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1.
Transfusion ; 62(5): 1010-1018, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35442519

RESUMEN

BACKGROUND: Transfusion carries a risk of transfusion reaction that is often underdiagnosed due to reliance on passive reporting. The study investigated the utility of digital methods to identify potential transfusion reactions, thus allowing real-time intervention for affected patients. METHOD: The hemovigilance unit monitored 3856 patients receiving 43,515 transfusions under the hemovigilance program. Retrospective comparison data included 298,498 transfusions. Transfusion medicine physicians designed and validated algorithms in the electronic health record that analyze discrete data, such as vital sign changes, to assign a risk score during each transfusion. Dedicated hemovigilance nurses remotely monitor all patients and perform real-time chart reviews prioritized by risk score. When a reaction is suspected, a hemovigilance trained licensed clinician responds to manage the patient and ensure data collection. Board-certified transfusion medicine physicians reviewed data and classified transfusion reactions under various categories according to the Centers for Disease Control hemovigilance definitions. RESULTS: Transfusion medicine physicians diagnosed 564 transfusion reactions (1.3% of transfusions)-a 524% increase compared to the previous passive reporting. The rapid response provider reached the bedside on average at 12.4 min demonstrating logistic feasibility. While febrile reactions were most diagnosed, recognition of transfusion-associated circulatory overload demonstrated the greatest relative increase. Auditing and education programs further enhanced transfusion reaction awareness. DISCUSSION: The model of digitally-enabled expert real-time review of clinical data that prompts rapid response improved recognition of transfusion reactions. This approach could be applied to other patient deterioration events such as early identification of sepsis.


Asunto(s)
Seguridad de la Sangre , Reacción a la Transfusión , Transfusión Sanguínea , Fiebre , Humanos , Estudios Retrospectivos
2.
Nanomedicine ; 32: 102327, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33220507

RESUMEN

This study evaluates a long-acting liposomal fluorescence / CT dual-modality contrast agent (CF800) in head and neck cancer to enhance intraoperative tumor demarcation with fluorescence imaging and cone-beam computed tomography (CBCT). CF800 was administered to 12 buccal cancer-bearing rabbits. Imaging was acquired at regular time points to quantify time-dependent contrast enhancement. Surgery was performed 5-7 days after, with intraoperative near-infrared fluorescence endoscopy and CBCT, followed by histological and ex-vivo fluorescence assessment. Tumor enhancement on CT was significant at 24, 96 and 120 hours. Volumetric analysis of tumor segmentation showed high correlation between CBCT and micro-CT. Fluorescence signal was apparent in both ex-vivo and in-vivo imaging. Histological correlation showed [100%] specificity for primary tumor. Sensitivity and specificity of CF800 in detecting nodal involvement require further investigation.CF800 is long acting and has dual function for CT and fluorescence contrast, making it an excellent candidate for image-guided surgery.


Asunto(s)
Medios de Contraste/química , Neoplasias de Cabeza y Cuello/cirugía , Imagen Óptica , Cirugía Asistida por Computador , Tomografía Computarizada por Rayos X , Animales , Biomarcadores de Tumor/metabolismo , Tomografía Computarizada de Haz Cónico , Fluorescencia , Neoplasias de Cabeza y Cuello/patología , Inyecciones , Liposomas/administración & dosificación , Liposomas/farmacocinética , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Conejos , Microtomografía por Rayos X
3.
Lancet Oncol ; 20(7): 915-923, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31151906

RESUMEN

BACKGROUND: Radiotherapy is standard of care for cervical cancer, but major global gaps in access exist, particularly in low-income and middle-income countries. We modelled the health and economic benefits of a 20-year radiotherapy scale-up to estimate the long-term demand for treatment in the context of human papillomavirus (HPV) vaccination. METHODS: We applied the Global Task Force on Radiotherapy for Cancer Control investment framework to model the health and economic benefits of scaling up external-beam radiotherapy and brachytherapy for cervical cancer in upper-middle-income, lower-middle-income, and low-income countries between 2015 and 2035. We estimated the unique costs of external-beam radiotherapy and brachytherapy and included a specific valuation of women's caregiving contributions. Model outcomes life-years gained and the human capital and full income net present value of investment. We estimated the effects of stage at diagnosis, radiotherapy delivery system, and simultaneous HPV vaccination (75% coverage) up to a time horizon set at 2072. FINDINGS: For the period from 2015 to 2035, we estimated that 9·4 million women in low-income and middle-income countries required treatment with external-beam radiotherapy, of which 7·0 million also required treatment with brachytherapy. Incremental scale-up of radiotherapy in these countries from 2015 to meet optimal radiotherapy demand by 2035 yielded 11·4 million life-years gained, $59·3 billion in human capital net present value (-$1·5 billion in low-income, $19·9 billion in lower-middle-income, and $40·9 billion in upper-middle-income countries), and $151·5 billion in full income net present value ($1·5 billion in low-income countries, $53·6 billion in lower-middle-income countries, and $96·4 billion in upper-middle-income countries). Benefits increased with advanced stage of cervical cancer and more efficient scale up of radiotherapy. Bivalent HPV vaccination of 12-year-old girls resulted in a 3·9% reduction in incident cases from 2015-2035. By 2072, when the first vaccinated cohort of girls reaches 70 years of age, vaccination yielded a 22·9% reduction in cervical cancer incidence, with 38·4 million requiring external-beam radiotherapy and 28·8 million requiring brachytherapy. INTERPRETATION: Effective cervical cancer control requires a comprehensive strategy. Even with HPV vaccination, radiotherapy treatment scale-up remains essential and produces large health benefits and a strong return on investment to countries at different levels of development. FUNDING: None.


Asunto(s)
Costos de la Atención en Salud , Necesidades y Demandas de Servicios de Salud , Modelos Económicos , Infecciones por Papillomavirus/economía , Infecciones por Papillomavirus/radioterapia , Neoplasias del Cuello Uterino/economía , Neoplasias del Cuello Uterino/radioterapia , Anciano , Niño , Países en Desarrollo , Femenino , Humanos , Renta , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus , Pobreza , Radioterapia/economía , Radioterapia/estadística & datos numéricos , Neoplasias del Cuello Uterino/virología
5.
Lancet ; 387(10033): 2133-2144, 2016 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-26578033

RESUMEN

Investments in cancer control--prevention, detection, diagnosis, surgery, other treatment, and palliative care--are increasingly needed in low-income and particularly in middle-income countries, where most of the world's cancer deaths occur without treatment or palliation. To help countries expand locally appropriate services, Cancer (the third volume of nine in Disease Control Priorities, 3rd edition) developed an essential package of potentially cost-effective measures for countries to consider and adapt. Interventions included in the package are: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioids. These interventions would cost an additional US$20 billion per year worldwide, constituting 3% of total public spending on health in low-income and middle-income countries. With implementation of an appropriately tailored package, most countries could substantially reduce suffering and premature death from cancer before 2030, with even greater improvements in later decades.


Asunto(s)
Atención a la Salud/economía , Salud Global/economía , Neoplasias/economía , Países en Desarrollo/estadística & datos numéricos , Salud Global/estadística & datos numéricos , Humanos , Renta , Neoplasias/diagnóstico , Neoplasias/mortalidad , Neoplasias/terapia
6.
Nanotechnology ; 28(15): 155704, 2017 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-28211793

