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OBJECTIVE: To identify the main risk factors for metachronous metastatic nasopharyngeal carcinoma (NPC) in different periods after radiotherapy and estimate the weight of various factors in the early or late metachronous metastasis (EMM/LMM) groups. METHODS: This retrospective registry consists of 4434 patients with newly diagnosed NPC. Cox regression analysis was used to assess the independent significance of various risk factors. The Interactive Risk Attributable Program (IRAP) was used to calculate the attributable risks (ARs) for metastatic patients during different periods. RESULTS: Among 514 metastatic patients, 346 (67.32%) patients diagnosed with metastasis within 2 years after treatment were classified into the EMM group, while other 168 patients were classified into the LMM group. The ARs of T-stage, N-stage, pre-Epstein-Barr virus (EBV) DNA, post-EBV DNA, age, sex, pre-neutrophil-to-lymphocyte ratio, pre-platelet-to-lymphocyte ratio, pre-hemoglobin (HB), and post-HB were 20.19, 67.25, 2.81, 14.28, 18.50, - 11.17%, 14.54, 9.60, 3.74% and - 9.79%, respectively, in the EMM group. In the LMM group, the corresponding ARs were 3.68, 49.11, - 18.04%, 2.19, 6.11, 0.36, 4.62, 19.77, 9.57 and 7.76%, respectively. After multivariable adjustment, the total AR for tumor-related factors was 78.19%, and that for patient-related factors was 26.07% in the EMM group. In the LMM group, the total AR of tumor-related factors was 43.85%, while the weights of patient-related factors was 39.97%. In addition, except for these identified tumor- and patient-related factors, other unevaluated factors played a more important role in patients with late metastasis, with the weight increasing by 15.77%, from 17.76% in the EMM group to 33.53% in the LMM group. CONCLUSION: Most metachronous metastatic NPC cases occurred in the first 2 years after treatment. Early metastasis was mainly affected by tumor-related factors, which accounted for a declining percentage in the LMM group.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Estudios Retrospectivos , Herpesvirus Humano 4/genética , Factores de Riesgo , Pronóstico , ADN ViralRESUMEN
BACKGROUND: SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer. METHODS: This cohort study used multidimensional genomic data of 6726 sequencing samples from our cooperative and non-public GenePlus institute from April 1 through April 10, 2020. MSIsensor score, HRD score, RNAseq, mutational data, and corresponding clinical data were obtained from the TCGA and MSKCC cohort for seven solid tumor types. RESULTS: A total of 1021 genes underwent target panel sequencing reveal that SETD2 mutations were associated with a higher TMB. SETD2 deleterious mutation dysfunction affected ICI treatment prognosis independently of TMB-H (p < 0.01) and had a lower death hazard than TMB-H in pancancer patients (0.511 vs 0.757). Significantly higher MSI and lower homologous recombination deficiency were observed in the SETD2 deleterious mutation group. Improved survival rate was found in the MSKCC-IO cohort (P < 0.0001) and was further confirmed in our Chinese cohort. CONCLUSION: We found that SETD2 dysfunction affects ICI treatment prognosis independently of TMB-H and has a lower death hazard than TMB-H in pancancer patients. Therefore, SETD2 has the potential to serve as a candidate biomarker for ICI treatment. Additionally, SETD2 should be considered when dMMR is detected by immunohistochemistry.
