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1.
BMJ Open ; 13(11): e076715, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37989364

RESUMO

OBJECTIVE: Pembrolizumab is a programmed cell death protein-1 (PD-1) inhibitor used to treat advanced patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50. Further sub-division of TPS-based stratification has not been evaluated in the UK, although smoking-induced tumour mutational burden and the immunogenic effects of prior radiotherapy are suggested to improve response. AIMS: To investigate if PD-L1 TPS ≥80%, smoking status or radiotherapy before or within 2 months of treatment influenced progression-free survival (PFS) in patients with NSCLC treated with pembrolizumab monotherapy. METHODS: PD-L1 TPS, smoking status and radiotherapy exposure were compared in patients with NSCLC in National Health Service (NHS) Tayside (n=100) treated with pembrolizumab monotherapy between 1 November 2017 and 18 February 2022. Survival estimates were compared using log-rank analysis, and Cox proportional hazards analysis was used to investigate the influence of potential confounding factors, including tumour stage and performance status. RESULTS: PFS was not significantly different (log-rank HR=0.330, p=0.566) comparing patients with PD-L1 TPS 50-79% and PD-L1 TPS ≥80%. Smokers had significantly improved PFS (log-rank HR=4.867, p=0.027), while patients receiving radiotherapy had significantly decreased PFS (log-rank HR=6.649, p=0.012). A Cox regression model confirmed that both radiotherapy (p=0.022) and performance status (p=0.009) were independent negative predictors of PFS. CONCLUSIONS: More rigorous PD-L1 TPS stratification did not influence survival outcomes. Smoking history improved PFS, although it was not an independent response predictor, while radiotherapy and performance status independently influenced clinical response. We suggest that further stratification of PD-L1 TPS is not warranted, while performance status and radiotherapy treatment may be additional clinically useful biomarkers of response to pembrolizumab in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Antígeno B7-H1 , Estudos Retrospectivos , Medicina Estatal , Reino Unido
2.
Neurology ; 101(23): e2448-e2453, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37816633

RESUMO

OBJECTIVES: To examine the agreement between published reference resources for neurofilament light chain (NfL) applied to a large population of people with multiple sclerosis (MS). METHODS: Six published reference resources were used to classify NfL in participants in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network as elevated or normal and to derive age-specific NfL Z-scores. NfL values were classified as elevated if they exceeded the >95th percentile (i.e., Z-score >1.645) of the age-specific reference range. Furthermore, age-specific NfL Z-scores could be derived for 4 of 6 reference resources. RESULTS: NfL measurements were assessed from 12,855 visits of 6,687 people with MS (median 2 samples per individual [range 1-7]). The mean ± SD age was 47.1 ± 11.7 years, 72.1% of participants were female, disease duration was 15.0 ± 10.6 years, body mass index was 28.6 ± 6.9 kg/m2, and serum NfL was 12.87 ± 12.86 pg/mL. Depending on the selection of the reference resource, the proportion of NfL measurements classified as elevated varied from 3.7% to 30.9%. The kappa coefficient across the 6 reference resources used was 0.576 (95% CI 0.571-0.580) indicating moderate agreement. Spearman correlations between Z-scores derived from the various reference resources exceeded 0.90; however, concordance coefficients were lower, ranging from 0.72 to 0.89. DISCUSSION: Interpretation of blood NfL values may vary markedly depending on the selection of the reference resource. Borderline elevated values should be interpreted with caution, and future studies should focus on standardizing NfL measurement and reporting across laboratories/platforms, better characterizing the effects of confounding/influencing factors, and defining the performance of NfL (including as part of multimodal predictive algorithms) for prediction of disease-specific outcomes.


Assuntos
Esclerose Múltipla , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Esclerose Múltipla/diagnóstico , Filamentos Intermediários , Proteínas de Neurofilamentos , Biomarcadores
3.
BMJ Case Rep ; 16(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37857539

RESUMO

Posterior fossa ependymomas (PFEs) are designated histologically as low-grade neoplasms. Despite being characterised as benign, cases of metastasis have been reported only a few times with the patients concurrently diagnosed with the primary tumour. Interval drop metastasis or spontaneous second distal tumours are extremely rare and, in most cases, are diagnosed within a few months of primary tumour resection. Here, we report a patient with a grade 2 paediatric PFE exhibiting a 20-year interval to a second sacral ependymoma. The patient was initially diagnosed with a PFE at the age of 10 years and underwent tumour resection and postoperative radiotherapy. In their late 20s, the patient presented with basilar artery occlusion complicated by life-threatening epistaxis. Post-thrombolysis, the patient presented with a large sacral grade 1 myxopapillary ependymoma with cauda equina syndrome-like symptoms. Here, we present a rare case of two ependymomas with a 20-year interval in the same patient with compounding comorbidities.


Assuntos
Ependimoma , Neoplasias da Medula Espinal , Humanos , Criança , Ependimoma/diagnóstico , Ependimoma/cirurgia , Ependimoma/patologia , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Medula Espinal/complicações
4.
Ann Neurol ; 92(4): 688-698, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35730070

RESUMO

OBJECTIVE: To assess the effects of demographics, lifestyle factors, and comorbidities on serum neurofilament light chain (sNfL) levels in people without neurologic disease and establish demographic-specific reference ranges of sNfL. METHODS: The National Health and Nutrition Examination Survey (NHANES) is a representative sample of the US population in which detailed information on demographic, lifestyle, routine laboratory tests, and overall health status are systematically collected. From stored serum samples, we measured sNfL levels using a novel high-throughput immunoassay (Siemens Healthineers). We evaluated the predictive capacity of 52 demographic, lifestyle, comorbidity, anthropometric, or laboratory characteristics in explaining variability in sNfL levels. Predictive performance was assessed using cross-validated R2 (R2 cv ) and forward selection was used to obtain a set of best predictors of sNfL levels. Adjusted reference ranges were derived incorporating characteristics using generalized additive models for location, scale, and shape. RESULTS: We included 1,706 NHANES participants (average age: 43.6 ± 14.8 y; 50.6% male, 35% non-white) without neurological disorders. In univariate models, age explained the most variability in sNfL (R2 cv  = 26.8%). Multivariable prediction models for sNfL contained three covariates (in order of their selection): age, creatinine, and glycosylated hemoglobin (HbA1c) (standardized ß-age: 0.46, 95% confidence interval [CI]: 0.43, 0.50; creatinine: 0.18, 95% CI: 0.13, 0.22; HbA1c: 0.09, 95% CI: 0.06, 0.11). Adjusted centile curves were derived incorporating identified predictors. We provide an interactive R Shiny application to translate our findings and allow other investigators to use the derived centile curves. INTERPRETATION: Results will help to guide interpretation of sNfL levels as they relate to neurologic conditions. ANN NEUROL 2022;92:688-698.


Assuntos
Doenças do Sistema Nervoso , Proteínas de Neurofilamentos , Adulto , Biomarcadores , Creatinina , Feminino , Hemoglobinas Glicadas , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Proteínas de Neurofilamentos/sangue , Inquéritos Nutricionais
5.
Neurology ; 99(7): e688-e697, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35618438

RESUMO

BACKGROUND AND OBJECTIVES: Serum neurofilament light chain (sNfL) and optical coherence tomography (OCT)-derived retinal measures (including peripapillary retinal nerve fiber layer [pRNFL] and macular ganglion cell layer/inner plexiform layer [GCIPL] thickness) have been proposed as biomarkers of neurodegeneration in multiple sclerosis (MS). However, studies evaluating the associations between sNfL and OCT-derived retinal measures in MS are limited. METHODS: In this retrospective analysis of a longitudinal, observational, single-center cohort study, sNfL levels were measured in people with MS and healthy controls (HCs) using single molecule array. Participants with MS were followed with serial OCT for a median follow-up of 4.5 years. Eyes with optic neuritis (ON) within 6 months of baseline OCT or ON during follow-up were excluded. Age-normative cutoffs of sNfL were derived using the HC data, and MS participants with sNfL greater than the 97.5th percentile for age were classified as having elevated sNfL (sNfL-E). Analyses were performed with mixed-effects linear regression models and adjusted for age, sex, race, and history of ON. RESULTS: A total of 130 HCs (age: 42.4 ± 14.2 years; 62% female) and 403 people with MS (age: 43.1 ± 12.0 years; 78% female) were included. Elevated sNfL levels were present at baseline in 80 participants with MS (19.9%). At baseline, sNfL-E participants had modestly lower pRNFL (-3.03 ± 1.50 µm; p = 0.044) and GCIPL thickness (-2.74 ± 1.02 µm; p = 0.007). As compared with those with sNfL within the reference range, eyes from NfL-E participants exhibited faster longitudinal thinning of the pRNFL (45% faster; -0.74 vs -0.51 µm/y; p = 0.015) and GCIPL (25% faster; -0.35 vs -0.28 µm/y; p = 0.021). Significant differences in rates of pRNFL and GCIPL thinning between sNfL groups were found only in those with relapsing-remitting MS but not progressive MS. DISCUSSION: Elevated baseline sNfL is associated with accelerated rates of retinal neuroaxonal loss in relapsing-remitting MS, independent of overt ON, but may be less reflective of retinal neurodegeneration in progressive MS.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Neurite Óptica , Degeneração Retiniana , Adulto , Biomarcadores , Estudos de Coortes , Feminino , Humanos , Filamentos Intermediários , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/complicações , Fibras Nervosas , Neurite Óptica/complicações , Neurite Óptica/diagnóstico por imagem , Células Ganglionares da Retina , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
6.
Mult Scler Relat Disord ; 59: 103676, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35158190

RESUMO

Blood neurofilament light chain (NfL) has been reported to be a promising biomarker of neurological disease. NfL is predominantly measured in serum (sNfL), but there is a lack of reports regarding the effects of collection tubes on sNfL levels. We assessed sNfL levels using a novel immunoassay in 18 participants using 3 different types of serum collection tubes (no additive, with silica clot activator, and serum separator tubes). Variation observed in sNfL levels between samples from different collection tubes was similar to that observed in duplicate runs from the same tube. These findings support a lack of effect of type of serum collection tube on sNfL levels.


Assuntos
Filamentos Intermediários , Biomarcadores , Humanos
7.
Neurotherapeutics ; 18(3): 1834-1848, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34260042

RESUMO

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by demyelination, gliosis, and neurodegeneration. While the currently available disease-modifying therapies effectively suppress the immune attack on the CNS, there are no therapies to date that directly mitigate neurodegeneration. Glucagon-like peptide-1 (GLP-1) is a small peptide hormone that maintains glucose homeostasis. A novel GLP-1 receptor (GLP-1R) agonist, NLY01, was recently shown to have neuroprotective effects in the animal models of Parkinson's disease and is now in a phase 2 clinical trial. In this study, we investigated the therapeutic potential of NLY01 in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our data show that NLY01 delays the onset and attenuates the severity of EAE in a prevention paradigm, when given before disease onset. NLY01 inhibits the activation of immune cells in the spleen and reduces their trafficking into the CNS. In addition, we show that NLY01 suppresses the production of chemokines that are involved in leukocyte recruitment to the site of inflammation. The anti-inflammatory effect of NLY01 at the early stage of EAE may block the expression of the genes associated with neurotoxic astrocytes in the optic nerves, thereby preventing retinal ganglion cell (RGC) loss in the progressive stage of EAE. In the therapeutic paradigm, NLY01 significantly decreases the clinical score and second attack in a model of relapsing-remitting EAE. GLP-1R agonists may have dual efficacy in MS by suppressing peripheral and CNS inflammation, thereby limiting neuronal loss.


Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/imunologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/imunologia , Fármacos Neuroprotetores/uso terapêutico , Animais , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo
8.
J Clin Invest ; 130(7): 3467-3482, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32182223

RESUMO

Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. Bile acids are cholesterol metabolites that can signal through receptors on cells throughout the body, including in the CNS and the immune system. Whether bile acid metabolism is abnormal in MS is unknown. Using global and targeted metabolomic profiling, we identified lower levels of circulating bile acid metabolites in multiple cohorts of adult and pediatric patients with MS compared with controls. In white matter lesions from MS brain tissue, we noted the presence of bile acid receptors on immune and glial cells. To mechanistically examine the implications of lower levels of bile acids in MS, we studied the in vitro effects of an endogenous bile acid, tauroursodeoxycholic acid (TUDCA), on astrocyte and microglial polarization. TUDCA prevented neurotoxic (A1) polarization of astrocytes and proinflammatory polarization of microglia in a dose-dependent manner. TUDCA supplementation in experimental autoimmune encephalomyelitis reduced the severity of disease through its effects on G protein-coupled bile acid receptor 1 (GPBAR1). We demonstrate that bile acid metabolism was altered in MS and that bile acid supplementation prevented polarization of astrocytes and microglia to neurotoxic phenotypes and ameliorated neuropathology in an animal model of MS. These findings identify dysregulated bile acid metabolism as a potential therapeutic target in MS.


