Microfluidic Chip-Based Cancer Diagnosis and Prediction of Relapse by Detecting Circulating Tumor Cells and Circulating Cancer Stem Cells

Detecting circulating tumor cells (CTCs) has been considered one of the best biomarkers in liquid biopsy for early diagnosis and prognosis monitoring in cancer. A major challenge of using CTCs is detecting extremely low-concentrated targets in the presence of high noise factors such as serum and hematopoietic cells. This review provides a selective overview of the recent progress in the design of microfluidic devices with optical sensing tools and their application in the detection and analysis of CTCs and their small malignant subset, circulating cancer stem cells (CCSCs). Moreover, discussion of novel strategies to analyze the differentiation of circulating cancer stem cells will contribute to an understanding of metastatic cancer, which can help clinicians to make a better assessment. We believe that the topic discussed in this review can provide brief guideline for the development of microfluidic-based optical biosensors in cancer prognosis monitoring and clinical applications.

Pretreatment Prediction of Relapse Risk in Patients with Osteosarcoma Using Radiomics Nomogram Based on CT: A Retrospective Multicenter Study

Objective. To develop and externally validate a CT-based radiomics nomogram for pretreatment prediction of relapse in osteosarcoma patients within one year. Materials and Methods. In this multicenter retrospective study, a total of 80 patients (training cohort: 63 patients from three hospitals; validation cohort: 17 patients from three other hospitals) with osteosarcoma, undergoing pretreatment CT between August 2010 and December 2018, were identified from multicenter databases. Radiomics features were extracted and selected from tumor regions on CT image, and then, the radiomics signature was constructed. The radiomics nomogram that incorporated the radiomics signature and clinical-based risk factors was developed to predict relapse risk with a multivariate Cox regression model using the training cohort and validated using the external validation cohort. The performance of the nomogram was assessed concerning discrimination, calibration, reclassification, and clinical usefulness. Results. Kaplan-Meier curves based on the radiomics signature showed a significant difference between the high-risk and the low-risk groups in both training and validation cohorts ( P < 0.001 and P = 0.015 , respectively). The radiomics nomogram achieved good discriminant results in the training cohort ( C -index: 0.779) and the validation cohort ( C -index: 0.710) as well as good calibration. Decision curve analysis revealed that the proposed model significantly improved the clinical benefit compared with the clinical-based nomogram ( P < 0.001 ). Conclusions. This multicenter study demonstrates that a radiomics nomogram incorporated the radiomics signature and clinical-based risk factors can increase the predictive value of the osteosarcoma relapse risk, which supports the clinical application in different institutions.

Ctdna Monitoring in Predicting Relapse of Primary Mediastinal B-Cell Lymphoma

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of aggressive B-cell lymphoma. The majority of relapses occur within the first few months resulting in a dismal prognosis, thus we need to identify the risk of early relapse. Circulating tumor DNA (ctDNA)-based response assessment may enable response adapted therapy and early prognostication. In this study, we aim to clarify the role of ctDNA-monitoring in early prediction of relapse. Methods: We retrospectively analyzed the characteristics of 38 patients with PMBCL. The genetic sequencing and ctDNA monitoring were conducted by target next-generation sequencing (NGS). Results: The median age was 32 years old and 26 (68.4%) were female. Most cases (31/38, 81.6%) were diagnosed with stage I or II disease and fourteen (36.8%) cases present with extranodal involvement. The 5-year PFS and OS for PMBCL patients were 65.7 and 72.1%, respectively. High IPI score were associated with poor survival by univariate analysis. The complete response (CR) rate and overall response rate of R-CHOP was similar to R-EPOCH (69.2% vs. 70.0%, P =1.000 and 84.6% vs. 95.0%, P =0.547, respectively), however the 5-year PFS and OS rate for R-EPOCH seems longer than those for the R-CHOP (PFS 82.9% vs. 53.8%, P=0.0569; OS 92.9% vs. 60.6%, P=0.0567). Radiotherapy was less delivered in the patients who received R-EPOCH than R-CHOP (5.0% vs.53.8%, P=0.003) and had no impact on prognosis. We performed genetic sequencing on twenty-three cases. STAT6(15/23, 65.2%), SOCS1(13/23, 56.5%), TNFAIP3(13/23, 56.5%) were the most common affected genes in both response and refractory/relapsed patients. Cell cycle, FoxO signaling pathway and TNF signaling pathway were more frequently involved in refractory patients. ctDNA monitoring was conducted in 16 cases and fifteen cases show undetectable ctDNA after a median of 2 (range from 1 to 5) cycles and one refractory case presented with durable positive ctDNA. Among 4 relapse cases, 3 had prior detectable ctDNA half a month earlier before imaging manifestations of relapse. Regarding prediction of relapse, positive predictive value of ctDNA is 100%. Conclusions: Intensive induction chemotherapy can improve prognosis of PMBCL and ctDNA precisely predicted relapse. As most cases relapse within a few months, ctDNA-monitoring is crucial to improve prognosis. Disclosures No relevant conflicts of interest to declare.