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Reparación del ADN , Inestabilidad de Microsatélites , Neoplasias Pancreáticas , Humanos , Pueblo Asiatico , Estudios de Cohortes , Reparación de la Incompatibilidad de ADN/genética , Reparación del ADN/genética , Inestabilidad Genómica , Inmunoterapia , Mutación , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidad , Reparación del ADN por Recombinación/genéticaRESUMEN
BACKGROUND: To rethink the clinical significance of standardized uptake values (SUVs) of nasopharyngeal carcinoma (NPC) on 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET). METHODS: We retrospectively reviewed 369 NPC patients who underwent pretreatment 18F-FDG PET. The predictive value of the SUVmax of the primary tumor (SUVmax-t) and regional lymph nodes (SUVmax-n) was evaluated using probability density functions. Receiver operating characteristic curves were used to determine optimal cutoffs for the SUVmax-n/SUVmax-t ratio (NTR). Kaplan-Meier and Cox regression analyses were used to assess survival. RESULTS: The optimal SUVmax-t and SUVmax-n cutoffs were 7.5 and 6.9, respectively. High SUVmax-t and SUVmax-n were related to local and regional recurrence, respectively. Patients with low SUVmax had better 3-year overall survival (OS). To avoid cross-sensitization of cutoff points, we stratified patients with high SUVmax into the low and high NTR groups. The 3-year distant metastasis-free survival (DMFS; 92.3 vs. 80.6%, P = 0.009), progression-free survival (PFS; 84.0 vs. 67.7%, P = 0.011), and OS (95.9 vs. 89.2%, P = 0.002) significantly differed between the high vs. low NTR groups for patients with high SUVmax. Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR]: 2.037, 95% CI: 1.039-3.992, P = 0.038), PFS (HR: 1.636, 95% CI: 1.021-2.621, P = 0.041), and OS (HR: 2.543, 95% CI: 1.214-5.325, P = 0.013). CONCLUSION: High SUVmax was associated with NPC recurrence. NTR is a potential prognosticator for DMFS, suggesting that heterogeneity in the pretreatment 18F-FDG uptake between the primary tumor and lymph nodes is associated with high invasion and metastatic potential.
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Fluorodesoxiglucosa F18 , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Pronóstico , Radiofármacos , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To assess the effect of pretreatment body mass index (BMI) and the extent of change in BMI (ΔBMI) during the treatment course on the treatment outcomes in patients with nasopharyngeal carcinoma (NPC) receiving volumetric modulated arc therapy (VMAT). METHODS: Data pertaining to 498 consecutive NPC patients with stage I-IVA disease who received VMAT between January 2010 and November 2011 at a single center were retrospectively analyzed. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the prognostic significance of pretreatment BMI and ΔBMI. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off point of ΔBMI. RESULTS: The 5-year loco-regional failure-free (L-FFR), distant failure-free survival (D-FFR), disease-free survival (DFS), and overall survival (OS) rates were 90.6%, 83.7%, 71.5% and 79.3%, respectively. The 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with ΔBMI ≤1 kg/m2 vs ΔBMI >1 kg/m2 were 92.3% vs 89.3% (P = .137), 90.9% vs 78.5% (P < .001), 80.4% vs 65.1% (P < .001), and 88.0% vs 73.0% (P < .001), respectively. ΔBMI >1 kg/m2 was an independent predictor of D-FFR (P = .002), DFS (P = .002), and OS (P = .001). CONCLUSIONS: ΔBMI during treatment course may have a significant impact on the prognosis of NPC patients receiving VMAT.
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Carcinoma , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Índice de Masa Corporal , Carcinoma/radioterapia , Supervivencia sin Enfermedad , Humanos , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Pronóstico , Estudios RetrospectivosRESUMEN
The PRKDC gene encodes the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) protein. DNA-PKcs plays an important role in nonhomologous end joining (NHEJ) of DNA double-strand breaks (DSBs) and is also closely related to the establishment of central immune tolerance and the maintenance of chromosome stability. The occurrence and development of different types of tumors and the results of their treatment are also influenced by DNA-PKcs, and it may also predict the results of radiotherapy, chemotherapy, and therapy with immune checkpoint inhibitors (ICIs). Here, we discuss and review the structure and mechanism of action of PRKDC and DNA-PKcs and their relationship with cancer.
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OBJECTIVE: To view and evaluate the prognosis factors in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy using nomogram and decision curve analysis (DCA). METHODS: Based on a primary cohort comprising consecutive patients with newly confirmed NPC (n = 1140) treated between January 2014 and December 2015, we identified independent prognostic factors of overall survival (OS) to establish a nomogram. The model was assessed by bootstrap internal validation and external validation in an independent validation cohort of 460 patients treated between January 2013 and December 2013. The predictive accuracy and discriminative ability were measured by calibration curve, concordance index (C-index) and risk-group stratification. The clinical usefulness was assessed by DCA. RESULTS: The nomogram incorporated T-stage, N-stage, age, concurrent chemotherapy and primary tumour volume (PTV). The calibration curve presented good agreement for between the nomogram-predicted OS and the actual measured survival probability in both the primary and validation cohorts. The model showed good discrimination with a C-index of 0.741 in the primary cohort and 0.762 in the validation cohort. The survival curves of different risk-groups were separated clearly. Decision curve analysis demonstrated that the nomogram provided a higher net benefit (NB) across a wider reasonable range of threshold probabilities for predicting OS. CONCLUSION: This study presents a predictive nomogram model with accurate prediction and independent discrimination ability compared with combination of T-stage and N-stage. The results of DCA supported the point that PTV can help improve the prognostic ability of T-stage and should be added to the TNM staging system.
