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BACKGROUND: Colorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting. METHODS: PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx. RESULTS: Patients (n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48-66) with the 3-CTx versus 48.4% (95% CI: 39-57) with the 2-CTx (P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx. CONCLUSION: We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Camptotecina/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológicoRESUMEN
BACKGROUND: The diagnosis of breast cancer (BC)-related leptomeningeal metastases (LM) relies on the detection of tumor cells in cerebrospinal fluid (CSF) using conventional cytology (gold standard). However, the sensitivity of this technique is low. Our goal was to evaluate whether circulating tumor cell (CTC) detection in CSF using the CellSearch® system could be used for LM diagnosis. METHODS: This prospective, monocentric study included adult patients with suspected BC-related LM. The clinical sensitivity and specificity of CTC detection in CSF for LM diagnosis were calculated relative to conventional CSF cytology. RESULTS: Forty-nine eligible patients were included and 40 were evaluable (CTC detection technical failure: n = 8, eligibility criteria failure: n = 1). Cytology was positive in 18/40 patients. CTCs were detected in these 18 patients (median: 5824 CTC, range: 93 to 45052) and in 5/22 patients with negative cytology (median: 2 CTC, range: 1 to 44). The detection of ≥1 CSF CTC was associated with a clinical sensitivity of 100% (95% CI, 82.4-100) and a specificity of 77.3% (95% CI, 64.3-90.3) for LM diagnosis. HER2+ CTCs were detected in the CSF of 40.6% of patients with HER2- BC (median: 500 CTC, range: 13 to 28 320). CONCLUSIONS: The clinical sensitivity of CTC detection in CSF with the CellSearch® system for LM diagnosis is higher than that of CSF cytology. CTC detection in patients with negative cytology, however, must be further investigated. The finding of HER2+ CTCs in patients with HER2- BC suggests that the HER2 status of LM should be evaluated to increase the treatment opportunities for these patients.
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Neoplasias de la Mama , Células Neoplásicas Circulantes , Adulto , Biomarcadores de Tumor , Neoplasias de la Mama/patología , Recuento de Células , Femenino , Humanos , Células Neoplásicas Circulantes/patología , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with confirmed metastatic clear-cell renal-cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS: A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib-alone group and 13.9 months in the nephrectomy-sunitinib group. No significant differences in response rate or progression-free survival were observed. Adverse events were as anticipated in each group. CONCLUSIONS: Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma who were classified as having intermediate-risk or poor-risk disease. (Funded by Assistance Publique-Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033 .).
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Indoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Nefrectomía , Pirroles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/cirugía , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Indoles/efectos adversos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nefrectomía/efectos adversos , Selección de Paciente , Complicaciones Posoperatorias , Pronóstico , Pirroles/efectos adversos , Medición de Riesgo , Sunitinib , Análisis de SupervivenciaRESUMEN
BACKGROUND: Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). PATIENTS AND METHODS: A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate. RESULTS: 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31-80 months]. Median OS was 11.5 months (95% CI 7.5-18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27-6.19; p = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14-0.78; p = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone (p = 0.049). CONCLUSIONS: The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.
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Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Metástasis de la Neoplasia/terapia , Tumor Filoide/terapia , Procedimientos Quirúrgicos Operativos , Adulto , Anciano , Anciano de 80 o más Años , Alquilantes/uso terapéutico , Neoplasias de la Mama/mortalidad , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Tumor Filoide/mortalidad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: The optimal threshold of surgical margins for breast malignant phyllodes tumors (MPTs) and the impact of adjuvant chemotherapy and radiotherapy were investigated. PATIENTS AND METHODS: We conducted a multicenter nationwide retrospective study of all MPT cases with central pathological review within the French Sarcoma Group. Endpoints were local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) rates. RESULTS: Overall, 212 patients were included in the study. All non-metastatic patients underwent primary surgical treatment, including 58.6% of conservative surgeries. An R0 resection was achieved in 117 patients (59.4%: 26.9% of patients with 1-2 mm margins, 12.2% of patients with 3-7 mm margins, 20.3% of patients with ≥ 8 mm margins). Ninety-four patients (45%) underwent a second surgery (SS) to obtain R0 margins, with a final mastectomy rate of 72.6%. Radiotherapy and chemotherapy were performed in 91 (43.1%) and 23 patients (10.9%), respectively, but were not associated with better outcomes. Mastectomy was significantly associated with better LRFS (p < 0.001). Margins of 0, 1, or 2 mm with SS were associated with better MFS (hazard ratio [HR] 0.3, p = 0.005) and OS (HR 0.32, p = 0.005) compared with margins of 0-1-2 mm without SS. Wider margins (> 8 mm) were not superior to margins of 3-7 mm (3-7 mm vs. > 8 mm; HR 0.81, p = 0.69). Age (HR 2.14, p = 0.038) and tumor necrosis (HR 1.96, p = 0.047) were found to be poor prognostic factors and were associated with MFS. CONCLUSIONS: This study suggests that 3 mm margins are necessary and sufficient for surgical management of MPTs, and emphasizes the importance of SS to obtain clear margins in case of 0-1-2 mm margins. No impact of adjuvant chemotherapy or radiotherapy was detected in this study.
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Neoplasias de la Mama/terapia , Quimioradioterapia Adyuvante/mortalidad , Márgenes de Escisión , Mastectomía/mortalidad , Recurrencia Local de Neoplasia/terapia , Tumor Filoide/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Tumor Filoide/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Background : In France, home parenteral nutrition (HPN) is managed by two parallel healthcare systems : in approved specialist centers (HPN > 12 weeks), and outside of these approved specialist centers (HPN<12 weeks).Objective : To prospectively evaluate infectious and vascular complications in adult cancer patients undergoing HPN administered via a central venous line, outside of approved specialist HPN centers.Methods : Our observational prospective study included adult patients with cancer, hospitalized for 48 hours or more, and under HPN. They had a WHO performance status of ≤ 2 and had had a nutritional consultation before discharge.Results : 25 patients were included in the study, with a median age of 63 years [19-74]. Weight loss of ≥ 5% was reported in 79% of patients. The Ingesta score was < 7 in 96% of cases. 87% of patients presented chill or body temperature variation episodes, with a median of 2 episodes [1-6] per patient. The median delay between end of hospitalization and the first chill episode was 11 days [1-85]. A vascular complication (obstruction without thrombosis) was reported in one patient.Discussion : This high number of infectious episodes requires improvement of patient care when it comes to strictly adhering to the recommendations. Getting the approved specialist HPN centers to work together and share care protocols could be the first important step.
RESUMEN
Background : In France, home parenteral nutrition (HPN) is managed by two parallel healthcare systems : in approved specialist centers (HPN > 12 weeks), and outside of these approved specialist centers (HPN<12 weeks). Objective : To prospectively evaluate infectious and vascular complications in adult cancer patients undergoing HPN administered via a central venous line, outside of approved specialist HPN centers. Methods : Our observational prospective study included adult patients with cancer, hospitalized for 48 hours or more, and under HPN. They had a WHO performance status of ≤ 2 and had had a nutritional consultation before discharge. Results : 25 patients were included in the study, with a median age of 63 years [1974]. Weight loss of ≥ 5% was reported in 79% of patients. The Ingesta score was < 7 in 96% of cases. 87% of patients presented chill or body temperature variation episodes, with a median of 2 episodes [16] per patient. The median delay between end of hospitalization and the first chill episode was 11 days [185]. A vascular complication (obstruction without thrombosis) was reported in one patient. Discussion : This high number of infectious episodes requires improvement of patient care when it comes to strictly adhering to the recommendations. Getting the approved specialist HPN centers to work together and share care protocols could be the first important step.
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Neoplasias/enfermería , Enfermeras Especialistas , Rol de la Enfermera , Nutrición Parenteral en el Domicilio/enfermería , Adulto , Anciano , Francia , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Sorafenib remains one major first-line therapeutic options for advanced hepatocellular carcinoma (aHCC), with modest efficacy. We investigated the addition of gemcitabine and oxaliplatin (GEMOX) to sorafenib in aHCC patients. METHODS: Our multicentre phase II trial randomised aHCC first-line patients to sorafenib (400 mg BID) or sorafenib-GEMOX every 2 weeks (1000 mg/m2 gemcitabine; 100 mg/m2 oxaliplatin). Primary endpoint was the 4-month progression-free survival (PFS) rate. RESULTS: Ninety-four patients were randomised (sorafenib-GEMOX: n = 48; sorafenib: n = 46). Median age was 64 years, PS 0 (69%) or 1 (31%), 63% patients had cirrhosis, 29% portal vein thrombosis and 70% extra-hepatic disease. Median duration of sorafenib treatment was 4 months (1-51); median number of GEMOX cycles was 7 (1-16). The 4-month PFS rates were 64% and 61% in the sorafenib-GEMOX and sorafenib arms, respectively; median PFS and OS were 6.2 (95% CI: 3.8-6.8) and 13.5 (7.5-16.2) months, and 4.6 (3.9-6.2) months and 14.8 (12.2-22.2), respectively. The ORR/DCR were 9%/70% and 15%/77% in the sorafenib-GEMOX and sorafenib alone arms, respectively. Main toxicities were (sorafenib-GEMOX/sorafenib) neutropenia (23%/0), thrombocytopenia (33%/0), diarrhoea (18%/9), peripheral neuropathy (5%/0) and hand-foot syndrome (5%/18). CONCLUSIONS: Addition of GEMOX had an inpact on ORR and was well-tolerated as frontline systemic therapy. The benefit on PFS seems moderate; no subsequent study was planned.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/uso terapéutico , Adulto , Anciano , Carcinoma Hepatocelular/sangre , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Humanos , Neoplasias Hepáticas/sangre , Masculino , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Sorafenib/administración & dosificación , GemcitabinaRESUMEN
BACKGROUND: Metastatic breast cancer (MBC) prognosis is variable, depending on several clinical and biological factors. A better prediction of a patient's outcome could allow for a more accurate choice of treatments. The role of serum biomarkers in predicting outcome remains unclear in this setting. Tau, a microtubule-associated protein, is a neuronal marker that is also expressed in normal breast epithelial cells and cancer cells. Its tissue expression is associated with prognosis in MBC. However, the prognostic value of Tau serum levels in these patients is unknown. We aimed at evaluating the prognostic value of Tau (and other classical biomarkers) in MBC patients, and to assess its association with the presence of brain metastases (BM). METHODS: 244 MBC patients treated at our institution (2007-2015) were retrospectively selected. The usual MBC clinical and pathological variables were collected, altogether with CA15-3, CEA and HER2 extra-cellular domain (ECD) serum levels. Tau serum levels were measured with a novel immunoassay (digital ELISA) using Single Molecule Array (Simoa) technology. Overall survival (OS) was estimated with the Kaplan-Meier method. To investigate prognostic factors, a multivariate analysis was performed. Cut-offs were set using the Youden index method associated with receiver-operating characteristics (ROC) curves to evaluate the accuracy of biomarkers to identify patients with BM. RESULTS: With a median follow-up of 40.8 months, median OS was 15.5 months (95%CI 12.4-20.2). Elevated serum levels of Tau were independently associated with a poor outcome in the whole population as well as in patients with (n = 86) and without BM (n = 158). Median serum Tau levels tended to be higher in patients with BM (p = 0.23). In univariate analysis, patients with BM had an increased risk of serum Tau > 3.17 pg/mL (OR = 2.2, p = 0.049). In multivariate analysis, high values of Tau (OR = 3.98, p = 0.034) accurately identified patients with BM in our cohort. CONCLUSIONS: Tau is a new biomarker of interest in MBC. Its serum level could represent an independent prognostic factor in these patients (both with and without BM). It also seems to be associated with the presence of BM. A validation of these results in an independent set of MBC patients is necessary to confirm these findings.