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BACKGROUND: Our previous study suggests that tumor CD8+ T cells and macrophages (defined as CD68+ cells) infiltration underwent dynamic and heterogeneous changes during concurrent chemoradiotherapy (CCRT) in cervical cancer patients, which correlated with their short-term tumor response. This study aims to develop a CT image-based radiomics signature for such dynamic changes. METHODS: Thirty cervical squamous cell carcinoma patients, who were treated with CCRT followed by brachytherapy, were included in this study. Pre-therapeutic CT images were acquired. And tumor biopsies with immunohistochemistry at primary sites were performed at baseline (0 fraction (F)) and immediately after 10F. Radiomics features were extracted from the region of interest (ROI) of CT images using Matlab. The LASSO regression model with ten-fold cross-validation was utilized to select features and construct an immunomarker classifier and a radiomics signature. Their performance was evaluated by the area under the curve (AUC). RESULTS: The changes of tumor-infiltrating CD8+T cells and macrophages after 10F radiotherapy as compared to those at baseline were used to generate the immunomarker classifier (AUC= 0.842, 95% CI:0.680-1.000). Additionally, a radiomics signature was developed using 4 key radiomics features to predict the immunomarker classifier (AUC=0.875, 95% CI:0.753-0.997). The patients stratified based on this signature exhibited significant differences in treatment response (p = 0.004). CONCLUSION: The radiomics signature could be used as a potential predictor for the CCRT-induced dynamic alterations of CD8+ T cells and macrophages, which may provide a less invasive approach to appraise tumor immune status during CCRT in cervical cancer compared to tissue biopsy.
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Linfócitos T CD8-Positivos , Quimiorradioterapia , Linfócitos do Interstício Tumoral , Macrófagos , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/imunologia , Quimiorradioterapia/métodos , Pessoa de Meia-Idade , Macrófagos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/imunologia , Braquiterapia/métodos , RadiômicaRESUMO
OBJECTIVES: To develop a contrast-enhanced CT (CECT) radiomics-based model to identify locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients who would benefit from deintensified chemoradiotherapy. METHODS: LA-NPC patients who received low-dose concurrent cisplatin therapy (cumulative: 150 mg/m2), were randomly divided into training and validation groups. 107 radiomics features based on the primary nasopharyngeal tumor were extracted from each pre-treatment CECT scan. Through Cox regression analysis, a radiomics model and patients' corresponding radiomics scores were created with predictive independent radiomics features. T stage (T) and radiomics score (R) were compared as predictive factors. Combining the N stage (N), a clinical model (T + N), and a substitution model (R + N) were constructed. RESULTS: Training and validation groups consisted of 66 and 33 patients, respectively. Three significant independent radiomics features (flatness, mean, and gray level non-uniformity in gray level dependence matrix (GLDM-GLN)) were found. The radiomics score showed better predictive ability than the T stage (concordance index (C-index): 0.67 vs. 0.61, AUC: 0.75 vs. 0.60). The R + N model had better predictive performance and more effective risk stratification than the T + N model (C-index: 0.77 vs. 0.68, AUC: 0.80 vs. 0.70). The R + N model identified a low-risk group as deintensified chemoradiotherapy candidates in which no patient developed progression within 3 years, with 5-year progression-free survival (PFS) and overall survival (OS) both 90.7% (hazard ratio (HR) = 4.132, p = 0.018). CONCLUSION: Our radiomics-based model combining radiomics score and N stage can identify specific LA-NPC candidates for whom de-escalation therapy can be performed without compromising therapeutic efficacy. CLINICAL RELEVANCE STATEMENT: Our study shows that the radiomics-based model (R + N) can accurately stratify patients into different risk groups, with satisfactory prognosis in the low-risk group when treated with low-dose concurrent chemotherapy, providing new options for individualized de-escalation strategies. KEY POINTS: ⢠A radiomics score, consisting of 3 predictive radiomics features (flatness, mean, and GLDM-GLN) integrated with the N stage, can identify specific LA-NPC populations for deintensified treatment. ⢠In the selection of LA-NPC candidates for de-intensified treatment, radiomics score extracted from primary nasopharyngeal tumors based on CECT can be superior to traditional T stage classification as a predictor.
