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1.
Nephrol Dial Transplant ; 37(5): 887-894, 2022 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-33547795

RESUMEN

BACKGROUND: Checkpoint inhibitors (CPIs) have drastically improved metastatic cancer outcomes. However, immunotherapy is associated with multiple toxicities, including acute kidney injury (AKI). Data about CPI-related AKI are limited. Our aim was to determine risk factors for CPI-related AKI as well as its clinical characteristics and its impact on mortality in patients undergoing immunotherapy. METHODS: All patients under CPI at our centre between March 2018 and May 2019 and with a follow-up through April 2020 were included. Demographic, clinical and laboratory data were collected. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines. We performed a logistic regression model to identify independent risk factors for AKI and actuarial survival analysis to establish risk factors for mortality in this population. RESULTS: A total of 759 patients were included, with a median age of 64 years. A total of 59% were men and baseline median creatinine was 0.80 mg/dL. The most frequent malignancy was lung cancer and 56% were receiving anti-programmed death protein 1 (PD-1). About 15.5% developed AKI during the follow-up. Age and baseline kidney function were identified as independent risk factors for CPI-related AKI. At the end of follow-up, 52.3% of patients had died. The type of cancer (not melanoma, lung or urogenital malignance), type of CPI (not cytotoxic T-lymphocyte-associated protein 4, PD-1, programmed death-ligand 1 or their combination) and the presence of an episode of AKI were identified as risk factors for mortality. CONCLUSIONS: A total of 15.5% of patients under immunotherapy presented with AKI. A single AKI episode was identified as an independent risk factor for mortality in these patients and age and baseline renal function were risk factors for the development of AKI.


Asunto(s)
Lesión Renal Aguda , Neoplasias , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Creatinina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Receptor de Muerte Celular Programada 1 , Estudios Retrospectivos , Factores de Riesgo
2.
Int J Mol Sci ; 23(13)2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35806142

RESUMEN

In resected non-small cell lung cancer (NSCLC), post-surgical recurrence occurs in around 40% of patients, highlighting the necessity to identify relapse biomarkers. An analysis of the extracellular vesicle (EV) cargo from a pulmonary tumor-draining vein (TDV) can grant biomarker identification. We studied the pulmonary TDV EV-miRNAome to identify relapse biomarkers in a two-phase study (screening and validation). In the screening phase, a 17-miRNA relapse signature was identified in 18 selected patients by small RNAseq. The most expressed miRNA from the signature (EV-miR-203a-3p) was chosen for further validation. Pulmonary TDV EV-miR-203a-3p was studied by qRT-PCR in a validation cohort of 70 patients, where it was found to be upregulated in relapsed patients (p = 0.0194) and in patients with cancer spread to nearby lymph nodes (N+ patients) (p = 0.0396). The ROC curve analysis showed that TDV EV-miR-203a-3p was able to predict relapses with a sensitivity of 88% (AUC: 0.67; p = 0.022). Moreover, patients with high TDV EV-miR-203a-3p had a shorter time to relapse than patients with low levels (43.6 vs. 97.6 months; p = 0.00703). The multivariate analysis showed that EV-miR-203a-3p was an independent, predictive and prognostic post-surgical relapse biomarker. In conclusion, pulmonary TDV EV-miR-203a-3p is a promising new relapse biomarker for resected NSCLC patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroARNs/genética , Biomarcadores , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Vesículas Extracelulares/genética , Vesículas Extracelulares/patología , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/genética
3.
Eur J Nucl Med Mol Imaging ; 49(1): 361-370, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34185137

RESUMEN

PURPOSE: Radioguided occult lesion localization (ROLL) of pulmonary nodules is an alternative to hook-wire. Both required of a histological margin assessment. The activity emerging from the radiotracer allows to obtain an intraoperative scintigraphic image of the surgical specimen by a portable gamma-camera (PGC) fitted with an optical view, which provides information about the localization of the nodule in relation to the margins. The aim of this study was to evaluate the intraoperative use of a PGC for margin assessment of pulmonary nodules. METHODS: ROLL technique was used in 38 nodules (36 pulmonary, 1 chest wall, and 1 pleural nodules). A PGC intraoperative image of the surgical specimen was obtained in 32. Scintigraphic results were compared to the histological assessment. Other factors, such as nodule size, distance from the pleural surface, or distance covered by the needle, were considered as possible factors for non-centered lesions. RESULTS: PGC images showed that the lesion was in contact with the margins in 8/32 cases and centered in 24. In all cases in which the lesion was considered as centered by the PGC, the margins were free of involvement (NPV 100%), although the PPV is low. CONCLUSIONS: The use of a PGC for margin assessment after pulmonary nodule resection is feasible and provides a high NPV in our series. In addition, the short intraoperative time required for its use makes the PGC a useful tool for providing supplementary information to histopathologic results. Further studies from different surgical teams are required for an external validation.


