Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
Cancer Sci ; 113(4): 1531-1534, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1779205

ABSTRACT

According to the current international guidelines, high-risk patients diagnosed with pathological T1 (pT1) colorectal cancer (CRC) who underwent complete local resection but may have risk of developing lymph node metastasis (LNM) are recommended additional intestinal resection with lymph node dissection. However, around 90% of the patients without LNM are exposed to the risk of being overtreated due to the insufficient pathological criteria for risk stratification of LNM. Circulating tumor DNA (ctDNA) is a noninvasive biomarker for molecular residual disease and relapse detection after treatments including surgical and endoscopic resection of solid tumors. The CIRCULATE-Japan project includes a large-scale patient-screening registry of the GALAXY study to track ctDNA status of patients with stage II to IV or recurrent CRC that can be completely resected. Based on the CIRCULATE-Japan platform, we launched DENEB, a new prospective study, within the GALAXY study for patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk stratification criteria for LNM. The aim of this study is to explore the ability of predicting LNM using ctDNA analysis compared with the standard pathological criteria. The ctDNA assay will build new evidence to establish a noninvasive personalized diagnosis in patients, which will facilitate tailored/optimal treatment strategies for CRC patients.


Subject(s)
Circulating Tumor DNA , Colorectal Neoplasms , Circulating Tumor DNA/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Humans , Liquid Biopsy , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prospective Studies , Retrospective Studies , Risk Factors
3.
JAMA Netw Open ; 4(9): e2124483, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1396814

ABSTRACT

Importance: The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. Objective: To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. Design, Setting, and Participants: This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. Exposures: mCRC. Main Outcomes and Measures: Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. Results: A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. Conclusions and Relevance: This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.


Subject(s)
Colorectal Neoplasms/pathology , Communicable Disease Control/organization & administration , Patient Acceptance of Health Care , Tumor Burden , Adult , Aged , Biomarkers, Tumor/genetics , COVID-19/epidemiology , Circulating Tumor DNA/blood , Clinical Trials, Phase II as Topic , Cohort Studies , Colorectal Neoplasms/mortality , Colorectal Neoplasms/therapy , Controlled Before-After Studies , Female , Humans , Male , Middle Aged , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2
4.
Cancer Sci ; 112(7): 2915-2920, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1294969

ABSTRACT

Adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival in patients with resected colorectal cancer. Potential utility of circulating tumor DNA (ctDNA) prior to and post surgery has been reported across various solid tumors. We initiated a new type of adaptive platform trials to evaluate the clinical benefits of ctDNA analysis and refine precision adjuvant therapy for resectable colorectal cancer, named CIRCULATE-Japan including three clinical trials. The GALAXY study is a prospectively conducted large-scale registry designed to monitor ctDNA for patients with clinical stage II to IV or recurrent colorectal cancer who can undergo complete surgical resection. The VEGA trial is a randomized phase III study designed to test whether postoperative surgery alone is noninferior to the standard therapy with capecitabine plus oxaliplatin for 3 months in patients with high-risk stage II or low-risk stage III colon cancer if ctDNA status is negative at week 4 after curative surgery in the GALAXY study. The ALTAIR trial is a double-blind, phase III study designed to establish the superiority of trifluridine/tipiracil as compared with placebo in patients with resected colorectal cancer who show circulating tumor-positive status in the GALAXY study. Therefore, CIRCULATE-Japan encompasses both "de-escalation" and "escalation" trials for ctDNA-negative and -positive patients, respectively, and helps to answer whether measuring ctDNA postoperatively has prognostic and/or predictive value. Our ctDNA-guided adaptive platform trials will accelerate clinical development toward further precision oncology in the field of adjuvant therapy. Analysis of ctDNA status could be utilized as a predictor of risk stratification for recurrence and to monitor the effectiveness of adjuvant chemotherapy. ctDNA is a promising, noninvasive tumor biomarker that can aid in tumor monitoring throughout disease management.


Subject(s)
Circulating Tumor DNA/blood , Colorectal Neoplasms/blood , Neoplasm Recurrence, Local/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/administration & dosage , Chemotherapy, Adjuvant , Colonic Neoplasms/blood , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colonic Neoplasms/therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Double-Blind Method , Humans , Japan , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Oxaliplatin/administration & dosage , Prospective Studies , Pyrrolidines/administration & dosage , Thymine/administration & dosage , Trifluridine/administration & dosage
5.
J Biomech ; 117: 110235, 2021 03 05.
Article in English | MEDLINE | ID: covidwho-1042535

ABSTRACT

Microfluidic devices can be thought of as comprising interconnected miniaturized compartments performing multiple experimental tasks individually or in parallel in an integrated fashion. Due to its small size, portability, and low cost, attempts have been made to incorporate detection assays into microfluidic platforms for diseases such as cancer and infection. Some of these technologies have served as point-of-care and sample-to-answer devices. The methods for detecting biomarkers in different diseases usually share similar principles and can conveniently be adapted to cope with arising health challenges. The COVID-19 pandemic is one such challenge that is testing the performance of both our conventional and newly-developed disease diagnostic technologies. In this mini-review, we will first look at the progress made in the past few years in applying microfluidics for liquid biopsy and infectious disease detection. Following that, we will use the current pandemic as an example to discuss how such technological advancements can help in the current health challenge and better prepare us for future ones.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , Liquid Biopsy/methods , Microfluidics/methods , Point-of-Care Testing , Biomarkers , Circulating Tumor DNA , Exosomes , Humans , Lab-On-A-Chip Devices , Machine Learning , Neoplasms/diagnosis , Neoplastic Cells, Circulating
6.
J Immunother Cancer ; 8(2)2020 08.
Article in English | MEDLINE | ID: covidwho-712954

ABSTRACT

To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3-12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4-7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in BRCA1 and BRCA2 in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Microsatellite Instability , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Biomarkers, Tumor/genetics , COVID-19 , Circulating Tumor DNA/blood , Coronavirus Infections , Humans , Liquid Biopsy , Male , Middle Aged , Mutation , Pandemics , Pneumonia, Viral , Prostatic Neoplasms/pathology
SELECTION OF CITATIONS
SEARCH DETAIL