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1.
Support Care Cancer ; 32(1): 18, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38091116

RESUMEN

INTRODUCTION: Bones are frequent sites of metastatic disease, observed in 30-75% of advanced cancer patients. Quality of life (QoL) is an important endpoint in studies evaluating the treatments of bone metastases (BM), and many patient-reported outcome tools are available. The primary objective of this systematic review was to compile a list of QoL issues relevant to BM and its interventions. The secondary objective was to identify common tools used to assess QoL in patients with BM, and the QoL issues they fail to address. METHODS: A search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases between 1946 and 27 January 2023 with the keywords "bone metastases", "quality of life", and "patient reported outcomes". Specific QoL issues in original research studies and the QoL tools used were extracted. RESULTS: The review identified the QoL issues most prevalent to BM in the literature. Physical and functional issues observed in patients included pain, interference with ambulation and daily activities, and fatigue. Psychological symptoms, such as helplessness, depression, and anxiety were also common. These issues interfered with patients' relationships and social activities. Items not mentioned in existing QoL tools were related to newer treatments of BM, such as pain flare, flu-like symptoms, and jaw pain due to osteonecrosis. CONCLUSIONS: This systematic review highlights that QoL issues for patients with BM have expanded over time due to advances in BM-directed treatments. If they are relevant, additional treatment-related QoL issues identified need to be validated prospectively by patients and added to current assessment tools.


Asunto(s)
Neoplasias Óseas , Calidad de Vida , Humanos , Neoplasias Óseas/secundario , Emociones , Ansiedad/terapia , Dolor/etiología
2.
BMC Musculoskelet Disord ; 23(1): 1009, 2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36424582

RESUMEN

BACKGROUND: The primary goal of palliative treatment of spinal metastases is to maintain or improve health-related quality of life (HRQOL). We translated and validated a Dutch version of The Spine Oncology Study Group Outcome Questionnaire (SOSGOQ2.0), a valid and reliable 20-item questionnaire to evaluate HRQOL in patients with spinal metastases. METHODS: After cross-cultural translation and adaptation, the questionnaire was pre-tested in fifteen patients referred for spine surgery and/or radiotherapy. This resulted in a final questionnaire that was sent to patients for assessment of internal consistency, construct (i.e., convergent and divergent) validity, discriminative power and test-retest reliability. RESULTS: Overall, 147 patients (mean age 65.6 years, SD = 10.4) completed the questionnaire after a median time of 45.4 months (IQR = 18.9-72.9) after spine surgery and/or radiotherapy. Internal consistency was good for the Physical function, Pain, and Mental health domains (α = 0.87, 0.86, 0.72), but not for Social function (α = 0.04). Good convergent validity was demonstrated except for Social function (rs = 0.37 95%CI = 0.21-0.51). Discriminative power between patients with ECOG performance scores of 0-1 and 2-4 was found on all domains and Neurological function items. Test-retest reliability was acceptable for Physical function, Pain and Mental health (ICC = 0.89 95%CI = 0.81-0.94, ICC = 0.88 95%CI = 0.78-0.93, ICC = 0.68 95%CI = 0.48-0.81), whereas ICC = 0.45 (95%CI = 0.17-0.66) for Social function was below threshold. After removing item 20 from the Social function domain, internal consistency improved, and convergent validity and test-retest reliability were good. CONCLUSION: The Dutch version of the SOSGOQ2.0 questionnaire is a reliable and valid tool to measure HRQOL in patients with spinal metastases. Item 20 was removed to retain psychometric properties.


Asunto(s)
Calidad de Vida , Neoplasias de la Columna Vertebral , Humanos , Anciano , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Neoplasias de la Columna Vertebral/cirugía , Encuestas y Cuestionarios , Dolor
3.
J Cell Mol Med ; 22(5): 2826-2837, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29516637

RESUMEN

Neovascularization, increased basal membrane thickness and increased airway smooth muscle (ASM) bulk are hallmarks of airway remodelling in asthma. In this study, we examined connective tissue growth factor (CTGF) dysregulation in human lung tissue and animal models of allergic airway disease. Immunohistochemistry revealed that ASM cells from patients with severe asthma (A) exhibited high expression of CTGF, compared to mild and non-asthmatic (NA) tissues. This finding was replicated in a sheep model of allergic airways disease. In vitro, transforming growth factor (TGF)-ß increased CTGF expression both in NA- and A-ASM cells but the expression was higher in A-ASM at both the mRNA and protein level as assessed by PCR and Western blot. Transfection of CTGF promoter-luciferase reporter constructs into NA- and A-ASM cells indicated that no region of the CTGF promoter (-1500 to +200 bp) displayed enhanced activity in the presence of TGF-ß. However, in silico analysis of the CTGF promoter suggested that distant transcription factor binding sites may influence CTGF promoter activation by TGF-ß in ASM cells. The discord between promoter activity and mRNA expression was also explained, in part, by differential post-transcriptional regulation in A-ASM cells due to enhanced mRNA stability for CTGF. In patients, higher CTGF gene expression in bronchial biopsies was correlated with increased basement membrane thickness indicating that the enhanced CTGF expression in A-ASM may contribute to airway remodelling in asthma.


Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Asma/metabolismo , Asma/fisiopatología , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Pulmón/metabolismo , Pulmón/fisiopatología , Músculo Liso/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Asma/genética , Asma/patología , Emparejamiento Base/genética , Membrana Basal/metabolismo , Membrana Basal/patología , Factor de Crecimiento del Tejido Conjuntivo/genética , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Regiones Promotoras Genéticas/genética , Pyroglyphidae , Estabilidad del ARN/genética , Ovinos , Adulto Joven
4.
Oncologist ; 22(8): 972-978, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28469043

RESUMEN

BACKGROUND: A substantial number of patients with spinal metastases experience no treatment effect from palliative radiotherapy. Mechanical spinal instability, due to metastatic disease, could be associated with failed pain control following radiotherapy. This study investigates the relationship between the degree of spinal instability, as defined by the Spinal Instability Neoplastic Score (SINS), and response to radiotherapy in patients with symptomatic spinal metastases in a multi-institutional cohort. METHODS AND MATERIALS: The SINS of 155 patients with painful thoracic, lumbar, or lumbosacral metastases from two tertiary hospitals was calculated using images from radiotherapy planning CT scans. Patient-reported pain response, available for 124 patients, was prospectively assessed. Pain response was categorized, according to international guidelines, as complete, partial, indeterminate, or progression of pain. The association between SINS and pain response was estimated by multivariable logistic regression analysis, correcting for predetermined clinical variables. RESULTS: Of the 124 patients, 16 patients experienced a complete response and 65 patients experienced a partial response. Spinal Instability Neoplastic Score was associated with a complete pain response (adjusted odds-radio [ORadj] 0.78; 95% confidence interval [CI] 0.62-0.98), but not with an overall pain response (ORadj 0.94; 95% CI 0.81-1.10). CONCLUSIONS: A lower SINS, indicating spinal stability, is associated with a complete pain response to radiotherapy. This supports the hypothesis that pain resulting from mechanical spinal instability responds less well to radiotherapy compared with pain from local tumor activity. No association could be determined between SINS and an overall pain response, which might indicate that this referral tool is not yet optimal for prediction of treatment outcome. IMPLICATIONS FOR PRACTICE: Patients with stable painful spinal metastases, as indicated by a Spinal Instability Neoplastic Score (SINS) of 6 or lower, can effectively be treated with palliative external beam radiotherapy. The majority of patients with (impending) spinal instability, as indicated by a SINS score of 7 or higher, will achieve a (partial) response after palliative radiotherapy; however, some patients might require surgical intervention. Therefore, it is recommended to refer patients with a SINS score of 7 or higher to a spine surgeon to evaluate the need for surgical intervention.


Asunto(s)
Inestabilidad de la Articulación/radioterapia , Neoplasias/radioterapia , Neoplasias de la Columna Vertebral/radioterapia , Columna Vertebral/efectos de la radiación , Anciano , Enfermedades de la Médula Ósea , Dolor en Cáncer/fisiopatología , Femenino , Humanos , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/patología , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Cuidados Paliativos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/secundario , Columna Vertebral/patología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
6.
Oncologist ; 21(1): 95-101, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26668252

