Safety and Efficacy of Ledipasvir/Sofosbuvir in a Genotype 1 HCV Infected Chinese Population: Results from a Phase 3, Clinical Trial

( Lai Wei ),( Qing Xie ),( Jin Lin Hou ),( Hong Tang ),( Qin Ning ),( Jun Cheng ),( Yuemin Nan ),( Lunli Zhang ),( Jun Li ),( Jianning Jiang ),( Megan Kim ),( Brian Mcnabb ),( Fangqiu Zhang ),( Gregor 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Chronic hepatitis C virus (HCV) infection remains a major health threat in China, affecting at least 10 million people, with approximately 58% having genotype (GT) 1 infection. There is a critical need for simple, all oral, direct-acting antiviral regimens to treat GT1 HCV in this region. Treatment with ledipasvir (LDV)/sofosbuvir (SOF) results in high sustained virologic response rates 12 weeks after therapy (SVR12) in GT1 HCV infected patients in clinical trials and real-world settings. This study evaluated the efficacy and safety of LDV/SOF for 12 weeks in Chinese patients with chronic GT1 HCV infection. Methods: Treatment experienced and treatment naïve patients with chronic GT1 HCV infection with no cirrhosis or with compensated cirrhosis were eligible to enroll in a single-arm, openlabel trial to receive a fixed dosed combination of LDV/SOF 90/400 mg daily for 12 weeks. The primary efficacy endpoint was SVR12 using the CAP/CTM HCV 2.0 assay (LLOQ =15 IU/mL) and the primary safety endpoint was adverse events (AEs) leading to LDV/SOF discontinuation. Results: A total of 206 Chinese patients were enrolled and treated. Of these, 50% were male, 16% had compensated cirrhosis, 49% were treatment-experienced, 76% had IL28B CC genotype, and 100% had GT1b HCV infection. The mean (range) age and body mass index of enrolled subjects were 47 (21-72) years and 23 (14-34) kg/m2, respectively. The overall SVR12 rate is 100% (206/206). All 32 patients with cirrhosis (15 of whom were treatment-experienced), achieved SVR12. There were no discontinuations due to AEs. No serious or severe AEs were assessed by the investigator as related to study drug and there were no deaths. Conclusions: Treatment with the single tablet regimen of LDV/SOF for 12 weeks resulted in 100% SVR12 and was well tolerated in treatment experienced and treatment naïve GT1 HCVinfected Chinese patients with and without cirrhosis.

Induction Chemotherapy Plus Concurrent Chemoradiotherapy versus Concurrent Chemoradiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma in Children and Adolescents: A Matched Cohort Analysis

Yang Li,Lin-Quan Tang,Li-Ting Liu,Shan-Shan Guo,Yu-Jing Liang,Xue-Song Sun,Qing-Nan Tang,Jin-Xin Bei,Jing Tan,Shuai Chen,Jun Ma,Chong Zhao,Qiu-Yan Chen,Hai-Qiang Mai 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The purpose of this study was to evaluate the long-term clinical outcome and toxicity of induction chemotherapy (IC) followed by concomitant chemoradiotherapy (CCRT) compared with CCRT alone for the treatment of children and adolescent locoregionally advanced nasopharyngeal carcinoma (LACANPC). Materials and Methods A total of 194 locoregionally advanced nasopharyngeal carcinoma patients younger than 21 years who received CCRT with or without IC before were included in the study population. Overall survival (OS) rate, progression-free survival (PFS) rate, locoregional recurrence-free survival (LRFS) rate, and distant metastasis-free survival (DMFS) rate were assessed by the Kaplan-Meier method and a log-rank test. Treatment toxicities were clarified and compared between two groups. Results One hundred and thiry of 194 patients received IC+CCRT. Patients who were younger and with more advanced TNM stage were more likely to receive IC+CCRT and intensive modulated radiotherapy. The addition of IC before CCRT failed to improve survival significantly. The matched analysis identified 43 well-balanced patients in both two groups. With a median follow-up of 51.5 months, no differences were found between the IC+CCRT group and the CCRT group in 5-year OS (83.7% vs. 74.6%, p=0.153), PFS (79.2% vs. 73.4%, p=0.355), LRFS (97.7% vs. 88.2%, p=0.083), and DMFS (81.6% vs. 81.6%, p=0.860). N3 was an independent prognostic factor predicting poorer OS, PFS, and DMFS. The addition of IC was associated with increased rates of grade 3 to 4 neutropenia. Conclusion This study failed to demonstrate that adding IC before CCRT could provide a significant additional survival benefit for LACANPC patients. Further investigations are warranted.

