BACKGROUND AND AIMS: There is an urgent need for effective prognostic biomarkers to better stratify patients with advanced hepatocellular carcinoma (HCC) undergoing systemic therapy. Shallow whole-genome sequencing (sWGS) of cell-free DNA (cfDNA) is a cost-effective approach for assessing circulating tumour DNA (ctDNA), genomic alterations, and fragmentomic patterns. This study aimed to evaluate sWGS-derived biomarkers as predictors of outcomes in advanced HCC patients receiving systemic treatment. METHODS: Pretreatment plasma samples from 134 patients treated with either tyrosine kinase inhibitors (TKIs; n = 83) or immune checkpoint inhibitors (ICIs; n = 51) were analysed using sWGS. Tumour fraction (TF) and copy number alterations (CNAs) were derived using ichorCNA, while DNA fragmentation was assessed using the DELFI approach. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: High TF was significantly associated with shorter median PFS (3.0 vs. 10.6 months; p<0.001) and OS (7.8 vs. 21.6 months; p=0.02). High fragmentation similarly correlated with reduced PFS (4.7 vs. 10.7 months; p<0.001) and OS (13.1 vs. 22.3 months; p<0.001). In multivariate analysis within the ICI subgroup, high fragmentation and BCLC stage independently predicted shorter PFS and OS. High AFP levels, advanced BCLC stage, and larger tumours correlated with elevated TF. Frequent CNA gains were observed in chromosomal arms 1q and 8q. CONCLUSION: High TF and high fragmentation levels are associated with worse clinical outcomes in advanced HCC patients treated with systemic therapy, making them promising prognostic biomarkers to consider for guiding treatment decisions.
- Klíčová slova
- Circulating cell-free DNA, Circulating tumour DNA, Hepatocellular carcinoma, Immunotherapy, Shallow whole-genome sequencing, Tumour fraction, Tyrosine kinase inhibitors,
- MeSH
- cirkulující nádorová DNA * genetika krev MeSH
- dospělí MeSH
- hepatocelulární karcinom * genetika farmakoterapie patologie krev mortalita MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * genetika krev MeSH
- nádory jater * genetika farmakoterapie patologie krev mortalita MeSH
- prognóza MeSH
- sekvenování celého genomu * metody MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- variabilita počtu kopií segmentů DNA MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cirkulující nádorová DNA * MeSH
- inhibitory kontrolních bodů MeSH
- inhibitory proteinkinas MeSH
- nádorové biomarkery * MeSH
BACKGROUND: PSMA-targeted radioligand therapies (PSMA RLT) are an effective and safe option for metastatic castration-resistant prostate cancer, but responsive subtypes and their biomarkers are not fully defined. METHODS: Plasma samples for cell-free DNA (cfDNA) analysis were collected from 17 patients undergoing [¹⁷⁷Lu]Lu-PSMA-I&T. CfDNA underwent whole-genome sequencing to establish copy number variation (CNV) profiles and circulating-tumor DNA (ctDNA) levels and compared between prostate-specific antigen (PSA) response- and 1-year overall survival (1YOS) groups. RESULTS: Non-responders exhibited higher degrees of cfDNA CNV burden (P = 0.048) and higher ctDNA levels (P = 0.036) than responders. Both markers allowed for the differentiation of responses (AUC: 0.792, 0.806) and 1YOS (AUC: 0.778, 0.847). CONCLUSION: Unresponsive patients exhibited higher levels of cfDNA genomic instability and ctDNA levels, warranting genome-wide CNV profiling studies next to targeted approaches for mechanistic radiobiological insights and their value as response biomarkers for PSMA RLTs.
- Klíčová slova
- CNV, CtDNA, Liquid biopsy, PSMA RLT, Prostate cancer,
- MeSH
- cirkulující nádorová DNA * krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- lutecium aplikace a dávkování MeSH
- míra přežití MeSH
- nádory prostaty rezistentní na kastraci * krev genetika mortalita radioterapie MeSH
- nestabilita genomu * MeSH
- prostatický specifický antigen krev MeSH
- radiofarmaka * aplikace a dávkování MeSH
- retrospektivní studie MeSH
- sekvenování celého genomu MeSH
- senioři MeSH
- tekutá biopsie MeSH
- variabilita počtu kopií segmentů DNA MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cirkulující nádorová DNA * MeSH
- lutecium MeSH
- Pluvicto MeSH Prohlížeč
- prostatický specifický antigen MeSH
- radiofarmaka * MeSH
INTRODUCTION: Pathogenesis of large B-cell lymphomas (LBCL) and follicular lymphomas (FL) is a multistep process associated with the development of diverse DNA alterations and consequent deregulation of critical cellular processes. Detection of tumor-associated mutations within non-tumor compartments (mainly plasma) is the basis of the 'liquid biopsy' concept. Apart from tumor mutational profiling, quantitative analysis of circulating tumor DNA (ctDNA) allows longitudinal assessment of tumor burden. ctDNA-based technologies provide a new tool for tumor diagnostics and treatment personalization. AREAS COVERED: Our review provides a comprehensive overview and summary of available ctDNA studies in LBCL and FL. The accuracy of ctDNA-based detection of lymphoma-associated DNA alterations is correlated to known LBCL and FL molecular landscape. Additionally, we summarized available evidence that supports and justifies the clinical use of ctDNA for lymphoma risk stratification, treatment response evaluation, and treatment response-adapted therapy. Lastly, we discuss other clinically important ctDNA applications: monitoring of lymphoma clonal evolution within resistance and/or relapse development and utilization of ctDNA for diagnostics in non-blood fluids and compartments (e.g. cerebrospinal fluid in primary CNS lymphomas). EXPERT OPINION: Despite certain challenges, including methodological standardization, ctDNA holds promise to soon become an integral part of lymphoma diagnostics and treatment management.
- Klíčová slova
- Circulating tumor DNA, DLBCL, FL, ctDNA, follicular lymphoma, large B-cell lymphoma, liquid biopsy, risk factors,
- MeSH
- cirkulující nádorová DNA * krev genetika MeSH
- difúzní velkobuněčný B-lymfom * diagnóza genetika terapie krev MeSH
- folikulární lymfom * diagnóza genetika terapie krev MeSH
- lidé MeSH
- mutace MeSH
- nádorové biomarkery * krev genetika MeSH
- prognóza MeSH
- tekutá biopsie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cirkulující nádorová DNA * MeSH
- nádorové biomarkery * MeSH
INTRODUCTION: Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) is a rare but serious condition requiring accurate diagnostics. Cerebrospinal fluid (CSF) analysis plays a crucial role, particularly in cases where biopsy is not feasible, and imaging is inconclusive. AREAS COVERED: Chemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including circulating tumor DNA (ctDNA) analysis and microRNAs (miRNAs), are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data.This review examines both traditional and emerging methods for CSF analysis in diagnosing CNS involvement in DLBCL. Conventional approaches such as cytomorphology, flow cytometry, and biochemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including ctDNA analysis and miRNAs, are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data. EXPERT OPINION: Advancements in CSF biomarker analysis are improving the diagnosis of CNS lymphoma, aiding early detection and personalized treatment approaches. However, further research and broader clinical validation are necessary for their routine implementation.
