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This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often > 2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections.
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PURPOSE: This systematic review provides an overview of literature on the impact of magnetic resonance-guided radiation therapy (MRgRT) on patient-reported outcomes (PROs) in patients with prostate cancer (PC). METHODS AND MATERIALS: A systematic search was performed in October 2023 in PubMed, EMBASE, and Cochrane Library. The Patient, Intervention, Comparison, Outcomes, and Study design (PICOS) framework was used to determine eligibility criteria. Included were studies assessing PROs following MRgRT for PC with a sample size >10. Methodological quality was assessed using the Cochrane's Risk of Bias in Nonrandomized Studies - of Interventions and Cochrane's risk of bias tool for randomized trials. Relevant mean differences (MDs) compared with pre-RT were interpreted using minimal important differences. Meta-analyses were performed using random-effects models. Between-study heterogeneity was assessed using the I2 statistic. RESULTS: Eleven observational studies and 1 randomized controlled trial (nâ¯=â¯897) were included. Nine studies included patients with primary PC with MRgRT as first-line treatment (nâ¯=â¯813) and 3 with MRgRT as second-line treatment (nâ¯=â¯84). Substantial risk of bias was found in 5 studies. European Organization for Research and Treatment Quality of Life Questionnaire (EORTC QLQ) core 30 (C30) and EORTC QLQ prostate cancer module (PR25) scores were pooled from 3 studies, and Expanded Prostate Cancer Index Composite (EPIC)-26 scores were pooled from 4 studies. Relevant MDs for the urinary domain were found with the EPIC-26 (MD, -10.0; 95% CI, -12.0 to -8.1; I2â¯=â¯0%) and the EORTC QLQ-PR25 (MD, 8.6; 95% CI, -4.7 to 22.0; I2â¯=â¯97%), both at end-RT to 1-month follow-up. Relevant MDs for the bowel domain were found with the EPIC-26 (MD, -4.7; 95% CI, -9.2 to -0.2; I2â¯=â¯82%) at end-RT or 1-month follow-up, but not with the EORTC QLQ-PR25. For both domains, no relevant MDs were found after 3 months of follow-up. No relevant MDs were found in the general quality of life domains of the EORTC QLQ C30. CONCLUSIONS: MRgRT for PC results in a temporary worsening of patient-reported urinary and bowel symptoms during the first month after treatment compared with pre-RT, resolving at 3 months. No clinically relevant changes were found for general quality of life domains. These results provide important information for patient counseling and can serve as a benchmark for future studies.
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Medición de Resultados Informados por el Paciente , Neoplasias de la Próstata , Calidad de Vida , Radioterapia Guiada por Imagen , Humanos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Masculino , Radioterapia Guiada por Imagen/métodos , Imagen por Resonancia Magnética , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
This work reports on the first seven patients treated with gating and baseline drift correction on the high-field MR-Linac system. Dosimetric analysis showed that the active motion management system improved congruence to the planned dose, efficiently mitigating detrimental effects of intrafraction motion in the upper abdomen.
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Neoplasias Abdominales , Radioterapia de Intensidad Modulada , Humanos , Movimiento , Movimiento (Física) , Radiometría , Neoplasias Abdominales/radioterapia , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
The shape of a word pronunciation time distribution supplies information about the dynamic interactions that support reading performance. Speeded word-naming pronunciation and response time distributions were collected from 20 sixth grade Dutch students with dyslexia and 23 age-matched controls. The participants' pronunciation times were modeled and contrasted with a lognormal inverse power-law mixture distribution. Identical contrasts were also conducted on the same participants' response time distributions derived from flanker, color-naming, and arithmetic tasks. Results indicated that children with dyslexia yield slower, broader, and more variable pronunciation time distributions than their age-matched counterparts. This difference approximated a self-similar rescaling between the two group's aggregate pronunciation time distributions. Moreover, children with dyslexia produced similar, but less prominent trends toward slower and more variable performance across the three non-reading tasks. The outcomes support a proportional continuum rather than a localized deficit account of dyslexia. The mixture distribution's success at describing the participants' pronunciation and response time distributions suggests that differences in proportional contingencies among low-level neurophysiological, perceptual, and cognitive processes likely play a prominent role in the etiology of dyslexia.
