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1.
BMC Cancer ; 12: 283, 2012 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-22780988

RESUMEN

BACKGROUND: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. METHODS: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. RESULTS: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. CONCLUSIONS: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Cuidados Paliativos , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Encuestas y Cuestionarios
2.
Strahlenther Onkol ; 187(5): 311-5, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21533759

RESUMEN

PURPOSE: Total body irradiation (TBI) is a standard treatment modality within the multidisciplinary approach for allogeneous stem cell or bone marrow transplantation. However, surviving patients are at risk for developing a variety of late sequelae. This analysis aimed to retrospectively characterize late effects after TBI in adults treated in a single center. PATIENTS AND METHODS: Patients ≥ 18 years treated with fractionated TBI (4-12 Gy) between 1996 and 2008 were included in this study. Treatment data were collected retrospectively from the treating departments. Late effects were evaluated using the clinic charts and/or were obtained from the general practitioners using a standardized questionnaire. Analyses were performed by calculation of the cumulative incidences using the Kaplan-Meier method and the log rank test. RESULTS: A total of 308 patients ≥ 18 years were treated including a TBI of whom 78 patients were excluded from further analysis due to death within less than 1 year after TBI. Patients suffered from leukemia in most cases. Late toxicity follow-up was available in 120 patients (mean age 46.1 years; range, 18-70 years) after a mean follow-up of 23 months (range, 12-96 months). The cumulative incidences (CI) at 3 years were 28% for pulmonary event, 8% for pulmonary toxicity, 25% for kidney toxicity, 8% for cataract, 17% for bone toxicity, and 10% for secondary malignancy. The CI of bone toxicity was higher in female than in male patients (p = 0.019). CONCLUSION: Late effects after TBI in the context of allogeneous stem cell or bone marrow transplantation can frequently be observed. Regular follow-up examinations are advised for the early registration and treatment of adverse effects.


Asunto(s)
Irradiación Corporal Total/efectos adversos , Adulto , Anciano , Trasplante de Médula Ósea/métodos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Trasplante de Células Madre/métodos , Factores de Tiempo , Adulto Joven
3.
Pediatr Blood Cancer ; 57(4): 549-53, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21442722

RESUMEN

BACKGROUND: The prognosis in patients with relapsed Ewing sarcoma is unfavorable. Our investigation identifies factors predicting for the outcome following relapse. PROCEDURE: We analyzed type of relapse, time to relapse and overall survival after relapse (OSr) in 714 patients with first recurrence. All patients had been treated within the Cooperative Ewing Sarcoma Studies (CESS) 81 or 86, or the European Intergroup CESS (EICESS 92). OSr time was calculated from diagnosis of first relapse to last follow-up or death. RESULTS: Median follow-up time from diagnosis of primary disease was 2.2 years (mean = 4.0; range: 0.2-24.9). Relapse sites were local in 15%, combined local and systemic in 12%, and systemic in 73%. Among patients with a localized primary tumor, 20% relapsed locally, while 12% showed combined and 68% systemic relapse. When the primary disease was disseminated, 82% developed systemic, 13% combined, and 5% local relapse. Five-year OSr was 0.13 (SE = 0.01). Outcome following local relapse, with a 5-year survival rate of 0.24 (P < 0.001), was superior to outcome after systemic or combined recurrence. Five-year OSr was 0.07 (SE = 0.01) in patients who relapsed 0-2 years after the diagnosis of primary disease, as compared to a 5-year OSr of 0.29 (SE = 0.03) when relapse occurred later. CONCLUSIONS: 5-year OSr in Ewing sarcoma is poor (<0.2). Prognostically favorable factors are: late onset (>2 years) and strictly localized relapse.


Asunto(s)
Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Sarcoma de Ewing/mortalidad , Sarcoma de Ewing/patología , Adolescente , Adulto , Neoplasias Óseas/terapia , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/terapia , Pronóstico , Sarcoma de Ewing/terapia , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
4.
Pediatr Blood Cancer ; 55(6): 1145-52, 2010 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-20734400

RESUMEN

BACKGROUND: To analyze the impact of mediastinal irradiation on the incidence of cardiac late effects in long-term survivors of pediatric Hodgkin disease (HD). METHODS: The study cohort comprised 1,132 survivors of HD who received treatment before 18 years of age in consecutive trials between 1978 and 1995. They had maintained remission without secondary malignancy for 3.1-29.4 years. The cumulative doxorubicin dose was uniformly 160 mg/m(2), the mediastinal radiation dose (MedRD) was 36, 30, 25, 20, or 0 Gy. Follow-up questionnaires complemented by additional contacts served to collect information on late effects from patients and physicians. A central expert panel reviewed all reported cardiac abnormalities. RESULTS: By October 2008, cardiac diseases (CD) had been diagnosed in 50 of 1,132 patients aged 15.0-41.7 (median 32.2) years. The interval since HD therapy was 3.0-28.2 (median 19.5) years. Valvular defects were diagnosed most frequently, followed by coronary artery diseases, cardiomyopathies, conduction disorders, and pericardial abnormalities. The cumulative incidence of CD after 25 years was highest in the MedRD-36 group (21%) decreasing to 10%, 6%, 5%, and 3% in the lower MedRD groups (P < 0.001). Multivariate Cox analysis of several putative risk factors showed MedRD to be the only significant variable predicting for CD-free survival (P = 0.0025). CONCLUSIONS: Our results indicate that lower MedRDs are less cardiotoxic. Consequently, reduction of cardiac late effects may be expected with the lower radiation doses used in current HD protocols. Longer follow-up is needed to confirm the present results.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cardiopatías/etiología , Enfermedades de las Válvulas Cardíacas/etiología , Enfermedad de Hodgkin/radioterapia , Neoplasias del Mediastino/radioterapia , Adolescente , Niño , Preescolar , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Cardiopatías/diagnóstico , Enfermedades de las Válvulas Cardíacas/diagnóstico , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Estudios Longitudinales , Masculino , Neoplasias del Mediastino/complicaciones , Neoplasias del Mediastino/tratamiento farmacológico , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Dosificación Radioterapéutica , Tasa de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación
5.
PLoS One ; 15(2): e0229271, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32084238

RESUMEN

BACKGROUND: Truncated tissue factor (tTF) retargeted by NGR-peptides to aminopeptidase N (CD13) in tumor vasculature is effective in experimental tumor therapy. tTF-NGR induces tumor growth inhibition in a variety of human tumor xenografts of different histology. To improve on the therapeutic efficacy we have combined tTF-NGR with radiotherapy. METHODS: Serum-stimulated human umbilical vein endothelial cells (HUVEC) and human HT1080 sarcoma cells were irradiated in vitro, and upregulated early-apoptotic phosphatidylserine (PS) on the cell surface was measured by standard flow cytometry. Increase of cellular procoagulant function in relation to irradiation and PS cell surface concentration was measured in a tTF-NGR-dependent Factor X activation assay. In vivo experiments with CD-1 athymic mice bearing human HT1080 sarcoma xenotransplants were performed to test the systemic therapeutic effects of tTF-NGR on tumor growth alone or in combination with regional tumor ionizing radiotherapy. RESULTS: As shown by flow cytometry with HUVEC and HT1080 sarcoma cells in vitro, irradiation with 4 and 6 Gy in the process of apoptosis induced upregulation of PS presence on the outer surface of both cell types. Proapoptotic HUVEC and HT1080 cells both showed significantly higher procoagulant efficacy on the basis of equimolar concentrations of tTF-NGR as measured by FX activation. This effect can be reverted by masking of PS with Annexin V. HT1080 human sarcoma xenografted tumors showed shrinkage induced by combined regional radiotherapy and systemic tTF-NGR as compared to growth inhibition achieved by either of the treatment modalities alone. CONCLUSIONS: Irradiation renders tumor and tumor vascular cells procoagulant by PS upregulation on their outer surface and radiotherapy can significantly improve the therapeutic antitumor efficacy of tTF-NGR in the xenograft model used. This synergistic effect will influence design of future clinical combination studies.