- Klíčová slova
- IL-10, MYD88, Primary CNS lymphoma (PNSCL), cerebrospinal fluid (CSF), circulating tumor DNA (ctDNA), cytomorphology, flow cytometry (FCM), secondary CNS lymphoma (SCNCSL),
- MeSH
- cirkulující nádorová DNA mozkomíšní mok genetika MeSH
- diagnostické techniky molekulární metody MeSH
- difúzní velkobuněčný B-lymfom * diagnóza mozkomíšní mok genetika patologie MeSH
- interleukin-10 genetika mozkomíšní mok MeSH
- lidé MeSH
- meningeální nádory * diagnóza mozkomíšní mok genetika MeSH
- mikro RNA genetika mozkomíšní mok MeSH
- mutace MeSH
- myeloidní diferenciační faktor 88 genetika MeSH
- nádorové biomarkery * mozkomíšní mok genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cirkulující nádorová DNA MeSH
- interleukin-10 MeSH
- mikro RNA MeSH
- MYD88 protein, human MeSH Prohlížeč
- myeloidní diferenciační faktor 88 MeSH
- nádorové biomarkery * MeSH
BACKGROUND: To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa). METHODS: 122 PCa patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried. PET scans were qualitatively and quantitatively assessed. PSA and meth-ctDNA markers were compared to PET findings, and their relative prognostic value was evaluated. RESULTS: PSA discriminated best between negative and tumor-indicative PET scans in all (AUC 0.77) and hormone-sensitive (hsPC) patients (0.737). In castration-resistant PCa (CRPC), the meth-ctDNA marker KLF8 performed best (AUC 0.824). CHST11 differentiated best between non- and metastatic scans (AUC 0.705) overall, KLF8 best in hsPC and CRPC (AUC 0.662, 0.85). Several meth-ctDNA markers correlated low to moderate with the tumor volume in all (5/8) and CRPC patients (6/8), while PSA levels correlated moderately to strongly with the tumor volume in all groups (all p < 0.001). CRPC overall survival was independently associated with LDAH and PSA (p = 0.0168, p < 0.001). CONCLUSION: The studied meth-ctDNA markers are promising for the minimally-invasive detection and prognostication of CRPC but do not allow for clinical characterization of hsPC. Prospective studies are warranted for their use in therapy response and outcome prediction in CRPC and potential incremental value for PCa monitoring in PSA-low settings.
- Klíčová slova
- DNA methylation, Epigenetics, PET/CT, PSMA, Prostate cancer, cfDNA,
- MeSH
- cirkulující nádorová DNA * krev genetika MeSH
- izotopy gallia MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA * MeSH
- nádorové biomarkery * genetika krev MeSH
- nádory prostaty * genetika diagnostické zobrazování krev MeSH
- PET/CT * metody MeSH
- prognóza MeSH
- prostatický specifický antigen krev MeSH
- průřezové studie MeSH
- radioizotopy galia MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- cirkulující nádorová DNA * MeSH
- gallium 68 PSMA-11 MeSH Prohlížeč
- izotopy gallia MeSH
- nádorové biomarkery * MeSH
- prostatický specifický antigen MeSH
- PSMA-11 MeSH Prohlížeč
- radioizotopy galia MeSH
High-grade B-cell lymphomas (HGBCLs) are aggressive blood cancers with a severe disease course, especially when the central nervous system (CNS) is involved. Standard histological examination depends on tissue availability and is currently supplemented with molecular tests, as the status of MYC, BCL2, or BCL6 gene rearrangements is required for proper lymphoma classification. This case report demonstrates the relevance of cerebrospinal fluid (CSF) cell-free DNA testing by integrative next-generation sequencing (NGS) panel. The benefit of this approach resided in tumor genotyping alongside the proof of CNS progression despite MRI negativity, revealing a clonal relationship with the primary tumor lesion. In addition, our strategy allowed us to classify the tumor as DLBCL/HGBL-MYC/BCL2 entity. In clinical practice, such a minimally invasive approach provides a more sensitive tool than standard imaging and cell analyzing techniques, enabling more accurate disease monitoring and relapse prediction in particular cases.
