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  • Qiu, Haibo  (9)
  • Zhou, Zhiwei  (9)
  • 1
    Online Resource
    Online Resource
    Next generation sequencing (NGS) in wild type GISTs.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e22507-e22507
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e22507-e22507
    Abstract: e22507 Background: The majority driven mutation of GIST are located in KIT and PDGFRA. A proportion of the remaining 10% of GIST without KIT or PDGFRA mutations called wild type GIST (wt-GIST). It is poor response to imatinib, sunitinib or regorafenib in these wt-GIST patients. It is lack of precise drug target of wt-GIST. We analyzed next generation exome sequencing (NGS) results in wt-GISTs. Methods: Whole exome sequencing was performed on freezing tumor tissue and peripheral blood DNA with 100X sequencing depth. The low frequency somatic mutation was confirmed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) and Sanger sequencing. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: A total of 11 wt-GIST samples were analyzed. ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) was mutated in one CD117 negative patients with 5.3% mutation frequency of c. 364G 〉 A (p. A122T). Sanger sequencing couldn’t found the ROS1 mutated in tumor tissue. But this low frequency somatic mutation was verified by MALDI-TOF. Conclusions: This is the first report showed a new ROS1 somatic mutation in wt-GIST. Our results indicated that ROS1 could be a new possible driven mutation in wt-GIST. ROS1 rearrangement have been described in a subset of non-small-cell lung cancers (NSCLC). Crizotinib shows a potent curative effect in ROS1 rearrangement NSCLC. Therefore, crizotinib might be an appropriate drug to GIST patients with mutated ROS1.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e22507
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
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    A comprehensive analysis comparing the eighth AJCC gastric cancer pathological classification to the seventh, sixth, and fifth editions
    Wiley ; 2017
    In:  Cancer Medicine Vol. 6, No. 12 ( 2017-12), p. 2804-2813
    Details
    In: Cancer Medicine, Wiley, Vol. 6, No. 12 ( 2017-12), p. 2804-2813
    Abstract: To perform a comprehensive analysis comparing the prognostic and discriminative ability of the eighth AJCC gastric cancer ( GC ) pathological classification to that of the seventh, sixth and fifth editions, and secondly to assess their long‐term significance. Patients who had undergone R0 gastrectomy were identified and restaged accordingly. To evaluate and confirm any difference in prognostic ability between the competing editions, the Akaike information criterion ( AIC ) and Bayesian information criterion ( BIC ) were computed and compared since both have different analytic strengths. The area under the curve ( AUC ) with 95% CI based on the time‐dependent receiver‐operating characteristics analyses were also calculated to assess any change in prognostic rankings from the first to tenth postoperative year. The rankings calculated by both statistical methods showed similar results, in which the seventh edition was identified as possessing the best prognostic ability. Additionally, these ranks were found to remain consistent over the ten postoperative years, but demonstrated no clinical significance as their respective 95% CI s calculated by the AIC , BIC , and AUC were found to overlap. However, the more detailed staging classifications of the eighth edition was shown to display the best prognostic demarcation for stratifying patients with higher‐staged disease. This study thereby identified the eighth AJCC GC edition to possess similar long‐term prognostic ability as to its previous three editions but contrastingly demonstrated the best distinctive ability for stratifying overall survival and can thus be considered as being clinically more reliable.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    URL: Article
    DOI: 10.1002/cam4.2017.6.issue-12
    DOI: 10.1002/cam4.1230
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2659751-2
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  • 3
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    Impact of pharmacogenomics on imatinib toxicity in gastrointestinal stromal tumors.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 11043-11043
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 11043-11043
    Abstract: 11043 Background: Imatinib-induced side effects are common, although most of these side effects are mild, some will be severe and lead to disruption of Imatinib treatment in gastrointestinal stromal tumor (GIST). It is necessary to explore a biological predictors to predict and optimal therapeutic strategy. But there were few studied conducted to explore the mechanisms of Imatinib-induced side effects. The present study comprehensively investigated the effects of genetic polymorphisms of cytokines involved in cell proliferation and metabolic enzymes and transporters involved in Imatinib metabolism on these side effects. Methods: A total of 154 GSIT patients treated with Imatinib were enrolled. 22 SNPs (single nucleotide polymorphisms) in KIT/ PDGFRA/ PDGFRB/ SHC1/ FLT1/ MAPK1/ EGFR/ CCL5/ CXCL14were detected using Agena Massarray matrix-assisted laser desorption / ionization-time of flight (MALDI-TOF) platform. Logistic regression analyses were performed to evaluate their effects on Imatinib-induced toxicities. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: Imatinibdose, FLT1 rs9951465, MAPK1 rs13515, PDGFRB rs55712339 and SHC1 rs3766920 were found to be correlated with the incidence of myelosuppression ( P= 0.027, 0.009, 0.002, 0.008, 〈 0.001, respectively), moreover, FLT1 rs9554314 was correlated with severe myelosuppression (Grade 0,1 vs. 2+, P= 0.009, OR (95%CI) = 3.042 (1.314-7,042)). Meanwhile, EGFR rs10228436 was found to be correlated with the incidence of skin rash ( P= 0.027), moreover, CCL5 rs4796120 and CXCL14 rs7716492 were correlated with severe skin rash (Grade 0,1 vs. 2+), with OR (95%CI) and p value were 8.542 (0.934-78.107), 13.504 (2.308-79.004) and 0.057, 0.020, respectively. Conclusions: This is the first comprehensive report on the biomarkers for Imatinib toxicities. These biomarkers might be able to distinguish patients with mild or more severe forms of Imatinib toxicities, thus enabling the optimization of Imatinib therapy and lead patients benefit from Imatinib treatment in a long-term.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.11043
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 4
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    A novel correlation between KIT promoter DNA methylation and prognostic of gastrointestinal stromal tumors.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. e23514-e23514
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e23514-e23514
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.e23514
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Relationship among ETV1 genetic polymorphisms, PFS, and microRNA in gastrointestinal stromal tumors.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e22513-e22513
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e22513-e22513
    Abstract: e22513 Background: In order to evaluate the pharmacokinetic and pharmacogenomic determinants for prognosis of gastrointestinal stromal tumor (GIST). It is necessary to explore a biological predictors to predict and optimal therapeutic strategy. But there were few studied conducted to explore the germline mutation and its mechanisms. Methods: A total of 75 GIST patients treated with Imatinib were enrolled. 35 SNPs (single nucleotide polymorphisms) in KIT/ PDGFRA/ PDGFRB/ ETV1/ FLT1/ MAPK1 et. al were detected using Agena Massarray matrix-assisted laser desorption / ionization-time of flight (MALDI-TOF) platform. COX regression analyses were performed to evaluate the key factors of PFS. The luciferase reporter system of rs3735343 wild type and mutation were established. The GIST-T1 cell line was used to evaluate the biology effect of rs3735343. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: Several factors influence the PFS, including KIT somatic mutation, tumor size and germline mutation ABCC4 rs4148551, ETV1 rs3735343, FLT1 rs3751397, KIT rs3822214. And COX regression showed that rs3735343 and tumor size are associated with PFS (P = 0.009 and 0.032, Risk Ratio = 8.995 and 4.173). And we found that rs3735343 mutation type can regulate ETV1 3’UTR and protein expression level through miR-4311 in vitro. Conclusions: The primary determinants of PFS in this somatic and germline mutation model suggested new biomarkers and different mechanisms involved in prognosis. This is the first report showed that ETV1 genetic polymorphisms may influence the prognosis through miRNA-4311. Targeting ETV1, miRNA-4311 or their relative pathway might be a new therapy strategy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e22513
    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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  • 6
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    Clinicopathological Outcomes and Prognosis of Elderly Patients (≥ 65 Years) with Gastric Gastrointestinal Stromal Tumors (GISTs) Undergoing Curative-Intent Resection: a Multicenter Data Review
    Springer Science and Business Media LLC ; 2019
    In:  Journal of Gastrointestinal Surgery Vol. 23, No. 5 ( 2019-5), p. 904-913
    Details
    In: Journal of Gastrointestinal Surgery, Springer Science and Business Media LLC, Vol. 23, No. 5 ( 2019-5), p. 904-913
    Type of Medium: Online Resource
    ISSN: 1091-255X , 1873-4626
    URL: Article
    DOI: 10.1007/s11605-018-3944-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2057634-1
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  • 7
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    Impact of preoperative anemia on outcomes in patients undergoing curative resection for gastric cancer: a single‐institution retrospective analysis of 2163 Chinese patients
    Wiley ; 2018
    In:  Cancer Medicine Vol. 7, No. 2 ( 2018-02), p. 360-369
    Details
    In: Cancer Medicine, Wiley, Vol. 7, No. 2 ( 2018-02), p. 360-369
    Abstract: We sought to evaluate whether preoperative anemia was an important determinant of survival in gastric cancer ( GC ). A single institution cohort of 2163 GC patients who underwent curative resection were retrospectively analyzed. Anemia was defined as a preoperative hemoglobin level 〈 120 g/L in males and 〈 110 g/L in females. Overall survival ( OS ) was analyzed using the Kaplan–Meier method, and a multivariate Cox proportional hazards model was performed to identify the independent prognostic factor. Anemic patients had a poorer OS compared with nonanemic patients after resection for tumor–nodes–metastasis ( TNM ) stage III tumors (5‐year OS rate: 32.2% vs. 45.7%, P   〈  0.001) but not stage I ( P   =  0.480) or stage II ( P   =  0.917) tumors. Multivariate analysis revealed that preoperative anemia was an independent prognostic factor in TNM stage III (hazard ratio [ HR ], 1.771; 95% CI , 1.040–3.015; P  =   0.035). In a stage‐stratified analysis, preoperative anemia was still independently associated with OS in TNM stages III a through III c ( P  〈   0.001, P  =   0.075, and P  =   0.012, respectively), though the association was only marginal in stage III b. Of note, preoperative mild anemia had a similar prognostic value in TNM stage III GC . Furthermore, preoperative anemia was significantly associated with more perioperative transfusions, postoperative complications and several nutritional‐based indices, including the prognostic nutritional index ( PNI ), preoperative weight loss and performance status (all P  〈   0.05). Preoperative anemia, even mild anemia, was an important predictor of postoperative survival for TNM stage III GC .
