Abstract
Purpose: The clinical potential of liquid biopsy in patients with advanced
cancer is real-time monitoring for early detection of treatment failure.
Our study aimed to investigate the clinical validity of circulating tumor
DNA (ctDNA) treatment monitoring in a real-life cohort of patients with
advanced non–small cell lung cancer (NSCLC).
Experimental Design: Patients with advanced or noncurative locally
advanced NSCLC were prospectively included in an exploratory study
(NCT03512847). Selected cancer-specific mutations were measured in
plasma by standard or uniquely designed droplet digital PCR assays before
every treatment cycle during first-line treatment until progressive disease
(PD). Correlation between an increase in ctDNA (= molecular progres-
sion) and radiologic PD was investigated, defined as lead time, and the
corresponding numbers of likely futile treatment cycles were determined.
Utility of ctDNA measurements in clarifying the results of nonconclusive
radiologic evaluation scans was evaluated.
Results: Cancer-specific mutations and longitudinal plasma sampling were
present in 132 of 150 patients. ctDNA was detectable in 88 (67%) of
132 patients treated by respectively chemotherapy (n = 41), immunotherapy
(n = 43), or combination treatment (n = 4). In 66 (90%) of 73 patients ex-
periencing PD, a ctDNA increase was observed with a median lead time of
1.5 months before radiologic PD. Overall, 119 (33%) of 365 treatment cy-
cles were administered after molecular progression. In addition, ctDNA
measurements could clarify the results in 38 (79%) of 48 nonconclusive
radiologic evaluations.
Conclusions: ctDNA monitoring leads to earlier detection of treatment
failure, and clarifies the majority of nonconclusive radiologic evaluations,
giving the potential of sparing patients from likely futile treatments and
needless adverse events.
Significance: Treatment monitoring by ctDNA has the clinical potential
to reveal PD before radiologic evaluation and consequently spare patients
with advanced cancer from likely ineffective, costly cancer treatments and
adverse events.
cancer is real-time monitoring for early detection of treatment failure.
Our study aimed to investigate the clinical validity of circulating tumor
DNA (ctDNA) treatment monitoring in a real-life cohort of patients with
advanced non–small cell lung cancer (NSCLC).
Experimental Design: Patients with advanced or noncurative locally
advanced NSCLC were prospectively included in an exploratory study
(NCT03512847). Selected cancer-specific mutations were measured in
plasma by standard or uniquely designed droplet digital PCR assays before
every treatment cycle during first-line treatment until progressive disease
(PD). Correlation between an increase in ctDNA (= molecular progres-
sion) and radiologic PD was investigated, defined as lead time, and the
corresponding numbers of likely futile treatment cycles were determined.
Utility of ctDNA measurements in clarifying the results of nonconclusive
radiologic evaluation scans was evaluated.
Results: Cancer-specific mutations and longitudinal plasma sampling were
present in 132 of 150 patients. ctDNA was detectable in 88 (67%) of
132 patients treated by respectively chemotherapy (n = 41), immunotherapy
(n = 43), or combination treatment (n = 4). In 66 (90%) of 73 patients ex-
periencing PD, a ctDNA increase was observed with a median lead time of
1.5 months before radiologic PD. Overall, 119 (33%) of 365 treatment cy-
cles were administered after molecular progression. In addition, ctDNA
measurements could clarify the results in 38 (79%) of 48 nonconclusive
radiologic evaluations.
Conclusions: ctDNA monitoring leads to earlier detection of treatment
failure, and clarifies the majority of nonconclusive radiologic evaluations,
giving the potential of sparing patients from likely futile treatments and
needless adverse events.
Significance: Treatment monitoring by ctDNA has the clinical potential
to reveal PD before radiologic evaluation and consequently spare patients
with advanced cancer from likely ineffective, costly cancer treatments and
adverse events.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cancer Res Commun |
| Vol/bind | 2 |
| Udgave nummer | 10 |
| Sider (fra-til) | 1174-1187 |
| Antal sider | 14 |
| ISSN | 2767-9764 |
| DOI | |
| Status | Udgivet - 2022 |