Primary Treatment For Nasopharyngeal Carcinoma Research Articles

34 Impact of antibiotic use in the primary treatment of nasopharyngeal carcinoma

34 Impact of antibiotic use in the primary treatment of nasopharyngeal carcinoma

The promising role of miRNAs in radioresistance and chemoresistance of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor that develops in the nasopharynx. It has a distinct ethnic and geographical distribution, and emerging evidence suggests that it is an ecological disease. Most patients respond well to radiation combined with chemotherapy as the primary treatment for NPC. However, some patients will eventually develop radio resistance and chemoresistance, resulting in recurrence and metastasis, which is a primary cause of poor prognosis. The processes underlying radio resistance and chemoresistance in NPC are complex and unknown. MicroRNAs (miRNAs) are endogenic non-coding RNA molecules. They play a role in a variety of cell functions as well as development of disease such as cancer. There has been considerable data demonstrating the existence of numerous aberrant miRNAs in cancer tissues, cells, and biofluids, which indicates the importance of studying the influence of miRNAs on NPC. Therefore, this review comprehensively analyzes the elaborate mechanisms of miRNAs affecting the radio resistance and chemoresistance of NPC. Multiple tumor-specific miRNAs can be employed as therapeutic and prognostic biological indicators.

A detailed dosimetric comparative study of IMRT and VMAT in normal brain tissues for nasopharyngeal carcinoma patients treated with radiotherapy.

Radiotherapy (RT) is the primary treatment for nasopharyngeal carcinoma (NPC). However, it can cause implicit RT-induced injury by irradiating normal brain tissue. To date, there have been no detailed reports on the radiated exact location in the brain, the corresponding radiation dose, and their relationship. We analyzed 803 Chinese NPC patients treated with RT and used a CT brain template in a Montreal Neurological Institute (MNI) space to compare the group differences in RT dose distribution for different RT technologies (IMRT or VMAT). Brain regions that received high doses (>50 Gy) of radiation were mainly located in parts of the temporal and limbic lobes, where radioactive damage often occurs. Brain regions that accepted higher doses with IMRT were mainly located near the anterior region of the nasopharyngeal tumor, while brain regions that accepted higher doses with VMAT were mainly located near the posterior region of the tumor. No significant difference was detected between IMRT and VMAT for T1 stage patients. For T2 stage patients, differences were widely distributed, with VMAT showing a significant dose advantage in protecting the normal brain tissue. For T3 stage patients, VMAT showed an advantage in the superior temporal gyrus and limbic lobe, while IMRT showed an advantage in the posterior cerebellum. For T4 stage patients, VMAT showed a disadvantage in protecting the normal brain tissue. These results indicate that IMRT and VMAT have their own advantages in sparing different organs at risk (OARs) in the brain for different T stages of NPC patients treated with RT. Our approach for analyzing dosimetric characteristics in a standard MNI space for Chinese NPC patients provides greater convenience in toxicity and dosimetry analysis with superior localization accuracy. Using this method, we found interesting differences from previous reports: VMAT showed a disadvantage in protecting the normal brain tissue for T4 stage NPC patients.

Nasopharyngeal Radiation-Induced Sarcoma: A Case Report.

The primary treatment for nasopharyngeal carcinoma (NPC) is radiotherapy. In rare cases, patients with NPC treated with radiotherapy may develop radiation-induced sarcoma (RIS), a malignant tumor, in the field of previous radiation. The prognosis is poor, and complete surgical resection is the only potentially curative treatment. We report a case of radiation-induced nasopharyngeal sarcoma after radiotherapy for NPC with suspected lung and liver metastases in a 69-year-old woman.

Genome-Scale CRISPR-Cas9 Knockout Screening in Nasopharyngeal Carcinoma for Radiosensitive and Radioresistant Genes

Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), and resistance of cancer cells to radiation is one of the major causes of treatment failure. In this study, the genome-wide CRISPR/Cas9-sgRNA library virus was used for the first time to screen for the functional genes associated with radiosensitivity and radioresistance in nasopharyngeal carcinoma, which lays the foundation for new research aiming to explain the mechanisms behind the radiosensitivity of nasopharyngeal carcinoma and makes some contribution to the discovery of new therapeutic targets and the development of new drugs to increase the sensitivity of NPC cells to radiotherapy.CRISPR/Cas9 library lentivirus screening in radiation-treated nasopharyngeal carcinoma cells was combined with second-generation sequencing technology to identify specific sgRNAs. A set of samples as contrast, and early library infection was the starting control for genetic change trend analysis. Two groups were exposed to doses of 0 and 2 Gy, and cell samples were collected 7 and 14 days after irradiation. The genomic DNA of living cells was used for PCR amplification in the coding region of sgRNA, and then high-throughput sequencing analysis was performed. The radiosensitivity or radioresistance of the screened functional genes in nasopharyngeal carcinoma were further verified by colony formation and cell proliferation experiments using a cell counting kit in a stable cell line with single gene knockout and qPCR analysis in radioresistant nasopharyngeal carcinoma cells.Eleven radiosensitive and radioresistant function genes were selected based on high-throughput sequencing and bioinformatics analysis. Compared with the control group, after the single gene FBLN5, FAM3C, MUS81, or DNAJC17 knockout, the colony formation and proliferation ability of nasopharyngeal carcinoma cells C666-1 and CNE1 were significantly promoted, while after the single gene CDKN2AIP and SP1 knockout, the colony formation and proliferation ability were significantly lower (P < 0.05). Compared to the negative control cells, the expression levels of FBLN5, FAM3C, MUS81, and DNAJC17 were significantly lower in the C666-1-Rs and 5-8F-Rs cell lines (P < 0.05), while the expression levels of TOMM20, CDKN2AIP, SNX22, and SP1 were significantly higher (P < 0.05). KEGG enrichment analysis showed that the potential signaling pathway contributed to radiosensitivity or radioresistance in NPC, including the Fanconi anemia pathway and the TGF-beta signaling pathway.We found nine genes through CRISPR/Cas9-mediated genome-wide knockout involved in the radiosensitivity or radioresistance of NPC cells: four genes for radiosensitivity, FBLN5, FAM3C, MUS81, and DNAJC17; two genes for radioresistance: CDKN2AIP, SP1, while TOMM20 and SNX22 are potential radioresistant genes, and CALD1 is a potential radiosensitive gene.

Outcomes for the treatment of locoregional recurrent nasopharyngeal cancer: Systematic review and pooled analysis

Despite advances in the treatment of primary nasopharyngeal carcinoma, locoregional recurrence (lrNPC) occurs at 10%-50% at 5 years. This review aims to evaluate salvage treatment for locally recurrent nasopharyngeal cancer. A literature search for all original articles published on the treatment of lrNPC from January 1990 to January 2021 was conducted. Pooled analysis was performed using a random effects model and assessed statistical heterogeneity of the combined results with I2 index. Overall, 66 studies were included for analysis. A total of 5286 patients treated with intensity-modulated radiation therapy (39%), conformal radiotherapy (31%), open nasopharyngectomy (12%), endoscopic nasopharyngectomy (10%), stereotactic radiosurgery (4%), and brachytherapy (4%) were included. Surgical therapy has similar overall survival outcomes to re-irradiation but with decreased treatment-related morbidity and mortality. Both surgical and re-irradiation for lrNPC have similar long-term survival. Surgical approaches to lrNPC may offer similar survival while avoiding treatment-associated morbidity and mortality.

Neck lymph node status on survival of regionally recurrent or persistent nasopharyngeal carcinoma

The aim of this study was to evaluate the impact of lymph node status from neck dissection pathological specimens on the survival for isolated regional nodal recurrence or persistence after primary treatment of nasopharyngeal carcinoma. Through a retrospective cohort study performed in an academic tertiary referral hospital in Hong Kong. Forty-six patients who underwent a salvage neck dissection between June 2001 and January 2013 for isolated regionally recurrent or persistent nasopharyngeal carcinoma was performed. Informed consent was waived for this retrospective study by The Joint CUHK-NTEC CREC. In the study forty-six patients had a salvage neck dissection for nodal failure with a mean age of 53 and 74% (34) were male. With a mean follow-up of 45.3 months, Overall survival, disease specific survival, loco-regional recurrence free survival, and regional recurrence free survival were 56.5%, 73.9%, 87.0%, and 91.3% respectively. For both univariate and multivariate analysis, patients with a number of positive lymph nodes more than 5 and a lymph node density more than 20% were significantly associated with poorer overall survival. Extracapsular spread and pathological cervical lymph node staging did not have an association with poorer survival. In conclusion, an absolute number of positive lymph nodes more than five and a lymph node density more than 20% were potentially useful prognostic factors affecting survival following a neck dissection for regional residual or recurrent nasopharyngeal carcinoma.

Effect of relevant factors on radiation-induced nasopharyngeal ulcer in patients with primary nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.

ObjectiveTo analyze the correlation between relevant factors and radiation‐induced nasopharyngeal ulcer (RINU) in primary nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiation therapy (IMRT).MethodsClinical data were collected for 599 patients with newly diagnosed NPC who had completed IMRT. The entire cohort was randomly divided into two subgroups. The relationship between RINU and IMRT dose‐volume were statistically analyzed with ROC curves and the Chi‐square test. Nutritional status during and after treatment was compared between patients with vs without RINU.ResultsThe results obtained showed that dose‐volume had no effect on the incidence of RINU (P > .05). Nutrition‐related parameters differed significantly between patients with vs without RINU (P < .05).ConclusionThe results obtained show that the incidence of RINU is not related to IMRT dose‐volume in the treatment of primary NPC. The incidence of RINU was found to be related to nutritional status during and after radiation therapy.Level of Evidence2a

Radiotherapy dose escalation in the primary treatment of nasopharyngeal carcinoma: a systematic review and meta-analysis

Background: Dose escalation with radiotherapy (RT) in nasopharyngeal carcinoma (NPC) remains underutilized despite significant advances in methods of radiation delivery. RT boost during primary treatment has been shown to improve local control rates, which could have an impact on survival. We summarize the currently available evidence for dose escalation in the primary treatment of NPC. Methods: Databases were systematically searched for eligible studies from the year 2000. Included studies utilized RT dose escalation (BED >70 Gy) in the form of brachytherapy, external beam RT or stereotactic RT boost after external beam RT for primary treatment of NPC. Local recurrence-free survival (LRFS), overall survival (OS), toxicities and other relevant factors for the chosen studies were then pooled and analyzed. Results: Two randomized trials and 7 retrospective cohort studies with a total of 2,145 patients were included in the final analysis. Nine hundred and eighty-eight patients received dose escalation, mainly in the form of brachytherapy (90%). Patients were mostly male, from China/Southeast Asia, had T1-T2 disease (80%), underwent RT via conventional techniques (87%). Less than half received concurrent chemotherapy. Three-year LRFS (RR 1.04; 95% CI: 0.85–1.28, P=0.71) and OS were not significantly improved with dose escalation. However, the subset of patients pooled from the retrospective studies who did not receive concurrent chemotherapy showed significant a 5-year locoregional failure-free survival (RR 1.05; 95% CI: 1.02–1.09, P=0.005) benefit. Toxicities were not significantly increased with dose escalation. Conclusions: RT dose escalation in the primary treatment of NPC does not lead to an increase in LRFS, OS, progression free-survival and disease free-survival. However, there seems to be a LRFS benefit with dose escalation using brachytherapy in patients with T1-T2 disease and in patients who did not receive concurrent chemotherapy. Dose escalation with brachytherapy is likewise not significantly associated with any increase in the rate of complications. Data for the efficacy and toxicity of EBRT and SRT boost is currently still lacking.

The treatment modalities and outcomes of recurrent nasopharyngeal carcinoma: a retrospective cohort study in the modern era

Background: While chemoradiotherapy being widely recognized as primary treatment for nasopharyngeal carcinoma (NPC), optimal salvage modalities for locoregionally recurrent NPC (LRrNPC) are still under debate. This study aimed to explore outcomes of different salvage modalities for LRrNPC. Methods: Non-metastatic LRrNPCs were retrospectively recruited. Clinical factors and salvage treatments were evaluated. The primary and secondary endpoint were locoregional-progression-free survival (LRPFS) and overall survival (OS), respectively. Outcomes were compared among re-irradiation (reRT), surgical resection (SR), combination therapy (SR + reRT), and systemic treatment only (STx). Results: From 2006–2017, 29 consecutive LRrNPCs were enrolled, including 37.9% rT1-2 and 62.1% rT3-4 diseases. Salvage treatments included 14 reRT, 6 SR, 6 SR + reRT, and 3 STx. All re-irradiations were intensity-modulated radiotherapy (IMRT) and 83.3% SRs were done by endoscopic approach. After median follow-up of 36 months, the 3-year LRPFS was 56.5% and 3-year OS was 64.1%. When compared to STx, reRT and SR + reRT both showed superior LRPFS (re-RT, HR: 0.06, P=0.009; SR + reRT, HR: 0.07, P=0.021, adjusted for rT), while SR revealed no significant benefit. However, there was no significant difference in LRPFS among the three local treatment modalities. Severe complication rates were 51.7% for ≥grade 3 and 6.9% for grade 5. Conclusions: For LRrNPCs, locoregional treatments including reRT and SR + reRT might have additional local control benefit from systemic therapy. The risk of fatal toxicity decreased with increasing use of IMRT and endoscopic resection. Considering the limited case number and retrospective design, prospective trials are warranted to further evaluate the efficacy and safety.

Comparing radiotherapy with or without intracavitary hyperthermia in the treatment of primary nasopharyngeal carcinoma: a retrospective analysis.

A retrospective study was performed to evaluate the contribution of intracavitary hyperthermia in patients with nasopharyngeal carcinoma who received radiation therapy. Patients with nasopharyngeal carcinoma were treated with radiotherapy alone or with radiotherapy plus hyperthermia of the primary tumor. All patients were treated in a uniform fashion by definitive-intent radiotherapy in both groups. In the radiotherapy plus hyperthermia group, patients were treated with microwave heating hyperthermia delivered twice a week in combination with radiation. Between November 1992 to September 1994, 225 patients were recruited, with 98 patients matched to the criteria of either treatment group (49 in the radiotherapy and 49 in the radiotherapy plus hyperthermia group). Ninety-eight patients were included in the treatment response and 87 patients in the survival analysis according to the intent-to-treat principle (11 patients were lost to follow-up). Overall survival did not show a significant difference between the two groups (81 vs 86 months of median survival time, respectively, P = 0.068). However, there were significant differences not only in progression-free survival (median months, 60 vs 100, respectively, P = 0.036), but also in local progression-free survival (median months, 54 vs 111, respectively, P = 0.029) between the radiotherapy and radiotherapy plus hyperthermia groups. No statistical difference was noted in the cumulative incidence of grade 3 adverse events or late radiation morbidity during follow-up between the two study groups. The retrospective study showed that hyperthermia combined with radiation therapy can improve progression-free survival and local progression-free survival, although no increase in overall survival was observed. Thus, the inclusion of hyperthermia in the treatment of nasopharyngeal carcinoma using radiation offers no survival benefit but may help to improve the current standard of care consisting of radiation and chemotherapy.

MiR-150 contributes to the radioresistance in nasopharyngeal carcinoma cells by targeting glycogen synthase kinase-3β.

Radiotherapy has been the primary treatment for nasopharyngeal carcinoma (NPC), but the NPC radiocurability was severely limited with the radioresistance. The research suggested the important role of miRNAs in cancer therapeutic response. A radioresistant NPC cell line CNE-2R, we exposed CNE-2 cells to a range of radiation doses. Levels of miR-150 were measured by quantitative reverse-transcriptase polymerase chain reaction in CNE-2R and CNE-2 cells. In this study, a cell line CNE-2R derived from parental CNE-2 was established via being exposed to stepwise escalated radiation dose. The expression of miR-150 was upregulated in CNE-2R cells. The radioresistance of CNE-2R cells was reversed after inhibiting miR-150 with specific inhibitor, while the radioresistance of CNE-2 cells was enhanced after the overexpression of miR-150. MiR-150b elicited these responses by directly targeting GSK3β. Moreover, GSK3β protein expression was downregulated in CNE-2R cells and restored GSK3β expression increased radiosensitivity of CNE-2R cells. Importantly, the negative correlation between miR-150 expression and GSK3β protein level was confirmed in the NPC tissues. High miR-150 expression and low GSK3β protein level were associated with poor prognosis in NPC patients. Our findings suggested that miR-150-GSK3β axis may be a novel candidate for developing rational therapeutic strategies for NPC treatment.

Knockdown of Annexin A1 Enhances Radioresistance and Inhibits Apoptosis in Nasopharyngeal Carcinoma.

Radiotherapy is the primary treatment for nasopharyngeal carcinoma while radioresistance can hinder efficient treatment. To explore the role of annexin A1 and its potential mechanisms in radioresistance of nasopharyngeal carcinoma, human nasopharyngeal carcinoma cell line CNE2-sh annexin A1 (knockdown of annexin A1) and the control cell line CNE2-pLKO.1 were constituted and CNE2-sh annexin A1 xenograft mouse model was generated. The effect of annexin A1 knockdown on the growth of xenograft tumor after irradiation and radiation-induced DNA damage and repair was analyzed. The results of immunohistochemistry assays and Western blotting showed that the level of annexin A1 was significantly downregulated in the radioresistant nasopharyngeal carcinoma tissues or cell line compared to the radiosensitive nasopharyngeal carcinoma tissues or cell line. Knockdown of annexin A1 significantly promoted CNE2-sh annexin A1 xenograft tumor growth compared to the control groups after irradiation. Moreover, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays revealed that knockdown of annexin A1 significantly inhibited apoptosis in vivo compared to the control groups. We assessed the intracellular reactive oxygen species levels and the extent of radiation-induced DNA damage and repair using reactive oxygen species assay, comet assays, and immunohistochemistry assay. The results showed that knockdown of annexin A1 remarkedly reduced the intracellular reactive oxygen species levels, level of DNA double-strand breaks, and the phosphorylation level of H2AX and increased the accumulation of DNA-dependent protein kinase in nasopharyngeal carcinoma cells after irradiation. The findings suggest that knockdown of annexin A1 inhibits DNA damage via decreasing the generation of intracellular reactive oxygen species and the formation of γ-H2AX and promotes DNA repair via increasing DNA-dependent protein kinase activity and therefore improves the radioresistance in nasopharyngeal carcinoma cells. Together, our findings suggest that knockdown of annexin A1 promotes radioresistance in nasopharyngeal carcinoma and provides insights into therapeutic targets for nasopharyngeal carcinoma radiotherapy.

EMP2 re-expression inhibits growth and enhances radiosensitivity in nasopharyngeal carcinoma.

Although radiation therapy is the primary treatment for nasopharyngeal carcinoma, radioresistance remains a major obstacle to successful treatment in many cases, and the exact underlying molecular mechanisms are still ill-defined. EMP2, epithelial membrane protein-2, was a recently identified potential oncogene involved in multiple biological processes including cell migration and cell proliferation. This study was to explore the potential relationship between EMP2 expression, nasopharyngeal carcinoma genesis, and radioresistance. EMP2 expression status in 98 nasopharyngeal carcinoma clinical samples was examined by immunohistochemical staining. As a result, most of the nasopharyngeal carcinoma tumor samples were weakly or negatively stained, while paired adjacent normal tissues were moderately or strongly stained. Moreover, patients with higher expression of EMP2 had significant longer survival times. EMP2 re-expression suppresses cell growth, induces S-phase cell cycle arrest, and promotes radiosensitivity and apoptosis in nasopharyngeal carcinoma cells. These results support that loss of EMP2 is common, and its re-expression may serve as an approach to enhance radiation sensitivity in nasopharyngeal carcinoma.

Bortezomib Relieves Immune Tolerance in Nasopharyngeal Carcinoma via STAT1 Suppression and Indoleamine 2,3-Dioxygenase Downregulation.

Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC). Patients with intermediate and advanced stage NPC receiving only radiotherapy have limited survival, so newer immunotherapeutic approaches are sought. The major impediment to better clinical outcomes is tumor immune tolerance. Indoleamine 2,3-dioxygenase (IDO), an IFNγ-inducible enzyme, is a major inducer of immune tolerance during tumor development; therefore, inhibition of the IDO pathway is an important modality for cancer treatment. We show that bortezomib, a proteasomal inhibitor, inhibited the pathways leading to STAT1 and IRF-1 activation, both of which are necessary for IDO expression. Bortezomib downregulated IFNγ-induced IDO expression via inhibition of STAT1 phosphorylation and nuclear translocation, thereby suppressing STAT1-driven IDO transcription in NPC cells. Bortezomib also promoted IκB-α phosphorylation-ubiquitination, which released NF-κB from IκB-α. However, the released NF-κB could not enter the nucleus to conduct its biological effects and accumulated in the cytoplasm. Negative feedback inhibited the transcription of NF-κB, which is important for activating IRF-1 expression. IDO expression is regulated by two important transcription factor binding sites, ISREs, which bind STAT1 and IRF-1, and GASs, which binds STAT1. Bortezomib upregulated IRF-1 protein by inhibiting its proteasome-dependent degradation, but it also inhibited STAT1 phosphorylation, which directly inhibited the activation of GAS and indirectly inhibited the activation of ISRE, which needs both STAT1 and IRF-1. These discoveries provide a mechanism for the antitumor action of bortezomib and have implications for the development of clinical cancer immunotherapy for preventing and treating NPC. Cancer Immunol Res; 5(1); 42-51. ©2016 AACR.

MicroRNA-19b-3p regulates nasopharyngeal carcinoma radiosensitivity by targeting TNFAIP3/NF-κB axis.

BackgroundNasopharyngeal carcinoma (NPC) is among the most common squamous cell carcinoma in South China and Southeast Asia. Radiotherapy is the primary treatment for NPC. However, radioresistance acts as a significant factor that limits the efficacy of radiotherapy for NPC patients. Growing evidence supports that microRNAs (miRNAs) play an important role in radiation response.MethodsReal-time quantitative PCR was used to analyze the expression of miR-19b-3p in NPC cell lines and NP69. miR-19b-3p expression profiles in NPC tissues were obtained from the Gene Expression Omnibus database. The effect of miR-19b-3p on radiosensitivity was evaluated by cell viability assays, colony formation assays and in vivo experiment. Apoptosis and cell cycle were examined by flow cytometry. Luciferase reporter assay was used to assess the target genes of miR-19b-3p. Expression of target proteins and downstream molecules were analyzed by Western blot.ResultsmiR-19b-3p was upregulated in NPC and served as an independent predictor for reduced patient survival. Radioresponse assays showed that miR-19b-3p overexpression resulted in decreased sensitivity to irradiation, whereas miR-19b-3p downregulation resulted in increased sensitivity to irradiation in vitro. Moreover, miR-19b-3p decreased the sensitivity of NPC cells to irradiation in vivo. Luciferase reporter assay confirmed that TNFAIP3 was a direct target gene of miR-19b-3p. Knockdown of TNFAIP3 reduced sensitivity to irradiation, whereas upregulation of TNFAIP3 expression reversed the inhibitory effects of miR-19b-3p on NPC cell radiosensitivity. Mechanistically, we found that miR-19b-3p increased NPC cell radioresistance by activating the TNFAIP3/ NF-κB axis.ConclusionsmiR-19b-3p contributes to the radioresistance of NPC by activating the TNFAIP3/ NF-κB axis. miR-19b-3p is a determinant of NPC radioresponse and may serve as a potential therapeutic target in NPC treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0465-1) contains supplementary material, which is available to authorized users.

Progress in cognitive dysfunction induced by radiotherapy in patients with nasopharyngeal carcinoma

Radiotherapy (RT) is the primary treatment for nasopharyngeal carcinoma (NPC). In order to achieve tumor control, nearby normal brain tissues, especially the temporal lobes, often receive unnecessary radiation. Patients with NPC treated by RT may occur cognitive impairments, which significantly compromises the quality of life. The symptoms of cognitive dysfunction induced by RT in NPC patients can exhibit at the early or later stage after RT, which may be related to temporal lobe injury or brain damage induced by radiation. However, the relationship between the cognitive declines induced by RT and the radiation dose or volume of the temporal lobe (or the dosimetry to treat NPC) has not yet been definitively established, and few reports have focused on cognitive impairment following intensity modulated RT. Therefore, this paper will review the progress in radiation-induced cognitive decline of NPC patients in order to provide the basis for preventing side effects of RT and improving the quality of life after RT. Key words: Nasopharyngeal carcinoma; Cognitive impairment; Radiotherapy

Downregulation of Annexin A1 is correlated with radioresistance in nasopharyngeal carcinoma.

Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance often remains an obstacle to successful treatment. In our previous study, it was demonstrated that Annexin A1 (ANXA1) was involved in the p53-mediated radioresponse in NPC cells, which suggested that it may be associated with radioresistance in NPC; however, the role of ANXA1 in NPC radioresistance is unknown. In the present study, CNE2 cells were stably transfected with pLKO.1-ANXA1-small hairpin (sh)RNAs to investigate the effects of ANXA1 on the radiosensitivity of NPC. CNE2 cells transfected with pLKO.1 were used as the control. The radiosensitivities of the cells in vitro were analyzed using the clonogenic survival assay, cell growth analysis, flow cytometry and Hoechst 33258 staining. ANXA1 downregulation significantly enhanced clonogenic survival and cell growth following treatment of CNE2 cells with ionizing radiation (IR), increased the number of cells in the S phase and decreased IR-induced apoptosis. These results suggested that the radiosensitivity of CNE2 cells transfected with ANXA1-specific shRNA was significantly lower compared with the control cells. Therefore, ANXA1 downregulation may be involved in the radioresistance of NPC, and ANXA1 may be considered a novel biomarker for predicting NPC response to radiotherapy.

Salvage surgery for nasopharyngeal cancer.

Nasopharyngeal carcinoma (NPC) is a special type of head and neck cancer with a widely variable geographical variation in incidence. The central location of the tumor inside the head coupled with the radiosensitivity of the tumor to radiation made radiation therapy the first choice in primary treatment of NPC. Advances in radiotherapy and chemotherapy have markedly improved the local control of NPC. Unfortunately, a small but significant number of patients still suffered from loco-regional failures that would be amenable to re-treatment. Traditional form of retreatment was to employ a second course of radiation. The efficacy of re-irradiation to treat local of regional recurrent NPC has been suboptimal. Moreover, the local tissue had already received a high dose of radiation and the second radiation could result in radiation toxicities to the local tissue, leading to significant complications.Surgical salvage, on the other hand, could spare the patients from complications of re-treatment. Due to the difficult access of the nasopharynx, various surgical approaches had been devised for nasopharyngectomy. The maxillary swing approach had the largest published experience with over 300 cases from various centers. In the recent decade, the endoscopic approach with or without robotic assistance had gained popularity for resecting small, centrally located recurrences. This minimally invasive approach further reduced the morbidity for treating locally recurrent NPC.Nodal recurrences had been a rare entity after the introduction of modern radiotherapy technique and concurrent chemotherapy. Treatment of nodal failure with second radiation has dismal results. Surgical removal of the lymph node harboring the recurrence should be in the form of a formal radical neck dissection. In cases of extensive nodal recurrence where microscopic disease may be present after a formal neck dissection, additional radiotherapy can be delivered with after-loading brachytherapy.Surgical treatment played a definitive role in salvage of loco-regional failures of nasopharyngeal carcinoma.

Evidence on effectiveness of intensity‐modulated radiotherapy versus 2‐dimensional radiotherapy in the treatment of nasopharyngeal carcinoma: Meta‐analysis and a systematic review of the literature

Current management of nasopharyngeal carcinoma (NPC) uses radiotherapy (RT) as the curative treatment modality. Radiation delivery techniques for NPC can be achieved using 2D conventional RT or intensity-modulated radiotherapy (IMRT). A systematic review and meta-analysis of the literature was undertaken to assess the effectiveness of IMRT versus 2D conventional RT in primary treatment of NPC. IMRT showed better results than 2D conventional RT in terms of local control, regional control, and overall survival, but when stratified, only in T4, N2, and stage III were the differences that were seen. Objective saliva measurements and physician-graded xerostomia were better in IMRT. However, patient-reported xerostomia showed minimal improvement only in IMRT. The evidence of superiority of IMRT over 2D conventional RT is not clear. In the absence of more clinical data demonstrating the superiority of IMRT in the treatment of nasopharyngeal carcinoma, 2D conventional RT seems to be a reasonable treatment option, especially in limited resource settings. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2130-E2142, 2016.