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The prediction and prevention of landslide hazard is a challenging topic involving the assessment and quantitative evaluation of several elements: geological and geomorphological setting, rainfalls, and ground motion. This paper presents the multi-approach investigation of the Nevissano landslide (Asti Province, Piedmont, NW Italy). It shows a continuous and slow movement, alongside few paroxysmal events, the last recorded in 2016. The geological and geomorphological models were defined through a field survey. An inventory of the landslide's movements and rainfall records in the period 2000-2016 was performed, respectively, through archive investigations and the application of "Moving Sum of Daily Rainfall" method, allowing for the definition of rain thresholds for the landslide activation (105 mm and 193 mm, respectively, in 3 and 30 days prior to the event). The displacements over the last 8 years (2016-2023) were monitored through an innovative in-continuum monitoring inclinometric system and Earth Observation (EO) data (i.e., relying on Interferometric Synthetic Aperture Radar, or InSAR data): it gave the opportunity to validate the rainfall thresholds previously defined. This study aims to provide information to public authorities for the appropriate management of the site. Moreover, the proposed workflow could be adopted as a guideline for investigating similar situations.
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Assessing the rock physical and mechanical behavior under different temperatures has become of utmost importance. It is well known that thermal stresses induce significant crack damage in rocks due to thermal expansion or phase transformation and volume changes. Quantifying and forecasting the evolution of rock physical and mechanical parameters with temperature is thus crucial for evaluating rock integrity in many applications such as geothermal fields, nuclear waste storage, wildfire or volcanic processes. In marbles the degree of previous exposure to temperature and the chemical composition (i.e. calcite vs dolomite) plays a key role for controlling the mechanical evolution under temperature. Moreover separating out the energy contribution provided by anelastic processes driving crack damage and elastic reversible deformation under increasing temperature remains an open challenge. With these aims, three sample sets of marbles with different contents of calcite and dolomite from two Brazilian quarries were tested under different temperature conditions (from room temperature up to 600 °C). A marked increase of thermal cracking was observed after 400 °C, accompanying mass loss up to 1% and porosity increase. Moreover, a significant drop in seismic wave velocities, uniaxial compressive strength and electrical resistivity, in wet conditions, was also detected. Spectral behavior from seismic traces and energy dissipation from stress-strain curves were analyzed. A dominance of the dissipated energy compared to the elastic one was observed and related to the generation of new fracturing surfaces. This hypothesis was supported by the spectral behavior showing multiple scattering effects in the high frequency components, with an increase in attenuation. The results suggested that the percentage of dolomite has a high influence on the mechanical behavior even at low temperature, mirroring the prevalence of brittle processes in dolomitic marbles. This study represents a comprehensive benchmark for the study of effect of temperature on rocks because of its multidisciplinary and multimethod approach and the demonstrated sensitivity to subtle textural changes. Moreover, it provides a reliable tool for crack damage analysis at each thermal stress.
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Bowing is a pathology known by the deformation experienced in some external covering systems in ornamental stones, especially in marble, and thermal action is one of the key factors that lead to this degradation. Previous studies presented remarkable contributions about the mechanical behavior of bowing but they were based on classical beam's theory and improper assumptions might mislead the evaluation of internal stresses. This study proposes to evaluate internal stresses in bowing due to thermal loading considering the true deformed shape in continuum media. Finite displacement concepts are proposed to calculate stress-strain relationship and comparison with linear elastic theory is also addressed. Internal stresses not predictable in the Euler-Bernoulli beam were found in parametric analyses. Moreover, the numerical analysis accomplished in this paper indicates that transient heat flux should induce higher stresses than just considering higher gradients of temperature in steady flux which could explain the larger decohesion through width in bowing tests.
