however, the prevalence of severe menopausal symptoms decreased with increasing BMI: <30 (45.5%), 30-39.9 (30.6%), 40-49.9 (22%), and ≥ 50 (14.7%); P = 0.002. Multivariate analysis confirmed that symptom prevalence decreased with increasing BMI. Compared to women with a BMI of <30, those with a BMI 40-49.9 (RR = 0.39, 95% CI: 0.17-0.87) or ≥ 50 (RR = 0.24, 95% CI: 0.08-0.70) were significantly less likely to experience menopausal symptoms. CONCLUSIONS: Women younger than 50 with BMI >40 and stage I endometrial cancer are significantly less likely than women with BMI <30 to experience menopausal symptoms after oophorectomy. This information may assist in peri-operative counseling.


Subject(s)
Body Mass Index , Endometrial Neoplasms/epidemiology , Menopause, Premature , Adult , Cross-Sectional Studies , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Female , Humans , Neoplasm Staging , Ovariectomy , Retrospective Studies , Washington/epidemiology
16.
Gynecol Obstet Invest ; 84(1): 50-55, 2019.
Article in English | MEDLINE | ID: mdl-30099446

ABSTRACT

OBJECTIVES: Gynecologic oncologists frequently care for patients at the end of life with the aid of palliative care (PC) specialists. Our primary objectives were to identify perceived barriers to integrating specialty PC into gynecologic cancer care. MATERIALS AND METHODS: Members of the Society of Gynecologic Oncology (SGO) were invited to participate in an anonymous online survey. A Likert scale captured perceptions regarding primary and specialty PC, frequent barriers to use of PC, and potential interventions. RESULTS: A total of 174 (16%) gynecologic oncologists completed the survey. The majority (75%) agreed or strongly agreed that PC should be integrated into cancer care at diagnosis of advanced or metastatic cancer. The most frequently perceived PC barriers included patients' unrealistic expectations (54%), limited access to specialty PC (25%), poor reimbursement (25%), time constraints (22%), and concern of reducing hope or trust (21%). The most agreed upon potential intervention was increased access to outpatient PC (80%). CONCLUSIONS: According to this cohort of SGO members, families' or patients' unrealistic expectations are the most frequent barriers to specialty PC. Understanding this communication breakdown is critically important.


Subject(s)
Attitude of Health Personnel , Genital Neoplasms, Female/therapy , Medical Oncology/organization & administration , Palliative Care , Adult , Ambulatory Care/organization & administration , Female , Genital Neoplasms, Female/psychology , Health Workforce , Hope , Humans , Insurance, Health, Reimbursement , Male , Medical Oncology/economics , Middle Aged , Palliative Care/economics , Surveys and Questionnaires , Time Factors , Trust
17.
Gynecol Oncol ; 148(3): 601-608, 2018 03.
Article in English | MEDLINE | ID: mdl-29329881

ABSTRACT

The incidence of endometrial cancer (EC) is steadily increasing due in large part to an aging world population and rise in rates of obesity. Patients with obesity and advancing age can be seen as vulnerable populations, as they are both often subject to physician bias regarding surgical choices and assumptions regarding long-term outcomes. As we operate on an older and/or obese patient population, it is increasingly important that we adopt peri-operative management strategies and surgical techniques to best serve this complex patient population. Careful orchestration pre-, intra- and postoperatively is key to successful outcomes in robotic and laparoscopic surgery. Here, we review existing literature regarding EC in women with older age and/or obesity, outline recommendations for peri-operative management and common intra-operative issues-specifically common anesthetic issues surrounding cardiovascular, respiratory and neuromuscular systems-that are of heightened importance in women with older age and/or obesity. The goal of this review is to help define and mitigate common complications for these vulnerable patients with an EC diagnosis who, in accordance with carefully assessed health risks, can and should be offered standard of care surgery and treatment.


Subject(s)
Genital Neoplasms, Female/surgery , Gynecologic Surgical Procedures/methods , Minimally Invasive Surgical Procedures/methods , Obesity/epidemiology , Perioperative Care/methods , Postoperative Complications/epidemiology , Age Factors , Comorbidity , Female , Frailty/epidemiology , Genital Neoplasms, Female/epidemiology , Healthcare Disparities , Humans , Laparoscopy , Patient Positioning , Pneumoperitoneum, Artificial , Robotic Surgical Procedures , Severity of Illness Index
18.
Gynecol Oncol ; 151(2): 337-344, 2018 11.
Article in English | MEDLINE | ID: mdl-30190114

ABSTRACT

OBJECTIVE: Paclitaxel, a microtubule inhibitor, is subject to tumor resistance while treating high-grade serous ovarian and uterine cancer. This study aims to directly compare the effects of SQ1274, a novel microtubule inhibitor that binds to the colchicine-binding site on tubulin, and paclitaxel in high-grade serous ovarian and uterine cancer cell lines both in vitro and in vivo. METHODS: We assessed the sensitivity of ovarian (OVCAR8) and uterine (ARK1) cancer cell lines to SQ1274 and paclitaxel using XTT assays. We used western blot and quantitative real-time PCR to analyze changes in AXL RNA and protein expression by SQ1274 and paclitaxel. Differences in cell-cycle arrest and apoptosis were investigated using flow cytometry. Finally, we treated ovarian and uterine xenograft models with vehicle, paclitaxel, or SQ1274. RESULTS: First, we demonstrate that SQ1274 has a much lower IC50 than paclitaxel in both ARK1 (1.26 nM vs. 15.34 nM, respectively) and OVCAR8 (1.34 nM vs. 10.29 nM, respectively) cancer cell lines. Second, we show SQ1274 decreases both RNA and protein expression of AXL. Third, we show that SQ1274 causes increased cell-cycle arrest and apoptosis compared to paclitaxel. Finally, we report that SQ1274 more effectively inhibits tumor growth in vivo compared to paclitaxel. CONCLUSIONS: SQ1274 presents as a viable alternative to paclitaxel for treating ovarian and uterine cancer. This study supports the development of SQ1274 as a chemotherapeutic to treat ovarian and uterine cancer.


Subject(s)
Endometrial Neoplasms/drug therapy , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Tubulin Modulators/pharmacology , Animals , Apoptosis/drug effects , Carcinoma, Ovarian Epithelial , Cell Cycle/drug effects , Cell Growth Processes/drug effects , Cell Line, Tumor , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/pathology , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Female , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Neoplasms, Glandular and Epithelial/genetics , Neoplasms, Glandular and Epithelial/metabolism , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Paclitaxel/pharmacology , Proto-Oncogene Proteins/biosynthesis , Proto-Oncogene Proteins/genetics , RNA, Neoplasm/biosynthesis , RNA, Neoplasm/genetics , Receptor Protein-Tyrosine Kinases/biosynthesis , Receptor Protein-Tyrosine Kinases/genetics , Xenograft Model Antitumor Assays , Axl Receptor Tyrosine Kinase
19.
Gynecol Obstet Invest ; 83(1): 83-89, 2018.
Article in English | MEDLINE | ID: mdl-28399524

ABSTRACT

AIMS: The study aimed to do the following: (1) describe progression free survival (PFS) and overall survival (OS) of women with cervical cancer presenting with occult supraclavicular lymph node (SCLN) metastases, identified by positron emission tomography CT (PET-CT) and (2) compare OS of patients with isolated SCLN metastases to that of patients with SCLN and extranodal metastatic disease. METHODS: Patients were identified retrospectively. Treatment intent was abstracted. PFS and OS in the high-dose chemo-radiotherapy (RT), palliative RT, and supportive treatment groups, as well as OS of patients with SCLN metastases only vs. SCLN and extranodal metastases were calculated. RESULTS: Fourteen patients received high-dose chemo-RT, 32 received palliative RT, and 6 received supportive care (n = 52). Median PFS was 3 months in high-dose chemo-RT group and 1 month in palliative RT (p = ns). Median OS was 12 months in high-dose chemo-RT group, 7 months in palliative RT group, and 2 months in palliative care group (p = 0.05). OS was significantly different between patients with isolated SCLN disease vs. SCLN and extranodal disease, that is, 10.5 vs. 3 months (p = 0.009, χ2 = 6.9). CONCLUSIONS: In this limited analysis, median OS of cervical cancer patients with PET/CT-positive SCLN metastases was the longest when treated with high-dose chemo-RT. Patients with SCLN and extranodal metastases experienced significantly shorter OS, as compared to patients with SCLN only disease.


Subject(s)
Lymph Nodes/diagnostic imaging , Palliative Care/statistics & numerical data , Positron Emission Tomography Computed Tomography/methods , Uterine Cervical Neoplasms/mortality , Adult , Aged , Chemoradiotherapy , Clavicle , Disease-Free Survival , Female , Fluorodeoxyglucose F18 , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Male , Middle Aged , Palliative Care/methods , Radiopharmaceuticals , Retrospective Studies , Time Factors , Treatment Outcome , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy
20.
Gynecol Oncol ; 147(2): 460-464, 2017 11.
Article in English | MEDLINE | ID: mdl-28784245

ABSTRACT

OBJECTIVES: To evaluate the effect of palliative care (PC) consultation on hospice enrollment and end-of-life care in gynecologic oncology patients. METHODS: A retrospective chart review of gynecologic oncology patients who died 1year before and after 2014 implementation of a PC initiative for patients at a single NCI-designated comprehensive cancer center. Patient demographics, admission and procedural history, anti-cancer therapy, and end-of- life care were collected retrospectively. Data was analyzed using Student's t-test, Mann-Whitney U test, Chi-Square test, or Fisher's exact test. RESULTS: We identified 308 patients. Median age at death was 63years (range 17 to 91). Most patients were white (78.2%), married (47.4%), and had ovarian (35.7%) or uterine cancers (35.4%). Introduction of the PC initiative was associated with increased PC consultations (40%, 53%, p=0.02), increased hospice enrollment (57%, 61%, p=0.29), and fewer procedures in the last 30days of life (44%, 31%, p=0.01). The rate of enrollment to inpatient hospice doubled from 12.5% to 25.7% (p=0.02) while time from inpatient hospice enrollment to death increased from 1.9 to 6.0days (p=0.02). Time from outpatient hospice enrollment to death increased from 26.2 to 35.4days (p=0.18). PC consultation was associated with a doubling of outpatient (40%) and inpatient (80%) hospice enrollment. CONCLUSIONS: The PC quality improvement initiative was associated with more palliative care consults, increased rates of inpatient and outpatient hospice utilization, increased time on hospice, and fewer procedures in the last 30days of life, although most women were not enrolled until the last days of life.


Subject(s)
Genital Neoplasms, Female/therapy , Terminal Care/methods , Adolescent , Adult , Aged , Aged, 80 and over , Female , Hospices/statistics & numerical data , Humans , Middle Aged , Palliative Care/methods , Retrospective Studies , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL