Utility of circulating tumor DNA (ctDNA) versus tumor tissue clinical sequencing for enrolling patients (Pts) with advanced gastrointestinal (GI) cancer to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA Combined Analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Yoshiaki Nakamura ◽  
Hiroya Taniguchi ◽  
Hideaki Bando ◽  
Ken Kato ◽  
Taito Esaki ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tumor Tissue ◽  
Objective Response ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Tissue Samples ◽  
Combined Analysis ◽  
Clinical Sequencing ◽  
Gi Cancer

5 Background: Blood-based genomic profiling by ctDNA analysis has a promise to potentially identify actionable genomic alterations. However, utility of clinical sequencing with ctDNA compared with that with tumor tissue for enrolling cancer pts to matched clinical trials remains unclear. Herein we investigated the utility of ctDNA clinical sequencing by the SCRUM-Japan GI-SCREEN and GOZILA Combined Analysis. Methods: In the GI-SCREEN, tumor tissue samples of pts with advanced GI cancer were analyzed by a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay since Feb 2015. In the GOZILA, plasma samples of pts with advanced GI cancer were analyzed by an NGS-based ctDNA assay, Guardant360 since Feb 2018. Tests were performed centrally by CLIA-certified and CAP-accredited laboratories. Pts with actionable alterations were enrolled to matched company-sponsored or investigator-initiated clinical trials. Results: As of Apr 2019, test results were generated in 5,029 out of 5,743 pts (88%) in GI-SCREEN and 1,089 out of 1,103 pts (99%) in GOZILA ( P < 0.0001).Median turnaround time (TAT) was 35 days in GI-SCREEN and 12 days in GOZILA ( P < 0.0001). There were no differences in other baseline characteristics between GI-SCREEN and GOZILA. Proportion of enrolling matched clinical trials in GOZILA was significantly higher than that in GI-SCREEN (126 pts [2.2%] in GI-SCREEN vs. 60 pts [5.4%] in GOZILA, P < 0.0001). Median time from GI-SCREEN or GOZILA enrollment to clinical trial enrollment was 5.9 and 1.0 months (mo), respectively ( P < 0.0001). The objective response rate (ORR) and progression-free survival (PFS) were not significantly different (ORR: 17.5 vs. 16.7%, P = 1.00; median PFS: 2.8 vs. 2.0 mo, P = 0.24). Conclusions: Clinical sequencing with ctDNA having the advantage of the shorter TAT enrolled more pts with advanced GI cancer to matched clinical trials than those with tumor tissue, without compromising the efficacy. Clinical trial information: UMIN000029315.

Utility of circulating tumor DNA (ctDNA) versus tumor tissue genotyping for enrollment of patients with metastatic colorectal cancer (mCRC) to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA combined analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4071-4071
Author(s):  
Yoshiaki Nakamura ◽  
Hiroya Taniguchi ◽  
Hideaki Bando ◽  
Taito Esaki ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Objective Response ◽  
Progression Free Survival ◽  
Turnaround Time ◽  
Circulating Tumor Dna ◽  
Combined Analysis ◽  
Wide Range

4071 Background: We recently reported that ctDNA genotyping had advantages compared with tumor tissue testing in terms of enrollment to matched clinical trials across a wide range of GI cancers (Nakamura Y, et al. ASCO-GI 2020). Here, we investigated the utility of ctDNA genotyping in mCRC in a SCRUM-Japan GI-SCREEN and GOZILA combined analysis. Methods: In GI-SCREEN, tumor tissue genotyping was performed using a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay since Feb 2015. In GOZILA, NGS-based ctDNA genotyping was performed using Guardant360 since Feb 2018. All tests were conducted centrally in a CLIA-certified and CAP-accredited laboratory. Patients with actionable alterations were enrolled into matched company-sponsored or investigator-initiated interventional clinical trials. Results: As of Apr 2019, 2,791 mCRC patients (2,754 eligible for analysis) in GI-SCREEN and 470 (464 eligible for analysis) in GOZILA were enrolled. There were no significant differences in baseline patient characteristics between GI-SCREEN and GOZILA. Most of trials affiliated with GI-SCREEN (81%) or GOZILA (78%) targeted the RTK/RAS/RAF pathway. Compared with tumor testing, ctDNA genotyping significantly improved turnaround time (median, 12 vs. 34 days, P < 0.0001), sequencing success rate (96.1 vs. 92.3%, P = 0.002), and detection rate of actionable alterations (73.3 vs. 62.2%, P = 0.02). Among patients with actionable alterations, enrollment to matched clinical trials was achieved in 5.0% in GI-SCREEN and 12.1% in GOZILA ( P < 0.0001). Median time from enrollment in the respective screening study to enrollment in a matched clinical trial was 6.5 months in GI-SCREEN and 0.9 months in GOZILA, respectively ( P < 0.0001). Objective response rate and progression-free survival were similar in both groups (tissue vs. ctDNA; ORR: 18.8 vs. 17.1%, P = 1.00; median PFS: 2.2 vs. 2.2 months, HR=1.05 [95% CI, 0.71–1.55], P = 0.79). Conclusions: For patients with mCRC, ctDNA genotyping had advantages over tissue genotyping with shorter turnaround time and higher sequencing success and actionable alteration detection rate, which were associated with improved clinical trial enrollment without compromising the efficacy. Funding: SCRUM-Japan Funds. Clinical trial information: UMIN000029315 .

