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OBJECTIVE: We conducted a multi-institutional observational study to investigate whether maintenance hormone therapy following primary treatment of low-grade advanced-stage ovarian cancer (LGSOC) is associated with an overall survival advantage. METHODS: We included patients with histologically confirmed stage III or IV LGSOC diagnosed between Jan 1, 2004, and Dec 31, 2019, treated in Commission on Cancer-accredited cancer programs in the US. Patients who received hormone therapy within six months of diagnosis were matched to controls who did not initiate hormone therapy during this timeframe by risk-set propensity score matching. The primary outcome was the risk of death from any cause within five years of initiation of HT or observation. RESULTS: There were 296 patients who initiated maintenance hormone therapy within six months of diagnosis and 2805 potential controls. Patients who received hormone therapy were more often treated in academic medical centers (55% vs. 44%), diagnosed later in the study period (62% vs. 23% diagnosed in 2018-2019), and frequently received no chemotherapy during initial treatment (45% vs. 17%). After risk set propensity score matching, we identified 225 patients treated with HT and 225 untreated controls who were otherwise similar with respect to measured covariates. In the matched cohort, hormone therapy was associated with a reduction in the risk of death (hazard ratio 0.60; 95% CI 0.38-0.94), corresponding to a 60-month survival of 75% compared with 65%. CONCLUSIONS: Following primary management of LGSOC, maintenance hormone therapy was associated with improved overall survival compared with observation.
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INTRODUCTION: Little is known as to how prolonged screening recommendations for cervical cancer have affected compliance. OBJECTIVE: We examined compliance with repeat cervical cancer screening among U.S. women aged 30-64 who underwent index screening between 2013 and 2019. STUDY DESIGN: The IBM Watson Health MarketScan Database was used to identify commercially-insured women 30-64 years old who underwent cervical cancer screening from 2013 to 2019. The cohort was limited to women with continuous insurance 12 months before and ≥ 2 months after index testing. Patients with prior hysterectomy, more frequent surveillance needs, or a history of abnormal cytology, histology, or HPV test were excluded. Index screening included cytology, co-testing, or primary HPV testing. Cumulative incidence curves described screening intervals. Compliance was considered if repeat screening occurred 2.5-4 years after index cytology and 4.5-6 years after index co-testing. Cause-specific hazard models examined factors associated with compliance. RESULTS: Of 5,368,713 patients identified, co-testing was performed in 2,873,070 (53.5%), cytology in 2,422,480 (45.1%), and primary HPV testing in 73,163 (1.4%). The cumulative incidence of repeat screening among all women by seven years was 81.9%. Of those who underwent repeat screening, 85.7% with index cytology and 96.6% with index co-testing were rescreened early. Only, 12.2% with index cytology had appropriate rescreening and 2.1% had delayed rescreening. Among the index co-testing group, 3.2% had appropriate rescreening and 0.3% had delayed rescreening. CONCLUSION: Appropriate cervical cancer follow-up screening is highly variable. The cumulative incidence rate of repeat screening was 81.9% and among women rescreened, the vast majority are tested earlier than recommended by current guidelines.
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Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Seguimentos , Detecção Precoce de Câncer , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Programas de Rastreamento , Esfregaço Vaginal , PapillomaviridaeRESUMO
OBJECTIVE: To assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials. METHODS: The National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens. RESULTS: A total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%-81.7% for patients meeting GOG-249 inclusion criteria, 40.2%-81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%-75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology. CONCLUSIONS: Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results.
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Neoplasias do Endométrio , Feminino , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Radioterapia Adjuvante , Estadiamento de Neoplasias , Neoplasias do Endométrio/patologia , Histerectomia , Quimioterapia AdjuvanteRESUMO
OBJECTIVE: To describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of cytoreductive surgery. METHODS: We identified women treated for stage III or IV serous ovarian cancer in a Commission on Cancer accredited program between January 2004-December 2020. Regression models were developed to evaluate trends in NACT use for LGSOC, to identify factors associated with receipt of NACT, and to quantify associations between NACT and bowel or urinary resection at the time of surgery. Demographic and clinical factors were used for confounder control. RESULTS: We observed 3350 patients who received treatment for LGSOC during the study period. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to an annual percent change of 7.2% (95% CI 5.6-8.9). Increasing age (rate ratio (RR) 1.15; 95% CI 1.07-1.24), and stage IV disease (RR 2.66; 95% CI 2.31-3.07) were associated with a higher likelihood of receiving NACT. For patients with high-grade disease, NACT was associated with a decrease in likelihood of bowel or urinary surgery (35.3% versus 23.9%; RR 0.68, 95% CI 0.65-0.71). For LGSOC, NACT was associated with a higher likelihood of these procedures (26.6% versus 32.2%; RR 1.24, 95% CI 1.08-1.42). CONCLUSION: NACT use among patients with LGSOC has increased from 2004 to 2020. While NACT was associated with a lower rate of gastrointestinal and urinary surgery among patients with high-grade disease, patients with LGSOC receiving NACT were more likely to undergo these procedures.