RESUMEN

Field emission (FE) uniformity and the mechanism of emitter failure of freestanding carbon nanotube (CNT) arrays have not been well studied due to the difficulty of observing and quantifying FE performance of each emitter in CNT arrays. Herein a field emission microscopy (FEM) method based on poly(methyl methacrylate) (PMMA) thin film is proposed to study the FE uniformity and CNT emitter failure of freestanding CNT arrays. FE uniformity of freestanding CNT arrays and different levels of FE current contributions from each emitter in the arrays are recorded and visualized. FEM patterns on the PMMA thin film contain the details of the CNT emitter tip shape and whether multiple CNT emitters occur at an emission site. Observation of real-time FE performance and the CNT emitter failure process in freestanding CNT arrays are successfully achieved using a microscopic camera. High emission currents through CNT emitters causes Joule heating and light emission followed by an explosion of the CNTs. The proposed approach is capable of resolving the major challenge of building the relationship between FE performance and CNT morphologies, which can significantly facilitate the study of FE non-uniformity, the emitter failure mechanism and the development of stable and reliable FE devices in practical applications.

8.
Lancet Oncol ; 16(10): 1153-86, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26419354

RESUMEN

Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015-35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015-35 is US$26·6 billion in low-income countries, $62·6 billion in lower-middle-income countries, and $94·8 billion in upper-middle-income countries, which amounts to $184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14·1 billion in low-income, $33·3 billion in lower-middle-income, and $49·4 billion in upper-middle-income countries-a total of $96·8 billion. Scale-up of radiotherapy capacity in 2015-35 from current levels could lead to saving of 26·9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278·1 billion in 2015-35 ($265·2 million in low-income countries, $38·5 billion in lower-middle-income countries, and $239·3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365·4 billion ($12·8 billion in low-income countries, $67·7 billion in lower-middle-income countries, and $284·7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16·9 billion in 2015-35 (-$14·9 billion in low-income countries; -$18·7 billion in lower-middle-income countries, and $50·5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104·2 billion (-$2·4 billion in low-income countries, $10·7 billion in lower-middle-income countries, and $95·9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits.


Asunto(s)
Países en Desarrollo/economía , Salud Global/economía , Costos de la Atención en Salud , Accesibilidad a los Servicios de Salud/economía , Disparidades en Atención de Salud/economía , Programas Nacionales de Salud/economía , Neoplasias/economía , Neoplasias/radioterapia , Análisis Costo-Beneficio , Difusión de Innovaciones , Predicción , Salud Global/tendencias , Costos de la Atención en Salud/tendencias , Accesibilidad a los Servicios de Salud/tendencias , Disparidades en Atención de Salud/tendencias , Humanos , Modelos Económicos , Programas Nacionales de Salud/tendencias , Neoplasias/diagnóstico , Neoplasias/mortalidad , Radioterapia/economía , Factores Socioeconómicos , Factores de Tiempo , Resultado del Tratamiento
9.
Anal Chem ; 87(15): 7683-9, 2015 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-26138213

RESUMEN

Mapping intratumoral heterogeneity such as vasculature and margins is important during intraoperative applications. Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated potential for intraoperative tumor imaging using validated MS profiles. The clinical translation of DESI-MS into a universal label-free imaging technique thus requires access to MS profiles characteristic to tumors and healthy tissues. Here, we developed contrast agent mass spectrometry imaging (CA-MSI) that utilizes a magnetic resonance imaging (MRI) contrast agent targeted to disease sites, as a label, to reveal tumor heterogeneity in the absence of known MS profiles. Human breast cancer tumors grown in mice were subjected to CA-MSI using Gadoteridol revealing tumor margins and vasculature from the localization of [Gadoteridol+K](+) and [Gadoteridol+Na](+) adducts, respectively. The localization of the [Gadoteridol+K](+) adduct as revealed through DESI-MS complements the in vivo MRI results. DESI-MS imaging is therefore possible for tumors for which no characteristic MS profiles are established. Further DESI-MS imaging of the flux of the contrast agent through mouse kidneys was performed indicating secretion of the intact label.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Medios de Contraste , Espectrometría de Masa por Ionización de Electrospray , Animales , Neoplasias de la Mama/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Ratones
10.
Radiology ; 274(1): 181-91, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25203127

