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BACKGROUND: Few data are available on long-term fatigue (LTF) and quality of life (QoL) among epithelial ovarian cancer survivors (EOCS). In this case-control study, we compared LTF, symptoms and several QoL domains in EOCS relapse-free ≥3 years after first-line treatment and age-matched healthy women. PATIENTS AND METHODS: EOCS were recruited from 25 cooperative GINECO centers in France. Controls were randomly selected from the electoral rolls. All participants completed validated self-reported questionnaires: fatigue (FACIT-F), QoL (FACT-G/O), neurotoxicity (FACT-Ntx), anxiety/depression (HADS), sleep disturbance (ISI), and physical activity (IPAQ). Severe LTF (SLTF) was defined as a FACIT-F score <37/52. Univariate and multivariate logistic regressions were conducted to analyze SLTF and its influencing factors in EOCS. RESULTS: A total of 318 EOCS and 318 controls were included. EOCS were 63-year-old on average, with FIGO stage I/II (50%), III/IV (48%); 99% had received platinum and taxane chemotherapy, with an average 6-year follow-up. There were no differences between the two groups in socio-demographic characteristics and global QoL. EOCS had poorer FACIT-F scores (40 versus 45, P < 0.0001), lower functional well-being scores (18 versus 20, P = 0.0002), poorer FACT-O scores (31 versus 34 P < 0.0001), and poorer FACT-Ntx scores (35 versus 39, P < 0.0001). They also reported more SLTF (26% versus 13%, P = 0.0004), poorer sleep quality (63% versus 47%, P = 0.0003), and more depression (22% versus 13%, P = 0.01). Fewer than 20% of EOCS and controls exercised regularly. In multivariate analyses, EOCS with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing SLTF (P < 0.01). CONCLUSION: Compared with controls, EOCS presented similar QoL but persistent LTF, EOC-related symptoms, neurotoxicity, depression, and sleep disturbance. Depression, neuropathy, and sleep disturbance are the main conditions associated with severe LTF.
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Sobreviventes de Câncer/estatística & dados numéricos , Carcinoma Epitelial do Ovário/epidemiologia , Fadiga/epidemiologia , Neoplasias Ovarianas/epidemiologia , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/epidemiologia , Ansiedade/etiologia , Carcinoma Epitelial do Ovário/fisiopatologia , Carcinoma Epitelial do Ovário/psicologia , Carcinoma Epitelial do Ovário/terapia , Estudos de Casos e Controles , Terapia Combinada , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Fadiga/etiologia , Feminino , França/epidemiologia , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/psicologia , Neoplasias Ovarianas/terapia , Inquéritos e Questionários , Adulto JovemRESUMO
Background: Lymphocytic infiltration at diagnosis is prognostic in EOC, however, the impact of NACT on tumour infiltrating lymphocytes (TILs) or PD-L1 expression remains poorly described. Patients and methods: Patients with EOC and sequential samples (pre-NACT, post-NACT or relapse) were retrospectively identified. TILs were evaluated on whole sections; stromal TILs (sTILs) scored as percentage of stromal area with high sTILs defined as ≥50%; intra-epithelial TILs (ieTILs) scored semi-quantitatively (0-3) with high ieTILs ≥2. A smaller number were available for PD-L1 evaluation, cut-off for positivity was ≥5% staining. Results: sTILs were detected in all tumours at diagnosis (range 2-90%, median 20%), with 22% (25/113) showing high sTILs. Among evaluable paired pre/post-NACT samples (N = 83), an overall increase in median sTILs from 20% to 30% was seen following NACT (P = 0.0005); individually the impact of NACT varied with sTILs increasing in 51% (42/83), decreasing in 25%, and stable in 24%. Post-NACT sTILs were predictive of platinum-free interval (PFI), patients with PFI ≥6 months had significantly higher post-NACT sTILs (sTILs 28% versus 18% for PFI <6 months, P = 0.026); pre-NACT sTILS were not predictive. At diagnosis, 23% showed high ieTILs, and following NACT 33% showed increasing ieTILs. Proportion of tumours with PD-L1-positive immune cells was 30% (15/50) pre-NACT and 53% (27/51) post-NACT (P = 0.026). Among paired tumours, 63% of PD-L1-negative tumours became positive after NACT, furthermore cisplatin induced PD-L1 expression in PD-L1-negative EOC cell lines. On multivariate analysis, high sTILs both pre- and post-NACT were independent prognostic factors for progression-free survival (PFS) (HR 0.49, P = 0.02 and HR 0.60, P = 0.05, respectively). No prognostic impact of ieTILs or PD-L1 expression was detected. Conclusions: In EOC, sTILs levels are prognostic at diagnosis and remain prognostic after NACT. TILs and PD-L1 expression increase following NACT. Evaluation of immune parameters in the post-NACT tumour may help select patients for immunotherapy trials.