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Cistadenocarcinoma Papilar , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Estados Unidos/epidemiologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Terapia Neoadjuvante/métodos , Quimioterapia Adjuvante/métodos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/cirurgia , Cistadenocarcinoma Seroso/patologia , Neoplasias Peritoneais/patologia , Cistadenocarcinoma Papilar/tratamento farmacológico , Procedimentos Cirúrgicos de Citorredução/métodos , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
OBJECTIVE: Patients with recurrent endometrial cancer treated with carboplatin and paclitaxel whose disease progresses have few effective treatment options. Based on promising clinical trial data, the anti-programmed cell death 1 (anti-PD-1) antibody dostarlimab was recently granted accelerated approval for endometrial cancer by the US Food and Drug Administration. We developed a decision model to examine the cost-effectiveness of dostarlimab for patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer whose disease has progressed with first-line chemotherapy. DESIGN: Cost-effectiveness study. POPULATION: Hypothetical cohort of 6000 women with progressive/recurrent dMMR endometrial cancer. METHODS: The initial decision point in the Markov model was treatment with dostarlimab, pembrolizumab or pegylated liposomal doxorubicin (PLD). Model probabilities, and cost and utility values were derived with assumptions drawn from published literature. Effectiveness was estimated as average quality-adjusted life years (QALYs) gained. One-way, two-way and probabilistic sensitivity analyses were performed to vary the assumptions across a range of plausible values. MAIN OUTCOME MEASURES: The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: Pegylated liposomal doxorubicin (PLD) was the least costly strategy, at $55,732, followed by dostarlimab ($151,533) and pembrolizumab ($154,597). Based on a willingness-to-pay threshold of $100,000/QALY, PLD was cost-effective compared with dostarlimab, with an ICER of $331,913 per QALY gained for dostarlimab, whereas pembrolizumab was ruled out by extended dominance (less effective, more costly), compared with dostarlimab. In one-way sensitivity analyses, dostarlimab was cost-effective when its cost was reduced to $4905 (52% reduction). These results were robust in a variety of sensitivity analyses. CONCLUSIONS: Dostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer. Although the agent is substantially more costly, dostarlimab became cost-effective when its cost was reduced to $5489 per cycle.
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Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio , Humanos , Feminino , Análise Custo-Benefício , Recidiva Local de Neoplasia/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genéticaRESUMO
OBJECTIVE: Utilization of neoadjuvant chemotherapy (NACT) for advanced stage uterine cancer is increasing. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS. METHODS: The National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy vs a minimally invasive approach. To account for imbalances in confounders, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. RESULTS: A total of 1618 women were identified. Minimally invasive IDS was performed in 31.1% and increased from 16.2% in 2010 to 40.4% in 2017 (P < 0.001). More recent year of diagnosis and performance of surgery at a comprehensive cancer center were associated with increased use of MIS (P < 0.05). Women with serous and clear cell tumors, and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance) were less likely to undergo an MIS approach (P < 0.05). The median OS was 28 months (95% CI 23.7-30.7) and 24.3 months (95% CI 22.3-26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and survival (HR = 0.90, 95% CI 0.71-1.14). CONCLUSIONS: Among women with stage IV uterine cancer treated with NACT performance of minimally invasive debulking surgery is increasing. Compared to laparotomy, MIS does not appear to negatively impact survival.
