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BMC Surgery Dec 2022Index cholecystectomy is insufficient for curing T3 incidental gallbladder cancer (IGC), and once residual cancer (RC) is found, the prognosis is often poor. The purpose...
BACKGROUND AND PURPOSE
Index cholecystectomy is insufficient for curing T3 incidental gallbladder cancer (IGC), and once residual cancer (RC) is found, the prognosis is often poor. The purpose of this study was to investigate the effect of RC on the prognosis and the optimal choice of adjuvant therapy for R0 reresection patients with T3 IGC.
METHODS
We retrospectively reviewed data from patients with T3 IGC who underwent radical reresection from January 2013 to December 2018. RC was defined as histologically proven cancer at reresection. Demographics and tumour treatment-related variables were analysed in correlation with RC and survival. Adjuvant (Adj) chemoradiotherapy (CRT) was correlated with overall survival (OS) and disease-free survival (DFS).
RESULTS
Of the 167 patients with IGC who underwent surgery, 102 underwent radical extended resection. Thirty-two (31.4%) RCs were found. Hepatic side tumours (T3h) and both side tumours (T3h + T3p) were associated with the presence of RC. In multivariate analysis, RC and lymph node metastasis were independent prognostic factors for DFS and OS (P < 0.05). RC was associated with a significantly shorter median OS (20 vs. 53 months; P < 0.01) and DFS (11 vs. 40 months; P < 0.001) despite R0 resection. For R0 reresection patients with RC and/or lymph node metastasis, Adj CRT significantly improved OS (P = 0.024).
CONCLUSION
Residual cancer and lymphatic metastasis are important factors for the poor prognosis of T3 IGC despite R0 resection, and these patients should actively receive adjuvant therapy.
Topics: Humans; Gallbladder Neoplasms; Neoplasm, Residual; Lymphatic Metastasis; Retrospective Studies; Prognosis; Neoplasm Staging
PubMed: 36577967
DOI: 10.1186/s12893-022-01869-5 -
Experimental Biology and Medicine... Feb 2018Liquid biopsy methodologies, for the purpose of plasma genotyping of cell-free DNA (cfDNA) of solid tumors, are a new class of novel molecular assays. Such assays are... (Review)
Review
Liquid biopsy methodologies, for the purpose of plasma genotyping of cell-free DNA (cfDNA) of solid tumors, are a new class of novel molecular assays. Such assays are rapidly entering the clinical sphere of research-based monitoring in translational oncology, especially for thoracic malignancies. Potential applications for these blood-based cfDNA assays include: (i) initial diagnosis, (ii) response to therapy and follow-up, (iii) tumor evolution, and (iv) minimal residual disease evaluation. Precision medicine will benefit from cutting-edge molecular diagnostics, especially regarding treatment decisions in the adjuvant setting, where avoiding over-treatment and unnecessary toxicity are paramount. The use of innovative genetic analysis techniques on individual patient tumor samples is being pursued in several advanced clinical trials. Rather than using a categorical treatment plan, the next critical step of therapeutic decision making is providing the "right" cancer therapy for an individual patient, including correct dose and timeframe based on the molecular analysis of the tumor in question. Per the 21st Century Cures Act, innovative clinical trials are integral for biomarker and drug development. This will include advanced clinical trials utilizing: (i) innovative assays, (ii) molecular profiling with cutting-edge bioinformatics, and (iii) clinically relevant animal or tissue models. In this paper, a mini-review addresses state-of-the-art liquid biopsy approaches. Additionally, an on-going advanced clinical trial for lung cancer with novelty through synergizing liquid biopsies, co-clinical trials, and advanced bioinformatics is also presented. Impact statement Liquid biopsy technology is providing a new source for cancer biomarkers, and adds new dimensions in advanced clinical trials. Utilizing a non-invasive routine blood draw, the liquid biopsy provides abilities to address perplexing issues of tumor tissue heterogeneity by identifying mutations in both primary and metastatic lesions. Regarding the assessment of response to cancer therapy, the liquid biopsy is not ready to replace medical imaging, but adds critical new information; for instance, through a temporal assessment of quantitative circulating tumor DNA (ctDNA) assay results, and importantly, the ability to monitor for signs of resistance, via emerging clones. Adjuvant therapy may soon be considered based on a quantitative cfDNA assay. As sensitivity and specificity of the technology continue to progress, cancer screening and prevention will improve and save countless lives by finding the cancer early, so that a routine surgery may be all that is required for a definitive cure.
