Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Stat Med ; 43(9): 1804-1825, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38356231

RESUMEN

Statistical data simulation is essential in the development of statistical models and methods as well as in their performance evaluation. To capture complex data structures, in particular for high-dimensional data, a variety of simulation approaches have been introduced including parametric and the so-called plasmode simulations. While there are concerns about the realism of parametrically simulated data, it is widely claimed that plasmodes come very close to reality with some aspects of the "truth" known. However, there are no explicit guidelines or state-of-the-art on how to perform plasmode data simulations. In the present paper, we first review existing literature and introduce the concept of statistical plasmode simulation. We then discuss advantages and challenges of statistical plasmodes and provide a step-wise procedure for their generation, including key steps to their implementation and reporting. Finally, we illustrate the concept of statistical plasmodes as well as the proposed plasmode generation procedure by means of a public real RNA data set on breast carcinoma patients.


Asunto(s)
Modelos Estadísticos , Humanos , Simulación por Computador
2.
Stat Pap (Berl) ; 63(4): 995-1012, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34629758

RESUMEN

To access the reliability of a new dichotomous test and to capture the random variability of its results in the absence of a gold standard, two measures, the inconsistent acceptance probability (IAP) and inconsistent rejection probability (IRP), were introduced in the literature. In this paper, we first analyze the limiting behavior of both measures as the number of test repetitions increases and derive the corresponding accuracy estimates and rates of convergence. To overcome possible limitations of IRP and IAP, we then introduce a one-parameter family of refined reliability measures, Δ ( k , s ) . Such measures characterize the consistency of the results of a dichotomous test in the absence of a gold standard as the threshold for a positive aggregate test result varies. Similar to IRP and IAP, we also derive corresponding accuracy estimates and rates of convergence for Δ ( k , s ) as the number k of test repetitions increases. Supplementary Information: The online version supplementary material available at 10.1007/s00362-021-01266-9.

3.
Eur J Immunol ; 47(7): 1153-1159, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28439878

RESUMEN

The origin of the thymic epithelium, i.e. the cortical (cTEC) and medullary (mTEC) epithelial cells, from bipotent stem cells through TEC progenitors and lineage-specific progeny still remains poorly understood. We sought to obtain an unbiased view of the incipient emergence of TEC subsets by following embryonic TEC development based on co-expression of EpCAM, CD80 and MHC class II (MHCII) on non-hematopoietic (CD45- ) thymic stromal cells in wild-type BL6 mice. Using a combination of ex vivo analysis, Re-aggregate Thymic Organ Culture (RTOC) reconstitution assays and mathematical modeling, we traced emergent lineage commitment in murine embryonic TECs. Both experimental and mathematical datasets supported the following developmental sequence: MHCII- CD80- → MHCIIlo CD80- → MHCIIhi CD80- → MHCIIhi CD80hi TECs, whereby MHCIIhi CD80- and MHCIIhi CD80hi TECs bear features of cTECs and mTECs respectively. These emergent MHCIIhi CD80- cTECs directly generate mature MHCIIhi CD80hi mTECs in vivo and in vitro, thus supporting the asynchronous model of TEC lineage commitment.


Asunto(s)
Diferenciación Celular , Células Epiteliales/fisiología , Timocitos/fisiología , Timo/citología , Animales , Antígeno B7-1/genética , Antígeno B7-1/inmunología , Linaje de la Célula , Células Cultivadas , Molécula de Adhesión Celular Epitelial/genética , Molécula de Adhesión Celular Epitelial/inmunología , Células Epiteliales/inmunología , Expresión Génica , Genes MHC Clase II/genética , Genes MHC Clase II/inmunología , Antígenos Comunes de Leucocito/deficiencia , Antígenos Comunes de Leucocito/genética , Antígenos Comunes de Leucocito/inmunología , Ratones , Modelos Teóricos , Técnicas de Cultivo de Órganos , Timo/embriología , Timo/inmunología
4.
Strahlenther Onkol ; 191(2): 133-40, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25156510

RESUMEN

PURPOSE: The purpose of this study was to evaluate postoperative radiotherapy regarding outcome and toxicity in patients with thymic epithelial tumors (TET) after surgery. MATERIALS AND METHODS: We retrospectively analyzed medical records of 41 patients with TET treated with postoperative radiotherapy at our institution between 1995 and 2012. The impact of prognostic factors (e.g., Masaoka stage, histological subtype) was investigated and radiation-related toxicity was assessed. RESULTS: Median age was 59.8 years and median follow-up was 61 months. In 24.4 %, TETs were associated with paraneoplastic syndromes. The 5-year overall survival (OS) was 89.5 % and the 5-year disease-free survival (DFS) was 88.9 %. Masaoka stage had a significant impact on OS (p = 0.007). Locally limited stages I + II had a 5-year OS of 100 % compared to 80 % for stage III and 66.7 % for stage IV. The 5-year DFS was excellent with 100 % for both WHO groups A/AB/B1 and B2, respectively, and significantly (p = 0.005) differed from B3/C-staged patients with a 5-year DFS of 63.6 %. Resection status, paraneoplastic association, radiation dose, or tumor size did not influence survival. There were no high-grade acute or late side effects caused by radiotherapy. CONCLUSION: Masaoka stage has a significant impact on OS as WHO type has on DFS in patients with TETs after surgery and adjuvant irradiation. Postoperative radiotherapy with doses around 50 Gy is safe and not likely to cause high-grade toxicity. Further prospective trials are necessary to separate patient subgroups that benefit from radiotherapy from those that do not.


Asunto(s)
Neoplasias Glandulares y Epiteliales/terapia , Radioterapia Adyuvante , Timectomía , Neoplasias del Timo/terapia , Adulto , Anciano , Terapia Combinada , Conducta Cooperativa , Supervivencia sin Enfermedad , Femenino , Alemania , Humanos , Comunicación Interdisciplinaria , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/patología , Dosificación Radioterapéutica , Radioterapia Adyuvante/efectos adversos , Estudios Retrospectivos , Neoplasias del Timo/mortalidad , Neoplasias del Timo/patología , Resultado del Tratamiento , Adulto Joven
5.
PLoS One ; 19(5): e0299989, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38748677

RESUMEN

Simulation is a crucial tool for the evaluation and comparison of statistical methods. How to design fair and neutral simulation studies is therefore of great interest for both researchers developing new methods and practitioners confronted with the choice of the most suitable method. The term simulation usually refers to parametric simulation, that is, computer experiments using artificial data made up of pseudo-random numbers. Plasmode simulation, that is, computer experiments using the combination of resampling feature data from a real-life dataset and generating the target variable with a known user-selected outcome-generating model, is an alternative that is often claimed to produce more realistic data. We compare parametric and Plasmode simulation for the example of estimating the mean squared error (MSE) of the least squares estimator (LSE) in linear regression. If the true underlying data-generating process (DGP) and the outcome-generating model (OGM) were known, parametric simulation would obviously be the best choice in terms of estimating the MSE well. However, in reality, both are usually unknown, so researchers have to make assumptions: in Plasmode simulation studies for the OGM, in parametric simulation for both DGP and OGM. Most likely, these assumptions do not exactly reflect the truth. Here, we aim to find out how assumptions deviating from the true DGP and the true OGM affect the performance of parametric and Plasmode simulations in the context of MSE estimation for the LSE and in which situations which simulation type is preferable. Our results suggest that the preferable simulation method depends on many factors, including the number of features, and on how and to what extent the assumptions of a parametric simulation differ from the true DGP. Also, the resampling strategy used for Plasmode influences the results. In particular, subsampling with a small sampling proportion can be recommended.


Asunto(s)
Simulación por Computador , Análisis de los Mínimos Cuadrados , Modelos Lineales , Humanos
6.
Math Biosci ; 343: 108729, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34762905

RESUMEN

In this paper we address the situation where a well-established, but invasive, expensive or time-consuming diagnostic test may be replaced by multiple repetitions of a different diagnostic test which is known to be imperfect but less invasive or expensive. With an imperfect diagnostic test repeated several times on the same patient, we first introduce the sensitivity and specificity of that test for any given number of test repetitions. We also derive the corresponding asymptotic limits for sensitivity and specificity as the number n of test repetitions increases. Given those limits, we then derive sharp upper bounds for the differences between the sensitivity and specificity, obtained for a given number n of test repetitions, and the corresponding asymptotic limit. Specifically, we provide exact rates for the convergence of the empirical sensitivities and specificities. Our analysis is motivated, among other things, by the current discussion on rapid SARS-CoV-2 testing where the real-time polymerase chain reaction (RT-PCR) test may be replaced with a sequence of rapid lateral-flow antigen tests.


Asunto(s)
Prueba de COVID-19 , COVID-19 , Humanos , SARS-CoV-2 , Sensibilidad y Especificidad
7.
PLoS One ; 14(6): e0218103, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31194780

RESUMEN

Hydroxymethylcytosine (5hmC) methylation is a well-known epigenetic mark that is involved in gene regulation and may impact genome stability. To investigate a possible role of 5hmC in cancer development and progression, one must be able to detect and quantify its level first. In this paper, we address the issue of 5hmC detection at a single base resolution, starting with consideration of the well-established 5hmC measure Δß and, in particular, with an analysis of its properties, both analytically and empirically. Then we propose several alternative hydroxymethylation measures and compare their properties with those of Δß. In the absence of a gold standard, the (pairwise) resemblance of those 5hmC measures to Δß is characterized by means of a similarity analysis and relative accuracy analysis. All results are illustrated on matched healthy and cancer tissue data sets as derived by means of bisulfite (BS) and oxidative bisulfite converting (oxBS) procedures.


Asunto(s)
5-Metilcitosina/análogos & derivados , Metilación de ADN , Sulfitos/química , 5-Metilcitosina/análisis , Estudios de Casos y Controles , Humanos , Neoplasias/genética , Oxidación-Reducción
8.
Immunotherapy ; 11(8): 667-676, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31088239

RESUMEN

Aim: Autoimmune colitis is a typical and possible severe side effect among patients treated with ipilimumab. Patients & methods: We prospectively included 100 patients with metastasized melanoma under ipilimumab treatment in a radiological study of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT). PET evidence of pancolitis ('PET-colitis') was correlated with clinical variables. Results: We observed a significant correlation between PET-colitis and clinically significant diarrhoea, although PET-colitis was more frequent (49 vs 29% of patients, respectively). Neither PET-colitis nor diarrhoea was significantly correlated with response to therapy. Other immune-related adverse events, however, such as hypophysitis and hepatitis were associated with response to therapy and overall survival. Conclusion: Increased 18F-FDG uptake in the colon correlated with clinical symptoms but did not predict clinical outcome to ipilimumab.


Asunto(s)
Enfermedades Autoinmunes , Colitis , Fluorodesoxiglucosa F18/administración & dosificación , Ipilimumab/administración & dosificación , Melanoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/diagnóstico por imagen , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/patología , Colitis/diagnóstico por imagen , Colitis/tratamiento farmacológico , Colitis/patología , Femenino , Humanos , Masculino , Melanoma/diagnóstico por imagen , Melanoma/tratamiento farmacológico , Melanoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias
9.
Front Oncol ; 9: 751, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31456941

RESUMEN

Introduction: This prospective, non-randomized phase II trial aimed to investigate the role of additional irradiation of the pelvic nodes for patients with prostate cancer and a high risk for nodal metastases using helical intensity-modulated radiotherapy with daily image guidance (IMRT/IGRT). Methods and materials: Between 2009 and 2012, 40 men with treatment-naïve prostate cancer and a risk of lymph node involvement of more than 20% were enrolled in the PLATIN-1 trial. All patients received definitive, helical IMRT of the pelvic nodes (total dose of 51.0 Gy) with a simultaneous integrated boost (SIB) to the prostate (total dose of 76.5 Gy) in 34 fractions. Antihormonal therapy (AHT) was administered for a minimum of 2 months before radiotherapy continuing for at least 24 months. Results: After a median follow-up of 71 months (range: 5-95 months), pelvic irradiation was associated with a 5-year overall survival (OS) and biochemical progression-free survival (bPFS) of 94.3% and 83.6%, respectively. For our cohort, no grade 4 gastrointestinal (GI) and genitourinary (GU) toxicity was observed. Quality of life (QoL) assessed by EORTC QLQ-C30 questionnaire was comparable to EORTC reference values without significant changes. Conclusion: The current trial demonstrates that elective IMRT/IGRT of the pelvic nodes with SIB to the prostate for patients with a high-risk of lymphatic spread is safe and shows an excellent clinical outcome without compromising the quality of life. The PLATIN-1 trial delivers eminent baseline data for future studies using modern irradiation techniques.

10.
Tumori ; 105(2): 174-180, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30484384

RESUMEN

INTRODUCTION: We evaluated acute and chronic side effects of 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) in female patients with anal carcinoma and accessed correlations between dosimetric parameters and the considered toxicities. METHODS: For 70 women with anal cancer treated at our department, acute and chronic side effects and quality of life (QoL) were evaluated with questionnaires using the Common Terminology Criteria for Adverse Events (CTCAE v. 4.0.) and Late Effects in Normal Tissue, Subjective, Objective Management and Analytic Scales (LentSoma) before, during, and after the treatment. RESULTS: Forty-seven out of 70 (67%) patients completed the questionnaire and were enrolled in the study. Only poor urinary stream, loss of pubic hair during chemoradiation, and chronic vaginal dryness were observed more frequently in the 3D-CRT group compared to the IMRT group (univariable logistic regression p = .032, p = .04, p = .049, respectively). After the treatment, 43% in the 3D-CRT group and 29% in the IMRT group reported a severe loss of QoL. A higher proportion among the patients receiving a genital V20 ⩾35% showed grade 1-3 side effects such as chronic dyspareunia ( p = .035; Fisher exact test). CONCLUSION: Our results suggest that the use of IMRT decreases acute and chronic adverse effects although reduced QoL also occurred in the IMRT group. These effects are likely to be underreported in retrospective studies using physician-reported outcome measures.


Asunto(s)
Neoplasias del Ano/terapia , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Traumatismos por Radiación/etiología , Radioterapia Conformacional/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioradioterapia/métodos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Persona de Mediana Edad , Mitomicina/administración & dosificación , Medición de Resultados Informados por el Paciente , Calidad de Vida , Traumatismos por Radiación/epidemiología , Estudios Retrospectivos , Encuestas y Cuestionarios
11.
Cancer Med ; 7(1): 95-104, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29266761

RESUMEN

Despite markedly improved treatment options for metastatic melanoma, resistance to targeted therapies such as BRAF inhibitors (BRAFi) or BRAFi plus MEK inhibitors (MEKi) remains a major problem. Our aim was to characterize progression on BRAFi therapy and outcome of subsequent treatment. One hundred and eighty patients with BRAF-mutant metastatic melanoma who had progressed on treatment with single-agent BRAFi from February 2010 to April 2015 were included in a retrospective data analysis focused on patterns of progression, treatment beyond progression (TBP) and subsequent treatments after BRAFi therapy. Analysis revealed that 51.1% of patients progressed with both new and existing metastases opposed to progression of only preexisting (28.3%) or only new (20.6%) metastases. Exclusive extracranial progression occurred in 50.6% of patients compared to both extra- and intracranial (29.4%) or sole cerebral progression (20%). Multivariable analyses demonstrated that single site progression and primary response to BRAFi were associated with improved progression-free survival. Progression with exclusively new or only existing metastases and a baseline Eastern Cooperative Oncology Group (ECOG) of 0 were associated with prolonged overall survival (OS). TBP had no significant impact on OS. Other subsequent treatments showed low efficacy with the exception of anti-PD-1 antibodies. In conclusion we identified specific patterns of progression which significantly correlate with further prognosis after progression on BRAFi treatment. In contrast to previously published data, we could not demonstrate a significant survival benefit for BRAFi TBP. Subsequent therapies had strikingly low efficacy except for PD-1 inhibitors.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Masculino , Melanoma/genética , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Mutación , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/genética , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Adulto Joven
12.
Cell Rep ; 20(8): 1906-1920, 2017 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-28834753