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Neoplasias Nasofaríngeas , Humanos , Quimiorradioterapia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Radiômica , Tomografia Computadorizada por Raios XRESUMO
Cancer stemness and osteosarcoma (OS) malignant progression are closely associated. However, the molecular mechanisms underlying this association have not been fully demonstrated. Long noncoding RNAs (lncRNAs) are an intriguing class of widely prevalent endogenous RNAs involved in OS progression, the vast majority of which have not been characterized functionally. Here, we identified tumor promoter lncRNA WAC-AS1 to be highly expressed in OS tumors and associated with worse survival. Further analysis revealed that WAC-AS1 increased tumorsphere formation of OS cells and promoted metastasis, as confirmed by cell proliferation, transwell and wound healing assays. MiR-5047 was identified as a downstream target of WAC-AS1. Subsequently, based on bioinformatics analysis, RIP assay and luciferase reporter assay, SOX2 mRNA was verified as a target of miR-5047. WAC-AS1 enhanced OS cell proliferation and stemness via acting as a ceRNA by binding to miR-5047, thereby increasing SOX2 expression. In addition, SOX2 bound to the promoter region of WAC-AS1 and promoted its transcription, thereby forming a positive feedback loop to regulate OS malignancy. Taken together, our findings show WAC-AS1 is a tumor promoter and a key regulator of OS cell stemness and metastasis via a miR-5047/SOX2 axis.
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Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Osteossarcoma/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Carcinógenos , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
Cysteine, an early sulfur-containing compound in plants, is of significant importance in sulfur metabolism. CYS encodes cysteine synthetase that further catalyzes cysteine synthesis. In this investigation, CYS genes, identified from genome-wide analysis of Gossypium hirsutum bioinformatically, led to the discovery of GhCYS2 as the pivotal gene responsible for Cd2+ response. The silencing of GhCYS2 through virus-induced gene silencing (VIGS) rendered plants highly susceptible to Cd2+ stress. Silencing GhCYS2 in plants resulted in diminished levels of cysteine and glutathione while leading to the accumulation of MDA and ROS within cells, thereby impeding the regular process of photosynthesis. Consequently, the stomatal aperture of leaves decreased, epidermal cells underwent distortion and deformation, intercellular connections are dramatically disrupted, and fissures manifested between cells. Ultimately, these detrimental effected culminating in plant wilting and a substantial reduction in biomass. The association established between Cd2+ and cysteine in this investigation offered a valuable reference point for further inquiry into the functional and regulatory mechanisms of cysteine synthesis genes.
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Cádmio , Gossypium , Gossypium/genética , Cádmio/toxicidade , Sobrevivência Celular , Cisteína , Fotossíntese/genética , Compostos de Enxofre , EnxofreRESUMO
Objective: Locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, even at the same stage, have different prognoses. We aim to construct a prognostic nomogram for predicting the overall survival (OS) to identify the high-risk LA-NPC patients. Materials and methods: Histologically diagnosed WHO type II and type III LA-NPC patients in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled as the training cohort (n= 421), and LA-NPC patients from Shantou University Medical College Cancer Hospital (SUMCCH) served as the external validation cohort (n= 763). Variables were determined in the training cohort through Cox regression to form a prognostic OS nomogram, which was verified in the validation cohort, and compared with traditional clinical staging using the concordance index (C-index), Kaplan-Meier curves, calibration curves and decision curve analysis (DCA). Patients with scores higher than the specific cut-off value determined by the nomogram were defined as high-risk patients. Subgroup analyses and high-risk group determinants were explored. Results: Our nomogram had a higher C-index than the traditional clinical staging method (0.67 vs. 0.60, p<0.001). Good agreement between the nomogram-predicted and actual survival were shown in the calibration curves and DCA, indicating a clinical benefit of the nomogram. High-risk patients identified by our nomogram had worse prognosis than the other groups, with a 5-year overall survival (OS) of 60.4%. Elderly patients at advanced stage and without chemotherapy had a tendency for high risk than the other patients. Conclusions: Our OS predictive nomogram for LA-NPC patients is reliable to identify high-risk patients.