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Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Nomogramas , Radioterapia de Intensidad Modulada , Adolescente , Adulto , Anciano , Calibración , Niño , Estudios de Cohortes , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Pronóstico , Radioterapia de Intensidad Modulada/mortalidad , Reproducibilidad de los Resultados , Análisis de Supervivencia , Adulto JovenRESUMEN
Background: Radiotherapy (RT) is a mainstay of head and neck squamous cell carcinoma (HNSCC) treatment. Due to the influence of RT on tumor cells and immune/stromal cells in microenvironment, some studies suggest that immunologic landscape could shape treatment response. To better predict the survival based on genomic data, we developed a prognostic model using tumor-infiltrating immune cell (TIIC) signature to predict survival in patients undergoing RT for HNSCC. Methods: Gene expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Data from HNSCC patients undergoing RT were extracted for analysis. TIICs prevalence in HNSCC patients was quantified by gene set variation analysis (GSVA) algorithm. TIICs and post-RT survival were analyzed using univariate Cox regression analysis and used to construct and validate a tumor-infiltrating cells score (TICS). Results: Five of 26 immune cells were significantly associated with HNSCC prognosis in the training cohort (all P<0.05). Kaplan-Meier (KM) survival curves showed that patients in the high TICS group had better survival outcomes (log-rank test, P<0.05). Univariate analyses demonstrated that the TICS had independent prognostic predictive ability for RT outcomes (P<0.05). Patients with high TICS scores showed significantly higher expression of immune-related genes. Functional pathway analyses further showed that the TICS was significantly related to immune-related biological process. Stratified analyses supported integrating TICS and tumor mutation burden (TMB) into individualized treatment planning, as an adjunct to classification by clinical stage and human papillomavirus (HPV) infection. Conclusions: The TICS model supports a personalized medicine approach to RT for HNSCC. Increased prevalence of TIIC within the tumor microenvironment (TME) confers a better prognosis for patients undergoing treatment for HNSCC.
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OBJECTIVE: We aimed to assess the significance of rENE and creat a predictive tool (nomogram) for estimating Overall Survival (OS) in locoregionally advanced Nasopharyngeal Carcinoma (NPC) patients with Lymph Node Metastasis (LNM) based on their clinical characteristics and Radiologic Extranodal Extension (rENE). METHODS: Five hundred and sixty-nine NPC patients with LNM were randomly divided into training and validation groups. Significant factors were identified using univariate and multivariate analyses in the training cohort. Then, the nomogram based on the screening results was established to predict the Overall Survival (OS). Calibration curves and the Concordance index (C-index) gauged predictive accuracy and discrimination. Receiver Operating Characteristic (ROC) analysis assessed risk stratification, and clinical utility was measured using Decision Curve Analysis (DCA). The nomogram's performance was validated for discrimination and calibration in an independent validation cohort. RESULTS: A total of 360 (63.2%) patients were present with radiologic extranodal extension at initial diagnosis. Patients with rENE had significantly lower OS than other patients. Multivariate analysis identified the five factors, including rENE, for the nomogram model. The C-index was 0.75 (0.71-0.78) in the training cohort and 0.76 (0.69-0.83) in the validation cohort. Notably, the nomogram outperformed the 8th TNM staging system, as evident from the higher AUC values (0.77 vs. 0.60 for 2year and 0.75 vs. 0.65 for 3year) and well-calibrated calibration curves. Decision curve analysis indicated improved Net Benefit (NB) with the nomogram for predicting OS. The log-rank test confirmed significant survival distinctions between risk groups in both training and validation cohorts. CONCLUSIONS: We demonstrated the prognostic value of rENE in nasopharyngeal carcinoma and developed a nomogram based on rENE and other factors to provide individual prediction of OS for locoregionally advanced nasopharyngeal carcinoma with lymph node metastasis. LEVEL OF EVIDENCE: III.
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Neoplasias Nasofaríngeas , Nomogramas , Humanos , Extensión Extranodal , Metástasis Linfática , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , PronósticoRESUMEN
OBJECTIVES: Current guidelines recommend universal PET/CT screening for metastases staging in newly diagnosed nasopharyngeal carcinoma (NPC) despite the low rate of synchronous distant metastasis (SDM). The study aims to achieve individualized screening recommendations of NPC based on the risk of SDM. METHODS AND MATERIALS: 18 pre-treatment peripheral blood indicators was retrospectively collected from 2271 primary NPC patients. A peripheral blood risk score (PBRS) was constructed by indicators associated with SDM on least absolute shrinkage and selection operator (LASSO) regression. The PBRS-based distant metastases (PBDM) model was developed from features selected by logistic regression analyses in the training cohort and then validated in the validation cohort. Receiver operator characteristic curve analysis, calibration curves, and decision curve analysis were applied to evaluate PBDM model performance. RESULTS: Pre-treatment Epstein-Barr viral DNA copy number, percentage of total lymphocytes, serum lactate dehydrogenase level, and monocyte-to-lymphocyte ratio were most strongly associated with SDM in NPC and used to construct the PBRS. Sex (male), T stage (T3-4), N stage (N2-3), and PBRS (≥1.076) were identified as independent risk factors for SDM and applied in the PBDM model, which showed good performance. Through the model, patients in the training cohort were stratified into low-, medium-, and high-risk groups. Individualized screening recommendations were then developed for patients with differing risk levels. CONCLUSION: The PBDM model offers individualized recommendations for applying PET/CT for metastases staging in NPC, allowing more targeted screening of patients with greater risk of SDM compared with current recommendations.
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Carcinoma Nasofaríngeo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/diagnóstico , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Adulto , Estudios Retrospectivos , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/diagnóstico , Anciano , Metástasis de la Neoplasia , Factores de Riesgo , Adulto Joven , Medicina de Precisión/métodosRESUMEN
OBJECTIVE: The role of Primary Tumor Volume (PTV) in Nasopharyngeal Carcinoma (NPC) treated with Volumetric Modulated Arc Therapy (VMAT) is still unclear. The aim of this study was to access the effect of PTV in prognosis prediction of nasopharyngeal carcinoma in era of VMAT. METHODS: Between January 20 and November 2011, 498 consecutive NPC patients with stage I-IVA disease who received VMAT at a single center were retrospectively analyzed. Receiver Operating Characteristic (ROC) was performed to access the cut-off point of PTV. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate prognostic value for PTV. The Propensity Score Matching (PSM) was used to adjust baseline potential confounders. RESULTS: The 5-year Locol-Regional Failure-Free (L-FFR), Distant Failure-Free Survival (D-FFR), Disease-Free Survival (DFS) and Overall Survival (OS) were 90.6%, 83.7%, 71.5% and 79.3%, respectively. Before PSM, the 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with PTVâ¯≤â¯38â¯mL vs. PTVâ¯>â¯38â¯mL were 94.1% vs. 90.4% (pâ¯=â¯0.063), 87.9% vs. 76.3% (pâ¯<â¯0.001), 78.5% vs. 58.5% (pâ¯<â¯0.001) and 86.3% vs. 66.7% (pâ¯<â¯0.001) respectively. Multivariate analysis showed PTV was an independent prognostic factor for D-FFS (pâ¯=â¯0.034), DFS (pâ¯=â¯0.002) and OS (pâ¯=â¯0.001). PTV classified was still an independent prognostic factor for OS after PSM (HR = 2.034, pâ¯=â¯0.025. CONCLUSIONS: PTV had a substantial impact on the prognosis of NPC patients treated with VMAT before and after PSM simultaneously. PTVâ¯>â¯38â¯mL may be considered as an indicator of the clinical stage of nasopharyngeal carcinoma. LEVEL OF EVIDENCE: III.
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Carcinoma , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patología , Estudios de Cohortes , Carcinoma/radioterapia , Estudios Retrospectivos , Radioterapia de Intensidad Modulada/efectos adversos , Puntaje de Propensión , Carga Tumoral , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patología , Pronóstico , Estadificación de NeoplasiasRESUMEN
BACKGROUND: To develop a common follow-up strategy for appropriate imaging examination at an appropriate time for nasopharyngeal carcinoma (NPC). METHODS: Independent prognostic factors were identified by Cox regression analysis, and a nomogram model was developed. Random survival forest (RSF) model was constructed to depict probability of disease failure during a 5-year follow-up and establish a reasonable risk-based follow-up strategy. RESULTS: The nomogram model finally categorized the patients into three risk groups. RSF model demonstrated distribution trends for local and regional recurrences, bone metastasis, liver metastasis, and lung metastasis of NPC. Adequate imaging at follow-up should be considered between 10 and 21 months for patients at moderate-risk of recurrence or metastasis and 7-36 months for those at high-risk. CONCLUSIONS: The temporal distribution of incidence rates of recurrence or metastasis varied among different risk groups. We recommend implementing a focused and targeted imaging surveillance intervention at appropriate times to improve its efficiency and reduce costs.
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Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Pronóstico , Estudios de Seguimiento , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: This study inventively combines epidermal growth factor receptor (EGFR) expression of the primary lesion and standardized uptake value (SUV) of positron emission tomography and computed tomography (PET/CT) to predict the prognosis of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the predictive efficacy of maximum standard uptake value (SUVmax) and EGFR for treatment failure in patients with NPC. METHODS: This retrospective study reviewed the results of EGFR expression and pretreatment 18F-FDG PET/CT of 313 patients with NPC. Time-dependent receiver operator characteristics was used for analyzing results and selecting the optimal cutoff values. Cox regression was used to screen out multiple risk factors. Cumulative survival rate was calculated by Kaplan-Meier. RESULTS: The selected cutoff value of SUVmax-T was 8.5. The patients were categorized into four groups according to EGFR expression and SUVmax-T. There were significant differences in the 3-year local recurrence-free survival (LRFS) (p = 0.0083), locoregional relapse-free survival (LRRFS) (p = 0.0077), distant metastasis-free survival (DMFS) (p = 0.013), and progression-free survival (PFS) (p = 0.0018) among the four groups. Patients in the EGFR-positive and SUVmax-T > 8.5 group had the worst survival, while patients in the EGFR-negative and SUVmax-T ≤ 8.5 group had the best prognosis. Subsequently, patients with only positive EGFR expression or high SUVmax-T were classified as the middle-risk group. There were also a significant difference in 3-year overall survival among the three risk groups (p = 0.034). SUVmax-T was associated with regional recurrence-free survival and LRRFS in multivariate analysis, whereas EGFR was an independent prognostic factor for LRRFS, DMFS, and PFS. CONCLUSION: The combination of SUVmax-T and EGFR expression can refine prognosis and indicate clinical therapy.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Receptores ErbB/metabolismo , Fluorodesoxiglucosa F18 , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/terapia , Recurrencia Local de Neoplasia/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Pronóstico , Radiofármacos , Estudios Retrospectivos , Insuficiencia del TratamientoRESUMEN
PURPOSE: To assess whether the high metabolic region of fluorine-18-fluorode-oxyglucose (18F-FDG) in the primary lesion is the crux for recurrence in patients with nasopharyngeal carcinoma (NPC), to assess the feasibility and rationale for use of biological target volume (BTV) based on 18F-FDG positron emission tomography/computed tomography (18F-FDG-PET/CT). METHODS: The retrospective study included 33 patients with NPC who underwent 18F-FDG-PET/CT at the time of initial diagnosis as well as the time of diagnosis of local recurrence. Paired 18F-FDG-PET/CT images for primary and recurrent lesion were matched by deformation coregistration method to determine the cross-failure rate between two lesions. RESULTS: The median volume of the Vpri (primary tumor volume using the SUV thresholds of 2.5), the Vhigh (the volume of high FDG uptake using the SUV50%max isocontour), and the Vrecur (the recurrent tumor volume using the SUV thresholds of 2.5) were 22.85, 5.57, and 9.98 cm3, respectively. The cross-failure rate of Vrecurâ©high showed that 82.82% (27/33) of local recurrent lesions had < 50% overlap volume with the region of high FDG uptake. The cross-failure rate of Vrecurâ©pri showed that 96.97% (32/33) of local recurrent lesions had > 20% overlap volume with the primary tumor lesions and the median cross rate was up to 71.74%. CONCLUSION: 18F-FDG-PET/CT may be a powerful tool for automatic target volume delineation, but it may not be the optimal imaging modality for dose escalation radiotherapy based on applicable isocontour. The combination of other functional imaging could delineate the BTV more accurately.
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Neoplasias Nasofaríngeas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Estudios Retrospectivos , Flúor , Recurrencia Local de Neoplasia , Tomografía de Emisión de Positrones , Carcinoma Nasofaríngeo , RadiofármacosRESUMEN
INTRODUCTION: This study aimed to evaluate the survival and prognosis of older patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy using propensity score matching (PSM). MATERIALS AND METHODS: We enrolled 841 older patients with NPC aged 60 years and above without metastasis receiving IMRT alone or chemoradiotherapy from 2012 to 2019. The comorbidity was assessed by adult comorbidity evaluation (ACE-27). PSM (1:3 ratio) was conducted between the two treatment groups based on four clinical factors including age, T-stage, N-stage, and ACE-27. Differences in overall survival (OS) and cancer-specific survival (CSS) were analyzed by the Kaplan-Meier method and Cox proportional hazard model. RESULTS: A total of 841 patients with NPC were included in the study, there were 94 patients in the IMRT alone group and 747 patients in the chemoradiotherapy (CRT) group. After a 1:3 ratio PSM, 89 patients underwent IMRT alone and 223 patients underwent CRT. The baseline analysis showed an insignificant difference after PSM (P > 0.05). In multivariate analysis, we found that ACE-27 (≥2) was associated with worse five-year OS and CSS (HR = 1.994, 95%CI: 1.276-3.116, P = 0.002; HR = 1.849, 95%CI: 1164-2.935, P = 0.009, respectively). Chemotherapy was an independent prognosticator of better five-year OS and CSS (HR = 0.333, 95%CI: 0.213-0.552, P < 0.001; HR = 0.327, 95%CI: 0.204-0.524, P < 0.001, respectively). In terms of subgroup analysis, chemotherapy was a statistically beneficial predictor for stage III-IV patients (P < 0.05), but no significant difference in stage II patients (P > 0.05). About the adverse events, the incidence of hepatotoxicity (P = 0.002), neutropenia (P < 0.001), anemia (P < 0.001), and thrombocytopenia (P < 0.001) were significantly higher in the CRT group. DISCUSSION: Combined modality therapy was associated with improved five-year OS and CSS in older adults with stage III-IV NPC, but was not associated with improved survival over IMRT alone in patients with stage II disease. Risk factors including T3-4 disease, positive lymph nodes, ACE-27 score ≥ 2, and IMRT alone were were associated with worse OS and CSS. There was a significantly higher incidence of hepatotoxicity and blood toxicity in the CRT group.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Humanos , Anciano , Carcinoma Nasofaríngeo/tratamiento farmacológico , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias Nasofaríngeas/tratamiento farmacológico , Puntaje de Propensión , Estudios Retrospectivos , Quimioradioterapia/métodos , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Estadificación de NeoplasiasRESUMEN
To explore the prognostic significance of PET/CT-based radiomics signatures and clinical features for local recurrence-free survival (LRFS) in nasopharyngeal carcinoma (NPC). We retrospectively reviewed 726 patients who underwent pretreatment PET/CT at our center. Least absolute shrinkage and selection operator (LASSO) regression and the Cox proportional hazards model were applied to construct Rad-score, which represented the radiomics features of PET-CT images. Univariate and multivariate analyses were used to establish a nomogram model. The concordance index (C-index) and calibration curve were used to evaluate the predictive accuracy and discriminative ability. Receiver operating characteristic analysis was performed to stratify the local recurrence risk of patients. The nomogram was validated by evaluating its discrimination ability and calibration in the validation cohort. A total of eight features were selected to construct Rad-score. A radiomics-clinical nomogram was built after the selection of univariate and multivariable Cox regression analyses, including the Rad-score and maximum standardized uptake value (SUVmax). The C-index was 0.71 (0.67-0.74) in the training cohort and 0.70 (0.64-0.76) in the validation cohort. The nomogram also performed far better than the 8th T-staging system with an area under the receiver operating characteristic curve (AUC) of 0.75 vs. 0.60 for 2 years and 0.71 vs. 0.60 for 3 years. The calibration curves show that the nomogram indicated accurate predictions. Decision curve analysis (DCA) revealed significantly better net benefits with this nomogram model. The log-rank test results revealed a distinct difference in prognosis between the two risk groups. The PET/CT-based radiomics nomogram showed good performance in predicting LRFS and showed potential to identify patients at high-risk of developing NPC.
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Neoplasias Nasofaríngeas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Nomogramas , Fluorodesoxiglucosa F18 , Carcinoma Nasofaríngeo/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Skin lesion segmentation from dermoscopy images is of great significance in the quantitative analysis of skin cancers, which is yet challenging even for dermatologists due to the inherent issues, i.e., considerable size, shape and color variation, and ambiguous boundaries. Recent vision transformers have shown promising performance in handling the variation through global context modeling. Still, they have not thoroughly solved the problem of ambiguous boundaries as they ignore the complementary usage of the boundary knowledge and global contexts. In this paper, we propose a novel cross-scale boundary-aware transformer, XBound-Former, to simultaneously address the variation and boundary problems of skin lesion segmentation. XBound-Former is a purely attention-based network and catches boundary knowledge via three specially designed learners. First, we propose an implicit boundary learner (im-Bound) to constrain the network attention on the points with noticeable boundary variation, enhancing the local context modeling while maintaining the global context. Second, we propose an explicit boundary learner (ex-Bound) to extract the boundary knowledge at multiple scales and convert it into embeddings explicitly. Third, based on the learned multi-scale boundary embeddings, we propose a cross-scale boundary learner (X-Bound) to simultaneously address the problem of ambiguous and multi-scale boundaries by using learned boundary embedding from one scale to guide the boundary-aware attention on the other scales. We evaluate the model on two skin lesion datasets and one polyp lesion dataset, where our model consistently outperforms other convolution- and transformer-based models, especially on the boundary-wise metrics. All resources could be found in https://github.com/jcwang123/xboundformer.
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Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/diagnóstico por imagen , Procesamiento de Imagen Asistido por ComputadorRESUMEN
Background: Circulating immune cells are associated with tumor development and poor prognosis in multiple solid tumors. However, the circulating immune-cell profile of nasopharyngeal carcinoma (NPC) remains largely unknown. Therefore, we aimed to determine the changes in immune status and the prognostic significance of circulating immune cells before and after chemoradiotherapy (CRT) in patients, which can provide clinicians with valuable insights to optimize treatment strategies, monitor immune function, and personalize interventions, ultimately improving patient outcomes. Methods: Circulating immune cells before and after CRT in 77 patients with NPC and in 30 healthy controls were measured with flow cytometry. A thorough follow-up was conducted to assess prognosis outcomes, including local failure-free rate (LFFR), distant failure-free rate (DFFR), disease-free survival (DFS), and overall survival (OS). The differences of the subpopulation distribution in the two groups were determined by t-tests or Mann-Whitney tests. The paired t-test or Wilcoxon matched-pairs signed rank test was used to compare differences in lymphocyte subsets before and after CRT. The prognostic significance of lymphocyte subsets was evaluated by Kaplan-Meier analysis and Cox proportional hazards model. Results: Compared with the control group, the NPC group showed significant decreases in the proportions of CD3+ cells, CD4+ T cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio (P<0.05) but a significant increase in the proportion of natural killer (NK) cells (P<0.05). After CRT, the proportions of CD4+ cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio were markedly decreased (P<0.05), while the proportions of CD8+ T cells and NK cells were significantly increased (P<0.05). Multivariate analysis showed that a lower percentage of CD19+ B cells [hazard ratio (HR) 6.550, 95% CI: 1.661-25.831; P=0.007] and a positive test for Epstein-Barr virus (EBV) DNA (HR 0.261, 95% CI: 0.074-0.926; P=0.038) before treatment independently predicted worse 5-year OS (P<0.05). Conclusions: The disproportion of circulating immune cells was observed in patients with NPC before treatment. CRT further aggravated immune dysfunction. Notably, a lower percentage of CD19+ B cells and EBV DNA-positive status before treatment were independent predictors of a worse prognosis. Thus, the measurement of circulating immune cells may help elucidate immune function status and predict the outcomes of patients with NPC.
