Subtype Specific Nasopharyngeal Carcinoma Incidence and Survival Trends: Differences between Endemic and Non-Endemic Populations.

BACKGROUND: While nasopharyngeal carcinoma (NPC) is rare in non-endemic regions such as the North America, endemic countries, such as Thailand, continue to struggle with high incidence and mortality rates. NPC has a complex etiology that varies by histological subtype. METHODS: NPC cases (1990-2014) were identified using the International Classification of Diseases for Oncology (ICD-O) code C11 from the Chiang Mai, Khon Kaen, Lampang, and Songkhla cancer registries and compared to Asian/Pacific Islanders (A/PI) from the US SEER program. Age-standardized incidence rates and changes in annual percent change (APC) for overall and subtype specific NPC were assessed using R and Joinpoint. Kaplan Meier curves were generated in SAS to evaluate differences in survival by sex, year of diagnosis and histological subtype. Five-year relative survival estimates were calculated between 2000-2014. RESULTS: Non-keratinizing NPC predominated across all registries except Songkhla, where the keretinizing subtype made up ~60% of all reported cases. Incidence of keratinizing NPC significantly decreased among Chiang Mai males between 1996 and 2014 (APC:-13.0 [95%CI:-16.2, -9.6]), Songkhla females (APC:-4.0 [95%CI: -7.4, -0.5]) and males between 2006 and 2014 (APC:-15.5 [95%CI:-25.0, -4.7]), as well as A/PI females (APC:-5.1 [95%CI:-6,7, -3.4]) and males (APC: -4.8 [95%CI:-5.9, -3.7]). Non-keratinizing NPC increased among Songkhla males (APC:4.3 [95%CI:1.8, 6.9]). The keratinizing subtype exhibited the worst survival, while the non-keratinizing undifferentiated subtype had the best survival. Although US A/PI had the highest 5-year relative survival estimates, among the Thai registries Chiang Mai had the best and Lampang the worst survival. CONCLUSION: Although US A/PIs exhibited similar rates of NPC as seen in the endemic Thai population, improved tobacco control has led to a decrease in keratinizing NPC incidence irrespective of geography. Additionally, while challenges associate with access to care may still exist among rural Thais, chemoradiation was shown to confer a survival benefit in non-keratinizing NPC treatment.

Whole exome sequencing and transcriptome-wide profiling identify potentially subtype-relevant genes of nasopharyngeal carcinoma.

BACKGROUND: To date, no targeted therapy has been approved for nasopharyngeal carcinoma (NPC), suggesting that comprehensive understanding of genomic changes turns out to be an urgent need to break through the calm of currently known therapies of NPC. METHODS: Whole exome sequencing (WES) was performed for 14 NPC patients, including 6 NPC-IIA cases, 8 NPC-IIB cases. The cancer chip expression data named GSE12452 was downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) of each subtype were obtained using the Lima R package. Then gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) network and Gene Set Enrichment Analysis (GSEA) were performed. Finally 7 potentially subtype relevant genes (PSRGs)1 were obtained. RESULTS: In total, 37 clinically relevant mutations (CRMs)2 were obtained from WES. The 2 NPC subtypes exhibited different mutational landscapes, indicating that different NPC subtypes harbor different CRMs. Notably, we discovered that mutations of CCND1 and FGF family appeared simultaneously in 3 NPC-IIB cases, but 0 in NPC-IIA. In addition, 1395 DEGs were identified from GSE12452. PI3K-Akt signaling pathway showed significant enrichment in both the pathway distribution of CRMs and KEGG analysis of DEGs, suggesting that it is a key pathway in the development of NPC. Through PPI analysis of genes involved in the PI3K-Akt pathways and expression significance analysis of DEGs co-expressed by the 2 subtypes, 54 genes finally were screened for expression significance analysis. The GSEA analysis between patients with high and low expression of 11 candidate genes were performed. As a result, 7 PSRGs were selected, including COL4A1, ASB9, RDH10, TNFRSF21, BACE2, EVA1C and LHX2. CONCLUSIONS: These results indicate that different NPC subtypes have different genetic changes, suggesting that they may be potential targets for the diagnosis and treatment of NPC, and ultimately point to new strategies for intelligence.

Nodal grouping in nasopharyngeal carcinoma: prognostic significance, N classification, and a marker for the identification of candidates for induction chemotherapy.

