RESUMEN
BACKGROUND: Baseline plasma androgen-receptor copy number (AR-CN) is a promising biomarker for metastatic castration-resistant prostate cancer (mCRPC) outcome and treatment response; however, the role of its longitudinal testing is unproven. We aimed to evaluate the prognostic role of AR-CN assessed before subsequent treatment lines in mCRPC patients. METHODS: A subgroup analysis of a prospective multicenter biomarker trial (IRSTB030) was carried out. Plasma AR-CN status (classified as normal or gain, cut-off value = 2) was assessed with digital PCR before each treatment line. RESULTS: Forty mCRPC patients receiving sequentially docetaxel, cabazitaxel and an AR signaling inhibitor (abiraterone or enzalutamide) were analyzed. At multivariate analysis, at each assessment overall survival (OS) was independently correlated with AR-CN status [first line: hazard ratio (HR) 4.1 [95% confidence interval (CI) 1.6-10.5]; second line: HR 2.4 (95% CI 1.1-5.3); third line: HR 2.1 (95% CI 1.0-4.3)] and median prostate-specific antigen [first line: HR 4.4 (95% CI 1.8-10.9); second line: HR 3.4 (95% CI 1.6-7.2); third line: HR 2.5 (95% CI 1.2-5.6)]. In the three subsequent assessments, AR-CN status changed from normal to gain in 15 (38%) patients. These patients had longer OS (47 months) compared with patients presenting AR-CN gain from first assessment (36 months), but shorter than those maintaining normal AR-CN (69 months) (P = 0.003). CONCLUSIONS: Plasma AR-CN correlates with survival not only at baseline (before first treatment), but also in the assessments before the following lines. Interestingly, AR-CN status may change from normal to gain across subsequent treatments in a significant number of cases, identifying a group of patients with intermediate outcomes. Longitudinal assessment of AR-CN status could represent a promising method to capture mCRPC intrinsic heterogeneity and to improve clinical management.
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Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Masculino , Humanos , Receptores Androgénicos/genética , Receptores Androgénicos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Variaciones en el Número de Copia de ADN , Estudios Prospectivos , Antígeno Prostático Específico/uso terapéuticoRESUMEN
In localized prostate cancer (PCa), Grade Group (GG) and Gleason Score (GS) have a well-established prognostic role. In metastatic castration resistant prostate cancer (mCRPC), the prognostic role of GS and GG is less defined. In first-line treatment of mCRPC, androgen receptor (AR)-directed drugs (abiraterone acetate, enzalutamide) and docetaxel represent the referring options. There is no evidence that the GS/GG systems can add information to guide the choice between AR-directed drugs and docetaxel in the first-line setting of mCRPC. Nowadays there are no validated biomarkers, which define patients who may benefit or not from hormonal treatments or chemotherapy. Androgen receptor (AR) copy number variations (CNV) are predictive factors of poor response to abiraterone and enzalutamide. There are no available data about the association between AR CNV and GG. In this retrospective study, we analysed the association of the highest GG score with AR CNV and their impact on the clinical outcome of AR-directed drugs and docetaxel as first-line therapy for mCRPC patients. Patients benefit from docetaxel, abiraterone or enzalutamide regardless the GG. However, the presence of GG5 and AR CNV gain identifies a subgroup of patients with poor prognosis, which could benefit from front-line docetaxel instead of AR-directed drugs.
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Neoplasias de la Próstata Resistentes a la Castración , Variaciones en el Número de Copia de ADN , Docetaxel/uso terapéutico , Humanos , Masculino , Nitrilos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/genética , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Pheochromocytoma and paraganglioma (PPGL) have currently only limited treatment options available for patients in the metastatic phase (mPPGL) in either post-surgery or inoperable settings. However, these rare tumors overexpress somatostatin receptors and can thus be treated with peptide receptor radionuclide therapy (PRRT). We present data about our 10-year experience treating 46 consecutive mPPGL patients with 90Y-DOTATOC or 177Lu-DOTATATE. PATIENTS AND METHODS: All patients (20 men and 26 women, median age 52 years) showed positive scintigraphic imaging at 111In-octreotide or 68Ga-DOTATOC positron emission tomography/computed tomography (PET/CT). 90Y-DOTATOC was administered in 12 patients, with cumulative dosages ranging from 7.4 to 11 GBq, while 34 patients received 18.5 or 27.5GBq of 177Lu-DOTATATE. We used Southwest Oncology Group Response Evaluation Criteria in Solid Tumors criteria to evaluate treatment efficacy and Common Terminology Criteria for Adverse Events criteria to assess toxicity. The prognostic role of primary tumor site, hormone secretion, succinate dehydrogenase (SDHx) mutation, and metastatic involvement was also evaluated. RESULTS: Both 90Y-DOTATOC and 177Lu-DOTATATE PRRT were well tolerated by patients without significant renal or bone marrow toxicity. The median follow-up was 73 months (range 5-146 months). The overall disease control rate (DCR) was 80% [95% confidence interval (CI) 68.9% to 91.9%] with a mean five cycles of therapy. However, 177Lu-DOTATATE patients showed a longer median overall survival (mOS) than those receiving 90Y-Dotatoc and a better DCR when higher dosages were administered, even if a direct comparison was not carried out. Syndromic patients had a poorer mOS. SDHx mutations did not interfere with treatment efficacy. CONCLUSIONS: PRRT is safe and effective for the treatment of patients with progressive mPPGL, especially at higher dosages. The longer mOS of 177Lu-DOTATATE-treated patients in our protocols indicates the former radiopharmaceutical as the better candidate for further clinical application.
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Neoplasias de las Glándulas Suprarrenales , Tumores Neuroendocrinos , Paraganglioma , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/radioterapia , Biomarcadores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paraganglioma/diagnóstico por imagen , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Receptores de Somatostatina , Radioisótopos de ItrioRESUMEN
PURPOSE: The role played by radiation therapy after pleurectomy/decortication or surgical biopsy in malignant pleural mesothelioma is uncertain. We treated patients with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy in an attempt to keep lung toxicity to a minimum. The present study reports the feasibility and toxicity of this approach. MATERIAL AND METHODS: Between 2008 and 2012, 36 patients with malignant pleural mesothelioma underwent accelerated hypofractionated radiotherapy to the hemithorax after pleurectomy/decortication (19 patients) or biopsy (17 patients). The prescription dose was 25Gy in five fractions over 5 consecutive days. RESULTS: We observed three patients with G3 pneumonitis, five cases of grade 2 dyspnea and six cases of grade 2 cough. The median follow-up was 37 months (range: 3-54 months). The median overall survival for patients who underwent pleurectomy/decortication followed by radiotherapy was 21.6 months [95% confidence interval (95% CI): 15.5-24.1] compared to 19.4 months for patients not submitted to surgery. CONCLUSION: Treatment of intact lung with pleural intensity-modulated arc irradiation in malignant pleural mesothelioma patients with malignant pleural mesothelioma proved safe and feasible, with an acceptable rate of pneumonitis. Survival rates were encouraging for both biopsy-only and pleurectomy/decortication groups. We are currently conducting a phase II dose escalation trial in a similar patient setting to prospectively evaluate the impact of radiotherapy on toxicity, disease-free survival and overall survival.
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Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Mesotelioma/radioterapia , Mesotelioma/cirugía , Pleura/cirugía , Neoplasias Pleurales/radioterapia , Neoplasias Pleurales/cirugía , Hipofraccionamiento de la Dosis de Radiación , Radioterapia de Intensidad Modulada , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Terapia Combinada , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/patología , Mesotelioma Maligno , Persona de Mediana Edad , Neoplasias Pleurales/patología , Estudios RetrospectivosRESUMEN
The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT. We analysed 80 mCRPC patients progressing after docetaxel treated with abiraterone (n = 47) or enzalutamide (n = 33). We analysed AR CN from plasma samples using digital PCR and Taqman CN assays and total lesion activity (TLA) and metabolic tumor volume (MTV) on FCH-PET/CT at baseline. A meaningful correlation was showed among AR gain and TLA/MTV compared to AR non-gained cases (P = 0.001 and P = 0.004, respectively), independently from type of treatment. Multivariate analysis revealed that AR CN and only TLA were associated with both shorter PFS (P < 0.0009 and P = 0.026, respectively) and OS (P < 0.031 and P = 0.039, respectively). AR gain appeared significantly correlated with choline uptake represented mainly by TLA. Further prospective studies are warranted to better address this pathway of AR-signalling and to identify multiplex biomarker strategies including plasma AR and FCH-PET/CT in mCRPC patients.
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Adenocarcinoma/tratamiento farmacológico , Cloro/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos/sangre , Receptores Androgénicos/genética , Adenocarcinoma/sangre , Adulto , Anciano , Anciano de 80 o más Años , Androstenos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas , Biomarcadores de Tumor/metabolismo , Colina/análogos & derivados , Colina/metabolismo , Docetaxel/uso terapéutico , Dosificación de Gen , Humanos , Masculino , Persona de Mediana Edad , Nitrilos , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata Resistentes a la Castración/sangre , Transducción de SeñalRESUMEN
BACKGROUND: High-dose chemotherapy (HDC) with hematopoietic progenitor cell transplantation is a standard option for relapsed/refractory testicular germ-cell tumor (GCT), but only few data have been reported in female patients with GCT. We conducted a retrospective analysis of female patients with GCT treated with HDC and registered with the European Society for Blood and Marrow Transplantation. PATIENTS AND METHODS: Between 1985 and 2013, 60 registered female patients with GCT, median age 27 years (range 15-48), were treated with salvage HDC. Forty patients (67%) had primary ovarian GCT, 8 (13%) mediastinal, 7 (12%) retroperitoneal and 5 (8%) other primary sites/unknown. Twenty-two patients (37%) received HDC as second-line therapy, 29 (48%) as third-line, and 9 (15%) as fourth- to sixth-line. Nine of 60 patients (15%) received HDC as late-intensification with no evidence of metastasis before HDC. The conditioning HDC regimens comprised carboplatin in 51 of 60 cases (85%), and consisted of a single HDC cycle in 31 cases (52%), a multi-cycle HDC regimen in 29 (48%). RESULTS: Nine cases who underwent late intensification HDC were not evaluable for response. Of the other 51 assessable patients, 17 (33%) achieved a complete response (CR), 8 (16%) a marker-negative partial remission (PRm-), 5 (10%) a marker-positive partial remission, 5 (10%) stable disease, and 13 (25%) progressive disease. There were 3 toxic deaths (6%). With an overall median follow-up of 14 months (range 1-219), 7 of 9 (78%) patients with late intensification and 18 of the 25 patients (72%) achieving a CR/PRm- following HDC were free of relapse/progression. In total, 25 of 60 patients (42%) were progression-free following HDC at a median follow-up of 87 months (range 3-219 months). CONCLUSIONS: Salvage HDC based on carboplatin represents a therapeutic option for female patients with relapsed/refractory GCT.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Terapia Recuperativa , Adolescente , Adulto , Antineoplásicos/administración & dosificación , Trasplante de Médula Ósea , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/terapia , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Acondicionamiento Pretrasplante , Adulto JovenRESUMEN
BACKGROUND: Genomic studies have shown that gene expression profiles are similar in in situ (CIS) and invasive breast cancers, suggesting that several biofunctional modifications of the transformation process occur before or during the development of CIS lesion. METHODS: We investigated 3 biomarkers in 44 patients with CIS: TG2 (transglutaminase 2), HJURP (Holliday junction recognition protein), and HIF-1α (hypoxia inducible factor-1 alpha). RESULTS: TG2 was more highly expressed than the other two markers and significantly more so in stromal than in tumor cells. HIF-1α evaluation showed a higher expression in both tumor and stromal cells in patients with relapsed G3 tumors, indicating a potential role of this marker in CIS evolution. A greater than sevenfold higher risk of relapse (P = 0.050) was observed in patients highly expressing HJURP in stroma and a tenfold higher recurrence risk (P = 0.026) was seen in those with a higher stromal HIF-1α expression. An important increase in risk accuracy (AUC 0.80) was obtained when HIF-1α and HJURP were evaluated together. CONCLUSIONS: Despite the limited number of relapsed patients, we formulated some hypotheses on the factors responsible for malignant evolution and recurrence which are now being tested in a large case series with a longer follow-up.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma in Situ/metabolismo , Proteínas de Unión al ADN/metabolismo , Progresión de la Enfermedad , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Adulto , Anciano , Área Bajo la Curva , Neoplasias de la Mama/patología , Carcinoma in Situ/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Recurrencia , Células del Estroma/patologíaRESUMEN
Our purpose was to investigate whether Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) expression could be linked to prognosis in invasive breast carcinomas. NHERF1, an ezrin-radixin-moesin (ERM) binding phosphoprotein 50, is involved in the linkage of integral membrane proteins to the cytoskeleton. It is therefore believed to have an important role in cell signaling associated with changes in cell cytoarchitecture. NHERF1 expression is observed in various types of cancer and is related to tumor aggressiveness. To date the most extensive analyses of the influence of NHERF1 in cancer development have been performed on breast cancer. However, the underlying mechanism and its prognostic significance are still undefined. NHERF1 expression was studied by immunohistochemistry (IHC) in a cohort of 222 breast carcinoma patients. Association of cytoplasmic and nuclear NHERF1 expression with survival was analyzed. Disease-free survival (DFS) and overall survival (OS) were determined based on the Kaplan-Meier method. Cytoplasmic NHERF1 expression was associated with negative progesterone receptor (PgR) (P=0.017) and positive HER2 expression (P=0.023). NHERF1 also showed a nuclear localization and this correlated with small tumor size (P=0.026) and positive estrogen receptor (ER) expression (P=0.010). Multivariate analysis identified large tumor size (P=0.011) and nuclear NHERF1 expression (P=0.049) to be independent prognostic variables for DFS. Moreover, the nuclear NHERF1(-)/ER(-) immunophenotype (27%) was statistically associated with large tumor size (P=0.0276), high histological grade (P=0.0411), PgR-negative tumors (P<0.0001) and high proliferative activity (P=0.0027). These patients had worse DFS compared with patients with nuclear NHERF1(+)/ER(+) tumors (75.4% versus 92.6%; P=0.010). These results show that the loss of nuclear NHERF1 expression is associated with reduced survival, and the link between nuclear NHERF1 and ER expression may serve as a prognostic marker for the routine clinical management of breast cancer patients.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Núcleo Celular/metabolismo , Fosfoproteínas/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Adulto , Anciano , Neoplasias de la Mama/genética , Femenino , Humanos , Inmunohistoquímica , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Fosfoproteínas/genética , Pronóstico , Intercambiadores de Sodio-Hidrógeno/genéticaRESUMEN
BACKGROUND: Usual interstitial pneumonia (UIP), is a necessary feature pathologically or radiologically for the diagnosis of idiopathic pulmonary fibrosis (IPF). The predictive value of transbronchial biopsy (TBB) in identifying UIP is currently unknown. The objective of this study is to assess the accuracy with which histopathologic criteria of usual interstitial pneumonia (UIP) can be identified in transbronchial biopsy (TBB) and to assess the usefulness of TBBx in predicting a the diagnosis of UIP pattern. We conducted a retrospective blinded and controlled analysis of TBB specimens from 40 established cases of UIP and 24 non-UIP interstitial lung diseases. RESULTS: Adequate TBB specimens were available in 34 UIP cases (85% of all UIP cases). TBB contained histopathologic criteria to suggest a UIP pattern (ie. at least one of three pathologic features of UIP present; patchy interstitial fibrosis, fibroblast foci, honeycomb changes) in 12 cases (30% of all UIP cases). Sensitivity, specificity, positive and negative predictive values for the two pathologists were 30% (12/40), 100% (24/24), 100% (12/12), 46% (24/52) and 30% (12/40), 92% (22/24), 86% (12/14), 55% (22/40) respectively. Kappa coefficient of agreement between pathologists was good (0.61, 95% CI 0.31-0.91). The likelihood of identifying UIP on TBB increased with the number and size of the TBB specimens. CONCLUSION: Although sensitivity is low our data suggest that even modest amount of patchy interstitial fibrosis, fibroblast foci, honeycomb changes detected on TBB can be highly predictive of a UIP pattern. Conversely, the absence of UIP histopathologic criteria on TBB does not rule out UIP.
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Bronquios/patología , Broncografía , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/patología , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with generally disappointing results in terms of survival, however, there are occasional long-term survivors probably due to the biologic characteristics of the disease. Standard uptake value (SUV) of [(18)F] Fluorodeoxyglucose (FDG) evaluated by photon emission tomography (PET) is now widely accepted as an indicator of biologic behavior in several malignancies. The aim of this study was to verify whether SUV(max) and SUV(mean) are inversely associated with the prognosis of patients with MPM and whether there was a correlation between grading/disease stage and SUV value. Patients with histologically proven MPM underwent integrated PET and computed tomography (CT) scanning. Patients fasted and received 5.18 MBq of FDG per kilogram of body weight. Based on the maximum Chi-Square method, a SUV(max) of 4.21 (range: 2.30-14.74) and a SUV(mean) of 2.78 (range: 1.80-7.00) were used to classify patients as having a good or poor prognosis, respectively. From January 2004 to March 2010, 27 patients were analyzed: median age was 65 years (range: 54-77) and histologic MPM subtypes were epithelioid (23 patients) and biphasic (4 patients). At a median follow-up of 23 months (range: 1-52), there was no difference in median survival for either high or low SUV(max) [26 months (range: 11-not reached) vs.19 months (range: 12-not reached); p=0.811] or for high or low SUV(mean) [26 months (range: 8-not reached) vs.19 months (range: 11-not reached); p=0.831]. High SUV(max) (p=0.018) was statistically correlated with high-stage disease. There was only a trend towards statistical significance between high-grade disease and high SUV(mean) (p=0.083); no such trend was found between advanced stages and SUV(max) (p=0.268). We observed a significant correlation only between high SUV(max) and high-grade disease. No other relationships between SUV(max) and SUV(mean) with biologic and clinical parameters were found. This is probably due to the patient characteristics and to the non-routine use of 18F-FDG PET/CT to stage rare tumors such as MPM.
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Fluorodesoxiglucosa F18 , Mesotelioma/diagnóstico por imagen , Imagen Multimodal , Neoplasias Pleurales/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Tomografía Computarizada por Rayos X/métodos , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Mesotelioma/mortalidad , Mesotelioma/patología , Mesotelioma/terapia , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/patología , Neoplasias Pleurales/terapia , Pronóstico , Tasa de SupervivenciaRESUMEN
The liver is the primary site of metastases in most uveal melanoma patients. We retrospectively investigated intraarterial chemotherapy (IAC) as treatment for patients with hepatic melanoma metastases.Twenty-three patients (18 with uveal melanoma) received fotemustine (14 patients, 61.9%) or carboplatin (9 patients, 31.1%) via hepatic IAC delivery. The catheter was introduced through percutaneous access to the femoral artery with drugs delivered directly to the hepatic artery, and was removed at the end of each treatment cycle. A total of 3 cycles was planned, repeated every 21 days. However, patients with a clinical response could receive more than 3 cycles, provided that the toxic effects were acceptable.IAC was well tolerated and no catheter-related complications or grade 4 toxicities were reported. Considering only uveal melanoma patients, the overall response rate and disease control rate was 16.7% and 38.9%, respectively. Median time to progression was 6.2 months (95% CI 3.7-10.5) and median overall survival was 21 months (95% CI 8-39).IAC is well tolerated and is a valid choice for patients with a poor prognosis since median survival rates are among the longest reported.
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Antineoplásicos/administración & dosificación , Carboplatino/administración & dosificación , Sistemas de Liberación de Medicamentos , Neoplasias Hepáticas/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Compuestos de Nitrosourea/administración & dosificación , Compuestos Organofosforados/administración & dosificación , Adulto , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carboplatino/efectos adversos , Carboplatino/uso terapéutico , Monitoreo de Drogas , Registros Electrónicos de Salud , Femenino , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/secundario , Masculino , Melanoma/secundario , Melanoma/terapia , Persona de Mediana Edad , Compuestos de Nitrosourea/efectos adversos , Compuestos de Nitrosourea/uso terapéutico , Compuestos Organofosforados/efectos adversos , Compuestos Organofosforados/uso terapéutico , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias de la Úvea/terapia , Adulto JovenRESUMEN
BACKGROUND: Palliative sedation therapy (PST) is indicated for and used to control refractory symptoms in cancer patients undergoing palliative care. We aimed to evaluate whether PST has a detrimental effect on survival in terminally ill patients. METHODS: This multicenter, observational, prospective, nonrandomized population-based study evaluated overall survival in two cohorts of hospice patients, one submitted to palliative sedation (A) and the other managed as per routine hospice practice (B). Cohorts were matched for age class, gender, reason for hospice admission, and Karnofsky performance status. RESULTS: Of the 518 patients enrolled, 267 formed cohort A and 251 cohort B. In total, 25.1% of patients admitted to the participating hospices received PST. Mean and median duration of sedation was 4 (standard deviation 6.0) and 2 days (range 0-43), respectively. Median survival of arm A was 12 days [90% confidence interval (CI) 10-14], while that of arm B was 9 days (90% CI 8-10) (log rank = 0.95, P = 0.330) (unadjusted hazard ratio = 0.92, 90% CI 0.80-1.06). CONCLUSION: PST does not shorten life when used to relieve refractory symptoms and does not need the doctrine of double effect to justify its use from an ethical point of view.
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Hipnóticos y Sedantes/uso terapéutico , Cuidados Paliativos/métodos , Estrés Psicológico/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hospitales para Enfermos Terminales , Humanos , Estimación de Kaplan-Meier , Estado de Ejecución de Karnofsky , Tablas de Vida , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/terapia , Estudios Prospectivos , Análisis de Regresión , Cuidado Terminal , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Resection line infiltration (RLI) after surgical treatment represents an unfavorable prognostic factor in advanced gastric cancer. We performed a retrospective analysis of 89 patients with resection line involvement who did not undergo reoperation. METHODS: On behalf of the Italian Research Group for Gastric Cancer, we present the characteristics and outcome of 89 patients who were submitted to surgical resection for gastric cancer from 1988 to 2001 and did not undergo reoperation because of disease extension or associated pathologies. RESULTS: RLI was significantly higher in patients with T4 tumors and diffuse histological type. Anastomotic leakages were observed in 4.8% of infiltrated esophageal resection margins, whereas 1.9% of infiltrated duodenal resection lines showed duodenal fistulas. Five-year overall survival of patients with RLI was 29%. Prognosis was not affected by RLI in early forms (100% 5-year survival); however, 5-year survival in T2 and T3 stages was significantly lower with respect to the same stages without residual tumor. The influence of RLI on prognosis was confirmed in N0 as well as in N1 and N2 patients. RLI also was an independent prognostic at multivariate analysis (odds ratio = 1.5; 95% confidence interval, 1.08-2.08; P = 0.0144). CONCLUSIONS: RLI significantly affects long-term survival of advanced gastric cancer. The impact on prognosis is independent of lymph node involvement. Patients in good general condition for whom radical surgery is possible should be considered for reoperation.