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BACKGROUND/AIM: The aim of the study was to assess the outcome of advanced ovarian cancer patients who i) underwent primary surgery followed by carboplatin/paclitaxel-based chemotherapy with or without bevacizumab, ii) were in complete response after chemotherapy, iii) and subsequently recurred. PATIENTS AND METHODS: The hospital records of 138 complete responders after chemotherapy with (n=58) or without (n=80) bevacizumab were reviewed. RESULTS: Both survival after recurrence and overall survival were related to age (≤61 vs. >61 years, p=0.002 and p=0.0001), performance status (0 vs. ≥1, p=0.002 and p=0.001), histotype (serous vs. non serous, p=0.005 and p=0.01), time to recurrence (≥12 vs. <12 months, p<0.0001 and p<0.0001) and treatment at recurrence (surgery plus chemotherapy vs. chemotherapy, p=0.01 and p=0.004), but not to first-line treatment. CONCLUSION: This investigation failed to detect a more aggressive behavior of recurrent ovarian cancer after bevacizumab-containing primary treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Bevacizumab/administración & dosificación , Carboplatino , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/patología , Procedimientos Quirúrgicos de Citorreducción , Femenino , Humanos , Italia/epidemiología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Paclitaxel , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: The aim of the study was to assess the clinical outcome of patients with malignant transformation of an ovarian mature teratoma. PATIENTS AND METHODS: This study was conducted on 23 patients who underwent primary surgery at three Italian Gynecological Centers. Histologically, nine (39.1%) patients had squamous cell carcinoma, five (21.7%) had a thyroid carcinoma, six (26.1%) had a carcinoid, one (4.3%) patient had papillary renal carcinoma, one (4.3%) had medulloblastoma and one (4.3%) had intestinal-type mucinous adenocarcinoma. RESULTS: All six patients with stage I squamous cell carcinoma had no evidence of disease (NED) after a median time of 141 months. Of the three patients with stage IIb-IIIc squamous cell carcinoma, two had NED after 119 and 154 months, and one died of the disease 9 months after diagnosis. All five women with stage I thyroid carcinoma had NED after a median of 60 months. Of the six patients with stage I carcinoid, five had NED after a median of 168 months, whereas one died due to carcinoid heart disease. The three patients with stage I renal carcinoma, medulloblastoma and mucinous adenocarcinoma had NED after 24, 141 and 149 months, respectively. CONCLUSION: The clinical outcome of early-stage malignancies associated with mature ovarian teratomas is excellent following treatment.
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Tumor Carcinoide/epidemiología , Neoplasias Ováricas/patología , Teratoma/patología , Neoplasias de la Tiroides/patología , Adulto , Anciano , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patología , Tumor Carcinoide/cirugía , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Meduloblastoma/diagnóstico , Meduloblastoma/epidemiología , Meduloblastoma/patología , Meduloblastoma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/clasificación , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/cirugía , Estudios Retrospectivos , Teratoma/diagnóstico , Teratoma/epidemiología , Teratoma/cirugía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/cirugíaRESUMEN
AIM: To assess the patterns of recurrence and clinical outcomes of patients with cervical adenocarcinoma who underwent neoadjuvant platinum-based chemotherapy (NACT) followed by radical hysterectomy. PATIENTS AND METHODS: Data were retrospectively analyzed for 82 patients with International Federation of Gynecology and Obstetrics stage Ib2-IIb cervical adenocarcinoma who underwent this chemo-surgical treatment. The median follow-up of survivors was 89 months (range=5-208 months). RESULTS: Pathological complete response, optimal response and suboptimal response with intra-cervical residual disease were obtained in five (6%), 10 (12%) and 36 (44%) patients, respectively. Adjuvant external-beam radiotherapy with or without concurrent chemotherapy was administered to 47 patients. Nineteen (23%) out of the 82 patients experienced recurrence after a median of 12 months (range=5.3-86.8 months). Recurrent disease was pelvic in 12 (63%) patients, extra-pelvic in five (26%), and both pelvic and extra-pelvic in two (10%). According to pathological response, tumor relapsed in 10% of optimal responders, 14% of sub-optimal responders with intra-cervical residual disease, and 36% of sub-optimal responders with extra-cervical residual disease or non-responders. Five-year recurrence-free and overall survival were 77% and 84%, respectively. Patients who achieved an optimal response or sub-optimal response with intra-cervical residual disease had better 5-year recurrence-free (87% vs. 64%, p=0.017) and overall (92% vs. 74%, p=0.012) survival than those who had sub-optimal response with extra-cervical residual disease or no response. The latter had a 1.441-fold higher risk of recurrence and a 1.652-fold higher risk of death than those who obtained an optimal response or a sub-optimal response with intra-cervical residual disease. CONCLUSION: NACT followed by radical hysterectomy may be an option for patients with stage Ib2-IIb adenocarcinoma of the uterine cervix.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Histerectomía/métodos , Neoplasias del Cuello Uterino/terapia , Adenocarcinoma/patología , Adulto , Anciano , Quimioradioterapia , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
BACKGROUND: Preterm babies are at high risk of iron deficiency. METHODS: We investigated current practices regarding iron prophylaxis in preterm and low birth weight newborns among Local Neonatal Units (LNUs, n = 74) and Neonatal Intensive Care Units (NICUs, n = 20) of three Italian Regions (Piemonte, Marche and Lazio). RESULTS: Birth weight is considered an indicative parameter in only 64% of LNUs and 71% of NICUs, with a significant difference between LNUs in the three regions (86%, 20% and 62%, respectively; p < 0.001). Iron is recommended to infants with a birth weight between 2000 and 2500 g in only 25% of LNUs and 21% of NICUs, and to late-preterm (gestational age between 34 and 37 weeks) in a minority of Units (26% of LNUs, 7% of NICUs). CONCLUSIONS: Our pilot survey documents a great variability and the urgent need to standardize practices according to literature recommendations.