Utility of circulating tumor DNA (ctDNA) versus tumor tissue clinical sequencing for enrolling patients (pts) with advanced non-colorectal (non-CRC) gastrointestinal (GI) cancer to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA combined analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3516-3516
Author(s):  
Akihiro Ohba ◽  
Yoshiaki Nakamura ◽  
Hiroya Taniguchi ◽  
Masafumi Ikeda ◽  
Hideaki Bando ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tumor Tissue ◽  
Cancer Type ◽  
Combined Analysis ◽  
Clinical Sequencing ◽  
Upper Gi ◽  
Gi Cancer ◽  
Wide Range ◽  
Gi Cancers

3516 Background: We recently reported that clinical assessment of genomic biomarkers using ctDNA had advantages over tumor tissue-based sequencing for enrollment into matched clinical trials across a wide range of GI cancers. Herein we investigated the utility of ctDNA in non-CRC cancers in a SCRUM-Japan GI-SCREEN and GOZILA combined analysis. Methods: In GI-SCREEN, tumor tissue samples of pts with non-CRC were analyzed by a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay, since Feb 2015. In GOZILA, plasma samples of non-CRC pts were analyzed by an NGS-based ctDNA assay, Guardant360, since Feb 2018. Results: As of Apr 2019, 2,952 pts in GI-SCREEN and 633 pts in GOZILA were enrolled. Baseline characteristics between the groups were well matched except that GOZILA included more pancreatic (P < 0.0001) and liver cancers (P = 0.016) but fewer gastric cancers (P < 0.0001) and GIST (P = 0.020) than GI-SCREEN. The success rates of the tests were 86.6% in GI-SCREEN and 87.3% in GOZILA (P = 0.649). Median turnaround time (TAT) was 37 days in GI-SCREEN and 12 days in GOZILA (P < 0.0001). The proportion of cases with actionable alterations detected (tissue vs blood; 29.8% vs 46.8%, P < 0.0001) and enrolled into matched clinical trials (4.8% vs 6.5%, P = 0.286) for each group by cancer type are shown in the Table. Pts with upper GI cancers, especially those in GOZILA, were more often enrolled into matched trials; trial enrollment for those with hepatobiliary and pancreatic (HBP) or other cancers was similar regardless of testing method. Median time from GI-SCREEN or GOZILA enrollment to clinical trial enrollment was 5.0 and 1.0 months (mo), respectively (P < 0.0001). Objective response rates (ORR) and progression-free survival (PFS) were not significantly different (tissue vs. blood; ORR: 14.6 vs. 26.3%, P = 0.30: median PFS: 3.3 vs. 2.6 mo, P = 0.71). Conclusions: Clinical sequencing of ctDNA, with its shorter TAT, contributed to rapid enrollment of non-CRC pts into matched clinical trials compared to those tested by tumor tissue sequencing, particularly for those with upper GI cancer, without compromising efficacy. Clinical trial information: UMIN000029315 . [Table: see text]

A randomized phase III study of mFOLFOX6/bevacizumab combination chemotherapy with or without atezolizumab or atezolizumab monotherapy in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) metastatic colorectal cancer (mCRC): Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) study (NRG-GI004/SWOG-S1610).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS260-TPS260
Author(s):  
Caio Max Sao Pedro Rocha Lima ◽  
Greg Yothers ◽  
Samuel A. Jacobs ◽  
Hanna Kelly Sanoff ◽  
Deirdre Jill Cohen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Mismatch Repair ◽  
Tumor Tissue ◽  
Dna Mismatch Repair ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Dna Mismatch

TPS260 Background: Deficient DNA mismatch repair (dMMR) colorectal cancer (CRC) is highly immunogenic. Preclinical data showed synergistic interactions among FOLFOX, anti-VEGF, and programmed cell death-1 (PD-1) pathway blockade. Prior phase I study of mFOLFOX6/ bevacizumab (bev) + atezolizumab (atezo) was well tolerated and enhanced intratumoral infiltration of CD8+ T cells. We hypothesize that the dMMR subset of CRC may be effectively targeted with combination of PD-1 pathway blockade and mFOLFOX6/bev. Methods: This is a prospective randomized phase III open-label trial. Pts (N=347) with mCRC dMMR will be randomized to three trial arms (1:1:1): mFOLFOX6/bev; atezo monotherapy; or mFOLFOX6/bev + atezo. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary endpoint is progression-free survival (PFS) assessed by study investigator of mFOLFOX6/bev/atezo and atezo monotherapy compared to mFOLFOX6/bev. Secondary endpoints include OS, objective response rate, safety profile, disease control rate, duration of response, and PFS by retrospective central review. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2); availability of archived tumor tissue for central confirmation of dMMR status; and measurable disease per RECIST. Activated 11-7-17. As of 9-11-19, enrollment continues with 44/347 pts enrolled. Clinical trial: NCT02997228. Support:U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.

Changes in circulating tumor DNA levels are associated with treatment response and progression-free survival in relapse/refractory DLBCL subjects.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7546-7546
Author(s):  
Alexander F. Lovejoy ◽  
Hai Lin ◽  
Ehsan Tabari ◽  
Seng Lor Saelee ◽  
David Matthew Kurtz ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Response To Therapy ◽  
P Value ◽  
Molecular Response ◽  
Plasma Samples ◽  
Tissue Samples ◽  
Tumor Dna

7546 Background: Detection of an initial molecular response to therapy in DLBCL could help differentiate patients who will relapse (30-40% of frontline subjects) from those who will not. Recent studies in DLBCL showed ability to detect residual disease and molecular response to therapy from analysis of circulating tumor DNA (ctDNA). Here we performed targeted next generation sequencing (NGS) of baseline ctDNA vs. tumor tissue, and on-treatment ctDNA samples in 32 relapse/refractory DLBCL subjects from the ROMULUS study to assess correlation of outcome with molecular response. Methods: We sequenced plasma, plasma depleted whole blood (PDWB), and tumor DNA from 32 subjects (range 2-6 samples / subject). Library preparation and NGS were performed using hybrid capture-based workflows, with a panel of ~300 kb targeting regions relevant for disease detection in DLBCL. Variants were called from tissue and plasma data, and PDWB data were used to filter out non-tumor specific variants. Results: 83% of variants detected in tissue (1441/1745) were found in the corresponding plasma samples, and 78% of variants detected in plasma (1441/1846) were found in corresponding tissue samples, in line with previous reports. To follow ctDNA changes with treatment, tumor-specific variants were determined from tissue or cycle 1 day 1 (C1D1) plasma samples. These variants were then monitored in C1D1 and later timepoints, with similar ctDNA levels based on variants determined from C1D1 plasma or tissue (R2=0.99). Change in ctDNA levels from C1D1 to C2D1 separated subjects that responded from subjects that progressed (Wilcoxon p-value: 9.39×10-4). Subjects that showed a 10-fold or higher drop in ctDNA levels between C1D1 and C2D1 had significantly longer PFS than those with a smaller ctDNA fold change (HR: 8.06; p=0.0008). Conclusions: This study showed that tumor-specific variants can be identified in baseline plasma with similar performance as from tumor tissue, and that monitoring molecular response as an early change in ctDNA levels after one cycle of treatment correlated with outcomes in this DLBCL study. Clinical trial information: NCT01691898.