Asunto(s)
Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Cirugía Asistida por Computador , Cámaras gamma , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Cintigrafía
4.
J Magn Reson Imaging ; 51(5): 1478-1486, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31654541

RESUMEN

BACKGROUND: Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE). PURPOSE: To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols. STUDY TYPE: Multicenter retrospective study. POPULATION: In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study. FIELD STRENGTH/SEQUENCE: 1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium-based contrast agent-enhanced T1 -weighted MRI, T2 - and FLAIR T2 -weighted, and dynamic susceptibility contrast (DSC) T2 * perfusion. ASSESSMENT: We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBVmax ) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into "vascular" groups were tested. The variability in the markers between individual centers was also assessed. STATISTICAL TESTS: Uniparametric Cox regression; Kaplan-Meier test; Mann-Whitney test. RESULTS: The rCBVmax derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into "moderate-" and "high-vascular" groups (P < 0.05). The Mann-Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02-0.685; LAT: P = 0.010-0.769; IPE: P = 0.093-0.939; VPE: P = 0.016-1.000). DATA CONCLUSION: The rCBVmax calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1478-1486.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/diagnóstico por imagen , Medios de Contraste , Glioblastoma/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Pronóstico , Estudios Retrospectivos
5.
BMC Health Serv Res ; 20(1): 207, 2020 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-32164687

RESUMEN

BACKGROUND: Multimodal prehabilitation is a preoperative intervention with the objective to enhance cancer patients' functional status which has been showed to reduce both postoperative morbidity and hospital length of stay in digestive oncologic surgery. However, in lung cancer surgery patients further studies with higher methodological quality are needed to clarify the benefits of prehabilitation. The main aim of the current protocol is to evaluate the cost-effectiveness of a multimodal prehabilitation program supported by information and communication technologies in moderate-to-high risk lung cancer patients undergoing thoracic surgery. METHODS: A Quadruple Aim approach will be adopted, assessing the prehabilitation program at the following levels: i) Patients' and professionals' experience outcomes (by means of standardized questionnaires, focus groups and structured interviews); ii) Population health-based outcomes (e.g. hospital length of stay, number and severity of postoperative complications, peak oxygen uptake and levels of systemic inflammation); and, iii) Healthcare costs. DISCUSSION: This study protocol should contribute not only to increase the scientific basis on prehabilitation but also to detect the main factors modulating service adoption. TRIAL REGISTRATION: NCT04052100 (August 9, 2019).


Asunto(s)
Neoplasias Pulmonares/cirugía , Cuidados Preoperatorios/economía , Cuidados Preoperatorios/métodos , Protocolos Clínicos , Terapia Combinada , Análisis Costo-Beneficio , Humanos , Tecnología de la Información , Medición de Riesgo
6.
BMC Womens Health ; 19(1): 124, 2019 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-31655582

RESUMEN

BACKGROUND: Müllerian adenosarcoma is a rare malignancy. These tumors occur mainly in the uterus, but also in extrauterine locations, usually related to endometriosis. Because of their rarity, there is limited data on optimal management strategies. CASE PRESENTATION: We present a 44-year-old woman with a history of endometriosis who consults for chronic pelvic pain. In the imaging tests, a heterogeneous mass is observed that impresses endometriosis, encompassing the uterus and left appendage. Surgery is performed by finding an extrauterine adenosarcoma that affected the uterus, ovary and bladder wall. CONCLUSION: This is a rare case but should be considered in a patient with atypical clinical characteristics or preoperative pathology, so we show the diagnostic and therapeutic strategies carried out for the resolution of the case.


Asunto(s)
Adenosarcoma/diagnóstico , Endometriosis/cirugía , Neoplasias Ováricas/diagnóstico , Dolor Pélvico/diagnóstico , Neoplasias Uterinas/diagnóstico , Adenosarcoma/etiología , Adenosarcoma/patología , Adulto , Diagnóstico Diferencial , Endometriosis/complicaciones , Femenino , Humanos , Clasificación del Tumor , Neoplasias Ováricas/etiología , Neoplasias Ováricas/patología , Dolor Pélvico/etiología , Neoplasias Uterinas/etiología , Neoplasias Uterinas/patología
7.
Br J Cancer ; 118(11): 1425-1433, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29765150

RESUMEN

BACKGROUND: Proviral integration Moloney virus (PIM) kinases (PIM1, 2 and 3) are overexpressed in several tumour types and contribute to oncogenesis. AZD1208 is a potent ATP-competitive PIM kinase inhibitor investigated in patients with recurrent or refractory acute myeloid leukaemia (AML) or advanced solid tumours. METHODS: Two dose-escalation studies were performed to evaluate the safety and tolerability, and to define the maximum tolerated dose (MTD), of AZD1208 in AML and solid tumours. Secondary objectives were to evaluate the pharmacokinetics, pharmacodynamics (PD) and preliminary efficacy of AZD1208. RESULTS: Sixty-seven patients received treatment: 32 in the AML study over a 120-900 mg dose range, and 25 in the solid tumour study over a 120-800 mg dose range. Nearly all patients (98.5%) in both studies experienced adverse events, mostly gastrointestinal (92.5%). Dose-limiting toxicities included rash, fatigue and vomiting. AZD1208 was not tolerated at 900 mg, and the protocol-defined MTD was not confirmed. AZD1208 increased CYP3A4 activity after multiple dosing, resulting in increased drug clearance. There were no clinical responses; PD analysis showed biological activity of AZD1208. CONCLUSIONS: Despite the lack of single-agent clinical efficacy with AZD1208, PIM kinase inhibition may hold potential as an anticancer treatment, perhaps in combination with other agents.


Asunto(s)
Compuestos de Bifenilo/administración & dosificación , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Tiazolidinas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Compuestos de Bifenilo/efectos adversos , Compuestos de Bifenilo/farmacología , Citocromo P-450 CYP3A/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/metabolismo , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/metabolismo , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacología , Tiazolidinas/efectos adversos , Tiazolidinas/farmacología , Regulación hacia Arriba , Adulto Joven
8.
Br J Cancer ; 119(9): 1052-1059, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30131546

RESUMEN

BACKGROUND: Despite most metastatic castration-resistant prostate cancer (mCRPC) patients benefit from abiraterone acetate plus prednisone 5 mg bid (AA + P), resistance eventually occurs. Long-term use of prednisone has been suggested as one of the mechanisms driving resistance, which may be reversed by switching to another steroid. METHODS: SWITCH was a single-arm, open-label, single-stage phase II study. The primary objective was to evaluate the antitumour activity of abiraterone acetate plus dexamethasone 0.5 mg daily (AA + D) in mCRPC patients progressing to AA + P. Clinically stable mCRPC patients who had prostate-specific antigen (PSA) and/or limited radiographic progression after at least 12 weeks on AA + P, were eligible. The primary endpoint was measured as the proportion of patients achieving a PSA decline of ≥ 30% (PSA30) from baseline after 6 weeks on AA + D. Secondary endpoints included: PSA50 response rate at 12 weeks, time to biochemical and radiological progression, overall survival, safety profile evaluation, benefit from subsequent treatment lines and the identification of biomarkers of response (AR copy number, TMPRSS2-ERG status and PTEN expression). RESULTS: Twenty-six patients were enrolled. PSA30 and PSA50 were 46.2% and 34.6%, respectively. Median time to biochemical and radiological progression were 5.3 and 11.8 months, respectively. Two radiological responses were observed. Median overall survival was 20.9 months. Patients with AR gain detected in plasma circulating tumour DNA did not respond to switch, whereas patients with AR normal status benefited the most. No significant toxicities were observed and PSA50 response rate to subsequent taxane was 50%. CONCLUSIONS: In selected clinical stable mCRPC patients with limited disease progression on AA + P, a steroid switch from prednisone to dexamethasone can lead to PSA and radiological responses.


Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Dexametasona/administración & dosificación , Prednisona/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Androstenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Dexametasona/uso terapéutico , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Fosfohidrolasa PTEN/genética , Proyectos Piloto , Prednisona/uso terapéutico , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Receptores Androgénicos/genética , Análisis de Supervivencia , Resultado del Tratamiento
9.
Future Oncol ; 14(6s): 29-31, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29400556

RESUMEN

Video-assisted thoracoscopic surgery (VATS) has showed benefits in terms of pain, hospital stay and accomplishment of adjuvancy therapy versus open surgery in early stage of non-small-cell lung cancer. Over the last years, the indication of VATS technique has been expanded to advanced lung cancer. In this article, we discuss the definition of VATS and advanced lung cancer, and the safety and feasibility of VATS technique for the resection of advanced tumors.


Asunto(s)
Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Complicaciones Posoperatorias/epidemiología , Cirugía Torácica Asistida por Video/métodos , Conversión a Cirugía Abierta/estadística & datos numéricos , Estudios de Factibilidad , Humanos , Tiempo de Internación/estadística & datos numéricos , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Selección de Paciente , Neumonectomía/efectos adversos , Neumonectomía/tendencias , Complicaciones Posoperatorias/etiología , Cirugía Torácica Asistida por Video/efectos adversos , Cirugía Torácica Asistida por Video/tendencias , Toracotomía/efectos adversos , Toracotomía/métodos , Resultado del Tratamiento
10.
Future Oncol ; 14(6s): 13-16, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29664353

RESUMEN

The correct treatment for patients with non-small-cell lung cancer and ipsilateral mediastinal involvement (N2) remains a challenge. The heterogeneity of this group of patients has been shown, as well as many different prognostic factors, that will determine a specific management to each of them. Although the standard treatment is based on a multimodality therapy consisting of chemotherapy, radiotherapy and surgery, surgery is not always indicated. The selection of patients who are going to be operated, reminds being a key point of the treatment of this disease. Recent reports on operable N2 disease have been reviewed by our group in order to discuss surgery indications and when to bring it about, with the possibility to go straight to surgery.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Neoplasias del Mediastino/terapia , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Neumonectomía/métodos , Carcinoma de Pulmón de Células no Pequeñas/secundario , Quimioradioterapia/métodos , Terapia Combinada/métodos , Terapia Combinada/tendencias , Humanos , Inmunoterapia/métodos , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/patología , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Neoplasias del Mediastino/secundario , Mediastino/patología , Mediastino/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/normas , Procedimientos Quirúrgicos Mínimamente Invasivos/tendencias , Estadificación de Neoplasias , Selección de Paciente , Neumonectomía/tendencias , Pronóstico , Resultado del Tratamiento
11.
Radiology ; 283(1): 168-177, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27875103

RESUMEN

Purpose To determine the usefulness of whole-body diffusion-weighted imaging (DWI) to assess the response of bone metastases to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods A phase II prospective clinical trial of the poly-(adenosine diphosphate-ribose) polymerase inhibitor olaparib in mCRPC included a prospective magnetic resonance (MR) imaging substudy; the study was approved by the institutional research board, and written informed consent was obtained. Whole-body DWI was performed at baseline and after 12 weeks of olaparib administration by using 1.5-T MR imaging. Areas of abnormal signal intensity on DWI images in keeping with bone metastases were delineated to derive total diffusion volume (tDV); five target lesions were also evaluated. Associations of changes in volume of bone metastases and median apparent diffusion coefficient (ADC) with response to treatment were assessed by using the Mann-Whitney test and logistic regression; correlation with prostate-specific antigen level and circulating tumor cell count were assessed by using Spearman correlation (r). Results Twenty-one patients were included. All six responders to olaparib showed a decrease in tDV, while no decrease was observed in all nonresponders; this difference between responders and nonresponders was significant (P = .001). Increases in median ADC were associated with increased odds of response (odds ratio, 1.08; 95% confidence interval [CI]: 1.00, 1.15; P = .04). A positive association was detected between changes in tDV and best percentage change in prostate-specific antigen level and circulating tumor cell count (r = 0.63 [95% CI: 0.27, 0.83] and r = 0.77 [95% CI: 0.51, 0.90], respectively). When assessing five target lesions, decreases in volume were associated with response (odds ratio for volume increase, 0.89; 95% CI: 0.80, 0.99; P = .037). Conclusion This pilot study showed that decreases in volume and increases in median ADC of bone metastases assessed with whole-body DWI can potentially be used as indicators of response to olaparib in mCRPC. Online supplemental material is available for this article.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias de la Próstata/patología , Adulto , Anciano , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor , Neoplasias Óseas/tratamiento farmacológico , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Ftalazinas/uso terapéutico , Proyectos Piloto , Piperazinas/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento , Imagen de Cuerpo Entero
12.
Radiology ; 280(1): 151-60, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26807894

