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1.
Cell ; 183(6): 1634-1649.e17, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33259803

RESUMO

Microsatellite instability-high (MSI-H) tumors are characterized by high tumor mutation burden and responsiveness to checkpoint blockade. We identified tumor-specific frameshifts encoding multiple epitopes that originated from indel mutations shared among patients with MSI-H endometrial, colorectal, and stomach cancers. Epitopes derived from these shared frameshifts have high population occurrence rates, wide presence in many tumor subclones, and are predicted to bind to the most frequent MHC alleles in MSI-H patient cohorts. Neoantigens arising from these mutations are distinctly unlike self and viral antigens, signifying novel groups of potentially highly immunogenic tumor antigens. We further confirmed the immunogenicity of frameshift peptides in T cell stimulation experiments using blood mononuclear cells isolated from both healthy donors and MSI-H cancer patients. Our study uncovers the widespread occurrence and strong immunogenicity of tumor-specific antigens derived from shared frameshift mutations in MSI-H cancer and Lynch syndrome patients, suitable for the design of common "off-the-shelf" cancer vaccines.


Assuntos
Epitopos/genética , Epitopos/imunologia , Mutação da Fase de Leitura/genética , Instabilidade de Microssatélites , Neoplasias/genética , Neoplasias/imunologia , Sequência de Aminoácidos , Antígenos de Neoplasias/imunologia , Antígenos Virais/imunologia , Linhagem Celular Tumoral , Análise Mutacional de DNA , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Humanos , Imunoterapia , Mutação de Sentido Incorreto/genética , Neoplasias/terapia , Peptídeos/química , Peptídeos/imunologia , Análise de Sobrevida , Linfócitos T/imunologia
2.
Gynecol Oncol ; 184: 43-50, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38277920

RESUMO

OBJECTIVE: To assess trends and differences in patient characteristics, complications, and distributions of hysterectomy for benign indications by benign gynecologists (BG) and gynecologic oncologists (GO). METHODS: This retrospective cohort study identified patients undergoing hysterectomy for benign indications using the National Surgical Quality Improvement Program data from 2014 to 2021. Exclusions were made for gynecologic or disseminated cancers, ascites, non-gynecologic surgeons, and cesarean hysterectomies. Primary outcome was major (≥Grade 3) 30-day complications, categorized into any complications, wound, cardiovascular and pulmonary, renal, infectious, andthromboembolic complications. Thirty-day readmissions, reoperations, and mortality were also analyzed. Propensity score matching was performed in a 1:1 match of GO to BG patients and was compared. Linear regressions assessed trends. RESULTS: Among 198,767 patients, 18% (n = 37,707) underwent hysterectomy for benign indications with GO. GO patients exhibited more risk factors for complications and differed significantly from BG patients in comorbidities and perioperative characteristics. Overall, GO patients had higher major complication rates (3.1% vs 2.2%, p < 0.001) and for several other composite complications. After matching, compared to BG, GO-performed hysterectomies had similar rates of major complications (3.0% vs 3.0%, p = 0.55) and no differences in other composite complications, except fewer reoperations (1.2 % vs 1.5%, p < 0.01) and wound complications (0.4% vs 0.5%, p = 0.02) in GO patients. Over the eight years, the percentage of GO-performed hysterectomy (ß = 0.41, R2 = 0.71,p < 0.01) increased significantly whereas BG-performed surgeries decreased by the same magnitude. BG had a significant decrease in frail patients (ß = -0.47, R2 = 0.90, p < 0.01), but GO did not (ß = -0.36, R2 = 0.38, p = 0.10). CONCLUSIONS: GO are performing more hysterectomies for benign indications on higher-risk patients. However, on a matched cohort, risks of major complications were similar between GO and BG.


Assuntos
Histerectomia , Complicações Pós-Operatórias , Humanos , Feminino , Estudos Retrospectivos , Histerectomia/métodos , Histerectomia/estatística & dados numéricos , Histerectomia/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Oncologistas/estatística & dados numéricos , Ginecologia/estatística & dados numéricos , Estudos de Coortes
3.
Gynecol Oncol ; 186: 176-181, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38696905

