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Expert Review of Molecular Diagnostics Jan 2021: Precision medicine is already a reality in oncology, since biomarker-driven therapies have clearly improved patient survival. Furthermore, a new, minimally invasive... (Review)
Review
: Precision medicine is already a reality in oncology, since biomarker-driven therapies have clearly improved patient survival. Furthermore, a new, minimally invasive strategy termed 'liquid biopsy' (LB) has revolutionized the field by allowing comprehensive cancer genomic profiling through the analysis of circulating tumor DNA (ctDNA). However, its detection requires extremely sensitive and efficient technologies. A powerful molecular tool based on the principle of 'divide and conquer' has emerged to solve this problem. Thus, digital PCR (dPCR) allows absolute and accurate quantification of target molecules.: In this review we will discuss the fundamentals of dPCR and the most common approaches used for partition of samples and quantification. The advantages and limitations of dPCR will be mentioned in the context of LB in oncology.: In our opinion, dPCR has proven to be one of the most sensitive methods available for LB analysis, albeit some aspects such as its capacity of multiplexing and protocol standardization still require further improvements. Furthermore, the increasing sensitivities and lower costs of next generation sequencing (NGS) methods position dPCR as a confirmatory and complementary technique for NGS results which will likely prove to be very useful for treatment monitoring and assessing minimal residual disease.
Topics: Humans; Liquid Biopsy; Neoplasm, Residual; Polymerase Chain Reaction
PubMed: 33305634
DOI: 10.1080/14737159.2021.1860759 -
Current Oncology Reports Nov 2021There has been a huge development in the assessment of malignancies through liquid biopsies last years, especially for NSCLC, where its use has become part of clinical... (Review)
Review
PURPOSE OF REVIEW
There has been a huge development in the assessment of malignancies through liquid biopsies last years, especially for NSCLC, where its use has become part of clinical practice in some settings. We aim to summarize current evidence about minimal residual disease and its use in lung cancer.
RECENT FINDINGS
Recent studies using ctDNA in NSCLC but also in other types of cancer found strong correlations between the presence of ctDNA and the risk of disease progression or death after curative intent, despite current technical difficulties in performing this analysis (high sensitivity and specificity required). Evaluation of MRD in NSCLC, especially through ctDNA, could be an important point in future trial designs and could permit a more "targeted" adjuvant treatment.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Circulating Tumor DNA; Humans; Neoplasm Recurrence, Local; Neoplasm, Residual
PubMed: 34735646
DOI: 10.1007/s11912-021-01131-w -
Archives of Gynecology and Obstetrics Apr 2023Cavity shaving (CS) is a surgical technique used in the treatment of breast cancer (BC). It may reduce margin positivity in histologic assessment and consequently...
PURPOSE
Cavity shaving (CS) is a surgical technique used in the treatment of breast cancer (BC). It may reduce margin positivity in histologic assessment and consequently reduces re- excision rates in breast conserving surgery (BCS). The evidence for this assumption is described in the present review.
METHODS
A systematic review of relevant literature in English from January 1999 to April 2019 was conducted. The analysis included studies on CS and its effects on re-excision rates and margin positivity. We searched PubMed databases for relevant publications. In total, 22 studies were included in the present review.
RESULTS
The benefit from CS on re-excision rates and histologic margin positivity was variable. Out of 22 studies, 17 reported a reduction in both re-excision rates and histologic margin positivity in margin shaved patients. Four studies could not find a significant reduction of second surgeries and residual tumor rates. One study suggested that CS after BCS was superior to single BCS only in subgroup analysis in IDC tumors.
CONCLUSION
CS is a surgical technique that was shown to reduce re-excision and margin positivity rates in most of the studies. Furthermore, it can be a useful tool to assess specimen margins and detect multifocality.
Topics: Female; Humans; Breast Neoplasms; Carcinoma, Ductal, Breast; Mastectomy, Segmental; Neoplasm, Residual; Reoperation; Retrospective Studies
PubMed: 35593951
DOI: 10.1007/s00404-022-06512-5 -
Pathology, Research and Practice May 2023To review the latest research of minimal residual disease (MRD) in breast cancer as well as some emerging or potential detection methods for MRD in breast cancer. (Review)
Review
PURPOSE
To review the latest research of minimal residual disease (MRD) in breast cancer as well as some emerging or potential detection methods for MRD in breast cancer.
METHODS
Springer, Wiley, and PubMed databases were searched for the electronic literature with search terms of breast cancer, minimal residual disease, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, etc. RESULTS: Minimal residual disease refers to the occult micrometastasis or minimal residual lesions detected in patients with tumor after radical treatment. An early and dynamic monitoring of breast cancer MRD can contribute to clinical treatment decision-making, improving the diagnosis accuracy and prognosis of breast cancer patients. The updated knowledge regarding MRD in breast cancer diagnosis and prognosis were summarized, followed by the review of several emerging or potential detection technologies for MRD in breast cancer. With the developed new MRD detection technologies referring to CTCs, ctDNA and exosomes, the role of MRD in breast cancer has been growingly verified, which is expected to serve as a new risk stratification factor and prognostic indicator for breast cancer.
CONCLUSION
This paper systematically reviews the research progress, opportunities and challenges in MRD in breast cancer in recent years.
Topics: Female; Humans; Breast Neoplasms; DNA, Neoplasm; Neoplasm, Residual; Prognosis
PubMed: 37028109
DOI: 10.1016/j.prp.2023.154428 -
Journal of Neurological Surgery. Part... Jan 2021Maximal safe resection is an essential part of the multidisciplinary care of patients with glioblastoma. A growing body of data shows that gross total resection is an... (Review)
Review
Maximal safe resection is an essential part of the multidisciplinary care of patients with glioblastoma. A growing body of data shows that gross total resection is an independent prognostic factor associated with improved clinical outcome. The relationship between extent of glioblastoma (GB) resection and clinical benefit depends critically on the balance between cytoreduction and avoiding neurologic morbidity. The definition of the extent of tumor resection, how this is best measured pre- and postoperatively, and its relation to volume of residual tumor is still discussed. We review the literature supporting extent of resection in GB, highlighting the importance of a standardized definition and measurement of extent of resection to allow greater collaboration in research projects and trials. Recent developments in neurosurgical techniques and technologies focused on maximizing extent of resection and safety are discussed.
Topics: Brain Neoplasms; Glioblastoma; Humans; Neoplasm, Residual; Neurosurgical Procedures
PubMed: 33049795
DOI: 10.1055/s-0040-1701635 -
Klinicka Onkologie : Casopis Ceske a... 2021Nowadays, modern treatment methods for cancer patients are based on targeting specific molecules involved in cellular signaling system associated with tumor initiation... (Review)
Review
BACKGROUND
Nowadays, modern treatment methods for cancer patients are based on targeting specific molecules involved in cellular signaling system associated with tumor initiation and progression. The success of such approach depends on a correctly chosen dia-gnostic test with high sensitivity that identifies the occurrence and level of bio-markers in patients to select those who will respond and benefit from the treatment. The development of new technologies and the upgrades of the known ones contribute to the innovations in molecular characterization of cancer, which allows the detection of patients mutational status with high sensitivity and specificity.
PURPOSE
Here, we discuss the utilization of the third-generation type of polymerase chain reaction (PCR), droplet digital PCR (ddPCR), in the molecular dia-gnostics of oncology diseases. According to the studies reported in our review, ddPCR represents a promising tool in genetic profiling of cancer patients. Therefore, the optimization and precise validation may enable gradual implementation of ddPCR into clinical practice in the field of oncology.
Topics: Humans; Neoplasm, Residual; Neoplasms; Polymerase Chain Reaction
PubMed: 33657817
DOI: 10.48095/ccko202133 -
Journal of Nanobiotechnology Mar 2022Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic...
Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1-π-A-D2-R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes.
Topics: Humans; Multifunctional Nanoparticles; Nanoparticles; Neoplasm, Residual; Optical Imaging; Theranostic Nanomedicine
PubMed: 35305654
DOI: 10.1186/s12951-022-01325-9 -
Journal of Cellular and Molecular... Aug 2021Major advances in the field of genomic technologies have led to an improvement in cancer diagnosis, classification and prognostication. However, many cancers remain... (Review)
Review
Major advances in the field of genomic technologies have led to an improvement in cancer diagnosis, classification and prognostication. However, many cancers remain incurable due to the development of drug resistance, minimal residual disease (MRD) and disease relapse, highlighting an incomplete understanding of the mechanisms underlying these processes. In recent years, the impact of non-genetic factors on neoplastic transformations has increasingly been acknowledged, and growing evidence suggests that low oxygen (O ) levels (ie hypoxia) in the tumour microenvironment play a critical role in the development and treatment of cancer. As a result, there is a growing need to develop research tools capable of reproducing physiologically relevant O conditions encountered by cancer cells in their natural environments in order to gain in-depth insight into tumour cell metabolism and function. In this review, the authors highlight the importance of hypoxia in the pathogenesis of malignant diseases and provide an overview of novel engineering tools that have the potential to further drive this evolving, yet technically challenging, field of cancer research.