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Anemia Ferropénica/prevención & control , Hierro/uso terapéutico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Oligoelementos/uso terapéutico , Edad Gestacional , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/prevención & control , Unidades de Cuidado Intensivo Neonatal , Italia , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Mitotane is the reference drug for the adrenocortical carcinoma treatment; its pharmacological activity seems to depend on drug transformation in two active metabolites: o,p'-DDE (dichlorodiphenylethene) and o,p'-DDA (dichlorodiphenylacetate). Mitotane and metabolites are lipophilic agents; thus, they tend to accumulate into adipose tissues (white and brown), which change their prevalence seasonally. Aim of the work was to evaluate mitotane and metabolites plasma levels variation over the year, in adrenocortical cancer patients treated with Lysodren® for at least 6 months. METHODS: We enrolled a group of 86 adrenocortical carcinoma diagnosed patients, who underwent radical surgery and started mitotane as adjuvant treatment. For drug and metabolites plasma level (from samples collected ~12 h after the dose administration of mitotane, just before the subsequent administration) determination, a validated chromatographic method was used. KEY FINDINGS: Results showed an evidence of a seasonal trend for the three substance (o,p'-DDD, o,p'-DDE and o,p'-DDA) plasma levels, in terms of acrophases and lower values. Furthermore, it came out that male patients need a higher significant mitotane drug dose than female patients to reach mitotane therapeutic window. CONCLUSIONS: In conclusion, this is the first study assessing a mitotane plasma level variation over the year, but further studies in larger cohorts are required.
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Neoplasias de la Corteza Suprarrenal/terapia , Carcinoma Corticosuprarrenal/terapia , Antineoplásicos Hormonales/administración & dosificación , Mitotano/administración & dosificación , Tejido Adiposo/metabolismo , Adulto , Antineoplásicos Hormonales/farmacocinética , Quimioterapia Adyuvante/métodos , Cromatografía Líquida de Alta Presión/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mitotano/análogos & derivados , Mitotano/farmacocinética , Estaciones del Año , Factores Sexuales , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: In the northwestern Italian region of Piedmont, current statistics on hospitalizations show that surgical treatment for ovarian cancer (OC) is taking place in many small hospitals, as opposed to a more centralized approach. A population-based clinical audit was promoted to investigate whether OC is being managed according to clinical guidelines, identify determinants of lack of adherence to guidelines, and evaluate the association between adherence to guidelines and survival. PATIENTS AND METHODS: Residents diagnosed with OC in 2009 were identified in the regional hospital discharge records database. All hospitalizations within 2 years from diagnosis were reviewed. Patients were classified according to their initial pattern of care, defined as "with curative intent" (CIPC) if including debulking surgery aimed at maximal cytoreduction. Adherence to guidelines for surgery and chemotherapy and the effects of this adherence on OC survival were investigated with logistic regression and Cox models. RESULTS: The final study sample consisted of 344 patients with OC, 215 (62.5%) of whom received CIPC. Increasing age, comorbidities, and metastases were negatively associated with receiving CIPC. In the CIPC group, surgical treatment was adherent to guidelines in 35.2%, whereas chemotherapy was adherent in 87.8%. Surgical treatment that was adherent to guidelines [hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.45-1.15] and absence of residual tumor (HR, 0.55; 95% CI, 0.32-0.94) were associated with better survival in the CIPC group, and chemotherapy that was adherent to guidelines was associated with a significant reduction in the risk of death (HR, 0.49; 95% CI, 0.28-0.87). CONCLUSIONS: Results support the need to reorganize the clinical pathway of patients with OC in the Piedmont Region and the need for better adherence to current guidelines.
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Adhesión a Directriz/estadística & datos numéricos , Neoplasias Ováricas/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Italia/epidemiología , Persona de Mediana Edad , Neoplasias Ováricas/mortalidadRESUMEN
BACKGROUND: We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset. METHODS: This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression. RESULTS: Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome. CONCLUSION: The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy. TRIAL REGISTRATION: Trial registration number NCT01203306.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Tumores Neuroendocrinos/tratamiento farmacológico , Octreótido/administración & dosificación , Administración Metronómica , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Capecitabina , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Tumores Neuroendocrinos/patología , Octreótido/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The management of advanced colorectal cancer patients differs among cancer centers. International guidelines recommend offering all the recognized active regimens in order to obtain survival advantage, but little information is given about the sequence and combination in which such regimens should be administered. CASE REPORT: We report the case of a man with multiple liver metastasis from colorectal cancer followed for more than 78 months at our Institution. Repeated response to the same oxaliplatin, 5-fluorouracil and folinic acid chemotherapy schedule was achieved, and repeated radiofrequency ablation of liver metastases was performed until progression of lung and brain disease at 50 and 72 months, respectively, after the diagnosis of advanced disease. Although the tumor became oxaliplatin and chemo-resistant after the onset of extra-hepatic disease, a more aggressive chemotherapy regimen, including a doublet with a biological, halted tumor growth. CONCLUSIONS: The patient survived for more than 78 months without experiencing a major impact on his quality of life. This case reflects the importance of following tumor biology in the therapeutic decision-making process, reintroducing oxaliplatin whenever possible, and adopting a more aggressive strategy when the tumor becomes oxaliplatin-resistant.
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Adenocarcinoma/secundario , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ablación por Catéter , Resistencia a Antineoplásicos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Neoplasias del Colon Sigmoide/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Neoplasias Encefálicas/secundario , Progresión de la Enfermedad , Cronoterapia de Medicamentos , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Calidad de Vida , Retratamiento , Sobrevivientes , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: The role of surgery for lung metastases (LM) secondary to colorectal cancer (CRC) remains controversial. The bulk of evidence is derived from single surgical series, hampering any definitive conclusions. The aim of this study was to compare the outcomes of CRC patients with LM submitted to surgery with those who were not. PATIENTS AND METHODS: Data from 409 patients with LM as the first evidence of advanced disease were extracted from a database of 1,411 patients. Patients were divided into three groups: G1, comprised of 155 patients with pulmonary and extrapulmonary metastases; G2, comprised of 104 patients with LM only and no surgery; G3, comprised of 50 patients with LM only and submitted to surgery. RESULTS: No difference in response rates emerged between G1 and G2. Median progression-free survival (PFS) times were: 10.3 months, 10.5 months, and 26.2 months for G1, G2, and G3, respectively. No difference in PFS times was observed between G1 and G2, whereas there was a statistically significant difference between G2 and G3. Median overall survival times were 24.2 months, 31.5 months, and 72.4 months, respectively. Survival times were longer in resected patients: 17 survived >5 years and three survived >10 years. In patients with LM only and no surgery, four survived for 5 years and none survived >10 years. CONCLUSIONS: Even though patients with resectable LM are more likely to be those with a better outcome, our study provides evidence suggesting an active role of surgery in improving survival outcomes in this patient subset.
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Neoplasias Colorrectales/terapia , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Anciano , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Introduction. We retrospectively report our experience with the utilization of an original procedure for total laparoscopic hysterectomy based on completely retrograde and retroperitoneal technique for surgical staging and treatment of the endometrial cancer. The surgical, financial, and oncological advantages are here discussed. Methods. The technique used here has been based on a combination of a retroperitoneal approach with a retrograde and lateral dissection of the bladder and retrograde culdotomy with variable resection of parametrium. No disposable instruments and no uterine manipulator were utilized. Results. Intraoperative and postoperative complications were observed in 10% of the cases overall. Operative time length and mean haemoglobin drop value results were 129 min and 125 mL, respectively. Most patients were dismissed on days 3-5 from the hospital. Seventy-eight percent of the patients were alive with no evidence of disease at mean followup of 49 months. Conclusions. Our original laparoscopic technique is based on a retroperitoneal approach in order to rapidly control main uterine vessels coagulation, constantly check the ureter, and eventually decide type and site of lymph nodes removal. This procedure has important cost saving implications and the avoidance of uterine manipulator is of matter in case such as these of uterine malignancy.
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The cellular apoptosis susceptibility gene CAS/CSE1L is overexpressed in cancer, although it was originally identified as a gene that renders cells vulnerable to apoptotic stimuli. CAS/CSE1L has roles in the nucleocytoplasmic recycling of importin-α and in the regulation of gene expression, cell migration, and secretion. We identified CAS/CSE1L as a survival factor for ovarian cancer cells in vitro and in vivo. In 3/3 ovarian cancer cell lines, CAS/CSE1L was down-modulated by the unorthodox proapoptotic signaling of the MET receptor. CAS/CSE1L knockdown with RNA interference committed the ovarian cancer cells to death, but not immortalized normal cells and breast and colon cancer cells. In 70 and 95% of these latter cells, respectively, CAS/CSE1L was localized in the cytoplasm, while it accumulated in the nucleus in >90% of ovarian cancer cells. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells. In the nucleus, CAS/CSE1L regulated the expression of the proapoptotic Ras-association domain family 1 gene products RASSF1C and RASSF1A, which mediated death signals evoked by depletion of CAS/CSE1L. Our data show that CAS/CSE1L protects ovarian cancer cells from death through transcriptional suppression of a proapoptotic gene and suggest that the localization of CAS/CSE1L dictates its function.
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Proteína de Susceptibilidad a Apoptosis Celular/genética , Neoplasias Ováricas/genética , Proteínas Supresoras de Tumor/efectos de los fármacos , Apoptosis/efectos de los fármacos , Núcleo Celular/metabolismo , Cisplatino/farmacología , Citoplasma/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Factor de Crecimiento de Hepatocito/farmacología , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Proteínas Supresoras de Tumor/biosíntesis , Regulación hacia ArribaRESUMEN
BACKGROUND: There is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells. OBJECTIVE: We assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro. DESIGN: Multicenter, prospective phase II trial. Setting Referral centers for ACC. METHODS: Twenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60 mg/m(2) every week) and oral sorafenib (400 mg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity. RESULTS: Tumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the in vitro study, sorafenib impaired the viability of H295R cells with dose-response and time-response relationships. The in vitro sorafenib activity was not increased in combination with paclitaxel. CONCLUSIONS: Despite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended.
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Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/patología , Adulto , Anciano , Bencenosulfonatos/administración & dosificación , Línea Celular Tumoral , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Paclitaxel/administración & dosificación , Compuestos de Fenilurea , Estudios Prospectivos , Piridinas/administración & dosificación , SorafenibRESUMEN
Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by poor prognosis. First-line systemic treatments in advanced disease include mitotane, either alone or in combination with chemotherapy. Studies evaluating second-line therapy options have obtained disappointing results. This trial assessed the activity and toxicity of gemcitabine plus metronomic fluoropyrimidines in heavily pretreated advanced ACC patients. From 1998 to 2008, 28 patients with advanced ACC progressing after mitotane plus one or two systemic chemotherapy lines were enrolled. They received a combination of i.v. gemcitabine (800 mg/m(2), on days 1 and 8, every 21 days) and i.v. 5-fluorouracil protracted infusion (200 mg/m(2)/daily without interruption until progression) in the first six patients, or oral capecitabine (1500 mg/daily) in the subsequent patients. Mitotane administration was maintained in all cases. The rate of non-progressing patients after 4 months of treatment was 46.3%. A complete response was observed in 1 patient (3.5%); 1 patient (3.5%) obtained a partial regression, 11 patients (39.3%) obtained a disease stabilization and 15 patients (53.7%) progressed. Treatment was well tolerated, with grade III and IV toxicities consisting of leukopenia in six patients (21.4%), thrombocytopenia in one patient (3.5%), and mucositis in one patient (3.5%). Median time to progression and overall survival in the patient population were 5.3 (range: 1-43) and 9.8 months (range: 3-73) respectively. Gemcitabine plus metronomic fluoropyrimidines is a well-tolerated and moderately active regimen in heavily pretreated ACC patients.