RESUMEN

Chromosomal instability is a hallmark of cancer and correlates with the presence of extra centrosomes, which originate from centriole overduplication. Overduplicated centrioles lead to the formation of centriole rosettes, which mature into supernumerary centrosomes in the subsequent cell cycle. While extra centrosomes promote chromosome missegregation by clustering into pseudo-bipolar spindles, the contribution of centriole rosettes to chromosome missegregation is unknown. We used multi-modal imaging of cells with conditional centriole overduplication to show that mitotic rosettes in bipolar spindles frequently harbor unequal centriole numbers, leading to biased chromosome capture that favors binding to the prominent pole. This results in chromosome missegregation and aneuploidy. Rosette mitoses lead to viable offspring and significantly contribute to progeny production. We further show that centrosome abnormalities in primary human malignancies frequently consist of centriole rosettes. As asymmetric centriole rosettes generate mitotic errors that can be propagated, rosette mitoses are sufficient to cause chromosome missegregation in cancer.


Asunto(s)
Centriolos/metabolismo , Inestabilidad Cromosómica/genética , Neoplasias/genética , Polos del Huso/metabolismo , Humanos , Neoplasias/metabolismo
13.
Nat Commun ; 7: 10893, 2016 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-26964756

RESUMEN

Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (DGKA). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced DGKA transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy.


Asunto(s)
Neoplasias de la Mama/radioterapia , Mama/patología , Metilación de ADN/genética , Diacilglicerol Quinasa/genética , Epigénesis Genética/genética , Fibroblastos/patología , ARN Mensajero/metabolismo , Traumatismos por Radiación/genética , Adulto , Anciano , Western Blotting , Estudios de Casos y Controles , Inmunoprecipitación de Cromatina , Cromatografía Liquida , Diacilglicerol Quinasa/antagonistas & inhibidores , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Femenino , Fibrosis/etiología , Fibrosis/genética , Células HCT116 , Células HEK293 , Humanos , Espectrometría de Masas , Persona de Mediana Edad , Radioterapia/efectos adversos , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Piel/citología , Transcriptoma
14.
Oncotarget ; 7(39): 64191-64202, 2016 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-27577081

RESUMEN

DNA methylation changes in peripheral blood DNA have been shown to be associated with solid tumors. We sought to identify methylation alterations in whole blood DNA that are associated with breast cancer (BC). Epigenome-wide DNA methylation profiling on blood DNA from BC cases and healthy controls was performed by applying Infinium HumanMethylation450K BeadChips. Promising CpG sites were selected and validated in three independent larger sample cohorts via MassARRAY EpiTyper assays. CpG sites located in three genes (cg06418238 in RPTOR, cg00736299 in MGRN1 and cg27466532 in RAPSN), which showed significant hypomethylation in BC patients compared to healthy controls in the discovery cohort (p < 1.00 x 10-6) were selected and successfully validated in three independent cohorts (validation I, n =211; validation II, n=378; validation III, n=520). The observed methylation differences are likely not cell-type specific, as the differences were only seen in whole blood, but not in specific sub cell-types of leucocytes. Moreover, we observed in quartile analysis that women in the lower methylation quartiles of these three loci had higher ORs than women in the higher quartiles. The combined AUC of three loci was 0.79 (95%CI 0.73-0.85) in validation cohort I, and was 0.60 (95%CI 0.54-0.66) and 0.62 (95%CI 0.57-0.67) in validation cohort II and III, respectively. Our study suggests that hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with BC and might serve as blood-based marker supplements for BC if these could be verified in prospective studies.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , ADN Tumoral Circulante/genética , Metilación de ADN , Epigénesis Genética , Perfilación de la Expresión Génica/métodos , Proteínas Musculares/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteína Reguladora Asociada a mTOR/genética , Ubiquitina-Proteína Ligasas/genética , Adulto , Anciano , Área Bajo la Curva , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , ADN Tumoral Circulante/sangre , Islas de CpG , Femenino , Predisposición Genética a la Enfermedad , Humanos , Modelos Logísticos , Persona de Mediana Edad , Proteínas Musculares/sangre , Oportunidad Relativa , Valor Predictivo de las Pruebas , Curva ROC , Proteína Reguladora Asociada a mTOR/sangre , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Ubiquitina-Proteína Ligasas/sangre
15.
Radiat Oncol ; 9: 113, 2014 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-24886574