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Background: Immunotherapy has been demonstrated favorable in head and neck squamous cell carcinoma (HNSCC). Studies indicated that immune-related gene prognostic index (IRGPI) was a robust signature, and N6-methyladenosine (m6A) methylation had a significant impact on the tumor immune microenvironment (TIME) and immunotherapy of head and neck squamous cell carcinoma. Thus, combining indicated that immune-related gene prognostic index with m6A status should offer a better predictive power for immune responses. Methods: Head and neck squamous cell carcinoma samples from the cancer genome atlas (TCGA, n = 498) and gene expression omnibus database (GSE65858, n = 270) were used in this study. Cox regression analysis was used to construct the indicated that immune-related gene prognostic index through immune-related hub genes which were identified by weighted gene co-expression network analysis (WGCNA). The m6A risk score was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis. Principal component analysis was used to construct a composite score, and systematically correlate subgroups according to tumor immune microenvironment cell-infiltrating characteristics. Results: A composite score was determined based on indicated that immune-related gene prognostic index and m6A risk score. Head and neck squamous cell carcinoma patients in the cancer genome atlas were divided into four subgroups: A (IRGPI-High&m6A-risk-High, n = 127), B (IRGPI-High&m6A-risk-Low, n = 99), C (IRGPI-Low&m6A-risk-High, n = 99), and D (IRGPI-Low&m6A-risk-Low, n = 128), and overall survival (OS) was significantly different between subgroups (p < 0.001). The characteristics of tumor immune microenvironment cell infiltration in the four subgroups were significantly different in subgroups (p < 0.05). The receiver operating characteristic (ROC) curves show the predictive value of composite score for overall survival was superior to other scores. Conclusion: The composite score is a promising prognostic signature which might distinguish immune and molecular characteristics, predict prognosis, and guide more effective immunotherapeutic strategies for head and neck squamous cell carcinoma.
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PURPOSE: Our study aimed to establish and validate prognostic nomograms based on gross tumor volume (GTV) and cervical nodal volume (CNV) for nasopharyngeal carcinoma (NPC) patients treated with two cycles of concurrent chemoradiotherapy (CCRT). METHODS: From 2012 to 2015, 620 eligible patients who received radical treatment at the Cancer Hospital of Shantou University Medical College were recruited for a nomogram study. Variables were determined in a training set of 463 patients from 2012 to 2014 by X-tile analysis, univariate and multivariate Cox proportional hazard analyses, and the least absolute shrinkage and selection operator (LASSO). Another cohort of 157 patients in 2015 was validated with bootstrap resampling. The concordance index (C-index) and calibration curves were applied to assess its predictive discriminative and accuracy ability, while decision curve analysis (DCA), X-tile analysis and Kaplan-Meier curve for clinical application. RESULTS: Independent prognostic variables for overall survival (OS) were age, GTV, CNV, cranial nerve, positive cervical lymph node laterality below the caudal border of cricoid cartilage (LNBC), and were selected for the nomogram. Optimal prognostic factors including Karnofsky performance status (KPS), age, GTV, CNV, LNBC were incorporated in the nomogram for progression-free survival (PFS). In the training set, the C-index of our nomograms for OS and PFS were 0.755 (95% CI, 0.704 to 0.807) and 0.698 (95% CI, 0.652 to 0.744). The calibration curve showed good agreement between nomogram-predicted and actual survival. DCA indicated that our nomograms were of clinical benefit. CONCLUSION: Our nomograms are capable of effective prognostic prediction for patients with NPC.
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To compare the efficacy and safety of induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) alone versus concurrent CCRT in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Patients with newly diagnosed stage III to IVB nasopharyngeal carcinoma (NPC) were randomized to receive IC plus IMRT (IC+RT arm), or concurrent chemotherapy plus IMRT (CCRT arm), using a random number table. Both treatment arms received the same chemotherapy regimen. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), treatment response, and acute treatment toxicities. From June 2013 to September 2018, a total of 204 patients histologically diagnosed with LA-NPC were enrolled in the study, with 102 patients randomly assigned to each arm. After a median follow-up duration of 45 months (range 4 to 84 months), the 3-year PFS, OS, LRRFS and DMFS were 72.2%, 87.8%, 92.3%, and 82.7% in the IC+RT arm, compared with 82.6%, 92.8%, 94.7%, and 88.2% in the CCRT arm. No statistical difference for PFS, OS, LRRFS, DMFS, or treatment response was observed between the two arms (p > 0.05). The incidences of leukopenia (p = 0.008) and anemia (p = 0.015) were significantly higher in patients in the CCRT arm than those in the IC+RT arm. Compared to CCRT, IC plus IMRT alone provided similarly favorable treatment outcomes in terms of PFS, OS, LRRFS, and DMFS for patients with LA-NPC, but resulted in fewer incidences of leukopenia and anemia.
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Quimiorradioterapia , Quimioterapia de Indução , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Anemia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/mortalidade , Leucopenia/epidemiologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/mortalidade , Fatores de Tempo , Adulto JovemRESUMO
The objective of this study was to build models to predict complete pathologic response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC) patients using radiomic features. A total of 55 consecutive patients pathologically diagnosed as having ESCC were included in this study. Patients were divided into a training cohort (44 patients) and a testing cohort (11 patients). The logistic regression analysis using likelihood ratio forward selection was performed to select the predictive clinical parameters for pCR, and the least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomic predictors in the training cohort. Model performance in the training and testing groups was evaluated using the area under the receiver operating characteristic curves (AUC). The multivariate logistic regression analysis identified no clinical predictors for pCR. Thus, only radiomic features selected by LASSO were used to build prediction models. Three logistic regression models for pCR prediction were developed in the training cohort, and they were able to predict pCR well in both the training (AUC, 0.84-0.86) and the testing cohorts (AUC, 0.71-0.79). There were no differences between these AUCs. We developed three predictive models for pCR after nCRT using radiomic parameters and they demonstrated good model performance.
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Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/radioterapia , Adulto , Idoso , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: CD24 is a highly glycosylated mucin-like antigen on the cell surface, which has recently emerged as a novel oncogene and metastasis promoter. We performed bioinformatics analysis to investigate whether CD24 can serve as a prognostic indicator in breast cancer. METHODS: CD24 expression was assessed using SAGE Genie tools and Oncomine analysis. The PrognoScan database, Kaplan-Meier Plotter, and bc-GenExMiner were used to identify the prognostic roles of CD24 in breast cancer. RESULTS: We found that CD24 was more frequently overexpressed in breast cancer than in normal breast tissue and correlated with worse prognosis. Meanwhile, high CD24 expression was associated with increased risk of HER2, basal-like, triple-negative breast cancer, and higher Scarff-Bloom-Richardson grade. Data mining in multiple big databases confirmed a positive correlation between CD24 mRNA expression and SDC1 mRNA expression in breast cancer tissue. CONCLUSIONS: Our findings suggest that CD24 overexpression is more common in breast cancer than in corresponding normal tissue. In addition, CD24 and SDC1 can serve as prognostic indicators for breast cancer. However, large-scale and comprehensive research is needed to further confirm these results.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Antígeno CD24/metabolismo , Biomarcadores Tumorais/genética , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Antígeno CD24/genética , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Fatores de Risco , Sindecana-1/genética , Sindecana-1/metabolismo , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
OBJECTIVES: Radiation-induced hypothyroidism is the most common thyroid disorder after radiotherapy in nasopharyngeal carcinoma (NPC) patients. This study evaluated the pattern of radiation-induced thyroid gland changes in 48 months after radiotherapy in NPC patients and the association of hypothyroidism incidence with thyroid dose. METHODS: Fifty-six NPC patients treated by intensity modulated radiotherapy in 2013 were recruited. All patients received baseline thyroid hormones (fT3, fT4 and TSH) tests and CT scan before radiotherapy. Repeated measures of the thyroid hormones and gland volume were performed at 3, 6, 12, 18, 24, 30, 36 and 48 months after treatment. Trend lines of the thyroid volume and hormone level changes against time were plotted. The incidence of hypothyroidism patients and its relationship with the dose were also evaluated. RESULTS: The mean thyroid volume followed a decreasing trend after radiotherapy, reaching a minimum (-39.8%) at 30 months and slightly increased afterward. The fT4 level followed a similar pattern with its mean value dropped by 21.5% at 30 months and became steady after 36 months. TSH level showed gradual rise from just after radiotherapy, reaching a peak at 24 months and became relatively steady after 36 months. The incidence of hypothyroidism increased to a maximum at 24 months (28.6%) and dropped afterwards. Thyroid Dmean and D50 were significantly correlated with hypothyroidism incidence in 12 to 30 months (ρ > 0.40, p < 0.05). CONCLUSION: The patterns of radiation induced thyroid volume shrinkage and fT4 level reduction were similar, with both of them showed decreasing trend from 0 to 30 months. The thyroid volume and function reached a relatively steady state after 36 months. The incidence of hypothyroidism increased up to 24 months and its frequency was associated with the thyroid dose.
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Hipotireoidismo/etiologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Glândula Tireoide/efeitos da radiação , Adulto , Idoso , Feminino , Seguimentos , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Lesões por Radiação/sangue , Lesões por Radiação/epidemiologia , Dosagem Radioterapêutica , Glândula Tireoide/patologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
BACKGROUND: The objectives of this study were to build a normal tissue complication probability (NTCP) model of radiation-induced hypothyroidism (RHT) for nasopharyngeal carcinoma (NPC) patients and to compare it with other four published NTCP models to evaluate its efficacy. METHODS: Medical notes of 174 NPC patients after radiotherapy were reviewed. Biochemical hypothyroidism was defined as an elevated level of serum thyroid-stimulating hormone (TSH) value with a normal or decreased level of serum free thyroxine (fT4) after radiotherapy. Logistic regression with leave-one-out cross-validation was performed to establish the NTCP model. Model performance was evaluated and compared by the area under the receiver operating characteristic curve (AUC) in our NPC cohort. RESULTS: With a median follow-up of 24 months, 39 (22.4%) patients developed biochemical hypothyroidism. Gender, chemotherapy, the percentage thyroid volume receiving more than 50 Gy (V50), and the maximum dose of the pituitary (Pmax) were identified as the most predictive factors for RHT. A NTCP model based on these four parameters were developed. The model comparison was made in our NPC cohort and our NTCP model performed better in RHT prediction than the other four models. CONCLUSIONS: This study developed a four-variable NTCP model for biochemical hypothyroidism in NPC patients post-radiotherapy. Our NTCP model for RHT presents a high prediction capability. TRIAL REGISTRATION: This is a retrospective study without registration.
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Hipotireoidismo/epidemiologia , Modelos Biológicos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Lesões por Radiação/sangue , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Tireotropina/sangue , Tiroxina/sangue , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to develop a nomogram for radiation-induced hypothyroidism (RHT) prediction. METHODS: We collected data from 164 patients with nasopharyngeal carcinoma (NPC) in our previous prospective study. Biochemical hypothyroidism was defined as a serum thyroid-stimulating hormone level greater than the normal value. We collected both clinical and dose-volume factors. A univariate Cox regression analysis was performed to identify RHT risk factors. Optimal predictors were selected according to the least absolute shrinkage and selection operator (LASSO). We then selected the Cox regression models that best balanced the prediction performance and practicability to build a nomogram for RHT prediction. RESULTS: There were 38 (23.2%) patients who developed RHT, and the median follow-up was 24 months. The univariate Cox regression analysis indicated that gender, minimum dose, mean dose (Dmean) and V25-V60 [Vx (%), the percentage of thyroid volume receiving >x Gy] of the thyroid were significantly associated with RHT. The variables of gender, receiving chemotherapy or not (chemo), Dmean and V50 were selected using the LASSO analysis. A nomogram based on a three-variable (gender, chemo and V50) Cox regression model was constructed, and its concordance index was 0.72. Good accordance between prediction and observation was showed by calibration curves in the probability of RHT at 18, 24 and 30 months. CONCLUSION: This study built a nomogram for RHT in NPC survivors by analyzing both clinical and dose-volume parameters using LASSO. Thus, the individual dose constraint could be achieved in a visual format. Advances in knowledge: This study used LASSO to more accurately address the multicollinear problem between variables. The resulting nomogram will help physicians predict RHT.
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Hipotireoidismo/etiologia , Neoplasias Nasofaríngeas/radioterapia , Nomogramas , Lesões por Radiação/diagnóstico , Radioterapia/efeitos adversos , Adolescente , Adulto , Idoso , Carcinoma , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Modelos de Riscos Proporcionais , Estudos Prospectivos , Doses de Radiação , Distribuição por Sexo , Glândula Tireoide/efeitos da radiação , Adulto JovemRESUMO
OBJECTIVE: To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). METHODS: We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. RESULTS: Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. CONCLUSION: ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. ADVANCES IN KNOWLEDGE: Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.