RESUMEN

PURPOSE: To determine if the integration of diagnostic magnetic resonance (MR) imaging and MR-guided biopsy would improve target delineation for focal salvage therapy in men with prostate cancer. MATERIALS AND METHODS: Between September 2008 and March 2011, 30 men with biochemical failure after radiation therapy for prostate cancer provided written informed consent and were enrolled in a prospective clinical trial approved by the institutional research ethics board. An integrated diagnostic MR imaging and interventional biopsy procedure was performed with a 1.5-T MR imager by using a prototype table and stereotactic transperineal template. Multiparametric MR imaging (T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted sequences) was followed by targeted biopsy of suspicious regions and systematic sextant sampling. Biopsy needle locations were imaged and registered to diagnostic images. Two observers blinded to clinical data and the results of prior imaging studies delineated tumor boundaries. Area under the receiver operating characteristic curve (Az) was calculated based on generalized linear models by using biopsy as the reference standard to distinguish benign from malignant lesions. RESULTS: Twenty-eight patients were analyzed. Most patients (n = 22) had local recurrence, with 82% (18 of 22) having unifocal disease. When multiparametric volumes from two observers were combined, it increased the apparent overall tumor volume by 30%; however, volumes remained small (mean, 2.9 mL; range, 0.5-8.3 mL). Tumor target boundaries differed between T2-weighted, dynamic contrast-enhanced, and diffusion-weighted sequences (mean Dice coefficient, 0.13-0.35). Diagnostic accuracy in the identification of tumors improved with a multiparametric approach versus a strictly T2-weighted or dynamic contrast-enhanced approach through an improvement in sensitivity (observer 1, 0.65 vs 0.35 and 0.44, respectively; observer 2, 0.82 vs 0.64 and 0.53, respectively; P < .05) and improved further with a 5-mm expansion margin (Az = 0.85 vs 0.91 for observer 2). After excluding three patients with fewer than six informative biopsy cores and six patients with inadequately stained margins, MR-guided biopsy enabled more accurate delineation of the tumor target volume be means of exclusion of false-positive results in 26% (five of 19 patients), false-negative results in 11% (two of 19 patients) and by guiding extension of tumor boundaries in 16% (three of 19 patients). CONCLUSION: The integration of guided biopsy with diagnostic MR imaging is feasible and alters delineation of the tumor target boundary in a substantial proportion of patients considering focal salvage.


Asunto(s)
Biopsia Guiada por Imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Anciano , Anciano de 80 o más Años , Humanos , Interpretación de Imagen Asistida por Computador , Esperanza de Vida , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Planificación de Atención al Paciente , Valor Predictivo de las Pruebas , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/cirugía , Factores de Riesgo , Terapia Recuperativa , Sensibilidad y Especificidad
11.
Nanomedicine ; 11(1): 155-65, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25200610

RESUMEN

Effective drug delivery to tumors is a barrier to treatment with nanomedicines. Non-invasively tracking liposome biodistribution and tumor deposition in patients may provide insight into identifying patients that are well-suited for liposomal therapies. We describe a novel gradient-loadable chelator, 4-DEAP-ATSC, for incorporating (64)Cu into liposomal therapeutics for positron emission tomographic (PET). (64)Cu chelated to 4-DEAP-ATSC (>94%) was loaded into PEGylated liposomal doxorubicin (PLD) and HER2-targeted PLD (MM-302) with efficiencies >90%. (64)Cu-MM-302 was stable in human plasma for at least 48h. PET/CT imaging of xenografts injected with (64)Cu-MM-302 revealed biodistribution profiles that were quantitatively consistent with tissue-based analysis, and tumor (64)Cu positively correlated with liposomal drug deposition. This loading technique transforms liposomal therapeutics into theranostics and is currently being applied in a clinical trial (NCT01304797) to non-invasively quantify MM-302 tumor deposition, and evaluate its potential as a prognostic tool for predicting treatment outcome of nanomedicines.


