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Published on: April 11, 2016
Cell-Free DNA Based Next-Generation Sequencing Does Not Differentiate Between Oligoprogression and Systemic
Pim Rozendal1, Hanneke Kievit2, Paul van der Leest1
1Department of Pathology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
Abstract:
Immune checkpoint inhibitors (ICIs) are a key treatment for advanced non-small cell lung cancer (NSCLC), but most patients will ultimately experience disease progression due to acquired resistance to ICI. Clinically, it is relevant to differentiate between systemic progression (SP) and oligoprogression (OP). Following SP, ICI treatment is usually discontinued, while in OP, patients are preferably treated with local ablative treatment with continuation of the ICI treatment. However, with progressive disease, it remains difficult to differentiate between true OP or SP. Circulating tumor DNA (ctDNA) analysis provides an accurate real-time reflection of the tumor burden. It remains elusive if ctDNA abundance and/or dynamics can discriminate between OP and SP. Therefore, the aim of this exploratory cohort study is to evaluate whether the sequential molecular tumor profiling of ctDNA is suitable for discriminating between true OP and SP in advanced NSCLC. Patients with stage III/IV NSCLC showing progression after ≥3 months of ICI were included. OP was defined retrospectively by RECIST response ≥ 6 months after local treatment and continued ICIs. Serial plasma samples were analyzed using the AVENIO ctDNA Expanded NGS assay targeting 77 cancer-related genes. Twenty patients (6 OP, 14 SP) were included. Somatic alterations were detected in 16 patients (median 4 mutations). No significant differences in baseline ctDNA levels, changes at progression, or mutation patterns were observed between OP and SP. Although ctDNA levels generally decreased early after the start of ICI treatment, and were increased at disease progression, mutational profiles of the 77 genes using the AVENIO Expanded ctDNA panel did not distinguish OP from SP.
Insights
Distinguishing between systemic progression and oligoprogression in advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) is crucial. This study found that circulating tumor DNA (ctDNA) analysis did not differentiate between these two progression types in NSCLC patients.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Immune checkpoint inhibitors (ICIs) are vital for advanced non-small cell lung cancer (NSCLC) but acquired resistance leads to disease progression.
- Differentiating systemic progression (SP) from oligoprogression (OP) is clinically significant for treatment decisions in NSCLC patients on ICI therapy.
- Circulating tumor DNA (ctDNA) offers real-time tumor burden assessment, but its utility in distinguishing OP from SP remains unclear.
Purpose of the Study:
- To investigate if sequential ctDNA molecular profiling can differentiate between true oligoprogression (OP) and systemic progression (SP) in advanced NSCLC patients treated with ICIs.
- To evaluate the diagnostic potential of ctDNA dynamics and mutational profiles in distinguishing progression patterns.
Main Methods:
- An exploratory cohort study included patients with stage III/IV NSCLC progressing after ≥3 months of ICI treatment.
- OP was retrospectively defined by RECIST response ≥ 6 months post-local treatment with continued ICIs.
- Serial plasma samples were analyzed using the AVENIO ctDNA Expanded NGS assay (77 genes).
Main Results:
- Six patients had OP and 14 had SP. Somatic alterations were detected in 16 patients.
- No significant differences in baseline ctDNA levels, changes at progression, or mutation patterns were observed between OP and SP groups.
- While ctDNA generally decreased with ICI treatment and increased at progression, mutational profiles did not distinguish OP from SP.
Conclusions:
- Sequential ctDNA profiling using the AVENIO Expanded NGS assay did not differentiate between oligoprogression and systemic progression in advanced NSCLC patients treated with ICIs.
- Further research is needed to identify reliable biomarkers for distinguishing progression patterns in NSCLC patients undergoing ICI therapy.
