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Cancer Dec 2020Reirradiation for locoregionally recurrent nasopharyngeal carcinoma (LR-NPC) after high-dose radiotherapy (RT) is challenging and usually is associated with poor...
BACKGROUND
Reirradiation for locoregionally recurrent nasopharyngeal carcinoma (LR-NPC) after high-dose radiotherapy (RT) is challenging and usually is associated with poor survival and severe toxicities. Because of its physical and biological advantages over photon-beam RT, carbon-ion RT (CIRT) could be a potential treatment option for patients with LR-NPC.
METHODS
Patients with LR-NPC who underwent salvage therapy using CIRT at the Shanghai Proton and Heavy Ion Center between May 2015 and June 2019 were analyzed. CIRT doses were 50 to 69 gray equivalent (GyE) (2.0-3.0 GyE per fraction). Overall survival (OS), local control, regional control, distant control, and acute and late toxicities were analyzed. Univariable and multivariable analyses of OS and local control were performed using the Cox regression model.
RESULTS
Among the 206 patients included, 139 patients (67.5%) had recurrent American Joint Committee on Cancer stage III or stage IV disease. With a median follow-up of 22.8 months, the 2-year OS, local control, regional control, and distant control rates were 83.7%, 58.0%, 87.3%, and 94.7%, respectively. Multivariable analysis revealed that older age (P = .017) was predictive of worse OS, whereas a larger tumor volume (P = .049) and a lower biological equivalent dose (P = .029) were associated with inferior local control. No patient developed an acute toxicity of ≥grade 3 during CIRT. Severe (≥grade 3) late toxicities included temporal lobe necrosis (0.97%), cranial neuropathy (0.49%), hearing loss (1.46%), xerostomia (0.49%), and mucosal necrosis (16.02%) (toxicities were graded using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer criteria).
CONCLUSIONS
Salvage treatment using CIRT is efficacious for patients with LR-NPC and its toxicities are acceptable. CIRT may improve the survival and toxicity profiles substantially for patients with LR-NPC compared with the reported results after photon-based intensity-modulated RT.
Topics: Adolescent; Adult; Aged; Dose Fractionation, Radiation; Female; Heavy Ion Radiotherapy; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Prognosis; Radiotherapy, Intensity-Modulated; Treatment Outcome; Young Adult
PubMed: 32931035
DOI: 10.1002/cncr.33197 -
The British Journal of Radiology Oct 2019Nasopharyngeal cancer (NPC) is notable for its wide geographic variation, with incidences as high as 30 in 100,000 in endemic regions but < 1 in 100,000 worldwide. This... (Comparative Study)
Comparative Study Review
Nasopharyngeal cancer (NPC) is notable for its wide geographic variation, with incidences as high as 30 in 100,000 in endemic regions but < 1 in 100,000 worldwide. This review aims to identify areas where there could be differences in prognosis, management or outcomes among countries with high or low incidence of NPC. The incidence has generally declined both in endemic and non-endemic regions throughout the years, which may be attributed to the decrease in exposure to risk factors such as early exposure to salted fish and smoking. Ethnicity has an impact both on incidence and prognosis, with Southeast Asians having the highest incidence but also better survival. Concurrent chemoradiotherapy, with or without adjuvant and/or induction chemotherapy, is the standard of care for locoregionally advanced disease, as reflected in clinical practice guidelines. Despite improvements in management, a proportion of patients relapse. Salvage treatment is associated with significant morbidity due to the critical location of the nasopharynx and the toxicities of initial therapy. Clinical expertise is paramount, but is easier to attain in endemic regions and high volume centers where enrollment of patients in clinical trials is more feasible. Collaboration between low and high incidence countries and between low and high volume facilities is key to improving NPC prognosis worldwide.
Topics: Biomarkers, Tumor; Chemoradiotherapy; Chemotherapy, Adjuvant; DNA, Viral; Herpesvirus 4, Human; Humans; Incidence; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Practice Guidelines as Topic; Radiotherapy; Risk Factors; Salvage Therapy; Treatment Outcome
PubMed: 31150279
DOI: 10.1259/bjr.20190068 -
Medicine Jul 2023Nasopharyngeal carcinoma (NPC) is the most common malignant neoplasm of the nasopharynx. Despite improvements in the clinical treatment strategies for NPC, NPC patients...
Nasopharyngeal carcinoma (NPC) is the most common malignant neoplasm of the nasopharynx. Despite improvements in the clinical treatment strategies for NPC, NPC patients usually have poor survival rates because of late diagnosis, tumor metastasis, and recurrence. Therefore, the identification of potential diagnostic and prognostic markers for NPC is imperative. We investigated the differential expression of cell adhesion-related genes (gene ontology:0003779) and tumorigenesis-related genes (GSE12452) in patients with NPC. The correlations between synaptopodin-2 (SYNPO2) immune expression and clinicopathological features were analyzed using Pearson chi-square test. Multivariate analysis was performed using Cox proportional hazards model. SYNPO2 expression was significantly higher in NPC tumor tissues than in nontumor tissues. High SYNPO2 expression was significantly associated with the advanced disease stage (P = .006). Univariate analysis showed that high expression of SYNPO2 was associated with poor disease-specific survival, distal metastasis-free survival, and local recurrence-free survival in patients with NPC. Notably, our multivariate analysis demonstrated that high SYNPO2 expression was substantially correlated with inferior disease-specific survival (hazard ratio = 1.968, P = .012) and local recurrence-free survival (hazard ratio = 3.386, P = .001). Overall, our findings reveal that SYNPO2 may aid in the development of potential prognostic biomarkers for NPC patients.
Topics: Humans; Nasopharyngeal Carcinoma; Carcinoma; Prognosis; Up-Regulation; Nasopharyngeal Neoplasms; Kaplan-Meier Estimate; Biomarkers, Tumor; Microfilament Proteins
PubMed: 37505159
DOI: 10.1097/MD.0000000000034426 -
Cancer Aug 2020
Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Induction Chemotherapy; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
PubMed: 32497251
DOI: 10.1002/cncr.32971 -
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 -
Frontiers in Immunology 2021The role of RNA N6-methyladenosine (m6A) modification in tumor progression and metastasis has been demonstrated. Nonetheless, potential biological function of m6A...
BACKGROUND
The role of RNA N6-methyladenosine (m6A) modification in tumor progression and metastasis has been demonstrated. Nonetheless, potential biological function of m6A modification patterns in nasopharyngeal carcinoma (NPC) remains unknown.
METHODS
The m6A modification patterns were comprehensively evaluated based on 26 m6A regulators in NPC, and m6A subtype and also m6A score were identified and systematically correlated with representative tumor characteristics.
RESULTS
Two distinct m6A subtypes were determined and were highly consistent with immune activated and immune suppressed phenotypes, respectively. More representative m6A scores of individual tumors could predict tumor microenvironment (TME) infiltration, mRNA based stemness index (mRNAsi), EBV gene expression, genetic variation, and prognosis of NPC patients. Low m6A score, characterized by activation of immunity and suppression of mRNAsi and EBV gene, indicated an activated TME phenotype and better PFS and also lower risk of recurrence and metastasis. High m6A score, characterized by activation of Wnt and NF-κB signaling pathway and lack of effective immune infiltration, indicated an immune suppressed TME phenotype and poorer survival. Low m6A score was also correlated with increased tumor mutation burden (TMB) and better response to immunotherapy, and vice versa. A significant therapeutic advantage in patients with low m6A score was confirmed with an anti-PDL1 immunotherapy cohort.
CONCLUSIONS
m6A patterns played an important role in the diversity and complexity of TME. m6A score could be used to evaluate the m6A pattern of individual tumor to enhance our understanding of TME infiltration and guide more effective immunotherapy strategies.
Topics: Adenosine; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; RNA, Neoplasm; Tumor Microenvironment; Wnt Signaling Pathway
PubMed: 35069534
DOI: 10.3389/fimmu.2021.762243 -
Revista de Saude Publica Sep 2019To estimate the years of life lost by the Brazilian population due to mouth and pharynx cancer from 1979 to 2013, and analyze the temporal trends in the studied period,...
OBJECTIVE
To estimate the years of life lost by the Brazilian population due to mouth and pharynx cancer from 1979 to 2013, and analyze the temporal trends in the studied period, according to the country's region, sex and anatomical site.
METHODS
The death records were obtained from the Mortality Information System and the data referring to the population, from the censuses of the Brazilian Institute of Geography and Statistics of 1980, 1991, 2000, 2010, and from intercensal estimates for the other years. The rates of potential years of life lost were calculated by applying the method suggested by Romeder and McWhinnie, and their trends were calculated using the Prais-Winsten method with first-order autocorrelation. The historical series were smoothed with the centered moving average technique of third order for white noise reduction.
RESULTS
In the period from 1979 to 2013 in Brazil, there were a total of 107,506 premature deaths due to mouth and pharynx cancer, which generated a total of 1,589,501 potential years of life lost, the equivalent to a rate of 3.6 per 10,000 inhabitants. Males, whose rate was six times higher than for females, contributed with 85% of the years lost. The trends in the rates of years of life lost showed an annual 0.72% increase for men, 1.13% for women and 1.05% for pharynx cancer.
CONCLUSIONS
The rate of potential years of life lost due to mouth and pharynx cancer in the country showed an upward trend within the studied period for both sexes, as well as for pharynx cancer and for the North, Northeast and Midwest regions.
Topics: Adolescent; Adult; Aged; Brazil; Child; Child, Preschool; Female; Geography; Humans; Infant; Infant, Newborn; Life Expectancy; Male; Middle Aged; Oropharyngeal Neoplasms; Pharyngeal Neoplasms; Residence Characteristics; Sex Factors; Young Adult
PubMed: 31483007
DOI: 10.11606/s1518-8787.2019053001054 -
JCO Clinical Cancer Informatics Feb 2023Tumor stage is crucial for prognostic evaluation and therapeutic decisions in locally advanced nasopharyngeal carcinoma (NPC) but is imprecise. We aimed to propose a new...
PURPOSE
Tumor stage is crucial for prognostic evaluation and therapeutic decisions in locally advanced nasopharyngeal carcinoma (NPC) but is imprecise. We aimed to propose a new prognostic system by integrating quantitative imaging features and clinical factors.
MATERIALS AND METHODS
This retrospective study included 1,319 patients with stage III-IVa NPC between April 1, 2010, and July 31, 2019, who underwent pretherapy magnetic resonance imaging (MRI) and received concurrent chemoradiotherapy with or without induction chemotherapy. The hand-crafted and deep-learned features were extracted from MRI for each patient. After feature selection, the clinical score, radiomic score, deep score, and integrative scores were constructed via Cox regression analysis. The scores were validated in two external cohorts. The predictive accuracy and discrimination were measured by the area under the curve (AUC) and risk group stratification. The end points were progression-free survival (PFS), overall survival (OS), and distant metastasis-free survival (DMFS).
RESULTS
Both radiomics and deep learning were complementary to clinical variables (age, T stage, and N stage; all < .05). The clinical-deep score was superior or equivalent to clinical-radiomic score, whereas it was noninferior to clinical-radiomic-deep score (all > .05). These findings were also verified in the evaluation of OS and DMFS. The clinical-deep score yielded an AUC of 0.713 (95% CI, 0.697 to 0.729) and 0.712 (95% CI, 0.693 to 0.731) in the two external validation cohorts for predicting PFS with good calibration. This scoring system could stratify patients into high- and low-risk groups with distinct survivals (all < .05).
CONCLUSION
We established and validated a prognostic system integrating clinical data and deep learning to provide an individual prediction of survival for patients with locally advanced NPC, which might inform clinicians in treatment decision making.
Topics: Humans; Nasopharyngeal Carcinoma; Retrospective Studies; Area Under Curve; Chemoradiotherapy; Nasopharyngeal Neoplasms
PubMed: 36877918
DOI: 10.1200/CCI.22.00015 -
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 -
Radiotherapy and Oncology : Journal of... Jun 2023The imaging criteria of malignant retropharyngeal lymph node (RLN) in nasopharyngeal cancer (NPC) have yet to be fully elucidated. This study aimed to establish...
Endonasopharyngeal ultrasound and magnetic resonance imaging features of recurrent retropharyngeal nodes in nasopharyngeal carcinoma patients: A radiologic-histopathologic study.
BACKGROUND
The imaging criteria of malignant retropharyngeal lymph node (RLN) in nasopharyngeal cancer (NPC) have yet to be fully elucidated. This study aimed to establish predictive models based on ultrasound (US) and magnetic resonance (MR) characteristics for identifying malignant RLN in NPC patients after radiotherapy.
METHODS
81 post-radiotherapy NPC patients with abnormal enlargement of RLN underwent endonasopharyngeal ultrasound-guided fine-needle aspirations (EPUS-FNA) to access the nature of RLN. The following features were assessed on US and MR: size, margin, vascular signal, echogenicity, enhancement signal and accompany with suspicious cervical nodes or not. A multivariate analysis was performed to screen out high-risk imaging features for recurrent RLN (RRLN), and models for the diagnosis of RRLN was constructed and tested with internal verification. We evaluated the clinical usefulness of the models through comparison of C-index and decision curve analysis.
RESULTS
High-risk features of RRLN were heterogeneous echo (p < 0.01), vascular signal (p < 0.01) on EPUS, heterogeneous enhancement (p < 0.01) and minimum axis diameter > 10 mm (p < 0.01) on MR. The models based on the US and MR features showed good discrimination (AUC of 0.76 in the US model, 0.74 in the MR model and 0.77 in the US + MR model) and good net benefit in the validation group.
CONCLUSION
Prediction models based on the US and MR features show good diagnostic performance for RRLN after radiotherapy in NPC patients. The combination of EPUS and MR may be constructed to provide prompt and reliable guidance to manage RLN.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Pharynx; Neoplasm Staging; Lymphatic Metastasis; Magnetic Resonance Imaging; Lymph Nodes; Ultrasonography; Retrospective Studies
PubMed: 36842662
DOI: 10.1016/j.radonc.2023.109579