Assuntos
Astrócitos/metabolismo , Microglia/metabolismo , Esclerose Múltipla/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Ácido Tauroquenodesoxicólico , Animais , Astrócitos/patologia , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Microglia/patologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia , Ácido Tauroquenodesoxicólico/metabolismo , Ácido Tauroquenodesoxicólico/farmacologia
9.
Int J Dev Biol ; 63(11-12): 631-639, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32149373

RESUMO

Fibroblast growth factors (FGFs) comprise a family of signalling molecules with essential roles in early embryonic development across animal species. The role of FGFs in mesoderm formation and patterning in Xenopus has been particularly well studied. However, little is known about FGF16 in Xenopus. Using in situ hybridisation, we uncover the expression pattern of FGF16 during early Xenopus laevis development, which has not been previously described. We show that the zygotic expression of FGF16 is activated in the mesoderm of the early gastrula as a ring around the blastopore, with its first accumulation at the dorsal side of the embryo. Later, FGF16 expression is found in the otic vesicle, the branchial arches and the anterior pituitary, as well as in the chordal neural hinge region of the tailbud. In addition, we show that FGF16 can activate the MAPK pathway and expression of sp5 and sp5l. Like FGF16, sp5 is expressed in the otic vesicle and the branchial arches, with all three of these genes being expressed in the tailbud. These data provide evidence that FGF16 is present in the early mesoderm and can activate the expression of developmentally important transcription factors.


Assuntos
Fatores de Crescimento de Fibroblastos/genética , Fatores de Transcrição/genética , Proteínas de Xenopus/genética , Xenopus laevis/genética , Animais , Região Branquial/embriologia , Região Branquial/metabolismo , Embrião não Mamífero/embriologia , Embrião não Mamífero/metabolismo , Fatores de Crescimento de Fibroblastos/classificação , Gástrula/embriologia , Gástrula/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Hibridização In Situ , Sistema de Sinalização das MAP Quinases/genética , Mesoderma/embriologia , Mesoderma/metabolismo , Filogenia , Xenopus laevis/embriologia
10.
Int J Palliat Nurs ; 19(9): 433-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24071834

RESUMO

AIM: The aim of this preliminary study was to evaluate the feasibility of conducting an effectiveness trial of early access to palliative care services for people with lung cancer through use of an integrated outpatient model. METHODS: Newly diagnosed patients with lung cancer receiving palliative-intent treatment or best supportive care treatment were recruited over a 5-month period from one out-patient clinic in Scotland. Patients were offered a clinical review appointment with a palliative medicine consultant at two time points: baseline and 12 weeks later. Prior to each appointment patients completed three outcome measures addressing symptom severity, wellbeing, and health-care needs. One-to-one interviews were also conducted to explore patients' experiences of being involved in the study. RESULTS: Three patients participated in the study. The main reasons for low recruitment were patients' deteriorating condition and unwillingness to undertake extra hospital visits. However, qualitative data indicated that the participants found this extra layer of supportive care useful in identifying and managing their needs, as well as enabling future planning. CONCLUSION: Further testing is needed to ascertain the feasibility of conducting a trial of integrating early access to palliative care services into routine practice for people with lung cancer.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Neoplasias Pulmonares/enfermagem , Cuidados Paliativos , Ensaios Clínicos como Assunto , Estudos de Viabilidade , Feminino , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Entrevistas como Assunto , Neoplasias Pulmonares/psicologia , Masculino , Escócia
11.
Lung Cancer ; 77(1): 235-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22503285

RESUMO

Two patients with rare sites of metastatic pleural mesothelioma are presented and the literature on similar cases is examined. One patient developed colonic metastases from a sarcomatoid mesothelioma. Another patient with epithelioid mesothelioma developed perineal metastases.


Assuntos
Neoplasias do Colo/secundário , Mesotelioma/secundário , Neoplasias Pélvicas/secundário , Períneo/patologia , Neoplasias Pleurais/patologia , Idoso , Neoplasias do Colo/diagnóstico por imagem , Humanos , Masculino , Mesotelioma/diagnóstico por imagem , Pessoa de Meia-Idade , Neoplasias Pélvicas/diagnóstico por imagem , Períneo/diagnóstico por imagem , Neoplasias Pleurais/diagnóstico por imagem , Radiografia
12.
Cancer Treat Rev ; 36(8): 629-36, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20417037

