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  • Xia, Xuefeng  (9)
  • 1
    Online Resource
    Online Resource
    ERBB2 mutation profiling with next-generation sequencing (NGS) in solid tumors.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. e24264-e24264
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e24264-e24264
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.e24264
    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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  • 2
    Online Resource
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    BRAF fusion in lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21598-e21598
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21598-e21598
    Abstract: e21598 Background: BRAF was a part of RAS/MAPK pathway, which regulated the proliferation, differentiation, migration, and apoptosis of cells. BRAF V600E was a potential treatment target for non-small cell lung cancer and other tumors. While BRAF fusion was rare in lung cancer. Here we focus on BRAF fusion in lung cancer. Methods: We retrospectively reviewed next-generation sequencing (NGS) results of lung cancers, with or without treatment history. The samples were subjected to NGS using 59 or 1021-gene panel, which enables simultaneously assess snv, indel, rearrangements and cnv variations. Patients with BRAF fusion were collected and used to analysis. Results: We found eighteen lung cancers have BRAF fusion from about twelve thousand patients, 13 are females. The median age at diagnosis was 47-year old (range 28 to 70). Tested samples included 13 tissues, 5 plasma, and 2 pleural effusion. BRAF fusion could occur in different stage, 12 stage Ⅳ and 1 stage Ⅰ, other were unknown. There were 14 lung adenocarcinoma, 1 squamous cell carcinoma and 1 adenosquamous carcinoma, other two patients were unknown. The partner genes of BRAF fusion were distinctly among the patient, TRIM24 was relatively common. The median tumor mutation burden (TMB) was 4.8muts/Mb (range 0 to 15.4), with low TMB-H frequency (10.5%, defined 9 as cutoff value). Seven patients had no system treatment history, and 1 had concurrent EGFR L858R mutation. Nine patients received EGFR-TKI therapy, 1 received ALK-TKI therapy, and 1 received chemotherapy. Among the EGFR-TKI treated patients, 7 received first and third generation TKI sequential therapy, the median TTD (time to discontinue) of TKIs was 26 months (range 17 to 46). The EGFR mutation still exist when EGFR-TKIs resistance, included EGFR primary mutation, T790M, and C797S, concurrent with BRAF fusion. Except for BRAF fusion, there also had other complex resistance mechanism occurred, like HER2 mutation, KRAS mutation, etc. Conclusions: BRAF fusion had low frequency in lung cancer and occurred at different stage during disease development. BRAF inhibitors maybe a potential strategy for BRAF fusion lung cancers. As TKIs resistance mechanism, BRAF fusion is a huge clinical challenge, indicate the importance of further research.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e21598
    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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  • 3
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    Concurrent TP53 mutation adversely impact the efficacy of crizotinib in ROS1- rearranged lung cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e20535-e20535
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e20535-e20535
    Abstract: e20535 Background: ROS1 tyrosine kinase inhibitors (TKIs) are now standard of care for patients with advanced ROS1-rearranged NSCLC. But factors that may affect the efficacy of ROS1 TKIs remain to be explored. Methods: We conducted a retrospective multicenter study of lung cancer patients with ROS1 rearrangements. Treatment and survival follow-up was done and clinical records were reviewed. PFS distribution was analyzed by Kaplan-Meier method with log-rank test. Results: In total, we included 94 lung cancer patients with ROS1 fusion genes profiled by next-generation sequencing from May 2016 to September 2018. Fifty of them were female. The median diagnosis age was 54 (25-83). The most common histologic type was adenocarcinoma, which was confirmed in 75 of 78 patients with available pathological results. The most common fusion partners were CD74, EZR, SDC4 and SLC34A2 identified in 42, 19, 12 and 8 patients respectively. Concurrent actionable mutations were uncommon for ROS1 fusion-positive patients. The most frequent concomitant mutated gene was TP53, which was detected in 33% of all the patients. After excluding 29 patients who were lost to follow-up at the very start, the median follow-up time was 8.5 (0-28) months from the moment when mutation profiling was performed. Thirty-nine patients received treatment with crizotinib, among whom 27 were treatment-naïve patients. The median PFS of the 39 patients with crizotinib was not reached yet. Patients with baseline CNS metastasis tend to have shorter PFS compared to patients without (median, 12 vs NR, p = 0.0073). Besides, concurrent TP53 mutations were correlated with worse PFS (median, both NR, p = 0.0417). Mutation profiles of 10 patients were derived from ctDNA testing. No difference was found in PFS between these 10 patients with others whose genomic profiles were based on fresh tissue or FFPE specimens, suggesting that plasma ctDNA serves as good specimen source for mutation profiling to monitor clinical treatment. Conclusions: Concurrent TP53 mutation and presence of CNS metastasis are associated with decreased PFS of ROS1-positive patients treated with crizotinib.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e20535
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 4
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    Online Resource
    Clonal dominance of EGFR and efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21501-e21501
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21501-e21501
    Abstract: e21501 Background: Though EGFR mutations in lung cancer are identified most often on the trunks of tumor phylogenetic trees in early stage, whether EGFR would always be the dominant clone in the advanced stage is unknown, as cancer evolution often follows a branched trajectory, with divergent subclones evolving simultaneously. The impact of clonal dominance of EGFR on outcomes with targeted therapies has not been explored. Methods: Paired tumor and plasma samples at diagnosis were obtained from systemic treatment naïve patients with advanced NSCLC in the clinical trial (NCT03059641). cfDNA and tumor DNA were sequenced by target-capture deep sequencing of 1021 genes related to solid tumors, with blood cells as the germline control. Clonal dominance analysis was performed on the basis of the CCF determined for SNVs and clustered in plasma or tumor sequencing data using a modified version of Pyclone. PFS was estimated using Kaplan-Meier method and compared using log-rank test. Results: From February 2017 to December 2019, 300 advanced NSCLC patients were enrolled prospectively from 14 centers cross China. One hundred and fourteen EGFR mutant patients treated with EGFR-TKI were followed until disease progression (PD). The medium follow-up time was 10 month (1-27 months) and 92 (80.7%) patients have reached PD, with the ORR of 74.6% (85/114), mPFS of 10.5 months. Clonal dominance analysis of EGFR showed 76 patients had EGFR as the dominant clone according to tissue NGS results, and 66 patients as the dominant clone according to plasma cfDNA NGS results (p = 0.04). The ORR was significantly higher for patients with EGFR as dominant clone according to plasma cfDNA NGS results (84.8% vs 60.9%, p = 0.016), and PFS was significantly longer (12 vs 8 months, HR = 2.58). There was no difference when using tissue NGS results to analyze EGFR clonal dominance. However, if comparing patients who were defined as EGFR dominant clone by both tissue and plasma (n = 44) with those defined as EGFR nondominant (n = 9), EGFR dominance was associated with higher ORR (84.1% vs 44.4%, p = 0.01), and longer PFS (11 vs 6 months, HR = 9.88) significantly. Moreover, multivariate Cox proportional hazard ratio analysis demonstrated it as an independent prognostic indicator of EGFR-TKIs. Conclusions: Clonal dominance of EGFR in the pretreatment plasma cfDNA is associated with the efficacy of EGFR-TKIs in NSCLC. This study indicated the importance of evaluating clonal dominance in the current clinical practice and future trial designs. Clinical trial information: NCT03059641.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e21501
    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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  • 5
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    Online Resource