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Antígeno B7-H1/genética , Quimioterapia Adjuvante , Recidiva Local de Neoplasia/genética , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , PrognósticoRESUMO
BACKGROUND: To evaluate the influence of treatment on health-related quality of life (HRQoL) in 919 women with recurrent ovarian cancer enrolled in the TRINOVA-1 study, a randomized, placebo-controlled phase III study that demonstrated that trebananib 15 mg/kg QW plus weekly paclitaxel significantly improved progression-free survival (PFS) compared with placebo plus weekly paclitaxel (7.2 versus 5.4 months; hazard ratio, 0.66; 95% confidence interval 0.57-0.77; P < 0.001). PATIENTS AND METHODS: HRQoL was assessed with the Functional Assessment of Cancer Therapy-Ovary [FACT-O; comprising FACT-G and the ovarian cancer-specific subscale (OCS)] and EuroQOL EQ-5D instruments before treatment on day 1 of weeks 1, 5, 9, 13, 17, and every 8 weeks thereafter and at the safety follow-up visit. A pattern-mixture model was used to evaluate the influence of patient dropout on FACT-O and OCS scores over time. RESULTS: Of 919 randomized patients, 834 (91%) had a baseline and ≥1 post-baseline HRQoL assessment. At baseline, scores for all instruments were similar for both arms. At 25 weeks, mean ± SD changes from baseline were negligible, with mean ± SD changes typically <1 unit from baseline: -2.4 ± 16.6 in the trebananib arm and -1.6 ± 15.2 in the placebo arm for FACT-O, -0.71 ± 5.5 in the trebananib arm and -0.86 ± 4.9 in the placebo arm for OCS, and -0.02 ± 0.22 in the trebananib arm and 0.02 ± 0.19 in the placebo arm for EQ-5D. Distribution of scores was similar between treatment arms at baseline and over the course of the study. In pattern-mixture models, there was no evidence that patient dropout affected differences in mean FACT-O or OCS scores. Edema had limited effect on either FACT-O or OCS scores in patients with grade ≥2 edema or those with grade 1 or no edema. CONCLUSIONS: Our results demonstrate that the improvement in PFS among patients in the trebananib arm in the TRINOVA-1 study was achieved without compromising HRQoL. CLINICALTRIALSGOV IDENTIFIER: NCT01204749.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Inibidores da Angiogênese/administração & dosagem , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neovascularização Patológica/patologia , Neoplasias Ovarianas/patologia , Efeito Placebo , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Based on registries, the European experience has been that <50% of patients are treated according to protocols and/or benefit from the minimum required surgery for ovarian cancer. The French Cancer Plan 2009-2013 considers the definition of qualitative indicators in ovarian cancer surgery in France. This endeavour was undertaken by the French Society of Gynaecologic Oncology (SFOG) in partnership with the French National College of Obstetricians and Gynecologists and all concerned learned societies in a multidisciplinary mindset. METHODS: The quality indicators for the initial management of patients with ovarian cancer were based on the standards of practice determined from scientific evidence or expert consensus. RESULTS: The indicators were divided into structural indicators, including material (equipment), human (number and qualification of staff), and organizational resources, process indicators, and outcome indicators. CONCLUSIONS: The enforcement of a quality assurance programme in any country would undoubtedly promote improvement in the quality of care for ovarian cancer patients and would result in a dramatic positive impact on their survival. Such a policy is not only beneficial to the patient, but is also profitable for the healthcare system.