RESUMEN

BACKGROUND: Stable spinal metastases are effectively treated with radiotherapy, whereas unstable spinal metastases often need surgical fixation followed by radiotherapy for local control. The Spinal Instability Neoplastic Score (SINS) was developed as a tool to assess spinal neoplastic related instability with the goal of helping to guide referrals among oncology specialists. We compare the average degree of spinal instability between patients with spinal metastases referred for surgery or for radiotherapy and evaluate whether this difference changed after introduction of the SINS in clinical practice. METHODS: All patients with spinal metastases treated with palliative surgery or radiotherapy in the period 2009-2013 were identified in two spine centers. For all patients, the SINS was scored on pretreatment imaging. The SINS before and after introduction of the SINS in 2011 were compared within the surgical and radiotherapy group. Furthermore, the overall SINS was compared between the two groups. RESULTS: The overall SINS was significantly higher in the surgical group, with a mean SINS of 10.7 (median 11) versus 7.2 (median 8) for the radiotherapy group. The mean SINS decreased significantly for both groups after introduction of the SINS in clinical practice from 11.2 to 10.3 in the surgical group and from 8.4 to 7.2 in the radiotherapy group. CONCLUSION: The SINS differed significantly between patients treated with surgery or radiotherapy. The introduction of SINS led to a decrease in SINS score for both groups, suggesting that using SINS in metastatic spinal disease increases awareness for instability and may subsequently result in earlier referrals for surgical intervention. IMPLICATIONS FOR PRACTICE: Spinal metastases can present with varying degrees of mechanical instability. Because unstable spinal metastases may respond insufficiently to palliative radiotherapy and can lead to loss of ambulation, timely detection and appropriate referral are important. The Spinal Instability Neoplastic Score (SINS) may help physicians caring for patients with metastasized disease to identify spinal instability before the onset of neurological deficits. In this study, it was shown that the introduction of SINS in routine practice led to a decrease in spinal instability in radiotherapy and surgical cohorts. The use of SINS may increase awareness of instability and subsequently result in earlier referrals.


Asunto(s)
Inestabilidad de la Articulación/radioterapia , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/radioterapia , Columna Vertebral/patología , Adulto , Anciano , Femenino , Humanos , Inestabilidad de la Articulación/patología , Inestabilidad de la Articulación/cirugía , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Cuidados Paliativos , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/cirugía , Columna Vertebral/efectos de la radiación
7.
Epidemiology ; 27(3): 389-92, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27035689

RESUMEN

The "cohort multiple randomized controlled trial," a new design for pragmatic trials, embeds multiple trials within a cohort. The cohort multiple RCT is an attractive alternative to conventional RCTs in fields where recruitment is slow, multiple new (competing) interventions for the same condition have to be tested, new interventions are highly preferred by patients and doctors, and the risk of disappointment bias, cross-over, and contamination is considerable. To prevent these unwanted effects, the cohort multiple RCT provides information on randomization to the intervention group/arm only, and only after randomization (i.e., prerandomization). To some, especially in a clinical setting, this is not ethically acceptable. In this article, we argue that prerandomization in the cohort multiple randomized controlled trial (cmRCT) can be avoided by adopting a staged-informed consent procedure. In the first stage, at entry into the cohort, all potential participants are asked for their informed consent to participate in a cohort study and broad consent to be either randomly selected to be approached for experimental interventions or to serve as control without further notice during participation in the cohort. In a second stage, at the initiation of an RCT within the cohort, informed consent to receive the intervention is then only sought in those randomly selected for the intervention arm. At the third stage, after completion of each RCT, all cohort participants receive aggregate disclosure of trial results. This staged-informed consent procedure avoids prerandomization in cmRCT and aims to keep participants actively engaged in the research process.


Asunto(s)
Consentimiento Informado/ética , Ensayos Clínicos Pragmáticos como Asunto/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Estudios de Cohortes , Humanos , Ensayos Clínicos Pragmáticos como Asunto/ética , Ensayos Clínicos Controlados Aleatorios como Asunto/ética
8.
BMC Cancer ; 16(1): 909, 2016 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-27871280

RESUMEN

BACKGROUND: Standard radiotherapy is the treatment of first choice in patients with symptomatic spinal metastases, but is only moderately effective. Stereotactic body radiation therapy is increasingly used to treat spinal metastases, without randomized evidence of superiority over standard radiotherapy. The VERTICAL study aims to quantify the effect of stereotactic radiation therapy in patients with metastatic spinal disease. METHODS/DESIGN: This study follows the 'cohort multiple Randomized Controlled Trial' design. The VERTICAL study is conducted within the PRESENT cohort. In PRESENT, all patients with bone metastases referred for radiation therapy are enrolled. For each patient, clinical and patient-reported outcomes are captured at baseline and at regular intervals during follow-up. In addition, patients give informed consent to be offered experimental interventions. Within PRESENT, 110 patients are identified as a sub cohort of eligible patients (i.e. patients with unirradiated painful, mechanically stable spinal metastases who are able to undergo stereotactic radiation therapy). After a protocol amendment, also patients with non-spinal bony metastases are eligible. From the sub cohort, a random selection of patients is offered stereotactic radiation therapy (n = 55), which patients may accept or refuse. Only patients accepting stereotactic radiation therapy sign informed consent for the VERTICAL trial. Non-selected patients (n = 55) receive standard radiotherapy, and are not aware of them serving as controls. Primary endpoint is pain response after three months. Data will be analyzed by intention to treat, complemented by instrumental variable analysis in case of substantial refusal of the stereotactic radiation therapy in the intervention arm. DISCUSSION: This study is designed to quantify the treatment response after (stereotactic) radiation therapy in patients with symptomatic spinal metastases. This is the first randomized study in palliative care following the cohort multiple Randomized Controlled Trial design. This design addresses common difficulties associated with classic pragmatic randomized controlled trials, such as disappointment bias in patients allocated to the control arm, slow recruitment, and poor generalizability. TRIAL REGISTRATION: The Netherlands Trials Register number NL49316.041.14. ClinicalTrials.gov registration number NCT02364115 . Date of trial registration February 1, 2015.


Asunto(s)
Protocolos Clínicos , Radiocirugia , Radioterapia , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/terapia , Humanos , Radiocirugia/efectos adversos , Radiocirugia/métodos , Radioterapia/efectos adversos , Radioterapia/métodos , Proyectos de Investigación , Neoplasias de la Columna Vertebral/diagnóstico , Resultado del Tratamiento
9.
Respir Res ; 15: 98, 2014 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-25355286

RESUMEN

BACKGROUND: The low toxicity of perfluorocarbons (PFCs), their high affinity for respiratory gases and their compatibility with lung surfactant have made them useful candidates for treating respiratory diseases such as adult respiratory distress syndrome. We report results for treating acute allergic and non-allergic bronchoconstriction in sheep using S-1226 (a gas mixture containing carbon dioxide and small volumes of nebulized perflubron). The carbon dioxide, which is highly soluble in perflubron, was used to relax airway smooth muscle. METHODS: Sheep previously sensitized to house dust mite (HDM) were challenged with HDM aerosols to induce early asthmatic responses. At the maximal responses (characterised by an increase in lung resistance), the sheep were either not treated or treated with one of the following; nebulized S-1226 (perflubron + 12% CO2), nebulized perflubron + medical air, 12% CO2, salbutamol or medical air. Lung resistance was monitored for up to 20 minutes after cessation of treatment. RESULTS: Treatment with S-1226 for 2 minutes following HDM challenge resulted in a more rapid, more profound and more prolonged decline in lung resistance compared with the other treatment interventions. Video bronchoscopy showed an immediate and complete (within 5 seconds) re-opening of MCh-constricted airways following treatment with S-1226. CONCLUSIONS: S-1226 is a potent and rapid formulation for re-opening constricted airways. Its mechanism(s) of action are unknown. The formulation has potential as a rescue treatment for acute severe asthma.


Asunto(s)
Broncoconstricción/efectos de los fármacos , Broncodilatadores/administración & dosificación , Dióxido de Carbono/administración & dosificación , Fluorocarburos/administración & dosificación , Hipersensibilidad/tratamiento farmacológico , Pulmón/efectos de los fármacos , Administración por Inhalación , Resistencia de las Vías Respiratorias/efectos de los fármacos , Alérgenos , Animales , Broncodilatadores/química , Broncoscopía , Dióxido de Carbono/química , Modelos Animales de Enfermedad , Femenino , Fluorocarburos/química , Gases , Hidrocarburos Bromados , Hipersensibilidad/inmunología , Hipersensibilidad/fisiopatología , Proteínas de Insectos , Pulmón/inmunología , Pulmón/fisiopatología , Tamaño de la Partícula , Pyroglyphidae , Ovinos , Factores de Tiempo , Grabación en Video
10.
JAMA Netw Open ; 7(2): e2355409, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38345820

RESUMEN

Importance: Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The effectiveness of SBRT compared with cEBRT in pain relief has been a subject of debate, and conflicting results have been reported. Objective: To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain. Data Sources: A structured search was performed in the PubMed, Embase, and Cochrane databases on June 5, 2023. Additionally, results were added from a new randomized clinical trial (RCT) and additional unpublished data from an already published RCT. Study Selection: Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases. Data Extraction and Synthesis: Two independent reviewers extracted data from eligible studies. Data were extracted for the intention-to-treat (ITT) and per-protocol (PP) populations. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Overall and complete pain response at 1, 3, and 6 months after radiotherapy, according to the study's definition. Relative risk ratios (RRs) with 95% CIs were calculated for each study. A random-effects model using a restricted maximum likelihood estimator was applied for meta-analysis. Results: There were 18 studies with 1685 patients included in the systematic review and 8 RCTs with 1090 patients were included in the meta-analysis. In 7 RCTs, overall pain response was defined according to the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE). The complete pain response was reported in 6 RCTs, all defined according to the ICPRE. The ITT meta-analyses showed that the overall pain response rates did not differ between cEBRT and SBRT at 1 (RR, 1.14; 95% CI, 0.99-1.30), 3 (RR, 1.19; 95% CI, 0.96-1.47), or 6 (RR, 1.22; 95% CI, 0.96-1.54) months. However, SBRT was associated with a higher complete pain response at 1 (RR, 1.43; 95% CI, 1.02-2.01), 3 (RR, 1.80; 95% CI, 1.16-2.78), and 6 (RR, 2.47; 95% CI, 1.24-4.91) months after radiotherapy. The PP meta-analyses showed comparable results. Conclusions and Relevance: In this systematic review and meta-analysis, patients with painful bone metastases experienced similar overall pain response after SBRT compared with cEBRT. More patients had complete pain alleviation after SBRT, suggesting that selected subgroups will benefit from SBRT.


Asunto(s)
Neoplasias Óseas , Dolor en Cáncer , Radiocirugia , Humanos , Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Dolor/etiología , Dolor/radioterapia , Dolor en Cáncer/radioterapia , Manejo del Dolor , Respuesta Patológica Completa , Ensayos Clínicos Controlados Aleatorios como Asunto
11.
Respir Res ; 14: 123, 2013 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-24215602

RESUMEN

BACKGROUND: LysoTracker Green DND-26 is a fluorescent dye that stains acidic compartments in live cells and has been shown to selectively accumulate in lamellar bodies in alveolar type II (AT2) cells in the lung. The aim of this study was to determine whether the accumulation of LysoTracker in lamellar bodies can be used to isolate viable AT2 cells by flow cytometry and track their differentiation in live-cell culture by microscopy. METHODS: Mouse lung cells were sorted on the basis of CD45(neg)CD31(neg)EpCAM(pos)LysoTracker(pos) expression and characterized by immunostaining for SP-C and cultured in a three-dimensional epithelial colony-forming unit (CFU-Epi) assay. To track AT2 cell differentiation, lung epithelial stem and progenitor cells were cultured in a CFU-Epi assay with LysoTracker-supplemented media. RESULTS: The purity of sorted AT2 cells as determined by SP-C staining was 97.4% and viability was 85.3%. LysoTracker(pos) AT2 cells generated SP-C(pos) alveolar epithelial cell colonies in culture, and when added to the CFU-Epi culture medium, LysoTracker marked the differentiation of stem/progenitor-derived AT2 cells. CONCLUSIONS: This study describes a novel method for isolating AT2 cells from mouse lungs. The high purity and viability of cells attained by this method, makes them suitable for functional analysis in vitro. The application of LysoTracker to live cell cultures will allow better assessment of the cellular and molecular mechanisms that regulate AT2 cell differentiation.