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Carcinoma Endometrioide/cirurgia , Carcinossarcoma/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Histerectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Terapia Neoadjuvante , Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Neoplasias Uterinas/cirurgia , Idoso , Carcinoma Endometrioide/secundário , Carcinossarcoma/secundário , Procedimentos Cirúrgicos de Citorredução/tendências , Feminino , Humanos , Histerectomia/tendências , Seguro Saúde/estatística & dados numéricos , Laparotomia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/secundário , Neoplasias Uterinas/patologiaRESUMO
BACKGROUND: Total vaginal hysterectomy (TVH) has been proposed as an alternative to laparoscopic (TLH) and abdominal hysterectomy (TAH), particularly for women with medical comorbidities. We examined the use and long-term outcomes of vaginal hysterectomy for women with early-stage endometrial cancer. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women with stage I-II endometrial cancer treated with primary hysterectomy from 2000 to 2015. Multivariable regression models were developed to examine clinical, demographic, and pathologic factors associated with performance of TVH. The association between route of hysterectomy and cancer-specific and overall survival was examined using multivariable Cox proportional hazards models. RESULTS: A total of 19,212 patients including 837 (4.6%) who underwent TVH were identified. Performance of TVH declined from 4.5% in 2000 to 2.2% in 2015 (P < 0.0001). Compared to patients 65-69 years of age, patients 75-79 years old (aRR = 1.46; 95% CI, 1.19-1.79) and those >80 years old (aRR = 1.60; 95% CI, 1.30-1.97) were more likely to undergo TVH. Women with high grade tumors were less likely to undergo TVH. Five-year overall and cancer specific survivals were similar for TAH, TLH, and TVH. In multivariable models, there was no association between TVH and either cancer-specific survival (HR = 0.89; 95% CI, 0.65-1.22) compared to laparoscopic hysterectomy. CONCLUSION: Use of TVH for stage I and II endometrial cancer has decreased in the U.S. Chronologic age is the greatest predictor of performance of TVH. Performance of TVH does not negatively impact survival for women with early-stage endometrial cancer.
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Neoplasias do Endométrio/cirurgia , Histerectomia Vaginal/tendências , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Medicare , Fatores de Risco , Análise de Sobrevida , Estados UnidosRESUMO
OBJECTIVES: The optimal adjuvant therapy for uterine leiomyosarcoma (uLMS) remains uncertain. We analyzed the utilization of adjuvant chemotherapy and radiation therapy for stage II and III uLMS and explored the association between use of adjuvant therapy and survival. METHODS: Patients with stage II or III uLMS treated from 2004 to 2016 and recorded in the National Cancer Database were identified. Multivariable regression models were fit to estimate predictors of use of either adjuvant radiation therapy or chemotherapy. To analyze the impact of chemotherapy on all-cause mortality, an inverse probability of treatment weighted (IPTW) propensity score method was used to account for measured confounders, and the receipt of radiation therapy was adjusted in the outcome model. The process was repeated to analyze the impact of radiation therapy on all-cause mortality by using an IPTW propensity score method and adjusting for the receipt of adjuvant chemotherapy. RESULTS: A total of 890 patients were identified. Adjuvant chemotherapy use increased from 62.2% in 2010 to 70.4% in 2016, whereas radiation usage decreased from 26.7% in 2010 to 10.4% in 2016. Patients with stage III (vs. stage II) disease were less likely to receive radiation therapy. After propensity score weighting, chemotherapy was associated with a 30% decreased risk of all-cause mortality in stage III patients (HR 0.70, 95% CI 0.45-0.98) but had no effect on mortality for stage II patients (HR 0.93, 95% CI 0.70-1.20). Radiation therapy was associated with a 26% decreased risk of mortality for stage II tumors (HR 0.74; 95% CI, 0.53-0.99) and a 57% decrease in mortality for stage III disease (HR 0.43, 95% CI 0.18-0.99). CONCLUSIONS: Among women with stage II-III uLMS, use of chemotherapy is increasing while use of radiation therapy is decreasing. Radiation therapy is associated with improved survival in both stage II and III disease, while there was no association between use of adjuvant chemotherapy and survival in stage II patients.