- Klíčová slova
- Cell-free DNA, Central nervous system involvement, High-grade B-cell lymphoma, Integrative diagnostics, Next-generation sequencing,
- MeSH
- B-buněčný lymfom * genetika patologie MeSH
- cirkulující nádorová DNA * genetika mozkomíšní mok MeSH
- difúzní velkobuněčný B-lymfom * genetika patologie mozkomíšní mok diagnóza MeSH
- lidé MeSH
- lokální recidiva nádoru genetika patologie MeSH
- magnetická rezonanční tomografie MeSH
- nádorové biomarkery * genetika mozkomíšní mok MeSH
- nádory centrálního nervového systému * genetika patologie MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- cirkulující nádorová DNA * MeSH
- nádorové biomarkery * MeSH
Gliomas are the most common brain tumor type in children and adolescents. To date, diagnosis and therapy monitoring for these tumors rely on magnetic resonance imaging (MRI) and histopathological as well as molecular analyses of tumor tissue. Recently, liquid biopsies (LB) have emerged as promising tool for diagnosis and longitudinal tumor assessment potentially allowing for a more precise therapeutic management. However, the optimal strategy for monitoring gliomas by LB remains to be determined. In this study, we analyzed circulating tumor DNA (ctDNA) from 78 liquid biopsies (plasma n = 44, cerebrospinal fluid n = 34 (CSF)) of 35 glioma patients, determining H3F3A K28M (K27M) and BRAF V600E mutation allele frequency using droplet digital PCR (ddPCR). All results were correlated to clinically relevant parameters including diagnostic imaging and CSF aspiration site (ventricular vs lumbar) with respect to tumor localization. Regarding diagnostic accuracy, the calculated sensitivity score in the H3F3A K27M cohort was 84.61% for CSF and 73.68% for plasma. In the BRAF V600E cohort, we determined a sensitivity of 83.3% in plasma and 80% in CSF. The overall specificity was 100%. With respect to the CSF aspiration, the intra-operatively obtained CSF demonstrated 100% detection rate, followed by ventricular CSF obtained via Ommaya Reservoir/shunt puncture (93%) and CSF obtained via lumbar puncture (66%). Notably, this further correlated with the proximity of the CSF site to tumor localization. Longitudinal CSF monitoring demonstrated a good correlation to clinical and radiological disease evolution. Importantly, we show for the first time that monitoring BRAF V600E by ddPCR could serve as treatment response assessment in gliomas. In summary, our observation may inform recommendations with regard to location of CSF aspiration when incorporating LB into future treatment protocols.
- Klíčová slova
- CSF sampling site, Droplet digital PCR, Glioma, Liquid biopsy, Longitudinal monitoring, Targeted therapy,
- MeSH
- cirkulující nádorová DNA mozkomíšní mok genetika MeSH
- dítě MeSH
- dospělí MeSH
- gliom * genetika patologie diagnóza MeSH
- histony * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- nádorové biomarkery * genetika mozkomíšní mok MeSH
- nádory mozku * genetika diagnóza patologie MeSH
- předškolní dítě MeSH
- protoonkogenní proteiny B-Raf * genetika MeSH
- tekutá biopsie metody MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- BRAF protein, human MeSH Prohlížeč
- cirkulující nádorová DNA MeSH
- H3-3A protein, human MeSH Prohlížeč
- histony * MeSH
- nádorové biomarkery * MeSH
- protoonkogenní proteiny B-Raf * MeSH
Background/Objectives: Although the overall survival prognosis of patients in advanced stages of pancreatic ductal adenocarcinoma (PDAC) is poor, typically ranging from days to months from diagnosis, there are rare cases of patients remaining in therapy for longer periods of time. Early estimations of survival prognosis would allow rational decisions on complex therapy interventions, including radical surgery and robust systemic therapy regimens. Understandably, there is great interest in finding prognostic markers that can be used for patient stratification. We determined the role of various KRAS mutations in the prognosis of PDAC patients using biopsy samples and circulating tumor DNA. Methods: A total of 118 patients with PDAC, clinically confirmed by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNB), were included in the study. DNA was extracted from cytological slides following a standard cytology evaluation to ensure adequacy (viability and quantity) and to mark the tumor cell fraction. Circulating tumor DNA (ctDNA) was extracted from plasma samples of 45 patients in stage IV of the disease. KRAS mutations in exons 12 