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Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Carcinoma , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Pescoço , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/mortalidade , Estudos Prospectivos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/mortalidade , Análise de Sobrevida , Falha de TratamentoRESUMO
INTRODUCTION: Flattening filter-free (FFF) radiation beams have recently become clinically available on modern linear accelerators in radiation therapy. This study aimed to evaluate the dosimetric impact of using FFF beams in intensity-modulated radiotherapy (IMRT) for early-stage upper thoracic oesophageal cancer. METHODS: Eleven patients with primary stage upper thoracic oesophageal cancer were recruited. For each patient, two IMRT plans were computed using conventional beams (Con-P) and FFF beams (FFF-P), respectively. Both plans employed a five-beam arrangement and were prescribed with 64 Gy to (planning target volume) PTV1 and 54 Gy to PTV2 in 32 fractions using 6 MV photons. The dose parameters of the target volumes and organs at risks (OARs), and treatment parameters including the monitor units (MU) and treatment time (TT) for Con-P and FFF-P were recorded and compared. RESULTS: The mean D 5 of PTV1 and PTV2 were higher in FFF-P than Con-P by 0.4 Gy and 0.3 Gy, respectively. For the OARs, all the dose parameters did not show significant difference between the two plans except the mean V 5 and V 10 of the lung in which the FFF-P was lower (46.7% vs. 47.3% and 39.1% vs. 39.6%, respectively). FFF-P required 54% more MU but 18.4% less irradiation time when compared to Con-P. CONCLUSION: The target volume and OARs dose distributions between the two plans were comparable. However, FFF-P was more effective in sparing the lung from low dose and reduced the mean TT compared with Con-P. Long-term clinical studies are suggested to evaluate the radiobiological effects of FFF beams.
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INTRODUCTION: Radiation-induced thyroid dysfunction after radiotherapy for nasopharyngeal cancer (NPC) has been reported. This study investigated the radiation effects of the thyroid and pituitary glands on thyroid function after radiotherapy for NPC. METHODS: Sixty-five NPC patients treated with radiotherapy were recruited. Baseline thyroid hormone levels comprising free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were taken before treatment and at 3, 6, 12 and 18 months. A seven-beam intensity-modulated radiotherapy plan was generated for each patient. Thyroid and pituitary gland dose volume histograms were generated, dividing the patients into four groups: high (>50 Gy) thyroid and pituitary doses (HTHP group); high thyroid and low pituitary doses (HTLP group); low thyroid and high pituitary doses; and low thyroid and pituitary doses. Incidence of hypothyroidism was analysed. RESULTS: Twenty-two (34%) and 17 patients (26%) received high mean thyroid and pituitary doses, respectively. At 18 months, 23.1% of patients manifested various types of hypothyroidism. The HTHP group showed the highest incidence (83.3%) of hypothyroidism, followed by the HTLP group (50%). CONCLUSIONS: NPC patients with high thyroid and pituitary gland doses carried the highest risk of abnormal thyroid physiology. The dose to the thyroid was more influential than the pituitary dose at 18 months after radiotherapy, and therefore more attention should be given to the thyroid gland in radiotherapy planning.
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Hipotireoidismo/epidemiologia , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/radioterapia , Hipófise/efeitos da radiação , Lesões por Radiação/epidemiologia , Radioterapia Conformacional/estatística & dados numéricos , Glândula Tireoide/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Causalidade , Comorbidade , Feminino , Hong Kong/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Resultado do TratamentoRESUMO
PURPOSE: Promoter hypermethylation of tumor suppressor genes may serve as a promising biomarker for the diagnosis of cancer. Cell-free circulating DNA (cf-DNA) shares hypermethylation status with primary tumors. This study investigated promoter hypermethylation of five tumor suppressor genes as markers in the detection of nasopharyngeal carcinoma (NPC) in serum samples. METHODS: cf-DNA was extracted from serum collected from 40 NPC patients and 41 age- and sex-matched healthy subjects. The promoter hypermethylation status of the five genes (RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1) was assessed by methylation-specific PCR after sodium bisulfite conversion. Differences in the methylation status of these five genes between NPC patients and healthy subjects were compared. RESULTS: The concentration of cf-DNA in the serum of NPC patients was significantly higher than that in normal controls. The five tumor suppressor genes - RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1 - were found to be methylated in 17.5%, 22.5%, 25.0%, 51.4% and 64.9% of patients, respectively. The combination of four-gene marker - CDKN2A, DLEC1, DAPK1 and UCHL1 - had the highest sensitivity and specificity in predicting NPC. CONCLUSION: Screening DNA hypermethylation of tumor suppressor genes in serum was a promising approach for the diagnosis of NPC.