OBJECTIVES: This study aimed to evaluate the value of nodal grouping (NG), defined as the presence of at least three contiguous lymph nodes (LNs) within one LN region, in staging and management of patients with non-metastatic nasopharyngeal carcinoma (NPC). METHODS: MR images were reviewed to evaluate LN variables, including NG. The Kaplan-Meier method and multivariate Cox regression models evaluated the association between the variables and survival. Harrell's concordance index (C-index) was used to measure the performance of prognostic models. The outcome of induction chemotherapy (IC) in patients with and without NG was compared using matched-pair analysis. RESULTS: In 1224 patients enrolled, NG was found to be an independent prognostic factor for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and regional recurrence-free survival. The hazard ratio and 95% confidence interval (CI) of NG for OS (3.86, 2.09-7.12) were higher than those of stage N2 (3.54, 1.89-6.70). On upgrading patients with NG from stages N1 to N2, the revised N staging yielded a higher C-index compared to the American Joint Committee on Cancer system in predicting PFS (0.664 vs. 0.658, p = 0.022) and DMFS (0.699 vs. 0.690, p = 0.005). Results of the matched-pair analysis revealed that for patients with NG in stages N1 and N2, IC was correlated with improved OS (p = 0.022), PFS (p = 0.007), and DMFS (p = 0.021). CONCLUSIONS: NG is a significant prognostic factor for patients with NPC. Patients with NG may be upgraded from stages N1 to N2. NG was also a marker for identifying patients who would benefit from IC. KEY POINTS: • Nodal grouping, defined as the presence of at least three contiguous LNs within one LN region on MRI, was identified as a significant prognostic factor. • In patients with nasopharyngeal carcinoma, nodal grouping may influence lymph node staging. • Nodal grouping was a marker for identifying patients who may benefit from induction chemotherapy.

Depicting distant metastatic risk by refined subgroups derived from the 8th edition nasopharyngeal carcinoma TNM.

BACKGROUND: Tumor-nodal-metastasis (TNM) is the most important survival predictor in nasopharyngeal carcinoma (NPC). Distant metastasis (DM) is the predominant failure pattern of NPC in the intensity-modulated radiotherapy (IMRT) era. The DM risk appears to be different for T-N subsets within the same clinical stage. Appropriately depicting DM risk has emerged as an important issue in tailoring individualized treatment and underpins the reason for this study. METHODS: A total of 1616 non-metastatic (M0) NPC patients treated with IMRT were included. All were re-staged according to the 8th edition AJCC/UICC TNM (TNM-8). DM-free survival (DMFS) was calculated and compared among T-N subsets within each stage and DM risk groups were derived by Recursive-partitioning analysis (RPA) based on ordinal T and N categories. RESULTS: Significant heterogeneity in DM risk was evident among T-N subsets within cTNM-8 stages II-IV. The RPA algorithm classified patients into four DM risk groups: RPA-I (T1N0-1 and T2-3N0), RPA-II (T2-3N1), RPA-III (T4N0-1 and T1-3N2) and RPA-IV (T4N2 and T1-4N3), with 5-year DMFS of 93.4% (95% CI: 91.3-96.1), 84.3% (80.8-87.8), 78.9% (75.4-82.4) and 63.6% (56.3-70.9), respectively (p < 0.001). Compared to cTNM-8 stage grouping, RPA grouping had a lower Akaike information criterion (AIC) and higher Harrell's concordance index (c-index) for DMFS. CONCLUSIONS: Significant heterogeneity in DM risk exists among T-N subsets within cTNM-8 stages. The RPA groups demonstrated improved intra-group hazard consistency compared to cTNM-8 stage groups. While further validation is warranted, these RPA prognostic groupings provide a strong anatomic foundation to augment DM prediction for optimal targeting in future clinical trials.

Validation and suggestion of eighth T classifications of the UICC/AJCC staging system for nasopharyngeal carcinoma patients: a retrospective analysis.

BACKGROUNDS: With the aim to validate the applicability of the eighth T classifications of AJCC/UICC staging system for nasopharyngeal carcinoma patients. MATERIALS AND METHODS: We compare the seventh and eighth T classifications of the UICC/AJCC staging system in 382 newly diagnosed nasopharyngeal carcinoma patients without cervical lymph node metastasis who were staged with magnetic resonance imaging and treated by intensity-modulated radiotherapy. Univariate analysis was performed using the log-rank test and multivariate analyses with the Cox proportional hazards model were used to evaluate the prognostic values between adjacent stage categories. The Akaike information criterion and Harrell's concordance index were applied to compare the two systems. RESULTS: The median follow-up time was 61.1 months. For local relapse-free survival and distant metastasis failure-free survival, the eighth editions had superior prognostic value to the seventh edition. The Akaike information criterion value was smaller and Harrell's concordance index value was larger for the eighth edition compared with the seventh edition staging system. Our research also found that the difference in overall survival, local relapse-free survival and distant metastasis failure-free survival rates between T1 and T2 patients was not significant according to the eighth edition of the UICC/AJCC staging system, indicating that the discrimination among T1-2 patients was diminished. CONCLUSIONS: Intensity-modulated radiotherapy with elective neck irradiation provides excellent local-regional control for nasopharyngeal carcinoma patients and the eighth T classification seems to be superior to the seventh T classification. Since local control has improved in the modern era, the study considered that the staging system could be further improved and simplified by downstaging the current T2 classification patients to T1 with modern treatment. Researchers are attempting to incorporate individualized prognostic factors, such as Epstein-Barr virus DNA, into nomogram.

[WHO classification of head and neck tumours 2017: Main novelties and update of diagnostic methods]. / Classification de l'OMS 2017 des tumeurs de la tête et du cou : principales nouveautés et mise à jour des méthodes diagnostiques.

The publication of the new WHO classification of head and neck tumours in 2017 brought major modifications. Especially, a new chapter is dedicated to the oropharynx, focusing on the description of squamous cell carcinoma induced by the virus Human Papilloma Virus (HPV), and new entities of tumors are described in nasal cavities and sinuses. In this article are presented the novelties and main changes of this new classification, as well as the updates of the diagnostic methods (immunohistochemistry, cytogenetics or molecular biology).

Prognostic value of masticatory muscle involvement in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.

BACKGROUND AND PURPOSE: In 2017, the 8th edition of the nasopharyngeal carcinoma (NPC) staging manual published by the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) defined new rules regarding the involvement of anatomical masticatory muscles (MM). The purpose of this study is to evaluate the validity of the current T-staging system after the addition of revisions regarding MM involvement. METHODS: We performed a retrospective review of 608 patients, who were newly diagnosed with NPC and treated with intensity-modulated radiotherapy (IMRT) between January 2008 and March 2010. RESULTS: We found MM involvement in 398 NPC cases (65.4%). We observed a significant difference in overall survival (OS; 75.6% vs. 86.7%, P = .043) and in local relapse-free survival (LRFS; 81.5% vs. 88.6%, P = .048) between patients with and without MM involvement, but no difference in distant metastasis-free survival (DMFS; 80.3% vs. 85.0%, P = .147) or disease-free survival (DFS; 77.9% vs. 81.6%, P = .081). Significant differences in OS and LRFS were also found among different types of MM involvement. Compared with patients who had concurrent involvement of the lateral pterygoid muscle (LP), patients with tumors invading only the medial pterygoid muscle (MP) had a higher OS and LRFS rates, according to univariate and multivariate analysis (P < .05). CONCLUSIONS: MM involvement is an independent prognostic factor for OS and LRFS. We conclude that the decision to down-stage MP as T2 in the 8th edition staging system is valid. However, tumors with LP involvement were more rational classified into a higher T-staging category than tumors with only-MP involvement.

Update From The 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Nasopharynx.

The current WHO classification system for tumors of the head and neck has made few changes from the previous edition with regards to tumors of the nasopharynx. The classification system is discussed here with particular attention to nasopharyngeal carcinoma, nasopharyngeal papillary adenocarcinoma, salivary gland anlage tumor, hairy polyp, juvenile angiofibroma, and other tumors.

Proposal for a new risk classification system for nasopharyngeal carcinoma patients with post-radiation nasopharyngeal necrosis.

PURPOSE: To analyze the clinical outcomes of nasopharyngeal carcinoma (NPC) patients with post-radiation nasopharyngeal necrosis (PRNN) and construct a new risk classification system for predicting survival of PRNN. METHODS: A total of 276 patients with PRNN were consecutively enrolled. Complete magnetic resonance (MR) images of the nasopharynx and neck were available for all patients and were used to assess nasopharyngeal necrosis status. After 2010, patients with PRNN were initially treated by radical endoscopic necrectomy followed by reconstruction with nasal flap (ENNF). RESULTS: The 1-year and 2-year overall survival (OS) was 65.0% and 51.6%, respectively. Three variables affected survival: osteoradionecrosis, re-irradiation, and internal carotid artery (ICA) exposure, and only two variables were found to be independent prognostic factors: re-irradiation (hazard ratio [HR] 1.75, P=0.001) and internal carotid artery (ICA) exposure (hazard ratio [HR] 1.80, P=0.001). These two variables were combined to create a new risk classification system for PRNN. 131 (47.5%), 110 (39.9%), and 35 (12.7%) patients were classified into low-, intermediate- and high-risk group, with the 2-year OS rates of 64.8%, 45.1%, and 22.5%, respectively (P<0.001). ENNF was associated with a better OS in these three group patients compared with conservative management with statistical or marginal statistical significance (2-year OS low-risk group, 90.9% vs 61.1%, p=0.081; intermediate-risk group: 100% vs 37.8%, P=0.001; and high-risk group, 57.1% vs 20.8%, p=0.066). CONCLUSION: The new risk classification system provides accurate estimates of prognosis. ENNF surgery may lead to better survival outcome than conservative management in PRNN patients.

[Transnasal endoscopic surgery of communicating neoplasm outside cerebral dura mater and orbital fasciae].

Objective:This paper is intend to observe the feasibility of surgical approach with which communicating neoplasm outside cerebral dura mater and orbital fasciae was removed by transnasal endoscopic surgery.Method:Nine patients suffered from communicating neoplasm in the area of naso-orbital-cranio complex were treated with transnasal endoscopic surgery. The size of skull base bone defect was from 1.25 cm×1.13 cm to 3.25 cm×2.69 cm. No eye enucleation was done. No reconstructions of skull base and medial wall of orbital cavity were done. Iodoform gauze was packed in paranasal sinuses fourteen days. Patients with malignant tumor were treated radiation therapy and chemical therapy after surgical treatment. The degree of resection, complications of intracranial and orbital cavities, survival condition were the focus of this study.Result:The tumor were completely removed and all operations were successfully completed by trasnasal endoscopic surgery. Only one patient was required blood transfusion due to seriously bleeding from tumor during the operation. There was no orbital, intracranial, and vascular complications. The defect of bone at skull base and lamina papyracea were automatic reconstructed. Three patients have showed recurrence of neoplasm, and two of them died during two years of following up time.Conclusion:Transnasal endoscopic surgery is a safe, reliable and effective approach to treat communicating neoplasm in the area of naso-orbital-cranio complex, of which main part of tumor exists in the sinunasal cavity.

A nation-wide epidemiological study on the risk of developing second malignancies in patients with different histological subtypes of nasopharyngeal carcinoma.

OBJECTIVE: Risk assessment of second head/neck and Epstein Barr Virus (EBV)-related malignancies in patients with different nasopharyngeal carcinoma (NPC) subtypes. METHODS: This is a cross-sectional study. Pathology records were retrieved from PALGA (a Dutch pathology registry database) between 1995 and 2013. Second primary malignancy (SPM) data was extracted from PALGA. Odds ratios (OR) for SPM in the head/neck, and the upper/lower airways were calculated using logistic regression. Pearson X(2)-test and Fisher's exact test were used to assess the relationship between NPC (and EBV-status) with SPM. Standardized incidence rates (SIR) were calculated. RESULTS: Histologically diagnosed NPC (keratinizing and undifferentiated and differentiated non-keratinizing subtypes) (n=1175) were identified. NPC patients have an increased risk of second head/neck malignancies (SIR 4.7 95% CI 3.3-6.5). Keratinizing NPCs have an OR of 1.947 (95% CI 1.362-2.782) for SPM, an OR of 4.026 (95% CI 2.308-7.023) for carcinomas of the upper/lower airways, an OR of 4.306 (95% CI 2.299-8.066) for head/neck malignancies, an OR of 5.289 (95% CI 2.740-10.211) for HNSCC with a SIR of 4.7 (95CI 3.3-6.5). Non-keratinizing NPCs also have an increased risk of head/neck malignancies with a SIR of 3.2 (95% CI 1.8-5.1), but less than keratinizing NPCs (p=<0.001). Positive EBV-status is not associated with (EBV-related) SPM. CONCLUSION: NPCs have a higher risk of SPM regardless of EBV status. SPM (especially HNSCC and malignancies of the upper aerodigestive tract) are more prevalent in keratinizing NPC compared to non-keratinizing NPC. Close clinical follow-up of NPC patients, with specific attention on SPM, is justified.

A simple classification of cranial-nasal-orbital communicating tumors that facilitate choice of surgical approaches: analysis of a series of 32 cases.

Cranial-nasal-orbital communicating tumors involving the anterior and middle skull base are among the most challenging to treat surgically, with high rates of incomplete resection and surgical complications. Currently, there is no recognized classification of tumors with regard to the choice of surgical approaches. From January 2004 to January 2014, we classified 32 cranial-nasal-orbital communicating tumors treated in our center into three types according to the tumor body location, scope of extension and direction of invasion: lateral (type I), central (type II) and extensive (type III). This classification considerably facilitated the choice of surgical routes and significantly influenced the surgical time and amount of hemorrhage during operation. In addition, we emphasized the use of transnasal endoscopy for large and extensive tumors, individualized treatment strategies drafted by a group of multidisciplinary collaborators, and careful reconstruction of the skull base defects. Our treatment strategies achieved good surgical outcomes, with a high ratio of total resection (87.5 %, 28/32, including 16 cases of benign tumors and 12 cases of malignant tumors) and a low percentage of surgical complications (18.8 %, 6/32). Original symptoms were alleviated in 29 patients. The average KPS score improved from 81.25 % preoperatively to 91.25 % at 3 months after surgery. No serious perioperative complications occurred. During the follow-up of 3 years on average, four patients with malignant tumors died, including three who had subtotal resections. The 3-year survival rate of patients with malignant tumors was 78.6 %, and the overall 3-year survival rate was 87.5 %. Our data indicate that the simple classification method has practical significance in guiding the choice of surgical approaches for cranial-nasal-orbital communicating tumors and may be extended to other types of skull base tumors.

Development of a ten-signature classifier using a support vector machine integrated approach to subdivide the M1 stage into M1a and M1b stages of nasopharyngeal carcinoma with synchronous metastases to better predict patients' survival.

The aim of this study was to develop a prognostic classifier and subdivided the M1 stage for nasopharyngeal carcinoma patients with synchronous metastases (mNPC). A retrospective cohort of 347 mNPC patients was recruited between January 2000 and December 2010. Thirty hematological markers and 11 clinical characteristics were collected, and the association of these factors with overall survival (OS) was evaluated. Advanced machine learning schemes of a support vector machine (SVM) were used to select a subset of highly informative factors and to construct a prognostic model (mNPC-SVM). The mNPC-SVM classifier identified ten informative variables, including three clinical indexes and seven hematological markers. The median survival time for low-risk patients (M1a) as identified by the mNPC-SVM classifier was 38.0 months, and survival time was dramatically reduced to 13.8 months for high-risk patients (M1b) (P < 0.001). Multivariate adjustment using prognostic factors revealed that the mNPC-SVM classifier remained a powerful predictor of OS (M1a vs. M1b, hazard ratio, 3.45; 95% CI, 2.59 to 4.60, P < 0.001). Moreover, combination treatment of systemic chemotherapy and loco-regional radiotherapy was associated with significantly better survival outcomes than chemotherapy alone (the 5-year OS, 47.0% vs. 10.0%, P < 0.001) in the M1a subgroup but not in the M1b subgroup (12.0% vs. 3.0%, P = 0.101). These findings were validated by a separate cohort. In conclusion, the newly developed mNPC-SVM classifier led to more precise risk definitions that offer a promising subdivision of the M1 stage and individualized selection for future therapeutic regimens in mNPC patients.

TNM classification of the oral cavity carcinomas: some suggested modifications.

TNM system is a universally recognized cancer classification. It's based on the assessment of anatomical extent of tumor (T), nodal (N) and distant metastases (M). The first edition of TNM was published in 1968 and has since been updated several times. Relevant characteristics that affect prognosis prognosis, such as depth of invasion, tumor volume, surgical margin infiltration, and the number of involved nodes as well as the presence of extracapsular spread (such data should be determined by the pathologist and included in pTNM staging ­ ed. note) are not included in the TNM classification. Following a discussion on most recent classification updates we will discuss the factors, which in our opinion and in concordance with the most recent literature, deserve special consideration and influence management of oral carcinomas.

Juvenile nasopharyngeal angiofibroma staging: An overview.

Staging of tumors is very important in treatment and surgical decision making, as well as in predicting disease recurrence and prognosis. This review focuses on the different available classifications of juvenile nasopharyngeal angiofibroma (JNA) and their impact on the evaluation, management, and prognosis of JNA. The literature was reviewed, and publications on JNA staging were examined. Our MEDLINE search of the entire English-language literature found no review article on the current available staging systems for JNA. In this article, we review the common JNA classification systems that have been published, and we discuss some of their advantages and disadvantages. The most commonly used staging systems for JNA are the Radkowski and the Andrews-Fisch staging systems. However, some newer staging systems that are based on advances in technology and surgical approaches-the Onerci, INCan, and UPMC systems-have shown promising utility, and they will probably gain popularity in the future.

Prognostic value of classifying parapharyngeal extension in nasopharyngeal carcinoma based on magnetic resonance imaging.

PURPOSE: To subclassify parapharyngeal extension in nasopharyngeal carcinoma (NPC) and investigate its prognostic value and staging categories based on magnetic resonance imaging (MRI). METHODS AND MATERIALS: Data from 1504 consecutive NPC patients treated with definitive-intent radiotherapy were analyzed retrospectively. Sites of parapharyngeal extension were defined by MRI. Overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by the Kaplan-Meier method and compared with the log-rank test. Hazard consistency and hazard discrimination were determined by multivariate analysis with Cox proportional hazards models. RESULTS: 1104 patients (73.4%) had parapharyngeal extension; 1.7-63.8% had involvement of various anatomic sites. The hazard ratio for death was significantly higher with extensive parapharyngeal extension (lateral pterygoid muscle of masticator space and beyond or parotid space) than with mild extension (medial pterygoid muscle of masticator space, or carotid, prestyloid, and prevertebral or retropharyngeal space). OS, LRFS, and DMFS with extensive parapharyngeal extension were similar to those in T4 disease; OS, LRFS, and DMFS with mild parapharyngeal extension were significantly higher than in those T3 disease (all P ≤ 0.015). CONCLUSIONS: Parapharyngeal extension in NPC should be subclassified as mild or extensive, which should be regarded as stages T2 and T4 diseases, respectively.

Concurrent chemotherapy for T4 classification nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy.

OBJECTIVE: To evaluate concurrent chemotherapy for T4 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). METHODS: From July 2004 to June 2011, 180 non-metastatic T4 classification NPC patients were retrospectively analyzed. Of these patients, 117 patients were treated by concurrent chemoradiotherapy (CCRT) using IMRT and 63 cases were treated by IMRT alone. RESULTS: The median follow-up time was 58.97 months (range, 2.79-114.92) months. For all the patients, the 1, 3 and 5-year local failure-free survival (LFFS) rates were 97.7%, 89.2% and 85.9%, regional failure free survival (RFFS) rates were 98.9%, 94.4% and 94.4%, distant failure-free survival (DFFS) rates were 89.7%, 79.9% and 76.2%, and overall survival (OS) rates were 92.7%, 78.9% and 65.3%, respectively. No statistically significant difference was observed in LFFS, RFFS, DFFS and OS between the CCRT group and the IMRT alone group. No statistically significant difference was observed in acute toxicity except leukopenia (p = 0.000) during IMRT between the CCRT group and the IMRT alone group. CONCLUSION: IMRT alone for T4 classification NPC achieved similar treatment outcomes in terms of disease local control and overall survival as compared to concurrent chemotherapy plus IMRT. However, this is a retrospective study with a limited number of patients, such results need further investigation in a prospective randomized clinical trial.

Role of Chemotherapy in Stage II Nasopharyngeal Carcinoma Treated with Curative Radiotherapy.

PURPOSE: To define the role of neoadjuvant and concurrent chemotherapy in stage II nasopharyngeal carcinoma, we compared the treatment outcomes of patients treated with curative radiotherapy with or without chemotherapy. MATERIALS AND METHODS: From 2004 to 2011, 138 patients with American Joint Committee on Cancer (AJCC) 2002 stage II nasopharyngeal carcinoma were treated with curative radiotherapy in 12 hospitals in South Korea. Treatment methods included radiotherapy alone in 34 patients, neoadjuvant chemotherapy followed by radiotherapy alone in seven, concurrent chemoradiotherapy in 80, and neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in 17. Adjuvant chemotherapy was used in 42 patients. Total radiation dose ranged from 64 Gy to 74.2 Gy (median, 70 Gy). RESULTS: Median follow-up was 48 months (range, 7 to 97 months) for all patients. At the last follow-up, 13 patients had died and 32 had experienced treatment failure; locoregional failure occurred in 14, distant failure in 16, and both in two. Five-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 86.2%, 85.5%, 74.4%, and 88.2%, respectively. Multivariate analyses showed that the significant prognostic factors were concurrent chemotherapy and N stage for locoregional relapse-free survival, concurrent chemotherapy for progression-free survival, and age and N stage for overall survival. Neither neoadjuvant nor concurrent chemotherapy improved distant metastasis-free survival. CONCLUSION: Concurrent chemotherapy significantly improved 5-year locoregional relapse-free survival and progression-free survival in stage II nasopharyngeal carcinoma. However, neoadjuvant chemotherapy failed to improve either.

Update report of T4 classification nasopharyngeal carcinoma after intensity-modulated radiotherapy: an analysis of survival and treatment toxicities.

OBJECTIVE: To evaluate the long-term survival outcomes and toxicity of a larger series of patients with non-metastatic T4 classification nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: From March 2004 to June 2011, 335 non-metastatic T4 classification NPC patients treated by IMRT were analyzed retrospectively. Treatment induced toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: With a median follow-up time of 53.6 months (range, 2.8-114.9 months), the 5-year local failure-free survival (LFFS), regional failure free survival (RFFS), distant failure-free survival (DFFS), and overall survival (OS) were 84.1%, 92.2%, 74.1%, and 63.0%, respectively. At their last follow-up visit, 118 patients (35.2%) had developed treatment failure. Distant metastasis was the major failure pattern after treatment. The most common toxicities were mainly in grade 1 or 2. Concurrent chemotherapy failed to improve survival rates for patients with T4 classification NPC. CONCLUSION: The results of T4 classification NPC treated by IMRT were excellent, and distant metastasis was the most commonly failure pattern. Treatment-related toxicities were well tolerable. The role of concurrent chemotherapy for T4 classification NPC needs to be further investigated in the era of IMRT.

Proposal of a clinical typing system and generation of a prognostic model in patients with nasopharyngeal carcinoma from Southern China.

PURPOSE: To propose a novel clinical typing classification focusing on the distinct progression patterns of nasopharyngeal carcinoma (NPC), to supplement our knowledge of the clinical-biological behavior, to provide useful knowledge for treatment planning, and to contribute to basic research in NPC. METHODS: 632 consecutive patients were retrospectively reviewed and analyzed according to the novel typing system. We considered that NPC can be divided into 5 types as follows: limited (L), ascending (A), descending (D) ascending- descending (mixed) (AD), and distant metastasis types (M). The distribution of these clinical types, their association with Epstein-Barr virus (EBV) serology and prognostic value were explored. RESULTS: 55 (8.70%), 59 (9.34%), 177 (28.01%), 321 (50.79%) and 20 (3.16%) patients were classified as Type L, A, D, AD and M, respectively. EBV (VCA)-IgA titers, EBV early antigen (EA)-IgA serum titers, and capsid antigen lg(EBV DNA) were positively associated with the clinical typing (p<0.05). The 3-year overall survival (OS) rates for Types L, A, D, AD and M were 100, 100, 95.10, 88.20 and 59.30%, respectively (p<0.001). A prognostic model was constructed based on pretreatment lg (EBV DNA) and clinical type, which were independent predictors of OS (multivariate Cox proportional model). The prognostic model stratified patients into 4 risk subgroups. The 3-year OS rates of the low, intermediate, high and extremely high risk groups were 99.5, 90.0, 85.5 and 53.2%, respectively (p<0.001). Compared with the low-risk group, the risk of death was 4.96, 8.75 and 35.9 in the intermediate, high and extremely high risk groups, respectively (p<0.001). The model also predicted OS independently of TNM classification. CONCLUSION: This novel clinical typing system and prognostic model can supplement TNM classification, and may help design novel treatment strategies, evaluate risk stratification and investigate the varied biological characteristics of NPC.