    A multicenter real-world study of tumor-derived DNA from pleural effusion supernatant in genomic profiling of advanced lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21584-e21584
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21584-e21584
    Abstract: e21584 Background: Pleural effusion (PE) is commonly observed in advanced lung cancer. Researches have suggested molecular profiling of PE represents a minimally invasive approach of detecting tumor driver mutations for clinical decision making. The objective of this study is to investigate the efficacy and precision of detecting gene alterations in PE samples in the real world setting. Methods: 656 metastatic lung cancer patients with pleural effusion were enrolled in this study. Seven hundred and thirty-two samples, including 351 samples of PE supernatant, 224 plasma, 138 tissue, and 25 PE sediments from these patients were collected and subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related genes in a real world setting. The efficacy of pleural effusion in detecting actionable mutations and identifying resistant mechanisms of targeted therapy were analyzed by comparing different samples. Results: Among the 656 NSCLC patients, 413 were in M1a stage and 243 were in M1b/M1c stage, while 272 were newly diagnosed and 384 was previously treated. When comparing different groups of stage and therapeutic history, PE supernatant was preferred as the choice for those patients (46.6% - 48.2% vs 23.3%-34.8% of plasma vs 16.8%-21.2% of tissue and 0.96%-7.3% of PE sediment). While mutant allele frequency (MAFs) of plasma in patients of M1a stage was significantly lower than that of M1b/c stages, MAFs was similar for PE supernatant. EGFR, KRAS, MET, ALK, BRAF, ERBB2, ROS1, and RET actionable mutations were identified in 60, 12, 9, 7, 6, 3, 2, and 1 of the 118 PE supernatant samples at M1a stage taken before treatment. PE-supernatant demonstrated higher sensitivity than plasma of detecting actionable mutations in M1a disease (84.7% of PE-supernatant vs 42.1% of plasma, p 〈 0.01) but not in M1b/c stages (80.7% of PE-supernatant vs 86.4% of plasma). Seventy-two of the 117 patients who were resistant to 1 st or 2 nd generation of EGFR-TKI, 22 of the 42 patients resistant to osimertinib, and 9 of the 13 patients resistant to crizotinib had known resistant mutations identified. Remarkably, PE supernatant outperformed plasma in identifying resistant mutations to 1 st /2 nd generation EGFR-TKI (75.4% vs 29.8%, p 〈 0.001). Conclusions: This real world large cohort study verified that genomic profiling of PE-supernatant has higher actionable mutation detection sensitivity than plasma. It offers an alternative approach in assessing tumor genomics in advanced lung cancer when tumor tissue is not available.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e21584
    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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    Online Resource
    ALK resistance mutations (muts) developed in different ALK fusion types.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e14741-e14741
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e14741-e14741
    Abstract: e14741 Background: Patients (pts) treated with ALK inhibitors (ALKi) inevitably develops resistance. Diverse mutations (muts) confer resistance to ALKis, which may be related to the diverse types of ALK fusion. The objective of this study is to see whether the resistance mechanisms developed during ALKi therapy are ALK fusion types dependent. Methods: The mutation profiles of 38 pts with known ALK fusion partners and positions, who ordered NGS test in our institution after progressed on ≥ 1 ALKis, were analyzed. Results: Resistant muts in ALK kinase domain ( ALK resistant muts) were detected in 53% (20/38) of the resistant pts. 100% (1/1) of the EML4-ALK V5’ variant (V5’), 81% (13/16) of the EML4-ALK V3 variant (V3), 60% (3/5) of the non- EML4-ALK, 23% (3/13) of EML4-ALK V1 variant (V1), and 0% (0/3) of the EML4-ALK V2 variant (V2) had ALK resistant muts. ALK G1202R was detected in 29% of the pts. 100% (1/1) of the V5’, 50% (8/16) of the V3, 20% (1/5, HIP1-ALK) of the non- EML4-ALK, and none of the V1 (0/13) and V2 (0/3) had G1202R. Amplification and gain of function muts in oncogenes and loss of function muts in tumor suppressor gene were detected in 16% (6/38) of the pts, namely 4 V1, 1 V2, and 1 V3. On average, pts treated with 3 rd generation ALKis had significantly more muts in ALK (7.5 vs. 3.6, p = 0.0008) and in all targeted regions (9.1 vs. 4.3, p = 0.0005) than pts treated with only 1 st and 2 nd generation ALKis. Conclusions: The type of resistance mechanisms developed during ALKi therapy may depend on the ALK fusion type of the pt. ALK resistant muts, especially G1202R, developed most frequently in V3/V5’, followed by non- EML4-ALK, and V1/V2, while amplification and grain of function muts in oncogenes and loss of function muts in tumor suppressor genes developed more often in V1/V2 than in V3/V5’. The 3 rd generation ALKi may increase the genomic alterations in treated pts.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e14741
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 7
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    Online Resource
    MET amplification and activating mutation analysis in solid tumors using comprehensive NGS panel.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. e24267-e24267
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e24267-e24267
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.e24267
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 8
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    Online Resource
    ALK actionable mutations (muts) within cancer types and their responses to crizotinib (CZ).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e14739-e14739
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e14739-e14739
    Abstract: e14739 Background: CZ was recommended by NCCN for ALK-rearranged metastasis NSCLC as first-line therapy. Knowledge on the occurrence of ALK actionable muts within cancer types and the responses of ALK fusion types to CZ could better guide the treatment of ALK-rearranged pts. Methods: 772 ALK-mutated pts (with any ALK muts) detected by tissue/ctDNA NGS in our institution from Oct. 2016 to Oct. 2018 were included. ALK + (with any ALK actionable muts) and EGFR - (with no EGFR actionable muts) pts treated with CZ at any line were included for survival analysis. Progress-free survival (PFS) was estimated using Kaplan-Meier method and compared using log-rank test. Results: 339 ALK + pts were analyzed, including 331 lung cancer (LC: 265 NSCLC; 1 SCLC; 65 Unknown histology), 3 brain cancer (BC), 1 colon cancer (CC), 3 cancer of unknown primary (CUP), and 1 with no clinical information. The most common ALK mut was fusion (331/339), including 315 EML4-ALK, 5 KIF5B-ALK, 4 STRN-ALK, 1 ACSL3-ALK, 1 CLIP4-ALK, 1 DCTN1-ALK, 1 HIP1-ALK, 1 SRBD1-ALK, 1 TFG-ALK, and 1 ZFP161-ALK. Fusion position was known for 308 EML4-ALK, including 132 V1, 108 V3, 32 V2, 19 V5’, and 17 other variants (Vx). Except for 2 V1 with CUP, 1 KIF5B-ALK with CUP, 1 Vx with CC, and 1 EML4-ALK (no variant information) with BC, all the other fusions occurred in LC. ALK F1174L was detected only in 2 pts, both of whom had BC, specifically neuroblastoma. CZ was given to 76 ALK + EGFR - pts (mPFS: 9 mo, 95% CI: 8 – 13), including 70 EML4-ALK and 6 non- EML4-ALK (mPFS: 10 vs. 9 mo, p = 0.7). Though non-significant, V1 (n = 32) on average had a longer mPFS than V3 (n = 28) (12 vs. 8 mo, p = 0.3), which may partially be explained by the younger age at diagnosis of V1 than V3 (48 vs. 53, p = 0.005). 1 TFG-ALK, 1 CLIP4-ALK, 1 DCTN1-ALK, 1 HIPI-ALK, 1 ZFP161-ALK, and 1 KIF5B-ALK achieved a PFS of 3, 4, 8, 9, 13, and 19 mo on CZ, respectively. 1 SCLC (V3) received CZ at first-line progressed after 6 mo. Conclusions: Though majority of the ALK actionable muts were commonly found in LC, some alterations may occur more often in other cancer types, such as F1174L in neuroblastoma. Some fusion types (e.g. TFG-ALK) may benefit less from CZ than others (e.g. KIF5B-ALK). Limited by relative small sample size, these results merit further validation and investigation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e14739
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 9
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    Online Resource
    Next generation sequencing (NGS) based mutation profiling and heterogeneity of resistance mechanisms to AZD9291.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. 9068-9068
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 9068-9068
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.9068
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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