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1.
Cancer Lett ; 472: 108-118, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31837443

RESUMO

Despite the common application and considerable efforts to achieve precision radiotherapy (RT) in several types of cancer, RT has not yet entered the era of precision medicine; the ability to predict radiosensitivity and treatment responses in tumors and normal tissues is lacking. Therefore, development of genome-based methods for individual prognosis in radiation oncology is urgently required. Traditional DNA sequencing requires tissue samples collected during invasive operations; therefore, repeated tests are nearly impossible. Intra- and inter-tumoral heterogeneity may undermine the predictive power of a single assay from tumor samples. In contrast, analysis of circulating tumor DNA (ctDNA) allows for non-invasive and near real-time sampling of tumors. By investigating the genetic composition of tumors and monitoring dynamic changes during treatment, ctDNA analysis may potentially be clinically valuable in prediction of treatment responses prior to RT, surveillance of responses during RT, and evaluation of residual disease following RT. As a biomarker for RT response, ctDNA profiling may guide personalized treatments. In this review, we will discuss approaches of tissue DNA sequencing and ctDNA detection and summarize their clinical applications in both traditional RT and in combination with immunotherapy.

2.
World Neurosurg ; 134: 434-437, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678437

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1), a dysregulated neurocutaneous disorder, is an autosomal dominant genetic disease caused by mutations in the NF1 gene. Anaplastic astrocytoma is rare in NF1 patients, and research has proposed that high-grade astrocytomas could be due to larger germ-line mutations in NF1.We present a clinical and molecular study of a Chinese family with NF1. CASE DESCRIPTION: A 28-year-old male patient with NF1 presents with headache, vertigo, and dizziness. Histopathologic examination and molecular features identified a cerebellar anaplastic astrocytoma, IDH-wildtype. The patient underwent gross total resection of the lesion and received radiotherapy and chemotherapy. A rare splice error mutation (c.4110+945A>G) in intron 23-2 of NF1 was identified by next-generation sequencing in the proband. Sanger sequencing identified and confirmed it in some affected family members. CONCLUSIONS: We present a unique case of NF1 with anaplastic astrocytoma that revealed a rare splice error mutation in the NF1 gene in the family.

3.
Hepatobiliary Pancreat Dis Int ; 18(4): 354-359, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31221569

RESUMO

BACKGROUND: Hepatic radiation injury severely restricts irradiation treatment for liver carcinoma. The purpose of this study was to investigate the clinical application of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI (EOB-MRI) in the assessment of liver function after external radiation therapy and to determine the relationship between focal liver reaction (FLR) and liver function. METHODS: A total of 47 patients with liver malignancies who underwent external beam radiation therapy were enrolled. EOB-MRI was performed on each patient at approximately one month post-radiotherapy. The hepatobiliary (HPB) phase images from EOB-MRI were fused with the planning CT images, and the isodose lines from the patients' treatment plans were overlaid onto the fused images. The correlation of the EOB-MR image intensity distribution with the isodose lines was studied. We also compared liver function in patients between pre-treatment and post-treatment. RESULTS: Decreased uptake of Gd-EOB-DTPA, which was manifested by well-demarcated focal hypointensity of the liver parenchyma or FLR to high-dose radiation, was observed in the irradiated areas of 38 patients. The radiotherapy isodose line of decreased uptake area of Gd-EOB-DTPA was 30-46 Gy. The median corresponding dose curve of FLR was 34.4 Gy. Nine patients showed the absence of decreased uptake area of Gd-EOB-DTPA in the irradiated areas. Compared to the 38 patients with the presence of decreased uptake area of Gd-EOB-DTPA, 9 patients with the absence of decreased uptake area of Gd-EOB-DTPA showed significant higher levels of total bile acid, total bilirubin, direct bilirubin and alpha-fetoprotein (P < 0.05). There were no significant differences in alanine transaminase, aspartate aminotransferase, gamma-glutamyl transpeptidase or albumin levels between the two groups (P > 0.05). CONCLUSIONS: Visible uptake of Gd-EOB-DTPA by the liver parenchyma was significantly associated with liver function parameters. EOB-MRI can be a valuable imaging biomarker for the assessment of liver parenchyma function outside of radiation area.

