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1.
Ann Oncol ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866180

RESUMO

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. RESULTS: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile.

3.
Gynecol Oncol ; 163(2): 312-319, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34563366

RESUMO

OBJECTIVE: Immuno-oncology (IO) has rapidly evolved, with many IO therapies either approved or under investigation for multiple malignancies. Biomarkers exist that can predict response to IO therapies including PD-L1 expression, microsatellite instability (MSI), and total mutation burden (TMB). This paper serves to analyze the presence of these biomarkers across gynecologic cancers. METHODS: A total of 16,300 gynecologic cancer specimens submitted for molecular profiling to Caris Life Sciences were reviewed. Immunohistochemistry was performed using the SP142 anti-PD-L1 clone and assessed for intensity. Next-generation sequencing, immunohistochemistry, and fragment analysis were used to determine MSI status. TMB was measured by counting all non-synonymous missense mutations found per tumor not previously described as germline alterations. Chi-Square, Fisher Exact, and the Kruskal-Wallis test were used to compare cohorts. RESULTS: Of 16,300 specimens, 54.1% were ovarian, 37.2% uterine, 7.2% cervical, 0.3% vulvar, 1.2% vaginal, with 0.1% unspecified. MSI-H was most frequent in uterine cancer (17.7%) and only 1% of ovarian cancers. PD-L1 expression was present in 38.3% of cervical and 62.5% of vulvar cancers, but less than 8% of ovarian and uterine cancers. TMB-H was present in 21.1% cervical, 19.7% uterine, and 5% ovarian cancers. Few specimens exhibited a "triple positive" phenotype - 0.3% ovarian, 1.5% uterine, and 1.5% cervical. Associations were seen between MSI, TMB, and PD-L1 across all cancer types. CONCLUSIONS: The frequency of individual biomarkers pertinent to IO therapy varies by cancer type. HPV-driven genital tract cancers have higher frequencies of PD-L1 expression, MSI-H, and TMBH. Endometrial cancers are characterized by MSI-H and TMB, whereas ovarian cancers have a low frequency of MSI-H and modest PD-L1 or TMBH. The incidence of 'triple positive" cases was less than 2%.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias dos Genitais Femininos/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Instabilidade de Microssatélites , Antígeno B7-H1 , Tomada de Decisão Clínica/métodos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/patologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Mutação , Seleção de Pacientes
4.
Gynecol Oncol ; 155(2): 186-191, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31519320

RESUMO

OBJECTIVE: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). METHODS: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. RESULTS: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805-1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863-2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713-0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. CONCLUSION: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT00866697.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Adulto , Idoso , Carcinoma Epitelial do Ovário/mortalidade , Intervalo Livre de Doença , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Indazóis , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
5.
Ann Oncol ; 30(5): 721-732, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30887020

RESUMO

BACKGROUND: Ovarian cancer remains the most deadly gynecologic cancer with the majority of patients relapsing within 3 years of diagnosis. Traditional treatment paradigms linked to platinum sensitivity or resistance are currently being questioned in the setting of new diagnostic methods and treatment options. DESIGN: Authors carried out review of the literature on key topics in treatment of recurrent epithelial ovarian cancer (EOC) when platinum is still an option; including secondary surgical cytoreduction, chemotherapy, novel treatment options, and maintenance therapy. A treatment algorithm is proposed. RESULTS: Molecular characterization of EOC is critical to help guide treatment decisions. The role of secondary cytoreductive surgery is currently being evaluated with results from Gynecologic Oncology Group (GOG) 213 and anticipated results from DESKTOP III clinical trials. Chemotherapy backbone has remained relatively unchanged but utilizing non-platinum-based regimens is under investigation. In addition, maintenance therapy with anti-angiogenic therapy and Poly (ADP-ribose) Polymerase (PARP) inhibitors has emerged as the standard of care. Novel combinations, including immunotherapy and anti-angiogenesis agents, may further change the current landscape. CONCLUSIONS: The treatment of recurrent EOC is rapidly changing. Clinical trial design will need to continue to evolve as many novel therapies move to the upfront setting. Ultimately, the treatment of patients with recurrent EOC must incorporate individual patient and tumor factors.


