RESUMEN
OBJECTIVES: The objective of this study was to examine whether the oncologic outcomes of BRCA1-associated and BRCA2-associated ovarian cancers correlate differently. METHODS: Genetic data and clinical characteristics were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Data from 147 BRCA-mutated patients (119 BRCA1-positive and 28 BRCA2-positive) were analyzed. At a median follow-up of 69 months, the median PFS was 27.2 and 45.46 months for BRCA1 and BRCA2 patients, respectively (p = 0.03). Median OS was 77.23 and 111.47 months for BRCA1 and BRCA2 patients, respectively (p = 0.08). CONCLUSION: BRCA2 mutations confer PFS and a trend to OS advantage compared with the BRCA1 mutation in BRCA-mutated epithelial ovarian cancer patients.
Asunto(s)
Adenocarcinoma/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Adulto , Anciano , Carcinoma Epitelial de Ovario , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/terapia , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVES: The aim of this phase II multicentric study was to evaluate the efficacy and toxicity of neo-adjuvant chemotherapy with weekly topotecan and cisplatin in locally-advanced squamous cervical cancer. PATIENTS AND METHODS: From November 2008 to January 2011, 92 patients met the inclusion criteria and were enrolled. Eligibility criteria were: squamous or adenosquamous cervical cancer; clinical stages IB2, IIA, IIB; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)≤ 2; neutrophils ≥1500/µL; platelets ≥100,000/µL, normal renal and liver function. Treatment consisted of six courses of weekly topotecan (2mg/m(2)) and cisplatin (40 mg/m(2)). All responsive and stable patients were submitted to radical surgery, while progressed cases underwent definitive radiotherapy±chemotherapy. Primary end-point was evaluation of efficacy and toxicity. All patients are evaluable for toxicity and efficacy. RESULTS: Ninety-six percent of patients completed the six planned courses of chemotherapy, and 95% of courses were administered at a full dose and without interruption or delay. Mean age was 49 years (35-64 years). FIGO Stage distribution was 30 IB2, 13 IIA and 49 IIB. Treatment was well tolerated and no death occurred. G3-G4 haematological toxicity was observed in 28% of patients (5% out of cycles). Support therapies (blood transfusions and/or erythropoietin and/or Granocyte-Colony Stimulating Factor) were given to 24% of patients. Clinical response rate was 77%. The nine progressed cases were irradiated, while the remaining 83 patients were submitted to radical surgery. An overall pathologic response was observed in 67% of patients, with an optimal response rate of 32% and a disease downstage in 57% of patients. Nodal metastases occurred in 36% of patients. Adjuvant therapy (radiotherapy and or chemotherapy) was prescribed in 55% of patients, because of lymph node metastases, parametrial or vaginal involvement or cut-through margins. Median follow-up was 18 months: 76% of patients are alive and free from recurrence, 24% of patients relapsed and 13% died. CONCLUSIONS: Weekly topotecan and cisplatin showed an acceptable toxicity profile; the promising response rate warrants further investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/administración & dosificación , Topotecan/administración & dosificación , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Adenoescamoso/tratamiento farmacológico , Carcinoma Adenoescamoso/mortalidad , Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cisplatino/efectos adversos , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Topotecan/efectos adversos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
OBJECTIVE: To prospectively evaluate the accuracy of a multiparameter, ultrasound-based triage and its impact on surgical management of adnexal masses. METHODS: Masses evaluated as normal according to Ferrazzi's sonographic morphological score were considered as being at low risk of malignancy and eligible for laparoscopic treatment without further evaluation. Masses evaluated as abnormal, but without additional risk factors such as ascites, diameter > or = 10 cm, bilaterality, immobility, resistance index < or = 0.6 and serum CA 125 > 35 IU/mL were considered at moderate risk and eligible for laparoscopic evaluation and treatment. Masses with abnormal morphological score and any of these additional risk factors were considered at high risk and treated by laparotomy. The results of pathological examination were obtained for each mass. RESULTS: Two hundred and four (87%) masses were benign and 30 (13%) were malignant. Among 182 low-risk, 19 moderate-risk and 33 high-risk masses, the odds of malignancy were 1 : 90, 1 : 18 and 4.5 : 1, respectively. To calculate the diagnostic accuracy of this algorithm, low- and moderate-risk groups were considered together: the sensitivity was 90%, specificity 97%, positive predictive value 82% and negative predictive value 99%. The new algorithm was significantly more accurate than was morphological score alone (P = 0.0002). Ninety-six percent of benign masses were treated by laparoscopy. All three patients with malignant masses that were incorrectly assigned to laparoscopy underwent laparoscopic adnexectomy and frozen section. CONCLUSIONS: The accuracy of this new algorithm was higher than that of the sonographic morphological scoring system alone. In the present series, it allowed the treatment by laparoscopy of 96% of benign adnexal masses without mismanagement of any cases of ovarian cancer.