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Quimioterapia Adjuvante , Leiomiossarcoma , Neoplasias Pélvicas , Neoplasias Uterinas , Quimioterapia Adjuvante/métodos , Terapia Combinada , Feminino , Humanos , Leiomiossarcoma/patologia , Leiomiossarcoma/terapia , Estadiamento de Neoplasias , Neoplasias Pélvicas/patologia , Neoplasias Pélvicas/terapia , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapiaRESUMO
OBJECTIVES: To compare the patterns of care and outcomes of Asian-Americans/Pacific Islanders (AAPI) to non-Hispanic White (NHW) women with uterine cancer, and examine differences across Asian country of origin. METHODS: National Cancer Database was used to identify AAPI and NHW women with uterine cancer diagnosed from 2004 to 2017. Marginal multivariable log-linear regression models and Cox proportional-hazards models were developed to estimate differences in quality-of-care and all-cause mortality between AAPI and NHW women and across AAPI ethnic groups. RESULTS: We identified 13,454 AAPI and 354,693 NHW women. Compared to NHW women, AAPI patients were younger at diagnosis (median age 57 vs. 62 years), had fewer comorbidities, more often had serous or sarcoma histologic subtypes and stage III/IV cancer. AAPI women had a slightly higher rate of receiving pelvic lymphadenectomy for deeply invasive or high-grade tumors (77.6% vs. 74.3%), and a lower rate of undergoing minimally invasive surgery (70.4% vs. 74.8%) for stage I-IIIC tumors. Among patients undergoing hysterectomy, AAPI women had a lower mortality compared with NHW women for cancer stage I/II/III, and a 28% reduction for type I (grade 1 or 2 endometrioid cancers) disease (aHR = 0.72; 95% CI, 0.64-0.81). Among AAPI subgroups, Pacific Islanders had the worst survival across different cancer stage and disease type. CONCLUSION: AAPI women are diagnosed with uterine cancer at a younger age and have more aggressive histologic subtypes and advanced stage than their White counterparts. They have a similar level of quality-of-care as NHW women, and an improved survival for early stage and type I disease.
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Asiático , Neoplasias do Endométrio , Povo Asiático , Feminino , Humanos , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico , Estadiamento de NeoplasiasRESUMO
OBJECTIVE: Cervical cancer screening guidelines have evolved over time with the incorporation of human papillomavirus (HPV) testing along with cytology. Current screening guidelines recommend cytological screening every 3 years or HPV testing with or without cytology every 5 years in women age 30-65 years. We examined the use of cervical cancer screening among average-risk Medicaid beneficiaries. DESIGN: Retrospective cohort study. POPULATION: Women age 30-64 years at average risk for cervical cancer who underwent cervical cancer screening with cytology, co-testing or primary HPV testing from 2013 to 2016. METHODS: The IBM Watson Health Multi-State Medicaid MarketScan Database was used. Subsequent screening rates within 3 years of the index test were examined. MAIN OUTCOME MEASURE: The rate of repeat cervical cancer screening was analysed using a cumulative incidence function. RESULTS: A total of 265 083 patients were identified. Overall, 43.1% (n = 114 312) had index co-testing, 55.2% (n = 146 309) had cytology and 1.7% (n = 4462) had primary HPV testing. The cumulative incidence of early, repeat cervical cancer screening was 3.9% at 12 months, 22.7% at 24 months and 33.3% at 36 months. During the period from 12 to 24 months after follow up, 20.9% of women underwent repeat screening while 19.4% underwent repeat screening 24-36 months after the index test. Among women who did not undergo repeat cervical cancer screening, a yearly gynaecological examination was performed in only 16 627 (10.7%) during year 2 and in 11 116 (8.8%) during year 3. CONCLUSION: Among average-risk Medicaid beneficiaries, cervical cancer screening is frequently overused. Women who do not undergo cervical cancer screening are unlikely to undergo routine gynaecological examination. TWEETABLE ABSTRACT: Among average-risk Medicaid beneficiaries, cervical cancer screening is frequently overused.