Assuntos
Carcinoma Epitelial do Ovário/terapia , Recidiva Local de Neoplasia/terapia , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/terapia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Imunoterapia/métodos , Terapia de Alvo Molecular , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
6.
Ann Oncol ; 29(3): 737-743, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29267856

RESUMO

Background: Health-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methods: HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ. Results: There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI - 0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P < 0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P [hazard ratio (HR) 0.72, 95% CI 0.69-0.86, P = 0.0001]. Conclusions: There were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS. Clinical Trials Registration Number: NCT00866697.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Quimioterapia de Manutenção/efeitos adversos , Neoplasias Ovarianas/tratamento farmacológico , Pirimidinas/efeitos adversos , Qualidade de Vida , Sulfonamidas/efeitos adversos , Adulto , Inibidores da Angiogênese/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Indazóis , Quimioterapia de Manutenção/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Intervalo Livre de Progressão , Tempo para o Tratamento
7.
Clin Transl Oncol ; 16(9): 761-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24986099

RESUMO

The objective of this review is to summarize recent scientific and medical literature regarding chemoresponse assays or chemotherapy sensitivity and resistance assays (CSRAs), specifically as applied to epithelial ovarian cancer. A total of sixty-seven articles, identified through PubMed using the key words "in vitro chemoresponse assay," "chemo sensitivity resistance assay," "ATP," "HDRA," "EDR," "MiCK," and "ChemoFx," were reviewed. Recent publications on marker validation, including relevant clinical trial designs, were also included. Recent CSRA research and clinical studies are outlined in this review. Published findings demonstrate benefits regarding patient outcome with respect to recent CSRAs. Specifically, analytical and clinical validations, as well as clinical utility and economic benefit, of the most common clinically used CSRA in the United States support its use to aid in making effective, individualized clinical treatment selections for patients with ovarian cancer.


Assuntos
Bioensaio/métodos , Bioensaio/normas , Resistencia a Medicamentos Antineoplásicos , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Biomarcadores Tumorais/análise , Carcinoma Epitelial do Ovário , Feminino , Humanos , Projetos de Pesquisa
9.
Int J Gynecol Cancer ; 18(5): 879-90, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18053062

RESUMO

Epidermal growth factor receptor (EGFR) inhibitors are a new biologically targeted therapy, which may offer new hope in the treatment of patients with advanced or recurrent ovarian cancers. In this review, we summarize and discuss the results of research to date on EGFR inhibitors with particular emphasis on ovarian cancer. We reviewed data identified by searches of MEDLINE, PubMed, and abstracts from the proceedings of the American Society of Clinical Oncology meetings from 1998 to 2006, with the search terms "Ovarian Cancer,""EGFR,""gefitinib, ZD1839, Iressa,""erlotinib, OSI-774, Tarceva,""CI-1033,"" GW 572016, lapatinib,""PKI-166,""EKB 569,""anti-EGFR antibodies,""trastuzumab, Herceptin,""cetuximab, Erbitux, IMC-C225,""matuzumab, EMD 72000,""panitumamab, ABX-EGF,""pertuzumab," and "vandetanib, rINN, Zactima, ZD6474." Phase II trials of both small molecule inhibitors of EGFR- and antibody-based inhibitors are currently ongoing in ovarian cancer and emerging data suggest that their activity in unselected women with advanced or recurrent ovarian cancer is modest, when utilized as a single agent. It is possible that these agents will be highly effective in smaller subsets of patients whose tumors are dependent on EGFR signaling, perhaps through activating mutations in EGFR or its downstream pathway. Targeted therapy with EGFR inhibitors is an untapped potential resource in the treatment of advanced or recurrent ovarian cancer. Ongoing trials will elucidate the most effective strategies to use these agents individually or in combination with traditional chemotherapeutic agents.


Assuntos
Antineoplásicos/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Receptores ErbB/metabolismo , Feminino , Humanos , Ligantes , Neoplasias Ovarianas/enzimologia
10.
Int J Gynecol Cancer ; 17(3): 561-70, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17504373

RESUMO

Ovarian cancer is the fourth leading cause of cancer death among women in the United States. First-line chemotherapy offered to patients with ovarian cancer generally consists of an intravenous (IV) platinum plus taxane regimen and has remained virtually unchanged for the past 10 years. A number of recently completed phase III randomized trials in the United States have reported improved progression-free survival (PFS) and/or overall survival (OS) with the intraperitoneal (IP) administration of cisplatin. The purpose of this study was to pool the published data to perform a meta-analysis of randomized trials of IP cisplatin in the initial chemotherapy treatment of ovarian cancer patients. This study was initiated to obtain a more valid estimate of the therapeutic impact of IP treatment for these patients. A search strategy was initiated that searched published findings of randomized trials of IP cisplatin therapy from multiple sources from January 1990 through January 2006. Six randomized trials of 1716 ovarian cancer patients were identified and included in this analysis. The pooled hazard ratio (HR) for PFS of IP cisplatin as compared to IV treatment regimens is 0.792 (95% CI: 0.688-0.912, P= 0.001), and the pooled HR for OS is 0.799 (95% CI: 0.702-0.910, P= 0.0007). These findings strongly support the incorporation of an IP cisplatin regimen to improve survival in the front-line treatment of stage III, optimally debulked ovarian cancer.