Characteristics of genomic alterations in circulating tumor DNA (ctDNA) in patients (Pts) with advanced gastrointestinal (GI) cancers in nationwide large-scale ctDNA screening:SCRUM-Japan Monstar-Screen.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 106-106
Author(s):  
Yoshiaki Nakamura ◽  
Takao Fujisawa ◽  
Shigenori Kadowaki ◽  
Naoki Takahashi ◽  
Masahiro Goto ◽  
...  
Keyword(s):  
Large Scale ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Genomic Alterations ◽  
Tissue Samples ◽  
Gi Cancer ◽  
Oncogenic Pathways ◽  
Treatment Naïve ◽  
Gi Cancers ◽  
Ctdna Analysis

106 Background: Analysis of ctDNA has been utilized in pts with advanced GI cancer for identification of genomic alterations for targeted therapy. However, the characteristics of ctDNA genomic alterations of GI cancers compared to non-GI cancers remains unclear. Methods: Pts with advanced solid tumors were eligible in MONSTAR-SCREEN, a nationwide ctDNA screening project in Japan. Plasma samples were analyzed by an NGS-based 70-gene ctDNA assay, FoundationOne Liquid (F1L) at a CLIA-certified and CAP-accredited laboratory since Jul 2019. For treatment-naïve pts, tumor tissue samples were analyzed by FoundationOne CDx (F1CDx), a 324-gene tissue-based panel. Results: As of Jun 18 2020, out of enrolled 540 pts with advanced solid tumor, 470 pts, consisting of 133 with advanced GI cancers (67 colorectal, 48 gastric, 14 esophageal, 2 gastrointestinal tumor (GIST) and 2 small intestinal) and 337 non-GI cancers (103 hepatobiliary and pancreatic, 70 genitourinary, 64 breast, 46 head and neck, 33 gynecologic, and 21 skin), had an available ctDNA result. Sequencing success rate was similar between GI and non-GI cancers (91.7% vs. 89.3%, P = 0.50). GI cancers had a significantly higher ctDNA level (maximum variant allele fraction) than non-GI cancers (median, 11.8% vs. 0.57%; P = 1.6E-7). The most frequently altered genes were TP53 (73%), APC (73%), KRAS (30%), BRAF (15%), and PIK3CA (12%) in colorectal cancer, TP53 (44%), KRAS (19%), PIK3CA (15%), ATM (10%), and ERBB2 (10%) in gastric cancer, and TP53 (79%), ATM (21%), ERBB2 (21%) in esophageal cancer. Mutations in genes in pathways related to RAS/RAF/MEK (39.1 % vs. 21.4 %, P = 1.8E-4), receptor tyrosine kinase (20.3% vs 11.9%, P = 0.027), p53 (66.2% vs 49.6%, P = 0.0014), and Wnt (41.4% vs 4.7%, P = 4.4E-21) were significantly enriched in GI cancers compared to non-GI cancers. Tumor tissue samples were analyzed using F1CDx for 63 treatment-naïve pts, in which 51 (31.3%) of 132 alterations identified by F1L were not detected by F1CDx. Conclusions: GI cancers had higher ctDNA levels and distinct characteristics of ctDNA genomic alterations from non-GI cancers with an enrichment in several oncogenic pathways. One-third of ctDNA alterations were detected in only ctDNA, indicating the potential of ctDNA analysis to identify heterogenous genomic alterations in advanced GI cancer. Clinical trial information: UMIN000036749.

scholarly journals Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stine Karlsen Oversoe ◽  
Michelle Simone Clement ◽  
Britta Weber ◽  
Henning Grønbæk ◽  
Stephen Jacques Hamilton-Dutoit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mutation Rate ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Treatment Modalities ◽  
Advanced Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
The Impact ◽  
Tumor Dna

Abstract Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

Concordance of BRCA1, BRCA2 (BRCA), and ATM mutations identified in matched tumor tissue and circulating tumor DNA (ctDNA) in men with metastatic castration-resistant prostate cancer (mCRPC) screened in the PROfound study.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 26-26
Author(s):  
Kim N. Chi ◽  
Alan Barnicle ◽  
Caroline Sibilla ◽  
Zhongwu Lai ◽  
Claire Corcoran ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Molecular Testing ◽  
Castration Resistant Prostate Cancer ◽  
Percentage Agreement ◽  
Tissue Samples ◽  
Recombination Repair ◽  
Invasive Method ◽  
High Concordance ◽  
Brca1 Brca2