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Neoplasias Ovarianas/cirurgia , Garantia da Qualidade dos Cuidados de Saúde , Indicadores de Qualidade em Assistência à Saúde , Feminino , França , Humanos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Ovário/patologia , Ovário/cirurgiaRESUMO
BACKGROUND: There is no proven benefit of adjuvant treatment of uterine sarcoma (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an increase ≥ 20% of 3-year PFS. METHODS: Patients with FIGO stage ≤ III US, physiological age ≤ 65 years; chemotherapy: four cycles of doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/day d1-2, cisplatin 75 mg/m² d3, (API) + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. RESULTS: Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%), febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B. The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). CONCLUSION: API adjuvant CT statistically increases the 3 year-DFS of patients with US.
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Quimioterapia Adjuvante , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/radioterapia , Sarcoma/tratamento farmacológico , Sarcoma/radioterapia , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/radioterapia , Adulto , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Estimativa de Kaplan-Meier , Leiomiossarcoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sarcoma/patologia , Neoplasias Uterinas/patologiaRESUMO
INTRODUCTION: Infectious complications of parietal mesh after prosthetic abdominal wall repair are rare. Their management is complex. Furthermore, the emergence of bacterial resistance, the presence of a foreign material, the need to continue an extended antibiotic therapy, and the choice of an appropriate treatment are crucial. The objective of this study is to access the microbiological epidemiology of infected parietal meshes in order to optimize the empirical antibiotic therapy. METHODS: Between January 2016 and December 2021, a monocentric and retrospective study was performed in patients hospitalized for infected parietal meshes at Avicenne hospital, in Paris area. Clinical and microbiological data such as antibiotic susceptibility were collected. RESULTS: Twenty-six patients with infected parietal meshes have been hospitalized during this period. Meshes were in preaponevrotic positions (n=10; 38%), retromuscular (n=6; 23%) and intraperitoneal (n=10; 38%). Among the 22 (84.6%) documented cases of infections, 17 (77.3%) were polymicrobial. A total of 54 bacteria were isolated, 48 of which had an antibiogram available. The most frequently isolated bacteria were: Enterobacterales (n=19), Enterococcus spp. (n=11) and Staphylococcus aureus (n=6), whereas anaerobes were poorly isolated (n=3). Concerning these isolated bacteria, amoxicillin-clavulanic acid, metronidazole-associated cefotaxime, piperacillin-tazobactam and meropenem were susceptible in 45.5%, 68.2%, 63.6%, 77.2%, of cases, respectively. CONCLUSION: This work highlights that infections of abdominal parietal meshes may be polymicrobial and the association amoxicillin-clavulanic acid cannot be used as a probabilist antibiotic therapy because of the high resistance rate in isolated bacteria. The association piperacillin-tazobactam appears to be a more adapted empirical treatment to preserve carbapenems, a broad-spectrum antibiotic class.
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Parede Abdominal , Combinação Amoxicilina e Clavulanato de Potássio , Humanos , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Combinação Piperacilina e TazobactamRESUMO
BACKGROUND: The aim of this study was to describe how recurrences were diagnosed in the largest series of patients treated for an advanced-stage serous borderline ovarian tumour. PATIENTS AND METHODS: From 1973 to 2006, 45 patients with a serous borderline tumour and peritoneal implants relapsed among 162 patients with a follow-up exceeding 1 year. Data concerning recurrences and the mode of diagnosis were reviewed. RESULTS: The median follow-up interval was 8.2 years (range 19-286 months). The mode of diagnosis of recurrences was imaging (n = 19), clinical symptoms (n = 8), cancer antigen (CA) 125 elevation (n = 7), secondary surgery (n = 5) and unknown (n = 6). The median time to recurrence was 31 months (range 4-242 month). The type of recurrence was invasive low-grade serous carcinoma in 14 patients. Five patients died of recurrent tumour. Among the 39 patients with a known mode of diagnosis of recurrence, the most frequent diagnostic method for invasive recurrences was blood CA 125 elevation (6 of 13) and the majority of noninvasive recurrences were diagnosed by imaging (16 of 23). CONCLUSIONS: This study demonstrates that ultrasound is the most relevant follow-up procedure in this context. Nevertheless, the blood CA 125 test is of particular interest for detecting invasive recurrent disease, which is the most crucial event.