Assuntos
Carcinoma/tratamento farmacológico , Cisplatino/administração & dosagem , Terapia Neoadjuvante , Neoplasias Ovarianas/tratamento farmacológico , Algoritmos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma/mortalidade , Cisplatino/efeitos adversos , Feminino , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
11.
Int J Gynecol Cancer ; 17(2): 311-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17362308

RESUMO

Over the past two decades, immunohistochemical techniques have improved to such a degree that it is now a common adjuvant test to the traditional hematoxylin and eosin-stained histologic sections. It is used in most realms of surgical pathology and can often aid in final diagnosis and, in some cases, prognosis. However, immunohistochemistry (IHC) is not always helpful and many pitfalls to its use exist. Understanding the basics of IHC, its utility and difficulties will aid clinicians in better understanding how diagnoses are rendered. This study reviews the general principles of IHC and demonstrates its utility with several commonly encountered problematic areas in gynecological pathology.


Assuntos
Carcinoma/diagnóstico , Carcinoma/patologia , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/patologia , Imuno-Histoquímica/métodos , Carcinoma/secundário , Análise Custo-Benefício , Inibidor p16 de Quinase Dependente de Ciclina/análise , Feminino , Neoplasias dos Genitais Femininos/secundário , Humanos , Imuno-Histoquímica/economia , Queratina-20/análise , Queratina-7/análise , Neoplasias Primárias Desconhecidas/diagnóstico
13.
Ann Oncol ; 13(11): 1819-25, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12419757

RESUMO

BACKGROUND: Rubitecan (9-nitrocamptothecin, 9-NC, Orathecin) and gemcitabine have single-agent activity in pancreatic and ovarian carcinoma. We conducted a phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in advanced malignancies. PATIENTS AND METHODS: Twenty-one patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of rubitecan at 0.75 mg/m(2)/day administered orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m(2) administered intravenously on days 1 and 8 of a 21-day cycle. RESULTS: The MTD was defined as rubitecan 1 mg/m(2) administered orally days 1-5 and 8-12, and gemcitabine 1000 mg/m(2) administered intravenously over 30 min days 1 and 8, given every 21 days. Dose-limiting toxicity was myelosuppression including neutropenia and thrombocytopenia. Other side effects included diarrhea, nausea, vomiting and fatigue. Five patients with stable disease were observed among 18 evaluable patients. CONCLUSIONS: The recommended phase II dose is rubitecan 1 mg/m(2) given orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m(2) as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Camptotecina/análogos & derivados , Desoxicitidina/análogos & derivados , Neoplasias/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Biópsia por Agulha , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Metástase Linfática , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias/patologia , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Gencitabina
14.
Gynecol Oncol ; 86(1): 62-8, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12079302

RESUMO

OBJECTIVE: MLH1 methylation is associated with the microsatellite instability (MSI) phenotype in endometrial cancer and atypical endometrial hyperplasia, a premalignant precursor to carcinoma. The observation that methylation is also seen in atypical endometrial hyperplasia without MSI suggests that methylation is an early event in endometrial tumorigenesis. Our objective was to determine if methylation is always present in MSI-positive atypical hyperplasia concomitant with MSI-positive, methylation-positive carcinoma. METHODS: We used laser capture microdissection to study MLH1 methylation and MSI in a large series of endometrial cancer cases that had previously been shown to have methylation and the MSI-high (MSI-H) phenotype. We resampled areas of carcinoma from 27 patients along with 51 foci of concomitant atypical endometrial hyperplasia. RESULTS: Consistent with previous reports, we saw MLH1 methylation in areas of atypical endometrial hyperplasia that did not show MSI. In addition, we noted that 18% of the MSI-H atypical endometrial hyperplasia DNAs lacked methylation of critical cytosines in the MLH1 promoter. Immunohistochemistry studies showed that these MSI-H unmethylated foci of atypical endometrial hyperplasia failed to express MLH1, as did regions of simple hyperplasia. CONCLUSION: Methylation of the MLH1 promoter is an early event in endometrial tumorigenesis. Given that not all MSI-positive tissues had methylation at cytosines -229 and -231, it appears that methylation may not be required for MLH1 silencing and loss of mismatch repair.