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Dislexia/fisiopatología , Lectura , Adolescente , Niño , Femenino , Humanos , Pruebas del Lenguaje/estadística & datos numéricos , Masculino , Países Bajos , Fonética , Tiempo de Reacción/fisiologíaRESUMEN
The recognition and neutralization of tumour cells is one of the big challenges in immunity. The immune system has to recognize syngeneic tumour cells and has to be primed and respond in an adequate manner. Priming of a leukaemia-specific immune response is a crucial step in tumour immunology that can mislead to tumour tolerance either by T cell ignorance, deletion or Treg induction. To resemble the situation of acute lymphoblastic leukaemia (ALL) in patients, we used the murine BALB/c model with syngeneic BM185 tumour cells. We established a tumour cell line that expresses the neo-antigen ovalbumin (BM185-OVA/GFP) to allow the application of T cell receptor transgenic, antigen-specific CD4(+) T cells. Here, we demonstrate that effective anti-ALL immunity can be established by in vivo priming of CD4(+) T cells that is sufficient to differentiate into effector cells. Yet they failed to control tumour alone, but initiated a Th1 response. An efficient tumour clearance was dependent on both antigen-specific CD4(+) T cells and CD8(+) effector T cells from the endogenous repertoire. The tolerogeneic milieu was characterized by increased Tregs numbers and elevated IL-10 level. Tregs hamper effective antitumour immune response, but their depletion did not result in reduced tumour growth. In contrast, neutralization of IL-10 improved median mouse survival. Future therapies should focus on establishing a strong CD4+ T cells response, either by adjuvant or by adoptive transfer.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/trasplante , Inmunoterapia Adoptiva/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Animales , Células de la Médula Ósea/inmunología , Linfocitos T CD4-Positivos/metabolismo , Línea Celular Tumoral , Células Cultivadas , Células Dendríticas/inmunología , Femenino , Citometría de Flujo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/inmunología , Interferón gamma/sangre , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-10/sangre , Interleucina-10/inmunología , Interleucina-10/metabolismo , Interleucina-12/sangre , Interleucina-12/inmunología , Interleucina-12/metabolismo , Interleucina-2/sangre , Interleucina-2/inmunología , Interleucina-2/metabolismo , Estimación de Kaplan-Meier , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones SCID , Ovalbúmina/genética , Ovalbúmina/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Factores de TiempoRESUMEN
Natural killer (NK) cells contribute to immunity as the first line of defence in numerous infections by early cytokine secretion and cytotoxicity. In Leishmania infection, NK cells contribute with interferon-gamma and may assist in directing the immune response towards T helper type 1, which is essential for successful control of the parasites. Thus, NK cells may play an important role in both resistance and control of the infection. However, during Leishmania infection NK cells show signs of suppression. To explore the reason for this suppression, we exposed naive and interleukin (IL)-2 activated NK cells directly to promastigotes of Leishmania major in vitro. As a rapid consequence of contact between naive NK cells and promastigotes, expression of NK cell receptors show significant changes. We identify one of the major surface molecules of promastigotes, glycoprotein (gp) 63, as an important agent for these suppressive effects by using promastigotes of a gp63ko strain of L. major. Furthermore, proliferation of IL-2-activated purified NK cells is suppressed after exposure to the wild-type but not to gp63ko promastigotes. However, gp63ko L. major induced no NK cell proliferation when NK cells were co-cultured with peripheral blood mononuclear cells populations such as CD14(+) monocytes or T cells.
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Antígenos de Protozoos/inmunología , Células Asesinas Naturales/inmunología , Leishmania major , Leishmaniasis Cutánea/inmunología , Metaloendopeptidasas/inmunología , Adulto , Animales , Estudios de Casos y Controles , Proliferación Celular , Pruebas Inmunológicas de Citotoxicidad , Citometría de Flujo , Humanos , Interferón gamma/análisis , Interleucina-2/inmunología , Activación de Linfocitos , Masculino , Unión ProteicaRESUMEN
The protozoan parasite Trypanosoma cruzi circulates in the blood as trypomastigotes and invades a variety of cells to multiply intracellularly as amastigotes. The acute phase triggers an immune response that restricts the proliferation of the parasite. However, parasites are able to persist in different tissues causing the pathology of Chagas' disease. Natural killer (NK) cells play an important role in innate resistance to a variety of pathogens. In the present study we demonstrate that NK cells trigger trypanocidal mechanisms in infected L929 cells that are critically dependent on inducible nitric oxide (NO) synthase (iNOS) induction which is, to a major degree, triggered by interferon (IFN)-gamma provided by NK cells. This work provides a more detailed analysis of how NK cells as a part of the innate immune system participate in the control of parasites that reside intracellularly in fibroblast-like L929 cells.