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Alphapapillomavirus , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Idoso , Colposcopia , Detecção Precoce de Câncer , Feminino , Humanos , Programas de Rastreamento , Medicaid , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Gravidez , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço Vaginal , Displasia do Colo do Útero/epidemiologiaRESUMO
OBJECTIVE: To examine the patterns and outcomes of sentinel lymph node (SLN) assessment in women with endometrial cancer. DESIGN: Retrospective cohort study. SETTING: United States inpatient and outpatient hospital services. POPULATION: Women with endometrial cancer who underwent a laparoscopic or robotic-assisted hysterectomy. METHODS: The Perspective Database from 2012 to 2018 was used. Performance of lymph node dissection was classified as SLN mapping, lymph node dissection or no nodal evaluation. Adjusted regression models were developed to examine the association between SLN mapping and morbidity and cost. MAIN OUTCOME MEASURES: Utilisation rates, morbidity and cost of both lymph node dissection and SLN mapping. RESULTS: Among 45 381 patients, SLN mapping was performed for 7768 patients (17.1%), lymph node dissection was performed for 23 214 patients (51.2%) and no lymphatic evaluation was performed for 14 399 patients (31.7%). SLN mapping increased from 1.8% in 2012 to 35.3% in 2018, whereas the rate of lymph node dissection decreased from 63.5% to 39.1% (p < 0.001). Among women who underwent nodal evaluation, residence in the west, White race and use of robotic-assisted hysterectomy were associated with SLN mapping (p < 0.05 for all). The complication rate was 5.9% for SLN mapping, compared with 7.3% in those that underwent lymph node dissection (aRR 0.85, 95% CI 0.77-0.95). The median hospital costs for women who underwent SLN mapping ($10 479) and lymph node dissection ($10 747) were higher than for those who did not undergo nodal assessment ($9149) (p < 0.001). CONCLUSIONS: The performance of SLN mapping is increasing for endometrial cancer. Compared with lymph node dissection, SLN mapping is associated with lower morbidity. SLN mapping significantly increases the costs compared with hysterectomy alone. TWEETABLE ABSTRACT: SLN mapping is increasing rapidly for endometrial cancer and is associated with decreased perioperative morbidity.
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Neoplasias do Endométrio , Laparoscopia , Linfonodo Sentinela , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo SentinelaRESUMO
In ovarian cancer patients, tumor fibrosis and angiotensin-driven fibrogenic signaling have been shown to inversely correlate with survival. We sought to enhance drug delivery and therapeutic efficacy by remodeling the dense extracellular matrix in two orthotopic human ovarian carcinoma xenograft models. We hypothesized that targeting the angiotensin signaling axis with losartan, an approved angiotensin system inhibitor, could reduce extracellular matrix content and the associated "solid stress," leading to better anticancer therapeutic effect. We report here four translatable findings: (i) losartan treatment enhances the efficacy of paclitaxel-a drug used for ovarian cancer treatment-via normalizing the tumor microenvironment, resulting in improved vessel perfusion and drug delivery; (ii) losartan depletes matrix via inducing antifibrotic miRNAs that should be tested as candidate biomarkers of response or resistance to chemotherapy; (iii) although losartan therapy alone does not reduce tumor burden, it reduces both the incidence and the amount of ascites formed; and (iv) our retrospective analysis revealed that patients receiving angiotensin system inhibitors concurrently with standard treatment for ovarian cancer exhibited 30 mo longer overall survival compared with patients on other antihypertensives. Our findings provide the rationale and supporting data for a clinical trial on combined losartan and chemotherapy in ovarian cancer patients.
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Antineoplásicos/farmacologia , Ascite/patologia , Losartan/farmacologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Células Estromais/patologia , Animais , Ascite/tratamento farmacológico , Colágeno/genética , Colágeno/metabolismo , Modelos Animais de Doenças , Sinergismo Farmacológico , Matriz Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hipóxia/metabolismo , Camundongos , MicroRNAs/genética , Modelos Teóricos , Estadiamento de Neoplasias , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Prognóstico , Estresse Fisiológico/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Ovarian cancer with miliary disease spread is an aggressive phenotype lacking targeted management strategies. We sought to determine whether adjuvant intravenous/intraperitoneal (IV/IP) chemotherapy is beneficial in this disease setting. METHODS: Patient/tumor characteristics and survival data of patients with stage IIIC epithelial ovarian cancer who underwent optimal primary