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1.
Gynecol Oncol ; 186: 1-8, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38554624

RESUMO

OBJECTIVE: Despite similar incidence, non-Hispanic Black women are twice as likely to die of endometrial cancer as non-Hispanic White women. The social determinants of health may contribute to this disparity. We studied barriers to care and social needs of endometrial cancer patients. METHODS: In a cohort of patients with endometrial cancer from the All of Us study, participants self-reported demographics and completed validated surveys (access to medical care, transportation, caregiving, finances, medication, general care, specialty care, housing insecurity). Univariate and multivariate logistic regression models evaluated demographic and access factors associated with any need. RESULTS: Of 568 participants, 77.7% identified as non-Hispanic White, 7.5% Black, and 8.8% Hispanic. 59% were > 65 years and 95.8% insured. Contributors to delays in care were paying out of pocket (9.9%), provider anxiety (7.6%), transportation (6.3%), cost of copay (6.2%), and insufficient leave from work (5.6%). To mitigate healthcare costs, 16.2% of participants inquired about lower-cost medications, 11.1% reported delaying filling prescriptions, 7.6% taking fewer prescribed medications, and 6.5% skipped doses. Regarding multivariate analysis, participants earning <$25,000 had a 7.3 (95% CI 1.7-31.7) higher adjusted odds of transportation needs and 3.6 (95% CI 1.4-9.7) higher difficulty accessing specialists. No racial/ethnic disparities were identified. CONCLUSIONS: Social needs and barriers to care are most pronounced among endometrial cancer survivors earning <$25,000. Unexpectedly, and possibly related to sample size or survey tool, race/ethnicity were not zassociated with barriers to care. Further studies on health-related social needs, optimal screening tools, and effective interventions are needed in order to achieve equity in cancer outcomes for endometrial cancer patients.

2.
J Natl Compr Canc Netw ; 22(2): 117-135, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38503056

RESUMO

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.


Assuntos
Neoplasias Vulvares , Feminino , Humanos , Adenocarcinoma/patologia , Neoplasias dos Genitais Femininos , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/etiologia , Doença de Paget Extramamária/terapia , Neoplasias Cutâneas , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/etiologia
3.
JCO Oncol Pract ; 20(4): 566-571, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38277618

RESUMO

PURPOSE: We previously implemented paper-based screening for health-related social resource needs (HRSN) in our gynecologic oncology clinic and found that 36% of patients who completed the screening reported HRSN. We identified two primary deficiencies with our process. First, only 52% of patients completed the screening. Second, 37% of patients with needs failed to indicate if they desired resource referral or not. Therefore, we conducted a quality improvement project to integrate screening and referral processes into the electronic medical record (EMR) and routine clinic workflow to achieve at least 90% screening compliance and 90% elicited referral preference. METHODS: A multidisciplinary team consisting of physicians, a health outcomes researcher, a computer programmer, project assistants, and the staff of a partner community organization designed and implemented an intervention that screened for HRSN online via the EMR patient platform or in person during visits. The primary outcome was the percentage of eligible patients who completed the HRSN screening (ie, reach). Outcomes were reviewed weekly, and feedback was provided to stakeholders monthly. Iterative changes were incorporated into five successive Plan-Do-Study-Act (PDSA) cycles completed from January 2021 to March 2023. RESULTS: Screening compliance increased from the baseline of 52% (paper-based) to 97% in PDSA 4. Completion via the online patient portal increased from 17% in prelaunch to 49% in PDSA 4. Of patients who reported needs, 100% had a documented referral preference. CONCLUSION: Compared with paper-based screening, an EMR-integrated HRSN screening and referral system significantly improved reach to patients at a gynecologic oncology clinic. Implementation efforts to expand to other ambulatory clinic settings are in process.


Assuntos
Neoplasias dos Genitais Femininos , Melhoria de Qualidade , Humanos , Feminino , Oncologia , Assistência Ambulatorial , Encaminhamento e Consulta
4.
Future Oncol ; 20(2): 83-94, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37701998

RESUMO

Aim: To assess maintenance preference and trade-offs for patients with advanced epithelial ovarian cancer. Methods: Patients completed a time trade-off exercise ranking five maintenance approaches. Patients' preferred approach was compared with alternatives to determine the progression-free time they would trade off to remain on their preferred approach. Results: Of 152 patients (median age 53 years, 68% White), 56% chose one of four maintenance medications, mostly to feel proactive and 44% chose active surveillance. Compared with their preferred approach, patients were willing to trade a mean progression-free time before switching of 2.3 months for once-daily oral medications, 3.2 months for twice-daily oral medications, 5.5 months for intravenous infusions every 3 weeks (iv. q3), 6.1 months for active surveillance and 7.5 months for iv. q3 and twice-daily oral. Conclusion: Findings highlight the importance of patients' awareness of all maintenance approaches and involving them in the decision-making process.


