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老年非小细胞肺癌的分子特征:老年患者精准医学之门。

Molecular Profile of Advanced Non-Small Cell Lung Cancers in Octogenarians: The Door to Precision Medicine in Elderly Patients.

作者信息

Fumagalli Caterina, Catania Chiara, Ranghiero Alberto, Bosi Carlo, Viale Giuseppe, de Marinis Filippo, Barberis Massimo, Guerini-Rocco Elena

机构信息

Unit of Histopathology and Molecular Diagnostics, Division of Pathology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy.

Division of Thoracic Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy.

出版信息

J Clin Med. 2019 Jan 18;8(1):112. doi: 10.3390/jcm8010112.

Abstract

BACKGROUND

There is a pressing need to expand the evidence base in geriatric lung oncology. Most non-small cell lung cancers (NSCLCs) are diagnosed in the elderly, with approximately 15% of cases affecting octogenarians. Treatment-related decisions are challenging in this population, and the role of biologically driven therapies is still underrated.

METHODS

A single-institution cohort of 76 NSCLCs from octogenarian patients was submitted to molecular analysis using a next-generation sequencing (NGS) multigene panel, fluorescence in situ hybridization (FISH) analyses, and immunohistochemistry for PD-L1 assessment. Treatment and clinical outcome data were available for 33 patients.

RESULTS

Most cases ( = 66, 87%) harbored at least one genomic alteration. and mutations were detected in 18 (24%) and 20 (26%) patients, respectively. No alterations were found, but in two patients translocation was identified. Of 22 cases tested, 17 were positive for PD-L1 staining. Octogenarian patients who received tyrosine kinase inhibitors (TKIs) based on molecular analysis showed clinical benefits, with long progression-free survival as expected in TKI-treated younger cohorts.

CONCLUSIONS

This study highlights the utility of molecular profiling in all advanced-stage NSCLCs, regardless of the age at diagnosis, to drive personalized treatment. The prevalence of druggable alterations and the clinical benefits obtained by biologically-driven therapies in octogenarians were comparable to those of the younger NSCLC population.

摘要

背景

迫切需要扩大老年肺癌肿瘤学的证据基础。大多数非小细胞肺癌(NSCLC)在老年人中被诊断出来,约15%的病例影响到八旬老人。在这一人群中,与治疗相关的决策具有挑战性,而生物驱动疗法的作用仍被低估。

方法

对来自八旬老人患者的76例NSCLC单机构队列进行分子分析,使用二代测序(NGS)多基因检测板、荧光原位杂交(FISH)分析以及用于PD-L1评估的免疫组织化学。33例患者有治疗和临床结果数据。

结果

大多数病例(n = 66,87%)至少有一个基因组改变。分别在18例(24%)和20例(26%)患者中检测到EGFR和ALK突变。未发现KRAS改变,但在2例患者中鉴定出ROS1易位。在检测的22例病例中,17例PD-L1染色呈阳性。根据分子分析接受酪氨酸激酶抑制剂(TKI)治疗的八旬老人患者显示出临床获益,无进展生存期长,这与TKI治疗的年轻队列预期情况相同。

结论

本研究强调了分子谱分析在所有晚期NSCLC中的实用性,无论诊断时的年龄如何,以推动个性化治疗。八旬老人中可靶向改变的发生率以及生物驱动疗法获得的临床获益与年轻NSCLC人群相当。

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