RESUMO

INTRODUCTION: Fertility-related concerns cause significant anxiety among patients with Hereditary Breast and Ovarian Cancer Syndrome (HBOC). The Society of Gynecologic Oncology and the American Society for Reproductive Medicine recommend patients diagnosed with HBOC receive early referral to a reproductive endocrinologist. However, evidence about fertility trends in this patient population are limited and guidelines are scarce. The aim of this study is to compare fertility preservation among patients with HBOC to control patients undergoing fertility treatment without a diagnosis of infertility. METHODS: This retrospective study included patients who presented to a single academic institution for fertility preservation in the setting of diagnosis of HBOC. In this study, HBOC patients are referred to as those who had tested positive for pathogenic mutations in BRCA1, BRCA2 or were at high-risk for HBOC based on a strong family history (defined as >3 family members diagnosed with HBOC) without a genetic mutation. HBOC patients were matched in a 1:1 fashion to a control group undergoing fertility preservation without a diagnosis of infertility or HBOC. All analysis was done using SPSS version 9.4 (SAS Institute, Cary, NC). RESULTS: Between August 1st, 2016 and August 1st, 2022, 81 patients presented to the study center for consultation in the setting of HBOC. Of those who presented, 48 (59.2%) ultimately underwent oocyte cryopreservation and 33 (40.7%) underwent embryo cryopreservation. Patients who underwent oocyte cryopreservation due to BRCA1 status were more likely to present for fertility consultation at a younger age compared to control patients (32.6 vs. 34.7 years, p = 0.03) and were more likely to undergo oocyte cryopreservation at a younger age (32.1 vs. 34.6 years, p = 0.007). There was no difference in age at initial consultation or age at procedure for patients with BRCA2 or patients with a strong family history compared to control patients (p > 0.05). There was no difference in the mean age of patients with HBOC at presentation for consultation for embryo cryopreservation or the mean age the patient with HBOC underwent embryo cryopreservation compared to control patients (p > 0.05). Patients with BRCA1 or BRCA2 did not have expedited time from consultation to first cycle start (p > 0.05). After adjusting for factors including anti-Müllerian hormone (AMH) level and age, patients considered in the HBOC group due to family history had less time between consultation and oocyte cryopreservation cycle compared to control patients. (179 vs. 317 days, p = 0.045). There was no difference in time from consultation to starting cycle for embryo cryopreservation for patients with HBOC compared to controls (p > 0.05). CONCLUSION: Patients with HBOC did not undergo expedited fertility treatment compared to control patients undergoing oocyte and embryo cryopreservation for non-infertility reasons. Patients diagnosed with BRCA1 had more oocytes retrieved compared to the control population which is possibly due to earlier age of presentation in the setting of recommended age of risk reducing surgery being age 35-40. When age matched, cycle outcomes did not differ between HBOC and control patients. Given the known cancer prevention benefit and recommendations for risk-reducing surgery, future studies should focus on guidelines for fertility preservation for patients with HBOC.


Assuntos
Preservação da Fertilidade , Síndrome Hereditária de Câncer de Mama e Ovário , Humanos , Preservação da Fertilidade/métodos , Feminino , Adulto , Estudos Retrospectivos , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Criopreservação , Proteína BRCA1/genética , Proteína BRCA2/genética , Adulto Jovem
5.
Gynecol Oncol ; 187: 151-162, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38781746

RESUMO

OBJECTIVE: In the U.S., uterine cancer incidence is rising, with racial and ethnic minorities experiencing the largest increases. We performed age-period-cohort analyses using novel methods to examine the contribution of age at diagnosis (age), year of diagnosis (period), and birth cohort (cohort), to trends in uterine cancer incidence. METHODS: We used uterine cancer incidence data from the Surveillance, Epidemiology, and End Result (SEER) 12 database (1992-2019), and performed hysterectomy-correction. We generated hexamaps to visualize age, period, and cohort effects, and used mutual information to estimate the percent contribution of age, period, and cohort effects, individually and combined, on uterine cancer incidence, overall and by race and ethnicity and histology. RESULTS: Hexamaps showed an increase in uterine cancer in later time periods, and a cohort effect around 1933 showing a lower incidence compared with earlier and later cohorts. Age, period, and cohort effects combined contributed 86.6% (95% CI: 86.4%, 86.9%) to the incidence. Age effects had the greatest contribution (65.1%, 95% CI: 64.3%, 65.9), followed by cohort (20.7%, 95% CI: 20.1%, 21.3%) and period (14.2%, 95% CI: 13.7%, 14.8%) effects. Hexamaps showed higher incidence in recent years for non-Hispanic Blacks and non-endometrioid tumors. CONCLUSIONS: Age effects had the largest contribution to uterine cancer incidence, followed by cohort and period effects overall and across racial and ethnic groups and histologies. IMPACT: These findings can inform uterine cancer modeling studies on the effects of interventions that target risk factors which may vary across age, period, or cohort.