Asunto(s)
Antineoplásicos/farmacología , Antígenos CD13/metabolismo , Terapia Molecular Dirigida , Sarcoma/tratamiento farmacológico , Sarcoma/radioterapia , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Antineoplásicos/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Coagulación Sanguínea/efectos de la radiación , Línea Celular Tumoral , Terapia Combinada , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Ratones , Fosfatidilserinas/metabolismo , Sarcoma/metabolismo , Sarcoma/patología
6.
Apoptosis ; 14(2): 226-35, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19142732

RESUMEN

In the present study, the predictive value of ionising radiation (IR)-induced cell death was tested in peripheral blood lymphocytes (PBLs) and their corresponding Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) in an interlaboratory comparison. PBLs and their corresponding LCLs were derived from 15 tumour patients, that were considered clinically radiosensitive based on acute side-effects, and matched controls. Upon coding of the samples, radiosensitivity of the matched pairs was analysed in parallel in three different laboratories by assessing radiation-induced apoptotic and necrotic cell death using annexin V. All participating laboratories detected a dose-dependent increase of apoptosis and necrosis in the individual samples, to a very similar extent. However, comparing the mean values of apoptotic and necrotic levels derived from PBLs of the radiosensitive cohort with the mean values of the control cohort did not reveal a significant difference. Furthermore, within 15 matched pairs, no sample was unambiguously and independently identified by all three participating laboratories to demonstrate in vitro hypersensitivity that matched the clinical hypersensitivity. As has been reported previously, apoptotic and necrotic cell death is barely detectable in immortalised LCL derivatives using low doses of IR. Concomitantly, the differences in apoptosis or necrosis levels found in primary cells of different individuals were not observed in the corresponding LCL derivatives. All participating laboratories concordantly reasoned that, with the methods applied here, IR-induced cell death in PBLs is unsuitable to unequivocally predict the individual clinical radiosensitivity of cancer patients. Furthermore, LCLs do not reflect the physiological properties of the corresponding primary blood lymphocytes with regard to IR-induced cell death. Their value to predict clinical radiosensitivity is thus highly questionable.


Asunto(s)
Tolerancia a Radiación/efectos de la radiación , Anciano , Muerte Celular/efectos de la radiación , Línea Celular , Relación Dosis-Respuesta en la Radiación , Femenino , Citometría de Flujo , Humanos , Linfocitos/patología , Linfocitos/efectos de la radiación , Masculino , Persona de Mediana Edad , Necrosis , Radiación Ionizante , Radioterapia/efectos adversos , Factores de Tiempo
7.
Strahlenther Onkol ; 185(5): 275-81, 2009 May.
Artículo en Alemán | MEDLINE | ID: mdl-19440665

RESUMEN

BACKGROUND AND PURPOSE: A sufficient number of well-trained specialists in radiation oncology is needed for an adequate supply in radiation oncology. Therefore, the training in radiation oncology is of utmost importance. This requirement is faced with a growing lack of physicians in Germany. The aim of this study was to characterize the current situation of radiation oncology training in Germany and to work out proposals to avoid a lack of radiotherapists. MATERIAL AND METHODS: In summer 2008, 233 questionnaires were sent out to potential trainers in radiation oncology in Germany. The questions included, among others, the individual training situation and problems in finding physicians. A second questionnaire was addressed to trainees in radiation oncology and contained, e.g., questions regarding satisfaction, motivation for the choice of radiation oncology, a previous work in another discipline, and future perspectives. RESULTS: Answers were obtained from 107 supervisor physicians of whom 84.1% had the permission to employ trainees in radiation oncology. The finding of new trainees provided large problems in 47.1%; 35.3% had few and 17.6% no problems. For specialists in radiation oncology, 47.2% reported large, 26.4% few and 26.4% no problems in finding candidates. 113 trainees answered the questionnaires. Almost half of them (46.9%) had previously worked in another discipline. The majority was quite (44.2%) or fully (46.0%) satisfied with their job, 84.1% stated good up to excellent future perspectives. The vast majority (88.5%) would decide for a training in radiation oncology again. CONCLUSION: Trainees in radiation oncology in Germany are satisfied with their training, see good future perspectives and would again decide to do their training in radiation oncology. However, there are large problems in finding candidates for open jobs. A positive promotion is recommended to face these problems.


Asunto(s)
Evaluación Educacional , Oncología por Radiación/educación , Oncología por Radiación/estadística & datos numéricos , Estudiantes/estadística & datos numéricos , Alemania
8.
Strahlenther Onkol ; 185(4): 260-5, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19370430

RESUMEN

PURPOSE: To investigate the impact of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) on planning of neoadjuvant radiotherapy for locally advanced rectal cancer (LARC) patients. PATIENTS AND METHODS: From January 2003 to December 2007, a total of 36 patients with LARC underwent a retroprospective PET/CT study for radiotherapy-planning purposes. Gross tumor volume (GTV), clinical target volume (CTV) and planning target volume (PTV) were defined in a retrospective analysis by a blinded reader. The hypothetical boost volume was defined primarily on CT alone, and afterwards on the fused PET/CT dataset. The CT- and PET/CT-based GTVs were quantitatively compared and percentage of overlap (OV%) was calculated and analyzed. The impact of PET/CT on radiation treatment planning and overall patient management was evaluated. RESULTS: PET/CT-GTVs were smaller than CT-GTVs (p < 0.05). PET/CT imaging resulted in a change of overall management for three patients (8 %). In 16 of 35 patients (46 %), PET/CT resulted in a need for modification of the usual target volumes (CT-PTV) because of detection of a geographic miss. CONCLUSION: FDG-PET/CT had significant impact on radiotherapy planning and overall treatment of patients with LARC.


Asunto(s)
Fluorodesoxiglucosa F18 , Aumento de la Imagen/métodos , Tomografía de Emisión de Positrones/métodos , Radioterapia Conformacional/métodos , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/radioterapia , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Radiofármacos , Radioterapia Adyuvante/métodos , Neoplasias del Recto/patología , Estudios Retrospectivos , Resultado del Tratamiento
9.
Strahlenther Onkol ; 185(3): 190-7, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19330297

RESUMEN

BACKGROUND: Prospective data on quality-of-life (QoL) effects of radiotherapy for brain metastases are currently lacking, but would be of great interest to guide therapeutic decisions. PATIENTS AND METHODS: From 01/2007 to 08/2007, 46 patients with previously untreated brain metastases were recruited at eight centers. QoL was measured at start of treatment (T(0)) and at 3 months (T(3mo)). In the pilot study, two combinations of QoL instruments could be used at the discretion of the centers (A: EORTC QLQ-C30 and B: EORTC QLQ-C15-PAL both with brain module BN20, assessment by proxies with A: Palliative Care Outcome Scale, B: self-constructed brain-specific instrument). RESULTS: All patients received whole-brain radiotherapy, four with an additional boost irradiation. At T(3mo), 26/46 patients (56.5%) had died. 17/20 survivors (85%) completed the questionnaires. In 3-month survivors, QoL deteriorated in most domains, significant in drowsiness, hair loss and weakness of legs. The scores for headaches and seizures were slightly better after 3 months. Assessment by proxies also suggested worsening of QoL. Initial QoL at T(0) was better in those alive than in those deceased at T(3mo), significant for physical function and for the symptom scales of fatigue and pain, motor dysfunction, communication deficit and weakness of legs. CONCLUSION: Practicability and compliance appeared better with the (shorter) version B. This version is now used in the ongoing main phase of the study with additional centers. First results indicate a moderate worsening of QoL during the first 3 months after start of palliative radiotherapy for brain metastases. QoL at initiation of radiotherapy may be prognostic for survival.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Calidad de Vida , Radioterapia Conformacional/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/epidemiología , Femenino , Alemania/epidemiología , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Proyectos Piloto , Medición de Riesgo/métodos , Factores de Riesgo , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento
10.
Anticancer Res ; 28(6B): 3885-90, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-19192645

RESUMEN

BACKGROUND: Radiotherapy plays a pivotal role in tumor treatment. Brachytherapy as an additional radiation technique allows local dose increments in areas at high risk of local failure. PATIENTS AND METHODS: Our past 15-year experience with tissue-equivalent bendy applicator brachytherapy at the University Hospital Münster, Germany was reviewed. A series of 74 consecutive patients who had mainly been treated for sarcomas with perioperative brachytherapy was analyzed with a focus on local relapse-free survival and side-effects. RESULTS: The 5-year local control rate was 73% in primary treatment situations with a significant influence of additional external irradiation, surgical margin depth and tumor entity. Late sequelae of combined modality treatment were observed in 40 patients (54%) and mainly concerned wound healing (n = 18, 24%). CONCLUSION: A high-risk collective, in view of local failure, showed adequate local control rates as well as acceptable late sequelae. Flab brachytherapy is a good treatment option to achieve local radiation dose increments in patients at high risk of local failure.


