Solid tumour tissue has traditionally been used for cancer molecular diagnostics. Recently, biomarker assessment in blood or liquid biopsies has become relevant because it allows genotyping in a less invasive and costly manner. In addition, it is a very useful technique in cases with insufficient tumour samples. Recent data have shown that this method can provide the baseline molecular characteristics of the tumour and resistance changes that emerge during cancer treatment. In terms of diagnostic application, the platforms available for clinical use in lung cancer focus on the isolation and detection of circulating DNA (ctDNA) and generally cover a limited number of mutations in genes such as epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF, as well as anaplastic lymphoma kinase (ALK) rearrangements. In parallel, there are plasma genotyping platforms based on next-generation sequencing (NGS) techniques, which are much broader in scope, allowing multiple genes to be studied simultaneously in a more efficient manner. More recently, promising research scenarios for liquid biopsy have emerged, such as its utility for early diagnosis and evaluation of minimal residual disease after oncological treatment. In light of these advances, knowledge of the benefits and limitations of liquid biopsy, as well as awareness of emerging information on new indications for this technique in non-small cell lung cancer (NSCLC), are of paramount importance in developing more effective management strategies for patients with this neoplasm.

UNASSIGNED: Cervical cancers are mainly caused by an oncogenic HPV. For locally advanced stages, the standard treatment is radio-chemotherapy (RTCT) followed by brachytherapy. Nevertheless, the prognosis remains highly heterogeneous between patients.
UNASSIGNED: We investigated the prognostic value of HPV circulating tumor DNA (ctDNA) in locally advanced cervical cancers alongside that of Squamous Cell Carcinoma Antigen (SCC-A).
UNASSIGNED: This single-center retrospective study included patients treated in curative intent for an IB3 to IVA squamous cell cervical cancer. Quantification of HPV ctDNA in serum collected at diagnosis was performed using a multiplex digital PCR assay for the simultaneous detection of 8 HPV genotypes.
UNASSIGNED: Among the 97 patients included, 76 patients (78.4%) were treated by RTCT, followed by brachytherapy for 57 patients (60%). HPV ctDNA was detected in 59/97 patients at diagnosis (60.8%). This detection was associated with lymph node invasion (p=0.04) but not with tumor stage. A high level of SCC-A at diagnosis was associated with tumor stage (p=0.008) and lymph node invasion (p=0.012). In univariate analysis, better disease-free survival (DFS) was associated with optimal RTCT regimen (p=0.002), exposure to brachytherapy (p=0.0001) and a low SCC-A at diagnosis (continuous analysis, p=0.002). Exploratory analysis revealed that 3/3 patients (100%) whose HPV ctDNA was still detectable at the end of treatment relapsed, while 6/22 patients (27.3%) whose HPV ctDNA was negative at the end of treatment relapsed.
UNASSIGNED: HPV ctDNA detection at diagnosis of locally advanced cervical squamous cell carcinomas is frequent and related to node invasion, but not to DFS. The prognostic value of HPV ctDNA detection after treatment warrants specific studies.

UNASSIGNED: Microsatellite instability (MSI) is a genetic marker that is useful in the detection and treatment of Lynch syndrome (Sd). Although conventional techniques such as immunohistochemistry (IHC) and polymerase chain reaction (PCR) are the standards for MSI detection, the advent of next-generation sequencing (NGS) has offered new possibilities, especially with circulating DNA.
UNASSIGNED: We present the case of a 26-year-old patient with Lynch Sd and a BRAF-mutated metastatic colon cancer. The discordant MSI results between the conventional methods and NGS posed challenges in making treatment decisions. Subsequent NGS analysis revealed a high MSI status, leading to participation in an immunotherapy trial, with remarkable clinical response.
UNASSIGNED: This case emphasizes the importance of comprehensive molecular profiling and strong interdisciplinary collaborations, especially in cases with ambiguous MSI results.

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OBJECTIVE: To assess the efficacy of ctDNA measurement at different time intervals in predicting response and prognosis in patients diagnosed with locally advanced rectal cancer (LARC) who underwent neoadjuvant treatment prior to curative resection.
METHODS: English language randomized controlled trials and observational studies, published from 1946 to January 2024, comparing outcomes between ctDNA-positive and ctDNA-negative patients with LARC undergoing neoadjuvant treatment prior to curative surgical resection were included in the search. The search included Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews (CDSR).
RESULTS: Data for 1022 patients were analysed. Patients with positive ctDNA in the preoperative period had more than five times the risk of developing distant metastasis (RR [95% CI] 5.03 [3.31-7.65], p < 0.001), while those with positive ctDNA in the postoperative period had more than six times the risk (RR [95% CI] 6.17 [2.38-15.95], p < 0.001). There was no significant relationship between ctDNA status at baseline, pre-, or postoperative periods and achievement of pCR (RR [95% CI] 1.21 [0.86-1.7], 1.82 [0.94-3.55], 1.48 [0.78-2.82], p = 0.27, 0.08, and 0.23, respectively). However, patients with positive ctDNA in the pre- and postoperative periods had more than 13 and 12 times the risk of overall disease relapse after curative-intent treatment (RR [95% CI] 13.55 [7.12-25.81], 12.14 [3.19-46.14], p < 0.001), respectively.
CONCLUSIONS: ctDNA could potentially guide treatment and follow-up in LARC, predicting high-risk patients for disease relapse, allowing individualized surveillance and treatment strategies. Prospective studies are needed for standardization.

Obesity has become a global health concern in recent decades. Utilizing biomarkers presents a promising approach to comprehensively monitor the progress of obesity and its associated health conditions. This review aims to synthesize the available evidence on the correlation between cfDNA level and obesity and to provide insights into the applicability of using cfDNA level as a tool for monitoring progression of obesity. Searches were performed in PubMed and Embase on April 1, 2022. Data and other relevant information were extracted and compiled into a structured table for further analysis. Among 1170 articles screened, 11 articles were included in this review and assessed qualitatively. The results demonstrated that existing evidence mainly focused on three populations, including healthy individuals, cancer patients and pregnant women. Majority of the studies on healthy individuals identified a significant association between cfDNA level and body weight status but not among cancer patients. Varying results were observed among pregnant women at different gestational trimesters. Our review summarized some preliminary evidence on the association between cfDNA level and obesity. More cohort studies in larger scale with comprehensive assessment have to be conducted to examine the applicability of cfDNA as a biomarker for severity and disease progression of obesity.

UNASSIGNED: Elevated circulating DNA (cirDNA) concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA release. We carried out the first prospective, multicenter study of the dynamics of cirDNA and neutrophil extracellular trap (NETs) markers during the perioperative period from 24 h before surgery up to 72 h after curative surgery in cancer patients.
UNASSIGNED: We examined the plasma levels of two NETs protein markers [myeloperoxidase (MPO) and neutrophil elastase (NE)], as well as levels of cirDNA of nuclear (cir-nDNA) and mitochondrial (cir-mtDNA) origin in 29 colon, prostate, and breast cancer patients and in 114 healthy individuals (HI).
UNASSIGNED: The synergistic analytical information provided by these markers revealed that: (i) NETs formation contributes to post-surgery conditions; (ii) post-surgery cir-nDNA levels were highly associated with NE and MPO in colon cancer [r = 0.60 (P < 0.001) and r = 0.53 (P < 0.01), respectively], but not in prostate and breast cancer; (iii) each tumor type shows a specific pattern of cir-nDNA and NETs marker dynamics, but overall the pre- and post-surgery median values of cir-nDNA, NE, and MPO were significantly higher in cancer patients than in HI.
UNASSIGNED: Taken as a whole, our work reveals the association of NETs formation with the elevated cir-nDNA release during a cancer patient\'s perioperative period, depending on surgical procedure or cancer type. By contrast, cir-mtDNA is poorly associated with NETs formation in the studied perioperative period, which would appear to indicate a different mechanism of release or suggest mitochondrial dysfunction.

Liquid biopsy has emerged as a valuable and minimally invasive tool for real-time detection of clinically actionable abnormalities across various cancer types. Its applicability is particularly compelling in the realm of prostate cancer, where novel therapeutic agents, including those targeting DNA repair systems, are under development. Despite these advancements, challenges persist in effectively screening for prostate cancer, enhancing risk stratification, and determining optimal approaches for treating advanced disease. Consequently, there is a pressing need for improved biomarkers to aid clinicians in decision-making within these contexts. Cell-free DNA and extracellular vesicle analysis have demonstrated promise in diagnosis, prognostication, assessment of treatment responses, and identification of emerging mechanisms of resistance. Nevertheless, obstacles must be addressed before liquid biopsies can be integrated into routine clinical practice. These challenges encompass preanalytical considerations such as sample collection and storage, methods of extracellular vesicle isolation and enrichment, and the need for enhanced interpretation of generated sequencing data. This review provides a comprehensive overview of current clinical opportunities in managing prostate cancer through blood-based liquid biopsy, highlighting the progress made, and acknowledging the challenges that remain. Additionally, we discuss the next steps required for the effective implementation of liquid biopsies in guiding personalized treatment strategies for prostate cancer.

[This corrects the article DOI: 10.3389/fmed.2023.1268748.].

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