Assuntos
Metilação de DNA , Reparo do DNA , Hiperplasia Endometrial/genética , Neoplasias do Endométrio/genética , Repetições de Microssatélites/genética , Proteínas de Neoplasias/genética , Proteínas Adaptadoras de Transdução de Sinal , Pareamento Incorreto de Bases , Proteínas de Transporte , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Proteína 1 Homóloga a MutL , Proteínas de Neoplasias/biossíntese , Proteínas Nucleares , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Regiões Promotoras Genéticas
15.
Gynecol Oncol ; 83(3): 533-6, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11733967

RESUMO

OBJECTIVE: We set out to determine the factors that predict subcutaneous implanted central venous port function. Specifically, we sought to determine whether the location of the catheter tip is correlated with port failure. METHODS: A review of all gynecologic oncology patients who underwent initial port placement between 1993 and 1998 was undertaken. The initial chest radiograph following port placement was reviewed, and the venous location of the catheter tip was recorded. Patients were followed until port removal, death, or the last documentation of port function. RESULTS: Two hundred thirty-six patients underwent port placement during the study period. The majority of patients (97%) had their port placed for intravenous chemotherapy. The median time of port duration in patients with a functional port was 21.6 months. Forty of the 236 ports (17%) were removed because of device malfunction. Catheter tips were located in the central venous system in 164 (69%) cases and outside of the central venous system in 72 (31%) cases. Removal secondary to malfunction was significantly higher when the catheter tip was located outside of the central venous system (30/72 (42%) versus 10/164 (6%), P = 0.001). By life-table analysis, ports removed for malfunction with their tips located centrally had a significantly longer median duration of functional use than those whose tips were located peripherally (78 versus 44 months, P = 0.0001). CONCLUSIONS: The rate of port removal secondary to malfunction is significantly less if the catheter tip is located in the central venous system. Confirmation of the location of the catheter tip is imperative for the long-term function of a subcutaneous implanted central venous port.


Assuntos
Cateterismo Venoso Central/métodos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/normas , Falha de Equipamento , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico
16.
Genes Chromosomes Cancer ; 32(4): 295-301, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11746970

RESUMO

We set out to determine the relative timing of loss of DNA mismatch repair and KRAS2 mutation in endometrial tumorigenesis. We studied endometrial carcinoma (CA) and synchronous atypical endometrial hyperplasia (AEH), the premalignant precursor of endometrial cancer. Carcinoma and hyperplasia were investigated for loss of mismatch repair as evidenced by microsatellite instability (MSI) and for KRAS2 mutations. Endometrial cancers previously shown to be MSI-positive were evaluated for KRAS2 codon 12 and 13 mutations. DNA was isolated from foci of AEH concomitant with, but physically remote from, the cancers by use of tissues prepared by laser capture microdissection (LCM). The AEH DNAs were then assessed for MSI and KRAS2 mutations. Of 210 endometrial CAs investigated, 51 (26%) were MSI-positive, and among those, 21 (41%) arose concomitantly with AEH. Of 41 foci of AEH (mean, two foci per patient) investigated, 34 (83%) were MSI-positive. KRAS2 mutations were seen in 5/51 (10%) MSI-positive carcinomas. From the five patients informative for both KRAS2 mutation and MSI, 10 foci of AEH were available for investigation. All 10 AEH specimens (100%) were MSI-positive, and six (60%) had the KRAS2 mutation present in the coexisting CA. The observation that some MSI-positive AEH specimens lack the KRAS2 mutation seen in the coexisting CA supports a model in which loss of DNA mismatch repair precedes KRAS2 mutation. However, in addition to the absence of KRAS2 mutations in AEH, we discovered mutations in LCM hyperplasia and carcinoma specimens that were not present in the portion of the cancers originally investigated. These discordant genotypes suggest genetic heterogeneity in endometrial hyperplasia and concomitant cancer.