Asunto(s)
Isótopos de Carbono/química , Quelantes/química , Doxorrubicina/análogos & derivados , Liposomas/química , Nanomedicina/métodos , Nanopartículas/química , Animales , Línea Celular Tumoral , Cobre/química , Radioisótopos de Cobre/química , Doxorrubicina/química , Sistemas de Liberación de Medicamentos , Humanos , Ratones , Trasplante de Neoplasias , Polietilenglicoles/química , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X
12.
Proc Natl Acad Sci U S A ; 109(26): 10175-80, 2012 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-22685209

RESUMEN

The platinum-based chemotherapy is the standard treatment for several types of cancer. However, cancer cells often become refractory with time and most patients with serious cancers die of drug resistance. Recently, we have discovered a unique dissociative electron-transfer mechanism of action of cisplatin, the first and most widely used platinum-based anticancer drug. Here, we show that the combination of cisplatin with an exemplary biological electron donor, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), may overcome the resistance of cancer cells to cisplatin. Our steady-state absorption and fluorescence spectroscopic measurements confirm the effective dissociative electron-transfer reaction between TMPD and cisplatin. More significantly, we found that the combination of 100 µM TMPD with cisplatin enhances double-strand breaks of plasmid DNA by a factor of approximately 3.5 and dramatically reduces the viability of cisplatin-sensitive human cervical (HeLa) cancer cells and highly cisplatin-resistant human ovarian (NIH:OVCAR-3) and lung (A549) cancer cells. Furthermore, this combination enhances apoptosis and DNA fragmentation by factors of 2-5 compared with cisplatin alone. These results demonstrate that this combination treatment not only results in a strong synergetic effect, but also makes resistant cancer cells sensitive to cisplatin. Because cisplatin is the cornerstone agent for the treatment of a variety of human cancers (including testicular, ovarian, cervical, bladder, head/neck, and lung cancers), our results show both the potential to improve platinum-based chemotherapy of various human cancers and the promise of femtomedicine as an emerging frontier in advancing cancer therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Apoptosis , Línea Celular Tumoral , Cisplatino/administración & dosificación , Daño del ADN , Transporte de Electrón , Femenino , Citometría de Flujo , Humanos , Neoplasias Pulmonares/patología , Neoplasias Ováricas/patología , Espectrometría de Fluorescencia , Tetrametilfenilendiamina/administración & dosificación , Neoplasias del Cuello Uterino/patología
13.
Proc Natl Acad Sci U S A ; 108(29): 11778-83, 2011 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-21730183

RESUMEN

Both water and electron-transfer reactions play important roles in chemistry, physics, biology, and the environment. Oxidative DNA damage is a well-known mechanism, whereas the relative role of reductive DNA damage is unknown. The prehydrated electron (e(pre)-), a novel species of electrons in water, is a fascinating species due to its fundamental importance in chemistry, biology, and the environment. e(pre)- is an ideal agent to observe reductive DNA damage. Here, we report both the first in situ femtosecond time-resolved laser spectroscopy measurements of ultrafast-electron-transfer (UET) reactions of e(pre)- with various scavengers (KNO(3), isopropanol, and dimethyl sulfoxide) and the first gel electrophoresis measurements of DNA strand breaks induced by e(pre)- and OH(•) radicals co-produced by two-UV-photon photolysis of water. We strikingly found that the yield of reductive DNA strand breaks induced by each e(pre)- is twice the yield of oxidative DNA strand breaks induced by each OH(•) radical. Our results not only unravel the long-standing mystery about the relative role of radicals in inducing DNA damage under ionizing radiation, but also challenge the conventional notion that oxidative damage is the main pathway for DNA damage. The results also show the potential of femtomedicine as a new transdisciplinary frontier and the broad significance of UET reactions of e(pre)- in many processes in chemistry, physics, biology, and the environment.