6.
Gynecol Oncol ; 183: 47-52, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38503141

RESUMO

INTRODUCTION: Gynecologic and breast cancers share several risk factors. Breast cancer risk assessment tools can identify those at elevated risk and allow for enhanced breast surveillance and chemoprevention, however such tools are underutilized. We aim to evaluate the use of routine breast cancer risk assessment in a gynecologic oncology clinic. METHODS: A patient-facing web-based tool was used to collect personal and family history and run four validated breast cancer risk assessment models (Tyrer-Cuzick (TC), Gail, BRCAPRO, and Claus) in a gynecologic oncology clinic. We evaluated completion of the tools and identification of patients at elevated risk for breast cancer using the four validated models. RESULTS: A total of 99 patients were included in this analysis. The BRCAPRO model had the highest completion rate (84.8%), followed by the TC model (74.7%), Gail model (74.7%), and the Claus model (52.1%). The TC model identified 21.6% of patients completing the model as having ≥20% lifetime risk of breast cancer, compared to 6.8% by the Gail model, and 0% for both the BRCAPRO and Claus models. The Gail model identified 52.5% of patients as having ≥1.67% 5-year risk of breast cancer. Among patients identified as high-risk for breast cancer and eligible for screening, 9/9 (100%) were referred to a high-risk breast clinic. CONCLUSION: Among patients that completed the TC breast cancer risk assessment in a gynecologic oncology clinic, approximately 1 in 5 were identified to be at significantly elevated lifetime risk for breast cancer. The gynecologic oncologist's office might offer a convenient and feasible setting to incorporate this risk assessment into routine patient care, as gynecologic oncologists often have long-term patient relationships and participate in survivorship care.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Medição de Risco/métodos , Pessoa de Meia-Idade , Adulto , Idoso , Neoplasias dos Genitais Femininos , Medicina de Precisão/métodos , Sobrevivência
7.
Gynecol Oncol ; 177: 9-13, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37603977

RESUMO

INTRODUCTION: Letters of recommendation (LOR) play a significant role in applicant selection for gynecologic oncology (GO) fellowship. LORs can be agentic, associated with competence, independence and strength, or communal, associated with being accommodating, cooperative and empathetic. Agentic LORs have been shown to reflect favorably on applicants, making them more likely to be selected for interview. The primary goal of this study was to determine linguistic differences in LORs for applicants applying to GO fellowship based on applicant gender and race. METHODS: All applications to a single academic institution from the years 2018-2020 were analyzed. LORs were extracted from all applicants who self-reported their gender and race/ethnicity. Analysis was performed using Linguistic Inquiry Word Count (LIWC) in terms of agentic and communal language. All analysis was done using SAS version 9.4. RESULTS: From 2018 to 2020, there were 239 GO fellowship applications to a single academic institution. There were 186 (78.1%) applicants who identified as female and 52 (21.8%) who identified as male. Female applicants were more likely to have more research (p = 0.047) and volunteer activities (p = 0.02) than male applicants. There were no differences between female and male applicants in terms of age, geographic location of residency, USMLE scores, AOA status, number of publications or attending a Doximitiy-rated top 20 residency program. There were 139 (60.7%) applicants who identified as White, 46 (20.1%) as Asian, 16 (7.0%) as Black, 19 (8.3%) as Latinx and 9 (3.9%) as other. On multivariable analysis, LORs written for male applicants had higher agentic scores compared to females (p < 0.05), and LORs of female applicants received higher communal scores (p < 0.05). LORs for applicants who identified as Black or Latinx were found to have lower agentic scores compared to individuals who identified as White(p < 0.05 for both). CONCLUSION: There were demonstrated linguistic differences in LOR for GO fellowship based on applicant gender and race/ethnicity. LORs written for white, male applicants were more likely to have higher agentic scores compared to minority, female applicants. LORs written for female applicants were more likely to have higher communal scores. As LORs have been shown to be instrumental in GO fellowship interview selection and linguistic differences exist based on applicant gender and race/ethnicity, this study highlights the need for a more objective GO fellowship application process. DISCLOSURES: Portion of this paper was presented at the Society for Gynecologic Oncology as part of a focus plenary.