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Proteínas tau/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Neoplasias Encefálicas/sangre , Neoplasias de la Mama/sangre , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: There has been interest in the potential benefit of vitamin D (VD) to improve breast cancer outcomes. Pre-clinical studies suggest VD enhances chemotherapy-induced cell death. Vitamin D deficiency was associated with not attaining a pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for operable breast cancer. We report the impact of VD on pCR and survival in an expanded cohort. METHODS: Patients from Iowa and Montpellier registries who had serum VD level measured before or during NAC were included. Vitamin D deficiency was defined as < 20 ng/mL. Pathological complete response was defined as no residual invasive disease in the breast and lymph nodes. Survival was defined from the date of diagnosis to the date of relapse (PFS) or date of death (OS). RESULTS: The study included 327 women. Vitamin D deficiency was associated with the odds of not attaining pCR (p = 0.04). Fifty-four patients relapsed and 52 patients died. In multivariate analysis, stage III disease, triple-negative (TN) subtype and the inability to achieve pCR were independently associated with inferior survival. Vitamin D deficiency was not significantly associated with survival in the overall sample; however a trend was seen in the TN (5-years PFS 60.4% vs. 72.3%, p = 0.3), and in the hormone receptor positive /human epidermal growth factor receptor 2 negative (HER2-) subgroups (5-years PFS 89% vs 78%, p = 0.056). CONCLUSION: Vitamin D deficiency is associated with the inability to reach pCR in breast cancer patients undergoing NAC.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Terapia Neoadyuvante/estadística & datos numéricos , Vitamina D/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Recurrencia , Estudios RetrospectivosRESUMEN
Breast cancer (BC) metastatic behavior varies according to the hormone receptors (HR) and HER2 statuses. Indeed, patients with triple-negative (TN) and HER2+ tumors are at higher risk of brain metastases (BM). The objective of this multinational cohort was to evaluate BM kinetics depending on the BC subtype. We retrospectively analyzed a series of BC patients with BM diagnosed in four European institutions (1996-2016). The delay between BC and BM diagnoses (BM-free survival) according to tumor biology was estimated with the Kaplan-Meier method. A multivariate analysis was performed using the Cox proportional hazards regression model. 649 women were included: 32.0% HER2-/HR+, 24.8% TN, 22.2% HER2+/HR- and 21.0% HER2+/HR+ tumors. Median age at BM diagnosis was 56 (25-85). In univariate analysis, BM-free survival differed depending on tumor biology: HER2-/HR+ 5.3 years (95% CI 4.6-5.9), HER2+/HR+ 4.4 years (95% CI 3.4-5.2), HER2+/HR- 2.6 years (95% CI 2.2-3.1) and TN 2.2 years (95% CI 1.9-2.7) (p < 0.001). It was significantly different between HR+ and HR- tumors (5.0 vs. 2.5 years, p < 0.001), and between HER2+ and HER2- tumors (3.2 vs. 3.8 years, p = 0.039). In multivariate analysis, estrogen-receptors (ER) and progesterone-receptors (PR) negativity, but not HER2 status, were independently associated with BM-free survival (hazard ratio = 1.36 for ER, p = 0.013, 1.31 for PR, p = 0.021, and 1.01 for HER2+ vs. HER2- tumors, p = 0.880). HR- and HER2+ tumors are overrepresented in BC patients with BM, supporting a higher risk of BM in these biological subtypes. HR status, but not HER2 status, impacts the kinetics of BM occurrence.
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Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Receptores de Péptidos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias de la Mama/mortalidad , Europa (Continente) , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
PURPOSE: Intermediate-risk early breast cancer (EBC) is a heterogeneous group in which adjuvant chemotherapy decision proves to be difficult. Clinical and pathological criteria are sometimes insufficient to determine the best therapeutic options, and validated biomarkers such as uPA/PAI-1, are needed to contribute to the decision-making. The objective of this study was to evaluate the clinical outcome of an unselected ER+/HER2- pN0 EBC cohort of patients in whom the routine clinical decision process included a prospective uPA/PAI-1 determination. METHOD: This monocentric retrospective study included 520 patients who underwent curative surgery in our institute between 2006 and 2011. Adjuvant therapeutic strategy was decided based on clinical-pathological data, altogether with a routine prospective determination of uPA/PAI-1 tumor levels using fresh, extemporaneously sampled tissue. We evaluated the correlation between uPA/PAI-1 levels, clinical-pathological variables, and the patient's outcome (relapse-free survival, RFS, and overall survival, OS). RESULT: Median follow-up was 5.4 years. The 5- and 10-year RFS rates were ,respectively, 95 and 89%, and the five-year OS rate was 96.3%. Forty percent of tumors had low uPA/PAI-1 levels. Seventy-five percent of patients with low uPA/PAI-1 levels did not receive chemotherapy, when 25% did. Sixty percent of patients with high uPA and/or PAI-1 levels received chemotherapy, while 40% did not. No statistical significant correlation was found between the uPA/PAI-1 levels and RFS or OS. CONCLUSION: The personalization of the patients' treatment using uPA/PAI-1 tumor levels allows the reversion of the well-known poor prognostic impact of high uPA/PAI-1 levels and strongly supports the use of this biomarker in clinical practice.