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Recidiva Local de Neoplasia/diagnóstico , Neoplasias Ovarianas/diagnóstico , Técnicas e Procedimentos Diagnósticos , Feminino , Seguimentos , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologiaRESUMO
PURPOSE: To explore whether adjuvant treatment options may impact on the prognosis in localized endometrial stromal sarcomas (ESSs; stages I and II). The historical options usually discussed in addition to hysterectomy and bilateral salpingoophorectomy (BSO) are active surveillance, pelvic radiotherapy, chemotherapy and hormonal therapy, alone or in combination. PATIENTS AND METHODS: Among 84 consecutive patients treated for ESS at a single referral center, 54 with localized stage disease were identified. Recurrence-free survival and overall survival were estimated and patterns of recurrences described. Univariate and multivariate analyses were carried out. RESULTS: With a median follow-up of 58 months, only one patient had died. None of the 23 patients who had received adjuvant therapy relapsed compared with 13 of 31 patients who had not received any adjuvant therapy. Adjuvant treatments were hormonal therapy (n = 10) and brachytherapy with/without pelvic radiotherapy (n = 13). Almost the majority of relapses were local (92%) and extra-pelvic metastasis was observed in nearly half of the patients (46%). In the multivariate analysis, the major determinants of relapse-free survival were adjuvant treatment, myometrial invasion (P = 0.005) and no BSO (P = 0.005). CONCLUSIONS: In this series, adjuvant treatment of localized ESSs was associated with the absence of recurrence.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Neoplasias do Endométrio/terapia , Histerectomia , Recidiva Local de Neoplasia/terapia , Neoplasias Pélvicas/terapia , Sarcoma do Estroma Endometrial/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Pélvicas/secundário , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Sarcoma do Estroma Endometrial/patologia , Taxa de SobrevidaRESUMO
BACKGROUND: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer. PATIENTS AND METHODS: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m(2)/cycle (0.8 mg/m(2)/day from day 1 to day 5) was administered, repeated every 28 days. RESULTS: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. CONCLUSION: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antineoplásicos/administração & dosagem , Camptotecina/administração & dosagem , Quimioterapia Adjuvante , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Platina/administração & dosagem , Recidiva , Taxoides/administração & dosagemRESUMO
Evaluation of the fetus using prenatal ultrasound has resulted in increased detection of asymptomatic adnexal masses during pregnancy. Such masses are rarely malignant (1/10 000 to 1/50 000 pregnancies), but the possibility of borderline or cancer must be considered. It is a common assumption by both patients and physicians that if an ovarian cancer is diagnosed during pregnancy, treatment necessitates sacrificing the well-being of the fetus. However, in most cases, it is possible to offer appropriate treatment to the mother without placing the fetus at serious risk. The care of a pregnant woman with cancer involves evaluation of sometimes competing maternal and fetal risks and benefits. These recommendation approaches attempt to balance these risks and benefits; however, they should be considered advisory and should not replace specific interdisciplinary consultation with specialists in maternal-fetal medicine, gynecologic oncology, and pediatrics, as well as imaging and pathology, as needed. Second level ultrasound including Doppler is needed. MRI is not often necessary, and CA 125 is of low contribution. We suggest surgery be performed after 15 SA for ovarian masses which (1) persist into the second trimester, (2) are greater than 5 to 10 cm in diameter, or (3) have solid or mixed solid and cystic ultrasound characteristics. During antepartum surgical staging and debulking, homolateral salpingo-oophorectomy and peritoneal cytology and exploration are necessary. Women found to have advanced stage epithelial ovarian cancer should consider having completion of the debulking of the reproductive organs at the conclusion of the pregnancy. If chemotherapy is indicated, we recommend delaying administration, if possible, after the delivery or at least after 20 SA in order to minimize the potential fetal toxicity.
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Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Guias de Prática Clínica como Assunto , Complicações Neoplásicas na Gravidez/cirurgia , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , França , Idade Gestacional , Humanos , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Ovarianas/diagnóstico , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Medição de Risco , Ultrassonografia Pré-NatalRESUMO
Early stage of cervical cancer is defined by disease confined to the cervix and upper vagina (stage IA to IIA). For early stage, no treatment has demonstrated clear superiority. Treatment options for women with early stage include either exclusive radiotherapy, or radical surgery, or brachytherapy before radical surgery. Radical hysterectomy or trachelectomy include the resection of the parametrium. The rational of parametrectomy is to remove occult disease in the parametrium and its removal is the cause of much of the morbidity of the surgery, specially urinary complications. This surgery can be performed by laparascopy with quality of life improvement and less blood loss but urinary morbidity is still important. The question is if it's possible to be less radical and still oncologically safe. Parametrial invasion is rare in patients with small tumours without lymphovascular space involvement and negative pelvic nodes (no poor prognostic factors). Sentinel node negative could be a strong criteria to predict parametrial involvement. This review reports studies exploring the safety of omitting parametrectomy in these low risk patients and the future possibilities to evaluate these new indications.
