-
JAMA Network Open Feb 2022Laryngeal preservation strategies for resectable locally advanced hypopharyngeal carcinoma (LAHPC) have been explored. However, the optimal strategy remains unclear.
IMPORTANCE
Laryngeal preservation strategies for resectable locally advanced hypopharyngeal carcinoma (LAHPC) have been explored. However, the optimal strategy remains unclear.
OBJECTIVE
To evaluate a response-adapted strategy based on an early response to radiotherapy (RT) in patients with resectable LAHPC.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was conducted from May 2009 to October 2019 with a median (IQR) follow-up period of 66.5 (44.7-97.0) months. The study was conducted at a tertiary academic medical center and included 423 patients pathologically confirmed stage III and IVB LAHPC. A total of 250 patients with previous cancer history, synchronous primary cancer, stage I or II, or with unresectable hypopharyngeal carcinoma were excluded.
EXPOSURES
Patients who reached 80% or greater tumor regression when evaluated endoscopically and by imaging methods at 50 Gy received definitive RT or concurrent chemoradiotherapy, and those with less than 80% regression underwent surgery 4 to 6 weeks after RT.
MAIN OUTCOMES AND MEASURES
Five-year overall survival and survival with a functional larynx.
RESULTS
Overall, 423 patients were included in the study (median [IQR] age, 55 [50-63] years; 408 [96.5%] men and 15 [3.5%] women). The response-adapted and primary surgery groups had significantly better survival than the primary RT group (52.7% and 54.4% vs 27.7%, respectively; P < .001). The response-adapted and primary surgery groups had similar 5-year overall survival of 52.7% vs 54.4%, respectively (hazard ratio [HR], 1.02; 95% CI, 0.75 to 1.39; P = .89). The response-adapted group had better 5-year survival with functional larynx than the primary surgery group (40.6% vs 33.9%; HR, 0.64; 95% CI, 0.49 to 0.84, P = .001). Surgery complications did not significantly differ between the 2 groups. Among patients in the response-adapted group who required total laryngectomy (n = 186) as indicated by pretreatment evaluation, the 5-year cumulative Kaplan-Meier survival with functional larynx was 39.8%.
CONCLUSIONS AND RELEVANCE
In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, maximum tumor control, and higher laryngeal preservation compared with primary surgery and primary RT strategies. This approach could provide a feasible laryngeal preservation strategy in patients with LAHPC.
Topics: Antineoplastic Agents; Chemoradiotherapy; Cohort Studies; Female; Humans; Hypopharyngeal Neoplasms; Laryngectomy; Larynx; Male; Middle Aged
PubMed: 35191967
DOI: 10.1001/jamanetworkopen.2022.0165 -
Medicine Jun 2020Nasopharyngeal carcinoma (NPC) is the most common malignant tumor with a remarkable racial and geographical distribution including people in southern China, South East...
Nasopharyngeal carcinoma (NPC) is the most common malignant tumor with a remarkable racial and geographical distribution including people in southern China, South East Asia, and the Middle East/North Africa. DNA methylation is an important manifestation of epigenetic modification, has been studied over several decades, and by regulating and controlling the expression of cancer-related genesits, abnormal DNA methylation can influence in a variety of human malignancy tumors.Until now, there is no analysis focus on differentially methylated, differential expressed genes (MDEGs) study, so we make a joint analysis for both gene methylation profiling microarray and gene expression profiling microarray in NPC. Two gene expression datasets (GSE64634 and GSE12452) and gene methylation profiling data set (GSE62336) were downloaded from GEO and analyzed using the online tool GEO2R to identify MDEGs. Gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differentially methylated genes were performed. The STRING database was used to evaluate the interactions of MDEGs and to construct a protein-protein interaction (PPI) network using Cytoscape software. Hub genes were validated with the cBioPortal database.The overlap among the 3 datasets contained 135 hypermethylation genes and 541 hypomethylation genes between NPC and non-NPC samples. A total of 4 genes (TROAP, PCOLCE2, HOXA4, and C1QB) in Hyper-LGs and 14 genes (DYNC1H1, LNX1, RAB37, ALDH3A1, SLC24A4, CP, CEP250, ANK2, DNAI2, MUC13, ACACB, GABRP, STX7, and TTC9) in Hypo-HGs were identified as hub genes.The study of DNA methylation and gene expression provides us a strong support as well as new comprehensive information of MDEGs to the revelation of nasopharyngeal carcinoma's complex pathogenesis. However, further studies are needed to elucidate the biological function of these genes in NPC in the future.
Topics: DNA Methylation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Microarray Analysis; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis
PubMed: 32541515
DOI: 10.1097/MD.0000000000020682 -
Disease Markers 2022The prognostic value of tumor-infiltrating immune cells has been widely studied in nasopharyngeal carcinoma (NPC). However, the role of tumor-infiltrating immune cells...
BACKGROUND
The prognostic value of tumor-infiltrating immune cells has been widely studied in nasopharyngeal carcinoma (NPC). However, the role of tumor-infiltrating immune cells in the diagnosis of NPC has not been fully elucidated. Thus, tumor-infiltrating immune cell-related biomarkers in the diagnosis of NPC patients were explored in the current study.
METHODS
Gene expression profiles of NPC patients were downloaded from the Gene Expression Omnibus (GEO) database. Differentially infiltrating immune cells (DDICs) between NPC and control samples were analyzed by the CIBERSORT algorithm. Weighted gene coexpression network analysis (WGCNA) was performed to screen hub genes significantly correlated with DDIC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of hub genes were performed with R package clusterProfiler. The diagnostic value of hub genes was evaluated by receiver operating characteristic (ROC) curves. RT-qPCR was conducted to validate the expression patterns of diagnostic markers in NPC and adjacent control tissues. The correlations between diagnostic markers and immunomodulators were analyzed using the TISIDB. The protein-protein interaction (PPI) network based on immunomodulators significantly associated with diagnostic biomarkers was constructed and visualized by STRING. The functional enrichment analysis of genes in the PPI network was analyzed by the WebGestalt online tool.
RESULTS
The abundances of memory B cells, plasma cells, follicular helper T cells, activated NK cells, M0 macrophages, M1 macrophages, M2 macrophages, resting mast cells, and activated mast cells were significantly different between NPC and control samples. Dark orange was identified as the hub module, with a total of 371 genes associated with memory B cells, plasma cells, and M0 and M1 macrophages defined as hub genes, which were enriched into immune-related biological processes and pathways. , , and were considered diagnostic biomarkers with areas under ROC curves as 0.985, 0.978, and 0.975, respectively. Moreover, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) suggested that the expression patterns of , , and were consistent with the results in GEO datasets. TISIDB analysis revealed that , , and had a strong association with 8 immunoinhibitors (, , , , , , , and ) and 11 immunostimulators (, , , , , , , , , , and or ). The PPI network implied that these 19 immunomodulators had interactions with other 50 genes. WebGestalt analysis demonstrated that 69 genes in the PPI network were enriched into cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and pathways in cancer.
CONCLUSION
Our study identified novel diagnostic biomarkers and revealed potential immune-related mechanisms in NPC. These findings enlighten the investigation of the molecular mechanisms of tumor-infiltrating immune cells regulating NPC.
Topics: Humans; Nasopharyngeal Carcinoma; Computational Biology; Gene Expression Profiling; Biomarkers; Nasopharyngeal Neoplasms
PubMed: 36438903
DOI: 10.1155/2022/3934704 -
PloS One 2024The prognosis of nasopharyngeal carcinoma (NPC) is challenging due to late-stage identification and frequently undetectable Epstein-Barr virus (EBV) DNA. Incorporating...
BACKGROUND
The prognosis of nasopharyngeal carcinoma (NPC) is challenging due to late-stage identification and frequently undetectable Epstein-Barr virus (EBV) DNA. Incorporating radiomic features, which quantify tumor characteristics from imaging, may enhance prognosis assessment.
PURPOSE
To investigate the predictive power of radiomic features on overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) in NPC.
MATERIALS AND METHODS
A retrospective analysis of 183 NPC patients treated with chemoradiotherapy from 2010 to 2019 was conducted. All patients were followed for at least three years. The pretreatment CT images with contrast medium, MR images (T1W and T2W), as well as gross tumor volume (GTV) contours, were used to extract radiomic features using PyRadiomics v.2.0. Robust and efficient radiomic features were chosen using the intraclass correlation test and univariate Cox proportional hazard regression analysis. They were then combined with clinical data including age, gender, tumor stage, and EBV DNA level for prognostic evaluation using Cox proportional hazard regression models with recursive feature elimination (RFE) and were optimized using 20 repetitions of a five-fold cross-validation scheme.
RESULTS
Integrating radiomics with clinical data significantly enhanced the predictive power, yielding a C-index of 0.788 ± 0.066 to 0.848 ± 0.079 for the combined model versus 0.745 ± 0.082 to 0.766 ± 0.083 for clinical data alone (p<0.05). Multimodality radiomics combined with clinical data offered the highest performance. Despite the absence of EBV DNA, radiomics integration significantly improved survival predictions (C-index ranging from 0.770 ± 0.070 to 0.831 ± 0.083 in combined model versus 0.727 ± 0.084 to 0.734 ± 0.088 in clinical model, p<0.05).
CONCLUSIONS
The combination of multimodality radiomic features from CT and MR images could offer superior predictive performance for OS, PFS, and DMFS compared to relying on conventional clinical data alone.
Topics: Humans; Nasopharyngeal Carcinoma; Epstein-Barr Virus Infections; Retrospective Studies; Nasopharyngeal Neoplasms; Radiomics; Herpesvirus 4, Human; Prognosis; DNA; DNA, Viral
PubMed: 38346058
DOI: 10.1371/journal.pone.0298111 -
International Journal of Oncology Apr 2021As a malignant tumor type, nasopharyngeal carcinoma (NPC) is characterized by distinct geographical, ethnic and genetic differences; presenting a major threat to human... (Review)
Review
As a malignant tumor type, nasopharyngeal carcinoma (NPC) is characterized by distinct geographical, ethnic and genetic differences; presenting a major threat to human health in many countries, especially in Southern China. At present, no accurate and effective methods are available for the early diagnosis, efficacious evaluation or prognosis prediction for NPC. As such, a large number of patients have locoregionally advanced NPC at the time of initial diagnosis. Many patients show toxic reactions to overtreatment and have risks of cancer recurrence and distant metastasis owing to insufficient treatment. To solve these clinical problems, high‑throughput '‑omics' technologies are being used to screen and identify specific molecular biomarkers for NPC. Because of the lack of comprehensive descriptions regarding NPC biomarkers, the present study summarized the research progress that has been made in recent years to discover NPC biomarkers, highlighting the existing problems that require exploration. In view of the lack of authoritative reports at present, study design factors that affect the screening of biomarkers are also discussed here and prospects for future research are proposed to provide references for follow‑up studies of NPC biomarkers.
Topics: Biomarkers, Tumor; Genome; Humans; Metabolome; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Prognosis; Proteome; Transcriptome
PubMed: 33649830
DOI: 10.3892/ijo.2021.5188 -
Acta Otorhinolaryngologica Italica :... Jun 2023
Review
Topics: Humans; Nasopharyngeal Carcinoma; Prognosis; Combined Modality Therapy; Nasopharyngeal Neoplasms; Head and Neck Neoplasms; Radiotherapy, Intensity-Modulated; Neoplasm Staging; Treatment Outcome
PubMed: 37204840
DOI: 10.14639/0392-100X-N2223 -
The International Journal of Biological... Mar 2022To evaluate the prognostic effect of pretreatment serum superoxide dismutase (SOD) activity in locoregionally advanced nasopharyngeal carcinoma.
PURPOSE
To evaluate the prognostic effect of pretreatment serum superoxide dismutase (SOD) activity in locoregionally advanced nasopharyngeal carcinoma.