debulking surgery from 01/2010 to 11/2014 were abstracted from records. Chi-square and Mann-Whitney U tests were used to compare categorical and continuous variables. The Kaplan-Meier method was used to estimate survival curves, and outcomes were compared using log-rank tests. Factors significant on univariate analysis were combined into multivariate logistic regression survival models. RESULTS: Among 90 patients with miliary disease spread, 41 (46%) received IV/IP chemotherapy and 49 (54%) received IV chemotherapy. IV/IP chemotherapy, compared with IV chemotherapy, resulted in improved progression-free survival (PFS; 23.0 versus 12.0 months; p = 0.0002) and overall survival (OS; 52 versus 36 months; p = 0.002) in patients with miliary disease. Among 78 patients with nonmiliary disease spread, 23 (29%) underwent IV/IP chemotherapy and 55 (71%) underwent IV chemotherapy. There was no PFS or OS benefit associated with IV/IP chemotherapy over IV chemotherapy in these patients. On multivariate analysis, IV/IP chemotherapy was associated with improved PFS (HR, 0.28; 95% CI 0.15-0.53) and OS (HR, 0.33; 95% CI 0.18-0.61) in patients with miliary disease compared with those with nonmiliary disease (PFS [HR, 1.53; 95% CI 0.74-3.19]; OS [HR, 1.47; 95% CI 0.70-3.09]). CONCLUSIONS: Adjuvant IV/IP chemotherapy was associated with oncologic benefit in miliary disease spread. This survival benefit was not observed in nonmiliary disease.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ovarianas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Humanos , Infusões Parenterais , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Fragmentation occurs when a patient receives care at more than one hospital, and the long-term effects in ovarian cancer are unknown. We examined the association between fragmentation of primary debulking surgery (PDS) and adjuvant chemotherapy (AC) and overall survival (OS). METHODS: The National Cancer Database was used to identify women with stage II-IV epithelial ovarian cancer between 2004 and 2016 who underwent PDS followed by AC. Fragmentation was defined as receipt of AC at a different institution than where PDS was performed. After propensity score weighting, proportional hazard models were developed to estimate the association between fragmented care and OS. RESULTS: Of the 36,300 patients identified, 13,347 (36.8%) had fragmented care. Patient factors associated with fragmentation included older age, higher income, and longer travel distance for PDS; hospital factors included PDS performed at a community center or a facility with lower annual surgical volume (P < 0.05, all). Fragmentation was associated with a 15% risk of 30-day delay to AC (aRR 1.15, 95% CI 1.09-1.22). In a propensity scoring weighted analysis, mortality was reduced when AC was fragmented (HR 0.95, 95% CI 0.92-0.97). Sensitivity analyses indicated fragmentation was associated with improved survival in metropolitan residents. Stratified analyses indicated patients who traveled 50 miles or more with PDS and AC at the same institution had the worst OS. CONCLUSION: Fragmentation of PDS and AC has no adverse effects on long-term survival. Survival outcomes were worst for those who received care at the same institution 50 miles or more away.
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Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/mortalidade , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Taxa de SobrevidaRESUMO
OBJECTIVE: To explore trends of ovarian conservation (OCN) over time in young women with early stage leiomyosarcoma (LMS) and examine the association between OCN and survival. METHODS: Patients under the age of 50 who were diagnosed with stage I LMS who underwent hysterectomy with and without oophorectomy between 2010 and 2016 were identified in the National Cancer Database (NCDB). Performance of oophorectomy vs. OCN was determined using surgery codes. Trends of OCN were reported. Multivariable regression models were fit to estimate predictors of OCN. An inverse probability of treatment weighted propensity score method was used to examine the association between all-cause mortality and OCN. RESULTS: Overall, 225 patients (28%) underwent OCN. Rates of OCN decreased from 41.2% (2010) to 14.3% (2016); this finding was consistent across age groups: <35, 35-39, 40-44, and 45-49 years. Race, insurance, and stage did not affect performance of OCN. Women with poorly differentiated tumors were less likely to undergo OCN compared to well-differentiated tumors (aRR 0.59; 95% CI 0.40-0.86). After propensity score weighting, there was no association between OCN and mortality (HR 1.19, 95% CI 0.80-1.77). Five-year survival for the OCN group was 67.1% (95% CI 59.8-75.2%) compared to 72.2% for the oophorectomy group (95% CI 67.2-77.5%). CONCLUSIONS: OCN for early stage LMS in premenopausal women has decreased over time. There was no association between OCN and mortality among women with stage I LMS. OCN should be considered in premenopausal women with stage I LMS given the health benefits.