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Diafragma da Pelve/patologia , Diafragma da Pelve/cirurgia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidadeRESUMO
BACKGROUND: Ovarian yolk sac tumor (YST) is a very rare malignancy arising in young women. Chemotherapy has dramatically improved the prognosis. Current treatment consists of surgery followed by bleomycin, etoposide, and cisplatin (BEP) chemotherapy. However, given the rarity of this tumor, ovarian YST-specific survival and outcome after such treatment are not precisely known. PATIENTS AND METHODS: This report concerns prospectively recorded cases that were either treated at Institut Gustave Roussy (Villejuif, France) or referred there for advice about therapy. From 1990 to 2006, 52 patients underwent surgery followed by BEP chemotherapy. Data on patient characteristics, treatment, survival, and fertility outcome were analyzed to assess treatment efficacy and gonadal toxicity after achieving a complete remission. RESULTS: Thirty-five patients had stage I/II tumors while 17 patients presented with stage III/IV disease. With a median follow-up of 68 months, the overall 5-year survival and disease-free survival rates were 94% and 90%, respectively. Forty-one women underwent fertility-sparing surgery. Pregnancy was achieved in 12 of 16 (75%) women who attempted conception. Overall, 19 pregnancies have been recorded. CONCLUSIONS: BEP chemotherapy following fertility-sparing surgery is a very effective treatment of ovarian YSTs. Most of the patients who attempt conception after complete remission will have children.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tumor do Seio Endodérmico/tratamento farmacológico , Tumor do Seio Endodérmico/cirurgia , Fertilidade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Tumor do Seio Endodérmico/fisiopatologia , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/fisiopatologia , Gravidez , Complicações Neoplásicas na Gravidez/fisiopatologia , Complicações Neoplásicas na Gravidez/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Cancer of the cervix occurs in approximately 500,000 women worldwide each year, with prognosis highly dependent on disease stage at diagnosis. Survival times are poor and therapy options are limited for patients who relapse following radiotherapy and chemotherapy regimens, suggesting alternative treatments are required. Evidence suggests the epidermal growth factor receptor (EGFR) is expressed at moderate to high levels in cervical carcinomas. We investigated whether gefitinib (IRESSA), an EGFR tyrosine kinase inhibitor, is a potential second- or third-line treatment option for women with recurrent cervical cancer. METHODS: This was a multicenter, open-label, non-comparative, phase II trial (study 1839IL/0075) evaluating the clinical outcomes of 500 mg/day gefitinib. An exploratory objective was to investigate the correlation of baseline EGFR expression with tumor response and disease control. RESULTS: Thirty patients with squamous-cell carcinoma or adenocarcinoma were recruited from six centers in France. Of these, 28 patients were evaluable for efficacy. Although there were no objective responses, six (20%) patients experienced stable disease with a median duration of 111.5 days. Median time to progression was 37 days and median overall survival was 107 days. Disease control did not appear to correlate with levels of EGFR expression. Gefitinib was well tolerated, with the most common drug-related adverse events being skin and gastrointestinal toxicities. CONCLUSIONS: In recurrent disease resistant to standard treatment, gefitinib has only minimal monotherapy activity. However, the observation that 20% of patients treated with gefitinib had stable disease may warrant further investigation.