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BACKGROUND: To identify patients at low risk of synchronous bone metastasis who should not receive bone scans when initially diagnosed with nasopharyngeal carcinoma (NPC). METHODS: In total, 6652 patients were enrolled in the training cohort and 1919 patients in the multicenter external validation cohort. Logistic regression analyses were performed to assess independent predictors of synchronous bone metastasis for the nomogram model. RESULTS: After risk stratification, 46.3% (3081/6652) patients were separated into the low-risk group with an incidence of 0.71% for synchronous bone metastasis. The odds ratio of the intermediate and high-risk groups was 5.61 and 23.82 times that of the low-risk group, respectively. For patients with high EBV DNA, we recommend routine screening for N2-3 female patients, but that all male subgroups are screened. CONCLUSIONS: Bone scans should not be routine. Patients in the low-risk group should not be screened, which would avoid excessive radiation and economize iatrical resource.
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Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/patología , Estudios Retrospectivos , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Nomogramas , Factores de Riesgo , PronósticoRESUMEN
Cone-beam CT (CBCT) of Elekta can be used to analyze the setup errors in intensity modulated radiotherapy. A total of 240 patients with head and neck cancer were chosen in the period from October, 2009 to October, 2010. Their CBCT images were obtained after initial setup, and registered to the planning CT images, and then the setup errors on translational directions (X, Y, Z) and on rotational directions (U, V, W) were obtained and analyzed. The results showed that the setup errors on translational directions in Y-axis and Z-axis were larger than in X-axis, and the setup errors on rotational directions in Y-axis was much more obvious than those on the other two directions, which should be taken care during the patient daily setup. It may be concluded that the CBCT system can improve the precision for radiotherapy.
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Tomografía Computarizada de Haz Cónico , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/radioterapia , Errores de Configuración en Radioterapia/estadística & datos numéricos , Radioterapia de Intensidad Modulada , Tomografía Computarizada de Haz Cónico/métodos , Humanos , Errores de Configuración en Radioterapia/prevención & controlRESUMEN
BACKGROUND/PURPOSE: Immunotherapy has become a research hotspot and is used for head and neck cancer treatment. This research aims to explore the prognostic value of PYHIN1 in oral cancer and the relationship between PYHIN1 and cancer immunity. MATERIALS AND METHODS: The expression of PYHIN1 in clinical specimens was evaluated by bioinformatics analyses and immunohistochemistry. RESULTS: Gene ontology term enrichment analyses and gene set enrichment analyses showed the involvement of PYHIN1 in the modulation of adaptive immunity-associated signaling according to The Cancer Genome Atlas database and Gene Expression Omnibus dataset. Interestingly, the correlation analyses in The Cancer Genome Atlas database revealed a positive correlation between PYHIN1 expression and activated CD8+ T cells infiltration and a negative correlation between PYHIN1 expression and tumor purity. Moreover, activated CD8+ T cells infiltration predicted good patient survival and was negatively correlated with tumor purity. Importantly, PYHIN1 expression was negatively correlated with the pathological stage and was positively associated with a good prognosis in patients with oral cancer. The data obtained from the Gene Expression Omnibus dataset and immunohistochemistry confirmed the positive association between PYHIN1 and CD8+ T cells infiltration in oral cancer tissues. CONCLUSION: We conclude that PYHIN1 is an indicator of cancer immunity, and is an independent prognostic factor that may be an alternative target for oral cancer treatment.