8.
Gynecol Oncol ; 174: 273-277, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37270906

RESUMO

OBJECTIVE: The objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/- para-aortic lymphadenectomy (LND). METHODS: Patients with newly diagnosed high-risk EC were identified. Inclusion criteria included patients who underwent primary surgical management from January 1, 2014 to September 1, 2020 at our institution. Patients were categorized into either the SLN or LND group based on their method of planned lymph node assessment. Patients in the SLN group had dye injected followed by successful bilateral lymph node mapping, retrieval, and processing per our institutional protocol. Clinicopathological and follow-up data were extracted from patient's medical records. The t-test or Mann-Whitney test was used to compare continuous variables and Chi-squared or Fisher's exact test were used for categorical variables. Progression-free survival (PFS) was calculated from the date of initial surgery to the date of progression, death, or last follow-up. Overall survival (OS) was calculated from the date of surgical staging to the date of death or last follow-up. Three-year PFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare cohorts. Multivariable Cox regression models were used to assess the relationship between nodal assessment cohort and OS/PFS while adjusting for age, adjuvant therapy, and surgical approach. A result was considered statistically significant at the p < 0.05 level of significance and all statistical analysis was done using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Out of 674 patients diagnosed with EC during the study period, 189 were diagnosed with high-risk EC based on our criteria. Forty-six (23.7%) patients underwent SLN assessment and 143 (73.7%) underwent LND. No difference was observed between the two groups in regards to age, histology, stage, body mass index, tumors myometrial invasion, lymphovascular space invasion, or peritoneal washing positivity. Patients in the SLN group underwent robotic-assisted procedures more frequently than those in the LND group (p < 0.0001). The three-year PFS rate was 71.1% (95% CI 51.3-84.0%) in the SLN group and 71.3% (95% CI 62.0-78.6%) in the LND group (p = 0.91). The unadjusted hazard ratio (HR) for recurrence in the SLN versus LND group was 1.11 (95% CI 0.56-2.18; p = 0.77), and after adjusting for age, adjuvant therapy, and surgical approach, the HR for recurrence was 1.04 (95% CI 0.47-2.30, p = 0.91). The three-year OS rate was 81.1% (95% CI 51.1-93.7%) in the SLN group and 95.1% (95% CI 89.4-97.8%) in the LND group (p = 0.009). Although the unadjusted HR for death was 3.74 in the SLN vs LND group (95% CI 1.39-10.09; p = 0.009), when adjusted for age, adjuvant therapy, and surgical approach, it was no longer significant with a HR of 2.90 (95% CI 0.94-8.95, p = 0.06). CONCLUSIONS: There was no difference in three-year PFS in patients diagnosed with high-risk EC who underwent SLN evaluation compared to those who underwent full LND in our cohort. The SLN group did experience shorter unadjusted OS; however, when adjusting for age, adjuvant therapy and surgical approach, there was no difference OS in patients who underwent SLN compared to LND.


Assuntos
Neoplasias do Endométrio , Linfadenopatia , Linfonodo Sentinela , Feminino , Humanos , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias do Endométrio/patologia , Estudos Retrospectivos , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Linfonodos/patologia , Linfadenopatia/patologia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias
9.
Gynecol Oncol ; 171: 76-82, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36827841

RESUMO

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


Assuntos
Neoplasias dos Genitais Femininos , Ginecologia , Oncologistas , Feminino , Humanos , Oncologia , Neoplasias dos Genitais Femininos/terapia
10.
Gynecol Oncol ; 173: 22-30, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37062188

RESUMO

OBJECTIVES: Approximately 1% of individuals have a hereditary cancer predisposition syndrome, however, the majority are not aware. Collecting a cancer family history (CFH) can triage patients to receive genetic testing. To rigorously assess different methods of CFH collection, we compared a web-based tool (WBT) to usual care (clinician collects CFH) in a randomized controlled trial. METHODS: New gynecologic oncology patients (seen 9/2019-9/2021) were randomized to one of three arms in a 2:2:1 allocation ratio: 1) usual care clinician CFH collection, 2) WBT completed at home, or 3) WBT completed in office. The WBT generated a cancer-focused pedigree and scores on eight validated cancer risk models. The primary outcome was collection of an adequate CFH (based on established guidelines) with usual care versus the WBT. RESULTS: We enrolled 250 participants (usual care - 110; WBT home - 105; WBT office - 35 [closed early due to COVID-19]). Within WBT arms, 109 (78%) participants completed the tool, with higher completion for office versus home (33 [94%] vs. 76 [72%], P = 0.008). Among participants completing the WBT, 63 (58%) had an adequate CFH versus 5 (5%) for usual care (P < 0.001). Participants completing the WBT were significantly more likely to complete genetic counseling (34 [31%] vs. 15 [14%], P = 0.002) and genetic testing (20 [18%] vs. 9 [8%], P = 0.029). Participant and provider WBT experience was favorable. CONCLUSIONS: WBTs for CFH collection are a promising application of health information technology, resulting in more comprehensive CFH and a significantly greater percentage of participants completing genetic counseling and testing.