RESUMO

HPV infection is associated with most squamous cell carcinomas (SCC) of the uterine cervix and many head and neck SCC. While recent understanding of the mechanisms of HPV-induced carcinogenesis has lead to the development of prophylactic vaccines, the principal modality of treatment is radiotherapy and despite concurrent chemotherapy, outcomes remain suboptimal. Improving the radiotherapeutic index thus remains an important challenge as well as defining predictive assays for treatment outcome of HPV-related tumours. Therefore elucidating the influence of the HPV virus on tumour radiosensitivity is of major interest due to the prevalence of HPV-related tumours worldwide and due to evidence that head and neck HPV-tumours have markedly different clinical outcomes compared to non-HPV-related tumours. This difference may allow for different treatment strategies to be developed. The present review aims to summarize the current understanding of radiosensitivity and HPV-related tumour biology in order to subsequently develop new approaches to enhance the therapeutic index. This review also emphasizes the relevance of E6 and E7 oncoproteins to tumour cell response to radiotherapy suggesting that specific targeted approaches such as concomitant modulation of additional pathways using targeted therapies should offer new therapeutic avenues.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/virologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/virologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Transformação Celular Neoplásica/patologia , Transformação Celular Neoplásica/efeitos da radiação , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Papillomaviridae/efeitos da radiação , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Lesões Pré-Cancerosas , Prognóstico , Tolerância a Radiação , Radiossensibilizantes/farmacologia , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
13.
Radiother Oncol ; 84(3): 307-13, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17692417

RESUMO

BACKGROUND AND PURPOSE: To control and account for bladder motion is a major challenge in radiotherapy (RT) of bladder cancer. This study investigates the relation between bladder volume variation and margins in conformal and image-guided RT (IGRT) for this disease. MATERIALS AND METHODS: The correlation between the relative bladder volume (RBV, defined as repeat scan volume/planning scan volume) and the margins required to account for internal motion was first studied using a series of 20 bladder cancer patients with weekly repeat CT scanning during treatment. Both conformal RT (CRT) and IGRT were simulated; in the latter translational movement of the bladder was accounted for by isocentre shifting. Further analysis of bladder volumes and margins was performed using a second series of eight patients with twice-weekly repeat CT scanning. In an attempt to control bladder volume variation these patients were given fluid intake restrictions on alternating weeks during treatment. RESULTS: IGRT gave the strongest correlation between the RBV and margin size (R(2)=0.75; p<0.001). Using IGRT, isotropic margins >10mm were required in only 1% of the situations when the RBV1, whereas isotropic margins >10mm were required in 55% of the situations when the RBV>1. Less marked correlation was found using CRT (R(2) in the range 0.43-0.53, p<0.001) for four different methods used to assess the margins required in the six directions, although a strong correlation was found for the superior margin (R(2)=0.63; p<0.001). Fluid intake restriction gave a small reduction in both bladder volume (average absolute volume reduced from 126 to 121cm(3); RBV from 0.83 to 0.80) and bladder volume variation, but not sufficient to translate into margin reduction. CONCLUSIONS: The study showed the potential for a large margin reduction in bladder RT if the bladder volume is controlled and this potential was even greater for IGRT. An attempt to control the bladder volume by restricting fluid intake prior to the treatment session failed to give any reduction in the margins required.


Assuntos
Neoplasias da Bexiga Urinária/radioterapia , Bexiga Urinária/anatomia & histologia , Humanos , Tamanho do Órgão , Planejamento da Radioterapia Assistida por Computador , Radioterapia Conformacional , Tomografia Computadorizada por Raios X , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/fisiologia
14.
Radiother Oncol ; 80(3): 349-54, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16930752

RESUMO

BACKGROUND AND PURPOSE: To account for internal organ motion and set-up uncertainties around organs at risk (OR) in radiotherapy (RT), the ICRU report no 62 introduced the planning organ at risk volume (PRV). In the present study, we have quantified PRV margins for the intestine, which is an important OR in pelvic RT. MATERIALS AND METHODS: The present study was based on intestine contours outlined in a total of 149 CT scans of 20 male bladder cancer patients (20 planning scans, 129 during treatment). From these data, we created location probability maps of the intestine for each patient. A commercial treatment planning system was used to add 3D isotropic intestine PRV margins (from 5 to 30 mm, in intervals of 5 mm) around the intestine planning outline. We then derived the fraction of patients for which a given PRV encompassed various degrees of intestine motion (85%, 90% and 95% of volumes with different probabilities of intestinal occupancy). As a measure of the specificity of the PRV, we also derived the fraction of the PRV containing volumes with zero probability of intestinal occupancy. RESULTS: Isotropic margins of up to 30 mm are required to account for all intestine motion in 90% of the patients, while isotropic margins of 5 - 10 mm will encompass 85 - 95% of the volumes having a probability of intestinal occupancy of > or = 75% in the same fraction of patients. Intestine PRVs are not very specific and will also include volumes where the intestine will rarely or never be located. CONCLUSIONS: Large intestinal motion was found, but isotropic PRV margins of 5-10 mm will include the major part of volumes with a large probability of intestinal occupancy in most patients.


Assuntos
Carcinoma de Células de Transição/radioterapia , Intestinos/fisiologia , Neoplasias Musculares/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Neoplasias Musculares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/diagnóstico por imagem
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