VLDL and LDL Subfractions Enhance the Risk Stratification of Individuals Who Underwent Epstein-Barr Virus-Based Screening for Nasopharyngeal Carcinoma: A Multicenter Cohort Study.

Serological tests for Epstein-Barr virus (EBV) antibodies have been widely conducted for the screening of nasopharyngeal carcinoma (NPC) in endemic areas. Further risk stratification of NPC can be achieved through plasma lipoprotein and metabolic profiles. A total of 297 NPC patients and 149 EBV-positive participants are enrolled from the NCT03919552 and NCT05682703 cohorts for plasma nuclear magnetic resonance (NMR) metabolomic analysis. Small, dense very low density lipoprotein particles (VLDL-5) and large, buoyant low density lipoprotein particles (LDL-1) are found to be closely associated with nasopharyngeal carcinogenesis. Herein, an NMR-based risk score (NRS), which combines lipoprotein subfractions and metabolic biomarkers relevant to NPC, is developed and well validated within a multicenter cohort. Combining the median cutoff value of the NRS (N50) with that of the serological test for EBV antibodies, the risk stratification model achieves a satisfactory performance in which the area under the curve (AUC) is 0.841 (95% confidence interval: 0.811-0.871), and the positive predictive value (PPV) reaches 70.08% in the combined cohort. These findings not only suggest that VLDL-5 and LDL-1 particles can serve as novel risk factors for NPC but also indicate that the NRS has significant potential in personalized risk prediction for NPC.

The Failure Patterns of Nasopharygeal Carcinoma After Intensity-Modulated Radiotherapy and Implications for Surveillance.

Objective: To investigate the treatment outcomes, failure patterns and surveillance strategy in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Methods: A cohort of patients with NPC who had received the full course of IMRT between 2008 and 2012 were retrospectively analyzed. The failure patterns, time to recurrence, and detection methods were recorded. The survival was calculated using the Kaplan-Meier method. Multivariate proportional hazard regression models were used to test the prognostic factors. Results: In total, 2607 patients with NPC treated with IMRT were recruited. After the median follow-up of 112 months, 402 (15.4%) patients experienced distant metastasis, 225 (8.6%) patients had local recurrence, and 77 (3.0%) patients had regional recurrences. The 10-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 74.5%, 90.1%, and 79.3%, respectively. The factors of male sex, age >50 years, lactate dehydrogenase >245 IU/L, advanced T classification, and advanced N classification were associated with poor OS. The N disease classification was the most important factor in predicting distant metastasis, and advanced T disease classification for high risk of local recurrence. For patients with T1 disease, the incidence of local recurrence was less than 2%, and the incidence of distant metastasis was less than 5% for patients with N0 disease. About 83% of the recurrence occurred in the first 5 years, and 20% of the recurrences showed no symptoms. Conclusion: High rate of local-regional control can be achieved for patients with NPC after IMRT, while distant metastasis remains as the major cause of failures. Patients with advanced N classification has high risk to develop distant metastasis, and most occurred within 5 years. Developing rational and individualized surveillance strategies based on the high risk factors of recurrence is helpful to balance the survival benefit and medical cost.

LncRNA SNHG11 enhances bevacizumab resistance in colorectal cancer by mediating miR-1207-5p/ABCC1 axis.

Long noncoding RNAs (lncRNAs) have been reported to serve as vital regulators in the chemoresistance of human cancers, including colorectal cancer (CRC). In this study, we aimed to explore the functions of lncRNA small nucleolar RNA host gene 11 (SNHG11) in the resistance of CRC to bevacizumab. Quantitative real-time PCR, western blot assay or immunohistochemistry assay were performed to examine the expression of SNHG11, microRNA-1207-5p (miR-1207-5p), ATP binding cassette subfamily C member 1 (ABCC1) and Ki67. Cell Counting Kit-8 assay was conducted to evaluate bevacizumab resistance and cell viability. 5'-ethynyl-2'-deoxyuridine analysis, flow cytometry analysis and wound-healing assay were conducted for cell proliferation, apoptosis and migration, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to analyze the relations among SNHG11, miR-1207-5p and ABCC1. Murine xenograft model assay was employed to analyze bevacizumab resistance in vivo. The exosomes were observed under transmission electron microscopy. SNHG11 was overexpressed in bevacizumab-resistant CRC tissues and cells. Knockdown of SNHG11 restrained bevacizumab resistance, repressed cell proliferation and migration, and promoted apoptosis in bevacizumab-resistant CRC cells. MiR-1207-5p served as the target of SNHG11 and SNHG11 regulated bevacizumab resistance by targeting miR-1207-5p. ABCC1 was the target gene of miR-1207-5p. Overexpression of miR-1207-5p inhibited bevacizumab resistance and cell progression in bevacizumab-resistant CRC cells, with ABCC1 elevation abrogated the impacts. SNHG11 silencing repressed bevacizumab resistance in vivo. In addition, exosomal SNHG11 was upregulated in bevacizumab-resistant CRC cells. SNHG11 contributes to bevacizumab resistance in CRC depending on the modulation of miR-1207-5p and ABCC1.

Efficacy and safety analysis of bevacizumab combined with capecitabine in the maintenance treatment of RAS-mutant metastatic colorectal cancer.

WHAT IS KNOWN AND OBJECTIVES: The optimal strategy for maintenance therapy in patients with metastatic colorectal cancer (mCRC) remains controversial. Considering that, beyond progression, co-therapy with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate. We aimed to investigate the differences in efficacy and safety between bevacizumab combined with capecitabine maintenance therapy and capecitabine monotherapy for RAS-mutant mCRC （as defined by mutations in KRAS and NRAS exons 2-4）controlled by bevacizumab plus FOLFIRI chemotherapy for at least 12 weeks. METHODS: We retrospectively analysed patients with RAS-mutant mCRC admitted to the Department of Oncology, Huizhou Municipal Central Hospital from December, 2015 to December, 2020. All patients were first treated with bevacizumab combined with FOLFIRI for at least 12 weeks of induction therapy. 154 patients whose disease was brought under control then continued maintenance therapy. 78 patients were in the observation group (bevacizumab plus capecitabine) and 76 patients were in the control group (capecitabine alone). The efficacy and adverse effects of maintenance treatment were compared between the two groups. The clinicopathological characteristics such as sex, age, performance status (PS) score, primary tumour site, degree of pathological differentiation, baseline carcinoembryonic antigen (CEA) level, microsatellite instability (MSI) status, number of metastatic tumour sites and efficacy of induction treatment were compared in terms of prognosis. RESULTS AND DISCUSSION: The median progression-free survival (mPFS)of patients was 9.0 months (95% CI 8.0-10.0) in the observation group and 7.2 months (95% CI 6.0-8.4) in the control group, with a statistically significant difference (p < 0.05). The baseline CEA level was an independent prognostic factor. Both groups tolerated the toxic side effects. WHAT IS NEW AND CONCLUSION: Bevacizumab combined with capecitabine was well tolerated and contributed to a longer PFS time than capecitabine alone, and it is worthy of popularization in clinical practice.

MicroRNA-195-3p inhibits cyclin dependent kinase 1 to induce radiosensitivity in nasopharyngeal carcinoma.

MicroRNAs (miRNAs) are revealed to participate in the progression of multiple malignancies, including nasopharyngeal carcinoma (NPC). This work is intended to decipher the function of microRNA-195-3p (miR-195-3p) in regulating the radiosensitivity of NPC cells and its mechanism. MiR-195-3p and cyclin-dependent kinase 1 (CDK1) expressions were detected in NPC tissues and cells using qRT-PCR and Western blot, respectively. Moreover, radiation-resistant cell lines were induced by continuous irradiation with different doses. Furthermore, the CCK-8 experiment, colony formation assay and flow cytometry were utilized to examine the growth, apoptosis and cell cycle of radioresistant cells. Bioinformatics prediction and dual-luciferase reporter gene assay were applied to prove the targeting relationship between miR-195-3p and CDK1 mRNA 3'UTR. The data showed that miR-195-3p was remarkably down-modulated in NPC tissues and was associated with increased tumor grade, lymph node metastasis and clinical stage of the patients. MiR-195-3p expression was significantly down-modulated in radiation-resistant NPC tissues and NPC cell lines relative to radiation-sensitive NPC tissues and human nasopharyngeal epithelial cells, while CDK1 expression was notably up-modulated. MiR-195-3p overexpression inhibited the growth of NPC cells, decreased radioresistance, promoted apoptosis, and impeded the cell cycle progression. CDK1 was a target gene of miR-195-3p, and CDK1 overexpression counteracted the effects of miR-195-3p on NPC cell growth, apoptosis, cell cycle progression and radiosensitivity. In summary, miR-195-3p improves the radiosensitivity of NPC cells by targeting and regulating CDK1.

The Value of Cervical Node Features in Predicting Long-Term Survival of Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era.

OBJECTIVE: To investigate the prognostic value of cervical node features in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and build a prognostic nomogram to predict the long-term survival. METHODS: In this study, 1752 patients after IMRT from 2008 to 2011 were recruited. The clinical and laboratory characteristics and the nodal features including the nodal number, maximum dimension diameter, extranodal extension (ENE), and cervical node necrosis (CNN) were retrospective analyzed. Univariate Cox and multivariate proportional hazard regression models were used to test the prognostic value of nodal features. Prognostic nomograms were established to predict survival. RESULTS: The 10-year distant metastases-free survival (DMFS) and disease-specific survival (DSS) rates were 86.5% and 80.8%, respectively. Multivariate analysis showed that age, sex, lactate dehydrogenase (LDH), CNN, ENE, T stage, and N stage were independent factors for DSS. Two nomograms-nomogram A (without nodal features) and nomogram B (with nodal features)-were built. The calibration curve for the probability of DSS showed good agreement between prediction by nomogram and the actual observation. The C-index of nomogram B was higher than that for nomogram A in predicting DSS (0.708 vs 0.676, P<0.01). CONCLUSION: The nodal features including ENE and CNN were negative prognostic factors for NPC, and the prognostic nomogram incorporating the nodal features was more accurate in predicting survival than the nomogram without nodal features.

microRNA-124 inhibits stem-like properties and enhances radiosensitivity in nasopharyngeal carcinoma cells via direct repression of expression of JAMA.

Cancer stem cells (CSCs) are a source of tumour recurrence in patients with nasopharyngeal carcinoma (NPC); however, the function of microRNA-124 (miR-124) in NPC CSCs has not been clearly defined. In this study, we investigated the role of miR-124 in NPC CSCs. qRT-PCR was performed to measure miR-124 expression in NPC tissues and cell lines and the effects of miR-124 on stem-like properties and radiosensitivity of NPC cells measured. Luciferase reporter assays and rescue experiments were used to investigate the interaction of miR-124 with the 3'UTR of junctional adhesion molecule A (JAMA). Finally, we examined the effects of miR-124 in an animal model and clinical samples. Down-regulation of miR-124 was detected in cancer tissues and was inversely associated with tumour stage and lymph node metastasis. Overexpression of miR-124 inhibited stemness properties and enhanced radiosensitivity of NPC cells in vitro and in vivo via targeting JAMA. Up-regulation of miR-124 was correlated with superior overall survival of patients with NPC. Our study demonstrates that miR-124 can inhibit stem-like properties and enhance radiosensitivity by directly targeting JAMA in NPC. These findings provide novel insights into the molecular mechanisms underlying therapy failure in NPC.

Development of a Comorbidity-Based Nomogram to Predict Survival After Salvage Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era.

PURPOSE: To assess the impact of comorbidity on treatment outcomes in patients with locally recurrent nasopharyngeal carcinoma (lrNPC) using intensity-modulated radiotherapy (IMRT) and to develop a nomogram that combines prognostic factors to predict clinical outcome and guide individual treatment. METHODS: This was a retrospective analysis of patients with lrNPC who were reirradiated with IMRT between 2003 and 2014. Comorbidity was evaluated by Adult Comorbidity Evaluation-27 grading (ACE-27). The significant prognostic factors (P < 0.05) by multivariate analysis using the Cox regression model were adopted into the nomogram model. Harrell concordance index (C-index) calibration curves were applied to assess this model. RESULTS: Between 2003 and 2014, 469 lrNPC patients treated in our institution were enrolled. Significant comorbidity (moderate or severe grade) was present in 17.1% of patients by ACE-27. Patients with no or mild comorbidity had a 5-year overall survival (OS) rate of 36.2 versus 20.0% among those with comorbidity of moderate or severe grade (P < 0.0001). The chemotherapy used was not significantly different in patients with lrNPC (P > 0.05). For the rT3-4 patients, the 5-year OS rate in the chemotherapy + radiation therapy (RT) group was 30.0 versus 16.7% for RT only (P = 0.005). The rT3-4 patients with no or mild comorbidity were associated with a higher 5-year OS rate in the chemotherapy + RT group than in the RT only group (32.1 and 17.1%, respectively; P=0.003). However, for the rT3-4 patients with a comorbidity (moderate or severe grade), the 5-year OS rate in the chemotherapy + RT group vs. RT alone was not significantly different (15.7 vs. 15.0%, respectively; p > 0.05). Eight independent prognostic factors identified from multivariable analysis were fitted into a nomogram, including comorbidity. The C-index of the nomogram was 0.715. The area under curves (AUCs) for the prediction of 1-, 3-, and 5-year overall survival were 0.770, 0.764, and 0.780, respectively. CONCLUSION: Comorbidity is among eight important prognostic factors for patients undergoing reirradiation. We developed a nomogram for lrNPC patients to predict the probability of death after reirradiation and guide individualized management.

Prognostic model and optimal treatment for patients with stage IVc nasopharyngeal carcinoma at diagnosis.

The treatment for patients with stage IVc nasopharyngeal carcinoma (NPC) at diagnosis was still controversial. In this study, we tried to build a prognostic score model and optimize the treatment for the patients. The prognostic model was based on the primary cohort involving 289 patients from 2002 to 2011 and the validation involving another 156 patients from 2012 to 2015.The prognostic model was built based on the hazard ratios of significant prognostic factors for overall survival (OS). By multivariate analysis, factors associated with poor OS were Karnofsky performance score ≤70, liver metastases, multiple-organ metastases, ≥2 metastatic lesions, lactate dehydrogenase >245 IU/I and poor response to chemotherapy (all P < 0.01). Based on these prognostic factors, patients were divided into the low-risk (0-2 points), intermediate-risk (3-6 points) and high-risk (≥7 points) groups. Five-year OS rates for the low-, intermediate- and high-risk groups were 49.3%, 9.7% and 0.0%, respectively (P < 0.01). Furthermore, loco-regional radiotherapy was associated with significantly better OS in low- and intermediate-risk patients, but not in high-risk patients. These results demonstrated that the prognostic score model based on six negative factors can effectively predict OS in patients with stage IVc NPC at diagnosis. Loco-regional radiotherapy may be beneficial for low- and intermediate-risk patients, but not for high-risk patients.

Clinical characteristics and prognostic value of pre-retreatment plasma epstein-barr virus DNA in locoregional recurrent nasopharyngeal carcinoma.

PURPOSE: To define the clinical characteristics and prognostic value of pre-retreatment plasma Epstein-Barr virus (EBV) DNA, we investigated EBV status in locoregional recurrent nasopharyngeal carcinoma (lrNPC) patients. METHODS: Between April 2008 and August 2016, the data of patients with nonmetastatic lrNPC were retrospectively reviewed. The survival indexes of patients between different pre-retreatment EBV status groups were compared. RESULTS: A total of 401 patients with nonmetastatic lrNPC were enrolled, and 197 (49.1%) patients had detectable pre-retreatment plasma EBV DNA. Treatment included radiotherapy alone (n = 37 patients), surgery alone (n = 105), radiotherapy (n = 208), surgery combined with radiotherapy (n = 20), chemotherapy and targeted therapy (n = 31). Median follow-up was 32 months. The 3-year locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates for the entire cohort were 64.8%, 89.4%, and 58.8%, respectively. The estimated 3-year LRRFS, DMFS, and OS rates for the pre EBV-positive group vs the pre EBV-negative group were 54.2% vs 75.0% (P < 0.001), 86.6% vs 91.9% (P = 0.05), 51.6% vs 65.9% (P = 0.01), respectively. Among patients in the clinical stage rI/II, there were 17 patients in the radiotherapy alone group and 49 patients in the surgery alone group. And there was no significant difference in overall survival between radiotherapy and surgery, even among the different pre-EBV statuses (P > 0.05). In terms of long-term toxic and side effects, the incidence of radioactive temporal lobe injury in the radiotherapy group was higher than that in the surgery group (35.3% vs 8.2%, P < 0.001), and no statistically significant difference was found in other long-term toxic and side effects. CONCLUSIONS: The positive rate of pre-retreatment plasma EBV DNA in lrNPC is lower than primary NPC. The prognosis of EBV DNA negative group is better than positive group. For locally early-stage lrNPC, regardless of EBV DNA status, radiotherapy and surgery are available options and both can achieve better long-term survival.

Long-term outcome and pattern of failure for patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

PURPOSE: To analyze the long-term outcome and pattern of failure for patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Patients with NPC after IMRT from 2001 to 2008 were recruited (n = 865). Clinical features, laboratory data, and treatments were collected. RESULTS: The 10-year local recurrence-free survival, distant metastasis-free survival, and disease-specific survival (DSS) were 92.0%, 83.4%, and 78.6%, respectively. A total of 209 patients died: 59% of whom died from distant metastasis. The 10-year DSS was higher in patients who received chemoradiotherapy than those who received IMRT alone for patients with high-risk stage III disease, while there was no survival difference for patients with stage II and low-risk stage III disease. CONCLUSIONS: IMRT provides satisfactory long-term survival for patients with NPC. Distant metastasis has been the most common reason for failure. Adding chemotherapy did not improve survival in patients with stage II and low-risk stage III disease.

Efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for patients with head and neck squamous cell carcinoma: a systematic review and meta-analysis of randomized controlled trials.

Agents targeting epidermal growth factor receptor (EGFR) are used to treat head and neck squamous cell carcinoma (HNSCC); however, their efficacy and safety is poorly understood. Here we evaluated the efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for HNSCC. Randomized controlled trials that evaluated addition of EGFR targeted therapy versus standard therapy alone were included. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate (ORR), locoregional control, and severe adverse events (SAEs, grade ≥ 3). Sixteen eligible trials with 4031 patients were included. Addition of anti-EGFR regimens to standard therapy significantly improved OS of patients with HNSCC (HR = 0.89; 95% CI, 0.82-0.96), with a moderately elevated rate of SAEs (RR = 1.08; 95% CI, 1.03-1.13). Subgroup analysis indicated that the survival benefit was observed when cetuximab was administered concurrently with radiotherapy (RT) for stage III/IV patients (HR = 0.76; 95% CI, 0.61-0.94; p = 0.01), or with chemotherapy for recurrent or metastatic (R/M) HNSCC (HR = 0.86; 95% CI, 0.78-0.95; p = 0.005). Significantly increased ORR (RR = 1.51; 95% CI 1.05-2.18) and PFS (HR = 0.72; 95% CI, 0.59-0.88) were found in R/M HNSCC patients treated with anti-EGFR plus chemotherapy, while no significant improvements were found in stage III/IV patients treated with anti-EGFR plus standard therapy. In conclusion, addition of cetuximab to standard therapy may improve outcomes for R/M HNSCC patients, while causing a moderate increase in SAEs. For stage III/IV patients, anti-EGFR mAb plus RT can improve OS compared with RT alone, while replacement of chemotherapy with EGFR mAb or adding EGFR mAb to combined chemotherapy and RT did not improve outcomes.

The long non-coding RNA SNHG3 functions as a competing endogenous RNA to promote malignant development of colorectal cancer.

Accumulating evidence has revealed that aberrantly expressed long non-coding transcripts are involved in the development and progression of colorectal cancer (CRC). Small nucleolar RNA host gene 3 (SNHG3) is a newly identified lncRNA, and little is known about its clinical significance and biological functions in the development of CRC. In the present study, we found that the expression of SNHG3 was significantly upregulated in CRC, and upregulation of SNHG3 predicted poor prognosis for patients with CRC as determined through analysis of the data obtained from TCGA database. Gain-of function and loss-of function assays revealed that SNHG3 markedly promoted cellular proliferation of CRC cells. Gene Set Enrichment Analysis (GSEA) suggested that high expression of SNHG3 was positively associated with c-Myc and its targets genes. Furthermore, ectopic overexpression of SNHG3 increased the expression of c-Myc and its target genes, whereas inhibition of SNHG3 had opposite effect on the expression of c-Myc and its targets. Mechanistic investigations demonstrated that SNHG3 functioned as a competing endogenous RNA (ceRNA) to 'sponge' miR-182-5p, thus leading to the release of c-Myc from miR-182-5p and modulating the expression of c-Myc. In conclusion, SNHG3 promoted CRC progression via sponging miR-182-5p and upregulating c-Myc and its target genes.

The challenge in treating locally recurrent T3-4 nasopharyngeal carcinoma: the survival benefit and severe late toxicities of re-irradiation with intensity-modulated radiotherapy.

BACKGROUND: Effective treatments for patients with advanced locally recurrent nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine the potential benefits from re-irradiation by intensity-modulated radiotherapy (IMRT) on survival and the effects of severe late toxicities. METHODS: A retrospective study was conducted in 245 patients diagnosed with locally recurrent T3-T4 NPC who had undergone re-irradiation with IMRT. Follow-up data was colletedand factors associated with survival and severe late toxicities were analyzed. RESULTS: The 5-year local-regional failure-free survival, distant failure-free survival and overall survival rates were 60.9%, 78.3% and 27.5%, respectively. The presence of severe late complications, recurrent T4 disease and gross tumor volume >30 cm3 were associated with poor survival. The incidences of mucosal necrosis, temporal lobe necrosis, cranial neuropathy and trismus were 22.0%, 14.6%, 27.0% and 14.6% respectively. CONCLUSIONS: Re-irradiation with IMRT is an effective choice in patients with locally recurrent T3-T4 NPC. However, the survival benefits can be partly offset by severe late complications and optimum treatments in these patients remain a challenge.

miR156a Mimic Represses the Epithelial-Mesenchymal Transition of Human Nasopharyngeal Cancer Cells by Targeting Junctional Adhesion Molecule A.

MicroRNAs (miRNAs) have been documented as having an important role in the development of cancer. Broccoli is very popular in large groups of the population and has anticancer properties. Junctional adhesion molecule A (JAMA) is preferentially concentrated at tight junctions and influences cell morphology and migration. Epithelial-mesenchymal transition (EMT) is a developmental program associated with cancer progression and metastasis. In this study we aimed to investigate the role of miRNAs from broccoli in human nasopharyngeal cancer (NPC). We demonstrated that a total of 84 conserved miRNAs and 184 putative novel miRNAs were found in broccoli by sequencing technology. Among these, miR156a was expressed the most. In addition, synthetic miR156a mimic inhibited the EMT of NPC cells in vitro. Furthermore, it was confirmed that JAMA was the target of miR156a mimic as validated by 3' UTR luciferase reporter assays and western blotting. Knockdown of JAMA was consistent with the effects of miR156a mimic on the EMT of NPC, and the up-regulation of JAMA could partially restore EMT repressed by miR156a mimic. In conclusion, these results indicate that the miR156a mimic inhibits the EMT of NPC cells by targeting the 3' UTR of JAMA. These miRNA profiles of broccoli provide a fundamental basis for further research. Moreover, the discovery of miR156a may have clinical implications for the treatment of patients with NPC.

Oligometastases in AJCC stage IVc nasopharyngeal carcinoma: A subset with better overall survival.

BACKGROUND: The purpose of this study was to analyze the patterns of metastasis and therapeutic approaches in American Joint Committee on Cancer (AJCC) stage IVc nasopharyngeal carcinoma (NPC). METHODS: A retrospective analysis of 263 patients with stage IVc NPC revealed the incidence of bone, liver, and lung metastases was 67.7%, 32.3%, and 16.0%, respectively. All patients received chemotherapy; 160 patients received radiotherapy (RT) to the primary tumor. RESULTS: The factors associated with poor overall survival (OS) were Karnofsky Performance Scale (KPS) ≤70, liver metastasis, multiple-organ metastasis, ≥6 lesions, no RT to the primary tumor, and <4 chemotherapy cycles. Two subgroups of M1 disease were divided into: M1a (oligometastases) = single-organ metastases or 1 to 5 lesions; and M1b = multiple-organ metastases or ≥6 lesions. The 5-year OS rates for M1a and M1b were 38.7% versus 7.0%, respectively. CONCLUSION: Patients with oligometastases have significantly better OS than patients with widespread metastases. Long-term disease-free survival can be achieved in selected patients with oligometastases after systemic chemotherapy and definitive RT. © 2016 Wiley Periodicals, Inc. Head Neck 38:1152-1157, 2016.

Long-term survival and late complications in intensity-modulated radiotherapy of locally recurrent T1 to T2 nasopharyngeal carcinoma.

BACKGROUND: We investigated the feasibility of reirradiation with intensity-modulated radiotherapy (IMRT) for recurrent T1 to T2 nasopharyngeal carcinoma (NPC) by assessing long-term survival and late complication rates. METHODS: Sixty patients who had been previously irradiated were diagnosed with locally recurrent T1 to T2 NPC and underwent reirradiation with IMRT. Severe radiation toxicities were assessed. RESULTS: The median follow-up time was 40.0 months. The 5-year local failure-free survival (LFFS), distant failure-free survival (DFFS), and overall survival (OS) rates were 85.7%, 96.1%, and 67.2%, respectively. Independent prognostic factors included primary gross tumor volume >20 cm and the presence of significant complications. The most common severe complications were headache (31.6%), mucosal necrosis (30.0%), cranial neuropathy (25.0%), and temporal lobe necrosis (21.6%). Thirty-nine patients (65.0%) developed at least one severe complication and 18 patients died as a result. CONCLUSION: Excellent disease control can be achieved by reirradiation with IMRT for recurrent T1 to T2 NPC. However, the main challenge remains severe late complications.

Impact of primary tumor volume and location on the prognosis of patients with locally recurrent nasopharyngeal carcinoma.

INTRODUCTION: The properties of a tumor itself were considered the main factors determining the survival of patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). However, recurrent tumors were mainly evaluated by using the American Joint Committee on Cancer staging system, which was modeled on primary tumors and did not incorporate the tumor volume. This study aimed to investigate the prognostic values of the primary tumor location and tumor volume, and to determine whether evaluating these parameters could improve the current staging system. METHODS: Magnetic resonance (MR) images for 229 patients with locally recurrent NPC who underwent IMRT were analyzed retrospectively. RESULTS: The skull base, parapharyngeal space, and intracranial cavity were the most common sites of tumors. There was a difference in the survival between patients with T1 and T2 diseases (77.6% vs. 50.0%, P<0.01) and those with T3 and T4 diseases (33.0% vs. 18.0%, P=0.04) but no difference between patients with T2 and T3 diseases (50.0% vs. 33.0%, P=0.18). Patients with a tumor volume≤38 cm3 had a significantly higher survival rate compared with those with a tumor volume>38 cm3 (48.7% vs. 15.2%, P<0.01). CONCLUSIONS: A new staging system has been proposed, with T3 tumors being down-staged to T2 and with the tumor volume being incorporated into the staging, which may lead to an improved evaluation of these tumors. This new system can be used to guide the treatment strategy for different risk groups of recurrent NPC.

Radioactive (125)I seeds inhibit cell growth and epithelial-mesenchymal transition in human glioblastoma multiforme via a ROS-mediated signaling pathway.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary central nervous system neoplasm in adults. Radioactive (125)I seed implantation has been widely applied in the treatment of cancers. Moreover, previous clinical trials have confirmed that (125)I seeds treatment was an effective therapy in GBM. We sought to investigate the effect of (125)I seed on GBM cell growth and Epithelial-mesenchymal transition (EMT). METHODS: Cells were exposed to irradiation at different doses. Colony-formation assay, EdU assay, cell cycle analysis, and TUNEL assay were preformed to investigate the radiation sensitivity. The effects of (125)I seeds irradiation on EMT were measured by transwell, Boyden and wound-healing assays. The levels of reactive oxygen species (ROS) were measured by DCF-DA assay. Moreover, the radiation sensitivity and EMT were investigated with or without pretreatment with glutathione. Additionally, nude mice with tumors were measured after treated with radiation. RESULTS: Radioactive (125)I seeds are more effective than X-ray irradiation in inhibiting GBM cell growth. Moreover, EMT was effectively inhibited by (125)I seed irradiation. A mechanism study indicated that GBM cell growth and EMT inhibition were induced by (125)I seeds with the involvement of a ROS-mediated signaling pathway. CONCLUSIONS: Radioactive (125)I seeds exhibit novel anticancer activity via a ROS-mediated signaling pathway. These findings have clinical implications for the treatment of patients with GBM by (125)I seeds.