Metastatic Axillary Lymph Node Ratio (LNR) is Prognostically Superior to pN Staging in Patients with Breast Cancer -- Results for 804 Chinese Patients from a Single Institution

Xiao, Xiang-Sheng,Tang, Hai-Lin,Xie, Xin-Hua,Li, Lai-Sheng,Kong, Ya-Nan,Wu, Min-Qing,Yang, Lu,Gao, Jie,Wei, Wei-Dong,Xie, Xiaoming Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

The number of axillary lymph nodes involved and retrieved are important prognostic factors in breast cancer. The purpose of our study was to investigate whether the lymph node ratio (LNR) is a better prognostic factor in predicting disease-free survival (DFS) for breast cancer patients as compared with pN staging. The analysis was based on 804 breast cancer patients who had underwent axillary lymph node dissection between 1999 and 2008 in Sun Yat-Sen University Cancer Center. Optimal cutoff points of LNR were calculated using X-tile software and validated by bootstrapping. Patients were then divided into three groups (low-, intermediate-, and high-risk) according to the cutoff points. Predicting risk factors for relapse were performed according to Cox proportional hazards analysis. DFS was estimated using the Kaplan-Meier method and compared by the log-rank test. The 5-year DFS rate decreased significantly with increasing LNRs and pN. Univariate analysis found that the pT, pN, LNR, molecule type, HER2, pTNM stage and radiotherapy well classified patients with significantly different prognosis. By multivariate analysis, only LNR classification was retained as an independent prognostic factor. Furthermore, there was a significant prognostic difference among different LNR categories for pN2 category, but no apparent prognostic difference was seen between different pN categories in any LNR category. Therefore, LNR rather than pN staging is preferable in predicting DFS in node positive breast cancer patients, and routine clinical decision-making should take the LNR into consideration.

Pretreatment Serum Amyloid A and C-reactive Protein Comparing with Epstein-Barr Virus DNA as Prognostic Indicators in Patients with Nasopharyngeal Carcinoma: A Prospective Study

Qiu-Yan Chen,Qing-Nan Tang,Lin-Quan Tang,Wen-Hui Chen,Shan-Shan Guo,Li-Ting Liu,Chao-Feng Li,Yang Li,Yu-Jing Liang,Xue-Song Sun,Ling Guo,Hao-Yuan Mo,Rui Sun,Dong-Hua Luo,Yu-Ying Fan,Yan He,Ming-Yuan C 대한암학회 2018 Cancer Research and Treatment Vol.50 No.3

Purpose The measuring Epstein-Barr virus (EBV) DNA is an important predictor of nasopharyngeal carcinoma (NPC). This study evaluated the predictive value of pretreatment serum amyloid A (SAA) and C-reactive protein (CRP) comparing with EBV DNA in patients with NPC. Materials and Methods In an observational study of 419 non-metastatic NPC patients, we prospectively evaluated the prognostic effects of pretreatment SAA, CRP, and EBV DNA on survival. The primary endpoint was progress-free survival (PFS). Results The median level of SAA and CRP was 4.28 mg/L and 1.88 mg/L, respectively. For the high- SAA group (> 4.28 mg/L) versus the low-SAA ( 4.28 mg/L) group and the high-CRP group (> 1.88 mg/L) versus the low-CRP ( 1.88 mg/L) group, the 5-year PFS was 64.5% versus 73.1% (p=0.013) and 65.2% versus 73.3% (p=0.064), respectively. EBV DNA detection showed a superior predictive result, the 5-year PFS in the EBV DNA  1,500 copies/mL group was obviously different than the EBV DNA < 1,500 copies/mL group (62.2% versus 77.8%, p < 0.001). Multifactorial Cox regression analysis confirmed that in the PFS, the independent prognostic factors were including EBV DNA (hazard ratio [HR], 1.788; p=0.009), tumour stage (HR, 1.903; p=0.021), and node stage (HR, 1.498; p=0.049), but the SAA and CRP were not included in the independent prognostic factors. Conclusion The results of SAA and CRP had a certain relationship with the prognosis of NPC, and the prognosis of patients with high level of SAA and CRP were poor. However, the predictive ability of SAA and CRP was lower than that of EBV DNA.

