Zhong-Guo Liang

Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy with or without adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: meta-analysis of 1,096 patients from 11 randomized controlled trials.

PURPOSE To evaluate the efficacy and toxicity of induction chemotherapy followed by concurrent chemoradiotherapy (the treatment group) versus concurrent chemoradiotherapy with or without adjuvant chemotherapy (the control group) for locoregionally advanced nasopharyngeal carcinoma. METHODS The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. All randomized controlled trials were included for a meta-analysis performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. RESULTS Eleven studies were included. Risk ratios of 0.99 (95%CI 0.72-1.36), 0.37 (95%CI 0.20-0.69), 1.08 (95%CI 0.84-1.38), 0.98 (95%CI 0.75-1.27) were observed for 3 years overall survival, 3 years progression-free survival, 2 years loco-regional failure-free survival and 2 years distant metastasis failure-free survival. There were no treatment-related deaths in either group in the 11 studies. Risk ratios of 1.90 (95%CI 1.24-2.92), 2.67 (95%CI 0.64-11.1), 1.04 (95%CI 0.79-1.37), 0.98 (95%CI 0.27-3.52) were found for grade 3-4 leukopenia, grade 3-4 thrombocytopenia, grade 3-4 mucous membrane, and grade 3-4 hepatic hematologic and gastrointestinal toxicity, the most significant toxicities for patients. CONCLUSION Compared with the control group, induction chemotherapy followed by concurrent chemoradiotherapy was well tolerated but could not significantly improve prognosis in terms of overall survival, loco-regional failure-free survival or distant metastasis failure-free survival.

PARP-1 promotes autophagy via the AMPK/mTOR pathway in CNE-2 human nasopharyngeal carcinoma cells following ionizing radiation, while inhibition of autophagy contributes to the radiation sensitization of CNE-2 cells

It was previously reported that poly-(adenosine diphosphate-ribose) polymerase-1 (PARP-1) regulated ionizing radiation (IR)-induced autophagy in CNE-2 human nasopharyngeal carcinoma cells. The present study aimed to investigate whether PARP-1-mediated IR-induced autophagy occurred via activation of the liver kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in CNE-2 cells. In addition, the effect of PARP-1 and AMPK inhibition on the radiation sensitization of CNE-2 cells was investigated. CNE-2 cells were treated with 10 Gy IR in the presence or absence of the AMPK activator 5-amino-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamide (AICAR). In addition, IR-treated CNE-2 cells were transfected with lentivirus-delivered small-hairpin RNA or treated with the AMPK inhibitor Compound C. Western blot analysis was used to assess the protein expression of PARP-1, phosphorylated (p)-AMPK, microtubule-associated protein 1 light chain 3 (LC3)-II and p-P70S6K. Cell viability and clone formation assays were performed to determine the effect of PARP-1 silencing and AMPK inhibition on the radiation sensitization of CNE-2 cells. The results showed that IR promoted PARP-1, p-AMPK and LC3-II protein expression as well as decreased p-P70S6K expression compared with that of the untreated cells. In addition, AICAR increased the expression of p-AMPK and LC3-II as well as decreased p-P70S6K expression compared with that of the IR-only group; however, AICAR did not increase PARP-1 expression. Furthermore, PARP-1 gene silencing decreased the expression of PARP-1, p-AMPK and LC3-II as well as increased p-P70S6K expression. Compound C decreased p-AMPK and LC3-II expression as well as increased p-P70S6K expression; however, Compound C did not increase PARP-1 expression. Western blot analysis detected limited expression of p-LKB1 in all treatment groups. Cell viability and clone formation assays revealed that PARP-1 or AMPK inhibition reduced the proliferation of CNE-2 cells following IR. In conclusion, the present study demonstrated that PARP-1 promoted autophagy via the AMPK/mTOR pathway; in addition, PARP-1 or AMPK inhibition contributed to the radiation sensitization of CNE-2 cells following IR. However, it remains to be elucidated whether PARP-1 is an upstream mediator of the LKB1 pathway in CNE-2 cells following IR.

Comparison of Concurrent Chemoradiotherapy Followed by Adjuvant Chemotherapy Versus Concurrent Chemoradiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma: a Meta-analysis of 793 Patients from 5 Randomized Controlled Trials

PURPOSE The main objective of the present study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone in the treatment of locoregionally advanced nasopharyngeal carcinoma. METHODS The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. Randomized controlled trials (RCTs) that compared concurrent chemoradiotherapy followed by adjuvant chemotherapy with concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma were included. Meta-analysis was performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. RESULTS Five studies were included. Risk ratios of 1.02 (95%CI 0.89-1.15), 0.93 (95%CI 0.72-1.21), 1.07 (95%CI 0.87-1.32), 0.95 (95%CI 0.80-1.13) were observed for 3 years overall survival, 5 years failure-free survival, 5 years loco- regional failure-free survival and 5 years distant metastasis failure-free survival. There were no treatment-related deaths in both groups of five studies. Hematologic and gastrointestinal toxicity were the most significant for patients during adjuvant chemotherapy. The level of evidence was low. CONCLUSION Compared with concurrent chemoradiotherapy alone, concurrent chemotherapy followed by adjuvant chemotherapy did not improve prognosis. More toxicity was found during adjuvant chemotherapy.

Short-term versus long-term hormone therapy plus radiotherapy or prostatectomy for prostate cancer: a systematic review and meta-analysis

PurposeTo compare the efficacy and safety of short-term versus long-term hormonotherapy (HT) plus radiotherapy (RT) or prostatectomy (RP) for prostate cancer.MethodsLiteratures were searched from Embase, PubMed, Web of science and Cochrane Library up to October, 2012. Quality of the study was evaluated according to the Cochrane’s risk of bias of randomized controlled trial (RCT); the Grading of Recommendations Assessment, Development and Evaluation System was used to rate the level of evidence. RevMan 5.1 was used for statistical analysis. Two comparisons were of interest: RT plus short-term HT versus RT plus long-term HT and RP plus short-term HT versus RP plus long-term HT. Pooled risk ratio or standardized mean differences were calculated; HT adverse reactions were descriptively evaluated.ResultsNine RCTs (total 4,743 patients) were included, 7 RCTs compared RT plus short-term HT with RT plus long-term HT, 2 RCTs compared RP plus short-term HT with RP plus long-term HT. Meta-analysis showed there was no significant difference in overall survival, disease-free survival and PSA level before RP; long-term was superior to short-term hormonotherapy in biochemical failure rate, clinical progression rate, prostate cancer-specific mortality, positive surgical margin rate and prostate volume before RP. Systematic review demonstrated adverse events caused by the increased length of HT were more common.ConclusionsLong-term HT plus RT showed a trend toward improved overall survival; long-term HT plus RP declined positive surgical margin rate and prostate volume before RP. So, long-term HT may benefit more, but it did not significantly improve the patients’ overall survival, and the adverse reactions are inevitable.

A Review: Proteomics in Nasopharyngeal Carcinoma

Although radiotherapy is generally effective in the treatment of major nasopharyngeal carcinoma (NPC), this treatment still makes approximately 20% of patients radioresistant. Therefore, the identification of blood or biopsy biomarkers that can predict the treatment response to radioresistance and that can diagnosis early stages of NPC would be highly useful to improve this situation. Proteomics is widely used in NPC for searching biomarkers and comparing differentially expressed proteins. In this review, an overview of proteomics with different samples related to NPC and common proteomics methods was made. In conclusion, identical proteins are sorted as follows: Keratin is ranked the highest followed by such proteins as annexin, heat shock protein, 14-3-3σ, nm-23 protein, cathepsin, heterogeneous nuclear ribonucleoproteins, enolase, triosephosphate isomerase, stathmin, prohibitin, and vimentin. This ranking indicates that these proteins may be NPC-related proteins and have potential value for further studies.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone for the treatment of locally advanced nasopharyngeal carcinoma: a retrospective controlled study

OBJECTIVE We evaluated the survival benefit of providing concurrent chemoradiotherapy (ccrt) plus adjuvant chemotherapy compared with ccrt alone to patients with locally advanced nasopharyngeal carcinoma. METHODS This retrospective study included 130 patients with nasopharyngeal carcinoma treated with ccrt plus adjuvant chemotherapy from June 2005 to December 2010. Another 130 patients treated with ccrt alone during the same period were matched on age, sex, World Health Organization histology, T stage, N stage, and technology used for radiotherapy. The endpoints included overall survival, locoregional failure-free survival, distant metastasis failure-free survival, and failure-free survival. RESULTS At a mean follow-up of 42.1 months (range: 8-85 months), the observed hazard ratios for the group receiving ccrt plus adjuvant chemotherapy compared with the group receiving ccrt alone were: for overall survival, 0.77 [95% confidence interval (ci): 0.37 to 1.57]; for locoregional failure-free survival, 1.00 (95% ci: 0.37 to 2.71); for distant metastasis failure-free survival, 1.15 (95% ci: 0.56 to 2.37); and for failure-free survival, 1.26 (95% ci: 0.69 to 2.28). There were no significant differences in survival between the groups. After stratification by disease stage, ccrt plus adjuvant chemotherapy provided a borderline significant benefit for patients with N2-3 disease (hazard ratio: 0.35; 95% ci: 0.11 to 1.06; p = 0.052). Multivariate analyses indicated that only tumour stage was a prognostic factor for overall survival. CONCLUSIONS Patients with locally advanced nasopharyngeal carcinoma received no significant survival benefit from the addition of adjuvant chemotherapy to ccrt. However, patients with N2-3 disease might benefit from the addition of adjuvant chemotherapy to ccrt.

Advances and Challenges in Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma is an endemic disease within specific regions in the world. Radiotherapy is the main treatment. In recent decades, intensity-modulated radiation therapy has undergone a rapid evolution. Compared with two-dimensional radiotherapy and/or three-dimensional conformal radiotherapy, evidence has shown it may improve quality of life and prognosis for patients with nasopharyngeal carcinoma. In addition, helical tomotherapy is an emerging technology of intensity-modulated radiation therapy. Its superiority in dosimetric and clinical outcomes has been demonstrated when compared to traditional intensity-modulated radiation therapy. However, many challenges need to be overcome for intensity-modulated radiation therapy of nasopharyngeal carcinoma in the future. Issues such as the status of concurrent chemotherapy, updating of target delineation, the role of replanning during IMRT, the causes of the main local failure pattern require settlement. The present study reviews traditional intensity-modulated radiation therapy, helical tomotherapy, and new challenges in the management of nasopharyngeal carcinoma.

Comparison of the efficacy between concurrent chemoradiotherapy with or without adjuvant chemotherapy and intensity-modulated radiotherapy alone for stage II nasopharyngeal carcinoma

Objective This study aimed to explore whether concurrent chemoradiotherapy (CCRT) with or without Adjuvant Chemotherapy (AC) could improved the survival in stage II nasopharyngeal carcinoma (NPC). Methods Patients with stage II NPC treated with CCRT (n=80) or CCRT+AC (n=40) or IMRT alone (n=42) between January 2007 and September 2014 were retrospectively analyzed. The three patient groups were matched based on prognostic factors. All patients were treated with IMRT. The endpoints were overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRRFS), and failure-free survival (FFS). The treatment-related acute toxicity reactions between the three groups were compared also. Results The three groups indicated similar outcomes: survival of the CCRT group, CCRT+AC group and RT alone group were (93.9%, 95.0%, 95.2%, P=0.937) for OS, (96.8%, 94.9%, 93.0%, P=0.756) for LRRFS, (91.1%, 97.5%, 100%, P=0.185) for DMFS and (84.9%, 92.5%, 93.0%, P=0.597) for FFS. Both the univariate and multivariate analysis indicated that older age predicted lower LRRFS and FFS. The CCRT and CCRT+AC groups showed more acute toxicity reactions, especially in bone marrow suppression, Liver dysfunction, gastrointestinal reactions (nausea/vomiting) and weight loss. Conclusion CCRT with/without AC could not improve the survival conditions of patients with stage II NPC, but remarkably increased treatment-associated acute toxic reactions when compared with IMRT alone.

IMRT combined with concurrent chemotherapy plus adjuvant chemotherapy versus IMRT combined with concurrent chemotherapy alone in patients with nasopharyngeal carcinoma

Purpose To evaluate the efficacy of IMRT combined with concurrent chemotherapy followed by adjuvant chemotherapy compared with IMRT combined with concurrent chemotherapy alone in patients with nasopharyngeal carcinoma. Methods From January 2007 to December 2014, we collected 797 staged II-IVb [UICC = Union for International Cancer Control criteria (7th edition)] NPC patients for analysis. After 1:1 matching,we selected 261 cases as the CCRT group, another 261 patients as the CCRT+AC group. Using Kaplan-Meier to calculate the overall survival (OS), locoregional failure-free survival(LFFS), distant metastasis failure-free survival(DMFS). The log-rank test and Cox-proportional hazards model to evaluate the prognostic factors. Results After matching, there were 261 patients in each group. In CCRT+AC group, The 1-,2- and 3- year os rates were a little higher than in CCRT group(99.6% vs 97.9%,97.4% vs 96.2%,93.8% vs 86.9%, P = 0.150). There were no significant difference in 1-,2-,3- year OS, LFFS, DMFS between the two groups. In subgroup analysis, a little higher OS rate in CCRT+AC group for staged III, IV and T4(III:100% vs 100%, 97.6% vs 95.8%, 94.0% vs 84.0%; IV: 99.1% vs 95.4%, 96.3% vs 95.4%, 90.5% vs 79.4%, P = 0.047;T4:99.1% vs 95.2%, 97.1% vs 95.2%, 90.9% vs 78.2%, P = 0.055). No significant difference were observed in OS, LFFS,DMFS between the groups. Conclusion IMRT combined with concurrent chemotherapy followed by adjuvant chemotherapy might improved 1-,2-,3- year of OS. Whether or not add adjuvant chemotherapy it had similar LFFS rate and DMFS rate in patients with nasopharyngeal carcinoma. Locally advanced NPC patients (III, IV and T4)might benefit from the adjuvant chemotherapy.

Comparison of Short-Course Radiotherapy Versus Long-Course Radiotherapy for Treatment of Metastatic Spinal Cord Compression: A Systematic Review and Meta-Analysis.

AbstractIn this study, we evaluate the efficacy of short-course radiotherapy (SCRT) versus long-course radiotherapy (LCRT) in the treatment of metastatic spinal cord compression (MSCC).PubMed, EMBASE, and Web of Science were searched up to April 2015. Relevant data were extracted based on inclusion and exclusion criteria. Methodological quality of randomized controlled trial (RCT) was evaluated using modified Jadad scale; non-RCT was evaluated using Newcastle-Ottawa Scale. Meta-analysis was performed using RevMan 5.3 software.Fourteen studies with 2239 patients were included. Results of meta-analysis showed that there were no significant differences between SCRT and long-course radiotherapy LCRT in 6-month overall survival rate (risk ratio [RR] = 0.97, 95% confidence interval [CI] 0.88, 1.07, P = 0.55), 1-year overall survival rate (RR = 0.94, 95% CI 0.85, 1.04, P = 0.22), motor function improvement (RR = 0.96, 95% CI 0.81, 1.13, P = 0.63), no change on motor function (RR = 0.98, 95% CI (0.88, 1.09), P = 0.74], and deterioration on motor function (RR = 0.96, 95% CI 0.71, 1.31, P = 0.78). Compared with SCRT, LCRT significantly increased 6-month local control rate (RR = 0.87, 95% CI 0.80, 0.95, P = 0.002), 1-year local control rate (RR = 0.83, 95% CI 0.71, 0.97, P = 0.02), and 2-year local control rate (RR = 0.83, 95% CI 0.79, 0.87, P < 0.00001).Both LCRT and SCRT provided similar survival rates and functional outcome, but LCRT showed better local control rates than SCRT. However, considering low cost and good patients compliance, SCRT may be a better choice.