Asunto(s)
Aminas , Diferenciación Celular , Citometría de Flujo/métodos , Colorantes Fluorescentes , Alveolos Pulmonares/citología , Animales , Supervivencia Celular , Células Cultivadas , Femenino , Técnicas In Vitro , Pulmón/citología , Ratones , Ratones Endogámicos C57BL , Modelos Animales
13.
Spine J ; 23(4): 571-578, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36623735

RESUMEN

BACKGROUND CONTEXT: Palliative radiotherapy (RT) can lead to remineralization of osteolytic lesions thereby potentially restoring some of the weight-bearing capacity and preventing vertebral collapse. It is not clear, however, under which circumstances remineralization of osteolytic lesions occurs. PURPOSE: The aim of this study was to investigate the change in bone mineral density in spinal metastases after RT compared to a reference region, and find associated factors. STUDY DESIGN: Retrospective analysis within prospective observational cohort OUTCOME MEASURES: change in bone mineral density measured in Hounsfield Units (HU). PATIENT SAMPLE: patients treated with RT for (painful) bone metastases. METHODS: Patients with spinal metastases were included if computed tomography scans both pre- and post-RT were available. Bone density was measured in HU. A region of interest (ROI) was drawn manually in the metastatic lesion. As a reference, a measurement of bone density in adjacent, unaffected, and non-irradiated vertebrae was used. Factors tested for association were origin of the primary tumor, RT dose and fractionation scheme, and concomitant use of bisphosphonates. RESULTS: A total of 31 patients with 49 spinal metastases, originating from various primary tumors, were included. The median age on baseline was 58 years (IQR: 53-63) and median time between baseline and follow-up scan was 8.2 months (IQR: 3.0-18.4). Difference in HU in the lesion before and after treatment was 146.9 HU (95% CI 68.4-225.4; p<.01). Difference in HU in the reference vertebra between baseline and first follow-up was 19.1 HU (95% CI -47.9 to 86.0; p=.58). Difference between reference vertebrae and metastatic lesions on baseline was -194.1 HU (95% CI -276.2 to -112.0; p<.01). After RT, this difference was reduced to -50.3 HU (95% CI -199.6 to 99.0; p=.52). Patients using bisphosphonates showed a greater increase in HU, 194.1 HU versus 60.6 HU, p=.01. CONCLUSIONS: Palliative radiation of osteolytic lytic spinal metastases is positively associated with an increased bone mineral density at follow-up. The use of bisphosphonates was linked to an increased bone mineral density when used during or after RT.


Asunto(s)
Neoplasias de la Columna Vertebral , Humanos , Preescolar , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/complicaciones , Estudios Retrospectivos , Densidad Ósea , Vértebras Lumbares/patología
14.
Ann Palliat Med ; 12(3): 620-632, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37081704

RESUMEN

BACKGROUND AND OBJECTIVE: The 30-day expected mortality rate is frequently used as a metric to determine which patients benefit from palliative radiation treatment (RT). We conducted a narrative review to examine whether its use as a metric might be appropriate for patient selection. METHODS: A literature review was conducted to identify relevant studies that highlight the benefits of palliative RT in timely symptom management among patients with a poor performance status, the accuracy of predicting survival near the end of life and ways to speed up the process of RT administration through rapid response clinics. KEY CONTENT AND FINDINGS: Several trials have demonstrated substantial response rates for pain and/or bleeding by four weeks and sometimes within the first two weeks after RT. Models of patient survival have limited accuracy, particularly for predicting whether patients will die within the next 30 days. Dedicated Rapid Access Palliative RT (RAPRT) clinics, in which patients are assessed, simulated and treated on the same day, reduce the number of patient visits to the radiation oncology department and hence the burden on the patient as well as costs. CONCLUSIONS: Single-fraction palliative RT should be offered to eligible patients if they are able to attend treatment and could potentially benefit from symptom palliation, irrespective of predicted life expectancy. We discourage the routine use of the 30-day mortality as the only metric to decide whether to offer RT. More common implementation of RAPRT clinics could result in a significant benefit for patients of all life expectancies, but particularly those having short ones.


Asunto(s)
Dolor , Cuidados Paliativos , Humanos , Dolor/radioterapia
15.
Radiother Oncol ; 189: 109914, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37739318

