Undifferentiated Non-keratinizing Carcinoma Research Articles

Nab-paclitaxel plus cisplatin versus docetaxel plus cisplatin and 5-FU induction chemotherapy followed by concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: A multicenter parallel controlled phase III trial.

6071 Background: Although several large phase III clinical trials and meta-analysis have demonstrated significant clinical benefit of docetaxel combined with cisplatin and 5-FU (TPF) chemotherapy in head and neck cancer, serious adverse reactions are unsatisfactory. Therefore, this study was designed to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin (TP) versus TPF induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: In this open-label, phase 3 trial, patients were randomized 1:1 to received TP (260 mg/m2 nab-paclitaxel and 80 mg/m2 cisplatin on days 1 and 22) or TPF (60 mg/m2 docetaxel and 60 mg/m2 cisplatin on days 1 and 22; 3 g/m2 5-Fu on days 1-5 and 22-26) every 3 weeks for 2 cycles, both groups of patients received CCRT (100mg/m2 cisplatin and IMRT on days 43 and 64) every 21 days for 2 cycles. The primary endpoint was failure-free survival. Secondary endpoints included overall survival, objective response rate (ORR), quality of life and safety. Results: From January 2019 to July 2021, 281 patients were randomized to TP (n = 142, TP arm) or TPF (n = 139, TPF arm). The median age was 44 years (range, 20-63) in the TP arm and 45 years (range, 18-69) in the TPF arm. The pathological stages were 40.85% stage III and 59.15% stage IVA in the TP arm, while those of the TPF arm were 43.17% stage III and 56.83% stage IVA. There were 99.30% and 97.12% undifferentiated nonkeratinizing carcinoma in the two groups, respectively. All patients had Karnofsky performance status of 90. ICT was completed in 98.93% (100% in the TP arm and 97.84% in the TPF arm). The median relative dose intensity of nab-paclitaxel and cisplatin were 99.96% and 99.81% in the TP arm, 99.83%, 100% and 100% for docetaxel, cisplatin and 5-FU in the TPF arm, respectively. The ORR were 80.28% in the TP arm and 78.26% in the TPF arm after two cycles of ICT. 85.77% (83.10% in the TP arm and 88.49% in the TPF arm) completed the CCRT. After two cycles of CCRT, the ORR were 99.25% and 99.24%, respectively. 3 months after completion of all treatment, the ORR were 99.25% and 99.25%, respectively. During ICT, all treatment-related adverse events occurred in 40.14% of patients in the TP arm and 57.55% in the TPF arm. The most frequent grade 3 adverse events were neutropenia (0.70% vs 2.16%), leucopenia (0 vs 2.88%), diarrhea (0 vs 0.72%) in the TP arm and in the TPF arm. Over the entire course of treatment, the most common was 1 grade adverse events, and no patient developed grade 4 adverse events in the two groups. Conclusions: In this study, TP regimen showed similar trends in the ORR but excellent safety profile in patients with LA-NPC compared with TPF regimen, suggesting a potential therapeutic option for this population. Clinical trial information: ChiCTR1800019922 .

Clinical features and outcomes of pediatric nasopharyngeal carcinoma: A SEER database study.