Topics: Bioengineering; Humans; Hypoxia; Neoplasm, Residual; Neoplasms; Neoplastic Stem Cells; Tumor Microenvironment
PubMed: 34213838
DOI: 10.1111/jcmm.16759 -
Pancreatology : Official Journal of the... Dec 2021The pathologic assessments of tumor response after neoadjuvant chemoradiotherapy (NACRT) are critical to improving the prognostic stratification for patients with...
BACKGROUND
The pathologic assessments of tumor response after neoadjuvant chemoradiotherapy (NACRT) are critical to improving the prognostic stratification for patients with pancreatic ductal adenocarcinoma (PDAC). Here we clarified the utility of our new grading system based on the area of residual tumor (ART) as compared to existing systems, such as the College of American Pathologists (CAP) and MD Anderson (MDA) score.
METHODS
Eight reviewers individually evaluated the tumor regression grade of 30 patients with PDAC based on three types of grading systems. The interobserver concordance and clinicopathological characteristics were compared between the three systems.
RESULTS
The interobserver concordance (kappa value) of the ART, CAP, and MDA score were 0.61, 0.48, and 0.53, respectively. Discrepant cases, which were 27% of the cases, exhibited smaller tumor and tumor bed sizes than concordant cases. The reduction in tumor size evaluated by microscopy showed a correlation with the rate of change in carcinoembryonic antigen (CEA) level, CA19-9 level, and tumor size on computed tomography (CT). The ART score was correlated with the tumor size on CT before and after NACRT and disease-free survival. The CAP and MDA scores were not associated with prognosis.
CONCLUSION
The ART grading system may be the most practical system to assess the tumor response in post-NACRT resections of PDAC.
Topics: Carcinoma, Pancreatic Ductal; Humans; Neoadjuvant Therapy; Neoplasm, Residual; Pancreatic Neoplasms; Prognosis; Reproducibility of Results; Retrospective Studies
PubMed: 34563448
DOI: 10.1016/j.pan.2021.09.006 -
Cancer Medicine Aug 2023Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection, which can identify disease relapse ahead of radiological imaging, has shown promising...
BACKGROUND
Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection, which can identify disease relapse ahead of radiological imaging, has shown promising performance. The objective of this study was to develop and validate OriMIRACLE S (Minimal Residual Circulating Nucleic Acid Longitudinal Detection in Solid Tumor), a highly sensitive and specific tumor-informed assay for MRD detection.
METHODS
Tumor-specific somatic single nucleotide variants (SNVs) were identified via whole exome sequencing of tumor tissue and matched germline DNA. Clonal SNVs were selected using the OriSelector algorithm for patient-specific, multiplex PCR-based NGS assays in MRD detection. Plasma-free DNA from patients with gastrointestinal tumors prior to and following an operation, and during monitoring, were ultradeep sequenced.
RESULTS
The detection of three positive sites was sufficient to achieve nearly 100% overall sample level sensitivity and specificity and was determined by calculating binomial probability based on customized panels containing 21 to 30 variants. A total of 127 patients with gastrointestinal tumors were enrolled in our study. Preoperatively, MRD was positive in 18 of 26 patients (69.23%). Following surgery, MRD was positive in 24 of 82 patients (29.27%). The positivity rate for MRD was 33.33% (n = 18) for gastric adenocarcinoma and 32.26% (n = 62) for colorectal cancer. Twenty (20) of 59 patients (34.48%) experienced a change in MRD status over the monitoring period. Patients 8 and 31 responded to 3 cycles of systemic therapy, after which levels for all ctDNA dropped below the detection limit. Patient 53 was an example of using MRD to predict tumor metastasis. Patient 55 showed a weak response to treatments first and respond to new systemic therapy after tumor progression.
CONCLUSION
Our study identified a sensitive and specific clinical detection method for low frequency ctDNA, and explored the detection performance of this technology in gastrointestinal tumors.
Topics: Humans; Circulating Tumor DNA; Neoplasm, Residual; Neoplasm Recurrence, Local; Gastrointestinal Neoplasms; Carcinoma
PubMed: 37602656
DOI: 10.1002/cam4.6286