Asunto(s)
Daño del ADN/fisiología , Transporte de Electrón/fisiología , Hidróxidos/química , Agua/química , Biofisica , Electroforesis en Gel de Agar , Depuradores de Radicales Libres/metabolismo , Hidróxidos/metabolismo , Oxidación-Reducción , Análisis Espectral , Agua/metabolismo
14.
Semin Radiat Oncol ; 34(1): 135-144, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38105088

RESUMEN

Magnetic resonance image guided radiation therapy (MRIgRT) is a relatively new technology that has already shown outcomes benefits but that has not yet reached its clinical potential. The improved soft-tissue contrast provided with MR, coupled with the immediacy of image acquisition with respect to the treatment, enables expansion of on-table adaptive protocols, currently at a cost of increased treatment complexity, use of human resources, and longer treatment slot times, which translate to decreased throughput. Many approaches are being investigated to meet these challenges, including the development of artificial intelligence (AI) algorithms to accelerate and automate much of the workflow and improved technology that parallelizes workflow tasks, as well as improvements in image acquisition speed and quality. This article summarizes limitations of current available integrated MRIgRT systems and gives an outlook about scientific developments to further expand the use of MRIgRT.


Asunto(s)
Inteligencia Artificial , Radioterapia Guiada por Imagen , Humanos , Radioterapia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Algoritmos , Flujo de Trabajo
15.
Cancers (Basel) ; 16(5)2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38473297

RESUMEN

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/- ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/- ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20-14.80 m versus 8.40 m, 95% Cl: 7.12-9.68 m, LogRank P=0.019) than docetaxel +/- ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/- ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/- ramucirumab in this patient population.

16.
Nat Commun ; 15(1): 3152, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605064

RESUMEN

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Fluorodesoxiglucosa F18 , Radiofármacos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Estudios Retrospectivos
17.
Mol Imaging ; 12(3): 148-60, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23490441

RESUMEN

The use of multimodal imaging as a tool to assess the in vivo pharmacokinetics and biodistribution of nanocarriers is important in understanding the nature of their in vivo transport. The current study reports the development of a nano-sized liposomal computed tomographic (CT)/optical imaging probe carrying iohexol and Cy5.5 and its use in micro-CT and optical imaging to quantitatively assess the whole-body (macroscopic), intratumoral, and microscopic distribution over a period of 8 days. These multimodal liposomes have a vascular half-life of 30.3 ± 8.9 hours in mice bearing subcutaneous H520 non-small cell lung cancer tumors, with the maximum liposome accumulation in tumor achieved 48 hours postinjection. The in vivo liposome distribution and stability were quantitatively assessed using both micro-CT and fluorescence molecular tomography. The combination of CT and optical imaging enables visualization of the liposomes at the whole-body, tumor, and cellular scales with high sensitivity. Such noninvasive tracking of therapeutic vehicles at the macro- and microscale is important for informed and rational development of novel nanocarrier systems.


Asunto(s)
Liposomas/metabolismo , Imagen Óptica/métodos , Tomografía Computarizada por Rayos X/métodos , Animales , Línea Celular Tumoral , Femenino , Humanos , Imagenología Tridimensional , Yohexol , Liposomas/administración & dosificación , Neoplasias Pulmonares/metabolismo , Ratones
18.
Cancer ; 119(10): 1878-84, 2013 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-23423841

RESUMEN

BACKGROUND: This study sought to determine if preoperative image-guided intensity-modulated radiotherapy (IG-IMRT) can reduce morbidity, including wound complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma. METHODS: The primary endpoint was the development of an acute wound complication (WC). IG-IMRT was used to conform volumes to avoid normal tissues (skin flaps for wound closure, bone, or other uninvolved soft tissues). From July 2005 to June 2009, 70 adults were enrolled; 59 were evaluable for the primary endpoint. Median tumor size was 9.5 cm; 55 tumors (93%) were high-grade and 58 (98%) were deep to fascia. RESULTS: Eighteen (30.5%) patients developed WCs. This was not statistically significantly different from the result of the National Cancer Institute of Canada SR2 trial (P = .2); however, primary closure technique was possible more often (55 of 59 patients [93.2%] versus 50 of 70 patients [71.4%]; P = .002), and secondary operations for WCs were somewhat reduced (6 of 18 patients [33%] versus 13 of 30 patients [43%]; P = .55). Moderate edema, skin, subcutaneous, and joint toxicity was present in 6 (11.1%), 1 (1.9%), 5 (9.3%), and 3 (5.6%) patients, respectively, but there were no bone fractures. Four local recurrences (6.8%, none near the flaps) occurred with median follow-up of 49 months. CONCLUSIONS: The 30.5% incidence of WCs was numerically lower than the 43% risk derived from the National Cancer Institute of Canada SR2 trial, but did not reach statistical significance. Preoperative IG-IMRT significantly diminished the need for tissue transfer. RT chronic morbidities and the need for subsequent secondary operations for WCs were lowered, although not significantly, whereas good limb function was maintained.


Asunto(s)
Extremidad Inferior , Terapia Neoadyuvante/métodos , Radioterapia de Intensidad Modulada/métodos , Sarcoma/radioterapia , Sarcoma/cirugía , Colgajos Quirúrgicos , Infección de la Herida Quirúrgica/prevención & control , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Canadá/epidemiología , Supervivencia sin Enfermedad , Femenino , Fibrosarcoma/radioterapia , Fibrosarcoma/cirugía , Hemangiosarcoma/radioterapia , Hemangiosarcoma/cirugía , Humanos , Imagenología Tridimensional , Incidencia , Estimación de Kaplan-Meier , Leiomiosarcoma/radioterapia , Leiomiosarcoma/cirugía , Liposarcoma/radioterapia , Liposarcoma/cirugía , Extremidad Inferior/patología , Extremidad Inferior/cirugía , Masculino , Persona de Mediana Edad , Morbilidad , Análisis Multivariante , Estudios Prospectivos , Dosificación Radioterapéutica , Radioterapia Adyuvante/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Sarcoma/diagnóstico por imagen , Sarcoma/patología , Sarcoma Sinovial/radioterapia , Sarcoma Sinovial/cirugía , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Resultado del Tratamiento
19.
Small ; 9(20): 3385-9, 2013 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-23653258

RESUMEN

A low density vertically aligned carbon nanotube-based field-emission cathode with a ballast resistor and coaxial gate is designed and fabricated. The ballast resistor can overcome the non-uniformity of the local field-enhancement factor at the emitter apex. The self-aligned fabrication process of the coaxial gate can avoid the effects of emitter tip misalignment and height non-uniformity.

20.
J Magn Reson Imaging ; 37(4): 909-16, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23097411

RESUMEN

PURPOSE: To evaluate regional and temporal changes in apparent diffusion coefficient (ADC) and T2 relaxation during radiation therapy (RT) in patients with low and intermediate risk localized prostate cancer. MATERIALS AND METHODS: Seventeen patients enrolled on a prospective clinical trial where MRI was acquired every 2 weeks throughout eight weeks of image-guided prostate IMRT (78 Gy/39 fractions). ADC and T2 quantification used entire prostate, central gland, benign peripheral zone, and tumor-dense regions-of-interest, and mean values were evaluated for common response trends. RESULTS: Overall, the RT responses were greater than volunteer measurement repeatability, and week 6 appeared to be an optimum time-point for early detection. RT effects on the entire prostate were best detected using ADC (5-7% by week 2, P < 0.0125), effects on peripheral zone were best detected using T2 (19% reduction at week 6; P = 0.004) and effects on tumors were best detected using ADC (14% elevation at week 6; P = 0.004). CONCLUSION: ADC and T2 may be candidate biomarkers of early response to RT warranting further investigation against clinical outcomes.


Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Próstata/patología , Próstata/efectos de la radiación , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radioterapia de Intensidad Modulada , Anciano , Biomarcadores de Tumor/sangre , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Riesgo , Resultado del Tratamiento
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