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Leiomiossarcoma/terapia , Tratamentos com Preservação do Órgão , Perimenopausa , Neoplasias Uterinas/terapia , Adulto , Bases de Dados Factuais , Feminino , Humanos , Histerectomia , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ovariectomia , Análise de Sobrevida , Estados Unidos , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologiaRESUMO
BACKGROUND: Clinical trials demonstrated that PARPi (poly [adenosine diphosphate-ribose]-ADP polymerase inhibitor) therapy is effective in solid tumors. However, long term effects such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) are poorly described. We sought to quantify whether PARPi therapy is associated with the development of MDS/AML. METHODS: Medline, Embase, and Cochrane databases were searched (inception to January 6, 2020) and phase 2 and 3 clinical trials that randomized patients with solid tumors to a PARPi or control therapy were included. The PRISMA guidelines were used to extract data independently by multiple authors. We extracted person-time and number of cases of MDS/AML in the PARPi and control arms of each study and pooled results with a random-effects Poisson regression model. The pooled incidence rate ratio (IRR) for MDS/AML among patients randomized to PARPi therapy was compared to those randomized to a control. RESULTS: We identified 14 studies that included 5739 patients. Accounting for intra-study clustering, the risk of MDS/AML was similar in patients who were randomly assigned to receive PARPi compared to controls (IRR 1.32, 95% confidence interval [CI] 0.78-2.26). In the front-line setting, PARPi therapy was associated with developing MDS/AML (IRR 5.43, 95% CI 1.51-19.60). Among patients treated for recurrence, however, the risk of MDS/AML appeared to be similar among patients randomized to PARPi or control treatment. Among studies that included only patients with a BRCA mutation, the risk of MDS/AML was similar in both treatment groups (IRR 0.83, 95% CI 0.45-1.53), but PARPi therapy was associated with MDS/AML in studies with an unrestricted population (IRR 2.43, 95% CI 1.17-5.06). CONCLUSION: The pooled overall effect was not statistically significant. However, treatment with PARPi was associated with a statistically significant increase in the incidence of MDS/AML among patients receiving front-line cancer therapy and those with limited prior exposure to chemotherapy.
Assuntos
Leucemia Mieloide Aguda/induzido quimicamente , Síndromes Mielodisplásicas/induzido quimicamente , Neoplasias/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Humanos , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the impact of size and distribution of residual disease after interval debulking surgery on the timing and patterns of recurrence for patients with advanced-stage epithelial ovarian cancer. METHODS: Patient demographics and data on disease treatment/recurrence were collected from medical records of patients with stage IIIC/IV epithelial ovarian cancer who were managed with neoadjuvant chemotherapy/interval debulking surgery between January 2010 and December 2014. Among patients without complete surgical resection but with ≤1 cm of residual disease, the number of anatomic sites (<1 cm single anatomic location vs <1 cm multiple anatomic locations) was used to describe the size and distribution of residual disease. RESULTS: A total of 224 patients were included. Of these, 70.5% (n=158) had a complete surgical resection, 12.5% (n=28) had <1 cm single anatomic location, and 17.0% (n=38) had <1 cm multiple anatomic locations. Two-year progression-free survival for complete surgical resection, <1 cm single anatomic location, and <1 cm multiple anatomic locations was 22.2%, 17.9% and 7%, respectively (p=0.007). Size and distribution of residual disease after interval debulking surgery did not affect location of recurrence and most patients had recurrence at multiple sites (complete surgical resection: 64.7%, <1 cm single anatomic location: 55.6%, and <1 cm multiple anatomic locations: 71.4%). Controlling for additional factors that may influence platinum resistance and surgical complexity, the rate of platinum-resistant recurrence was similar for patients with complete surgical resection and <1 cm single anatomic location (OR=1.07, 95% CI 0.40 to 2.86; p=0.888), but women with <1 cm multiple anatomic locations had an increased risk of platinum resistance (OR=3.09, 95% CI 1.41 to 6.78 p=0.005). CONCLUSIONS: Despite current classification as 'optimal,' <1 cm multiple anatomic location at the time of interval debulking surgery is associated with a shorter progression-free survival and increased risk of platinum resistance.
Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Neoplasia Residual/patologia , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/métodos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
INTRODUCTION: Fifteen per cent of women with cervical cancer are diagnosed with advanced disease and carry a 5 year survival rate of only 17%. Cervical cancer may lead to particularly severe symptoms that interfere with quality of life, yet few studies have examined the rate of palliative care referral in this population. This study aims to examine the impact of palliative care referral on women who have died from cervical cancer in two tertiary care centers. METHODS: We conducted a retrospective review of cervical cancer decedents at two tertiary institutions from January 2000 to February 2017. We examined how aggressive measures of care at the end of life, metrics defined by the National Quality Forum, interacted with clinical variables to understand if end-of-life care was affected. Univariate and multivariate parametric and non-parametric testing was used, and linear regression models were generated to determine unadjusted and adjusted associations between aggressive measures of care at the end of life with receipt of palliative care as the main exposure. RESULTS: Of 153 cervical cancer decedents, 73 (47%) received a palliative care referral and the majority (57%) of referrals occurred during an inpatient admission. The median time from palliative care consultation to death was 2.3 months and 34% were referred to palliative care in the last 30 days of life. Palliative care referral was associated with fewer emergency department visits (OR 0.18, 95% CI 0.05 to 0.56), inpatient stays (OR 0.21, 95% CI 0.07 to 0.61), and intensive care unit admissions (OR 0.24, 95% CI 0.06 to 0.93) in the last 30 days of life. Palliative care did not affect chemotherapy or radiation administration within 14 days of death (p=0.36). Women evaluated by palliative care providers were less likely to die in the acute care setting (OR 0.19, 95% CI 0.07 to 0.51). DISCUSSION: In two tertiary care centers, less than half of cervical cancer decedents received palliative care consultations, and those referred to palliative care were often evaluated late in their disease course. Palliative care utilization was also associated with a lower incidence of poor-quality end-of-life care.
