Impact of molecular testing in advanced melanoma on outcomes in a tertiary cancer center and as reported in a publicly available database.
Impact of molecular testing in advanced melanoma on outcomes in a tertiary cancer center and as reported in a publicly available database.
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DOI：
10.1002/cnr2.1380
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Jour G
中科院分区：
文献类型：
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作者：
Dimitrova M;Kim MJ;Osman I;Jour G
在晚期黑色素瘤（MM）患者中，基因组分析可能会指导一线及以后的治疗决策，因为特定的肿瘤突变可以通过靶向治疗（TT）进行治疗。用于鉴定可靶向突变（TM）的组大小的范围可以从几十个到全外显子组测序（WES）。我们研究了样本组大小和突变状态对MM一线治疗选择和结局的影响。我们分析了来自三个队列的1109例MM患者的数据：NYULH的169例患者，使用50个基因的离子激流样本组（IT）进行分析; MSKCC的195例患者，使用400个基因的MSK‐IMPACT样本组（MSK‐I）进行分析;以及7个不同研究中心的745例患者，使用WES进行分析。队列2和3的数据是从公开可用的cBioPortal中推断出来的。队列1、2和3中分别有100%、25%和0%的患者获得治疗信息。BRAF和NRAS是IT和MSK‐I中前五个最常见的突变基因，而对于WES，只有BRAF是前五个突变。队列1中接受免疫检查点抑制剂（ICI）治疗的BRAF MUT患者与接受TT治疗的BRAF MUT患者的OS无显著差异（P = .19），队列1中接受ICI治疗的BRAF MUT患者与队列2中接受TT治疗的BRAF MUT患者的OS也无显著差异（P = .762）。公共数据集提供了人群水平的数据;然而，报告的临床信息的异质性限制了其价值，并要求数据标准化。没有证据表明较大的板尺寸具有明确的临床获益，因此有理由在MM中采用更小、更具成本效益的板。
In patients with advanced melanoma (MM), genomic profiling may guide treatment decisions in the frontline setting and beyond as specific tumor mutations can be treated with targeted therapy (TT). The range of panel sizes used to identify targetable mutations (TM) can range from a few dozen to whole exome sequencing (WES). We investigated the impact of panel size and mutation status on first‐line treatment selection and outcomes in MM. We analyzed data for 1109 MM patients from three cohorts: 169 patients at NYULH and profiled with the 50 gene Ion Torrent panel (IT), 195 patients at MSKCC, profiled with the 400‐gene MSK‐IMPACT panel (MSK‐I) and 745 patients at seven different sites profiled with WES. Data for cohorts 2 and 3 were extrapolated from the publicly available cBioPortal. Treatment information was available for 100%, 25%, and 0% of patients in cohort 1, 2, and 3, respectively. BRAF and NRAS were among the top five most commonly mutated genes in the IT and MSK‐I, whereas for WES only BRAF was a top five mutation. There was no significant difference in OS for BRAF MUT patients treated with immune checkpoint inhibitors (ICI) vs TT in cohort 1 (P = .19), nor for BRAF MUT patients from cohort 1 treated with ICI vs those from cohort 2 treated with TT (P = .762). Public datasets provide population‐level data; however, the heterogeneity of reported clinical information limits their value and calls for data standardization. Without evidence of clear clinical benefit of a larger panel size, there is a rationale for adopting smaller, more cost effective panels in MM.