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Neoplasias de la Mama/sangre , Neoplasias de la Mama/mortalidad , Inhibidor 1 de Activador Plasminogénico/sangre , Activador de Plasminógeno de Tipo Uroquinasa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Toma de Decisiones Clínicas , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Recurrencia , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Breast cancer (BC) is the second most common cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM. Elevated serum S100ß protein and neuron-specific enolase (NSE) could reflect the brain damages induced by BM. Matrix metalloproteinase 9 (MMP-9) is involved in tumor invasion and metastatic dissemination, including BM. Also, HER2-amplified BC were shown to have a particular tropism for central nervous system (CNS). This study evaluated the correlation of these biomarkers with the presence of BM in metastatic BC patients. In this case-control study, 88 consecutive metastatic BC patients with BM (BM group) treated in our institution (2008-2015) were retrospectively selected, based on the availability of frozen serum samples for tumor marker determination. Patients were matched by age, tumor biology and number of previous metastatic chemotherapy lines to 162 metastatic BC patients without CNS involvement (control group). Serum NSE, MMP-9 and HER2 extracellular domain (ECD) levels were significantly higher in the BM group (p = 0.0051, p = 0.0062 and p = 0.0057, respectively). In multivariate analysis, serum HER2 and MMP-9 levels accurately discriminated patients with BM: odds ratios 4.4 (p < 0.001; 95%CI: 1.9-9.6) for HER2 ECD and 3.5 (p = 0.005; 95%CI: 1.5-8.4) for MMP-9. In multivariate analysis, HER2 ECD and NSE serum levels were independent prognostic factors in patients with BM. Serum HER2 ECD and MMP-9 appear to be associated with BM in metastatic BC patients. Their predictive value for BM still needs to be evaluated in further prospective studies.
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Neoplasias Encefálicas/enzimología , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Metaloproteinasa 9 de la Matriz/sangre , Fosfopiruvato Hidratasa/sangre , Receptor ErbB-2/sangre , Anciano , Biomarcadores de Tumor/sangre , Neoplasias Encefálicas/sangre , Neoplasias de la Mama/sangre , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Subunidad beta de la Proteína de Unión al Calcio S100/sangreAsunto(s)
Neoplasias Renales , Nefrectomía , Antineoplásicos , Carcinoma de Células Renales , Humanos , Indoles , Pirroles , Sunitinib , Resultado del TratamientoRESUMEN
Few data are currently available regarding the efficacy and safety of T-DM1 in breast cancer (BC) patients with unselected brain metastases (BM), since most clinical trials have excluded BM patients or have only included highly selected patients. HER2 + BC patients with BM treated with T-DM1 in 5 French centers were included in this retrospective study. Clinical management was performed according to the product guidelines. Efficacy was evaluated recording tumor response rates, progression-free (PFS) and overall survival, treatment compliance, and safety. Thirty nine patients received T-DM1, among whom 82 % presented with concomitant extra-cerebral disease. Median number of previous metastatic chemotherapy and HER2-directed targeted therapy regimens was 2 (range 0-8) and 1 (0-7), respectively. Thirty six patients had received BM loco-regional treatment (72 % whole-brain radiation therapy). After a median follow-up of 8.1 months (1.4-39.6), 24 patients had progressed (first site of progression: brain 14; meningeal 2; outside of the central nervous system 5; both intra- and extra-cerebral 3), 12 patients had died (disease progression), and 27 patients were still alive. Median number of T-DM1 cycles was 8 (1-43). There were 17 partial responses (44 %) and 6 patients achieved disease stabilization (59 % clinical benefit rate). Median PFS was 6.1 months (95 %CI 5.2-18.3), with one- and two-year PFS rates of 33 and 17 %, respectively. Treatment was well tolerated, without unexpected toxicities, treatment delay, or dose reduction. In this retrospective study, T-DM1 appeared to be an effective and well-tolerated therapeutic option in unselected HER2 + BC patients with BM. These findings require a prospective validation.
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Antineoplásicos Inmunológicos/administración & dosificación , Neoplasias Encefálicas/radioterapia , Neoplasias de la Mama/tratamiento farmacológico , Maitansina/análogos & derivados , Receptor ErbB-2/genética , Trastuzumab/administración & dosificación , Ado-Trastuzumab Emtansina , Adulto , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Maitansina/administración & dosificación , Maitansina/efectos adversos , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Análisis de Supervivencia , Trastuzumab/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Metastatic breast cancer (MBC) prognosis is highly variable, depending on various factors such as the biological subtype, the performance status, disease extension . A better evaluation of a patient's prognostic factors could allow for a more accurate choice of treatments. The role of serum tumor markers remains, however, unclear in this population. Considering the recent interest in phenotypic changes and tumor heterogeneity during breast cancer progression, additional tumor markers could be interesting in this setting. METHODS: Two hundred fifty MBC patients treated at the Montpellier Cancer Institute (2008-2015) were retrospectively selected, based on the availability of frozen serum samples. The usual MBC clinical and pathological variables were collected, altogether with Cancer Antigen 15-3 (CA15-3), Carcinoembryonic Antigen (CEA), HER2 extra-cellular domain (ECD), Neuron Specific Enolase (NSE), S100ß protein and Matrix Metalloproteinase 9 (MMP-9) serum levels in order to determine their prognostic value. RESULTS: With a median follow-up of 40.8 months, median overall survival was 16.2 months (95 % CI 12.4-20.6). In multivariate analysis, the performance status, brain or subcutaneous metastases, the number of previous metastatic chemotherapy lines and the tumor biological subtype were independent prognostic factors. Elevated CA 15-3 (HR = 1.95, IC 95 % 1.31-2.93, p = 0.001), HER2 ECD (regardless of tumor HER2 status, HR = 2.51, IC 95 % 1.53-4.12, p < 0.001) and S100ß (HR = 1.93, IC 95 % 1.05-3.54, p = 0.033) serum levels were independently associated with a poor outcome. CONCLUSIONS: Serum CA 15-3, HER2 ECD and S100ß could represent useful independent prognostic factors in MBC. Of particular interest is the independent value of serum HER2 ECD levels, regardless of the tumor HER2 status, possibly linked to metastatic tumor heterogeneity.
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Neoplasias de la Mama/metabolismo , Mucina-1/sangre , Receptor ErbB-2/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
AIMS: Following the introduction of new adjuvant therapies we wanted to reappraise the prognostic and predictive value of uPA/PAI-1 in early breast cancer. PATIENTS & METHODS: This monocentric retrospective study included 652 patients who had curative surgery between 2006 and 2011 and adjuvant treatment decision-making, taking into account uPA/PAI-1 tumor levels. RESULTS: uPA and PAI-1 levels were associated with classical clinicopathological parameters and adjuvant chemotherapy decision, but not with peritumoral vascular invasion (PVI; also known as peritumoral vascular emboli). HER2 overexpression, PVI and uPA/PAI-1 levels were not significantly associated with relapse-free survival in univariate analysis. In multivariate analysis, T stage, N stage and progesterone receptors were the only independent relapse-free survival predictive factors. CONCLUSION: The absence of an association between uPA/PAI-1 and PVI allows their concomitant consideration in adjuvant treatment discussion. The overall good prognosis of patients with high uPA/PAI-1 levels might be linked to the uPA/PAI-1 predictive value and the inclusion of these parameters in adjuvant guidelines.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Inhibidor 1 de Activador Plasminogénico/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Toma de Decisiones , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Triplet chemotherapy plus cetuximab showed promising results in phase II trials in unsystematically selected RAS population. We evaluated FOLFIRINOX+cetuximab efficacy as first-line treatment in extended RAS wild-type metastatic colorectal cancer (mCRC) patients. METHODS: We retrospectively analyzed patients treated with FOLFIRINOX+cetuximab, using data from clinical trials and real-life practice. Extended mutation analysis was performed when RAS/BRAF status was unavailable. The primary endpoint was progression-free survival (PFS). RESULTS: Seventy patients (61.4 % male, median age 58.7 years) were analyzed. Eighty percent had left-sided mCRC and 97.1 % had liver metastases. Median PFS and overall survival (OS) were 13.3 and 48.5 months, respectively. The objective response rate was 85.7 %, with 20 % complete response. Primary tumor location did not affect OS and PFS. BRAF wild-type patients (n = 65) had longer PFS (13.3 vs. 6.0 months; p = 0.005) and OS (50.1 vs. 21.2 months; p = 0.007) than BRAF mutated patients (n = 5, including four BRAFV600E). Median OS was significantly longer in resected patients (n = 39, 55.1 vs. 30.7 months; p = 0.030). Main toxicities were diarrhea (31.4 %) and neutropenia (21.4 %). CONCLUSION: FOLFIRINOX+cetuximab provides good PFS, high response rate and prolonged disease control in initially unresectable extended RAS wild-type mCRC. This combination is particularly interesting for selected patients with liver-limited disease eligible to secondary resection.