Combination of Tumor Volume and Epstein-Barr Virus DNA Improved Prognostic Stratification of Stage II Nasopharyngeal Carcinoma in the Intensity Modulated Radiotherapy Era: A Large-Scale Cohort Study

Qiu-Yan Chen,Shao-Yan Guo,Lin-Quan Tang,Tong-Yu Lu,Bo-Lin Chen,Qi-Yu Zhong,Meng-Sha Zou,Qing-Nan Tang,Wen-Hui Chen,Shan-Shan Guo,Li-Ting Liu,Yang Li,Ling Guo,Hao-Yuan Mo,Rui Sun,Dong-Hua Luo,Chong Zha 대한암학회 2018 Cancer Research and Treatment Vol.50 No.3

Purpose Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. Materials and Methods By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. Results Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm3; EBV DNA 0 copy/mL, GTVtotal  30 cm3; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm3) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal  30 cm3). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. Conclusion Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.

Patterns of Failure and Survival Trends in 3,808 Patients with Stage II Nasopharyngeal Carcinoma Diagnosed from 1990 to 2012: A Large-Scale Retrospective Cohort Study

Xue-Song Sun,Di-Han Liu,Sai-Lan Liu,Qiu-Yan Chen,Shan-Shan Guo,Yue-Feng Wen,Li-Ting Liu,Hao-Jun Xie,Qing-Nan Tang,Yu-Jing Liang,Xiao-Yun Li,Jin-Jie Yan,Ming-Huang Hong,Jun Ma,Lin-Quan Tang,Hai-Qiang M 대한암학회 2019 Cancer Research and Treatment Vol.51 No.4

Purpose The purpose of this study was to investigate the survival trends and patterns of failure in patients with stage II nasopharyngeal carcinoma (NPC) treated with radiotherapy (RT) and chemotherapy over the last 20 years. Materials and Methods Thirty-eight hundred and eight patients diagnosed with stage II NPC between January 1990 and December 2012 were involved in this retrospective cohort study. All patients were treated with RT. According to the main imaging techniques and RT technology, we categorized these patients into four calendar periods: 1990-1996, 1997-2002, 2003-2007, and 2008-2012. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis–free survival (DMFS) were served as the clinical outcome. Results After a median follow-up period of 84.7 months, we observed increasing trends in survival and disease control. The 3- and 5-year OS rates increased from 87.1% and 78.7% in the first calendar period to 97.4% and 94.5% in the last calendar period, respectively (p < 0.001). Additionally, significant increasing trends could be seen in the PFS and LRFS during the four calendar periods. In the subgroup analysis, the LRFS in patients older than 50 years at diagnosis showed greater improvement than younger patients. However, the rate of distant metastasis was stable and relatively low, as the 5-year DMFS ranged from 90.5% to 94.7% among the four calendar periods. Conclusion The survival rates in patients with stage II NPC showed increasing trends from 1990 to 2012. The advance of RT provided excellent locoregional control and enhanced OS.

Subdivision of Nasopharyngeal Carcinoma Patients with Bone-Only Metastasis at Diagnosis for Prediction of Survival and Treatment Guidance

Xue-Song Sun,Yu-Jing Liang,Sai-Lan Liu,Qiu-Yan Chen,Shan-Shan Guo,Yue-Feng Wen,Li-Ting Liu,Hao-Jun Xie,Qing-Nan Tang,Xiao-Yun Li,Jin-Jie Yan,Lin-Quan Tang,Hai-Qiang Mai 대한암학회 2019 Cancer Research and Treatment Vol.51 No.4

Purpose The purpose of this study was to subdivide M1 stage nasopharyngeal carcinoma (NPC) patients with bone-only metastases for prognosis prediction while identifying the treatment effect of locoregional radiotherapy (LRRT) and metastasis radiotherapy (MRT) among patients with different risk. Materials and Methods From November 2006 to October 2016, a total of 226 patients with bone-only metastasic NPC were retrospectively enrolled. All patients developed distant lesions before receiving treatment. All potential prognostic factors were considered and the correlation of the M1 subdivisions with overall survival (OS) was determined by Cox regression hazards model. Kaplan-Meier curves were used to appraise survival condition and log-rank testing was used to compare the differences. Results The median follow-up time was 33.9 months (range, 3 to 126 months). According to multivariate Cox proportional hazard analysis, the number of metastatic lesions and Epstein-Barr virus (EBV) DNA status after palliative chemotherapy (PCT) were independent prognostic factors for OS. Thus, we subdivided patients into three risk groups according to these two factors. Systemic chemotherapy combined with LRRT may benefit patients in low- and intermediate-risk groups but not in the high-risk group. Further aggressive MRT based on systemic chemotherapy showed no survival benefit in any risk group. Conclusion The stratification of NPC patients with bone-only metastasis based on EBV DNA after PCT and the number of metastatic lesions provided promising prognostic value and could aid clinicians in person-specific treatment.