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Translational research

5385 - A Systematic Rapid Autopsy Program Tracks Temporal and Spatial Heterogeneity of Human Tumors and Identifies Mechanisms of Resistance to Targeted Therapies

Date

09 Sep 2017

Session

Translational research

Topics

Translational Research

Presenters

Charlotte Walmsley

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

C.S. Walmsley1, D. Juric1, A. Bardia1, L. Henderson1, J. Gurski1, J.R. Stone2, C. Pinto1, S.J. Isakoff1, D.M. Fitzgerald1, J.F. Gainor1, L. Goyal1, M. Broudo1

Author affiliations

  • 1 Termeer Center For Targeted Therapies, Massachusetts General Hospital Cancer Center, 02114 - Boston/US
  • 2 Department Of Pathology, Massachusetts General Hospital, Boston, MA/US
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Abstract 5385

Background

Temporal and spatial heterogeneity of human tumors pose a significant barrier in the identification of effective anticancer therapies. Rapid autopsy, defined as post-mortem examination with collection of tissues for diagnosis and research within 6 hours of death, is a critical tool offering insight into this phenomenon.

Methods

Since January 2014, an on-call rapid autopsy team consisting of a pathologist, medical oncologist, pathology assistant and a tissue collection coordinator performed rapid autopsies on 51 patients with genomically-defined advanced solid tumors. Samples were collected from the primary tumor when present, multiple metastatic lesions, blood, as well as multiple uninvolved sites. All samples were recorded in a centralized database linked to patient’s treatment history, as well as all previously collected tissue and liquid biopsies, under one clinical data and sample collection protocol. Samples meeting minimum viability and tumor cellularity criteria were selected for downstream analyses, including next-generation sequencing and protein-based assays.

Results

In 51 rapid autopsies, a median of 12 tissue samples were collected per autopsy (range 5-24), after a median of 2 hours and 50 minutes post mortem (range 32 minutes - 9 hours). 47 autopsies (92.2%) were completed < 6 hours post mortem, and 4 autopsies (7.8%) were completed > 6 hours post mortem due to delays in the confirmation of the autopsy consent from the patient’s healthcare proxy and transportation delays. Tumor cellularity of collected samples ranged from 0-90% (median 60%), making these samples highly suitable for subsequent genomic analyses. Full analysis of 3 autopsy series revealed molecular alterations driving resistance to PI3K-alpha inhibitors, CDK4/6 inhibitors and FGFR inhibitors in patients with PIK3CA-altered metastatic breast cancer and FGFR2 fusion positive cholangiocarcinoma.

Conclusions

Rapid autopsies complement serially collected tissue and liquid biopsies, providing invaluable samples for analysis of tumor heterogeneity, evolutionary dynamics and determination of resistance mechanisms to targeted therapies.

Clinical trial identification

Legal entity responsible for the study

Dejan Juric

Funding

Susan Eid Tumor Heterogeneity Initiative

Disclosure

All authors have declared no conflicts of interest.

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