e22011 Background: Nasopharyngeal carcinoma (NPC) is a rare malignant tumor. Little is known about the clinical, histological and survival characteristics of this disease in pediatric patients. Methods: We searched 17 registries of the surveillance, epidemiology, and end results (SEER) database for pediatric patients (£20 years old) with NPC who were diagnosed between 2000 to 2019. Data obtained included the demographics, histological subtype, stage, median household income, place of residence, cause specific survival (CSS) and overall survival (OS). We describe the clinical features and survival outcomes by race of pediatric patients. Results: A total of 373 primary pediatric NPC patients were reported between 2000-2019. Median age of diagnosis was 16 years (inter-quartile range 11.5 – 19 years). Of these, 68% were males, 59% were white and 27% were black. Undifferentiated non-keratinizing carcinoma group (WHO type III) was the most frequent (70%) histological sub-type. WHO type I and II disease was found to be present in 12% and 18% cases respectively. Nearly, 4 in 5 patients (83%) had stage III – IV NPC at presentation. Stage I and II disease at presentation was found to be present in 5% and 12% of NPC patients respectively. The median follow-up was 10.1 years. The 5 and 10 year survival estimates were 83% (95% CI 78.8% to 86.9%) and 79% (95% CI 73.9% to 83.1%) respectively. On multivariate Cox regression analysis, gender (Male vs Female: HR: 1.00, 95% CI 0.39-2.57; p = 0.998) and race (White vs Black: HR: 0.81 95% CI 0.311-2.10; p = 0.663) were not found to be significant predictors of survival. Conclusions: Pediatric patients at presentation with NPC were more commonly male, had undifferentiated non-keratinizing carcinoma (WHO type III) and stage III-IV disease. Gender and race were not found to be associated with an increased risk for mortality in pediatric patients presenting with NPC.

EBV Serology and Plasma EBV DNA Load as a Combined Tool for Nasopharyngeal Carcinoma (NPC) Diagnosis and Monitoring in Non-Endemic Regions

There is limited information regarding the clinical significance of Epstein-Barr virus (EBV) markers for nasopharyngeal carcinoma (NPC) diagnoses and monitoring in non-endemic areas. Low NPC incidence in non-endemic countries made it difficult to form a representative group of patients for research this issue. Moreover, NPC cases are often characterized into morphologically different tumor types based upon the geographic and ethnic variability. Since viral and serological markers reflect the different biological events accompanying the development of NPC, it is important to compare their clinical value in the context of different disease manifestations. The implementation of such a study in a non-endemic region is of particular interest, allowing the investigation of the potential impact of differences in the genetic and ethnic characteristics of the population, versus those in populations from endemic regions. In present study, we analyzed clinical significance of two EBV markers (serological and molecular) in large group (96 cases) of undifferentiated non-keratinizing carcinoma of nasopharyngeal type (UNPC) Russian patients. It has been shown that IgA/ VCA antibody titers elevated on patient's admission and being valuable markers for primary UNPC diagnosis do not allow to adequately assessing patients’ state after the treatment. In contrast to EBV serology, the plasma EBV DNA load was found to be valuable marker for clinical evaluation of UNPC patient’s state, such as remission and relapse. It was also shown that the concentration of viral DNA correlated with the UNPC patients' overall survival. The proposed study, conducted on UNPC patients from a non-endemic region, for the first time revealed a direct correlation between IgG/IgA antibody titers to EBV virus capsid antigen (VCA) and the levels of plasma EBV DNA load, and the absence of such correlation between plasma EBV DNA burden and serological responses to EBV. It has also been demonstrated that the combined assessment of plasma EBV DNA load and EBV-specific antibody titers provides a reliable approach to UNPC diagnosis, disease monitoring, and therapeutic response assessment.

The effect of histological subtypes on survival outcome in nasopharyngeal carcinoma after extensive follow up.

No consensus exists regarding the follow-up of nasopharyngeal carcinoma (NPC) patients stratified by different histological subtypes. The purpose of this study was to determine the hazard function of disease-related death and assess the prognostic effect of early and late disease-related death in NPC according to histological subtypes. We included non-metastatic NPC patients between 2004 and 2014 using the Surveillance, Epidemiology and End-Results (SEER) program. Life-table methods, Kaplan-Meier methods, and a multivariate Cox regression model were used in the analysis. We identified 2,845 patients in this study including 1,218 (42.8%), 849 (29.8%), and 778 (27.3%) patients with keratinizing squamous cell carcinoma (KSCC), differentiated non-keratinizing carcinoma (DNKC), and undifferentiated non-keratinizing carcinoma (UNKC), respectively. Most NPC-related death (89.8%) occurred within 5 years of diagnosis. In the entire cohort, the hazard curve for NPC-related death peaked at 2 years. It peaked at 1 year, 2- and 5-year, and 2- and 6-year in patients with KSCC, DNKC, and UNKC, respectively. Within the follow-up period over 5 years, patients with DNKC had poorer NPC-specific survival (NPC-SS) compared to UNKC, and had comparable NPC-SS between the two subtypes after more than 5 years of follow-up. Moreover, within the follow-up period of 1, 2, and 3 years, patients with KSCC experienced poorer NPC-SS compared to UNKC but there was comparable NPC-SS between KSCC and UNKC patients after more than 3 years of follow-up. The hazard rate patterns for NPC-related mortality significantly differed between histological subtypes. Tailored surveillance and follow-up strategies should be designed in NPC patients according to histological subtypes.