What is the article about? The VOCAL study looked at maintenance approach preferences of patients with advanced epithelial ovarian cancer. Maintenance approach refers to the methods used after a patient has completed their initial chemotherapy to prevent disease progression for as long as possible. US patients completed an online survey, ranking five different maintenance approaches: No medication (active surveillance); Once-daily oral medication (e.g. pills); Twice-daily oral medication; Medication by intravenous infusion every 3 weeks; Medication by intravenous infusion every 3 weeks and oral twice-daily. Patients were asked to assume the same time to disease progression for all five approaches and the same side effects for the four approaches involving medications (2­5). Each patient then indicated how much time to disease progression they were willing to trade off to remain on their preferred approach before switching to an alternative. What were the results? Overall, 152 patients completed the survey (median age: 53 years, 68% White). Most patients preferred a medication approach (56%, n = 85) to active surveillance (44%, n = 67). Of the 85 patients who preferred medication, 66% (n = 56) reported this was to feel proactive in preventing their cancer returning. Once-daily oral medication was the most acceptable alternative to the patients' preferred maintenance approach, given they were willing to trade the least 'disease-free' time (2.3 months) before accepting a switch. What do the results mean? Individual patient preferences vary, and healthcare professionals should work with patients to determine which approach is most appropriate for them.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Carcinoma Epitelial do Ovário
5.
Obstet Gynecol ; 142(3): 688-697, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37535956

RESUMO

OBJECTIVE: To use a spatial modeling approach to capture potential disparities of gynecologic oncologist accessibility in the United States at the county level between 2001 and 2020. METHODS: Physician registries identified the 2001-2020 gynecologic oncology workforce and were aggregated to each county. The at-risk cohort (women aged 18 years or older) was stratified by race and ethnicity and rurality demographics. We computed the distance from at-risk women to physicians. Relative access scores were computed by a spatial model for each contiguous county. Access scores were compared across urban or rural status and racial and ethnic groups. RESULTS: Between 2001 and 2020, the gynecologic oncologist workforce increased. By 2020, there were 1,178 active physicians and 98.3% practiced in urban areas (37.3% of all counties). Geographic disparities were identified, with 1.09 physicians per 100,000 women in urban areas compared with 0.1 physicians per 100,000 women in rural areas. In total, 2,862 counties (57.4 million at-risk women) lacked an active physician. Additionally, there was no increase in rural physicians, with only 1.7% practicing in rural areas in 2016-2020 relative to 2.2% in 2001-2005 ( P =.35). Women in racial and ethnic minority populations, such as American Indian or Alaska Native and Hispanic women, exhibited the lowest level of access to physicians across all time periods. For example, 23.7% of American Indian or Alaska Native women did not have access to a physician within 100 miles between 2016 and 2020, which did not improve over time. Non-Hispanic Black women experienced an increase in relative accessibility, with a 26.2% increase by 2016-2020. However, Asian or Pacific Islander women exhibited significantly better access than non-Hispanic White, non-Hispanic Black, Hispanic, and American Indian or Alaska Native women across all time periods. CONCLUSION: Although the U.S. gynecologic oncologist workforce increased steadily over 20 years, this has not translated into evidence of improved access for many women from rural and underrepresented areas. However, health care utilization and cancer outcomes may not be influenced only by distance and availability. Policies and pipeline programs are needed to address these inequities in gynecologic cancer care.


Assuntos
Ginecologia , Acesso aos Serviços de Saúde , Disparidades em Assistência à Saúde , Oncologia Cirúrgica , Feminino , Humanos , Asiático , Etnicidade , Acesso aos Serviços de Saúde/estatística & dados numéricos , Hispânico ou Latino , Grupos Minoritários , Oncologistas , Estados Unidos/epidemiologia , Ginecologia/estatística & dados numéricos , Oncologia Cirúrgica/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Adolescente , Adulto Jovem , Adulto , Brancos , Negro ou Afro-Americano , Havaiano Nativo ou Outro Ilhéu do Pacífico , Indígena Americano ou Nativo do Alasca
6.
Clin Cancer Res ; 29(15): 2800-2807, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37097611