Assuntos
Cuidados Paliativos/estatística & dados numéricos , Qualidade de Vida , Encaminhamento e Consulta/estatística & dados numéricos , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Oncologia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Assistência Terminal/métodos , Fatores de Tempo , Neoplasias do Colo do Útero/mortalidadeRESUMO
OBJECTIVE: To synthesize evidence from studies investigating survival outcomes for patients with ovarian cancer undergoing minimally invasive surgery (traditional or robotic laparoscopy) compared with those for patients with ovarian cancer undergoing laparotomy. DATA SOURCES: We searched Ovid MEDLINE and Embase (from inception to December 2019). METHODS OF STUDY SELECTION: Observational cohort studies and randomized controlled trials that compared risk of recurrence or death between women undergoing minimally invasive and open procedures for staging (10), interval cytoreduction (4), secondary cytoreduction (2), and evaluation of resectability (1) were included. TABULATION, INTEGRATION, AND RESULTS: Data on the number of participants, number of deaths and recurrences, and results of analyses of overall or progression-free survival were abstracted for all studies. A random-effects meta-analysis was used to pool the results of studies comparing minimally invasive staging and open staging. The surgical approach (minimally invasive versus open) was not significantly associated with hazard of death or recurrence (pooled hazard ratio 0.92; 95% confidence interval, 0.61-1.38) or all-cause mortality (pooled hazard ratio 0.96; 95% confidence interval, 0.49-1.89). One randomized trial demonstrated that diagnostic laparoscopy could triage patients to neoadjuvant chemotherapy and avoid suboptimal primary surgery, without affecting recurrence-free or overall survival. Most studies included in this review were observational and at high risk for bias, and few studies accounted for potential confounding. CONCLUSION: Although existing studies do not demonstrate deleterious survival effects associated with minimally invasive surgery for ovarian cancer, these data must be viewed with caution given the significant methodologic shortcomings in the existing literature.
Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Ovarianas/cirurgia , Adulto , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/patologia , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/métodos , Procedimentos Cirúrgicos em Ginecologia/estatística & dados numéricos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Laparotomia/efeitos adversos , Laparotomia/métodos , Laparotomia/estatística & dados numéricos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Estudos Observacionais como Assunto/estatística & dados numéricos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricosRESUMO
OBJECTIVE: The objective of the current study was to analyze the outcomes of short versus long leg casts in the treatment of childhood accidental spiral tibial (CAST) fractures. METHODS: A retrospective review was performed of medical records at a single tertiary children's hospital from 2009 to 2014 of children with distal, spiral tibial fractures (CAST fractures). The following points were documented for each patient: sex, laterality of fracture, age at presentation, type of cast, length of time in cast, use of a controlled ankle motion boot after cast removal, suspicion for abuse, and complications including skin irritation, skin breakdown, infection, compartment syndrome, fracture displacement, and gait disturbances. RESULTS: A total of 21 patients with an age range of 12 to 62 months were found to have CAST fractures as confirmed by x-ray. Fourteen were treated with short leg casts, whereas 7 were treated with long leg casts. Both groups healed with equal outcomes, and there was no documented suspicion for abuse in any case. CONCLUSIONS: A short leg walking cast seems to be an effective and safe method of treatment for CAST fractures and could be considered as potentially preferable to long leg casts because of the added benefits of increased mobility and function. Follow-up to this preliminary study is warranted to better elucidate any differences in benefit between these treatment options, and clinical judgment should be used when considering immobilization options.