4.
JAMA Netw Open ; 2(5): e190103, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31099859

RESUMO

Importance: Although thoracic twice-daily radiotherapy (TDRT) is one of the standards of care for small cell lung cancer, its association with brain metastases remains unknown. Objective: To investigate the association of TDRT vs once-daily radiotherapy (ODRT) with brain metastases after prophylactic cranial irradiation in patients with small cell lung cancer. Design, Setting, and Participants: In this multicenter cohort study, data on 778 consecutive patients with small cell lung cancer who had undergone thoracic radiotherapy (609 received ODRT and 169 received TDRT), chemotherapy, and prophylactic cranial irradiation were retrieved from the databases of 8 hospitals in China between July 1, 2003, and June 30, 2016. A 1:1 propensity score matching approach was used to control for confounding between the ODRT and TDRT groups. Confounding covariates included 8 demographic variables and 8 treatment-related covariates. Data analysis was conducted from November 1, 2017, to May 31, 2018, and reanalyzed for revision. Exposures: The ODRT group received 50 to 66 Gy given in 25 to 33 fractions. The TDRT group received 45 Gy given in 30 fractions. Main Outcomes and Measures: The primary end point was brain metastases. Secondary end points included progression-free survival and overall survival. Results: Of the 778 patients (median age, 55 years [interquartile range, 48-61 years]), 204 were women and 574 were men. At a median follow-up of 23.6 months (interquartile range, 14.2-38.2 months), 131 patients (16.8%) experienced brain metastases. The rate of brain metastasis at 3 years in the TDRT group was significantly higher than in the ODRT group (26.0% vs 16.9%; hazard ratio, 1.55; 95% CI, 1.06-2.26; P = .03). Of the 338 matched patients (169 in the ODRT group vs 169 in the TDRT group), 60 (17.8%) experienced brain metastases, with a rate at 3 years of 14.9% in the ODRT group vs 26.0% in the TDRT group (hazard ratio, 1.71; 95% CI, 1.02-2.88; P = .04). Progression-free survival was similar in both the whole cohort and the matched cohort. Median overall survival in the ODRT group tended to be significantly longer than in the TDRT group after matching (47.2 vs 32.8 months; hazard ratio, 1.41; 95% CI, 0.99-2.01; P = .06). Conclusions and Relevance: In this study, patients with small cell lung cancer who received thoracic TDRT appeared to have a higher risk of brain metastases than those who received ODRT, which supports the need for further prospective randomized clinical trials, especially in China and other parts of Asia.

5.
Radiat Oncol ; 14(1): 46, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876444

RESUMO

AIMS: To perform a dosimetric evaluation of four different simultaneous integrated boost whole brain radiotherapy modalities with hippocampus and inner ear avoidance in the treatment of limited brain metastases. METHODS: Computed tomography/magnetic resonance imaging data of 10 patients with limited (1-5) brain metastases were used to replan step-and-shoot intensity-modulated radiotherapy (sIMRT), dynamic intensity-modulated radiation therapy (dIMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (Tomo). The prescribed doses of 40-50 Gy in 10 fractions and 30 Gy in 10 fractions were simultaneously delivered to the metastatic lesions and the whole-brain volume, respectively. The hippocampal dose met the RTOG 0933 criteria for hippocampal avoidance (Dmax ≤17 Gy, D100% ≤10 Gy). The inner ear dose was restrained to Dmean ≤15 Gy. Target coverage (TC), homogeneity index (HI), conformity index (CI), maximum dose (Dmax), minimum dose (Dmin) and dose to organs at risk (OARs) were compared. RESULTS: All plans met the indicated dose restrictions. The mean percentage of planning target volume of metastases (PTVmets) coverage ranged from 97.1 to 99.4%. For planning target volume of brain (PTVbrain), Tomo provided the lowest average D2% (37.5 ± 2.8 Gy), the highest average D98% (25.2 ± 2.0 Gy), and the best TC (92.6% ± 2.1%) and CI (0.79 ± 0.06). The two fixed gantry IMRT modalities (step and shot, dynamic) provided similar PTVbrain dose homogeneity (both 0.76). Significant differences across the four approaches were observed for the maximum and minimum doses to the hippocampus and the maximum doses to the eyes, lens and optic nerves. CONCLUSION: All four radiotherapy modalities produced acceptable treatment plans with good avoidance of the hippocampus and inner ear. Tomo obtained satisfactory PTVbrain coverage and the best homogeneity index. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03414944 . Registered 29 January 2018.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana , Orelha Interna/efeitos da radiação , Hipocampo/efeitos da radiação , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Prognóstico , Radiometria/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
6.
Biomed Res Int ; 2019: 8534761, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30733968