RESUMO

PURPOSE: Addition of ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) to PARP inhibitors (PARPi) overcomes PARPi resistance in high-grade serous ovarian cancer (HGSOC) cell and mouse models. We present the results of an investigator-initiated study of combination PARPi (olaparib) and ATRi (ceralasertib) in patients with acquired PARPi-resistant HGSOC. PATIENTS AND METHODS: Eligible patients had recurrent, platinum-sensitive BRCA1/2 mutated or homologous recombination (HR)-deficient (HRD) HGSOC and clinically benefited from PARPi (response by imaging/CA-125 or duration of maintenance therapy; > 12 months first-line or > 6 months ≥ second-line) before progression. No intervening chemotherapy was permitted. Patients received olaparib 300 mg twice daily and ceralasertib 160 mg daily on days 1 to 7 of a 28-day cycle. Primary objectives were safety and objective response rate (ORR). RESULTS: Thirteen patients enrolled were evaluable for safety and 12 for efficacy; 62% (n = 8) had germline BRCA1/2 mutations, 23% (n = 3) somatic BRCA1/2 mutations, and 15% (n = 2) tumors with positive HRD assay. Prior PARPi indication was treatment for recurrence (54%, n = 7), second-line maintenance (38%, n = 5) and first-line treatment with carboplatin/paclitaxel (8%, n = 1). There were 6 partial responses yielding an ORR of 50% (95% confidence interval, 0.15-0.72). Median treatment duration was 8 cycles (range 4-23+). Grade (G) 3/4 toxicities were 38% (n = 5); 15% (n = 2) G3 anemia, 23% (n = 3) G3 thrombocytopenia, 8% (n = 1) G4 neutropenia. Four patients required dose reductions. No patient discontinued treatment due to toxicity. CONCLUSIONS: Combination olaparib and ceralasertib is tolerable and shows activity in HR-deficient platinum-sensitive recurrent HGSOC that benefited and then progressed with PARPi as the penultimate regimen. These data suggest that ceralasertib resensitizes PARPi-resistant HGSOCs to olaparib, warranting further investigation.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Antineoplásicos/uso terapêutico , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Recombinação Homóloga , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ftalazinas , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
7.
J Natl Compr Canc Netw ; 21(2): 181-209, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36791750

RESUMO

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.


Assuntos
Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Carcinossarcoma , Neoplasias do Endométrio , Neoplasias Uterinas , Feminino , Humanos , Carcinoma Endometrioide/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/terapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Neoplasias Uterinas/patologia
8.
Urol Case Rep ; 45: 102191, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36033164

RESUMO

Urachal cancer is a rare but aggressive malignancy. A urachal mass concerning for adenocarcinoma was identified in a 32-year-old G2P1 female on 12-week ultrasound and confirmed on pelvic MRI. Due to progressive growth of the mass and refractory abdominal pain, a multi-disciplinary meeting was held, after which the patient chose to undergo an exploratory laparotomy. A tubo-ovarian abscess was identified involving the intestine, right ovary, fallopian tube, and communicating with a patent, necrotic urachus. This is the first reported case of a tubo-ovarian abscess masquerading as a urachal malignancy, which can present similarly with abdominal pain and irritative urinary symptoms.

9.
J Am Coll Surg ; 235(2): 306-314, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35839408

RESUMO

BACKGROUND: Perioperative venous thromboembolism (VTE) is a significant cause of morbidity and mortality after gynecologic cancer surgery. Here we report a quality improvement intervention to increase perioperative VTE chemoprophylaxis compliance. STUDY DESIGN: All operations performed by a gynecologic oncologist at a tertiary urban university medical center admitted to the hospital for at least one midnight were included. Using a pre/post design with a washout period, we sought to increase perioperative VTE chemoprophylaxis compliance from 22% in the historical control (HC) cohort to 90% in the quality improvement (QI) cohort. The perioperative VTE chemoprophylaxis process was standardized by addressing four domains: preoperative VTE chemoprophylaxis, surgical time-out, postoperative VTE chemoprophylaxis, and intervention education and compliance tracking. Pearson's chi-square test was used to compare HC vs QI cohort compliance. RESULTS: There were 130 surgical cases in the HC cohort and 131 in the QI cohort. Forty-two percent underwent laparotomy, and 57% had cancer at the time of operation. VTE chemoprophylaxis compliance improved from 22% in the HC cohort to 82% in the QI cohort (p < 0.001). Preoperative VTE chemoprophylaxis compliance improved from 76% in the HC cohort to 94% in the QI cohort (p < 0.001), and postoperative VTE chemoprophylaxis compliance improved from 27% to 87% (p < 0.001). Thirty-day postoperative VTE occurred in three patients (2%) in the HC cohort and none in the QI cohort (p = 0.08). CONCLUSIONS: A low-cost and low-technology QI initiative intervention improved perioperative compliance with VTE chemoprophylaxis.