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Gastrectomía , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Adolescente , Adulto , Anciano , Estudios de Cohortes , Humanos , Italia , Escisión del Ganglio Linfático , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasia Residual , Reoperación , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenAsunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Ciclooxigenasa 2/sangre , ADN de Neoplasias/sangre , Neoplasias Pulmonares/diagnóstico , Adulto , Anciano , Estudios de Casos y Controles , Ciclooxigenasa 2/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismoRESUMEN
We conducted a prospective randomized clinical trial to assess the mobilizing efficacy of filgrastim, lenograstim and molgramostim following a disease-specific chemotherapy regimen. Mobilization consisted of high-dose cyclophosphamide in 45 cases (44%), and cisplatin/ifosfamide/etoposide or vinblastine in 22 (21%), followed by randomization to either filgrastim or lenograstim or molgramostim at 5 microg/kg/day. One hundred and three patients were randomized, and 82 (79%) performed apheresis. Forty-four (43%) patients were chemonaive, whereas 59 (57%) were pretreated. A median number of one apheresis per patient (range, 1-3) was performed. The median number of CD34+ cells obtained after mobilization was 8.4 x 10(6)/kg in the filgrastim arm versus 5.8 x 10(6)/kg in the lenograstim arm versus 4.0 x 10(6)/kg in the molgramostim arm (P=0.1). A statistically significant difference was observed for the median number of days of growth factor administration in favor of lenograstim (12 days) versus filgrastim (13 days) and molgramostim (14 days) (P<0.0001) and for the subgroup of chemonaive patients (12 days) versus pretreated patients (14 days) (P<0.001). In conclusion, all three growth factors were efficacious in mobilizing peripheral blood progenitor cells with no statistically significant difference between CD34+ cell yield and the different regimens, and the time to apheresis is likely confounded by the different mobilization regimens.
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Adyuvantes Inmunológicos/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Movilización de Célula Madre Hematopoyética , Neoplasias/terapia , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Etopósido/administración & dosificación , Femenino , Filgrastim , Humanos , Ifosfamida/administración & dosificación , Lenograstim , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Factores de Tiempo , Trasplante Autólogo , Vinblastina/administración & dosificaciónRESUMEN
We investigated a number of biological markers, evaluated under strict intralaboratory quality control conditions, in terms of their role in predicting clinical outcome of patients with colon cancer treated with 5-FU-containing regimens. Colon cancer tissue from 263 patients enrolled onto two randomised clinical trials were studied for their cytofluorimetrically determined DNA content and their immunohistochemically evaluated microvessel density, vascular endothelial growth factor expression, thymidylate synthase expression and tumour lymphocyte infiltration. Disease-free survival and overall survival of patients were analysed as a function of the different variables. At a median follow up of 57 months, age, gender and Dukes' stage showed an impact on disease-free survival, whereas no biological marker emerged as an indicator of better or worse disease-free survival. Only histological grade and Dukes' stage were found to influence overall survival. The different biological variables, studied with particular attention for determination reliability, proved to have no impact on the clinical outcome of patients with colon cancer. Therefore, other markers must be identified to complement clinico-pathological variables in the management of this disease.