RESUMEN

Purpose To determine the correlation between the volume of bone metastasis as assessed with diffusion-weighted (DW) imaging and established prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) and the association with overall survival (OS). Materials and Methods This retrospective study was approved by the institutional review board; informed consent was obtained from all patients. The authors analyzed whole-body DW images obtained between June 2010 and February 2013 in 53 patients with mCRPC at the time of starting a new line of anticancer therapy. Bone metastases were identified and delineated on whole-body DW images in 43 eligible patients. Total tumor diffusion volume (tDV) was correlated with the bone scan index (BSI) and other prognostic factors by using the Pearson correlation coefficient (r). Survival analysis was performed with Kaplan-Meier analysis and Cox regression. Results The median tDV was 503.1 mL (range, 5.6-2242 mL), and the median OS was 12.9 months (95% confidence interval [CI]: 8.7, 16.1 months). There was a significant correlation between tDV and established prognostic factors, including hemoglobin level (r = -0.521, P < .001), prostate-specific antigen level (r = 0.556, P < .001), lactate dehydrogenase level (r = 0.534, P < .001), alkaline phosphatase level (r = 0.572, P < .001), circulating tumor cell count (r = 0.613, P = .004), and BSI (r = 0.565, P = .001). A higher tDV also showed a significant association with poorer OS (hazard ratio, 1.74; 95% CI: 1.02, 2.96; P = .035). Conclusion Metastatic bone disease from mCRPC can be evaluated and quantified with whole-body DW imaging. Whole-body DW imaging-generated tDV showed correlation with established prognostic biomarkers and is associated with OS in mCRPC. (©) RSNA, 2016 Online supplemental material is available for this article.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias de la Próstata Resistentes a la Castración/patología , Imagen de Cuerpo Entero/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/patología , Huesos/diagnóstico por imagen , Huesos/patología , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Estudios Retrospectivos , Carga Tumoral
13.
Lancet Oncol ; 16(6): e279-92, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26065613

RESUMEN

Until 2010, docetaxel was the only agent with proven survival benefit for castration-resistant prostate cancer. The development of cabazitaxel, abiraterone acetate, enzalutamide, radium-223, and sipuleucel-T has increased the number of treatment options. Because these agents were developed concurrently within a short period of time, prospective data on their sequential use efficacy are scarce. The challenge now is to reach a consensus on the best way to sequence effective treatments, ideally by the use of an approach specific to patient subgroups. However, the absence of robust surrogates of survival and the lack of predictive biomarkers makes data for the sequential use of these agents difficult to obtain and interpret.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/epidemiología , Resultado del Tratamiento , Acetato de Abiraterona , Androstenos/uso terapéutico , Benzamidas , Docetaxel , Humanos , Masculino , Nitrilos , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/patología , Radioisótopos/uso terapéutico , Radio (Elemento)/uso terapéutico , Taxoides/uso terapéutico , Extractos de Tejidos/uso terapéutico
14.
Curr Opin Oncol ; 27(3): 267-75, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25811347

RESUMEN

PURPOSE OF REVIEW: Understanding the basis of exceptional responses may increase our knowledge of disease biology and the mechanism of action of targeted agents, and identify subpopulations of patients who derive important benefit from drugs that would otherwise not be developed due to lack of sufficient activity in the general population. We will discuss in this review the value of a systematic phenotype-to-genotype approach in these outlier responders to identify actionable therapeutic targets that can help to personalize the delivery of cancer treatment. RECENT FINDINGS: Genomic mapping of outlier responders by next-generation sequencing is deciphering cancer biology at the individual level and providing insight in the somatic DNA alterations resulting in exceptional sensitivity to targeted agents in mono or combinational therapy. SUMMARY: In the era of targeted drugs, outlier or exceptional responders are frequently witnessed within early phase clinical trials. The genomic analysis of anecdotal 'exceptional responders' in trials that may otherwise not achieve prespecified efficacy endpoints may lead to the identification of predictive biomarkers for targeted therapies and revitalize or reposition the use of targeted agents in enriched populations. The era of unselected early clinical trials has passed with the advent of genomic-driven medicine and novel adaptive and biomarker-enrichment trials will accelerate drug approval, and overcome the challenges of testing targeted drugs against aberrations with low prevalence.