RESUMO

The purpose of this study was to assess the diagnostic value of arginine-glycine-aspartic acid (RGD) PET/CT for tumor detection in patients with suspected malignant lesions and to determine the predictive performance of RGD PET/CT in identifying responders. Methods. The PubMed (Medline), EMBASE, Cochrane Library, and Web of Science databases were systematically searched for potentially relevant publications (last updated on July 28th, 2018) reporting the performance of RGD PET in the field of oncology. Pooled sensitivities, specificities, and diagnostic odds ratios (DORs) were calculated for parameters. The areas under the curve (AUCs) and Q⁎ index scores were determined from the constructed summary receiver operating characteristic (SROC) curve. We explored heterogeneity by metaregression. Results. Nine studies, five including 216 patients that determined diagnostic performance and three including 75 patients that determined the predictive value of parameters, met our inclusion criteria. The pooled sensitivity, pooled specificity, DOR, AUC, and Q⁎ index score of RGD PET/CT for the detection of underlying malignancy were 0.85 (0.79-0.89), 0.93 (0.90-0.96), 48.35 (18.95-123.33), 0.9262 (standard error=0.0216), and 0.8606 for SUVmax and 0.86 (0.80-0.91), 0.92 (0.88-0.94), 40.49 (14.16-115.77), 0.9312 (SE=0.0177), and 0.8665 for SUVmean, respectively. The pooled sensitivity, pooled specificity, DOR, AUC, and Q⁎ index score of RGD PET/CT for identifying responders were 0.80 (0.59-0.93), 0.74 (0.60-0.85), 15.76 (4.33-57.32), 0.8682 (0.0539), and 0.7988, respectively, for SUVmax at baseline. Conclusion. The interesting but preliminary data in this meta-analysis demonstrate that RGD PET/CT may be an ideal diagnostic tool for detecting underlying malignancies in patients suspected of having tumors and may be able to efficiently predict short-term outcomes.


Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/diagnóstico , Oligopeptídeos/química , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Distribuição de Qui-Quadrado , Humanos , Valor Preditivo dos Testes , Viés de Publicação , Garantia da Qualidade dos Cuidados de Saúde , Curva ROC , Resultado do Tratamento
7.
Cancer Manag Res ; 11: 339-346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643459

RESUMO

Background: For the melanoma patients who are with the primary tumor and metastatic disease concurrently (the newly diagnosed metastatic patients), the effect of primary tumor surgery on survival has never been discussed. Objective: We sought to estimate this effect based on data from the Surveillance, Epidemiology, and End Results database. Patients and methods: We identified patients with newly diagnosed metastatic melanoma from 2004 to 2015. The effect of primary tumor surgery was assessed by using Cox proportional hazard regression modeling and propensity score matching. Results: Eight thousand three hundred and forty-one patients who had been diagnosed with primary melanoma and metastatic disease at the same time were included in this analysis, of whom 2,554 (30.6%) received primary tumor surgery. In multivariable analysis of the unmatched cohort, primary tumor surgery was an independent protective factor of overall survival (HR =0.617, 95% CI 0.565-0.674; P<0.001) and melanoma-specific survival (HR =0.599, 95% CI 0.537-0.668; P<0.001). In the matched cohort, primary tumor surgery was still associated with better overall survival (13 vs 6 months, P<0.001) and melanoma-specific survival (18 vs 6 months, P<0.001). Conclusion: Our results reveal the benefit of primary tumor surgery on the survival of patients with newly diagnosed metastatic melanoma and may fill in the gaps of guidelines for this population. IRB: IRB approval is not required because the SEER data are freely accessible.