Topics: Biomarkers, Tumor; Cell-Free Nucleic Acids; Clinical Decision-Making; DNA, Neoplasm; Genotype; Humans; Liquid Biopsy; Lung Neoplasms; Neoplasm, Residual; Precision Medicine
PubMed: 29405770
DOI: 10.1177/1535370217750087 -
Seminars in Oncology Nursing Dec 2019To review the current state of molecular and genetic profiling of acute myeloid leukemia (AML) and its implications. (Review)
Review
OBJECTIVE
To review the current state of molecular and genetic profiling of acute myeloid leukemia (AML) and its implications.
DATA SOURCE
Peer-reviewed journal articles.
CONCLUSION
Significant advances in the understanding of the pathology of acute myeloid leukemia have led to refined risk stratification of patients and application of novel targeted therapies based on genetic profiles. Minimal residual disease testing allows for highly sensitive disease surveillance that can be used to predict relapse and assess treatment response.
IMPLICATIONS FOR NURSING PRACTICE
Accurate prognostication and therapeutic decision-making for patients with acute myeloid leukemia is dependent on molecular profiling. Being knowledgeable of the implications of minimal residual disease testing is critical for patient-centered care.
Topics: Genetic Profile; Humans; Leukemia, Myeloid, Acute; Neoplasm, Residual; Peer Review, Research; Prognosis; Recurrence; Risk Assessment
PubMed: 31759819
DOI: 10.1016/j.soncn.2019.150957 -
Archives of Pathology & Laboratory... Aug 2013Cancer stem cells (CSCs) comprise a minor cell population in a tumor; however, they possess self-renewal capacity and are responsible for tumor recurrence and the... (Review)
Review
CONTEXT
Cancer stem cells (CSCs) comprise a minor cell population in a tumor; however, they possess self-renewal capacity and are responsible for tumor recurrence and the emerging issue of tumor resistance. Despite recent advances in the study of pathogenesis and mechanisms of CSC-mediated disease recurrence and multidrug resistance, many questions remain unanswered.
OBJECTIVES
To provide an overview of CSC theory and to describe major methods of CSC detection and isolation, with the emphasis on those techniques that are potentially relevant in clinical laboratory practice. Particular attention is given to CSC markers, such as cancer testis antigens, which could become promising targets in the development of immunotherapy in settings of minimal residual disease.
DATA SOURCES
The review is based on analysis of peer-reviewed literature cited in PubMed, as well as preliminary results of studies conducted in our laboratory.
CONCLUSIONS
Despite a lack of consensus in the scientific community on research methodology, CSCs have demonstrated significant potential as therapeutic targets in the treatment of cancer. Further research of CSC biology and markers will eventually lead to the development of novel therapeutic approaches for targeting these cells to treat resistant and recurrent tumors and minimal residual disease.
Topics: Animals; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Immunotherapy; Male; Neoplasm Recurrence, Local; Neoplasm, Residual; Neoplasms; Neoplastic Stem Cells; Prognosis
PubMed: 23153183
DOI: 10.5858/arpa.2012-0494-RA -
Med (New York, N.Y.) Oct 2021In this issue of Med, Sobesky et al. investigate the translational utility of sequencing cell-free DNA to describe genetic features of classic Hodgkin Lymphoma (HL) and...
In this issue of Med, Sobesky et al. investigate the translational utility of sequencing cell-free DNA to describe genetic features of classic Hodgkin Lymphoma (HL) and to evaluate minimal residual disease (MRD) for patients treated in a clinical trial.
Topics: Cell-Free Nucleic Acids; Clinical Trials as Topic; Hodgkin Disease; Humans; Neoplasm, Residual
PubMed: 35590203
DOI: 10.1016/j.medj.2021.09.006 -
Nature Reviews. Cancer Apr 2018Therapeutics that block kinases, transcriptional modifiers, immune checkpoints and other biological vulnerabilities are transforming cancer treatment. As a result, many... (Review)
Review
Therapeutics that block kinases, transcriptional modifiers, immune checkpoints and other biological vulnerabilities are transforming cancer treatment. As a result, many patients achieve dramatic responses, including complete radiographical or pathological remission, yet retain minimal residual disease (MRD), which results in relapse. New functional approaches can characterize clonal heterogeneity and predict therapeutic sensitivity of MRD at a single-cell level. Preliminary evidence suggests that iterative detection, profiling and targeting of MRD would meaningfully improve outcomes and may even lead to cure.
Topics: Drug Therapy; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasm, Residual; Precision Medicine; Treatment Outcome
PubMed: 29376520
DOI: 10.1038/nrc.2017.125 -
Methods in Molecular Biology (Clifton,... 2022Selection of the proper target is crucial for clinically relevant monitoring of minimal residual disease (MRD) in patients with acute lymphoblastic leukemia using the... (Review)
Review
Selection of the proper target is crucial for clinically relevant monitoring of minimal residual disease (MRD) in patients with acute lymphoblastic leukemia using the quantitation of clonal-specific immunoreceptor (immunoglobulin/T cell receptor) gene rearrangements. Consequently, correct interpretation of the results of the entire analysis is of utmost importance. Here we present an overview of the quality control measures that need to be implemented into the process of marker identification, selection, and subsequent quantitation of the MRD level.
Topics: Biomarkers; Humans; Immunoglobulins; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Quality Control
PubMed: 35622322
DOI: 10.1007/978-1-0716-2115-8_6 -
Molecular Diagnosis & Therapy Nov 2021The detection of circulating tumor DNA via liquid biopsy has become an important diagnostic test for patients with cancer. While certain commercial liquid biopsy... (Review)
Review
The detection of circulating tumor DNA via liquid biopsy has become an important diagnostic test for patients with cancer. While certain commercial liquid biopsy platforms designed to detect circulating tumor DNA have been approved to guide clinical decisions in advanced solid tumors, the clinical utility of these assays for detecting minimal residual disease after curative-intent treatment of nonmetastatic disease is currently limited. Predicting disease response and relapse has considerable potential for increasing the effective implementation of neoadjuvant and adjuvant therapies. As a result, many companies are rapidly investing in the development of liquid biopsy platforms to detect circulating tumor DNA in the minimal residual disease setting. In this review, we discuss the development and clinical implementation of commercial liquid biopsy platforms for circulating tumor DNA minimal residual disease detection of solid tumors. Here, we aim to highlight the technological features that enable highly sensitive detection of tumor-derived genomic alterations, the factors that differentiate these commercial platforms, and the ongoing trials that seek to increase clinical implementation of liquid biopsies using circulating tumor DNA-based minimal residual disease detection.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Genomics; Humans; Liquid Biopsy; Neoplasm Recurrence, Local; Neoplasm, Residual
PubMed: 34725800
DOI: 10.1007/s40291-021-00559-x -
Molecular Diagnosis & Therapy Jun 2019Circulating tumor DNA (ctDNA) is a component of cell-free DNA that is shed by malignant tumors into the bloodstream and other bodily fluids. Levels of ctDNA are... (Review)
Review
Circulating tumor DNA (ctDNA) is a component of cell-free DNA that is shed by malignant tumors into the bloodstream and other bodily fluids. Levels of ctDNA are typically low, particularly in patients with localized disease, requiring highly sophisticated methods for detection and quantification. Multiple liquid biopsy methods have been developed for ctDNA analysis in solid tumor malignancies and are now enabling detection and assessment of earlier stages of disease, post-treatment molecular residual disease (MRD), resistance to targeted systemic therapy, and tumor mutational burden. Understanding ctDNA biology, mechanisms of release, and clearance and size characteristics, in conjunction with the application of molecular barcoding and targeted error correction, have increased the sensitivity and specificity of ctDNA detection techniques. Combinatorial approaches including integration of ctDNA data with circulating protein biomarkers may further improve assay sensitivity and broaden the scope of ctDNA applications. Circulating viral DNA may be utilized to monitor disease in some virally induced malignancies. In spite of increasingly accurate methods of ctDNA detection, results need to be interpreted with caution given that somatic mosaicisms such as clonal hematopoiesis of indeterminate potential (CHIP) may give rise to genetic variants in the bloodstream unrelated to solid tumors, and the limited concordance observed between different commercial platforms. Overall, highly precise ctDNA detection and quantification methods have the potential to transform clinical practice via non-invasive monitoring of solid tumor malignancies, residual disease detection at earlier timepoints than standard clinical and/or imaging surveillance, and treatment personalization based on real-time assessment of the tumor genomic landscape.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Genomics; High-Throughput Nucleotide Sequencing; Humans; Liquid Biopsy; Molecular Diagnostic Techniques; Neoplasm, Residual; Neoplasms
PubMed: 30941670
DOI: 10.1007/s40291-019-00390-5 -
Genome Biology Aug 2014DNA fragments released from cancer cells into the blood can be used to generate molecular profiles of tumors. Non-invasive 'liquid biopsies' can be used to monitor... (Review)
Review
DNA fragments released from cancer cells into the blood can be used to generate molecular profiles of tumors. Non-invasive 'liquid biopsies' can be used to monitor minimal residual disease and detect the emergence of drug resistance.
Topics: Cell-Free System; DNA, Neoplasm; Drug Resistance, Neoplasm; Genotype; Humans; Neoplasm, Residual; Neoplasms
PubMed: 25222559
DOI: 10.1186/s13059-014-0449-4