RESUMEN

INTRODUCTION: This study aimed to compare SBRT and cEBRT for treating spinal metastases through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, EMBASE and Cochrane Library were searched up to 6 May 2023 for RCTs comparing SBRT and cEBRT for spinal metastases. Overall and complete pain response, local progression, overall survival, quality of life and adverse events were extracted. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) for dichotomous outcomes, and hazard ratios (HRs) for time-to-event outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic. RESULTS: Three RCTs were identified involving 642 patients. No differences were seen in overall pain response comparing SBRT and cEBRT (RR at 3 months: 1.12, 95% CI, 0.74-1.70, p = 0.59; RR at 6 months: 1.29, 95% CI, 0.97-1.72, p = 0.08). Only two of three studies presented complete pain response data. SBRT demonstrated a statistically significant improvement in complete pain response compared to cEBRT (RR at 3 months: 2.52; 95% CI, 1.58-4.01; P < 0.0001; RR at 6 months: 2.48; 95% CI, 1.23-4.99; P = 0.01). There were no significant differences in local progression and overall survival. Adverse events were similar, except for any grade radiation dermatitis, which was significantly lower in SBRT arm (RR 0.17, 95% CI 0.03-0.96, P = 0.04). CONCLUSION: SBRT is a safe treatment option for spine metastases. It may provide better complete pain response compared to cEBRT. Additional trials are needed to determine the potential benefits of SBRT in specific patient subsets.


Asunto(s)
Radiocirugia , Neoplasias de la Columna Vertebral , Humanos , Radiocirugia/efectos adversos , Radiocirugia/métodos , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/secundario , Ensayos Clínicos Controlados Aleatorios como Asunto , Dolor/etiología
16.
Ann Palliat Med ; 12(6): 1318-1330, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37303218

RESUMEN

Radiotherapy is an important treatment modality for pain control in patients with bone metastases. Stereotactic body radiation therapy (SBRT), which allows delivering a much higher dose per fraction while sparing critical structures compared to conventional external beam radiotherapy (cEBRT), has become more widely used, especially in the oligometastatic setting. Randomized controlled trials (RCTs) comparing the pain response rate of SBRT and cEBRT for bone metastases have shown conflicting results, as have four recent systematic reviews with meta-analyses of these trials. Possible reasons for the different outcomes between these reviews include differences in methodology, which trials were included, and the endpoints examined and how they were defined. We suggest ways to improve analysis of these RCTs, particularly performing an individual patient-level meta-analysis since the trials included heterogeneous populations. The results of such studies will help guide future investigations needed to validate patient selection criteria, optimize SBRT dose schedules, include additional endpoints (such as the time to onset of pain response, durability of pain response, quality of life (QOL), and side effects of SBRT), and better assess the cost-effectiveness and trade-offs of SBRT compared to cEBRT. An international Delphi consensus to guide selection of optimal candidates for SBRT is warranted before more prospective data is available.


Asunto(s)
Neoplasias Óseas , Radiocirugia , Humanos , Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Dolor/etiología , Manejo del Dolor , Radiocirugia/métodos
17.
Exp Lung Res ; 38(6): 307-15, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22734813

RESUMEN

BACKGROUND: Increases in blood vessel density and vascular area are now recognized as important features of remodeled airways in asthma. However, the time sequence for these vascular changes and whether they resolve in the absence of continued antigenic exposure is not well elucidated. The aim of the present study was to correlate progressive changes in airway vascularity with changes in functional airway responses in sheep chronically challenged with house dust mite (HDM) allergen, and to examine the resolution of vascular remodeling following allergen withdrawal. METHODS: Progressive changes in vascular indices were examined in four spatially separate lung segments that received weekly challenges with HDM allergen for 0, 8, 16, or 24 weeks. Reversibility of these changes was assessed in a separate experiment in which two lung segments received 24 weeks of HDM challenges and either no rest or 12 weeks rest. Lung tissue was collected from each segment 7 days following the final challenge and vascular changes assessed by a morphometric analysis of airways immunohistochemically stained with an antibody against type IV collagen. RESULTS: Blood vessel density and percent airway vascularity were significantly increased in bronchi following 24 weeks of HDM challenges compared to untreated controls (P < .05), but not at any of the other time-points. There was no significant correlation between vascular indices and airway responses to allergic or nonspecific stimuli. The increase in blood vessel density induced by repeated allergen exposures did not return to baseline levels following a 12-week withdrawal period from allergen. CONCLUSIONS: Our results show for the first time that the airways of sheep chronically exposed to HDM allergen undergo vascular remodeling. These findings show the potential of this large animal model for investigating airway angiogenesis in asthma.


Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/inmunología , Asma/inmunología , Asma/patología , Vasos Sanguíneos/patología , Pulmón/inmunología , Pulmón/patología , Alérgenos/inmunología , Animales , Modelos Animales de Enfermedad , Femenino , Pyroglyphidae/inmunología , Ovinos
18.
Radiother Oncol ; 173: 240-253, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35688398

RESUMEN

This is the second part of the guidelines on the management of bone metastases. In the first part, the diagnosis and management of uncomplicated bone metastases have been addressed. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications. The most common symptoms include pain and neurologic deficits. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. Diffuse bone metastases may lead to hypercalcaemia that can be fatal if untreated. The growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment if oligometastatic or systemic treatment for diffuse bone metastases to try to avoid the development of SRE.


Asunto(s)
Neoplasias Óseas , Fracturas Espontáneas , Compresión de la Médula Espinal , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/radioterapia , Fracturas Espontáneas/etiología , Fracturas Espontáneas/radioterapia , Humanos , Dolor/etiología , Calidad de Vida , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/radioterapia
19.
Radiother Oncol ; 173: 197-206, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35661676

RESUMEN

After liver and lungs, bone is the third most common metastatic site (Nystrom et al., 1977). Almost all malignancies can metastasize to the skeleton but 80% of bone metastases originate from breast, prostate, lung, kidney and thyroid cancer (Mundy, 2002). Introduction of effective systemic treatment in many cancers has prolonged patients' survival, including those with bone metastases. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications, such as pain and neurologic compromise. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. In turn, growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment avoiding development of SRE. The treatment for bone metastases should focus on relieving existing symptoms and preventing new ones. Radiotherapy is the standard of care for patients with symptomatic bone metastases, providing durable pain relief with minimal toxicity and reasonable cost-effectiveness. Historically, the dose was prescribed in one to five fractions and delivered using simple planning techniques. While 3D-conformal radiotherapy is still widely used for treating bone metastases, introduction of highlyconformal radiotherapy techniques such as stereotactic body radiotherapy (SBRT) have opened new therapeutic possibilities that should be considered in selected patients with bone metastases.


Asunto(s)
Neoplasias Óseas , Fracturas Espontáneas , Radiocirugia , Neoplasias Óseas/secundario , Fracturas Espontáneas/etiología , Fracturas Espontáneas/radioterapia , Humanos , Masculino , Dolor/etiología , Calidad de Vida , Radiocirugia/métodos
20.
Radiother Oncol ; 171: 182-188, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35489444

RESUMEN

BACKGROUND AND PURPOSE: Magnetic resonance (MR)-guided linear accelerators (MR-Linac) enable accurate estimation of delivered doses through dose accumulation using daily MR images and treatment plans. We aimed to assess the association between the accumulated bladder (wall) dose and patient-reported acute urinary toxicity in prostate cancer (PCa) patients treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: One-hundred-and-thirty PCa patients treated on a 1.5 T MR-Linac were included. Patients filled out International Prostate Symptom Scores (IPSS) questionnaires at baseline, 1 month, and 3 months post-treatment. Deformable image registration-based dose accumulation was performed to reconstruct the delivered dose. Dose parameters for both bladder and bladder wall were correlated with a clinically relevant increase in IPSS (≥ 10 points) and/or start of alpha-blockers within 3 months using logistic regression. RESULTS: Thirty-nine patients (30%) experienced a clinically relevant IPSS increase and/or started with alpha-blockers. Bladder D5cm3, V10-35Gy (in %), and Dmean and Bladder wall V10-35Gy (cm3 and %) and Dmean were correlated with the outcome (odds ratios 1.04-1.33, p-values 0.001-0.044). Corrected for baseline characteristics, bladder V10-35Gy (in %) and Dmean and bladder wall V10-35Gy (cm3 and %) and Dmean were still correlated with the outcome (odds ratios 1.04-1.30, p-values 0.001-0.028). Bladder wall parameters generally showed larger AUC values. CONCLUSION: This is the first study to assess the correlation between accumulated bladder wall dose and patient-reported urinary toxicity in PCa patients treated with MR-guided SBRT. The dose to the bladder wall is a promising parameter for prediction of patient-reported urinary toxicity and therefore warrants prospective validation and consideration in treatment planning.


Asunto(s)
Neoplasias de la Próstata , Radiocirugia , Radioterapia Guiada por Imagen , Humanos , Masculino , Medición de Resultados Informados por el Paciente , Neoplasias de la Próstata/patología , Radiocirugia/efectos adversos , Radiocirugia/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia Guiada por Imagen/efectos adversos , Radioterapia Guiada por Imagen/métodos , Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/patología
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