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  • Denda, Tadamichi  (6)
  • Nishina, Tomohiro  (6)
  • Takashima, Atsuo  (6)
  • 1
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    Online Resource
    Expression of PD-L1 and PD-L2 in colorectal cancer (CRC): A post-hoc integrated analysis of SCRUM-Japan GI-SCREEN CRC.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 3_suppl ( 2021-01-20), p. 120-120
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 3_suppl ( 2021-01-20), p. 120-120
    Abstract: 120 Background: PD-1, PD-L1/L2 axis is responsible for cancer immune escape which facilitate disease progression. However, expression of these proteins in CRC and its significance in clinical prognosis are yet to be fully clarified. Methods: This was a post-hoc analysis using FFPE tumor samples from the Nationwide Cancer Genome Screening Project, SCRUM-Japan GI-SCREEN for metastatic CRC. Patients (Pts) with MSI-H or BRAF V600E mutant tumors were prioritized to be included. PD-L1 (22C3) and PD-L2 expressions were centrally assessed using immunohistochemical assays at QualTek and NeoGenomics, respectively. Tumor infiltrating lymphocytes (TILs) were morphologically evaluated by H & E staining. Clinical information including biomarker status and overall survival (OS) were extracted from SCRUM-Japan GI-SCREEN database. Results: In total, 200 pts were included in this study with a median age of 65 (range, 29–88) years; male/female (116/84); MSI status MSI-H/non-MSI-H/unknown (8/189/3); RAS wild-type/mutant (113/87); and BRAF V600E wild-type/mutant (173/27). Positivity rate of PD-L1 in tumor cells (TC), immune cells (IC), PD-L2 on TC and IC were 10.8%, 46.9%, 0% and 20.3%, respectively. Expression of PD-L1 on TC or IC and PD-L2 on IC were associated with TIL (p = 0.023, p = 0.009, respectively). PD-L1 on TC was highly seen in BRAF V600E-mutated tumors (p = 0.043), but not related to other factors including RAS and MSI status. The pts with PD-L1+ tumors on TC or IC had longer OS than those with PD-L1- (Median, 31.9 vs 23.5 months; HR = 0.67, 95% CI, 0.46–0.99; p = 0.040), while OS in pts with PD-L2+ tumors was similar to that with PD-L2- (Median, 21.4 vs 27.3 months; HR = 0.87, 95% CI, 0.53–1.44; p = 0.60). The PD-L1 expression was also associated with the longer OS in pts with BRAF wild-type or non-MSI-H tumors. Conclusions: Our study suggested different prognostic impact of PD-L1 and PD-L2 expression in CRC pts, which require further evaluations as potential therapeutic targets for CRC. Clinical trial information: UMIN000016343.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.3_suppl.120
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Analysis of plasma angiogenesis factors on the efficacy of first-line (1L) chemotherapy (chemo) combined with biologics in RAS wild-type metastatic colorectal cancer (mCRC): Results from GI-SCREEN CRC Ukit study.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 3530-3530
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 3530-3530
    Abstract: 3530 Background: Angiogenesis factors have been reported as prognostic and predictive biomarkers of angiogenesis inhibitors for mCRC (Weickhardt AJ. Br J Cancer 2015. Tabernero J. Ann Oncol 2018). We investigated whether plasma angiogenesis factors could predict the efficacy of biologics combined with chemo in 1L treatment in patients (pts) with RAS wild-type mCRC. Methods: Serial plasma samples were prospectively collected at the time points of pre- and post-treatments in mCRC pts receiving biologics in either 1L or 2nd-line (2L) chemo. From Sep 2017 to Dec 2020, 497 pts were enrolled [1L chemo plus bevacizumab (1L BEV, n=102), 1L chemo plus anti-EGFR antibody (1L aEGFR, n=100), 2L chemo plus bevacizumab (n=100), 2L FOLFIRI plus RAM (n=99), 2L FOLFIRI plus aflibercept (n=85) and other treatment (n=11)]. Total of 17 plasma angiogenesis factors (HGF, PlGF, VEGF-A, VEGF-D, Angiopoietin-2, IFN-γ, IL-6, IL-8, sNeuropilin-1, TSP-2, OPN, sVEGFR1, sVEGFR2, sVEGFR3, sICAM-1, sVCAM-1, and TIMP-1) were analyzed by the multiplex assay with Luminex ® technology. Interactions of their pre-treatment measurements with treatment groups on PFS and OS were assessed via Cox proportional hazards model. The strength of interactions was estimated using a propensity score weighting analysis, and the continuous plasma angiogenesis variables were categorized according to the median. The significance level in the interaction was defined as p≤0.1. Results: 133 pts were included in adjusted RAS wild-type 1L cohort (1L BEV: n=33, 1L aEGFR [reference]: n=100). Baseline characteristics of adjusted RAS wild-type 1L cohort were as follows; median age 64 years; male 62.4%; left-sided tumor 88.7%; triplet chemo 15.0%. Propensity-score weighted Cox model for OS showed significant interactions in IL-8 (median 8.03 pg/mL, high: HR 1.738, p=0.0838, Low: HR 0.479, p=0.2624, interaction p=0.0283), sVEGFR-1 (median 1,350 pg/mL, high: HR 0.333, p=0.1770, Low: HR 1.311, p=0.3004, interaction p=0.0777), and sVCAM-1 (median 1,020,000 pg/mL, high: HR 0.100, p=0.0558, Low: HR 1.616, p=0.1765, interaction p=0.0011). In terms of PFS, there were significant interactions in IL-8 (high: HR 1.322, p=0.0418, Low: HR 0.517, p=0.0528, interaction p=0.0752) and sVCAM-1 (high: HR 0.285, p=0.0414, Low: HR 1.200, p=0.7725, interaction p=0.0156). Conclusions: Pre-treatment plasma IL-8 and sVCAM-1 could be predictive biomarkers for efficacy of biologics combined with chemo in 1L treatment of RAS wild-type mCRC. Clinical trial information: UMIN000028616. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.3530
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Role of plasma angiogenesis factors in the efficacy of first‐line chemotherapy combined with biologics in RAS wild‐type metastatic colorectal cancer: Results from the GI‐SCREEN CRC‐Ukit study
    Wiley ; 2023
    In:  Cancer Medicine Vol. 12, No. 18 ( 2023-09), p. 18702-18716
    Details
    In: Cancer Medicine, Wiley, Vol. 12, No. 18 ( 2023-09), p. 18702-18716
    Abstract: Several biomarkers have been established for metastatic colorectal cancer (mCRC). We investigated whether plasma angiogenesis factors could predict the efficacy of biologics combined with chemotherapy in first‐line (1L) treatment in patients with RAS wild‐type mCRC and the dynamics of plasma angiogenesis factors at progression during 1L treatment. Methods In this multicenter prospective observational study, serial plasma samples were prospectively collected at pretreatment and progression stages; 17 plasma angiogenesis factors were analyzed using the multiplex assay with Luminex® technology. Interactions between the pretreatment measurements and treatment groups on progression‐free survival (PFS) and overall survival (OS) in patients with RAS wild‐type were assessed using the propensity‐score weighted Cox proportional hazards model. Results From February 2018 to September 2020, 202 patients were enrolled in the 1L cohort; 133 patients had RAS wild‐type (chemotherapy plus bevacizumab [BEV group, n = 33] and plus anti‐epidermal growth factor receptor monoclonal antibodies [aEGFR group, n = 100]). A trend of strong interaction on PFS was observed for interleukin‐8 (IL‐8) ( p = 0.0752) and soluble vascular cell adhesion molecule‐1 (sVCAM‐1) ( p = 0.0156). Regarding OS, IL‐8 ( p = 0.0283), soluble vascular endothelial growth factor‐receptor‐1 (sVEGFR‐1) ( p = 0.0777) and sVCAM‐1 ( p = 0.0011) tended to differentiate the treatment effect. In 112 patients, plasma samples were evaluable for dynamic analysis (57 and 55 from the BEV and aEGFR groups, respectively). In the BEV group, six factors significantly increased during progression, whereas two decreased. In the aEGFR group, three factors significantly increased, and six decreased. Conclusion Pretreatment plasma IL‐8 and sVCAM‐1 levels could be predictive biomarkers to distinguish BEV and anti‐EGFR mAbs when combined with chemotherapy in the 1L treatment of RAS wild‐type mCRC. Several plasma angiogenesis factors showed significant change at progression in 1L chemotherapy plus biologics for RAS wild‐type mCRC, which are potential biomarkers for selecting an optimal angiogenesis inhibitor in second‐line treatment.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    URL: Article
    DOI: 10.1002/cam4.v12.18
    DOI: 10.1002/cam4.6486
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2659751-2
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  • 4
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    NOTCH gene alterations in metastatic colorectal cancer in the Nationwide Cancer Genome Screening Project in Japan (SCRUM-Japan GI-SCREEN)
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Cancer Research and Clinical Oncology Vol. 148, No. 10 ( 2022-10), p. 2841-2854
    Details
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 148, No. 10 ( 2022-10), p. 2841-2854
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    URL: Article
    DOI: 10.1007/s00432-022-04064-4
    RVK:
    XA 52301
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1459285-X
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  • 5
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    Plasma VEGF-D and PlGF levels according to prior use of biologics among metastatic colorectal cancer: Preliminary results from GI-SCREEN CRC-Ukit study.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 4_suppl ( 2020-02-01), p. 178-178
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. 178-178
    Abstract: 178 Background: Plasma vascular endothelial growth factor-D (VEGF-D) level is a potential predictor for ramucirumab efficacy in patients (pts) with metastatic colorectal cancer (mCRC), while a high VEGF-A and placental growth factor (PlGF) level in bevacizumab naïve pts receiving 2nd-line FOLFIRI plus aflibercept may suggest relatively higher activity. However, there are a few data associating 1st-line antiangiogenic treatments as well as anti-EGFR with angiogenic factors. Methods: This prospective longitudinal study aims to investigate an association between plasma angiogenesis-related mediators and clinical outcomes in mCRC. Serial plasma collections were done at time points of pre- and post-treatments of either 1st- or 2nd-line. Comprehensive measurements of 17 mediators were analyzed by the multiplex assay with Luminex technology. Here we report an association between levels of VEGF-D, PlGF and patient backgrounds. Results: From Sep 2017 to Aug 2019, 375 samples from 317 pts were enrolled in this analysis. Baseline characteristics were follows; 169 samples at pre-1st-line (pre-1L), 151 with prior bevacizumab treatment (post-bev) and 55 with prior anti-EGFR antibody (post-EGFR); median age, 66 years; male gender, 58%; RAS mutant, 46%; left-sided primary, 76%. In pre-1L, the median values of VEGF-D/ PlGF were 264/ 7.21 pg/mL without a clear association between the two in each patient (r = 0.094) and any baseline characteristics. Compared to pre-1L, the values of VEGF-D/ PlGF showed significantly higher in post-bev (median VEGF-D/ PlGF; 346/ 23.5 pg/mL, respectively). Moreover, there was no clear relationship between the two cytokines in each patient (r = 0.190). In 37 pts with serial blood collection, VEGF-D/ PlGF levels showed similar trends. In addition, VEGF-D/ PlGF levels in post-EGFR tended to be higher than those in pre-1L (median VEGF-D/ PlGF; 395/ 9.11 pg/mL, respectively). Conclusions: The VEGF-D/ PlGF may be separately induced by bev treatment as well as anti-EGFR therapy, suggesting the possibility of usefulness for selecting a better antiangiogenic inhibitor by measuring baseline VEGF-D/ PlGF. Clinical trial information: UMIN000028616.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.4_suppl.178
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 6
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    Identification of site-specific genome alterations in metastatic colorectal cancer: Sub-study 003 of the SCRUM-Japan GI-SCREEN.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 4_suppl ( 2019-02-01), p. 578-578
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 578-578
    Abstract: 578 Background: Primary tumor sidedness is known to be an independent prognostic factor and a predictor for the efficacy of anti-EGFR antibody. However, limited information is available regarding the role of primary tumor site for the treatment of metastatic colorectal cancer (mCRC) patients (pts), including gene mutation profiles, prognosis, and prediction for treatment. This study was conducted as a sub-study of the SCRUM-Japan GI-SCREEN, the Nationwide Cancer Genome Screening Project in Japan. Methods: Among participants of the GI-Screen 2013-01-CRC, untreated pts with mCRC which samples were collected from primary site were eligible. DNA and RNA were extracted from FFPE tumor samples and then were analyzed by the Oncomine Cancer Research Panel detecting gene mutations, copy number variants (CNV), and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. Results: Among 1011 enrolled pts from Feb. 2015 to Mar 2017, a total of 561 samples were analyzed (median age, 66.0 years; 232 [41.4 %] female). Frequency of female, undifferentiated, mucinous or signet ring cell subtype were gradually increased as the primary site became the right side. Median site-specific survival was 22.4 months (m) in the cecum, 25.3 m in the ascending colon, 21.2 m in the transverse colon, 72.5 m in the descending colon, 36.5 m in the sigmoid colon, and 39.6 m in the rectum. Gene alterations differed in each primary site. Among frequently observed gene alterations, FBXW7 mutation in rectum, ATM mutation in transverse colon, BRAF and SMAD4 mutations in ascending colon significantly contributed to poor prognosis. Conclusions: This study revealed the site-specific survival and gene alterations in Japanese mCRC pts. These novel knowledges provide an intriguing background to investigate new targeted approaches in these pts and represent the progress toward precision medicine. We will analyze the site-specific therapeutic effect of molecular targeting agents, including anti-EGFR antibody. Clinical trial information: UMIN000031242.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.4_suppl.578
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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