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Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Quinazolinas/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/biossíntese , Feminino , Gefitinibe , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/patologia , Quinazolinas/efeitos adversos , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologiaRESUMO
The objective is to investigate the activity and toxicity of bleomycin, etoposide, and cisplatin (BEP) regimen in ovarian granulosa cell tumors (OGCTs). Twenty consecutive patients with initial metastatic (5 patients) or recurrent (15 patients) OGCT were treated; BEP regimen: B: 30 mg intravenously or intramurally on days 1, 8, and 15; E: 100 mg/m2/day on days 1-5; and P: 20 mg/m2/day on days 1-5. Median age: 42 years (range: 17-60); median follow-up: 45 months (range: 3-112). The overall response rate is 90% (nine clinical complete response [CR], nine clinical partial response) with a median duration of 24 months (range: 4-77). A second-look laparotomy performed in 11 patients showed a pathologic CR in 7 cases and microscopic disease in 1 case. Seven patients remain free of disease (at 4-84 months); 11 patients relapsed (median: 24 months, range: 13-58), 12 patients are still alive, and 9 patients are without disease (2 patients in second CR). At 4 years, overall survival and event-free survival are respectively 58% and 30%. Toxicity is evaluable for 19 patients (48 cycles). A grade 4 neutropenia occurred in 15% of cycles (in seven patients) with a febrile neutropenia in four patients. Five patients experienced a low bleomycin pulmonary toxicity. BEP regimen appears to be an active regimen for OGCT in first-line chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Tumor de Células da Granulosa/tratamento farmacológico , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Tumor de Células da Granulosa/mortalidade , Tumor de Células da Granulosa/patologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Estudos Prospectivos , Cirurgia de Second-Look , Análise de Sobrevida , Resultado do TratamentoRESUMO
Even if the prognosis of patients with cervical cancer has been dramatically improved with concomitant chemoradiation, brachytherapy still plays fundamental role in the therapeutic approach of patients with Figo stage I-IV cervical carcinoma. The development of imaging with three-dimensional dosimetry has contributed to the improvement in target and organs at risk knowledge. In 2005 and 2006, GEC-ESTRO recommendations on 3-D based image brachytherapy have defined the different volumes of interest. These recommendations have been validated with intercomparison delineation studies. Data on dose to normal tissues are better known with dose volume-histograms analysis. Dose limits to the bladder are high in the range of 90 Gy to the 2 cm3 while 2 cm3 limits to the rectum do not differ from ICRU point. The sigmoid is currently under study as this organ was not extensively studied before the era of imaging. Doses to the tumour (HR-CTV or IR-CTV) are not clearly stated and will likely depend on tumour extension.
Assuntos
Braquiterapia/métodos , Neoplasias do Colo do Útero/radioterapia , Braquiterapia/efeitos adversos , Braquiterapia/normas , Diagnóstico por Imagem , Feminino , Humanos , Radiografia , Radiometria , Dosagem Radioterapêutica , Reto/efeitos da radiação , Bexiga Urinária/efeitos da radiação , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologiaRESUMO
S. Gouy, C. Uzan, Y. Zafrani, C. Lhommé, P. Pautier, P. Duvillard, C. Haie-Meder, P. Morice Uterine cancer can metastasize to both the pelvic and para-aortic levels. No one questions the diagnostic and prognostic value of lymphadenectomy, but its therapeutic value is still open to debate. In early cervical cancer (<4 cm.), pelvic lymphadenectomy is a routine part of radical hysterectomy. If pelvic lymph nodes show involvement, one can propose an extension of the lymphadenectomy to the para-aortic level. Studies of sentinel lymph node identification and biopsy at this level are currently under way. The standard treatment of cervical cancer > 4 cm is radiotherapy. A pre-radiation laparoscopy to investigate lymph node involvement at the lumbo-aortic level may help to define the extent of the radiation field. For endometrial cancer, the role and benefit of lymphadenectomy are much less clear since these patients often have major co-morbidities which increase the risk of complications from an extended lymph node dissection.
RESUMO
S. Gouy, C. Uzan, Y. Zafrani, C. Lhommé, P. Pautier, P. Duvillard, C. Haie-Meder, P. Morice Uterine cancer can metastasize to both the pelvic and para-aortic levels. No one questions the diagnostic and prognostic value of lymphadenectomy, but its therapeutic value is still open to debate. In early cervical cancer (<4 cm.), pelvic lymphadenectomy is a routine part of radical hysterectomy. If pelvic lymph nodes show involvement, one can propose an extension of the lymphadenectomy to the para-aortic level. Studies of sentinel lymph node identification and biopsy at this level are currently under way. The standard treatment of cervical cancer > 4 cm is radiotherapy. A pre-radiation laparoscopy to investigate lymph node involvement at the lumbo-aortic level may help to define the extent of the radiation field. For endometrial cancer, the role and benefit of lymphadenectomy are much less clear since these patients often have major co-morbidities which increase the risk of complications from an extended lymph node dissection.