Asunto(s)
Braquiterapia/métodos , Sarcoma/radioterapia , Neoplasias de los Tejidos Blandos/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia/efectos adversos , Braquiterapia/instrumentación , Niño , Preescolar , Terapia Combinada , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Perioperativa , Dosificación Radioterapéutica , Estudios Retrospectivos , Sarcoma/cirugía , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Tasa de Supervivencia , Adulto Joven
11.
Brachytherapy ; 6(4): 280-5, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17991624

RESUMEN

PURPOSE: Different doses and techniques used in high-dose-rate (HDR) prostate brachytherapy make it difficult to define universal quality parameters. The aim of this study was to develop individual, objective parameters for the evaluation of an HDR brachytherapy plan for prostate radiation. METHODS: Fifty-three patients who received an HDR brachytherapy boost after external radiation were analyzed in this study. Brachytherapy was performed with a (192)Ir source after ultrasound-guided, transperineal metal needle application followed by removal of the ultrasound probe to reduce organ dose levels at the anterior rectum wall. The rectum and prostate locations as well as the dose at the anterior rectum wall were estimated under the anatomical conditions of HDR prostate brachytherapy. The doses at the organs at risk (rectum and urethra) were analyzed for several parameters, which were compared to values of former patients before the start of treatment. In cases of major deviations, modifications of the treatment plan were performed before starting the treatment. RESULTS: Deflating of the water balloon led to an increase of the space between the anterior rectal wall and the dorsal margin of the prostate (mean, 6mm; 1-10mm). The dose of the introduced "virtual rectum," represented by the ventral surface of the ultrasound probe, in the treatment plan correlated to dose measurements in the rectum. Pretreatment evaluation and comparison of the established individual quality parameters led in two cases to a treatment plan modification. CONCLUSIONS: This method allows a fast and objective individual brachytherapy treatment plan evaluation and improvement.


Asunto(s)
Braquiterapia/métodos , Neoplasias de la Próstata/radioterapia , Recto/diagnóstico por imagen , Terapia Combinada , Humanos , Radioisótopos de Iridio , Masculino , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico por imagen , Dosis de Radiación , Radiografía , Ultrasonografía , Uretra/diagnóstico por imagen
12.
Cancer Lett ; 230(1): 122-33, 2005 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-16253768

RESUMEN

Hypoxia-inducible factor-1alpha (HIF-1alpha) is both a potential endogenous marker of tumor hypoxia and therapeutic target, and elevated HIF-1alpha protein levels have been shown to be associated with increased hypoxic radiation resistance in FaDu human pharyngeal carcinoma cells in vitro. Here, we found that in FaDu xenografts, no significant HIF-1alpha protein accumulation was detectable by either flow cytometry or Western blot, despite the presence of hypoxic (pimonidazole-positive, radiation resistant) cells. To investigate the effect of different tumor microenvironment conditions on hypoxic HIF-1alpha accumulation, we performed in vitro hypoxia experiments (0.1% O2, 24 h) with manipulation of pH (7.4 vs. 6.7), glucose (0-5.5 mM) and serum (0 or 10%) availability in FaDu and HT 1080 human fibrosarcoma cells. Hypoxic induction of HIF-1alpha protein was strongly dependent on glucose availability and largely abolished at 0.55 mM glucose or less in both cell lines. This glucose effect was confirmed in a hypoxia-responsive-element (HRE)/enhanced-green-fluorescent-protein (EGFP) reporter assay in transfected HT 1080 cells and possibly explains a lack of HIF-1alpha protein in hypoxic tumor cells.


Asunto(s)
Carcinoma/patología , Hipoxia de la Célula , Fibrosarcoma/patología , Glucosa/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Neoplasias Faríngeas/patología , Animales , Biomarcadores/análisis , Western Blotting , Citometría de Flujo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Ratones , Ratones SCID , Tolerancia a Radiación , Trasplante Heterólogo , Células Tumorales Cultivadas
13.
Head Neck ; 37(8): 1137-41, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24764129