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    URL: Article
    DOI: 10.1002/cam4.2018.7.issue-2
    DOI: 10.1002/cam4.1309
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2659751-2
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  • 8
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    Circulating tumor DNA and recurrence risk in stage II-III gastric cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 4054-4054
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4054-4054
    Abstract: 4054 Background: Circulating tumor DNA (ctDNA) is a promising biomarker for detecting molecular residual disease (MRD) and relapse after definitive treatment in multiple solid cancers. However, the significance of ctDNA is rarely clarified in locoregional gastric cancer (GC). Here, we conducted a prospective and observational study to evaluate the utility of ctDNA in predicting the recurrence risk of GC. Methods: From October 2016 to June 2019, 100 patients with stage II/III resectable GC were recruited in this study (NCT02887612). Primary tumors and plasma samples were collected perioperatively and after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma of patients was defined as ctDNA positive only if one or more variants detected in the plasma presented in at least 2% of the primary tumors. All the patients received curative-intent standard-of-care therapy. Results: Preoperative ctDNA was detectable in 38 (38.0%) patients but showed limited value for predicting recurrence. After surgery (median days, 4), the plasma of 25 (25.0%) patients were still ctDNA positive and they had higher recurrence risk than the non-positive patients (hazard ratio [HR], 2.74 (95% CI: 1.37–5.48); P = 0.003). Forty-one patients had evaluable plasma after ACT and 10 (24.4%) of them who were ctDNA positive had remarkably higher recurrence and death risk compared with ctDNA-negative patients (recurrence-free survival [RFS] HR = 14.99 (95% CI: 3.08–72.96); P 〈 0.001; overall survival HR, 11.88 (95% CI: 2.38–59.24); P 〈 0.001). In particular, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and post-treatment tumor biomarkers (i.e., CEA, CA199, and CA72-4). In all multivariate analyses, ctDNA positivity was an independent factor of RFS. Patients with ERBB4 mutation in their primary tumors had poorer RFS compared to those were ERBB4 wildtype (HR = 3.46 (95% CI: 1.32–9.03); P = 0.007). A comprehensive model incorporating ctDNA status for recurrence risk prediction showed a higher concordance index (0.78; 95%CI, 0.71–0.84) than the model without ctDNA status (0.71; 95%CI, 0.64–0.79; P = 0.009). Conclusions: Postoperative and post-ACT ctDNA was associated with MRD and high risk of relapse in patients with stage II/III GC and can be utilized to guide GC management in post-surgical settings.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.4054
    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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  • 9
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    Tumor necrosis and 〉20 mitoses per 50 high-power fields can distinguish ‘very high-risk’ and ‘highest-risk’ within ‘high-risk’ gastric gastrointestinal stromal tumor
    Future Medicine Ltd ; 2018
    In:  Future Oncology Vol. 14, No. 7 ( 2018-03), p. 621-629
    Details
    In: Future Oncology, Future Medicine Ltd, Vol. 14, No. 7 ( 2018-03), p. 621-629
    Abstract: Graphical abstract [Formula: see text]
    Type of Medium: Online Resource
    ISSN: 1479-6694 , 1744-8301
    URL: Article
    DOI: 10.2217/fon-2017-0509
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2018
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