HLA-B alleles and nasopharyngeal carcinoma in Xinjiang, China: relationship and clinical significance

Objective To explore the relationship between HLA-B allele polymorphisms and nasopharyngeal carcinoma (NPC) in Xinjiang, China and its clinical significance. Methods A total of 226 patients were assigned to NPC group, while 207 healthy volunteers were assigned to control group. PCR amplification with sequence-specific primers was used to determine HLA-B alleles. Comparison of HLA-B allele frequency between the above two groups, between Han and Uygur populations, and between patients with various clinical characteristics of NPC was made by chi-square test. The Kaplan-Meier method was used to calculate the survival rates and the log-rank univariate analysis was used to explore the relationship between survival rates and HLA-B allele frequency. Results In all the subjects or Han population alone, the allele frequency of HLA-B*46 in the NPC group was significantly higher than that in the control group (P=0.000; P=0.000). In Uygur population, however, there was no significant difference in the allele frequency of HLA-B*46 between the NPC group and the control group (P>0.05). In the patients with NPC, those less than 30 years old had a significantly higher allele frequency of HLA-B*44 than those no less than 30 years old (P=0.029); those with differentiated non-keratinizing carcinoma had a significantly higher allele frequency of HLA-B*48 than those with undifferentiated non-keratinizing carcinoma (P=0.029); those with stage T1+ T2 disease had a significantly higher allele frequency of HLA-B*48 than those with stage T3+ T4 disease (P=0.029). The 5-year overall survival, disease-free survival, distant metastasis-free survival, and local relapse-free survival rates had no relationship with the expression of HLA-B*46, HLA-B*44, or HLA-B*48 in NPC patients (all P>0.05). Conclusions HLA-B*46 allele is probably a NPC susceptibility gene in Han population in Xinjiang. HLA-B*44 is probably associated with early age of onset, while HLA-B*48 is probably associated with the pathological type and T stage of NPC. Therefore, HLA-B alleles are probably associated with the development and progression of NPC. Key words: Nasopharyngeal carcinoma; HLA-B gene; Clinic characteristics; Prognosis

Long-Term Outcomes of Nasopharyngeal Carcinoma in 148 Children and Adolescents.

The aim of this study was to investigate the survival and long-term morbidities of nasopharyngeal carcinoma (NPC) in children and adolescents.We retrospectively reviewed children and adolescents with NPC treated at Sun Yat-sen University Cancer Center from February 1991 to October 2010, where the prognostic factors and long-term effects of therapy were analyzed.A total of 148 patients were identified. The median age was 15 years old (range, 5–18 years) and the male to female ratio was 3.6:1. Most of the tumor histopathology was undifferentiated nonkeratinizing carcinoma (97.3%). The number of patients staged with IVa, IVb, IVc, III, and II were 45 (30.4%), 12 (8.1%), 5 (3.4%), 70 (47.3%), and 16 (10.8%), respectively. For the whole series with a median follow-up of 81 months (range, 6–282 months), the 5-year overall survival (OS) and disease-free survival (DFS) ratios were 79.3% and 69.7%, respectively. We observed significant differences in the 5-year OS (81.1% vs 25.0%, P = 0.002) and the DFS rates (72.2% vs 0.0%, P = 0.000) between patients with stage II to IVb disease and stage IVc disease. For patients with stage II, III, IVa, and IVb disease, we found a high radiation dose (dose > 66 Gy to the primary lesion) would not significantly improve the survival compared to the sub-high radiation dose group (dose = 60–66 Gy to the primary lesion), even considering the type of radiation therapy technologies. However, the incidences of sequelae (grades I–IV) in patients with high radiation dose were apparently higher than those in patients with low radiation dose.Considering the late sequelae, a dose of 60 to 66 Gy to the primary lesions seems to be enough for children and adolescents with NPC.

Synchronous nasopharyngeal carcinoma and cardia adenocarcinoma accompanied with suspected dermatomyositis: A case report and literature review

Synchronous multiple primary cancers are relatively uncommon and synchronous multiple cancers in coexistence with dermatomyositis (DM) are extremely rare. In the present study, we report a case of a 64-year-old male with nasopharyngeal undifferentiated non-keratinizing carcinoma and cardia adenocarcinoma which were diagnosed synchronously. In addition, suspected DM was diagnosed during the course of chemotherapy. The symptoms of DM were exaggerated even when methylprednisolone while administered. The patient succumbed to nutritional deterioration four months following his initial admission. In the present study, the etiologies of multiple primary cancers are discussed and a brief review of the literature on the correlation between malignance and DM was conducted.

Epidemiology of nasopharyngeal carcinoma in the United States: improved survival of Chinese patients within the keratinizing squamous cell carcinoma histology

This study examined potential survival differences among nasopharyngeal carcinoma (NPC) patients from various ethnicities in the United States. A total of 2436 newly diagnosed NPC patients from 1992 to 2002 were analyzed from the population-based Surveillance, Epidemiology, and End Results (SEER) program. Five-year survival rate estimates and Kaplan-Meier survival curves were calculated. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. By multivariate analyses, early age of diagnosis, localized stage at presentation (versus distant, HR=0.35; P<0.0001), radiation therapy (versus none; HR=0.48; P<0.0001), undifferentiated non-keratinizing carcinoma (versus keratinizing squamous cell carcinoma; HR=0.67; P<0.0001), and Chinese ethnicity (versus Caucasian; HR=0.78; P=0.0010) were associated with improved survival. Within keratinizing squamous cell carcinoma histology, the survival advantage of Chinese patients remained even after adjustment for other prognostic factors. The significant survival advantage of Chinese NPC patients within the keratinizing squamous cell carcinoma histology contributed largely to Chinese ethnicity being an independent and favorable prognostic factor for survival in NPC.

Second primary epithelial malignancy of nasopharynx and nasal cavity after successful curative radiation therapy of nasopharyngeal carcinoma

Patients with head and neck cancer are at high risk of developing additional second primary tumors in the aerodigestive tract as a result of the field cancerization phenomenon. In this context, the appearance of a new neoplasm often poses a problem in differential diagnosis between recurrence and new primary tumor. Twelve patients with nasopharyngeal carcinoma (NPC) who received radiation therapy for the primary tumor and developed a second epithelial malignancy in the nasal cavity or nasopharynx during the follow-up period are presented in this report. The differentiation between the 2 entities based on the spatiotemporal relations, histological features, and the status of Epstein-Barr virus in tumor lesions are also presented. Our study showed that the epithelial malignancy after NPC having late-onset or prolonged interval (range, 5 to 18 years), different histological patterns (keratinizing squamous cell carcinoma, neuroendocrine carcinoma, or small cell carcinoma) distinct from the primary NPC (differentiated or undifferentiated nonkeratinizing carcinoma), and absence of Epstein-Barr virus, indicate a newly developed tumor rather than recurrent NPC. Our observations showed for the first time that second primary epithelial malignancy developed in the nasal cavity or nasopharynx years after curative therapy for NPC with a prevalence of 0.4% (12/2,794). Wild-type p53 protein was expressed more often in the original NPC (9 of 12) than in the second tumors (4 of 10), but the significance was not statistically significant (P = .2048). Genomic analysis for p53 mutation and in situ hybridization for human papillomavirus showed negative results, indicating that both important molecular events in NPC or head and neck cancer play a small role in this particular type of newly developed second malignant tumor. More studies are warranted for further clarification for the development of second epithelial malignancies in treated NPC patients.