26 Background: Not all mCRPC patients have available or sufficient tissue for multigene molecular testing. In the Phase 3 PROfound study, olaparib significantly improved radiographic progression-free survival compared with physician’s choice of abiraterone or enzalutamide in men with homologous recombination repair (HRR)-gene-mutated mCRPC (de Bono et al. N Engl J Med 2020). Overall, 31% of patients’ tissue samples failed molecular screening during the study, showing the need for additional testing methods to detect patients with HRR-gene-mutated cancers. We evaluated the utility of plasma-derived ctDNA to identify deleterious BRCA and ATM mutations in screened patients from PROfound. Methods: Tumour samples were prospectively tested at Foundation Medicine, Inc (FMI) using an investigational next-generation sequencing test (based on FoundationOne CDx) to inform trial eligibility. Matched ctDNA samples were sequenced at FMI with the FoundationOne Liquid CDx assay. Tissue samples were clinically heterogeneous regarding location and timing of collection; plasma samples were collected as part of screening in PROfound. Results: 81% (503/619) of ctDNA samples tested yielded a result, of which 491 had a tumour result. BRCA and ATM status in tissue compared with ctDNA reported 81% (95% CI 75–87%) positive percentage agreement (PPA) and 92% (95% CI 89–95%) negative percentage agreement (NPA), with tissue as reference (Table). Further concordance and discordance measures will be presented. Conclusions: High concordance between tumour tissue and ctDNA supports the development of ctDNA testing as a minimally invasive method to identify patients with HRR-gene-mutated mCRPC and guide treatment decisions, particularly for those with insufficient tissue for genomic analyses. Clinical trial information: NCT02987543. [Table: see text]

scholarly journals Indicadores (Outcomes) Primários e Secundários em Ensaios Clínicos Oncológicos: Definição e Usos

2014 ◽  
Vol 27 (4) ◽  
pp. 498
Author(s):  
António Vaz-Carneiro ◽  
Ricardo Da Luz ◽  
Margarida Borges ◽  
João Costa
Keyword(s):  
Clinical Trials ◽  
Methodological Issue ◽  
Objective Response ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patient Reported ◽  
Oncology Clinical Trials ◽  
Alternative Drug ◽  
Selection Of

<strong>Introduction:</strong> The proof of efficacy from a therapeutic intervention in oncology must be defined through well conducted clinical trials. One of the most important methodological issue is the outcome selection needed to calculate measures of association allowing definition of clinical efficacy.<br /><strong>Material and Methods:</strong> We designed a narrative revision based on some of the international regulatory instructions from drug agencies, as well as consensus papers from scientific oncology societies, listing and critically assessing each outcome used in oncology clinical trials.<br /><strong>Results:</strong> We identified as being the most important outcomes in oncology trials the overall survival, the progression free survival/ disease-free survival, the toxicity, the quality of life/patient- reported outcomes and the objective response rate.<br /><strong>Discussion:</strong> The selection of the primary outcome must be based on therapeutic efficacy as well as toxicity, expected survival, alternative drug regimens and even disease prevalence.<br /><strong>Conclusion:</strong> The selection of efficacy outcomes for clinical trials in oncology is very important and its selection must be well justified, and depends on the type of disease, the patients and the drug being studied.<br /><strong>Keywords:</strong> Clinical Trials as Topic; Neoplasms; Medical Oncology; Treatment Outcome.

scholarly journals PATH-06. ASSESSMENT OF CIRCULATING TUMOR DNA IN CEREBROSPINAL FLUID BY WHOLE EXOME SEQUENCING TO DETECT GENOMIC ALTERATIONS OF GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii165-ii165
Author(s):  
Hao Duan ◽  
Zhenqiang He ◽  
Zhenghe Chen ◽  
Yonggao Mou
Keyword(s):  
Cerebrospinal Fluid ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Genomic Alterations ◽  
Tissue Samples ◽  
Whole Exome ◽  
Resected Tumor ◽  
Tumor Dna

Abstract Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF comparing with the corresponding tumor tissue samples (3.56±0.75 vs. 2.22±0.32, P=0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.12% ± 6.03% vs. 73.83% ± 5.95%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3F3A which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

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