METHODS
A total of 498 patients diagnosed with stage III-IVA nasopharyngeal carcinoma between January 2013 and December 2016 were involved in this study. The X-tile program was used to determine the cut-off value of pretreatment serum SOD activity based on disease-free survival. Kaplan-Meier methods and Cox proportional hazards models were used to evaluate the impact of serum SOD levels on survival outcomes. The receiver operating characteristic (ROC) curve analysis was used to compare the prognostic value of clinical stage, pretreatment serum SOD level, and the combination of them regarding disease-free survival.
RESULTS
Based on the X-tile plot, the optimal cutoff value of pretreatment serum SOD activity for disease-free survival was 146.0U/mL. As a dichotomous variable, SOD was significantly higher in non-keratinizing differentiated disease ( = 0.027) and early T stage ( = 0.011). Compared with the lower subset, higher SOD activity predicted an inferior 3-year rates of overall survival (84.6 vs. 94.7%, < 0.001), distant metastasis-free survival (78.3 vs. 92.8%, < 0.001) and disease-free survival (78.2 vs. 92.8%, < 0.001). Multivariate analysis verified that the SOD activity was an independent prognostic indicator to predict distant metastasis, disease progression, and death. The area under the ROC curve (AUC) of the combination was superior to that of clinical stage or SOD alone for disease-free survival (both < 0.01).
CONCLUSION
Serological SOD activity before treatment is an important prognostic indicator for patients with stage III-IV non-metastatic nasopharyngeal carcinoma undergoing chemoradiation therapy.
Topics: Disease-Free Survival; Humans; Kaplan-Meier Estimate; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Staging; Prognosis; Superoxide Dismutase
PubMed: 35099330
DOI: 10.1177/17246008221075042 -
Journal of Translational Medicine Sep 2021The purpose of this study was to evaluate if HPV status serves as an independent predictor of early and late dysphagia outcomes when considered alongside standard...
PURPOSE
The purpose of this study was to evaluate if HPV status serves as an independent predictor of early and late dysphagia outcomes when considered alongside standard patient characteristics and dose metrics for head and neck cancer patients treated with radiotherapy.
METHODS AND MATERIALS
The age, sex, smoking history, cancer type (oropharyngeal vs non-oropharyngeal), HPV status, and early and late dysphagia outcomes were obtained for 99 retrospective head and neck cancer patients treated at our clinic with radiotherapy. Additionally for each patient, the mean radiation dose to the pharynx, superior/middle/inferior pharyngeal constrictor muscles, and cricopharyngeus was calculated. The predictive power of these clinical characteristics and radiation metrics was evaluated using chi-square tests for categorical variables and t-tests for continuous variables. Then multi-variate logistic models were built for each outcome using a single dose metric at a time, and either HPV status, cancer type, or both. Multi-variate models were built using both top-down and bottom-up technique to establish the most predictive independent covariates.
RESULTS
In the univariate analysis for early dysphagia, cancer type (p = 0.04) and four dose metrics (p ≤ 0.02) were significantly associated with outcome, while for late dysphagia, only cancer type (p = 0.04) was associated with outcome. In the multivariate analysis for early dysphagia, cancer type, smoking history, and mean dose to the five structures were consistently selected as covariates. For late dysphagia, either HPV status or cancer type was selected in each model and the mean dose to the cricopharyngeus was selected in one model.
CONCLUSION
While HPV is a known contributing factor for tumor prognosis in oropharyngeal cancers, its role in normal tissue toxicities for head and neck cancers has not previously been evaluated. Our results indicate having an oropharyngeal cancer may increase a patient's risk of high-grade early and late dysphagia while HPV status was seldom selected.
Topics: Deglutition Disorders; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Pharyngeal Muscles; Retrospective Studies
PubMed: 34493300
DOI: 10.1186/s12967-021-03047-2 -
Cancer Imaging : the Official... Dec 2023Nasopharyngeal carcinoma (NPC) is a relatively common type of cancer in Southern China, with local recurrence or distant metastases even after radical treatment;...