8.
Melanoma Res ; 29(1): 77-84, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30379726

RESUMO

Brain metastases (BM) from cutaneous melanoma are associated with poor prognosis. Population-based data describing the associated factors of incidence and prognosis of BM from melanoma are still lacking. We identified 121 255 melanoma patients diagnosed during 2010-2015 from the Surveillance, Epidemiology, and End Results program, and identified predictive factors for incidence and survival of BM patients by using multivariable logistic and Cox's proportional hazard regression, respectively. We identified 1547 patients with BM at the time of diagnosis of malignant cutaneous melanoma, representing 1.3% of the entire cohort and 35.4% of the subset with metastatic disease. The characteristics associated with higher BM incidence were male sex, age 40-60 years, melanoma location of face/head/neck, histologic type of nodular, higher T-stage, ulceration and extracranial metastases. The median overall survival and median cutaneous melanoma specific survival of patients with BM was 5 and 6 months, respectively. The relative factors of poor survival were older age and more extracranial metastatic sites. In summary, we provided insight into the epidemiology of BM from cutaneous melanoma. These results may provide significant help to improve the screening strategy of BM strategy and update the existing prognosis evaluation system.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/secundário , Melanoma/epidemiologia , Melanoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/cirurgia , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Taxa de Sobrevida
9.
Eur J Nucl Med Mol Imaging ; 46(4): 940-947, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30187104

RESUMO

PURPOSE: To explore the relationship between metabolic uptake of the 18F-ALF-NOTA-PRGD2 (18F-RGD) tracer on positron emission tomography/computerized tomography (PET/CT) and the antiangiogenic effect of apatinib in patients with solid malignancies. MATERIALS AND PATIENTS: Patients with measurable lesions scheduled for second- or third-line single-agent therapy with apatinib were eligible for this prospective clinical trial. All patients underwent 18F-RGD PET/CT examination before the start of treatment. Standardized uptake values (SUVs) of contoured tumor lesions were computed and compared using independent sample t-tests or the Mann-Whitney U test. Receiver-operating characteristic (ROC) curve analysis was used to determine accuracy in predicting response. Survival curves were compared using the Kaplan-Meier method. RESULTS: Of 38 patients who consented to study participation, 25 patients with 42 measurable lesions met the criteria for inclusion in this response assessment analysis. The median follow-up time was 3 months (range, 1-10 months), and the median progression-free survival (PFS) was 3 months (95% confidence interval, 1.04-4.96). The SUVpeak and SUVmean were significantly higher in responding tumors than in non-responding tumors (4.98 ± 2.34 vs 3.59 ± 1.44, p = 0.048; 3.71 ± 1.15 vs 2.95 ± 0.49, P = 0.036). SUVmax did not differ between responding tumors and non-responding tumors (6.58 ± 3.33 vs 4.74 ± 1.83, P = 0.078). An exploratory ROC curve analysis indicated that SUVmean [area under the ROC curve (AUC) = 0.700] was a better parameter than SUVpeak (AUC = 0.689) for predicting response. Using a threshold value of 3.82, high SUVmean at baseline was associated with improved PFS (5.0 vs. 3.4 months, log-rank P = 0.036). CONCLUSION: 18F-RGD uptake on PET/CT imaging pretreatment may predict the response to antiangiogenic therapy, with higher 18F-RGD uptake in tumors predicting a better response to apatinib therapy.

