Advances in nasopharyngeal carcinoma
Nasopharyngeal carcinoma prognosis is related to its potential locoregional invasion and metastatic spread. Among prognostic factors, initial tumor-node-metastasis stage is the main one, besides other biological parameters. Worldwide development of positron emission tomography imaging is changing modalities of staging. Concomitant chemoradiotherapy represents one of the most recent advances in the treatment of nasopharyngeal carcinoma patients, besides intensity-modulated radiation therapy. This review updates these recent advances in diagnosis and treatment of nasopharyngeal carcinoma. Recent publications have shown the superiority of fused positron emission tomography/computed tomography over positron emission tomography alone and conventional imaging to do an accurate staging and to impact on patient management. Circulating Epstein-Barr virus DNA load may be a useful prognostic marker in endemic regions. Recent meta-analysis confirmed the superiority of concurrent chemoradiotherapy to radiotherapy alone. Previous publications have shown that induction chemotherapy with new agents might be promising. Data demonstrating targeted therapies efficacy in metastatic nasopharyngeal carcinoma are limited to date. Positron emission tomography-computed tomography is replacing conventional imaging in the initial M staging of nasopharyngeal carcinoma. Its usefulness in response evaluation after therapy and its place in the follow-up need to be prospectively evaluated. Cisplatin-based concomitant chemoradiotherapy is now the standard treatment for locally advanced patients. However, incidence of relapses remains high, and new multimodal therapy is needed.
[Show abstract] [Hide abstract] ABSTRACT: Objectives: This retrospective study reassessed nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT), to determine the significance how magnetic resonance imaging (MRI)-derived masticator space involvement (MSI) affected patients' prognosis. Methods: One thousand one hundred ninety seven NPC patients who had complete set of MRI and medical records were enrolled. Basing on their MRI findings, the T-categories of tumors were identified according to the seventh edition of American Joint Committee on Cancer staging system, which considers MSI a prognostic indicator for NPCs. Rates of overall survival (OS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS) and distant metastasis-free survival (DMFS) were analyzed by the Kaplan-Meier method, and the Log-Rank test compared their differences. Cox regression analysis was employed to evaluate various prognostic factors systematically. Statistical analyses were conducted with SPSS 18.0 software, P value < 0.05 was considered statistically significant. Results: Medial pterygoid muscle (MPM) was involved in 283 (23.64 %) cases, of which lateral pterygoid muscle (LPM) was concurrently affected in 181 (15.12 %) and infratemporal fossa (ITF) in 19 (1.59 %). Generally, MSI correlated with an OS, LRFS, and DMFS consistent with a T4-stage diagnosis (P > 0.05). Although different degrees of MSI presented a similar OS and DMFS (P > 0.1), tumors involving LPM had a relatively poorer LRFS than those affected the MPM only (P = 0.027), even for subgroup of patients composed of T3 and T4 classifications (P = 0.035). A tumor involving MPM brought an LRFS consistent with a T2 or T3-stage disease (P > 0.1). If the tumor affected LPM or ITF concurrently, the survival outcomes were more consistent with a T4-stage disease (P > 0.1). Nevertheless, compared to tumor infiltrating MPM, those invading LPM or ITF more frequently spread into other concurrent sites that earned higher T-staging categories. Moreover, multivariate analyses indicated the degree of MSI was a significant prognostic factor for the OS of NPCs (P = 0.036). Conclusions: Degree of MSI is a significant prognosticator for the OS of IMRT-treated NPCs, and the prognosis of patients with lateral MSI extension (LPM and ITF) were shown to be significantly worse than those affected only MPM or the T3-stage disease. Thus, it is highly recommended that lateral MSI extension be a higher T-staging category.0Comments 0Citations
- "Nasopharyngeal carcinoma (NPC) arises from nasopharyngeal mucosa, and presents an invasive biological behavior that is prone to infiltrate the surrounding structures , especially those lying laterally in parapharyngeal space, masticator space (MS), and infratemporal fossa (ITF) . NPC is known to be a radiosensitive tumor type, and chemoradiotherapy (CRT) is the primary treatment modality234. Reported 5-year overall survival (OS) rates for NPC patients have ranged from 58.6 to 83 %, and pretreatment tumor-node-metastasis (TNM) staging is used to guide assessments of the patient's prognosis5678. "
[Show abstract] [Hide abstract] ABSTRACT: Data mining on public domain identified that stathmin 1 (STMN1) transcript was significantly higher expressed in nasopharyngeal carcinoma (NPC). Also known as the oncoprotein 18, STMN1 performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cellular conditions. Immunoexpression of STMN1 was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high STMN1 expressions (50 %) were correlated with advanced age (p = 0.027), higher T stage (p = 0.003), and overall clinical stage (p = 0.006) by the 7th American Joint Committee of Cancer Staging. In multivariate analyses, high STMN1 expression emerged as an independent prognosticator for worse disease-specific survival (p = 0.001), distal metastasis-free survival (p = 0.003), and local recurrence-free survival (p = 0.006). Exogenous expression of E2F transcription factor 1 (E2F1) or/and its dimeric partner, transcription factor Dp-1 (TFDP1), notably induced the STMN1 protein level in a NPC-derived cell line, TW01. Accordingly, high STMN1 protein level is commonly associated with adverse prognosticators and confers tumor aggressiveness in patients with NPC, and its upregulation might be attributed to E2F1 and/or TFDP1 transactivation.0Comments 16Citations
- "Despite the fact that treatment is successful in the majority of the patients, challenges still exist, such as how to prevent a relapse of the disease, and how to treat patients with refractory or metastatic NPC (Razak et al., 2010). Identification of biomarkers that independently correlate with tumor aggressiveness will facilitate appropriate allocation of adjuvant therapy and will be valuable for patient-tailored strategy to manage high-risk NPCs (Guigay, 2008). Here, we demonstrate that TYMS represents such a marker. "
[Show abstract] [Hide abstract] ABSTRACT: Nasopharyngeal carcinoma (NPC) is a very regional malignant head and neck cancer that has attracted widespread attention for its unique etiology, epidemiology and therapeutic options. To achieve high cure rates in NPC patients, theranostic approaches are actively being pursued and improved efforts remain desirable in identifying novel biomarkers and establishing effective therapeutic approaches with low long-term toxicities. Here, we discovered that the scavenger receptor class B type I (SR-B1) was overexpressed in all investigated NPC cell lines and 75% of NPC biopsies, demonstrating that SR-B1 is a potential biomarker of NPC. Additional functional analysis showed that SR-B1 has great effect on cell motility while showing no significant impact on cell proliferation. As high-density lipoproteins (HDL) exhibit strong binding affinities to SR-B1 and HDL mimetic peptides are reportedly capable of inhibiting tumor growth, we further examined the SR-B1 targeting ability of a highly biocompatible HDL-mimicking peptide-phospholipid scaffold (HPPS) nanocarrier and investigated its therapeutic effect on NPC. Results show that NPC cells with higher SR-B1 expression have superior ability in taking up the core constituents of HPPS. Moreover, HPPS inhibited the motility and colony formation of 5-8F cells, and significantly suppressed the NPC cell growth in nude mice without inducing tumor cell necrosis or apoptosis. These results indicate that HPPS is not only a NPC-targeting nanocarrier but also an effective anti-NPC drug. Together, the identification of SR-B1 as a potential biomarker and the use of HPPS as an effective anti-NPC agent may shed new light on the diagnosis and therapeutics of NPC.0Comments 18Citations
- "Although these biomarkers play a key role in the diagnostics of NPC, the number of existing biomarkers is generally limited . Moreover, along with the improved cure rates in patients using current therapeutic methods, such as radiotherapy, chemotherapy, surgery and immuno- therapy7891011 , the issue of long-term side effects remains problematic . Therefore, the next challenge of NPC is to seek novel biomarkers for early diagnosis and highly biocompatible drugs for therapy121314. "