Development and validation of a transcriptomics-based gene signature to predict distant metastasis and guide induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma

2022 ◽  
Vol 163 ◽  
pp. 26-34
Author(s):  
Sai-Lan Liu ◽  
Xue-Song Sun ◽  
Qiu-Yan Chen ◽  
Ze-Xian Liu ◽  
Li-Juan Bian ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Distant Metastasis ◽  
Gene Signature ◽  
Development And Validation

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.

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 Adjuvant Chemotherapy Following Combined Induction Chemotherapy and Concurrent Chemoradiotherapy Improves Survival in N2-3-positive Nasopharyngeal Carcinoma Patients

2021 ◽  
Author(s):  
Hao-Yun Tao ◽  
Hui Liu ◽  
Cai-Xian He ◽  
Ran Li ◽  
Kun-Peng Du ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Distant Metastasis ◽  
Concurrent Chemoradiotherapy ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Clinical Value ◽  
Free Survival ◽  
Kaplan Meier

Abstract Objective: This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) in locoregionally advanced nasopharyngeal carcinoma (LANC) following concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT).Methods: We included 839 newly diagnosed LANC patients in the study. ICT plus CCRT (ICT+CCRT group) was administered to 443 patients and 396 patients who received ACT after receiving ICT plus CCRT (ICT+CCRT+ACT group). Univariate and multivariate Cox regression analyses were carried out in this study. Furthermore, to balance the study and control groups, propensity score matching (PSM) was applied.Results: 373 pairs of LANC patients were obtained after the PSM analysis. We found that ACT following ICT+CCRT had no significant effect on improving the survival of LANC patients. By further exploring the ICT+CCRT+ACT regimen, we excluded N0-1-positive patients and performed PSM in the ICT+CCRT and ICT+CCRT+ACT groups again. Each group consisted of 237 patients. Kaplan-Meier analysis revealed that there was a difference between the ICT+CCRT and ICT+CCRT+ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT+CCRT+ACT group had a higher incidence of grade 3-4 acute leukocytopenia/neutropenia.Conclusion: Compared with ICT+CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2-3-positive LANC and improve the OS and DFS of these patients, thus demonstrating higher clinical feasibility.

scholarly journals Plasma protein-based signature predicts distant metastasis and induction chemotherapy benefit in Nasopharyngeal Carcinoma

Theranostics ◽  
2020 ◽  
Vol 10 (21) ◽  
pp. 9767-9778
Author(s):  
Yelin Liang ◽  
Junyan Li ◽  
Qian Li ◽  
Linglong Tang ◽  
Lei Chen ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Plasma Protein ◽  
Distant Metastasis

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 With Mitomycin, Epirubicin, Cisplatin, Fluorouracil, and Leucovorin Followed by Radiotherapy in the Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma

2001 ◽  
Vol 19 (23) ◽  
pp. 4305-4313 ◽  
Author(s):  
Ruey-Long Hong ◽  
Lai-Lei Ting ◽  
Jenq-Yuh Ko ◽  
Mow-Ming Hsu ◽  
Tzung-Shiahn Sheen ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Distant Metastasis ◽  
Elevated Serum ◽  
Staging System ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Neck Node ◽  
Neck Lymph Node ◽  
Free Rate

PURPOSE: Survival in advanced nasopharyngeal carcinoma (NPC) is compromised by distant metastasis. Because mitomycin is active against hypoxic and G0 cells, which may help to eradicate micrometastasis, we investigated the effect of mitomycin-containing cisplatin-based induction chemotherapy. PATIENTS AND METHODS: Recruited for this study were American Joint Committee on Cancer (AJCC) 1992 staging system stage IV NPC patients with the following adverse features: obvious intracranial invasion, supraclavicular or bilateral neck lymph node metastasis, large neck node (> 6 cm), or elevated serum lactate dehydrogenase (LDH) level. Patients were given three cycles of chemotherapy before radiotherapy. The chemotherapy comprised a 3-week cycle of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL). RESULTS: From January 1994 to December 1997, 111 patients were recruited. The median follow-up period was 43 months. The actuarial 5-year overall survival rate was 70% (95% confidence interval [CI], 60% to 80%; n = 111). For patients having completed radiotherapy (n = 100), the 5-year locoregional control rate was 70% (95% CI, 55% to 84%) and the distant metastasis–free rate was 81% (95% CI, 73% to 89%). The 5-year distant metastasis–free rate of N3a and N3b disease of AJCC 1997 staging system were 79% (95% CI, 62% to 95%) and 74% (95% CI, 60% to 89%), respectively. By Cox multivariate analysis, high pretreatment serum LDH level (P = .04) and neck nodal enlargement before radiotherapy (P = .001) were adverse prognostic factors of survival. CONCLUSION: The good 5-year survival of N3 disease supports the effectiveness of induction MEPFL in the primary treatment of advanced NPC. Further investigation to incorporate concurrent chemoradiotherapy is warranted.

scholarly journals Chemotherapy in Nasopharyngeal Carcinoma

2021 ◽  
Author(s):  
Lekha Madhavan Nair ◽  
Rejnish Ravi Kumar ◽  
Malu Rafi ◽  
Farida Nazeer ◽  
Kainickal Cessal Thommachan ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Distant Metastasis ◽  
Early Stage ◽  
Locally Advanced ◽  
Concurrent Chemotherapy ◽  
Concurrent Chemoradiation ◽  
Standard Regimen ◽  
Free Survival

Nasopharyngeal carcinoma is a unique disease entity among head and neck cancers due to its epidemiology and clinical behavior. Non-keratinizing or undifferentiated carcinoma is the most common histological type in endemic areas. Radiotherapy is the treatment for early-stage disease. With the widespread use of IMRT, loco-regional control has improved significantly in locally advanced diseases. But distant metastasis continues to be the most common pattern of failure. To address this issue, chemotherapy has been incorporated into radiotherapy in various settings; as concurrent, induction, and adjuvant. The initial trials of concurrent chemotherapy incorporated adjuvant chemotherapy also and the magnitude of benefit contributed by each treatment was not clear. Later trials proved that adjuvant chemotherapy was not beneficial. Induction chemotherapy when added to concurrent chemoradiation resulted in improvement in Failure Free Survival, Overall Survival, and Distant Metastasis Free Survival. Thus, induction chemotherapy followed by concurrent chemoradiation became the standard of care for locally advanced disease (stage III and IVA). The role of chemotherapy in stage II disease is still evolving. Metastatic nasopharyngeal carcinoma is treated by platinum doublet chemotherapy, Cisplatin-gemcitabine is the standard regimen.

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