Assuntos
COVID-19 , Neoplasias , Humanos , Feminino , Estudos Prospectivos , Neoplasias/diagnóstico , Neoplasias/genética , Testes Genéticos , Internet
11.
Support Care Cancer ; 31(8): 485, 2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37480403

RESUMO

PURPOSE: Pain, fatigue, sleep disturbance, and depression are four of the most common symptoms in patients with gynecologic cancer. The purposes were to identify subgroups of patients with distinct co-occurring pain, fatigue, sleep disturbance, and depression profiles (i.e., pre-specified symptom cluster) in a sample of patients with gynecologic cancer receiving chemotherapy and assess for differences in demographic and clinical characteristics, as well as the severity of other common symptoms and QOL outcomes among these subgroups. METHODS: Patients completed symptom questionnaires prior to their second or third cycle of chemotherapy. Latent profile analysis was used to identify subgroups of patients using the pre-specified symptom cluster. Parametric and nonparametric tests were used to evaluate for differences between the subgroups. RESULTS: In the sample of 233 patients, two distinct latent classes were identified (i.e., low (64.8%) and high (35.2%)) indicating lower and higher levels of symptom burden. Patients in high class were younger, had child care responsibilities, were unemployed, and had a lower annual income. In addition, these women had a higher body mass index, a higher comorbidity burden, and a lower functional status. Patients in the high class reported higher levels of anxiety, as well as lower levels of energy and cognitive function and poorer quality of life scores. CONCLUSIONS: This study identified a number of modifiable and non-modifiable risk factors associated with membership in the high class. Clinicians can use this information to refer patients to dieticians and physical therapists for tailored interventions.


Assuntos
Neoplasias dos Genitais Femininos , Qualidade de Vida , Humanos , Feminino , Síndrome , Fadiga/epidemiologia , Fadiga/etiologia , Neoplasias dos Genitais Femininos/complicações , Dor
12.
Cancer ; 128(4): 654-664, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34787913

RESUMO

The high lethality of ovarian cancer in the United States and associated complexities of the patient journey across the cancer care continuum warrant an assessment of current practices and barriers to quality care in the United States. The objectives of this study were to identify and assess key components in the provision of high-quality care delivery for patients with ovarian cancer, identify challenges in the implementation of best practices, and develop corresponding quality-related recommendations to guide multidisciplinary ovarian cancer programs and practices. This multiphase ovarian cancer quality-care initiative was guided by a multidisciplinary expert steering committee, including gynecologic oncologists, pathologists, a genetic counselor, a nurse navigator, social workers, and cancer center administrators. Key partnerships were also established. A collaborative approach was adopted to develop comprehensive recommendations by identifying ideal quality-of-care program components in advanced epithelial ovarian cancer management. The core program components included: care coordination and patient education, prevention and screening, diagnosis and initial management, treatment planning, disease surveillance, equity in care, and quality of life. Quality-directed recommendations were developed across 7 core program components, with a focus on ensuring high-quality ovarian cancer care delivery for patients through improved patient education and engagement by addressing unmet medical and supportive care needs. Implementation challenges were described, and key recommendations to overcome barriers were provided. The recommendations emerging from this initiative can serve as a comprehensive resource guide for multidisciplinary cancer practices, providers, and other stakeholders working to provide quality-directed cancer care for patients diagnosed with ovarian cancer and their families.