Assuntos
Neoplasias dos Genitais Femininos , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Quimioprevenção/efeitos adversos , Estudos de Coortes , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Melhoria de Qualidade , Estudos Retrospectivos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
11.
Int J Gynecol Cancer ; 32(6): 769-780, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35459709

RESUMO

OBJECTIVE: To identify patient, clinical and hospital factors associated with long-term survival (≥10 years) in women with serous ovarian cancer. METHODS: This National Cancer Database cohort study included women with stage II-IV serous ovarian cancer. Multivariate logistic regression models were used to examine the association of long-term survival with patient (race, insurance, location, household income, education, distance traveled), clinical (age, comorbidities, stage, grade, primary treatment) and hospital factors (region, institution, hospital volume ≥20). RESULTS: Of the 4640 women identified, 12% (n=561) experienced long-term survival. Median overall survival was 41 months (95% CI 39 to 42). The odds of long-term survival were lower for women with public or no insurance (adjusted OR 0.71, 95% CI 0.55 to 0.92), age ≥75 years (0.33, 0.22 to 0.50), any comorbidities (0.70, 0.54 to 0.92), higher stage (stage III: 0.31, 0.25 to 0.41; stage IV: 0.16, 0.12 to 0.22), and moderately/poorly differentiated, undifferentiated, or tumors of unknown grade (moderately/poorly differentiated: 0.30, 0.20 to 0.47; undifferentiated: 0.28, 0.17 to 0.47; unknown: 0.30, 0.18 to 0.50). The odds of long-term survival among women who were publicly insured were lower with neoadjuvant chemotherapy (0.13, 0.04 to 0.044) and higher with optimal cytoreduction (2.24, 1.49 to 3.36). Among women who were privately insured, the odds of long-term survival were higher with optimal cytoreduction (1.99, 1.46 to 2.70) and unaffected by neoadjuvant chemotherapy. CONCLUSIONS: While immutable clinical factors such as age, stage, and grade are associated with long-term survival in women with serous ovarian cancer, modifiable factors, such as insurance type, optimal cytoreductive status, and neoadjuvant chemotherapy provide an opportunity for targeted improvement in care with potential to affect long-term patient outcomes.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Idoso , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Estudos de Coortes , Cistadenocarcinoma Seroso/tratamento farmacológico , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco
12.
Gynecol Oncol Rep ; 40: 100952, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35284612

RESUMO

Objective: HPV vaccination is an important form of cancer prevention. Gynecologic oncologists have an opportunity to improve adult vaccination rates. We aimed to describe current HPV vaccination practices and barriers to vaccination reported by gynecologic oncologists. Methods: An online survey was developed, pilot tested and sent to U.S. members of the Society of Gynecologic Oncology. Results: Of the 226 respondents, most were female (73%), < 45 years old (64%) and practiced in urban (60%) and academic settings (69%). Ninety percent had recommended the HPV vaccine in the past year. Nearly half (47%) had facilitated vaccination by: administering the HPV vaccine in clinic (40%), stocking the vaccine (35%), or prescribing the vaccine (30%). Recommending the vaccine was associated with higher outpatient volume, practicing in the South vs. Northeast, and having higher levels of vaccine knowledge.Of the 90% who recommended the vaccine, 60% did not prescribe or know if they could prescribe the vaccine in their state. Prioritization of cancer treatment was the most commonly reported barrier to HPV vaccination (88%). Approximately half of providers reported other systems-level hinderances such as high cost of stocking the vaccine, clinic flow disruption, or uncertainty surrounding insurance coverage. Almost all recommenders offered the vaccine at HPV-related dysplasia (92%) or cancer (80%) visits, while only 24-50% offered it at non-HPV-related visits. Conclusions: These survey results identify patient, provider, and systems-level barriers that could be targeted to help increase adult HPV vaccination in gynecologic oncology clinics.

