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Ming Chen
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EP1.12 - Small Cell Lung Cancer/NET (ID 202)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.12-35 - Comparison of Long Term Results Between Matched Chemoradiotherapy and Surgery for Limited Stage Small Cell Lung Cancer (ID 247)
08:00 - 18:00 | Author(s): Ming Chen
- Abstract
Background
The role of surgery in patients with SCLC is undefined. Our study was conducted to compare the long term results of chemoradiotherapy with surgical treatment for limited stage SCLC.To compare the efficacy of chemoradiotherapy or surgery for limited-stage small cell lung cancer (SCLC).
Method
A retrospective analysis was performed on 138 patients with limited-stage SCLC who received surgery (69 patients) or chemoradiotherapy (69 patients) between January 2000 and September 2016 in Zhejiang Cancer Hospital. Patients of the chemoradiotherapy group were selected by using ‘pair-matched case-control’ methodology from a cohort of 503 patients who received chemoradiotherapy.
Result
The major prognostic factors including T, N stage, treatment duration, age, gender, and whether or not received prophylactic cranial irradiation were well balanced between two groups. The median overall survival (OS) time and 5-year OS rate were 37.1 months and 45.0% in surgical group versus 45.0 months and 45.0% in chemoradiotherapy group (P=0.846). The median progression-free survival (PFS) time and 5-year PFS rate were 27.1 months and 37.8% versus 36.2 months and 40.0% respectively in the two groups (P=0.610). The 5-year OS rate (62.3% vs. 40.1%, P=0.038) and 5-year PFS rate (80.1% vs. 40.1%, P=0.048) in surgical group were significantly higher than those of chemoradiotherapy group in patients with stage I disease. While the 5-year OS rate (41.2% vs. 50.6%, P=0.946), 5-year PFS rate (64.7% vs. 42.1%, P=0.280) of surgery for stage II SCLC were comparable to chemoradiotherapy. As for stage III SCLC, compared with the surgical group, the chemoradiotherapy group had a better 5-year OS trend (25.1% vs. 47.6%, P=0.220).
Conclusion
Surgery could confer survival benefit in patients with p-stage I disease, but not in patients with p-stage II and III disease.
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EP1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 206)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.16-15 - Subclinical Interstitial Lung Disease Is a Risk Factor for Radiation Pneumonitis in Patients with Lung Cancer After Thoracic Radiation Therapy (ID 1512)
08:00 - 18:00 | Author(s): Ming Chen
- Abstract
Background
Previous studies reported that patients with subclinical interstitial lung disease were more susceptible to developing radiation pneumonitis after thoracic stereotactic body radiotherapy or thoracic 3-dimensional conformal radiotherapy . The present study aimed to evaluate the incidence and predictors of RP after TRT in patients with lung cancer with or without preexisting subclinical interstitial pulmonary disease.
Method
Patients with lung cancer between May 2016 and August 2018, who were treated with thoracic intensity-modulated radiation therapy in our institutions, were prospectively analyzed. Statistical analysis was performed using SPSS software 22.0 for Mac. Univariate and multivariate analyses were used to assess the correlation of subclinical interstitial lung disease with radiation pneumonitis and risk factors of radiation pneumonitis. A P value < 0.05 was considered statistically significant.
Result
A total of 123 patients with lung cancer were prospectively analyzed. The median follow-up time was 13.9 months. Radiation pneumonitis was observed in 30, 18, 2 and 1 patient with grades 1, 2, 3 and 5 radiation pneumonits, respectively. No patient suffered from ≥grade 4 radiation pneumonitis. The incidence of ≥grade 2 radiation pneumonitis was 17.1%. Mean lung dose, V10, V20, V30 and subclinical interstitial lung disease before radiotherapy were associated with an increased incidence of ≥grade 2 radiation pneumonits in univariate analysis. Subclinical interstitial lung disease and mean lung dose were significantly associated with ≥grade 2 radiation pneumonits in multivariate analysis (P=0.022, P=0.018, respectively).
Conclusion
Preexisting subclinical interstitial lung disease and mean lung dose are predictors of ≥grade 2 radiation pneumonits.
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OA15 - Targeted Agents and Immunotherapy for Small Cell Lung Cancer (ID 152)
- Event: WCLC 2019
- Type: Oral Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:Raffaele Califano, Charles M Rudin
- Coordinates: 9/10/2019, 14:30 - 16:00, Hilton Head (1978)
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OA15.04 - Genomic and TCR Intratumor Heterogeneity of Small-Cell Lung Cancer by Multiregion Sequencing: An Association with Survival (Now Available) (ID 1458)
14:30 - 16:00 | Author(s): Ming Chen
- Abstract
- Presentation
Background
Small cell lung cancer (SCLC) is an aggressive cancer. Although sensitive to initial therapy, recurrence is almost inevitable. The molecular mechanisms underlying recurrence are unknown. We have previously demonstrated that complex genomic and T cell receptor (TCR) intratumor heterogeneity (ITH) was associated with increased risks of relapse in non-small cell lung cancers (NSCLC). Genomic ITH and TCR architecture of SCLC and its clinical impact have not been well studied, largely due to lack of tumor specimens as surgery is rarely used to treat SCLC.
Method
We performed multiregion whole-exome sequencing and TCR sequencing of 49 tumor samples from 18 resected limited-stage SCLCs to delineate the immunogenomic ITH of SCLC. We compared the results to those in NSCLC and assessed the association of genomic and TCR attributes with patient’s survival.
Result
On average, 544 mutations/sample were detected. The median proportion of trunk mutations (mutations identified in all regions within the same tumors) was 80.4% versus 70% in NSCLC (TRACERx, Jamal-Hanjani, NEJM, 2017, p=0.08) and all TP53 and RB1 mutations were trunk mutations, suggesting these mutations were early events during carcinogenesis of this cohort of SCLCs. A higher non-synonymous tumor mutational burden (TMB) was associated with a higher T cell density (infiltration) in the tumor (r=0.46, p=0.005). Compared to the TCR repertoire of NSCLC (Reuben, WCLC, 2017), these SCLC tumors demonstrated significantly lower T-cell density (0.05 versus 0.24, p<0.0001), richness (diversity, 1,043 versus 3,666, p<0.0001) and clonality (reactivity, average 0.02 versus 0.15, p<0.0001) despite similar non-synonymous TMB (average 187 in SCLC versus 176 mutations/sample in NSCLC). Only 0.2% to 14.6% of T cells were detectable across all regions from the same tumors, suggesting substantial TCR ITH. Jaccard index (JI), a parameter quantifying TCR ITH was significantly lower in SCLC than in NSCLC (0.06 versus 0.1, p<0.0001) implying higher level of TCR ITH in SCLC than NSCLC. Interestingly, higher T-cell density, richness or clonality appeared to be associated with lower risk of recurrence numerically. Furthermore, higher TCR JI (less degree of ITH) was associated with significantly longer overall survival (HR=0.15, p=0.04).
Conclusion
Limited-stage SCLC tumors have distinct TCR repertoire and genomic ITH architecture. Overall, SCLC may have a more pronounced immunosuppressive microenvironment and higher level of TCR repertoire ITH than NSCLC. Nevertheless, higher degree of T cell infiltration and clonal expansion as well as more homogeneous T cell response may be associated with more favorable clinical outcome in patients with limited-stage SCLC.
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P1.12 - Small Cell Lung Cancer/NET (ID 179)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.12-12 - Factors Affecting the Risk of Brain Metastasis in Limited-Stage Small Cell Lung Cancer After Prophylactic Cranial Irradiation (ID 243)
09:45 - 18:00 | Author(s): Ming Chen
- Abstract
Background
Prophylactic cranial irradiation (PCI) can reduce brain metastases (BM) and improve overall survival (OS) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete response to primary therapy. However, some SCLC patients still suffer from BM after PCI with unknown risk factors.This study conducted to assess the factors affecting the risk of BM in patients with LS-SCLC after PCI and identify characteristics of patients who may not benefit from PCI.
Method
We identified 550 patients who received chemoradiotherapy at Zhejiang Cancer Hospital in 2002–2017. All patients received PCI. Kaplan–Meier analyses and Cox regression analyses were used to identify factors influencing OS and BM.
Result
The median survival time for this patient population was 27.9 months, and the 5-year overall survival rate was 31%. Pathologic stage not only correlated with overall survival but also significantly affected the risk of BM. For the whole group, 15.6% (86/550) of the patients had evidence of metastases to brain. The frequency of BM in patients with pathologic stages I, II, and III were 9.3% (4/43), 13.4% (7/52), and 16.5% (75/455), (P=0.026), Having tumors ≥5 cm increased the risk of BM (HR: 1.781 95%CI：1.044-3.039, P=0.034) but not death (HR:1.126 95%CI：0.925-1.663, P=0.182). The median survival time among patients ＜60 years were significantly higher than patients ≥60 years (34.9 months VS. 24.6 months，P=0.001)，however, the difference of the BM risk in two group was not statistically significant.