Asunto(s)
Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/genética , Análisis Mutacional de ADN/métodos , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Medicina de Precisión , Terapia Combinada , Genotipo , Humanos , Terapia Molecular Dirigida/métodos , Neoplasias/genética , Neoplasias/patología , Fenotipo
15.
J Pediatr Hematol Oncol ; 37(5): e278-84, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25929608

RESUMEN

INTRODUCTION: The treatment of Ewing Sarcoma family of tumors is multimodal, both in children and adults. Axial location and metastases are classic prognostic factors. However, the worse prognosis in older patients is more controversial. METHODS: Retrospective analysis was performed of pediatric and adult patients treated with the 2001 SEOP protocol: 6 cycles of VIDE chemotherapy (CT). If no progression was observed, local (surgery and/or radiotherapy) and consolidation treatments were performed adjusted to prognosis: 8 cycles of VAC in standard-risk patients or 1 cycle of VAC and high-dose CT and autologous transplant in the case of increased risk.We analyzed induction CT toxicity, type of consolidation treatment, and disease-free (DFS) and overall (OS) survival by the Kaplan-Meier method, with a log-rank analysis of prognostic factors with regard to OS. RESULTS: Thirty-six patients were analyzed (2003 to 2011). Sixty percent were male, with a median age of 16 years (range, 7 to 57 y). The most frequent location was axial (43%), followed by extremities (34%), extraosseous (18%), and ribs (9%). Fifty-four percent of patients had metastases, of which, 58% were pulmonary.The median follow-up period was 36 months (5 to 101 mo). Median DFS was 25 months (16 to 34 mo) and median OS 29 months (19 to 40 mo), with a 3-year OS of 40%. Median OS from progression was 7 months (0.4 to 15 mo). Age <15 years and normal lactate dehydrogenase levels were associated with prolonged OS. CONCLUSIONS: Induction CT with the VIDE regimen was feasible in most patients, with a low risk for early progression. Hematological toxicity was substantial but manageable. Adult patients had a worse prognosis. Survival after progression was dismal.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Sarcoma de Ewing/mortalidad , Sarcoma de Ewing/terapia , Adolescente , Adulto , Niño , Terapia Combinada , Quimioterapia de Consolidación , Supervivencia sin Enfermedad , Femenino , Humanos , Quimioterapia de Inducción , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos , Radioterapia Adyuvante , Estudios Retrospectivos , Trasplante de Células Madre , Trasplante Autólogo , Adulto Joven
16.
Artículo en Inglés | MEDLINE | ID: mdl-38747474

RESUMEN

The current treatment for mesothelioma, in selected cases, consists of extended pleurodecortication and intrathoracic hyperthermic chemotherapy. This technique is laborious and detailed and must be followed step by step to achieve good results. We present the case of a patient with epithelioid mesothelioma meeting surgical criteria who underwent the mentioned technique, experiencing an adequate postoperative period and an early discharge. This experience demonstrates that the technique is safe when performed in centres with experience and the means to address this complex pathology.


Asunto(s)
Hipertermia Inducida , Mesotelioma Maligno , Neoplasias Pleurales , Humanos , Neoplasias Pleurales/terapia , Mesotelioma Maligno/cirugía , Mesotelioma Maligno/terapia , Hipertermia Inducida/métodos , Terapia Combinada , Mesotelioma/terapia , Mesotelioma/patología , Mesotelioma/cirugía , Masculino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/cirugía , Persona de Mediana Edad
17.
Clin Transl Oncol ; 26(7): 1647-1663, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38530556

RESUMEN

INTRODUCTION: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team. OBJECTIVE: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP. METHODS: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes. RESULTS: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up. CONCLUSIONS: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Consenso , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , España , Grupo de Atención al Paciente , Técnica Delphi , Estadificación de Neoplasias
18.
Cir Esp (Engl Ed) ; 101(12): 833-840, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37544607

