In-patient hospice and rapid autopsy to interrogate tumor heterogeneity

我们今年写了这份临床方案。这在概念和完整的方案审查中由医学肿瘤科及其附属机构的临床方案审查过程进行了审查。几个月前，IRB终于批准了这一计划。我们已经确认了几名正在接受家庭临终关怀的患者。我们已经开始与这些患者和家属讨论，以解释这一方案。通过快速尸检获取组织为研究原发和广泛转移部位的肿瘤生物学提供了一种有效的方法，这是任何其他方法都不可能实现的。除了肿瘤的异质性，尸检获得的组织还可以对与肿瘤进展相关的继发突变的频率和性质、新的生物标记物和耐药机制产生重要的生物学见解。肿瘤异质性的全面程度和后果可以通过对来自原发灶和转移灶的几个区域的同时核心活检的蛋白质水平的基因改变的深度测序和全局分析以及与临床结果的相关性来评估。据我们所知，在非小细胞肺癌中还没有进行过这样的研究。我们打算从多达十个不同的转移性疾病部位收集肿瘤组织，以研究肿瘤间的异质性。每个部位的最多六个不同的核心将被适当地存储，以询问肿瘤内的异质性。下一代测序和深入的基于质谱学的蛋白质组学分析将对这些样本进行，以分析肿瘤的异质性。我们还将尝试从患者的几个部位产生细胞系，这些细胞系有望成为研究肿瘤异质性和肿瘤生物学的独特试剂。

We wrote this clinical protocol this year. This was reviewed in the Concept and full protocol reviews by the Medical Oncology Branch and Affiliates' clinical protocol review process. Finally this was approved by the IRB couple of months back. We have identified couple of patients who are on home hospice now. We have initiated discussions with those patients and family members to explain this protocol. Tissue procurement by rapid autopsies provides an effective way to investigate tumor biology of primary and a broad range of metastatic sites in a manner not possible by any other means. In addition to tumor heterogeneity, tissue obtained at autopsy could yield important biologic insights into frequency and nature of secondary mutations associated with tumor progression, novel biomarkers and mechanisms of resistance to treatment. The full extent and consequences of tumor heterogeneity can be evaluated by deep sequencing and global analysis of genetic alterations at the protein level of simultaneous core biopsies from several areas of the primary tumor and metastases and correlation with clinical outcome. To our knowledge, no such studies have been done in NSCLC. We intend to collect tumor tissue from up to ten different sites of metastatic disease to study inter-tumor heterogeneity. Up to six different cores from each site will be stored properly to interrogate intra-tumor heterogeneity. Next generation sequencing and in-depth mass spectrometry-based proteomics analyses will be performed on these samples to assay tumor heterogenety. We will also attempt to generate cell lines from several sites from a patient that are expected to be unique reagents to study tumor heterogenety and tumor biology.