10.
Mol Imaging Biol ; 21(1): 175-182, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29869060

RESUMO

PURPOSE: To assess a novel radiotracer aluminum [18F]fluoride-1,4,7-triazacyclononane-triacetic acid-pegylated dimeric RGD ([18F]ALF-NOTA-PRGD2, denoted as [18F]Alfatide) for positron emission tomography (PET)/X-ray computed tomography (CT) and explore the relationships between clinicopathological characteristics and maximum standard uptake values in primary (SUVP) and metastatic lymph nodes (SUVLN) of patients with esophageal squamous cell carcinoma (ESCC), as verified by pathologic examination and compared with those obtained with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) PET. PROCEDURES: We prospectively enrolled patients with newly diagnosed ESCC who agreed to undergo [18F]Alfatide PET/CT or [18F]FDG PET/CT scans before surgery at Shandong Cancer Hospital from May 2011 to July 2017. SUVs and the pathological tumor-node-metastasis (pTNM) stages of primary tumors and metastatic lymph nodes (LNs) were measured and confirmed pathologically. Immunohistochemical (IHC) staining for integrin αvß3 was performed on tumor samples (both primary tumors and metastatic LNs) collected from nine patients. RESULTS: Of 61 patients who underwent PET/CT scans, 46 then underwent curative surgery and were included in our analysis (n = 21 for [18F]Alfatide PET/CT and n = 25 for [18F]FDG PET/CT). No significant differences in the SUVP on [18F]Alfatide PET/CT or [18F]FDG PET/CT were observed among the cohorts according to gender, pathological stage, T stage, status of LNs, and differentiation (all P > 0.05). The SUVLN differed significantly between the pathological stages and status of LNs both on [18F]Alfatide PET/CT (P = 0.03, 0.003) and [18F]FDG PET/CT (P = 0.001. < 0.001), but not according to gender (P = 0.128, 0.129), T stage (P = 0.791, 0.727), or tumor differentiation (P = 0.049, 0.053). Significant positive correlations were observed between the SUVLN on [18F]Alfatide PET/CT and [18F]FDG PET/CT, and pathological stage (r = 0.52, P = 0.016; r = 0.503, P = 0.01), LN status (r = 0.73, P < 0.001; r = 0.649, P < 0.001), and differentiation (r = 0.509, P < 0.019; r = 0.459, P = 0.021) were observed. No significant differences were found between the relationships of SUVP with SUVLN, length, age, gender, pathological stage, T stage, status of LN, or differentiation, or of SUVLN with length, age, gender, or T stage both on [18F]Alfatide PET/CT and [18F]FDG PET/CT (all P > 0.05). The quantitated expression levels of αvß3 in primary tumors and metastatic LNs were 1.67 ± 1.12 and 3.42 ± 2.93, respectively (P = 0.031). CONCLUSIONS: Our results suggest that SUVLN is influenced by pathological stage, LN status, and differentiation. SUVLN may therefore serve as a new parameter for risk stratification of with ESCC patients. Moreover, [18F]Alfatide PET can provide complementary molecular information about ESCC metastasis.


Assuntos
Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Fluordesoxiglucose F18/farmacocinética , Peptídeos Cíclicos/farmacocinética , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Feminino , Radioisótopos de Flúor/efeitos adversos , Radioisótopos de Flúor/farmacocinética , Fluordesoxiglucose F18/efeitos adversos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Peptídeos Cíclicos/efeitos adversos
11.
Radiother Oncol ; 129(2): 242-248, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30471708

RESUMO

PURPOSE: To investigate the predictive value of the perfusion (Q) single-photon emission computed tomography (SPECT)-weighted dose-function histogram (DFH) obtained mid-treatment (mid-Tx) with radiotherapy (RT) for radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The study population consisted of NSCLC patients who were undergoing RT treatment and enrolled in prospective imaging studies. Q-SPECT was performed prior to and during RT (at ∼40-45 Gy). A baseline dose-volume histogram (DVH) and mid-Tx DVH based on simulation CT as well as a baseline DFH and mid-Tx DFH based on Q-SPECT were calculated. Only patients with stage III NSCLC and visible functional lung (FL) changes on the mid-Tx scan were eligible for this enriched analysis. RILT was graded according to a reported scale. RESULTS: Forty-two stage III NSCLC patients met the criteria for inclusion. The accumulative incidence of grade ≥2 RILT was 31% in this high-risk population. Significant differences in functional metrics such as functional lung volume FV5-FV20 at increments of 5 Gy and functional MLD (FMLD) were observed between patients with and without grade ≥2 RILT (p < 0.05). Similar results were also obtained for anatomical metrics from V5-V20 and MLD (p < 0.05). The areas under the receiver operating characteristic curves (AUCs) ranged from 0.724to 0.812 for baseline DVH parameters, from 0.745 to 0.830 for mid-Tx DVH parameters, from 0.764 to 0.878 for baseline DFH parameters, and from 0.767 to 0.891 for mid-Tx DFH parameters. Further principal components analysis showed that the AUCs were 0.814/0.817 and 0.790/0.857 for baseline/mid-Tx DVH and baseline/mid-Tx DFH, respectively. CONCLUSIONS: Mid-Tx DFH parameters based on Q-SPECT were significantly elevated in patients with grade ≥2 RILT in this study population. Among the metrics compared, mid-Tx DFH seemed to have better predictive accuracy, but this difference did not reach statistical difference.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Doses de Radiação , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Pneumonite por Radiação/diagnóstico por imagem , Pneumonite por Radiação/etiologia , Radiometria/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos
13.
Oncol Rep ; 40(5): 2896-2905, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30226599

