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T. Chu
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Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Track:
- Presentations: 4
- Moderators:
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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162P - Responses to EGFR TKIs and ALK TKIs in advanced NSCLC patients harboring concomitant EGFR and ALK alterations (ID 503)
12:30 - 13:00 | Author(s): T. Chu
- Abstract
Background:
Previous studies indicated that Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement are mutually exclusive in non-small cell lung cancer (NSCLC). However, cases diagnosed with concomitant EGFR and ALK alterations has been occasionally reported. This study aimed to assess the prevalence of this small subset patients and optimize clinical management.
Methods:
We retrospectively collected clinical outcomes of 29 cases who had concomitant EGFR and ALK alterations from 5816 lung cancer patients tested EGFR mutation and ALK rearrangement between 2011–2017 in the Shanghai Chest Hospital. Meanwhile, we identified 103 cases harboring double positive mutations from a literature search. Of these 132 cases, 81 patients received EGFR tyrosine kinase inhibitor (EGFR-TKI) or ALK-TKI treatment.
Results:
The frequency of EGFR/ALK co-alterations was 0.5% (29/5816; 95%CI:0.3%-0.7%) in NSCLC in our center. For all 132 cases, there is a prevalence of women (67 female, 46 male, 19 not reported), Asian (87Asian, 44 Caucasian, 1 not reported) and never smoker patients (77 never smokers, 21 smokers, 34 not reported). We divided the patients into three groups according to EGFR or ALK TKIs treatment: A: single EGFR TKI group (36 cases), B: single ALK TKI group (14 cases) and C: both TKIs (31 cases). All patients were assessed for TKIs responses. The disease control rate (DCR) of EGFR-TKI was 81.5%, whereas the DCR of ALK-TKI was 89.1%. The median PFS of three groups were 12.4, 15.9 and 24.1months, respectively (P = 0.02). The PFS of group A and C had statistically sigificant difference (P = 0.006). But the PFS of group A and B, B and C did not have statistical significance (P = 0.338, P = 0.335).
Conclusions:
EGFR mutations and ALK rearrangement do coexist in NSCLC. In cases with double positive mutations, our preliminary study suggests that PFS of those who received double TKIs is longer than those who received only one TKI. Combination of both TKIs might be an appropriate choice. The result of the study indicates that ALK TKI might be preferentially administered when TKI is initiated as first-line treatment.
Clinical trial identification:
Legal entity responsible for the study:
Wang shuyuan
Funding:
Has not received any funding
Disclosure:
All authors have declared no conflicts of interest.
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167P - Efficacy of pemetrexed-based chemotherapy in advanced lung adenocarcinoma patients with ROS-1 rearrangement (ID 413)
12:30 - 13:00 | Author(s): T. Chu
- Abstract
Background:
When chemotherapy is commenced as first-line treatment in advanced lung adenocarcinoma patients with ROS-1 rearrangement, it is unclear that which agent should be preferentially administered. The aim of this study is to compare the therapeutic efficacy of pemetrexed-containing (Pem-C) and non-pemetrexed-containing (Non-Pem-C) chemotherapy in these patients.
Methods:
We retrospectively identified patients who were demonstrated to be ROS-1 positive by multiplex reverse-transcriptase polymerase chain reaction (RT-PCR) between October 2014 and December 2016. Those who received platinum-based dual agent chemotherapy as palliative treatment were included for further analysis.
Results:
A total of 4596 consecutive individuals were screened and 55 eligible individuals were enrolled into this study. In first-line treatment, patients who received Pem-C treatment (n = 39) derived a higher objective response rate (ORR, 40.0% vs. 7.1%, P = 0.02) and progression-free survival (PFS1, 7.0 months vs. 3.9 months, P < 0.01) compared with those who received Non-Pem-C treatment (n = 16). However, in later-line treatment, progression-free survival (PFS2) was not statistically superior in the Pem-C group (3.1 months, 95% CI: 0.6–5.6 months) compared with the Non-Pem-C group (1.9 months, 95% CI: 0.1–3.1 months, P = 0.12).
Conclusions:
Pem-C treatment resulted in better clinical outcomes compared with other agents in patients with ROS-1 rearrangement when initiated as first-line treatment.
Clinical trial identification:
Legal entity responsible for the study:
Bo Zhang
Funding:
Has not received any funding
Disclosure:
All authors have declared no conflicts of interest.
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61P - mir-125b plays a tumor suppressor role in inflammation-related non-small cell lung cancer via repressing IGF-1 signal pathway (ID 509)
12:30 - 13:00 | Author(s): T. Chu
- Abstract
Background:
Epidemiologic data have indicated that chronic inflammation was highly associated with the pathogenesis of lung cancer. However, the molecular relations between inflammation and lung cancer have not been well understood. MicroRNAs could connect the inflammatory response with tumorigenesis through regulating their cancer-related targets. The aim of the present study was to identify the core miRNA in inflammation-related lung cancer and its potential mechanisms.
Methods:
RT-PCR was used to detect the expression of miRNAs and mRNAs. CKK8 and flow cytometry assays was performed for the function experiments. Microarray analysis and IPA analysis were used to predict the potential signal pathway.
Results:
Mir-125b was the most dramatically up-regulated miRNAs after treated with IFN-r, whereas after stimulated with IL-10, mir-125b was the most strikingly down-regulated ones. Restoration of mir-125b expression could completely overrode the impact of IL-10 on both cell proliferation and apoptosis in NSCLC cell lines. And the level of mir-125b was significantly lower in 30 NSCLC tumor tissues compared with normal controls (P < 0.0001). Microarray analysis found 69 up-regulated genes and 105 down-regulated genes after down-regulate mir-125b. And IPA analysis indicated that IGF-1 signaling pathway was dramatically activated. The results were validated by RT-PCR.
Conclusions:
MiR-125b might play a tumor suppressor role via inhibiting IGF-1 signaling in inflammation-related lung cancer.
Clinical trial identification:
Legal entity responsible for the study:
Yanwei Zhang
Funding:
Has not received any funding
Disclosure:
All authors have declared no conflicts of interest.
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92P - Expression of TNFRII in serum is correlated with the significant risk of subcentimeter lung adenocarcinoma (ID 312)
12:30 - 13:00 | Author(s): T. Chu
- Abstract
Background:
With the rapid advances of LDCT screening for lung cancer, the opportunity to detect subcentimeter NSCLC is gradually increasing. But, even subcentimeter NSCLCs are not always in the early stage. Thus, it is quite important for us to judge the possibility of malignancy for these patients, even the tumor size is less than 10 mm. Chronic inflammation is well established as a hallmark in lung carcinogenesis. The aim of the present study is to evaluate the correlation between inflammation biomarkers and the risk for subcentimeter lung adenocarcinoma.
Methods:
Inflammatory biomarkers were measured in 71 subcentimeter lung adenocarcinoma patients and 71 age-, sex- and smoking-matched healthy controls by using the Luminex bead-based assay.
Results:
The expression level of TNFRII is significantly down-regulated in subcentimeter lung adenocarcinoma patients compared with the healthy controls (P < 0.001). And the results were validated by oncomine data mining analysis. Elevated levels of TNFRII were associated with an 89% reduced risk for subcentimeter lung adenocarcinoma. (OR = 0.11, 95% CI: 0.04–0.30, P = 2.4 × 10[−5]). BLC was associated with a 2.70-fold (95% CI: 1.31–5.58, P = 7.0 × 10[−3]) increased risk of subcentimeter lung adenocarcinoma for the comparison of patients in the higher-level group with the lower-level group. To yield more information, the BLC/TNFRII ratio was created to examine their prediction for the risk of subcentimeter lung adenocarcinoma, and there was a 35-fold increased risk for patients in the higher-level group relative to patients in the lower-level group. Further ROC curve analysis revealed that TNFRII was a significant diagnostic biomarker for subcentimeter lung adenocarcinoma, with the area under the curve of 0.73 (95% CI: 0.65–0.82, P = 2.0 × 10[−6]). The sensitivity, specificity and accuracy were 0.75, 0.72 and 0.73, respectively.
Conclusions:
Our findings demonstrated that TNFRII was associated with the significant risk of subcentimeter lung adenocarcinoma and could be a promising biomarker for accessorily diagnosing subcentimeter lung adenocarcinoma.
Clinical trial identification:
Legal entity responsible for the study:
Yanwei Zhang
Funding:
Has not received any funding
Disclosure:
All authors have declared no conflicts of interest.