Conclusion
PCI remains standard therapy after complete response to chemoradiotherapy for LS-SCLC. However, patients with tumors ≥5 cm may have a higher risk of developing brain metastases after PCI. Further work is warranted to identify patients who may not benefit from PCI.
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-17 - Genomic Evolution During TKI Treatment in Non-Small Cell Lung Cancer Patients With or Without Acquired T790M Mutation (ID 2988)
09:45 - 18:00 | Author(s): Ming Chen
- Abstract
Background
EGFR-mutant non-small-cell lung cancer (NSCLC) patients inevitably develop drug resistance when treated with EGFR tyrosine kinase inhibitors (TKIs). Clonal and clinical analyses of genetic alterations at baseline and progressive disease (PD), as well as differences between acquired T790M and T790M-negative patients in drug-resistant mechanisms, have not been systematically studied.
Method
We performed targeted sequencing of pre-treatment and PD tumor samples from 54 EGFR-mutant NSCLC patients. Ten additional patients were sequenced using whole exome sequencing to infer the clonal evolution patterns.
Result
We observed new co-occurring alterations and pathways limiting EGFR-inhibitor response, including 9p34.3/19p13.3 (NOTCH1/STK11) co-deletion and TGF-beta pathway alterations. Besides acquired T790M mutation, chromosomal instability (CIN) related genes including AURKA and TP53 alterations were the most frequently acquired events. CIN significantly increased with TKI treatment in T790M-negative patients. Transcriptional regulators including HNF1A, ATRX and NKX2-1 acquired alterations were enriched in T790M-positive patients, and diverse oncogenic pathway alterations were more common in T790M-negative patients. T790M-positive patients had improved PFS compared to T790M-negative patients. We further identified subgroups within T790M-positive or T790M-negative patients with distinct PFS. Clonal evolution analysis indicated progression of T790M-positive patients depends on competition between T790M and non-T790M resistant subclones.
Conclusion
Our study is the first attempt to identify co-occurring copy number events to stratify patients resistant to TKI treatment. Besides acquired T790M mutation, chromosomal instability (CIN) related genes were identified as the most frequently acquired events. Clonal evolution analysis indicated indicate that higher competitive advantage of T790M was associated with improved PFS.
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P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.16-13 - Risk Factors of Radiation Pneumonitis in Lung Cancer Patients with Subclinical Interstitial Lung Disease After Thoracic Radiotherapy (ID 1495)
10:15 - 18:15 | Author(s): Ming Chen
- Abstract
Background
Previous studies reported that patients with subclinical interstitial lung disease were more susceptible to developing radiation pneumonitis after thoracic stereotactic body radiotherapy or thoracic radiation therapy. The present study aimed to evaluate the incidence and risk factors of radiation pneumonitis after thoracic radiation therapy in lung cancer patients with subclinical interstitial lung disease.
Method
Patients with subclinical interstitial lung disease between January 2016 and December 2017, who were treated with thoracic intensity-modulated radiation therapy in our institutions, were prospectively analyzed. The diagnosis of subclinical interstitial lung disease was based on the pretreatment high-resolution computed tomography imaging, such as honeycombing, subpleural reticular opacities, ground-glass opacity, and traction bronchiectasis. Statistical analysis was performed using SPSS software 22.0 for Mac. Univariate and multivariate analyses were used to assess the correlation of clinical factors, dose-volume histogram-based dosimetric parameters，and imaging characteristics of preexisting subclinical interstitial lung disease with radiation pneumonitis. A P value < 0.05 was considered statistically significant.
Result
A total of 87 consecutive patients with subclinical interstitial lung disease were prospectively analyzed. The median follow-up time was 14.1 months. RP was observed in 19 (21.8%), 27 (31.0%), 10 (11.5%), 3 (3.4%), and 5 (5.7%) patients with grades 1, 2, 3, 4 and 5 RP, respectively. The location of tumors and mean lung dose were significantly associated with ≥grade 2 RP in univariate analysis (P=0.043, P=0.024, respectively). Patients who received gemcitabine in the past and the involvement of subclinical interstitial lung disease ≥ 25% of the lung volume were significantly associated with ≥grade 3 radiation pneumonitis in univariate analysis (P=0.031, P=0.037, respectively). Patients who received gemcitabine in the past and the involvement of subclinical interstitial lung disease ≥ 25% of the lung volume were significantly associated with ≥grade 3 RP in multivariate analysis (P=0.046，P=0.017, respectively).
Conclusion
Subclinical interstitial lung disease is associated with an increased risk of radiation pneumonitis. Patients who received gemcitabine in the past and the involvement of subclinical interstitial lung disease ≥ 25% of the lung volume are associated with an increased risk of ≥grade 3 radiation pneumonitis.