RESUMO

As the crucial issue in the development of anti­angiogenic drugs is how to predict which patients will and will not benefit prior to the initiation of therapy, angiogenic 18F­alfatide positron emission computed tomography (PET) was assessed in the present study. Lung adenocarcinoma A549 (high angiogenesis) and prostate PC­3 (low angiogenesis) cell xenografted tumor­bearing mice underwent 18F­alfatide PET at baseline and following treatment with either an anti­angiogenic therapy or vehicle. The evaluation index for the inhibition of tumor growth in the individuals in the treated groups was represented by treatment/control (T/C) ratio (%). Anti­angiogenic responses were denoted by the changes in 18F­alfatide uptake in the same animal. The T/C ratio was lower in high­uptake tumors than in low­uptake tumors (P=0.001). A significant difference in the tumor volumes between the anti­angiogenic therapy group and the control group occurred earlier in the A549 model than in the PC­3 model. 18F­alfatide uptake decreased more for A549 tumors than for PC­3 tumors following anti­angiogenic therapy. In each treatment group, the degree of tumor response to anti­angiogenic therapy was associated well with the tumor uptake prior to treatment (P<0.05). These results indicated that 18F­alfatide PET may be a useful molecular imaging tool for individual selection prior to anti­angiogenic drug therapy.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Peptídeos Cíclicos/administração & dosagem , Células A549 , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Animais , Humanos , Camundongos , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/patologia , Tomografia por Emissão de Pósitrons , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Nucl Med Commun ; 39(8): 732-740, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30001264

RESUMO

OBJECTIVE: This study explored whether integrated texture parameter (ITP) of the fluorine-18-fluorodeoxyglucose PET (F-FDG PET) is a stratification factor for the survival of nonoperative patients with locally advanced non-small-cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Thirty-five patients with LA-NSCLC treated with chemoradiotherapy or radiotherapy were included in the retrospective study. Eight principal components (PCs) were extracted from 72 F-FDG PET texture features (TFs) using PC analysis. The survival rates between PC subgroups (group by median value) were compared using Kaplan-Meier method. Seventy-two factor loadings for PC7 were evaluated using t-test. Standardized values of the TFs with significant factor loading were multiplied by the corresponding PC7 component coefficient, and the products were added together to obtain ITP. The survival rates between ITP subgroups (group by median value) were compared using Kaplan-Meier method. Patient characteristics between ITP subgroups were compared using χ -test, Mann-Whitney U-test, or t-test. RESULTS: The median follow-up time was 20.7 months. The median overall survival (OS) and progression-free survival (PFS) were 32.5 and 14.4 months, respectively. The patients with high PC7 value had lesser OS (P=0.006) and PFS (P=0.010) than those with lower value. Factor loadings of standardized uptake value kurtosis, run percentage, and zone percentage were significant for PC7 (P<0.01). The patients with high ITP value had lesser OS (P=0.001) and PFS (P=0.002) than those with lower value. There were no significant differences in patient characteristics between ITP subgroups (P>0.2). CONCLUSION: This study demonstrated that ITP might be a stratification factor for the survival of nonoperative patients with LA-NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos
15.
Thorac Cancer ; 9(7): 865-873, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29774659

RESUMO

BACKGROUND: This study used magnetic resonance imaging (MRI) to monitor changes to brain metastases and investigate the imaging signs used to evaluate treatment efficacy and determine prognosis following radiotherapy for brain metastases from lung cancer. METHODS: A total of 60 non-small cell lung cancer patients with brain oligometastases were selected. MRI scans were conducted before and 3, 6, 9, 12, 18, 24, and 30 months after radiotherapy. The tumor and peritumoral edema diameters, Cho/Cr values, elevation of the Lip peak value, and whether the island (yu-yuan) sign or high-signal ring were present on T2 fluid-attenuated inversion recovery (FLAIR) imaging were recorded for each metastasis. RESULTS: The mortality risk was higher the earlier the maximum value of peritumoral edema diameter was reached, when there were fewer island signs, and when brain metastases did not present as tumor progression on imaging. There were significant differences in the average peritumoral edema diameter, apparent diffusion coefficient value, the number of elevated Lip peak values, and the number of T2 FLAIR imaging high-signal rings in a year after radiotherapy in 14 patients with a survival period < 1 year compared to patients with a survival period > 2 years. CONCLUSION: After radiotherapy for brain metastases, patients with the island sign had longer survival periods, high-signal rings in T2 FLAIR, elevated Lip peaks, and reduced apparent diffusion coefficient values, indicating tumor necrosis. Increased diameter of metastases and Cho/Cr > 2 cannot serve as reliable indicators of brain metastasis progression.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Pulmonares/radioterapia , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Mol Imaging Biol ; 20(6): 1061-1067, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29623510

RESUMO

PURPOSE: To explore a representative hypoxic parameter to predict the treatment response and prognosis for [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET)/X-ray computed tomography (CT) in patients with non-small cell lung cancer (NSCLC). PROCEDURES: Twenty-nine patients with NSCLC underwent FMISO-PET scans before chemoradiotherapy (CRT). The maximum standard uptake values (SUVmax) in the tumor, normal lung, aortic arch, and vertical ridge muscle were measured, and the tumor-to-lung (T/L) ratios, tumor-to-blood (T/B) ratios, ands tumor-to-muscle (T/M) ratios were calculated and analyzed. Fractional hypoxic volume (FHV) was expressed as percentage of hypoxic volume. RESULTS: SUVmax, T/L ratio, T/B ratio, and FHV were all significantly different between the responders and the non-responders (SUVmax, 2.07 ± 0.53 vs. 2.61 ± 0.69, P = 0.026; T/L ratio, 3.16 ± 0.85 vs. 4.09 ± 1.46, P = 0.047; T/B ratio, 1.27 ± 0.20 vs. 1.48 ± 0.32, P = 0.042; 38.92 ± 18.47 vs. 52.91 ± 11.29 %, P = 0.020). However, the T/M ratio was not significantly different between the two populations (1.46 ± 0.31 vs. 1.67 ± 0.33, P = 0.098). The correlation ratio between hypoxic parameters and treatment responses ranged from high to low as FHV (r = 0.412); SUVmax (r = 0.400); T/L ratio (r = 0.379), P < 0.05; and T/B ratio (r = 0.355), P = 0.059. According to the area under curve (AUC) to predict response, the hypoxic parameters were arranged as FHV (AUC = 0.748), SUVmax (AUC = 0.731), T/L ratio (AUC = 0.719), and T/B ratio (AUC = 0.705). Binary logistic regression analyses showed that FHV was the only independent predictor for treatment response with the P value of 0.038. In the progression-free survival (PFS) prediction, both FHV and SUVmax reached statistical significance by Kaplan-Meier plots (FHV, 46.99 %, P = 0.010; SUVmax, 1.99, P = 0.046) while only FHV was the independent prognostic factor in multivariate analysis by Cox proportional hazard model (P = 0.037). CONCLUSION: FHV may be a representative hypoxic parameter to predict the CRT response and PFS in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Hipóxia/diagnóstico por imagem , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico por imagem , Misonidazol/análogos & derivados , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Misonidazol/química , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Resultado do Tratamento
17.
Oncotarget ; 8(50): 87971-87979, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29152134