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cetuximab , Neoplasias Colorrectales , Fluorouracilo , Irinotecán , Leucovorina , Oxaliplatino , Humanos , Cetuximab/administración & dosificación , Cetuximab/uso terapéutico , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Femenino , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Irinotecán/uso terapéutico , Irinotecán/administración & dosificación , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Anciano , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Adulto , Supervivencia sin Progresión , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogénicas B-raf/genética , MutaciónRESUMEN
BACKGROUND: Real-world data (RWD) related to the health status and care of cancer patients reflect the ongoing medical practice, and their analysis yields essential real-world evidence. Advanced information technologies are vital for their collection, qualification, and reuse in research projects. METHODS: UNICANCER, the French federation of comprehensive cancer centres, has innovated a unique research network: Consore. This potent federated tool enables the analysis of data from millions of cancer patients across eleven French hospitals. RESULTS: Currently operational within eleven French cancer centres, Consore employs natural language processing to structure the therapeutic management data of approximately 1.3 million cancer patients. These data originate from their electronic medical records, encompassing about 65 million medical records. Thanks to the structured data, which are harmonized within a common data model, and its federated search tool, Consore can create patient cohorts based on patient or tumor characteristics, and treatment modalities. This ability to derive larger cohorts is particularly attractive when studying rare cancers. CONCLUSIONS: Consore serves as a tremendous data mining instrument that propels French cancer centres into the big data era. With its federated technical architecture and unique shared data model, Consore facilitates compliance with regulations and acceleration of cancer research projects.
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Investigación Biomédica , Neoplasias , Humanos , Minería de Datos , Registros Electrónicos de Salud , Neoplasias/terapia , LenguajeRESUMEN
PURPOSE: This study was designed to evaluate neoadjuvant intensified chemotherapy in potentially resectable or unresectable liver metastases (LM) from colorectal cancer (CRC). METHODS: Criteria for potentially resectable LM were complex hepatectomy and/or risky procedure, close contact with major vascular structures, and for unresectable LM, a future liver remnant predicted to be less than 25-30 % of total liver volume. Between October 2004 and August 2007, 125 patients were randomized to either standard (FOLFIRI/FOLFOX4) or intensified chemotherapy (FOLFIRI-HD/FOLFOX7/FOLFIRINOX). Primary endpoint was objective response rate (ORR) after 4 cycles of chemotherapy. Secondary endpoints included safety, R0 surgical resection, best ORR, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 122 patients were treated; 45 % of patients had less than 30 % of remaining liver tissue, 20 % had major vascular contact, and 35 % were potentially resectable. Grade 3/4 toxicities were neutropenia (24, 19, 10, 23 %) diarrhoea (0, 6, 3, 23 %), mucositis (0, 3, 0, 7 %), vomiting (7, 9, 0, 3 %), and neurotoxicity (0, 0, 10, 3 %) in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. ORR was 33, 47, 43, and 57 % after the first 4 cycles in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. FOLFIRINOX offered the best conversion rate to resectability (67 %). Disease-free status after chemotherapy and surgery (R0, R1, Rx) was achieved in 54 of 64 operated patients. Median PFS was 9.2 months in control arms versus 11.9 months in experimental arms (hazards ratio [HR] = 0.76, p = 0.115), and the median OS was 17.7 versus 33.4 months (HR = 0.73, p = 0.297), respectively. CONCLUSIONS: FOLFIRINOX showed promising activity in CRC patients with LM compared with standard or intensified bi-chemotherapy regimens.