RESUMEN

BACKGROUND: The registry for the evaluation of side effects after radiotherapy in childhood and adolescence (RiSK) was established to prospectively characterize radiation-associated side effects. The purpose of this analysis was to characterize side effects after radiotherapy to the head and neck in children and adolescents. METHODS: Radiation doses have been collected across Germany since 2001. Acute and late side effects were characterized. RESULTS: Until January 2010, 133 patients (median age, 12.7 years) were recruited who had received radiotherapy to the salivary glands. Toxicity evaluation was available for 114 patients (median follow-up, 2.9 years). Acute and late toxicity significantly depended on the maximum radiation dose to the salivary glands. An increase of the mean value of maximum dose of 1 Gray (Gy) to the submandibular glands resulted in an odds ratio of 1.04 (range, 1.00-1.08; p = .039) for acute toxicities of the salivary glands and 1.08 (range, 1.03-1.13; p = .001) for acute mucosal toxicities. CONCLUSION: These data can be used for an individual risk assessment in pediatric head and neck radiotherapy.


Asunto(s)
Relación Dosis-Respuesta en la Radiación , Mucosa Bucal/efectos de la radiación , Traumatismos por Radiación/etiología , Radioterapia Adyuvante/efectos adversos , Glándulas Salivales/efectos de la radiación , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Lactante , Masculino , Estudios Prospectivos , Traumatismos por Radiación/epidemiología , Radiofármacos , Dosificación Radioterapéutica , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
15.
Strahlenther Onkol ; 185 Suppl 2: 21-2, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19685030
16.
Strahlenther Onkol ; 180(12): 811-4, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15592702

RESUMEN

BACKGROUND: Scleredema adultorum Buschke is a rare disorder characterized by thickening of the dermis of the neck, head and upper trunk. Its etiology is unknown, but there may be a preceding history of infection and there is a known association with diabetes mellitus. Women are more frequently affected. Usually, the disease is self-limiting but some patients show progressive disease. In these cases therapeutic options are poor, with only case reports and small series supporting their use. CASE REPORT: A 58-year-old patient with a scleredema of the neck and upper trunk is described, who was treated twice within 6 months by electron-beam radiation therapy. After the second course his symptoms improved significantly. A review of the literature of radiation treatment of this disease is given. CONCLUSION: . Regardless of the possible mechanisms in pathogenesis and treatment of scleredema adultorum Buschke, the application of ionizing radiation is an important, effective and well-tolerated therapy option in the treatment of severe cases and may candidate as the first-line treatment of this disease.


Asunto(s)
Radioterapia Conformacional/métodos , Escleredema del Adulto/diagnóstico , Escleredema del Adulto/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Resultado del Tratamiento
18.
Anticancer Res ; 24(3a): 1637-44, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15274334

RESUMEN

BACKGROUND: Adhesion molecules are involved in cell-cell and cell-matrix interactions and may be informative to characterize intercellular mechanisms of invasion and metastasis. This study was performed to characterize radiation-induced changes in the adhesion molecule profile of Ewing tumor subpopulations on a single cell level. MATERIALS AND METHODS: In the present study, two Ewing tumors were characterized in vitro 4, 24 and 72 hours after radiation with 5 Gy and in vivo in a xenograft model 4, 6 and 15 days after radiation with 30 Gy, together with non-irradiated controls, by five parameter flow cytometry. Directly fluorescence-conjugated antibodies that were directed against adhesion molecules (LFA-1 (CD11a), HCAM (CD44), VLA-2 (CD49b), ICAM-1 (CD54), NCAM (CD56), LECAM-1 (CD62L) and CD86) were used. Annexin V and 7-AAD were used to characterize radiation-induced apoptosis. RESULTS: Tumor cell subpopulations were identified by the expression of adhesion molecules, apoptotic markers and DNA content. Heterogeneous changes of the adhesion molecule profile were identified on tumor cell subpopulations after radiation. The expression of CD11a and CD62L correlated with the expression of apoptosis-associated markers. CONCLUSION: The changes of flow cytometric profile under radiation may potentially correlate with a changed metastatic potential of tumor cell subpopulations.


