-
EBioMedicine May 2023Liquid biopsy is a promising non-invasive alternative for cancer screening and minimal residual disease (MRD) detection, although there are some concerns regarding its...
Multi-omics integrated circulating cell-free DNA genomic signatures enhanced the diagnostic performance of early-stage lung cancer and postoperative minimal residual disease.
BACKGROUND
Liquid biopsy is a promising non-invasive alternative for cancer screening and minimal residual disease (MRD) detection, although there are some concerns regarding its clinical applications. We aimed to develop an accurate detection platform based on liquid biopsy for both cancer screening and MRD detection in patients with lung cancer (LC), which is also applicable to clinical use.
METHODS
We applied a modified whole-genome sequencing (WGS) -based High-performance Infrastructure For MultIomics (HIFI) method for LC screening and postoperative MRD detection by combining the hyper-co-methylated read approach and the circulating single-molecule amplification and resequencing technology (cSMART2.0).
FINDINGS
For early screening of LC, the LC score model was constructed using the support vector machine, which showed sensitivity (51.8%) at high specificity (96.3%) and achieved an AUC of 0.912 in the validation set prospectively enrolled from multiple centers. The screening model achieved detection efficiency with an AUC of 0.906 in patients with lung adenocarcinoma and outperformed other clinical models in solid nodule cohort. When applied the HIFI model to real social population, a negative predictive value (NPV) of 99.92% was achieved in Chinese population. Additionally, the MRD detection rate improved significantly by combining results from WGS and cSMART2.0, with sensitivity of 73.7% at specificity of 97.3%.
INTERPRETATION
In conclusion, the HIFI method is promising for diagnosis and postoperative monitoring of LC.
FUNDING
This study was supported by CAMS Innovation Fund for Medical Sciences, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Beijing Natural Science Foundation and Peking University People's Hospital.
Topics: Humans; Multiomics; Neoplasm, Residual; Lung Neoplasms; Genomics; Cell-Free Nucleic Acids; Biomarkers, Tumor
PubMed: 37027928
DOI: 10.1016/j.ebiom.2023.104553 -
Neurosurgery Clinics of North America Jan 2021This article discusses intraoperative imaging techniques used during high-grade glioma surgery. Gliomas can be difficult to differentiate from surrounding tissue during... (Review)
Review
This article discusses intraoperative imaging techniques used during high-grade glioma surgery. Gliomas can be difficult to differentiate from surrounding tissue during surgery. Intraoperative imaging helps to alleviate problems encountered during glioma surgery, such as brain shift and residual tumor. There are a variety of modalities available all of which aim to give the surgeon more information, address brain shift, identify residual tumor, and increase the extent of surgical resection. The article starts with a brief introduction followed by a review of with the latest advances in intraoperative ultrasound, intraoperative MRI, and intraoperative computed tomography.
Topics: Brain Neoplasms; Glioma; Humans; Monitoring, Intraoperative; Neoplasm, Residual; Neuronavigation; Neurosurgical Procedures
PubMed: 33223025
DOI: 10.1016/j.nec.2020.09.003 -
Trends in Cancer Jul 2022Genetic studies suggest that sequential dissemination from a primary metastasis, usually at the bone, is a major route of metastatic progression in early, radically... (Review)
Review
Genetic studies suggest that sequential dissemination from a primary metastasis, usually at the bone, is a major route of metastatic progression in early, radically resected cancer. Disseminated tumor cells (DTCs) can likely infiltrate but not grow, and may remain dormant once disseminated for extended intervals (from months to decades). The stationary nature of DTCs prevents them from being successfully treated as an asymptomatic residual disease in the adjuvant setting; critically, they can eventually relapse, adapt, and develop therapy resistance, causing incurable overt metastasis. Metastatic lesions usually first appear in one tissue, which invigorates metastatic cells for further dissemination to other organs, with a fatal outcome. Clinical and genetic data now indicate that metastatic lesions in one organ can seed secondary metastases in other organs: in other words, metastasis arising from metastasis. Herein we discuss recent insight into metastasis cell dormancy mechanisms, survival, communication with the local microenvironment, and eventual changes that endow DTCs with the capacity to expand and colonize to other metastatic sites.
Topics: Disease Progression; Humans; Neoplasm Recurrence, Local; Neoplasm, Residual; Tumor Microenvironment
PubMed: 35370115
DOI: 10.1016/j.trecan.2022.03.002 -
Current Hematologic Malignancy Reports Dec 2023The utility of analyzing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and disease in the bone marrow as an adjunctive tool in caring for hematologic... (Review)
Review
PURPOSE OF REVIEW
The utility of analyzing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and disease in the bone marrow as an adjunctive tool in caring for hematologic cancer patients is expanding. This holds true for lymphoma where these biomarkers are being explored as a means of genotyping and quantifying disease. Regarding the latter, they can be used to monitor measurable residual disease (MRD) during and after treatment. This holds potential for aiding clinical decisions amidst treatment, detecting earlier relapse, and improving prognostication. Here, we review the evidence to support these applications in a variety of lymphoma subtypes.