RESUMEN

BACKGROUND: Concurrent chemotherapy and radiation therapy is the preferred standard of care for patients with anal cancer. Several studies have suggested a benefit of intensity-modulated radiation therapy (IMRT) compared with 3D-conformal radiation (3D-CRT) regarding acute toxicity. This study evaluates outcome and toxicity of patients undergoing IMRT/Tomotherapy or 3D-CRT at our institution. METHODS: A cohort of 105 anal cancer patients was treated with chemoradiation or radiation alone (16.2%) between January 2000 and December 2011. 37 patients received 3D-CRT while 68 patients were treated with IMRT. Follow-up exams were performed every 3 to 6 months for a minimum of 3 years and then annually. RESULTS: Median follow-up was 41.4 months (2.8 - 158.4). Overall survival (OS), Progression-free survival (PFS) and local control (LC) at 3 years was 70.3%, 66.5%, 78.3% in the 3D-CRT group and 82.9%, 66.5%, 75.3% in the IMRT group without statistically significant difference. 3-year Colostomy-free survival (CFS) was 85.7% in the IMRT/Tomotherapy group and 91.8% in the 3D-CRT group (p = 0.48). No grade 4 toxicity was found in both groups. Severe (G2/3) acute skin toxicity (94.6% vs. 63.2%; p < 0.001) and acute gastrointestinal toxicity rate (67.6% vs. 47.1%; p = 0.03) was significantly higher with 3D-CRT compared to IMRT/Tomotherapy. CONCLUSION: The use of IMRT can reduce acute severe side effects of the skin and gastrointestinal tract but did not demonstrate improved results regarding OS, PFS, LC and CFS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Ano/radioterapia , Carcinoma de Células Escamosas/radioterapia , Quimioradioterapia/efectos adversos , Traumatismos por Radiación/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Ano/mortalidad , Neoplasias del Ano/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
16.
Radiother Oncol ; 113(3): 331-6, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25465729

RESUMEN

BACKGROUND: The purpose of this study was to evaluate HPV-DNA and p16(INK4a) (p16) expression as prognostic markers for outcome in patients with anal cancer. METHODS: From January 2000 to December 2011 a cohort of 105 anal cancer patients was treated with definitive chemoradiation at our institution. Tumor biopsies from 90 patients were analyzed for HPV-DNA by polymerase chain reaction and for p16 expression by immunohistochemistry. RESULTS: Median follow-up was 48.6months (range 2.8-169.1months). HPV-DNA or p16-expression was found in 75 anal cancers each (83.3%), concordance was detectable in 70 tumors (77.8%). Significantly improved overall survival (OS) [77.1% vs. 51.4%, p=0.005], progression-free survival (PFS) [64.0% vs. 35.0%, p<0.001] and improved local control [81.0% vs. 55.9%, p=0.023] was found for concomitant HPV- and p16-positive anal carcinomas (cHPPAC) in univariate analysis. Multivariate analysis showed better OS [p=0.015] and PFS [p=0.002] for cHPPAC. CONCLUSION: The combination of HPV-DNA and p16 can be used as an independent prognostic parameter in anal cancer patients.


Asunto(s)
Neoplasias del Ano/diagnóstico , Neoplasias del Ano/terapia , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Papillomaviridae/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Ano/mortalidad , Neoplasias del Ano/patología , Neoplasias del Ano/virología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Quimioradioterapia/métodos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Reacción en Cadena de la Polimerasa/métodos , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA