Abstract 5141
Background
SCLC is an aggressive disease with poor prognosis. Despite initial response to chemotherapy and radiotherapy, relapse occurs in most cases. To characterize genomic changes in SCLC over the course of therapy, we explored tracking tumor mutations in cell-free DNA (cfDNA) across post-treatment blood draws and comparing them to pre-treatment plasma and tissue profiles.
Methods
We retrospectively evaluated 235 samples collected from 24 subjects with late stage SCLC treated with first-line chemotherapy or chemoradiation in a prospective observational study. Tumor tissue samples were analyzed with the AVENIO Tumor Tissue Surveillance Kit (For Research Use Only, not for use in diagnostic procedures), a 198-kb next-generation sequencing panel covering 197 cancer genes. Matched peripheral blood mononuclear cells (PBMC), pre-treatment plasma, and multiple plasma from post-treatment timepoints were analyzed with the same panel using the AVENIO ctDNA Surveillance Kit (For Research Use Only, not for use in diagnostic procedures). A median input amount of 29 ng cfDNA, 129 ng tumor tissue DNA, and 50 ng PBMC DNA were sequenced to median deduplicated depths of 4491, 1315, and 6512, respectively. Somatic single nucleotide variants (SNVs) in tissue and plasma were identified by removing PBMC-matched germline or clonal hematopoietic mutations.
Results
We detected a median of 4 SNVs in tissue samples and a median of 100% (range 66 - 100%) of tissue SNVs in matched pre-treatment plasma. 96% (23/24) of subjects had at least one shared SNV between tissue and plasma, most commonly a TP53 mutation. A median of 7 SNVs were detected in pre-treatment plasma, whereas across all available post-treatment plasma (range 2 - 20 time points per subject), a median of 4 SNVs were detected. 53% of these mutations were not present in pre-treatment plasma or tissue.
Conclusions
Somatic mutations found in pre-treatment plasma were concordant with matched tissue, consistent with the highly metastatic nature of SCLC. ctDNA sequencing can provide additional molecular insights; in particular, detecting emergent mutations in ctDNA during treatment could advance our knowledge of SCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Roche Sequencing Solutions, Inc.
Funding
Roche Sequencing Solutions, Inc.
Disclosure
S. Yaung: Full / Part-time employment: Roche. C. Woestmann: Full / Part-time employment: Roche. L. Xi: Full / Part-time employment: Roche. C. Ju: Full / Part-time employment: Roche. B. Hinzmann: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. M. Thomas: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. F. Lasitschka: Research grant / Funding (institution): Roche. M. Meister: Research grant / Funding (institution): Roche. M. Schneider: Research grant / Funding (institution): Roche. F.J.F. Herth: Honoraria (institution): Roche. T. Muley: Research grant / Funding (institution), Licensing / Royalties: Roche. B. Wehnl: Full / Part-time employment: Roche. J. Palma: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. X.M. Ma: Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Roche.
Resources from the same session
2831 - Interleukin-6 as a Predictive Marker for Early Response to Induction Chemotherapy in Acute Myeloblastic Leukaemia
Presenter: Salah Khallaf
Session: Poster Display session 1
Resources:
Abstract
6014 - Impact of FLT3-ITD mutation on post-transplant outcome of adult AML is modified by the concomitant NPM1 mutation and pre-transplant remission status: A report from Taiwan Bone Marrow Transplant Registry (TBMTR)
Presenter: Su-peng Yeh
Session: Poster Display session 1
Resources:
Abstract
2914 - Efficacy endpoints studied in clinical trials for early-onset leukaemia
Presenter: Dylan Said
Session: Poster Display session 1
Resources:
Abstract
4691 - High triglyceride is a major risk factor of DIC and differentiation syndrome in acute promyelocytic leukemia
Presenter: Tomohiro Yamakawa
Session: Poster Display session 1
Resources:
Abstract
4395 - DREAMM 4: A Phase I/II single-arm open-label study to explore safety and clinical activity of belantamab mafodotin (GSK2857916) administered in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM)
Presenter: Suzanne Trudel
Session: Poster Display session 1
Resources:
Abstract
2808 - A Phase 1 Study of HMPL-523, a Selective Oral Anti-Spleen Tyrosine Kinase Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Nathan Fowler
Session: Poster Display session 1
Resources:
Abstract
4403 - A Phase 1 Study of HMPL-689, a Selective Oral Phosphoinositide 3-Kinase-Delta Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Jonathon Cohen
Session: Poster Display session 1
Resources:
Abstract
3357 - A global patient-driven Facebook study in a very rare sarcoma: Health-related quality of life in Epithelioid Hemangioendothelioma (EHE) patients
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
2475 - Qualitative study of patients’ experiences of living with and beyond a soft tissue sarcoma diagnosis: the impact of sarcoma specialist services
Presenter: Ana Martins
Session: Poster Display session 1
Resources:
Abstract
2640 - Health-related quality of life issues of patients affected by desmoid-type fibromatosis; experiences from two countries
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract