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PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS: Patients with clinical stage IA2, IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m2 and a 96-hour infusion of fluorouracil 1,000 mg/m2/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P = .003) and 1.96 (P = .007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.
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OBJECTIVES: This study aimed to determine whether carbonic anhydrase-IX (CA-IX) was associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated with adjuvant pelvic radiotherapy with or without radiosensitizing chemotherapy. METHODS: CA-IX expression was detected using an immunohistochemistry assay and categorized as low when
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Antígenos de Neoplasias/biosíntesis , Anhidrasas Carbónicas/biosíntesis , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Anhidrasa Carbónica IX , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Factores de Riesgo , Tasa de Supervivencia , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVES: To determine whether markers of tumor angiogenesis were associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated on a phase III trial. METHODS: One hundred seventy-three tumor specimens were analyzed by semi-quantitative immunohistochemical (IHC) staining for vascular endothelial growth factor (VEGF, pro-angiogenesis factor), thrombospondin-1 (TSP-1, anti-angiogenesis factor), CD31 (non-specific endothelial marker), and CD105 (tumor-specific endothelial marker). Tumoral histoscores (HS) were calculated for VEGF using the formula: [% cells positivex(intensity+1)]. TSP-1 specimens were categorized as negative or positive. CD31 and CD105 microvessel density (MVD) "hotspots" were counted in three 20x high-power fields. Associations between angiogenesis markers and survival were evaluated. RESULTS: TSP-1 expression was observed in 65% of cases while 66% expressed high VEGF (>or=200), 34% exhibited high CD31 (CD31>or=110) and 66% displayed high CD105 (CD105>or=28). In univariate analyses CD31 MVD, but not tumor TSP-1, was associated with improved PFS (HR=0.37; 95% CI=0.18-0.76; p=0.007) and OS (HR=0.37; 95% CI=0.17-0.79; p=0.010). After adjusting for prognostic clinical covariates, high CD31 MVD, but not TSP-1, VEGF or CD105 MVD, was an independent prognostic factor for PFS (HR=0.36; 95% CI=0.17-0.75; p=0.006) and OS (HR=0.36; 95% CI=0.17-0.79; p=0.010). CONCLUSIONS: Tumor angiogenesis measured by CD31 MVD is an independent prognostic factor for both PFS and OS in high-risk, early-stage cervical cancer. We hypothesize that this finding may be explained by improved treatment response in well-vascularized, well-oxygenated tumors.
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Biomarcadores de Tumor/metabolismo , Neoplasias del Cuello Uterino/irrigación sanguínea , Adulto , Anciano , Antígenos CD/metabolismo , Estudios de Cohortes , Terapia Combinada , Supervivencia sin Enfermedad , Endoglina , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Receptores de Superficie Celular/metabolismo , Factores de Riesgo , Trombospondina 1/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/radioterapia , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To retrospectively analyze data from a previously reported randomized trial of either pelvic radiation (RT) or RT + chemotherapy (CT) in patients undergoing radical hysterectomy and pelvic lymphadenectomy with positive pelvic lymph nodes, parametrial involvement, or surgical margins; to explore associations between RT + CT; and to investigate histopathologic and clinical factors which might be predictive of recurrence. METHODS: Histopathologic sections from biopsies and hysterectomies and clinical data were reviewed from patients with stage IA2, IB, or IIA cervical cancer treated with RT or RT + CT (cisplatin 70 mg/m2 plus fluorouracil 1000 mg/m2 every 3 weeks for four cycles). A univariate analysis was performed because the relatively small sample size limited the interpretation of a multivariate analysis. RESULTS: Of the 268 enrolled women, 243 (RT = 116; RT + CT = 127) were evaluable. The beneficial effect of adjuvant CT was not strongly associated with patient age, histological type, or tumor grade. The prognostic significance of histological type, tumor size, number of positive nodes, and parametrial extension in the RT group was less apparent when CT was added. The absolute improvement in 5-year survival for adjuvant CT in patients with tumors < or =2 cm was only 5% (77% versus 82%), while for those with tumors >2 cm it was 19% (58% versus 77%). Similarly, the absolute 5-year survival benefit was less evident among patients with one nodal metastasis (79% versus 83%) than when at least two nodes were positive (55% versus 75%). CONCLUSIONS: In this exploratory, hypothesis-generating analysis, adding CT to RT after radical hysterectomy, appears to provide a smaller absolute benefit when only one node is positive or when the tumor size is < 2 cm. Further study of the role of CT after radical hysterectomy in patients with a low risk of recurrence may be warranted.