Development and validation of a gene expression-based signature predicting efficacy of induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A multicenter cohort study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6522-6522
Author(s):  
Yuan Lei ◽  
Ying-Qin Li ◽  
Wei Jiang ◽  
Xiao-Hong Hong ◽  
Wen-Xiu Ge ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Tumor Response ◽  
Gene Signature ◽  
Short Term ◽  
Free Survival ◽  
Training Cohort ◽  
Independent Cohort

6522 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene expression signature that can identify patients who will benefit from IC. Methods: We screened chemoresistance-related genes by comparing gene expression profiles of patients with short-term tumor response or non-response to IC (n = 95) using microarray analysis. Chemoresistance-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Results: We identified 43 chemoresistance-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] 0.87, sensitivity = 87.5%, specificity = 75.6%). We then apply the 6-gene signature to classify patients into the benefit group and the no-benefit group. In the benefit group, patients could benefit from IC in terms of failure-free survival (hazard ratio [HR] 0.54 [95% confidence interval 0.34-0.87]; p = 0.01), while patients in the no-benefit group could not (HR 1.25 [95%CI 0.62-2.51]; p = 0.53). In the clinical trial cohort, the developed 6-gene signature was also highly accurate at predicting the response to IC (AUC = 0.82; sensitivity = 87.5%; specificity = 71.8%). Additionally, IC conferred failure-free survival benefits only on patients in the benefit group (HR 0.37 [95%CI 0.18-0.75], p = 0.004) and not on those in the no-benefit group (HR 0.70 [95%CI 0.27-1.82]; p = 0.46). In the external independent cohort, similar results were observed. Conclusions: The 6-gene signature can help select patients who will benefit from IC and thus lay a foundation for a more individualized therapeutic strategy for LA-NPC patients.

scholarly journals A Gene-Expression Predictor for Efficacy of Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

2020 ◽  
Author(s):  
Yuan Lei ◽  
Ying-Qin Li ◽  
Wei Jiang ◽  
Xiao-Hong Hong ◽  
Wen-Xiu Ge ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Tumor Response ◽  
Gene Signature ◽  
Short Term ◽  
Free Survival ◽  
Training Cohort ◽  
Independent Cohort

Abstract Background Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC. Methods We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided. Results We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed. Conclusions The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.

Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicenter randomized controlled trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6004-6004 ◽  
Author(s):  
Ming-Yuan Chen ◽  
Qi Yang ◽  
Minghuang Hong ◽  
Ming-Huang Hong
Keyword(s):  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Long Term Results ◽  
Phase 3 ◽  
Free Survival ◽  
Multicenter Randomized Controlled Trial

6004 Background: Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil (PF) resulted in improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival (LRRFS) and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results. Methods: Our trial was a randomized, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m² d1) and fluorouracil (800 mg/m² d1-5) every three weeks for two cycles before CCRT. Both groups were treated with 80 mg/m² cisplatin every three weeks concurrently with radiotherapy. The primary endpoints were DFS and DMFS. We did efficacy analyses in the 476 randomized patients (intention-to-treat population). Results: After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval (CI) 67.7-79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8-69.4) in the CCRT alone group (P = 0.005). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9-87.7) than in the CCRT alone group (73.1%, 95% CI 67.2-79.0, P = 0.013). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (P = 0.045). There were no significant differences in the rate of grade 3–4 late adverse events during follow-up between the two groups. Conclusions: IC followed by CCRT provides long-term DFS, DMFS, and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients. Clinical trial information: NCT00705627.

scholarly journals Prognostic value of serum uric acid and tumor response to induction chemotherapy in locally advanced nasopharyngeal carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuanji Xu ◽  
Zijie Wu ◽  
Wangzhong Ye ◽  
Youping Xiao ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Uric Acid ◽  
Nasopharyngeal Carcinoma ◽  
Serum Uric Acid ◽  
Induction Chemotherapy ◽  
Predictive Value ◽  
Tumor Response ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Free Survival

Abstract Background To explore the combined predictive value of serum uric acid (SUA) and tumor response to induction chemotherapy (IC) in locally advanced nasopharyngeal carcinoma (LANPC) patients receiving IC followed by concurrent chemoradiation therapy (CCRT). Methods A total of 341 LANPC patients treated with IC + CCRT were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared by the Kaplan-Meier analysis and the log-rank test, and multivariable survival analysis was carried out to investigate the independent prognostic factors. Results Univariate analysis showed that a low SUA level and unsatisfactory tumor response to two cycles of IC both were negative predictors for OS, PFS, and DMFS in patients with LANPC. multivariable analysis demonstrated that the SUA level after two cycles of IC was an independent prognostic factor for OS (P = 0.012) but of borderline significance for PFS and DMFS (P = 0.055 and P = 0.067, respectively). Furthermore, tumor response to IC was of independent significance for predicting OS, PFS, and DMFS, respectively. Finally, LANPC patients with satisfactory tumor response and a high SUA level after two cycles of IC had a better OS, PFS, and DMFS than those with unsatisfactory tumor response and a low SUA level. Conclusion The SUA level and the tumor response to two cycles of IC had predictive value for LANPC patients treated with IC plus CCRT. However, more aggressive therapeutic strategies are recommended for those with a low SUA level and unsatisfactory tumor response to two cycles of IC.

A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6032-6032
Author(s):  
Wang Fang FangZheng
Keyword(s):  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Long Term Outcomes ◽  
First Line ◽  
Grade 3

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P > 0.05) and 97.8% (P > 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.

scholarly journals Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592092821
Author(s):  
Li-Ting Liu ◽  
Yu-Jing Liang ◽  
Shan-Shan Guo ◽  
Hao-Yuan Mo ◽  
Ling Guo ◽  
...  
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Risk Group ◽  
Risk Groups ◽  
Rank Test ◽  
Intermediate Risk ◽  
Free Survival ◽  
Alternative Treatment Strategy

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups ( p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

scholarly journals Treatment of Childhood Nasopharyngeal Carcinoma With Induction Chemotherapy and Concurrent Chemoradiotherapy: Results of the Children’s Oncology Group ARAR0331 Study

2019 ◽  
Vol 37 (35) ◽  
pp. 3369-3376 ◽  
Author(s):  
Carlos Rodriguez-Galindo ◽  
Mark D. Krailo ◽  
Matthew J. Krasin ◽  
Li Huang ◽  
M. Beth McCarville ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Advanced Disease ◽  
Black Children ◽  
Oncology Group ◽  
Event Free Survival ◽  
Free Survival ◽  
The Impact ◽  
To Receive

PURPOSE The treatment of childhood nasopharyngeal carcinoma has been adapted from adult regimens; pediatric-specific studies are limited. The ARAR0331 study sought to evaluate the impact of induction chemotherapy (IC) and concurrent chemoradiotherapy (CCR). PATIENTS AND METHODS Patients with American Joint Committee on Cancer stages IIb to IV were scheduled to receive three cycles of IC with cisplatin and fluorouracil, followed by CCR with three cycles of cisplatin. Patients with complete or partial response to IC received 61.2 Gy to the nasopharynx and neck, and patients with stable disease received 71.2 Gy. RESULTS Between February 2006 and January 2012, 111 patients (75 male) were enrolled. Median age was 15 years, and 46.8% of the patients were African American. After a feasibility analysis, the study was amended to reduce cisplatin to two cycles during CCR. The 5-year event-free survival (EFS) and overall survival estimates were 84.3% and 89.2%, respectively. The 5-year EFS for stages IIb, III, and IV were 100%, 82.8%, and 82.7%, respectively. The 5-year cumulative incidence estimates of local, distant, and combined relapse were 3.7%, 8.7%, and 1.8%, respectively. Patients treated with three versus two CCR cycles of cisplatin had improved 5-year postinduction EFS (90.7% v 81.2%, P = .14). CONCLUSION Patients in ARAR0331 were characterized by advanced disease and by a high proportion of black children and adolescents. Treatment with IC and CRT resulted in excellent outcomes. A radiation dose reduction is possible for patients responding to IC. Although the outcomes are comparable, we observed a trend toward decreased EFS for patients assigned to receive fewer doses of cisplatin during CCR.

scholarly journals Treatment effects of cumulative cisplatin dose during radiotherapy following induction chemotherapy in nasopharyngeal carcinoma: propensity score analyses

2020 ◽  
Vol 12 ◽  
pp. 175883592093742 ◽  
Author(s):  
Liang Peng ◽  
Jia-Luo Chen ◽  
Guang-Li Zhu ◽  
Cheng-Long Huang ◽  
Jun-Yan Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Distant Metastasis ◽  
Treatment Effects ◽  
Concurrent Chemoradiotherapy ◽  
Propensity Scores ◽  
Stage Ii ◽  
Similar Treatment ◽  
Free Survival ◽  
Secondary Endpoints

Background: The treatment effects of cumulative cisplatin dose (CCD) during radiotherapy (RT) following induction chemotherapy (IC) have not been determined for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 3460 patients with locoregionally advanced NPC who were treated with IC plus cisplatin-based concurrent chemoradiotherapy or RT alone were included in this retrospective study. Three CCD groups (0 mg/m2 ⩽ CCD <100 mg/m2, 100 mg/m2 ⩽ CCD <200 mg/m2, CCD ⩾200 mg/m2) were balanced through the inverse probability of treatment weighting based on propensity scores estimated by a general boosted model. The primary endpoint was overall survival (OS); the secondary endpoints were distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS). Results: CCD ⩾200 mg/m2 and <200 mg/m2 exhibited similar treatment effects for OS and DMFS, and were both superior to CCD <100 mg/m2 for OS and DMFS in patients with stage IVa NPC. The three CCD groups achieved similar treatment effects for patients with stage II–III NPC. After IC, CCD during RT appeared to exert little treatment effect on LRFS. Conclusion: The CCD during RT exerts treatment effects and improves OS by reducing the risk of distant metastasis for patients with stage IVa NPC following IC, and CCD <200 mg/m2 (mainly 160 mg/m2 in this group) is recommended. However, RT alone may be sufficient after IC in patients with stage II–III NPC.

scholarly journals A Five-Gene Prognostic Nomogram Predicting Disease-Free Survival of Differentiated Thyroid Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Pan Ruchong ◽  
Tang Haiping ◽  
Wang Xiang
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Disease Free Survival ◽  
Gene Signature ◽  
Training Dataset ◽  
Prediction Ability ◽  
Free Survival ◽  
Testing Dataset ◽  
Disease Free

Background. Differentiated thyroid cancer (DTC) is the most common type of thyroid tumor with a high recurrence rate. Here, we developed a nomogram to effectively predict postoperative disease-free survival (DFS) in DTC patients. Methods. The mRNA expressions and clinical data of DTC patients were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Seventy percent of patients were randomly selected as the training dataset, and thirty percent of patients were classified into the testing dataset. Multivariate Cox regression analysis was adopted to establish a nomogram to predict 1-year, 3-year, and 5-year DFS rate of DTC patients. Results. A five-gene signature comprised of TENM1, FN1, APOD, F12, and BTNL8 genes was established to predict the DFS rate of DTC patients. Results from the concordance index (C-index), area under curve (AUC), and calibration curve showed that both the training dataset and the testing dataset exhibited good prediction ability, and they were superior to other traditional models. The risk score and distant metastasis (M) of the five-gene signature were independent risk factors that affected DTC recurrence. A nomogram that could predict 1-year, 3-year, and 5-year DFS rate of DTC patients was established with a C-index of 0.801 (95% CI: 0.736, 0.866). Conclusion. Our study developed a prediction model based on the gene expression and clinical characteristics to predict the DFS rate of DTC patients, which may be applied to more accurately assess patient prognosis and individualized treatment.

scholarly journals Hemastatic biomarkers as prognostic factors in locoregionally advanced nasopharyngeal carcinoma treated with nimotuzumab plus chemoradiotherapy

2019 ◽  
Author(s):  
Jianda Sun ◽  
Zhijie Chen ◽  
Jun Xiong ◽  
Hanxiong Zhang ◽  
Yibiao Chen ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Nasopharyngeal Carcinoma ◽  
Primary Tumor ◽  
Tumor Response ◽  
Binary Logistic Regression ◽  
International Normalized Ratio ◽  
Binary Logistic Regression Analysis ◽  
Thrombin Time ◽  
Short Term ◽  
And Gender

Abstract Background: The prognostic value of hemostatic biomarkers in many tumors are well recognized. However, it remains unclear in locoregionally advanced nasopharyngeal carcinoma (NPC) patients treated with nimotuzumab plus chemoradiotherapy . In this study, we investigated pretreatment hemostatic biomarkers as prognostic factors for short-term efficacy after treatment. Methods: In total, 101 patients with stage Ⅲ or stage Ⅳa NPC were enrolled from March 2016 to December 2018. All patients received chemoradiotherapy with concurrent nimotuzumab (200 mg/week) administration. Platelet count (PLT), prothrombin time (PT), international normalized ratio (INR), thrombin time (TT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were collected before treatment. Results: There was a statistically significant association between APTT and gender ( P =0.006), while PT and INR were found to be correlated with age ( P = 0.020 and P = 0.011, respectively). Prolonged PT or elevated INR was associated with a higher CR rate after treatment ( P = 0.008 and P = 0.003, respectively). Binary logistic regression analysis demonstrated that age, T category, N category, PT and INR were independent prognostic factors for primary tumor response, whereas N category and the overall stage could independently predict cervical lymph node response. Conclusion: Pretreatment PT and INR may serve as useful prognostic biomarkers for predicting the primary tumor response to combined nimotuzumab and chemoradiotherapy in patients with locoregionally advanced NPC.

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