RESUMO

Systemic inflammation and hematological markers have prognostic value in patients with esophageal squamous cell carcinoma (ESCC). The objective of this study was to evaluate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), combined neutrophil-platelet (CNP) score, and hemoglobin (Hb) to inform treatment decisions and predict outcomes in patients with locally advanced ESCC treated with chemoradiotherapy (CRT). A total of 168 patients with locally advanced ESCC were retrospectively evaluated. Patients were stratified by marker value using a receiver operating characteristic curve analysis to determine the cutoff point. Logistic regression was used to identify markers associated with sensitivity to treatment. Overall survival (OS) was calculated by the Kaplan-Meier method. Multivariate Cox logistic regression modeling was used to assess the influences of OS. Smoking history, tumour site, clinical stage, NLR, PLR, CNP, and Hb (p ≤ 0.05) were associated with the sensitivity to therapy. In multivariate analysis, a high CNP score was independently associated with poor treatment sensitivity (OR = 2.066, p = 0.021). Univariate analysis revealed that PLR, CNP, and Hb levels were associated with OS, and Cox multivariate analysis found that CNP (HR = 1.47, p = 0.027) and Hb level (HR = 0.44, p = 0.007) were independent predictors of OS. In conclusion, CNP and Hb are inexpensive and universally available prognostic markers in patients with locally advanced ESCC patients. CNP score is a systemic inflammatory marker that predicted sensitivity to CRT.

19.
Nucl Med Commun ; 38(11): 919-926, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28863122

RESUMO

BACKGROUND: Gliomas are rich in blood vessels and are the most primary and malignant type of brain tumor affecting the central nervous system. A few fluorine-18 (F)-labeled imaging agents can be used for imaging of tumor angiogenesis. In the current study, F-labeled recombinant human endostatin (rh-endostatin) was developed and evaluated as a probe for PET imaging of tumor angiogenesis. MATERIALS AND METHODS: F-fluorobenzoyl-endostatin (F-FB-endostatin) was synthesized from radiolabeling of rh-endostatin with N-succinimidyl-4-F-fluorobenzoate produced by a facile module-assisted radiosynthesis procedure. Blocking studies were used to measure the relative affinities of F-FB-endostatin to human glioblastoma U87MG cells in tumor tissues rich with vessels. In addition, biodistribution, metabolic stability, and small-animal PET imaging studies were carried out with F-FB-endostatin using Institute of Cancer Research and U87MG tumor-bearing mice. RESULTS: Noninvasive small-animal PET imaging indicated that F-FB-endostatin showed rapid and good tumor uptake. The probe was rapidly cleared from the blood and most organs, resulting in excellent tumor-to-normal tissue contrasts. Tumor uptake and rapid clearance were further confirmed with biodistribution studies. Metabolite assays showed that the probe was highly stable, making it suitable for in-vivo applications. CONCLUSION: F-FB-endostatin shows promising in-vivo properties. Therefore, the promising properties of F-FB-endostatin indicate that this probe can be a powerful tool to evaluate the antiangiogenic therapy for gliomas and thus warrants further investigation as a novel PET probe for imaging of tumor angiogenesis.


Assuntos
Endostatinas , Glioma/irrigação sanguínea , Neovascularização Patológica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Animais , Linhagem Celular Tumoral , Endostatinas/farmacocinética , Radioisótopos de Flúor , Glioma/diagnóstico por imagem , Humanos , Marcação por Isótopo , Camundongos , Distribuição Tecidual
20.
Oncotarget ; 8(36): 60581-60588, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28947996

RESUMO

Tumor glucose metabolism and amino acid metabolism are usually enhanced, 18F-FDG for tumor glucose metabolism PET imaging has been clinically well known, but tumor amino acid metabolism PET imaging is not clinically familiar. Radiolabeled amino acids (AAs) are an important class of PET/CT tracers that target the upregulated amino acid transporters to show elevated amino acid metabolism in tumor cells. Radiolabeled amino acids were observed to have high uptake in tumor cells but low in normal tissues and inflammatory tissues. The radionuclides used in labeling amino acids include 15O, 13N, 11C, 123I, 18F and 68Ga, among which the most commonly used is 18F [1]. Available data support the use of certain 18F-labeled AAs for PET/CT imaging of gliomas, neuroendocrine tumors, prostate cancer and breast cancer [2, 3]. With the progress of the method of 18F labeling AAs [4-6], 18F-labeled AAs are well established for tumor PET/CT imaging. This review focuses on the current status of key clinical applications of 18F-labeled AAs in tumor PET/CT imaging.

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