RESUMEN

INTRODUCTION: Robot-assisted thoracic surgery (RATS) is a rapidly expanding technique. In our study, we aimed to analyze the results of the process to adopt robotic surgery in our Department of Thoracic Surgery. METHODS: This is an intention-to-treat analysis of a series of consecutive patients operated on using the RATS approach in our hospital from January 2021 to March 2022. Data were registered for patient characteristics, type of surgery, operative times, conversion rate, chest tube duration, length of hospital stay and complications. The IBM SPSS® statistical software was used for the statistical analysis. A cumulative sum analysis of the operating time was performed to define the learning curve. RESULTS: During the study period, 51 patients underwent robotic surgery, including pulmonary and non-pulmonary interventions. In addition, 15 patients (29.4%) underwent non-pulmonary interventions: one pleural (2%), 2 diaphragmatic (3.9%), and 12 mediastinal (23.5%). Among the mediastinal surgeries, one conversion was necessary (8.3%) for a complex vascular malformation, and 11 were completed by RATS, including 7 (58.3%) thymomas, 3 (25%) pleuro-pericardial cysts, and one (8.3%) neurogenic tumor. Mean operative time was 141 min (104-178), mean chest tube duration was 0.9 days (0-2), and mean length of stay was 1.45 days (1-2). Thirty-six patients underwent lung surgery (70.6%). The complete RATS resections (34; 94.4%) included: 3 wedge resections (11.1%), 2 segmentectomies (3.7%), 28 lobectomies (81.5%), and one sleeve lobectomy (3.7%). Mean surgery time was 194.56 min (141-247), chest tube duration was 3.92 days (1-8), and length of stay was 4.6 days (1-8). Complications occurred in 4 patients (11.1%). No 90-day mortalities were registered. CONCLUSIONS: The implementation of RATS was achieved with good clinical results and operative times for all indications. A rapid learning curve was accomplished in short time. Previous VATS experience, patient selection, team training and program continuity are fundamental to successfully develop a RATS program.


Asunto(s)
Neoplasias Pulmonares , Procedimientos Quirúrgicos Robotizados , Robótica , Cirugía Torácica , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Pulmonares/cirugía , Neumonectomía/efectos adversos , Neumonectomía/métodos
19.
J Clin Oncol ; 41(20): 3608-3615, 2023 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-36753698

RESUMEN

PURPOSE: To assess the efficacy and safety of darolutamide maintenance after successful taxane chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Swiss Group for Clinical Cancer Research (SAKK) 08/16 is a randomized phase II study. Patients with mCRPC who received prior androgen-receptor pathway inhibitors (ARPIs) and subsequently had nonprogressive disease on a taxane were randomly assigned to darolutamide 600 mg twice a day or placebo twice a day. The primary end point was radiographic progression-free survival (rPFS) at 12 weeks. Secondary end points were rPFS, event-free survival, overall survival (OS), prostate-specific antigen (PSA) 50% response rate, and adverse events. RESULTS: Overall, 92 patients were recruited by 26 centers. Prior taxane was docetaxel in 93% and cabazitaxel in 7%. Prior ARPI was abiraterone in 60%, enzalutamide in 31%, and both in 9%. rPFS at 12 weeks was significantly improved with darolutamide (64.7% v 52.2%; P = .127). Median rPFS on darolutamide was 5.5 versus 4.5 months on placebo (hazard ratio [HR], 0.54 [95% CI, 0.32 to 0.91]; P = .017), and median event-free survival was 5.4 versus 2.9 months (HR, 0.46 [95% CI, 0.29 to 0.73]; P = .001). PSA 50% response rate was improved (22% v 4%; P = .014). Median OS for darolutamide was 24 versus 21.3 months for placebo (HR, 0.62 [95% CI, 0.3 to 1.26]; P = .181). Treatment-related adverse events were similar in both arms. CONCLUSION: SAKK 08/16 met its primary end point, showing that switch maintenance with darolutamide after prior taxane chemotherapy and at least one ARPI resulted in a statistically significant but clinically modest rPFS prolongation with good tolerability. The median OS with darolutamide maintenance appears promising. Should these findings be confirmed in a larger trial, maintenance treatment could be a novel strategy in managing patients with mCRPC, especially those who responded well to prior ARPI.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/patología , Antígeno Prostático Específico , Taxoides/efectos adversos , Antagonistas de Receptores Androgénicos/uso terapéutico , Resultado del Tratamiento , Supervivencia sin Enfermedad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
20.
Eur Urol Oncol ; 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37838555

RESUMEN

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

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