In-patient hospice and rapid autopsy to interrogate tumor heterogeneity

我们今年写了这个临床方案。这在肿瘤医学分部和附属机构的临床方案审查过程的概念和完整方案审查中进行了审查。最终这在几个月前得到了IRB的批准。我们已经确认了几个正在接受家庭临终关怀的病人。我们已经开始与患者及其家属讨论，以解释该方案。通过快速尸检获取组织提供了一种有效的方法来研究原发性和大范围转移部位的肿瘤生物学，这是任何其他方法都无法做到的。除了肿瘤异质性外，解剖获得的组织还可以对与肿瘤进展相关的继发性突变的频率和性质、新的生物标志物和耐药机制等方面提供重要的生物学见解。肿瘤异质性的全面程度和后果可以通过深度测序和对原发肿瘤和转移灶的几个区域同时进行核心活检的蛋白质水平上的遗传改变的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这样的研究。我们打算从10个不同的转移性疾病部位收集肿瘤组织来研究肿瘤间的异质性。每个位点多达6个不同的核心将被妥善储存，以询问肿瘤内的异质性。下一代测序和基于深度质谱的蛋白质组学分析将在这些样品上进行，以测定肿瘤的异质性。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.