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Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Fluorouracilo/administración & dosificación , Neoplasias de la Corteza Suprarrenal/mortalidad , Carcinoma Corticosuprarrenal/mortalidad , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/efectos adversos , Humanos , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Mucositis/inducido químicamente , Trombocitopenia/inducido químicamente , Resultado del Tratamiento , GemcitabinaRESUMEN
OBJECTIVES: To assess the clinical outcome of epithelial ovarian cancer patients who developed an apparently isolated lymph node recurrence after primary therapy. METHODS: The authors retrospectively assessed 69 patients with epithelial ovarian cancer who were clinically or pathologically free of disease after primary therapy and who subsequently developed an apparently isolated lymph node recurrence. The median follow-up of survivors was 74.5 months. RESULTS: Median age was 58 years, FIGO stage was III-IV in 52 (75%) patients, residual disease after primary surgery was >1 cm in 36 (52%), first-line chemotherapy consisted of paclitaxel-/platinum-based chemotherapy in 44 (64%), time to recurrence was >12 months in 43 (62%), recurrence was pelvic and/or para-aortic in 41 (59%), and treatment at recurrence consisted of chemotherapy alone in 44 (64%), surgery plus chemotherapy in 22 (32%), surgery alone in one patient, surgery plus irradiation in one, and irradiation alone in one patient. Survival after recurrence was significantly related to the type of treatment (chemotherapy alone versus surgery plus chemotherapy, median: 20.8 months versus not reached, p=0.0002), and patient age (>58 versus <58 years, median: 26.8 versus 44.0 months, p=0.02). Overall survival was significantly related to the type of treatment (chemotherapy alone versus surgery plus chemotherapy, median: 45.4 months versus not reached, p=0.0001), patient age (>58 versus <58 years, median: 45.4 versus 62.9 months, p=0.03) and time to recurrence (<12 months versus >12 months, median: 45.4 versus 66.9 months, p=0.01). Cox model showed that treatment at recurrence was the strongest independent prognostic variable for both survival after recurrence (hazard ratio [HR]=0.277, p=0.0003) and overall survival (HR=0.249, p=0.0002). CONCLUSION: Patients who underwent surgery plus chemotherapy had a 72% reduction in the risk of death after recurrence and a 75% reduction in the risk of death after initial diagnosis when compared with those treated with chemotherapy alone. Secondary cytoreductive surgery appears to be able to prolong survival in epithelial ovarian cancer patients with apparently isolated lymph node recurrence.
Asunto(s)
Ganglios Linfáticos/patología , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Adulto , Anciano , Células Epiteliales/patología , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma. METHODS: Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. RESULTS: Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable. CONCLUSION: Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. TRIAL REGISTRATION: NCT00953394.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Neuroendocrino/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Octreótido/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Neuroendocrino/patología , Esquema de Medicación , Femenino , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Octreótido/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: There is no standard treatment for patients with advanced colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment and having good performance status (PS). PATIENTS AND METHODS: We investigated gemcitabine 1,000 mg/m2 days 1, 8 and 15 q28d combined with protracted 5-fluorouracil continuous infusion at 200 mg/m2/day, in 37 consecutive patients progressing after oxaliplatin-irinotecan-containing chemotherapies. RESULTS: Partial response (PR) was achieved in 4 (10.8%) and disease stabilization (SD) in 19 (51.4%) cases (PR+SD: 62.2%). Median time to progression and survival were 4.2 and 8.9 months, respectively. Grade III toxicities were thrombocytopenia, neutropenia (in 3 patients) and mucositis (in 2 patients). Clinical benefit was observed in 18 patients (48.6% of the entire population; 64.3% of those patients with PS>0 at study entry). CONCLUSION: The combination of gemcitabine and 5-fluorouracil continuous infusion was found to be an active and manageable palliative regimen for heavily pre-treated patients with metastatic CRC.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Irinotecán , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , GemcitabinaRESUMEN
BACKGROUND: Adrenocortical carcinoma (ACC) is an extremely rare aggressive disease. Few data are available on the efficacy of systemic antineoplastic treatments (mitotane and cytotoxic therapy) in the treatment of advanced disease. OBJECTIVE/METHODS: this paper will review the existing treatment strategies and new perspectives in the management of ACC patients. RESULTS/CONCLUSION: An ongoing randomized international trial aims to define the best combination chemotherapy plus mitotane regimen. Based on the results of a case control study, mitotane is being explored as adjuvant therapy. Genetic and biological studies have identified molecular targets for specific targeted drugs such as IGF receptor inhibitors and antiangiogenetic drugs. Phase II trials are exploring the activity of these drugs either alone or in combination with chemotherapy.