Assuntos
Neoplasias Ovarianas , Qualidade de Vida , Carcinoma Epitelial do Ovário/terapia , Atenção à Saúde , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Qualidade da Assistência à Saúde , Estados Unidos
13.
Cancer ; 128(24): 4241-4250, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36305018

RESUMO

BACKGROUND: Cascade genetic testing for hereditary cancer syndromes offers affected relatives the opportunity to pursue cancer screening and risk-reducing surgery and thus reduces morbidity and mortality. The purpose of this study was to measure the long-term utilization of targeted cancer prevention and quality of life among at-risk relatives offered clinician-facilitated cascade genetic testing. METHODS: In a pilot study, at-risk relatives of patients with a hereditary cancer syndrome were contacted directly by the clinical team and offered telephone genetic counseling and genetic testing via an at-home, mailed saliva kit. Two-year follow-up results evaluating the use of targeted cancer prevention strategies and the quality of life for enrolled relatives were reported. Quality-of-life was measured with validated surveys, and scores were compared to the time of initial contact by the Wilcoxon signed-rank test. RESULTS: Ninety-five at-risk relatives were enrolled in the initial pilot study, and 72 (76%) participated in the 2-year follow-up; 57 of these (79%) had completed genetic testing. Twenty-five of those 57 relatives (44%) were found to harbor an inherited pathogenic variant. Guideline-based cancer surveillance was recommended to 18 relatives; 13 (72%) completed at least one recommended screening, and six (33%) completed all recommended screenings. Risk-reducing surgery was recommended to 10 relatives; four (40%) completed a total of eight procedures. Quality-of-life surveys demonstrated low levels of anxiety, depression, distress, and uncertainty. CONCLUSIONS: The 2-year follow-up of the original pilot study revealed that clinician-facilitated cascade testing resulted in genetically targeted cancer screening and prevention with preserved quality of life. These results, to be confirmed by larger randomized controlled trials, suggest that medical systems should consider supporting clinician-facilitated cascade testing programs.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Projetos Piloto , Aconselhamento Genético/métodos , Testes Genéticos/métodos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/genética
14.
Gynecol Oncol ; 164(2): 304-310, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34922769

RESUMO

BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.


Assuntos
COVID-19/complicações , COVID-19/mortalidade , Carcinoma/complicações , Carcinoma/mortalidade , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/mortalidade , Hospitalização/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/terapia , Carcinoma/terapia , Feminino , Neoplasias dos Genitais Femininos/terapia , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Gravidade do Paciente , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
15.
Cancer ; 127(7): 1057-1067, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33294978

RESUMO

BACKGROUND: Mounting evidence suggests disproportionate coronavirus disease 2019 (COVID-19) hospitalizations and deaths because of racial disparities. The association of race in a cohort of gynecologic oncology patients with severe acute respiratory syndrome-coronavirus 2 infection is unknown. METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 New York City area hospital systems. A multivariable mixed-effects logistic regression model accounting for county clustering was used to analyze COVID-19-related hospitalization and mortality. RESULTS: Of 193 patients who had gynecologic cancer and COVID-19, 67 (34.7%) were Black, and 126 (65.3%) were non-Black. Black patients were more likely to require hospitalization compared with non-Black patients (71.6% [48 of 67] vs 46.0% [58 of 126]; P = .001). Of 34 (17.6%) patients who died from COVID-19, 14 (41.2%) were Black. Among those who were hospitalized, compared with non-Black patients, Black patients were more likely to: have ≥3 comorbidities (81.1% [30 of 37] vs 59.2% [29 of 49]; P = .05), to reside in Brooklyn (81.0% [17 of 21] vs 44.4% [12 of 27]; P = .02), to live with family (69.4% [25 of 36] vs 41.6% [37 of 89]; P = .009), and to have public insurance (79.6% [39 of 49] vs 53.4% [39 of 73]; P = .006). In multivariable analysis, among patients aged <65 years, Black patients were more likely to require hospitalization compared with non-Black patients (odds ratio, 4.87; 95% CI, 1.82-12.99; P = .002). CONCLUSIONS: Although Black patients represented only one-third of patients with gynecologic cancer, they accounted for disproportionate rates of hospitalization (>45%) and death (>40%) because of COVID-19 infection; younger Black patients had a nearly 5-fold greater risk of hospitalization. Efforts to understand and improve these disparities in COVID-19 outcomes among Black patients are critical.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , COVID-19/etnologia , Neoplasias dos Genitais Femininos/etnologia , Disparidades nos Níveis de Saúde , População Branca/estatística & dados numéricos , Adulto , Idoso , COVID-19/complicações , COVID-19/virologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Cidade de Nova Iorque , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/fisiologia , Análise de Sobrevida
16.
Cancer Immunol Immunother ; 70(10): 2951-2960, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33713153

RESUMO

INTRODUCTION: The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens. METHODS: We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection. RESULTS: A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4+ TILs were evident in 76.9% of cases, CD8+ in 92.3%, CD45RO+ in 92.3%, and FOXP3+ in 46.2%, as well as CD68+ TAMs in 100% and CD163+ in 100%. For the 15 BM cases, CD4+ TILs were evident in 60.0% of cases, CD8+ in 93.3%, CD45RO+ in 73.3%, and FOXP3+ in 35.7%, as well as CD68+ TAMs in 86.7% and CD163+ in 100%. CONCLUSION: An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias dos Genitais Femininos/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Neoplasias dos Genitais Femininos/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Microambiente Tumoral
17.
Gynecol Oncol ; 162(2): 506-516, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34023131

RESUMO

PURPOSE: Several professional organizations recommend universal genetic assessment for people with ovarian cancer as identifying pathogenic variants can affect treatment, prognosis, and all-cause mortality for patients and relatives. We sought to evaluate the literature on genetic assessment for women with ovarian cancer and determine if any interventions or patient characteristics drive utilization of services. METHODS: We searched key electronic databases to identify trials that evaluated genetic assessment for people with ovarian cancer. Trials with the primary aim to evaluate utilization of genetic assessment with or without interventions were included. Eligible trials were subjected to meta-analysis and the moderating influence of health interventions on rates of genetic assessment were examined. RESULTS: A total of 35 studies were included (19 report on utilization of genetic services without an intervention, 7 with an intervention, and 9 with both scenarios). Without an intervention, pooled estimates for referral to genetic counseling and completion of genetic testing were 39% [CI 27-53%] and 30% [CI 19-44%]. Clinician-facilitated interventions included: mainstreaming of genetic services (99% [CI 86-100%]), telemedicine (75% [CI 43-93%]), clinic-embedded genetic counselor (76% [CI 32-95%]), reflex tumor somatic genetic assessment (64% [CI 17-94%]), universal testing (57% [28-82%]), and referral forms (26% [CI 10-53%]). Random-effects pooled proportions demonstrated that Black vs. White race was associated with a lower rate of genetic testing (26%[CI 17-38%] vs. 40% [CI 25-57%]) as was being un-insured vs. insured (23% [CI 18-28%] vs. 38% [CI 26-53%]). CONCLUSIONS: Reported rates of genetic testing for people with ovarian cancer remain well below the goal of universal testing. Interventions such as mainstreaming can improve testing uptake. Strategies aimed at improving utilization of genetic services should consider existing disparities in race and insurance status.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Aconselhamento Genético/organização & administração , Testes Genéticos/estatística & dados numéricos , Neoplasias Ovarianas/diagnóstico , Encaminhamento e Consulta/organização & administração , Proteína BRCA1/genética , Proteína BRCA2/genética , Análise Mutacional de DNA/estatística & dados numéricos , Feminino , Aconselhamento Genético/estatística & dados numéricos , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Encaminhamento e Consulta/estatística & dados numéricos , Telemedicina/organização & administração , Telemedicina/estatística & dados numéricos
18.
Gynecol Oncol ; 160(2): 492-498, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33308865

RESUMO

BACKGROUND: The COVID-19 pandemic has resulted in unprecedented challenges for people living with cancer, impacting not only physical health but psychological well-being. The psychological response affects the individual as well as the community and can persist long after the outbreak. We aim to assess coping strategies employed by women with ovarian cancer during the COVID-19 pandemic. METHODS: Women with a current or prior diagnosis of ovarian cancer completed an online survey which included a query about coping strategies during the COVID-19 pandemic. The survey was distributed from March 30th through April 13, 2020 through survivor networks and social media. RESULTS: Six hundred and three women visited the survey website during the study period and 555 (92.0%) completed the survey. Four hundred and eight (73.5%) provided information on coping strategies utilized during COVID-19. Among those who responded, the median age was 58 years (range 20-85) and 150 participants (40.8%) were undergoing active cancer treatment. Commonly utilized adaptive coping strategies included emotional support (159, 39.0%), self care (148, 36.3%), hobbies (139, 34.1%), planning (87, 21.3%), positive reframing (54, 13.2%), religion (50, 12.3%) and instrumental support (38, 9.3%). Many participants also relied on avoidance coping strategies including self distraction (111, 27.2%) and substance use (19, 4.7%). CONCLUSIONS: Most ovarian cancer survivors are using adaptive, problem-focused coping strategies during the COVID-19 pandemic, however many are practicing avoidance strategies as well. As coping mechanisms profoundly impact quality of life, oncology providers must assist patients in identifying coping strategies that optimize physical and psychological well-being.


