Min Kang

Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-κB-Related Mechanism

Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis because of the lack of an effective treatment. Here we explored the efficiency and the molecular mechanisms of combined treatment with triptolide and ionizing radiation for treating NPC. Human nasopharyngeal carcinoma (CNE) cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation in vitro. Tumor potency was examined in an in vivo CNE cell xenograft mouse model, which was treated as above. Our results demonstrated that triptolide caused a significant reduction in cell growth and colony number, and induced a marked apoptosis that was further enhanced with increasing doses of ionizing radiation. Combination treatment synergistically reduced tumor weight and volume without obvious toxicity. Western blot analysis in vitro and in vivo showed that triptolide induced apoptotic protein Bax expression and inhibited phosph-NF-κB p65, Bcl-2 and VEGF proteins without affecting other NF-κB related protein expression. In conclusion, our findings revealed that triptolide plus ionizing radiation had synergistic anti-tumor and anti-angiogenesis effects in NPC via down-regulating NF-κB p65 phosphorylation. The combination therapy may provide novel mechanism insights into inhibit NPC.

A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results of a prospective multicentric clinical study

Purpose To establish a new clinical staging standard for nasopharyngeal carcinoma (NPC), based on intensity-modulated radiotherapy (IMRT), through a prospective multicenter clinical trial. Experiment Design 492 NPC patients were selected from six hospitals in the Guangxi Zhuang Autonomous Region, China from January 2006 to December 2009. Kaplan-Meier method was adopted to calculate survival rates. Log-rank test was used to compare survival differences. Results According to the seventh edition of the UICC/AJCC staging system, the differences between T1, T2 and T3 are not statistically significant, suggesting that T1, T2 and T3 could be combined as new T1. There were significant differences between all N stages except those of N3a and N3b, suggesting that N3a and N3b could be combined as new N3. Additionally, the overall survival (OS) curves of stages I, II, III and IVa were not significantly different. Therefore, we propose a new clinical NPC staging standard based on magnetic resonance imaging (MRI) and IMRT as T stage (including T1 and T2), N stage (including N0, N1, N2 and N3) and clinical staging includes I (T1N0M0), II (T1N1-2M0, T2N0M0), III (T2N1-2M0), IVa (TxN3M0) and IVb (TxNxM1). Recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences in the 5-year curves of local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and OS were all statistically more significant than the seventh edition of the UICC/AJCC staging system. Conclusions Proposed staging system is more adaptable to IMRT and predicts the prognosis of NPC patients more accurately.

Long-term Efficacy of Microwave Hyperthermia Combined with Chemoradiotherapy in Treatment of Nasopharyngeal Carcinoma with Cervical Lymph Node Metastases

OBJECTIVE The long-term efficacy of microwave hyperthermia combined with chemoradiotherapy in treating nasopharyngeal carcinoma (NPC) with metastatic foci in cervical lymph nodes was evaluated. METHODS A total of 154 cases of N2 or N3 stage NPC were randomized into two groups: hyperthermia group (76 cases) and control group (78 cases). Both received cisplatin chemotherapy and radiotherapy. In addition, the hyperthermia group further received microwave hyperthermia to the metastatic cervical nodes with different patterns (before or after radiotherapy), heating temperatures (T90 < 43° and T90 ≥ 43°) and hyperthermia episodes (< 4 times, 4-10 times and > 10 times). RESULTS The 3-month and 5-year complete response (CR) rates of cervical lymph nodes in the hyperthermia group were significantly higher than those in the control group. The 5-year disease-free survival (DFS) rate and the 3-year / 5-year overall survival rate in the hyperthermia group were also significantly higher. There was no significant difference in 5-year metastatic rates. In the hyperthermia group, the 3-month and 5-year CR rates of T90 < 43° treatment were significantly lower than with T90 ≥ 43° treatment. The CR rate was highest when the hyperthermia was performed 4-10 times. There were no significant differences in 3-month and 5-year CR rates between hyperthermia before or after radiotherapy treatment. CONCLUSION Microwave hyperthermia combined with chemoradiotherapy can increase local control, DFS and 3, 5-year overall survival rates of patients with N2 ~ N3 stage NPC. The heating temperature should be over 43° with hyperthermia repeated 4-10 times.

A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy (IMRT)

Objective This study is to establish a new staging system for nasopharyngeal carcinoma (NPC) based on the magnetic resonance imaging (MRI) and intensity-modulated radiation therapy (IMRT). Methods Totally 492 patients with nasopharyngeal carcinoma were included in this study. These patients were diagnosed by pathological detection (without distant metastasis) and underwent the initial treatment of IMRT. These patients were subjected to the staging with the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system. Survival rates were calculated by the Kaplan-Meier method. Log-rank test was used to calculate the single factor prognosis, and the COX risk model was used to analyze the multivariate prognosis. Results In these 492 patients, according to our recommended new T and N staging criteria, there were 290 cases of T1 and 202 cases of T2; there were 64 cases of N0, 159 cases of N1, 226 cases of N2, and 43 cases of N3. Univariate and multivariate analyses showed that the T and N staging combination parameters were independent prognostic factors, which affected the overall survival rates and tumor-free survival rates. According to risk difference and survival curve distribution, the following new clinical staging criteria were established: stage I (T1N0M0), stage II (T1N1M0 and T2N0M0), stage III (T1N2M0 and T2N1-2M0), stage IVa (T1-2N3M0), and stage IVb (TxNxM1). Conclusion A new staging system for NPC based on MRI and IMRT has been recommended, which provides valuable evidence for disease treatment and prognosis prediction.

Validation of the 8th edition of the UICC/AJCC staging system for nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

An accurate TNM staging system is crucial for treatment guidance and prognosis prediction in nasopharyngeal carcinoma (NPC) patients. In this retrospective study, we evaluated the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for NPC treated with intensity-modulated radiotherapy (IMRT). A total of 608 patients with biopsy-proven, non-metastatic NPC, treated with IMRT between January 2008 and March 2010, were enrolled. The 5-year overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 81.5%, 80.1%, 86.0%, and 81.1%, respectively. The LRFS rates of patients with stages T1 vs. T2, T2 vs. T3, and T1 vs. T3 did not differ between the 7th and 8th editions. By contrast, the DMFS rates of patients with N0 vs. N1, N1 vs. N2, and N2 vs. N3 differed between the 8th and the 7th editions, though no difference was observed between N3a and N3b, according to the 7th edition. The difference in OS between stages II and III, and between stages III and IVa, was larger according to the 8th edition than the 7th edition. There was no difference in the OS between stages I and II. These data indicate that in the IMRT era, the 8th edition staging system can predict the prognosis of NPC patients more accurately than the 7th edition.

A novel N staging system for NPC based on IMRT and RTOG guidelines for lymph node levels: Results of a prospective multicentric clinical study

The present study aimed to investigate the cervical lymph node metastasis of nasopharyngeal carcinoma (NPC) and to establish a novel N staging standard for NPC, based on intensity modulated radiation therapy (IMRT) via a prospective multicenter clinical trial. Between January 2006 and December 2009, a total of 492 patients with NPC without distant metastasis were included in the present study. All patients were treated with IMRT. According to Radiation Therapy Oncology Group division standards, the present study proposed a novel N staging system following the review of magnetic resonance images in comparison with the 7th edition of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system. Retropharyngeal lymph nodes, cervical lymph node level and cervical lymph node laterality were independent prognostic factors used in multivariate analyses. According to the results of the risk variety, the present study suggested that the novel N staging system included: N0 (no lymph node metastasis), N1 [retropharyngeal or/and unilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis], N2 [bilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis] and N3 (lymph node metastasis in IVa and Vb regions and their lower regions). The novel N staging system proposed in the present study performs better in risk difference and distribution balance. Furthermore, the differences of 5-year curves of distant metastasis-free survival and overall survival had greater statistically significant differences compared with the 7th edition of the UICC/AJCC staging system. The present study suggested a novel N staging system for cervical lymph node metastasis of NPC, which may predict the prognosis of patients with NPC in a more objective and accurate way.