RECENT FINDINGS
Numerous clinical trials across a variety of lymphomas have demonstrated value in MRD monitoring. MRD monitoring is often prognostic for progression free survival (PFS) and even overall survival (OS) at several time points in a disease course, particularly when utilizing serial measurements. With regards to tailoring treatment, there are a growing number of trials examining MRD-adaptive treatment strategies to intensify or de-escalate treatment to individualize care. Lastly, MRD monitoring has been utilized successfully in detecting earlier relapse when compared to more standard methods of clinical surveillance such as radiographic assessment. Although not routinely implemented into clinical practice, MRD monitoring in lymphoma is helping shape the future landscape of this disease by aiding in prognostication, guiding therapy, and detecting earlier relapse. Steps to standardize and further examine this technology prospectively are being taken to bring MRD monitoring to the forefront of the field.
Topics: Humans; Neoplasm Recurrence, Local; Lymphoma; Prognosis; Circulating Tumor DNA; Recurrence; Neoplasm, Residual
PubMed: 37930608
DOI: 10.1007/s11899-023-00715-6 -
Current Oncology (Toronto, Ont.) May 2023In recent years, major advances in the understanding of acute myeloid leukemia (AML) pathogenesis, together with technological progress, have led us into a new era in... (Review)
Review
In recent years, major advances in the understanding of acute myeloid leukemia (AML) pathogenesis, together with technological progress, have led us into a new era in the diagnosis and follow-up of patients with AML. A combination of immunophenotyping, cytogenetic and molecular studies are required for AML diagnosis, including the use of next-generation sequencing (NGS) gene panels to screen all genetic alterations with diagnostic, prognostic and/or therapeutic value. Regarding AML monitoring, multiparametric flow cytometry and quantitative PCR/RT-PCR are currently the most implemented methodologies for measurable residual disease (MRD) evaluation. Given the limitations of these techniques, there is an urgent need to incorporate new tools for MRD monitoring, such as NGS and digital PCR. This review aims to provide an overview of the different technologies used for AML diagnosis and MRD monitoring and to highlight the limitations and challenges of current versus emerging tools.
Topics: Humans; Leukemia, Myeloid, Acute; Neoplasm, Residual; Prognosis; High-Throughput Nucleotide Sequencing; Mutation
PubMed: 37366878
DOI: 10.3390/curroncol30060395 -
Trends in Cancer Jul 2023Tumor recurrence following potentially curative therapy constitutes a major obstacle to achieving cures in patients with cancer. Recurrent tumors frequently arise from a... (Review)
Review
Tumor recurrence following potentially curative therapy constitutes a major obstacle to achieving cures in patients with cancer. Recurrent tumors frequently arise from a population of residual cancer cells - also referred to as minimal residual disease (RD) or persister cells - that survive therapy and persist for prolonged periods prior to tumor relapse. While there has been significant recent progress in deciphering tumor-cell-intrinsic pathways that regulate residual cancer cell survival and recurrence, much less is known about how the tumor microenvironment (TME) of residual tumors impacts persister cancer cells or tumor recurrence. In this review, we highlight recent studies exploring the regulation and function of immune cells in RD and discuss therapeutic opportunities to target immune cells in residual tumors.
Topics: Humans; Neoplasm, Residual; Neoplasm Recurrence, Local; Cell Line, Tumor; Cell Survival; Tumor Microenvironment
PubMed: 37150627
DOI: 10.1016/j.trecan.2023.04.001 -
Clinical Cancer Research : An Official... Jun 2022The prognostic significance of minimal residual disease (MRD) detection in multiple myeloma is well established. Understanding factors that predict for MRD negativity,...
The prognostic significance of minimal residual disease (MRD) detection in multiple myeloma is well established. Understanding factors that predict for MRD negativity, such as tumor burden, cytogenetic, and immune-related biomarkers, may enable us to improve outcome prediction at diagnosis, and in the future move toward tailored treatment approaches. See related article by Guerrero et al., p. 2598.
Topics: Biomarkers; Humans; Machine Learning; Multiple Myeloma; Neoplasm, Residual; Prognosis
PubMed: 35357437
DOI: 10.1158/1078-0432.CCR-22-0219 -
Medical Image Analysis Nov 2022An important challenge and limiting factor in deep learning methods for medical imaging segmentation is the lack of available of annotated data to properly train models....
