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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5654 - Ecological diversity indices as measurements of tumor heterogeneity correlates with clinical outcomes in late stage small cell lung cancer (SCLC)

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Translational Research

Tumour Site

Presenters

Stephanie Yaung

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

S. Yaung1, L. Xi1, C. Woestmann2, S. McNamara2, B. Hinzmann3, S. Froehler2, N. Tikoo4, C. Ju4, A. Balasubramanyam4, H. Adams5, M. Thomas6, F. Lasitschka6, M. Meister6, M. Schneider6, F.J.F. Herth6, T. Muley6, B. Wehnl7, J. Palma8, X.M. Ma9

Author affiliations

  • 1 Bioinformatics, Roche Sequencing Solutions, Inc., 94588 - Pleasanton/US
  • 2 Bioinformatics, Roche Sequencing Solutions, Inc., Potsdam/DE
  • 3 Assay Development, Roche Sequencing Solutions, Inc., Potsdam/DE
  • 4 Biostatistics, Roche Sequencing Solutions, Inc., 94588 - Pleasanton/US
  • 5 Biostatistics, Roche Sequencing Solutions, Inc., Potsdam/DE
  • 6 Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, 69126 - Heidelberg/DE
  • 7 Clinical Operations, Roche Diagnostics GmbH, Penzberg/DE
  • 8 Medical Scientific Affairs, Roche Sequencing Solutions, Inc., CA 94588 - Pleasanton/US
  • 9 Medical Scientific Affairs, Roche Sequencing Solutions, Inc., Pleasanton/US
More

Resources

Abstract 5654

Background

Tumor heterogeneity is difficult to characterize with tissue biopsies in late stage cancers, in which primary and metastatic tumors may have diverged in their mutational profiles. Assessing the diversity of mutations detected by sequencing circulating tumor DNA (ctDNA) from liquid biopsies can quantify the genetic complexity of tumors shedding DNA into the blood.

Methods

In a prospective, observational study, we obtained pre-treatment plasma samples from 56 subjects with Stage IV small cell lung cancer (SCLC) treated with first-line chemo or chemoradiation therapies. Plasma samples were analyzed with the AVENIO ctDNA Surveillance Kit, a targeted next-generation sequencing panel of 198 kilobases. We applied the Shannon and Simpson diversity indices by considering each somatic variant as a species and the number of detected duplex molecules with that mutation as the abundance of that species. Samples were ranked as low tumor heterogeneity if their plasma variant diversity score was below the first tertile of the cohort.

Results

Stage IV SCLC subjects with low tumor heterogeneity evaluated by the Shannon diversity had shorter overall survival (hazard ratio = 1.8; 95% CI 1-3.3; log-rank p = 0.034; median survival difference = 4.5 months). Furthermore, subjects with low tumor heterogeneity evaluated by the Gini-Simpson or inverse Simpson diversity index had shorter overall survival (hazard ratio = 1.8; 95% CI 1-3.3; log-rank p = 0.033; median survival difference = 4.5 months).

Conclusions

The molecular barcoding scheme in the AVENIO kit allows for each strand of the original double-stranded ctDNA molecule to be tracked. From this reconstructed profile of circulating duplex molecules harboring tumor variants, we derived a tumor heterogeneity measure based on the Shannon and Simpson diversity indices commonly used in ecology. We found that late stage SCLC subjects with low tumor heterogeneity had shorter overall survival, suggesting that highly heterogeneous SCLC tumors may respond better to chemotherapy or radiation. Studies to further validate these findings are ongoing.

Clinical trial identification

Legal entity responsible for the study

Roche Sequencing Solutions, Inc.

Funding

Roche Sequencing Solutions, Inc.

Editorial Acknowledgement

Disclosure

S. Yaung, L. Xi, C. Woestmann, S. McNamara, B. Hinzmann, S. Froehler, C. Ju, A. Balasubramanyam, H-P. Adams, B. Wehnl, X.M. Ma: Employment: Roche. N. Tikoo: Employment: Roche; Stock ownership: BeiGene, Celgene, Denali Therapeutics, Exelixis, Gilead Sciences. F. Lasitschka: Consulting role: Roche; Research funding: Boehringer Ingelheim International GmbH. M. Meister, M. Schneider: Research funding: Roche. F.J.F. Herth: Stock ownership: Roche, Lilly, Novartis; Consulting role: Novartis. T. Muley: Royalty sharing agreement: Roche; Research funding: Roche. J. Palma: Employment: Roche; Stock ownership: Exact Sciences, Clovis Oncology, Johnson & Johnson, Roche. All other authors have declared no conflicts of interest.

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