Assuntos
Adaptação Psicológica , COVID-19/epidemiologia , Neoplasias Ovarianas/psicologia , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/terapia
19.
Curr Treat Options Oncol ; 22(12): 117, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34812973

RESUMO

OPINION STATEMENT: COVID-19 has transformed the care we provide to gynecologic oncology patients. In addition to directly impacting the diagnosis and treatment of women with gynecologic cancer, it has affected our patient's ability to undergo recommended surveillance and has made an impact on every caregiver providing care during this time. Herein we review the current literature on the impact of COVID-19 on gynecologic oncology and highlight new approaches and innovations that have resulted in gynecologic cancer care as a result of the pandemic. The impact of COVID-19 on the field of gynecologic oncology has been profound. In addition to directly impacting the diagnosis and treatment of women with cancer, it has also challenged the very ethics with which we practice medicine. The equitable distribution of resources is paramount to upholding the Hippocratic Oath which we all invoke. The COVID-19 pandemic has stripped this oath down to its very core, forcing all medical practitioners to scrutinize who gets what resources and when. As the pandemic continues to unfold, the question remains - in the setting of a strained and overburdened healthcare system, how do we maximize beneficence to one group of patients, while maintaining non-maleficence to others? As gynecologic oncologists, we are responsible for advocating for our patients to ensure that the quality of their cancer care is not compromised, while also not overutilizing resources that are sorely needed for the care of COVID-19 victims, and not making them more likely to succumb to COVID-19 by the very nature of the treatment we provide. The effects of the pandemic are far-reaching and broad, and many of these are yet to be determined. Future studies are needed to analyze how the above-utilized strategies in GYN cancer care during the pandemic will impact the long-term outcomes of our patients.


Assuntos
COVID-19/prevenção & controle , Atenção à Saúde/normas , Neoplasias dos Genitais Femininos/terapia , Controle de Infecções/métodos , Oncologistas/normas , Padrões de Prática Médica/normas , SARS-CoV-2/isolamento & purificação , COVID-19/diagnóstico , COVID-19/transmissão , Feminino , Neoplasias dos Genitais Femininos/virologia , Humanos
20.
Int J Gynecol Cancer ; 31(2): 238-244, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32540894

RESUMO

INTRODUCTION: With the global incidence of ovarian cancer set to rise by 55% to 371 000 per year by 2035, current 5-year survival rates below 50%, and 15% of women with ovarian cancer dying within 2 months of diagnosis, urgent action is required to improve survival and quality of life. OBJECTIVE: To deal with the evidence gap relating to the experience of women with the disease around the globe and identify opportunities to drive progress. METHODS: The study included a review of global trends in incidence, mortality, and survival (October 2017); qualitative interviews with women and clinicians in 16 countries (December 2017); and an online survey for women available in 15 different languages (open for 2 months, March to early May 2018). Women were eligible to participate if they had been diagnosed in the previous 5 years and were proficient in one of the 15 languages offered. RESULTS: A total of 1531 women from 44 countries took part in the analysis. On average, 69.1% of women were not aware of ovarian cancer before their own diagnosis, varying from 50.9% (Hungary) to 86.4% (Brazil). A total of 78.3% of symptomatic women sought medical help, varying from 62.8% (Japan) to 87.7% (UK). Fewer than half of the women visited a doctor within 1 month (46.3%) of experiencing symptoms, varying from 38.5% (USA) to 77.3% (Germany), and a quarter of women waited 3 months or more. On average, 43.2% of women were diagnosed within 1 month of visiting a doctor, ranging from 30% (UK) to 62.3% (Italy). The average estimated time from experiencing symptoms to diagnosis was 31 weeks, but this ranged from 21.3 (Germany) to 39.7 (Brazil). Rates of post-diagnosis genetic testing ranged from 5.0% (Japan) to 79.1% (USA). Clinicians indicated that access to specialist treatment in high-volume centers varies greatly by country and region. CONCLUSION: The findings of this study identify some of the major challenges and opportunities to improve the time to diagnosis and management of women with ovarian cancer. These problems vary widely by country, and reducing the variability is an important first step towards improving outcomes for women with ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário/mortalidade , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/terapia , Feminino , Saúde Global , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Defesa do Paciente , Prevalência , Inquéritos e Questionários , Adulto Jovem
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