14.
Int J Gynecol Pathol ; 41(6): 642-648, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723848

RESUMO

NTRK1/2/3 rearrangements have been identified as oncogenic drivers in a variety of tumors including those in the uterine cervix, and rarely, the uterine corpus. We report 2 cases of cervical sarcoma with NTRK gene rearrangements. Case 1 was a 54-yr-old woman who presented with postmenopausal bleeding and a 5.4 cm friable mass in the cervix. Microscopic examination of the tumor revealed proliferation of epithelioid and spindle cells arranged in alternating hypercellular and hypocellular areas, with subtle fibrosarcoma-like features. Coagulative tumor cell necrosis and readily recognizable mitoses (up to 40 mitotic figures per 10 high-power fields) were identified. Case 2 was a 52-yr-old woman who presented with abnormal vaginal bleeding and a 1.3 cm cervical mass. The resected cervical tumor showed proliferation of spindled cells with fascicular and storiform growth pattern, infiltrating into the smooth muscle with entrapment of normal endocervical glands. The tumor cells displayed mild cytologic atypia and low mitotic activity (1 mitotic figure per 10 high-power fields). The mixed inflammatory infiltrate was seen throughout the lesion, mimicking morphology of inflammatory myofibroblastic tumor. Immunohistochemical staining for S100 and CD34 demonstrated variable expression in case 1 and uniformly diffuse positivity in case 2. The tumor cells in both cases were focally positive for CD10, Cyclin D1, ER, and PR, and negative for AE1/AE3, desmin, SOX10, HMB-45. RNA fusion analysis identified SPECC1L-NTRK3 gene rearrangements in case 1 and TPM3-NTRK1 in case 2; DNA-based mutational analysis also revealed CDKN2A/B homozygous deletion in case 1. Despite accumulating literature on NTRK fusion mesenchymal tumors in gynecologic pathology, these tumors are still rare and lack well-established morphologic diagnostic criteria. Diagnostic and clinical recognition of these tumors is critical given the potential patient benefit from targeted therapy.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Colo do Útero/patologia , Homozigoto , Deleção de Sequência , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Biomarcadores Tumorais/análise
15.
Int J Gynecol Pathol ; 41(6): 600-607, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34856571

RESUMO

Adult granulosa cells tumors (AGCTs) are typically low-grade indolent tumors. On rare occasions, they undergo high-grade/sarcomatous transformation and behave aggressively. This transformation is postulated to occur as the result of acquired genetic alterations, some of which may be eligible for targeted therapy. Here we report a rare case of AGCT with sarcomatous transformation that harbored distinct molecular alterations from those typically seen with AGCTs supporting a molecularly driven approach to these malignancies. The patient is a 56-yr-old G3P3 woman with a history of multiple recurrences of ovarian AGCT for which the first diagnosis was made at the age of 25 when she was evaluated for infertility. The ovarian tumor displayed typical features of AGCT with low-grade, bland morphology. The first extraovarian spread of tumor involving the cul-de-sac was reported at the age of 39. After that, recurrences occurred every 2 to 3 yr with involvement of multiple anatomic sites and repeated surgical resections. At the age of 55 she developed a symptomatic recurrence in the pelvis and underwent resection of an isolated lesion (specimen 1) to no gross residual disease. Within 4 wk of resection she developed significant pelvic pain and imaging showed recurrence of the mass. Therefore, in 5 mo after the initial resection she underwent repeat excision of the lesion (specimen 2) and associated bowel. The sections from specimen 1 showed a biphasic morphology: a low-grade component with morphology and immunophenotype consistent with a typical AGCT and a high-grade spindle cell component with features consistent with a high-grade sarcoma. Specimen 2 featured a pure high-grade sarcoma characterized by coagulative tumor cell necrosis, readily recognizable mitoses, highly atypical cells with vesicular nuclei and prominent nucleoli. SF-1 positivity and the presence of FOXL2 C134W mutation in the sarcomatous component support the notion of transformation of typical AGCT. While detected TERT promoter C228T mutation may play a role in this process, we further identified genetic alterations affecting PI3K/AKT/mTOR pathway, including mutations in PIK3CA , PIK3R1 , AKT1 , and NF2 , which may also contribute to tumor progression/transformation. These findings provide rationale for molecular/pathway-based targeted therapy for patients with advanced AGCT.