Assuntos
Pareamento Incorreto de Bases/genética , Carcinoma/genética , Reparo do DNA/genética , Neoplasias do Endométrio/genética , Mutação/genética , Proteínas Proto-Oncogênicas/genética , Progressão da Doença , Hiperplasia Endometrial/genética , Neoplasias do Endométrio/etiologia , Feminino , Genótipo , Humanos , Fenótipo , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras
17.
Obstet Gynecol ; 98(5 Pt 2): 980-2, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11704231

RESUMO

BACKGROUND: Meigs' syndrome refers to solid, benign ovarian tumors, ascites, hydrothorax, and resolution of these signs after surgery. Meigs' syndrome with an elevated CA 125 secondary to benign Brenner tumors is exceedingly rare. CASE: A postmenopausal woman presented with a large pelvic mass, ascites, and a right pleural effusion. Serum CA 125 was 759 IU/mL. Ascitic fluid, pleural fluid, and fine needle aspiration of the mass were without evidence of malignancy. Exploratory laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy revealed benign Brenner tumors. Immunohistochemical staining for CA 125 showed immunoreactivity in the omentum only. Postoperatively, her signs and symptoms resolved completely and did not recur. CONCLUSION: Cytologic or histologic confirmation of malignancy is imperative in patients with a pelvic mass, ascites, hydrothorax, and elevated CA 125 before initiating chemotherapy.


Assuntos
Tumor de Brenner/complicações , Antígeno Ca-125/sangue , Síndrome de Meigs/etiologia , Neoplasias Ovarianas/complicações , Idoso , Ascite/etiologia , Feminino , Humanos , Hidrotórax/etiologia , Pós-Menopausa
18.
Clin Obstet Gynecol ; 44(3): 531-7, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11685877

RESUMO

After the logic of evidence-based medicine, there are several conclusions to be reached from these recent prospective, randomized phase III clinical trials. Patients with stages IB2 and IIA cervical carcinoma, although technically manageable, should be treated with external pelvic irradiation and brachytherapy and weekly (cisplatin 40 mg/m2 x 6 wk), if it is suspected that the likelihood of positive lymph nodes or margins requiring adjuvant treatment after radical surgery would be significant. In those patients in whom the risks of either positive margins or lymph nodes are low, either radical surgery or radiation are equally efficacious options. A recent report that surveyed the Surveillance, Epidemiology, and End Results program database suggested that there may be a survival advantage for surgical intent-to-treat patients compared with the radiation intent-to-treat patients for tumors 4 cm or smaller in patients with stage IB and IIA cervical cancers. Certainly, toxicity criteria for these patients in terms of long-term problems need to be further examined. For those patients who undergo a radical hysterectomy and lymph node dissection, postoperative irradiation is indicated if high-risk factors such as large tumor size, lymph vascular space invasion, and deep stromal invasion are identified. Patients who are found to have positive lymph nodes, positive parametrial invasion, or positive margins at the time of hysterectomy should receive postoperative irradiation with chemotherapy. All other patients with more advanced clinical stages of cervical carcinoma should be treated with external pelvic irradiation, brachytherapy, and concurrent chemotherapy. Based on the results of the randomized studies, there appears to be no role for either hydroxyurea or fluorouracil. The chemotherapy agent of choice, at present, is cisplatin administered concurrently with irradiation at a dose of 40 mg/m2 weekly for 6 weeks. Concurrent chemotherapy should be avoided in patients with a poor performance status and other severe comorbidities, and these patients should be treated with irradiation alone. Further refinement of treatment for those patients who require combined chemo/radiation versus those with comorbidities such that combination chemotherapy is actually too toxic must be defined.


Assuntos
Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Humanos , Estadiamento de Neoplasias , Taxa de Sobrevida , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia
20.
Fertil Steril ; 76(4): 826-9, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11591422

RESUMO

OBJECTIVE: To report a successful IVF pregnancy in an infertile couple after conservative treatment of endometrial cancer. DESIGN: Case report and literature review. SETTING: University teaching hospital. PATIENT(S): A 29-year-old infertile white woman. MAIN OUTCOME MEASURE(S): Successful pregnancy after conservative management of endometrial cancer. INTERVENTION(S): Grade 1 endometrial adenocarcinoma diagnosed at hysteroscopy, followed by dilatation and curettage (D&C). On follow-up D&C, pathologic examination was normal after high-dose progesterone therapy. The patient subsequently underwent an IVF cycle with transfer of three blastocysts. RESULT(S): The patient delivered triplets by cesarean section. Laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy was then done. No residual endometrial cancer was evident in the hysterectomy specimen, but a 1.1-cm cystic mixed endometrioid and clear cell-type adenocarcinoma was discovered in the left ovary. The patient is doing well after 3 cycles of chemotherapy; her CA-125 level is normal. The triplets are also doing well. CONCLUSION(S): In carefully chosen situations, deferring surgery in infertile patients with endometrial cancer may be a viable option permitting subsequent successful pregnancy.


Assuntos
Adenocarcinoma/terapia , Neoplasias do Endométrio/terapia , Fertilização in vitro , Gravidez , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia Vaginal , Segunda Neoplasia Primária/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento
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