An important challenge and limiting factor in deep learning methods for medical imaging segmentation is the lack of available of annotated data to properly train models. For the specific task of tumor segmentation, the process entails clinicians labeling every slice of volumetric scans for every patient, which becomes prohibitive at the scale of datasets required to train neural networks to optimal performance. To address this, we propose a novel semi-supervised framework that allows training any segmentation (encoder-decoder) model using only information readily available in radiological data, namely the presence of a tumor in the image, in addition to a few annotated images. Specifically, we conjecture that a generative model performing domain translation on this weak label - healthy vs diseased scans - helps achieve tumor segmentation. The proposed GenSeg method first disentangles tumoral tissue from healthy "background" tissue. The latent representation is separated into (1) the common background information across both domains, and (2) the unique tumoral information. GenSeg then achieves diseased-to-healthy image translation by decoding a healthy version of the image from just the common representation, as well as a residual image that allows adding back the tumors. The same decoder that produces this residual tumor image, also outputs a tumor segmentation. Implicit data augmentation is achieved by re-using the same framework for healthy-to-diseased image translation, where a residual tumor image is produced from a prior distribution. By performing both image translation and segmentation simultaneously, GenSeg allows training on only partially annotated datasets. To test the framework, we trained U-Net-like architectures using GenSeg and evaluated their performance on 3 variants of a synthetic task, as well as on 2 benchmark datasets: brain tumor segmentation in MRI (derived from BraTS) and liver metastasis segmentation in CT (derived from LiTS). Our method outperforms the baseline semi-supervised (autoencoder and mean teacher) and supervised segmentation methods, with improvements ranging between 8-14% Dice score on the brain task and 5-8% on the liver task, when only 1% of the training images were annotated. These results show the proposed framework is ideal at addressing the problem of training deep segmentation models when a large portion of the available data is unlabeled and unpaired, a common issue in tumor segmentation.
Topics: Humans; Deep Learning; Image Processing, Computer-Assisted; Neoplasm, Residual; Neural Networks, Computer; Magnetic Resonance Imaging
PubMed: 36208571
DOI: 10.1016/j.media.2022.102624 -
Clinical & Translational Oncology :... Dec 2020Radiotherapy is the treatment of choice for many cancer patients. Residual tumor leads to local recurrence after a period of an equilibrium created between... (Review)
Review
Radiotherapy is the treatment of choice for many cancer patients. Residual tumor leads to local recurrence after a period of an equilibrium created between proliferating, quiescent and dying cancer cells. The tumor microenvironment is a main obstacle for the efficacy of radiotherapy, as impaired blood flow leads to hypoxia, acidity and reduced accessibility of radiosensitizers. Eradication of remnant disease is an intractable clinical quest. After more than a century of research, anti-tumor immunity has gained a dominant position in oncology research and therapy. Immune cells play a significant role in the eradication of tumors during and after the completion of radiotherapy. The tumor equilibrium reached in the irradiated tumor may shift towards cancer cell eradication if the immune response is appropriately modulated. In the modern immunotherapy era, clinical trials are urged to standardize immunotherapy schemes that could be safely applied to improve clearance of the post-radiotherapy remnant disease.
Topics: Humans; Immunity; Immunotherapy; Neoplasm Recurrence, Local; Neoplasm, Residual; Neoplasms; Neovascularization, Pathologic; Radiation Tolerance; Radiation-Sensitizing Agents; Tumor Hypoxia; Tumor Microenvironment
PubMed: 32445035
DOI: 10.1007/s12094-020-02378-8 -
Expert Review of Molecular Diagnostics 2023The advance of diagnostics and treatments has greatly improved the prognosis of non-small cell lung cancer (NSCLC) patients. However, relapse and metastasis are still... (Review)
Review
INTRODUCTION
The advance of diagnostics and treatments has greatly improved the prognosis of non-small cell lung cancer (NSCLC) patients. However, relapse and metastasis are still common problems encountered by NSCLC patients who have achieved complete remission. Therefore, overcoming the challenge of relapse and metastasis is particularly important for improving the prognosis of NSCLC patients. Research has shown that minimal residual disease (MRD) was a potential source of tumor relapse and metastasis, and circulating tumor DNA (ctDNA) MRD has obvious advantages in predicting the relapse and metastasis of NSCLC and evaluating treatment effectiveness. Therefore, dynamic monitoring of MRD is of great significance for NSCLC patient management strategies.
AREAS COVERED
We have reviewed articles related to NSCLC MRD included in PubMed and describes the biological significance and historical context of MRD research, reasons for using ctDNA to evaluate MRD, and potential value and challenges of ctDNA MRD in assessing relapse and metastasis of NSCLC, ultimately guiding clinical therapeutic strategies and management.
EXPERT OPINION
The standardized scope of ctDNA MRD detection for NSCLC requires more clinical research evidence to minimize study differences, making it possible to include in the clinical staging as a reliable indicator.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Circulating Tumor DNA; Lung Neoplasms; Neoplasm, Residual; Recurrence; Biomarkers, Tumor
PubMed: 37702546
DOI: 10.1080/14737159.2023.2252334