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a relatively common type of cancer in Southern China, with local recurrence or distant metastases even after radical treatment; consequently, it is critical to identify the patients at higher risk for these events beforehand. This study aimed to assess the prognostic value of regional lymph node density (RLND) associated nomograms in NPC and to evaluate the utility of nomograms in risk stratification.
METHODS
A total of 610 NPC patients without distant metastases (425 in the training and 185 in the validation cohort) were enrolled. The MRI-identified nodal features and clinical characteristics were documented, and the RLND was calculated. Cox analyses were conducted to identify prognostic-associated factors. Nomograms were generated based on the multivariate analysis results. The predictive accuracy and discriminative ability of the nomogram models were determined using the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve; the results were compared with those of the tumor-node-metastasis (TNM) classification. Decision curve analysis (DCA) and C-index were used to assess the prognostic effect and added discriminative ability of RLND. We also estimated the optimal RLND-based nomogram score cut-off values for survival prediction.
RESULTS
RLND was an independent predictor of overall survival (OS) and disease-free survival (DFS), with hazard ratios of 1.36 and 1.30, respectively. RLND was utilized in the construction of nomograms, alongside other independent prognostic factors. The RLND-based nomogram models presented a more effective discriminative ability than the TNM classification for predicting OS (C-index, 0.711 vs. 0.680) and DFS (C-index, 0.681 vs. 0.669), with favorable calibration and consistency. The comparison of C-index values between the nomogram models with and without RLND provided substantiation of the crucial role RLND plays in these models. DCA confirmed the satisfactory clinical practicability of RLND. Moreover, the nomograms were used to categorize the patients into three groups (high-, middle-, and low-risk), and the Kaplan-Meier curves showed significant differences in prognosis between them (p < 0.05). These results were verified in the validation cohort.
CONCLUSION
RLND stands as a robust prognostic factor in NPC. The RLND-based nomograms excel in predicting survival, surpassing the TNM classification.
Topics: Humans; Nomograms; Nasopharyngeal Carcinoma; Neoplasm Staging; Prognosis; Nasopharyngeal Neoplasms; Lymph Nodes
PubMed: 38102725
DOI: 10.1186/s40644-023-00641-z -
BMC Medicine Nov 2023Treatment options beyond the first-line setting for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are limited. The role of the multitarget tyrosine kinase...
BACKGROUND
Treatment options beyond the first-line setting for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are limited. The role of the multitarget tyrosine kinase inhibitor anlotinib in RM-NPC is unclear.
METHODS
In this prospective, single-arm, phase 2 trial, patients with histologically confirmed RM-NPC and failure of at least two lines of prior systemic treatments were eligible. Anlotinib was given at 12 mg once daily on days 1-14 every 3 weeks until disease progression or intolerable toxicities. The primary end point was disease control rate, defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria.
RESULTS
From April 2019 to March 2021, 39 patients were enrolled and received a median of 4 cycles (range, 0.5-20) of anlotinib treatment. Partial response and stable disease were observed in 8 and 20 patients, respectively. The disease control rate was 71.8%, and objective response rate was 20.5%. With a median follow-up of 17.2 months, the median progression-free survival was 5.7 months. The 12-month overall survival was 58.3%, and the median overall survival was not reached. The most frequent grade 3/4 treatment-related adverse events were hand-foot syndrome (23.7%), oral mucositis (21.0%), hypertension (7.9%), and triglyceride elevation (7.9%). Hemorrhage, all grade 1 or 2, occurred in 34.2% of the patients.
CONCLUSIONS
Anlotinib monotherapy exhibited promising anti-tumor activities and disease control for heavily pretreated RM-NPC patients with a tolerable toxicity profile.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT03906058.
Topics: Humans; Nasopharyngeal Carcinoma; Prospective Studies; Neoplasm Recurrence, Local; Nasopharyngeal Neoplasms
PubMed: 37936166
DOI: 10.1186/s12916-023-03140-x