and 13 were detected by denaturing capillary electrophoresis (DCE), revealing a minute presence of mutation-specific heteroduplexes. Kaplan-Meier survival curves were calculated for individual KRAS mutation types. Results:KRAS mutations were detected in 90% of tissue (106/118) and 44% of plasma (20/45) samples. All mutations were localized at exon 2, codon 12, with G12D (GGT > GAT) being the most frequent at 44% (47/106) and 65% (13/20), followed by other types including G12V (GGT > GTT) at 31% (33/106) and 10% (2/20), G12R (GGT > CGT) at 17% (18/106) and 10% (2/20), G12C (GGT/TGT) at 5% (5/106) and 0% (0/20) and G12S (GGT/AGT) at 1% (1/106) and 5% (1/20) in tissue and plasma samples, respectively. Two patients had two mutations simultaneously (G12V + G12S and G12D + G12S) in both types of samples (2%, 2/106 and 10%, 2/20 in tissue and plasma samples, respectively). The median survival of patients with the G12D mutation in tissues was less than half that of other patients (median survival 101 days, 95% CI: 80-600 vs. 228 days, 95% CI: 184-602), with a statistically significant overall difference in survival (p = 0.0080, log-rank test), and furthermore it was less than that of all combined patients with other mutation types (101 days, 95% CI: 80-600 vs. 210 days, 95% CI: 161-602, p = 0.0166). For plasma samples, the survival of patients with this mutation was six times shorter than that of patients without the G12D mutation (27 days, 95% CI: 8-334 vs. 161 days, 95% CI: 107-536, p = 0.0200). In contrast, patients with detected KRAS G12R in the tissue survived nearly twice as long as other patients in the aggregate (286 days, 95% CI: 70-602 vs. 162 days, 95% CI: 122-600, p = 0.0374) or patients with other KRAS mutations (286 days, 95% CI: 70-602 vs. 137 days, 95% CI: 107-600, p = 0.0257). Conclusions: Differentiation of specific KRAS mutations in EUS-FNB and ctDNA (above all, the crucial G12D and G12R) is feasible in routine management of PDAC patients and imperative for assessment of prognosis.
- Klíčová slova
- EUS-FNB, KRAS, ctDNA, liquid biopsy, mutation type, pancreatic cancer, prognosis,
- MeSH
- biopsie tenkou jehlou pod endosonografickou kontrolou * MeSH
- cirkulující nádorová DNA genetika krev MeSH
- dospělí MeSH
- duktální karcinom slinivky břišní * genetika patologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- nádorové biomarkery genetika MeSH
- nádory slinivky břišní * genetika patologie mortalita MeSH
- prognóza MeSH
- protoonkogenní proteiny p21(ras) * genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tekutá biopsie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cirkulující nádorová DNA MeSH
- KRAS protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- protoonkogenní proteiny p21(ras) * MeSH
BACKGROUND: Circulating-tumor DNA (ctDNA) and prostate-specific membrane antigen (PSMA) ligand positron-emission tomography (PET) enable minimal-invasive prostate cancer (PCa) detection and survival prognostication. The present study aims to compare their tumor discovery abilities and prognostic values. METHODS: One hundred thirty men with confirmed PCa (70.5 ± 8.0 years) who underwent [68Ga]Ga-PSMA-11 PET/CT (184.8 ± 19.7 MBq) imaging and plasma sample collection (March 2019-August 2021) were included. Plasma-extracted cell-free DNA was subjected to whole-genome-based ctDNA analysis. PSMA-positive tumor lesions were delineated and their quantitative parameters extracted. ctDNA and PSMA PET/CT discovery rates were compared, and the prognostic value for overall survival (OS) was evaluated. RESULTS: PSMA PET discovery rates according to castration status and PSA ranges did differ significantly (P = 0.013, P < 0.001), while ctDNA discovery rates did not (P = 0.311, P = 0.123). ctDNA discovery rates differed between localized and metastatic disease (P = 0.013). Correlations between ctDNA concentrations and PSMA-positive tumor volume (PSMA-TV) were significant in all (r = 0.42, P < 0.001) and castration-resistant (r = 0.65, P < 0.001), however not in hormone-sensitive patients (r = 0.15, P = 0.249). PSMA-TV and ctDNA levels were associated with survival outcomes in the Logrank (P < 0.0001, P < 0.0001) and multivariate Cox regression analysis (P = 0.0023, P < 0.0001). CONCLUSION: These findings suggest that PSMA PET imaging outperforms ctDNA analysis in detecting prostate cancer across the whole spectrum of disease, while both modalities are independently highly prognostic for survival outcomes.