Assuntos
Metilação de DNA , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Genes Supressores de Tumor , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/genética , Células Neoplásicas Circulantes , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , DNA Viral/sangue , DNA Viral/genética , Proteínas Quinases Associadas com Morte Celular/sangue , Proteínas Quinases Associadas com Morte Celular/genética , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Genes p16 , Herpesvirus Humano 4/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/virologia , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor/sangue , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/sangue , Ubiquitina Tiolesterase/genética , Adulto JovemRESUMO
This study compared the oral cavity dose between the routine 7-beam intensity-modulated radiotherapy (IMRT) beam arrangement and 2 other 7-beam IMRT with the conventional radiotherapy beam arrangements in the treatment of nasopharyngeal carcinoma (NPC). Ten NPC patients treated by the 7-beam routine IMRT technique (IMRT-7R) between April 2009 and June 2009 were recruited. Using the same computed tomography data, target information, and dose constraints for all the contoured structures, 2 IMRT plans with alternative beam arrangements (IMRT-7M and IMRT-7P) by avoiding the anterior facial beam and 1 conventional radiotherapy plan (CONRT) were computed using the Pinnacle treatment planning system. Dose-volume histograms were generated for the planning target volumes (PTVs) and oral cavity from which the dose parameters and the conformity index of the PTV were recorded for dosimetric comparisons among the plans with different beam arrangements. The dose distributions to the PTVs were similar among the 3 IMRT beam arrangements, whereas the differences were significant between IMRT-7R and CONRT plans. For the oral cavity dose, the 3 IMRT beam arrangements did not show significant difference. Compared with IMRT-7R, CONRT plan showed a significantly lower mean dose, V30 and V-40, whereas the V-60 was significantly higher. The 2 suggested alternative beam arrangements did not significantly reduce the oral cavity dose. The impact of varying the beam angles in IMRT of NPC did not give noticeable effect on the target and oral cavity. Compared with IMRT, the 2-D conventional radiotherapy irradiated a greater high-dose volume in the oral cavity.
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Carcinoma/radioterapia , Boca , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/instrumentação , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
BACKGROUND AND OBJECTIVE: The 2008 staging system of nasopharyngeal carcinoma (NPC) was generated based on the NPC 92 and AJCC staging system. It remains open to be consummated. This study was to evaluate its rationality as well as compare the stage distribution among the 3 staging systems, by using of MRI imaging. METHODS: MRI data was collected from a cohort of 177 cases of untreated NPC for retrospective review. We accepted the nasal involvement criteria of 2008 staging system, in which the borderline between the nasal cavity and nasopharynx was a line linked between both posterior walls of the maxillary sinus, for all of the 3 systems. RESULTS: Involvement of oropharynx, nasopharynx, soft palatine, prevertebral muscles, post-styloid space, intracranial, orbit, 1st and/or 2nd cervical body are 100% accompanied with other same or more advanced T-stage classifications. The same situations happened in more than 95% of involvement of the medial pterygoid muscle or masticator space beyond it. Cervical lymph node metastasis (LNM) accounted for 76.3%. Proportion of metastatic lymph node extracapsular extension (ECE) and/or bilateral neck LNM elevated as maximum diameter of the node increased, no matter transverse or longitudinal. There were 11 cases of parotid LNM in this group. Advanced stage accounted for 81.4%, 78.5% and 75.7% in 2008, UICC and NPC 92 staging system, respectively, without statistic difference. CONCLUSION: Nasal involvement criteria and T-stage classification of the medial pterygoid muscle defined by NPC 2008 staging system seems reasonable. Stage distribution is also similar to the other 2 systems. However, diameter of the LNM might not be a prognostic factor. Parameters such as how to classify a parotid LNM, or a node which occupies more than one region, require further clarify.