Dynamic Changes in Circulating Tumor DNA During Chemoradiation for Locally Advanced Lung Cancer
| Autor: | John Calaway, Ace J. Hatch, Jordan A. Torok, Greg Jones, Corbin D. Jacobs, Eric Xanthopoulos, Chris R. Kelsey, Kyle Lafata, Andrew B. Nixon, Michael N. Corradetti, Christel Rushing |
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| Rok vydání: | 2019 |
| Předmět: |
lcsh:Medical physics. Medical radiology. Nuclear medicine
Oncology medicine.medical_specialty genetic structures lcsh:R895-920 Locally advanced Improved survival Thoracic Cancer lcsh:RC254-282 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Internal medicine Medicine Radiology Nuclear Medicine and imaging Lung cancer business.industry Concurrent chemoradiation lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Circulating tumor DNA Treatment modality 030220 oncology & carcinogenesis Baseline time business After treatment |
| Zdroj: | Advances in Radiation Oncology, Vol 4, Iss 4, Pp 748-752 (2019) Advances in Radiation Oncology |
| ISSN: | 2452-1094 |
| Popis: | Purpose Concurrent chemoradiation therapy (CRT) is the principal treatment modality for locally advanced lung cancer. Cell death due to CRT leads to the release of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) into the bloodstream, but the kinetics and characteristics of this process are poorly understood. We hypothesized that there could be clinically meaningful changes in cfDNA and ctDNA during a course of CRT for lung cancer. Methods and materials Multiple samples of plasma were obtained from 24 patients treated with CRT for locally advanced lung cancer to a mean dose of 66 Gy (range, 58-74 Gy) at the following intervals: before CRT, at weeks 2 and 5 during CRT, and 6 weeks after treatment. cfDNA was quantified, and a novel next generation sequencing (NGS) technique using enhanced tagged/targeted-amplicon sequencing was performed to analyze ctDNA. Results Patients for whom specific mutations in ctDNA were undetectable at the baseline time point had improved survival, and potentially etiologic driver mutations could be tracked throughout the course of CRT via NGS in multiple patients. We quantified the levels of cfDNA from patients before CRT, at week 2, week 5, and at 6 weeks after treatment. No differences were observed at weeks 2 and 5 of therapy, but we noted a significant increase in cfDNA in the posttreatment follow-up samples compared with samples collected before CRT (P = .05). Conclusions Dynamic changes in both cfDNA and ctDNA were observed throughout the course of CRT in patients with locally advanced lung cancer. Specific mutations with therapeutic implications can be identified and tracked using NGS methodologies. Further work is required to characterize the changes in cfDNA and ctDNA over time in patients treated with CRT and to assess the predictive and prognostic potential of this powerful technology. |
| Databáze: | OpenAIRE |
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