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

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

Combined Ki67 and ERCC1 for prognosis in non-keratinizing nasopharyngeal carcinoma underwent chemoradiotherapy

This study aimed to assess the predictive value of combined Ki67 and ERCC1 in distant metastasis-free nasopharyngeal carcinoma. 334 such cases were retrospectively assessed. Immunohistochemistry was used to evaluate Ki67 and ERCC1 protein levels in tumor tissues. Associations of Ki67 and ERCC1 amounts with clinical characteristics and survival were analyzed. Medium follow-up was 48.7 months; overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) were 91.3%, 76.0%, 82.0%, and 91.9%, respectively. High Ki67 expression was found in 35.6% patients, and positively correlated with clinical- and N- staging (P = 0.005, P < 0.001); 4-year OS, DFS, and DMFS were significantly lower in the high Ki67 group than patients with low-medium expression (P = 0.001, P = 0.012, P = 0.007). High ERCC1 expression was found in 35.3% of patients, and positively correlated with clinical- and T- staging. Compared with low ERCC1 expression cases, 4-year OS, DFS, DMFS, and LRFS were decreased significantly in those with high levels. High Ki67 and ERCC1 levels were related to adverse prognoses of OS (HR=4.977, 95% CI 2.31–12.292, P<0.001), DFS (HR = 4.178, 95% CI 2.421–7.212, P < 0.001), DMFS (HR = 3.722, 95% CI 2.028–7.015, P < 0.001), and LRFS (HR = 3.689, 95% CI 1.423–9.566, P = 0.007). Compared with the low-medium Ki67 and low ERCC1 groups, no significant difference in survival prognosis was obtained in the low-medium Ki67 and high ERCC1 groups, and patients with high Ki67 and low ERCC1 levels. Combined Ki67 and ERCC1 can better predict nasopharyngeal carcinoma prognosis than individual parameters.This study aimed to assess the predictive value of combined Ki67 and ERCC1 in distant metastasis-free nasopharyngeal carcinoma. 334 such cases were retrospectively assessed. Immunohistochemistry was used to evaluate Ki67 and ERCC1 protein levels in tumor tissues. Associations of Ki67 and ERCC1 amounts with clinical characteristics and survival were analyzed. Medium follow-up was 48.7 months; overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) were 91.3%, 76.0%, 82.0%, and 91.9%, respectively. High Ki67 expression was found in 35.6% patients, and positively correlated with clinical- and N- staging (P = 0.005, P < 0.001); 4-year OS, DFS, and DMFS were significantly lower in the high Ki67 group than patients with low-medium expression (P = 0.001, P = 0.012, P = 0.007). High ERCC1 expression was found in 35.3% of patients, and positively correlated with clinical- and T- staging. Compared with low ERCC1 expression cases, 4-year OS, DFS, DMFS, and LRFS were decreased significantly in those with high levels. High Ki67 and ERCC1 levels were related to adverse prognoses of OS (HR=4.977, 95% CI 2.31-12.292, P<0.001), DFS (HR = 4.178, 95% CI 2.421-7.212, P < 0.001), DMFS (HR = 3.722, 95% CI 2.028-7.015, P < 0.001), and LRFS (HR = 3.689, 95% CI 1.423-9.566, P = 0.007). Compared with the low-medium Ki67 and low ERCC1 groups, no significant difference in survival prognosis was obtained in the low-medium Ki67 and high ERCC1 groups, and patients with high Ki67 and low ERCC1 levels. Combined Ki67 and ERCC1 can better predict nasopharyngeal carcinoma prognosis than individual parameters.