Assuntos
Tumor de Células da Granulosa , Neoplasias Ovarianas , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Feminino , Humanos , Tumor de Células da Granulosa/patologia , Fosfatidilinositol 3-Quinases , Neoplasias Ovarianas/patologia , Sarcoma/genética
16.
Gynecol Oncol ; 163(2): 246-253, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34620496

RESUMO

OBJECTIVE: Platinum-resistant, high-grade serous ovarian cancer (HGSOC) has limited treatment options. Preclinical data suggest that poly(ADP-ribose) polymerase inhibitors (PARPi) and ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) are synergistic. CAPRI (NCT03462342) is an investigator-initiated study of olaparib plus ceralasertib in recurrent HGSOC. Herein, we present results from the platinum-resistant cohort. METHODS: A Simon 2-stage design was utilized. Platinum-resistant HGSOC patients received ceralasertib 160 mg orally daily, days 1-7 and olaparib 300 mg orally twice daily, days 1-28 of a 28-day cycle until toxicity or progression. Primary endpoints were toxicity and efficacy including objective response rate (ORR) by RECIST. Secondary endpoint was progression-free survival (PFS). The null hypothesis (≤5% ORR) would be rejected if there were ≥ 1 responses in 12 patients. RESULTS: Fourteen PARPi-naïve patients were evaluable for toxicity; 12 were evaluable for response. Three had BRCA1 mutations (1 germline, 2 somatic). Adverse events possibly related to treatment were primarily grade (G) 1/2. G3 toxicities included nausea (14.3%), fatigue (7.1%), anorexia (7.1%), and anemia (7.1%). No objective responses occurred. Best response was stable disease in 9 patients and progressive disease in three. Five patients had a ≥ 20% to <30% reduction in disease burden, including 3 with BRCA1 mutations. Three of 11 patients (27%; 2 with BRCA1 mutations) evaluable by Gynecologic Cancer Intergroup criteria had >50% CA-125 decline, including 2 with CA-125 normalization. Median PFS was 4.2 months overall (90% CI:3.5-8.2) and 8.2 months (3.6 months-not determined) for patients with BRCA1 mutations. CONCLUSIONS: Olaparib plus ceralasertib is well-tolerated. No objective responses occurred, though a signal of activity was seen particularly in disease associated with BRCA1. Further evaluation of this combination should include alternate dosing strategies in genomically-selected populations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Indóis/efeitos adversos , Morfolinas/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Ftalazinas/administração & dosagem , Piperazinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonamidas/efeitos adversos , Administração Oral , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteína BRCA1/genética , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Indóis/administração & dosagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Ovário/diagnóstico por imagem , Ovário/patologia , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases , Pirimidinas/administração & dosagem , Critérios de Avaliação de Resposta em Tumores Sólidos , Sulfonamidas/administração & dosagem , Tomografia Computadorizada por Raios X
20.
Obstet Gynecol ; 137(5): 831-836, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33831922

RESUMO

OBJECTIVE: To characterize the indications for and complication rates of excision of the retained cervix after supracervical hysterectomy. METHODS: We performed a retrospective cohort study of women undergoing excision of the retained cervix after supracervical hysterectomy in the 2010-2014 National Inpatient Sample. International Classification of Diseases, Ninth Revision codes were used to identify indication for the procedure and surgical complications. We weighted the hospital-level data to obtain nationwide estimates of patient characteristics, surgical complications, and length of stay. RESULTS: Nationwide, 1,140 women underwent excision of the retained cervix after hysterectomy. Their mean age was 49 years, and the majority were White and privately insured. Leiomyomas were the most commonly coded indication (35%, 95% CI 29-42), followed by prolapse (14%, 95% CI 9-18). Eighteen percent (95% CI 13.0-23.1) were performed for malignancy, including 5.3% (95% CI 2.3-8.2) for cervical cancer. Only 11.5% (95% CI 7.3-15.6) of cases were performed laparoscopically. The overall complication rate was high (38%, 95% CI 32-45), particularly for bleeding complications (26%, 95% CI 20-31) and transfusion (15%, 95% CI 11-20). Gastrointestinal complication rates were second highest (8%, 95% CI 5-12); ileus was the most common gastrointestinal complication (7.0%, 95% CI 3.7-10.4). The median length of stay was 2 days (range 0-34). CONCLUSION: Women who undergo excision of the retained cervix after supracervical hysterectomy experience high rates of complications, the most common of which was bleeding. Patient counseling regarding removal of the cervix at the time of hysterectomy should include this information.


Assuntos
Colo do Útero/cirurgia , Histerectomia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Hemorragia Pós-Operatória , Estudos Retrospectivos , Resultado do Tratamento
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