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- W4366253516 abstract "<div>AbstractPurpose:<p>Patients with small-cell lung cancer (SCLC) have an exceptionally poor prognosis, calling for improved real-time noninvasive biomarkers of therapeutic response.</p>Experimental Design:<p>We performed targeted error-correction sequencing on 171 serial plasmas and matched white blood cell (WBC) DNA from 33 patients with metastatic SCLC who received treatment with chemotherapy (<i>n</i> = 16) or immunotherapy-containing (<i>n</i> = 17) regimens. Tumor-derived sequence alterations and plasma aneuploidy were evaluated serially and combined to assess changes in total cell-free tumor load (cfTL). Longitudinal dynamic changes in cfTL were monitored to determine circulating cell-free tumor DNA (ctDNA) molecular response during therapy.</p>Results:<p>Combined tiered analyses of tumor-derived sequence alterations and plasma aneuploidy allowed for the assessment of ctDNA molecular response in all patients. Patients classified as molecular responders (<i>n</i> = 9) displayed sustained elimination of cfTL to undetectable levels. For 14 patients, we observed initial molecular responses, followed by ctDNA recrudescence. A subset of patients (<i>n</i> = 10) displayed a clear pattern of molecular progression, with persistence of cfTL across all time points. Molecular responses captured the therapeutic effect and long-term clinical outcomes in a more accurate and rapid manner compared with radiographic imaging. Patients with sustained molecular responses had longer overall (log-rank <i>P</i> = 0.0006) and progression-free (log-rank <i>P</i> < 0.0001) survival, with molecular responses detected on average 4 weeks earlier than imaging.</p>Conclusions:<p>ctDNA analyses provide a precise approach for the assessment of early on-therapy molecular responses and have important implications for the management of patients with SCLC, including the development of improved strategies for real-time tumor burden monitoring.</p><p><i><a href=https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-23-0420 target=_blank>See related commentary by Pellini and Chaudhuri, p. 2176</a></i></p></div>" @default.
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- W4366253516 date "2023-06-13" @default.
- W4366253516 modified "2023-10-16" @default.
- W4366253516 title "Data from Dynamics of Sequence and Structural Cell-Free DNA Landscapes in Small-Cell Lung Cancer" @default.
- W4366253516 doi "https://doi.org/10.1158/1078-0432.c.6605167" @default.
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