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Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/metabolismo , Neoplasias del Colon/diagnóstico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Supervivencia sin Enfermedad , Factores de Crecimiento Endotelial/metabolismo , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Linfocinas/metabolismo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , Timidilato Sintasa/metabolismo , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The predictivity of tumour size, oestrogen (ER) and progesterone (PgR) receptors, 3H-thymidine labelling index (TLI), c-erbB-2 and p27kip1 expression on clinical outcome was analysed on a consecutive series of 118 postmenopausal patients with ER-positive, node-positive tumours. All patients were treated with surgery +/- radiotherapy and adjuvant tamoxifen (30 mg/day) for at least 2 years. TLI, ER, c-erbB-2 and p27kip1 were generally unrelated to each other. PgR was directly related to ER and inversely to c-erbB-2. Tumour size was inversely related to both c-erbB-2 and p27kip1 expression. At a median follow-up of 75 months, 5-year relapse-free survival was significantly lower for patients with very rapidly proliferating (HR = 2.61, 95% CI = 1.34-5.08), PgR negative (HR = 2.76, 95% CI = 1.43-5.33) or relatively low ER content (HR = 2.20, 95% CI = 1.14-4.25) tumours than for patients with tumours expressing the opposite biological profiles. Overall survival was also significantly different as a function of TLI (HR = 3.47, 95% CI = 1.52-7.93) and PgR (HR = 2.27, 95% CI = 1.00-5.15). TLI and PgR maintained an independent relevance in multivariate analysis and together were capable of identifying subgroups of patients at significantly different risk of relapse and death.
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Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Proteínas Musculares , Tamoxifeno/uso terapéutico , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Quimioterapia Adyuvante , Femenino , Humanos , Ganglios Linfáticos/patología , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tasa de Supervivencia , Timidina/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of the present study was to summarise evidence from scientific studies on cancer anorexia-cachexia syndrome in order to assess and highlight the efficacy of high-dose progestins (megestrol acetate and medroxyprogesterone acetate) compared with placebo in patients with hormone-independent tumors. MATERIALS AND METHODS: A systematic review of published randomised clinical trials was carried out by an extensive electronic and hand search through databases, relevant journals and books, congress, proceedings, reference lists, without any language or year of publication restriction. The research was conducted by two independent operators who collected the data in a form specifically designed for this review. Among the several possible outcomes, appetite and body weight were chosen. RESULTS: Fifteen randomised clinical trials (more than 2000 patients) were retrieved for the review. There was a statistically significant advantage for high-dose progestins as regards improved appetite: pooled odds ratio (OR) = 4.23, 95% confidence interval (CI): 2.53-7.04. Although the effect of high-dose progestins on body weight was less impressive, statistical significance was also reached for this outcome: pooled OR = 2.66, 95% CI: 1.80-3.92. Treatment morbidity was very low, due to the brief period of the treatment in most of the studies. CONCLUSIONS: The effects of high-dose progestins on appetite and body weight were clearly demonstrated. However, further studies are undoubtedly warranted to investigate other aspects of progestin activity, especially as regards dosage, duration and timing with best therapeutic index.
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Anorexia/tratamiento farmacológico , Caquexia/tratamiento farmacológico , Neoplasias/complicaciones , Progestinas/uso terapéutico , Anorexia/etiología , Apetito/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Caquexia/etiología , Estudios Cruzados , Método Doble Ciego , Humanos , Neoplasias/fisiopatología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , SíndromeRESUMEN
BACKGROUND: Although lymph node metastases in patients with early gastric cancer (EGC) is an important prognostic factor, the prognostic relevance of lymph node micrometastases is still uncertain. METHODS: The authors studied 1488 lymph nodes, which were histologically confirmed as pN0, dissected from 139 patients who were treated for EGC between 1976-1994. Micrometastases were defined as a single or small cluster of neoplastic cells identifiable only by immunohistochemical methods. RESULTS: Lymph node micrometastases was observed in 24 of the 139 patients (17%). No significant correlation was observed between micrometastases and other clinicopathological characteristics. Analysis of overall survival showed no significant difference between the micrometastases positive and negative groups. CONCLUSION: The results of our study show that the presence of lymph node micrometastases in EGC does not have an influence on patient prognosis.