Santi Irene, Vellekoop Heleen, M Versteegh Matthijs, A Huygens Simone, Dinjens Winand N M, Mölken Maureen Rutten-van
Institute for Medical Technology Assessment, Erasmus University Rotterdam, Burgemeester Oudlaan 50, 3062 PA, Rotterdam, The Netherlands.
Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Mol Diagn Ther. 2024 May;28(3):319-328. doi: 10.1007/s40291-024-00704-2. Epub 2024 Apr 14.
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.
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.
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.
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.
通过比较NTRK阳性肿瘤患者与非NTRK阳性肿瘤患者的生存率，评估神经营养性酪氨酸受体激酶（NTRK）基因融合的预后价值。
我们使用了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，该研究包含一组2012年至2020年期间在荷兰临床实践中接受治疗的癌症患者。我们进行了倾向评分匹配分析，将NTRK阳性患者与NTRK阴性患者按1:4的比例进行匹配。随后，我们使用Kaplan - Meier方法和Cox回归分析了匹配后的NTRK阳性和NTRK阴性患者样本的生存率，并进行了可信度分析以评估我们结果的合理性。
在CPCT - 02研究中已知肿瘤位置的3556例患者中，鉴定出24例NTRK阳性患者。NTRK阳性患者分布在九种不同的肿瘤类型中：骨/软组织、乳腺、结肠直肠、头颈部、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融合最为常见。生存分析得出NTRK阳性患者的风险比（HR）为1.44（95%CI 0.81 - 2.55）。根据之前三项关于NTRK融合预后价值研究的点估计，我们发现HR>1这一结果被认为是合理的。
与NTRK阴性患者相比，NTRK阳性患者的死亡风险可能更高。因此，在使用历史对照数据评估TRK抑制剂的比较疗效时，应考虑NTRK融合生物标志物的预后价值。