- Klíčová slova
- Liquid biopsy, PET/CT, PSMA, Prostate cancer, ctDNA,
- MeSH
- cirkulující nádorová DNA * krev genetika MeSH
- EDTA * analogy a deriváty MeSH
- izotopy gallia * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty * diagnostické zobrazování genetika krev MeSH
- oligopeptidy MeSH
- PET/CT * MeSH
- prognóza MeSH
- průřezové studie MeSH
- radioizotopy galia * MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- cirkulující nádorová DNA * MeSH
- EDTA * MeSH
- gallium 68 PSMA-11 MeSH Prohlížeč
- izotopy gallia * MeSH
- oligopeptidy MeSH
- PSMA-11 MeSH Prohlížeč
- radioizotopy galia * MeSH
BACKGROUND: To determine if circulating tumor DNA (ct-DNA) dynamics of epidermal growth factor receptor (EGFR) mutation in plasma can identify a subset of patients with EGFR-mutant (EGFR- m) non-small cell lung cancer (NSCLC) with inferior survival outcomes, we analyzed and compared survival outcomes among patients with and without baseline presence and early clearance of EGFR ct-DNA in plasma. MATERIAL AND METHODS: For 66 patients newly dia-gnosed with EGFR- m NSCLC, plasma samples were collected at baseline and 1st response assessment at 12-24 weeks for extraction of ct-DNA. Estimation of ct-DNA (EGFR exons 18, 19, 20 and 21) was done using droplet digital polymerase chain reaction (dd-PCR) on the QX200 ddPCR system (BioRad, USA). Patients with detectable EGFR ct-DNA at baseline (sample 1), with either undetectable or persistent detectable ct-DNA in sample 2 were classified as clearers and non-clearers, respectively. RESULTS: Fifty-three patients received 1st/ 2nd generation EGFR tyrosine kinase inhibitors (TKIs) and 13 received either 3rd generation TKI (osimertinib) or chemotherapy plus gefitinib. The baseline ct-DNA-positive group had more patients with extra thoracic disease (60.4 vs. 48.5%). For the entire cohort, there was no difference in median progression-free survival (PFS) among baseline ct-DNA-negative (13.57 months) vs. ct-DNA-positive patients (12.32 months) (HR 0.74). There was a significant improvement of PFS among early ct-DNA clearers vs. non-clearers (12.32 vs. 9.92 months; HR 0.57). For those treated with 1st/ 2nd generation EGFR TKIs, this improvement in median PFS among early ct-DNA clearers vs. non-clearers was more apparent (11.76 vs. 6.8 months; HR 0.34). CONCLUSIONS: Baseline detection of the presence of ct-DNA of EGFR mutation in plasma was not predictive of first-line PFS, but is associated with extra thoracic disease. Patients with EGFR mutation and persistence of ct-DNA at first follow-up have worse PFS and overall survival (OS) in comparison to those clearing the same in plasma, especially among those treated with 1st/ 2nd generation EGFR TKIs.
- Klíčová slova
- EGFR mutation, EGFR mutations, EGFR tyrosine kinase inhibitors, advanced non-small cell lung cancer, ct-DNA, mutant allele frequency,
- MeSH
- cirkulující nádorová DNA * krev genetika MeSH
- erbB receptory * genetika MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- nádory plic * genetika farmakoterapie mortalita MeSH
- nemalobuněčný karcinom plic * genetika farmakoterapie mortalita MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cirkulující nádorová DNA * MeSH
- EGFR protein, human MeSH Prohlížeč
- erbB receptory * MeSH
- inhibitory proteinkinas MeSH