RESUMO
Uterine cancer can metastasize to both the pelvic and para-aortic levels. No one questions the diagnostic and prognostic value of lymphadenectomy, but its therapeutic value is still open to debate. In early cervical cancer (<4 cm.), pelvic lymphadenectomy is a routine part of radical hysterectomy. If pelvic lymph nodes show involvement, one can propose an extension of the lymphadenectomy to the para-aortic level. Studies of sentinel lymph node identification and biopsy at this level are currently under way. The standard treatment of cervical cancer>4 cm is radiotherapy. A pre-radiation laparoscopy to investigate lymph node involvement at the lumbo-aortic level may help to define the extent of the radiation field. For endometrial cancer, the role and benefit of lymphadenectomy are much less clear since these patients often have major co-morbidities which increase the risk of complications from an extended lymph node dissection.
Assuntos
Histerectomia , Excisão de Linfonodo , Neoplasias do Colo do Útero/cirurgia , Neoplasias Uterinas/cirurgia , Ensaios Clínicos como Assunto , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Medicina Baseada em Evidências , Feminino , Humanos , Histerectomia/métodos , Excisão de Linfonodo/métodos , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias Uterinas/patologia , Neoplasias Uterinas/radioterapiaRESUMO
BACKGROUND: The evaluation of first-line intensive combination therapy in small cell carcinoma of the ovary (SCCO). PATIENTS AND METHODS: Debulking surgery; four to six cycles of chemotherapy with cisplatin (P) 80 mg/m(2) day 1, adriamycin (A) 40 mg/m(2) day 1, vepeside (V) 75 mg/m(2)/day days 1-3, cyclophosphamide (EP) 300 mg/m(2)/day days 1-3, every 3 weeks and granulocyte colony-stimulating factor with, in case of a complete remission, high-dose chemotherapy with carboplatin, vepeside, cyclophosphamide and stem-cell support. RESULTS: Twenty-seven patients (median age 25 years); International Federation of Gynecology and Obstetrics stage: five I, four IIC, 17 IIIC-IV and one unknown. Twenty patients underwent complete surgery. Eight patients progressed under chemotherapy. Among 18 patients in complete response (CR), 10 received high-dose chemotherapy (CT) (three stem-cell collection failures, two protocol violations, two disease progression and one refusal). The main grade 3-4 toxic effects were hematologic. There were eight relapses among the 18 CR, four of which were pelvic alone. Among the 27 patients, 13 died and 10 patients are in CR1, three in CR2. The median follow-up is 37 months (8-166) and the median duration of the 18 CR is 30 months (5-111). Overall survival at 1 and 3 years is 58% [confidence interval (CI) 40% to 75%] and 49% (CI 30% to 67%). CONCLUSIONS: Initial dose-intensive therapy achieves interesting overall survival in SCCO.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Hipercalcemia/complicações , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Pequenas/complicações , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Ovarianas/complicações , Estudos Prospectivos , Resultado do TratamentoRESUMO
Topotecan has demonstrated activity in ovarian carcinomas. In order to increase the tumour response rate and to define the maximum tolerated dose (MTD) of topotecan, we decided to develop a high-dose phase I regimen supported by stem cell support. High-doses schedules using a 1-day single administration have MTDs of 10.5 (24 h continuous infusion (CI)) or 22.5 mg/m2 (30 min infusion). Five-day CI induces grade IV mucositis at high doses (MTD<12 mg/m2). We chose to administer topotecan in a 5-day schedule with a 30 min daily infusion. Patients were scheduled to receive one cycle of therapy. The first dose level was 4.0 mg/m2/day x 5 days. Limiting toxicities were defined as toxic death, grade IV non-haematopoietic or haematopoietic toxicity >6 weeks. From August 1998 to April 2002, 49 patients were included. Forty-three patients have completed one course and 15 have received two cycles. One patient treated at level 7 mg/m2/day died of sepsis. Median duration of grade IV neutropenia was 9 days. Two episodes of grade IV diarrhoea were observed at level 9.5 mg/m2/day. Pharmacokinetic data were linear within the dose range of 4-9.0 mg/m2/day. The MTD was reached at 9 mg/m2/day x 5 days.