Asunto(s)
Moléculas de Adhesión Celular/biosíntesis , Moléculas de Adhesión Celular/efectos de la radiación , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/radioterapia , Animales , Antígenos CD/biosíntesis , Antígenos CD/efectos de la radiación , Apoptosis/fisiología , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Citometría de Flujo , Técnica del Anticuerpo Fluorescente Directa , Humanos , Ratones , Ratones Desnudos , Sarcoma de Ewing/patología , Factores de Tiempo , Regulación hacia Arriba/efectos de la radiación , Ensayos Antitumor por Modelo de Xenoinjerto
19.
PLoS One ; 7(10): e47185, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23110060

RESUMEN

Radiotherapy is a powerful cure for several types of solid tumours, but its application is often limited because of severe side effects in individual patients. With the aim to find biomarkers capable of predicting normal tissue side reactions we analysed the radiation responses of cells from individual head and neck tumour and breast cancer patients of different clinical radiosensitivity in a multicentric study. Multiple parameters of cellular radiosensitivity were analysed in coded samples of peripheral blood lymphocytes (PBLs) and derived lymphoblastoid cell lines (LCLs) from 15 clinical radio-hypersensitive tumour patients and compared to age- and sex-matched non-radiosensitive patient controls and 15 lymphoblastoid cell lines from age- and sex- matched healthy controls of the KORA study. Experimental parameters included ionizing radiation (IR)-induced cell death (AnnexinV), induction and repair of DNA strand breaks (Comet assay), induction of yH2AX foci (as a result of DNA double strand breaks), and whole genome expression analyses. Considerable inter-individual differences in IR-induced DNA strand breaks and their repair and/or cell death could be detected in primary and immortalised cells with the applied assays. The group of clinically radiosensitive patients was not unequivocally distinguishable from normal responding patients nor were individual overreacting patients in the test system unambiguously identified by two different laboratories. Thus, the in vitro test systems investigated here seem not to be appropriate for a general prediction of clinical reactions during or after radiotherapy due to the experimental variability compared to the small effect of radiation sensitivity. Genome-wide expression analysis however revealed a set of 67 marker genes which were differentially induced 6 h after in vitro-irradiation in lymphocytes from radio-hypersensitive and non-radiosensitive patients. These results warrant future validation in larger cohorts in order to determine parameters potentially predictive for clinical radiosensitivity.


Asunto(s)
Biomarcadores/análisis , Tolerancia a Radiación/fisiología , Células Cultivadas , Ensayo Cometa , Daño del ADN/fisiología , Relación Dosis-Respuesta en la Radiación , Histonas/metabolismo , Humanos , Linfocitos/metabolismo , Linfocitos/efectos de la radiación , Radiación Ionizante
20.
Anticancer Res ; 31(11): 3903-8, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22110217

RESUMEN

AIM: To assess the overall impact of the most common contemporary prostate cancer therapies (radical prostatectomy, percutaneous irradiation, brachytherapy, hormonal therapy) with regard to physical and psychological well-being, as well as to general patient satisfaction. PATIENTS AND METHODS: In October 2006, a questionnaire focused on patients' opinions and satisfaction regarding their previous prostate cancer therapies was published in a patient cancer journal (Krebsmagazin). Results were collected until March, 2007 and analyzed using Wilcoxon and Student's t-tests. RESULTS: Answers were obtained from 634 patients (radical prostatectomy: 61%; percutaneous irradiation: 17%; brachytherapy: 2%; hormonal therapy: 15%; other/combined: 5%). Concerning late side effects and convenience of treatment, 96% of all patients who had undergone percutaneous irradiation were very satisfied with their choice and would choose the same therapy again (brachytherapy: 93%; hormonal therapy: 84%; radical prostatectomy: 79%). Erectile dysfunction with inability to perform sexual intercourse was reported by 32% of all patients who underwent percutaneous irradiation (brachytherapy: 21%; hormonal therapy: 63%; radical prostatectomy: 52%). No sexual problems at all were reported by 22% of patients who underwent percutaneous irradiation (brachytherapy: 21%; hormonal therapy: 13%; radical prostatectomy: 4%). With regard to psychological and physical deficits (fear; depression; urinary, bowel, erectile dysfunction; hormonal disorders), percutaneous irradiation was superior to the other treatment options (no deficits: percutaneous irradiation; 49%; brachytherapy: 36%; hormonal therapy: 17%; radical prostatectomy: 15%). CONCLUSION: Radiotherapy showed superior results regarding patient convenience and satisfaction in comparison to hormonal therapy and surgery in the treatment of patients with prostate cancer.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Braquiterapia , Satisfacción del Paciente , Prostatectomía , Neoplasias de la Próstata/terapia , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/psicología , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios
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