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Abstract：
OBJECTIVE: We evaluated the prognostic value of the neurotrophic tyrosine receptor kinase (NTRK) gene fusions by comparing the survival of patients with NTRK+ tumours with patients without NTRK+ tumours.
METHODS: We used genomic and clinical registry data from the Center for Personalized Cancer Treatment (CPCT-02) study containing a cohort of cancer patients who were treated in Dutch clinical practice between 2012 and 2020. We performed a propensity score matching analysis, where NTRK+ patients were matched to NTRK- patients in a 1:4 ratio. We subsequently analysed the survival of the matched sample of NTRK+ and NTRK- patients using the Kaplan-Meier method and Cox regression, and performed an analysis of credibility to evaluate the plausibility of our result.
RESULTS: Among 3556 patients from the CPCT-02 study with known tumour location, 24 NTRK+ patients were identified. NTRK+ patients were distributed across nine different tumour types: bone/soft tissue, breast, colorectal, head and neck, lung, pancreas, prostate, skin and urinary tract. NTRK fusions involving the NTRK3 gene (46%) and NTRK1 gene (33%) were most common. The survival analysis rendered a hazard ratio (HR) of 1.44 (95% CI 0.81-2.55) for NTRK+ patients. Using the point estimates of three prior studies on the prognostic value of NTRK fusions, our finding that the HR is > 1 was deemed plausible.
CONCLUSIONS: NTRK+ patients may have an increased risk of death compared with NTRK- patients. When using historic control data to assess the comparative effectiveness of TRK inhibitors, the prognostic value of the NTRK fusion biomarker should therefore be accounted for.
METHODS: We used genomic and clinical registry data from the Center for Personalized Cancer Treatment (CPCT-02) study containing a cohort of cancer patients who were treated in Dutch clinical practice between 2012 and 2020. We performed a propensity score matching analysis, where NTRK+ patients were matched to NTRK- patients in a 1:4 ratio. We subsequently analysed the survival of the matched sample of NTRK+ and NTRK- patients using the Kaplan-Meier method and Cox regression, and performed an analysis of credibility to evaluate the plausibility of our result.
RESULTS: Among 3556 patients from the CPCT-02 study with known tumour location, 24 NTRK+ patients were identified. NTRK+ patients were distributed across nine different tumour types: bone/soft tissue, breast, colorectal, head and neck, lung, pancreas, prostate, skin and urinary tract. NTRK fusions involving the NTRK3 gene (46%) and NTRK1 gene (33%) were most common. The survival analysis rendered a hazard ratio (HR) of 1.44 (95% CI 0.81-2.55) for NTRK+ patients. Using the point estimates of three prior studies on the prognostic value of NTRK fusions, our finding that the HR is > 1 was deemed plausible.
CONCLUSIONS: NTRK+ patients may have an increased risk of death compared with NTRK- patients. When using historic control data to assess the comparative effectiveness of TRK inhibitors, the prognostic value of the NTRK fusion biomarker should therefore be accounted for.
摘要：
目的：我们通过比较有NTRK+肿瘤患者和无NTRK+肿瘤患者的生存率来评估神经营养酪氨酸受体激酶(NTRK)基因融合的预后价值。
方法：我们使用来自个性化癌症治疗中心（CPCT-02）研究的基因组和临床登记数据，该研究包含2012年至2020年在荷兰临床实践中接受治疗的癌症患者队列。我们进行了倾向得分匹配分析，其中NTRK+患者与NTRK-患者的匹配比例为1:4。我们随后使用Kaplan-Meier方法和Cox回归分析了NTRK+和NTRK-患者的匹配样本的存活率。并进行了可信度分析，以评估我们结果的合理性。
结果：在来自CPCT-02研究的3556名已知肿瘤位置的患者中，确定了24名NTRK+患者。NTRK+患者分布在9种不同的肿瘤类型：骨/软组织，乳房,结直肠,头部和颈部,肺，胰腺,前列腺,皮肤和泌尿道。涉及NTRK3基因（46％）和NTRK1基因（33％）的NTRK融合最常见。生存分析显示NTRK+患者的风险比(HR)为1.44(95%CI0.81-2.55)。使用先前关于NTRK融合的预后价值的三项研究的点估计，我们发现HR>1被认为是合理的。
结论：与NTRK患者相比，NTRK+患者的死亡风险可能增加。当使用历史对照数据评估TRK抑制剂的相对有效性时，因此,应考虑NTRK融合生物标志物的预后价值.
方法：我们使用来自个性化癌症治疗中心（CPCT-02）研究的基因组和临床登记数据，该研究包含2012年至2020年在荷兰临床实践中接受治疗的癌症患者队列。我们进行了倾向得分匹配分析，其中NTRK+患者与NTRK-患者的匹配比例为1:4。我们随后使用Kaplan-Meier方法和Cox回归分析了NTRK+和NTRK-患者的匹配样本的存活率。并进行了可信度分析，以评估我们结果的合理性。
结果：在来自CPCT-02研究的3556名已知肿瘤位置的患者中，确定了24名NTRK+患者。NTRK+患者分布在9种不同的肿瘤类型：骨/软组织，乳房,结直肠,头部和颈部,肺，胰腺,前列腺,皮肤和泌尿道。涉及NTRK3基因（46％）和NTRK1基因（33％）的NTRK融合最常见。生存分析显示NTRK+患者的风险比(HR)为1.44(95%CI0.81-2.55)。使用先前关于NTRK融合的预后价值的三项研究的点估计，我们发现HR>1被认为是合理的。
结论：与NTRK患者相比，NTRK+患者的死亡风险可能增加。当使用历史对照数据评估TRK抑制剂的相对有效性时，因此,应考虑NTRK融合生物标志物的预后价值.
