scholarly journals Clinical benefit of whole genome and transcriptome analysis (WGTA) in metastatic colorectal cancer (MCRC): Results from the personalized oncogenomics program (POG)

2018 ◽  
Vol 29 ◽  
pp. viii195
Author(s):  
S.L. Liu ◽  
J. Loree ◽  
D. Renouf ◽  
M. Jones ◽  
S. Yip ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Transcriptome Analysis ◽  
Clinical Benefit ◽  
Whole Genome

scholarly journals Clinical-grade whole-genome sequencing and 3′ transcriptome analysis of colorectal cancer patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Agata Stodolna ◽  
Miao He ◽  
Mahesh Vasipalli ◽  
Zoya Kingsbury ◽  
Jennifer Becq ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Transcriptome Analysis ◽  
Variant Calling ◽  
Standard Of Care ◽  
Genomic Variation ◽  
Whole Genome ◽  
Clinical Grade ◽  
Pathway Gene

Abstract Background Clinical-grade whole-genome sequencing (cWGS) has the potential to become the standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3′ transcriptome analysis would give new insights into colorectal cancer. Methods Patients underwent PCR-free whole-genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into the mutational signatures and tumour biology were gained by the use of 3′ RNA-seq. Results Fifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 30% of patients had a tumour mutational burden of > 10 mutations/Mb of DNA, suggesting suitability for immunotherapy. Conclusions Clinical whole-genome sequencing offers a potential avenue for the identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.

Clinical benefit rate (CBR) of panitumumab monotherapy among patients with KRAS wild-type metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14176-e14176
Author(s):  
Hagen F. Kennecke ◽  
Howard John Lim ◽  
Balvindar Singh Johal ◽  
Muhammad Zulfiqar ◽  
Caroline Speers
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Endpoint ◽  
Clinical Benefit ◽  
Single Agent ◽  
Wild Type ◽  
Clinical Benefit Rate ◽  
Previous Therapy ◽  
Study Results ◽  
Third Line

e14176 Background: Panitumumab (Pmab) improves progression free survival as first-, second- and third-line therapy for KRAS wild-type (wt) metastatic colorectal cancer (mCRC). Only in the third-line setting is there evidence of benefit of Pmab monotherapy. In this analysis of an exploratory biomarker study of Pmab monotherapy, the clinical benefit rate of Pmab according to previous lines of therapy is described. Methods: Patients (pts) with KRAS non-mutated, measurable MCRC previously treated with or ineligible for oxaliplatin/5-FU and irinotecan were treated with Pmab 6mg/kg IV q2w until progression or toxicity. The primary endpoint is clinical benefit rate (complete (CR) or partial response (PR) + prolonged stable disease (PSD) > = 24 weeks) by RECIST criteria. Results: The study completed accrual and (40) evaluable patients were treated between September 2009 and December 2011 of which 32 were evaluable for the primary endpoint. Median follow-up was 8.8 months, median age was 64.5 years and 90% were ECOG 0/1. Previous therapy was: 5-FU/Capecitabine(C) only in 12 pts, Irinotecan/5-FU/C only in 2 patients, Oxaliplatin/5-FU/C only in 3 pts, Oxaliplatin/Irinotecan/5-FU/C in 23 pts. 22 patients received prior Bevacizumab. Median number of cycles was 8 and 6 pts required a dose modification. There were 7 (22%) PRs and 7 (22%) pts experienced PSD >=24 weeks. Clinical benefit rate (PR+PSD) according to previous therapy was 33% (3/9) for 5FU/C only, 100% (2/2) Oxaliplatin/FU/C only, 0% (0/2) Irinotecan/FU/C only, and 47% (9/19) for Oxaliplatin/Irinotecan/5FU/C. Conclusions: Pmab monotherapy is well tolerated and response rates vary according to previous lines of therapy. Patients ineligible for irinotecan and/or oxaliplatin experience a high clinical benefit rate with single agent Panitumumab and should be considered for such therapy. Updated study results will be presented.

Does panitumumab have a clinical benefit in cetuximab-refractory KRAS wild-type metastatic colorectal cancer?

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 654-654
Author(s):  
Toshiyasu Watanabe ◽  
Eiji Shinozaki ◽  
Sho Kijima ◽  
Yoshihito Ohhara ◽  
Yasutoshi Kuboki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tumor Marker ◽  
Clinical Benefit ◽  
Chemotherapy Response ◽  
Chimeric Mouse ◽  
Serum Tumor Marker ◽  
Wild Type ◽  
Tumor Marker Level ◽  
Marker Level

654 Background: Panitumumab and cetuximab can be used in metastatic colorectal cancer (mCRC) and these drugs are IgG2 fully human and IgG1 chimeric (mouse/human) monoclonal antibody against the epidermal growth hactor receptor (EGFR) respectively. The efficacy of panitumumab as a salvage chemotherapy after cetuximab-based chemotherapy failure is not clarified. Methods: This study aimed to evaluate the panitumumab efficacy to KRAS wild-type mCRC patients who failed cetuximab-based chemotherapy. Response, progression-free survival (PFS) and serum tumor marker level (CEA and CA19-9), were assesed. We studied response by days from last cetuximab-based chemotherapy to panitumumab induction (C-P days). Results: 22 patients (11 men, 11 women, median age 54 years m4 0-78 n) were enrolled. All of thease patients were cetuximab-based chemotherapy refractory KRAS wild-type mCRC. After progression, they received panitumumab monotherapy (6 mg/kg every 2 weeks).The best response was SD 10/22 (45.5%), PD 11/22 (50%) and NE 1/22 (4.5%). Overall median PFS was 90 days (13 to 182). The patients C-P days less than 30 days were 15 patients(5:SD, 10:PD). The patients more than 79 days were 7 patient(5:SD, 1:PD, 1:NE). Serum tumor marker level was decreased more than 50% patients. Conclusions: This study suggested that it might be limited as possibility of clinical benefit with panitumumab administration after cetuximab failure.

Predictive significance of VEGF and HIF-1α expression in metastatic colorectal cancer patients receiving chemotherapy combined with bevacizumab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14672-e14672
Author(s):  
Veli Berk ◽  
Kemal Deniz ◽  
Halit Karaca ◽  
Mevlude Inanc ◽  
Oktay Bozkurt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Benefit ◽  
Hypoxia Inducible Factor ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Vegf Expression ◽  
Primary Tumors ◽  
Colorectal Cancer Patients ◽  
Low Expression

e14672 Background: There is no suggested molecular indicator in identifying which patients will benefit from anti-angiogenic treatment in metastatic colorectal cancer. Over expression of vascular endothelial growth factor (VEGF) and Hypoxia Inducible Factor 1-alpha (HIF-1α) are associated with bad prognosis. In this study, VEGF and HIF-1α expression and their clinical significance are studied in tumor tissues of patients with colorectal cancer receiving treatment with bevacizumab. Methods: VEGF and HIF-1α were observed immunohistochemically in primary tumors of 53 patients. The expressions were separated by evaluating low and high of VEGF and HIF-1α expression. We evaluated whether expression of VEGF and HIF-1α can help to predict treatment response, progression free survival (PFS), and overall survival (OS). Results: Fifty-three patients were enrolled in the study. Median age was 55. VEGF was strongly expressed in 30 patients (57%) whilst low expression was observed in 23 of them (43%). When VEGF expression was evaluated in association with therapy response rates; the clinical benefit rate was 38% in the low expression group whereas it was 62% in high expression group. This difference was statistically significant (p=0.01). In the group with strong VEGF expression PFS was 10 months whereas it was 8 months in the low expression group (p=0.009). When evaluated for OS, 26 months versus 15 months was in favor of highly expressed VEGF group (p=0.03). Highly expressed HIF-1α was found in 29 patients (55%), on the other hand low expressed HIF-1α was detected in 24 (%45) patients. For clinical benefit rates, PFS and OS there was no difference between high and low expressed HIF-1α groups. Conclusions: It has been demonstrated that VEGF and HIF-1α expressions are associated with poor prognosis in several tumors, mainly colorectal carcinomas. With the better understanding of carciogenesis and angiogenesis at molecular level, especially VEGF and HIF-1α became target molecules of the therapy. According to results of our study, VEGF expression is a predictive factor in designating the metastatic colorectal cancer treatment.

scholarly journals Clinical-grade whole genome sequencing of colorectal cancer and 3’ transcriptome analysis demonstrate targetable alterations in the majority of patients

2020 ◽  
Author(s):  
Agata Stodolna ◽  
Miao He ◽  
Mahesh Vasipalli ◽  
Zoya Kingsbury ◽  
Jennifer Becq ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Transcriptome Analysis ◽  
Variant Calling ◽  
Standard Of Care ◽  
Genomic Variation ◽  
Whole Genome ◽  
Clinical Grade ◽  
Pathway Gene

AbstractIntroductionClinical grade whole genome sequencing (cWGS) has the potential to become standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3’ transcriptome analysis would give new insights into colorectal cancer.MethodsPatients underwent PCR-free whole genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into mutational signatures and tumour biology were gained by the use of 3’ RNAseq.ResultsFifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 20% of patients had a tumour mutational burden of >10 mutations/Mb of DNA, suggesting suitability for immunotherapy.ConclusionsClinical whole genome sequencing offers a potential avenue for identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.

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