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Ming Chen
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OA13 - Therapeutics and Radiation for Small Cell Lung Cancer (ID 927)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 10:30 - 12:00, Room 203 BD
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OA13.06 - Final Report of a Prospective Randomized Study on Thoracic Radiotherapy Target Volumes in Limited-stage Small Cell Lung Cancer with Radiation Dosimetric and Pathologic Analyses (ID 11970)
11:25 - 11:35 | Author(s): Ming Chen
- Abstract
- Presentation
Background
The interim analysis of our prospective trial, which compared irradiation to pre-chemotherapy or post-chemotherapy tumour extent while application of involved field radiotherapy (IFRT) for limited-stage small cell lung cancer (SCLC), showed that reduced field did not result in increased local/regional out-field recurrence. This report presents the final results of the clinical study with radiation dosimetric and pathologic analysis as interpretations.
a9ded1e5ce5d75814730bb4caaf49419 Method
Chemotherapy consisted of 4 to 6 cycles of etoposide and cisplatin (EP). After 2 cycles of EP, patients were randomly assigned to receive thoracic radiotherapy (TRT) to either the post- or pre-chemotherapy tumour extent as study arm or control. TRT was administered concurrently with cycle 3 chemotherapy. IFRT was applied for both arms. The lymph node regions (groups 1 to 10) were contoured in treatment planning system. The intentional or incidental radiation doses to each lymph node regions were recorded. Patients with stage T1-2N0-1M0 SCLC received radical lobectomy. The minimal distances between microscopic nidus and the edge of gross tumor were measured. The clinical target volume of the primary tumor (CTV-T) was defined as the margins covering 95% of microscopic disease extension.
4c3880bb027f159e801041b1021e88e8 Result
Between June, 2002 and January, 2017, 159 and 150 patients were randomly assigned to study arm or control. The 1-, 3-, and 5-year local/regional progression free probability were 79.4%, 60.1% and 60.1% respectively in the study arm versus 79.8%, 64.5%, and 57.3% in the control (p=0.73). The median overall survival (OS) time was 22.1 months in the study arm (95% CI, 18.2-26.0) and 26.9 months (95% CI, 23.5-30.3) in the control, the 1-, 3-, 5-, and 7-year OS rates were 81.1%, 31.6%, 23.9% and 22.2% respectively in the study arm versus 85.3%, 36.6%, 26.1% and 20.0% in the control arm (p=0.51). A total of 1680 lymph node regions in 105 patients were contoured. The lymph node regions that received incidental radiation doses over 30Gy were: 7, 3P, 4L, 6, 4R, 5 and 2L. Eight patients were enrolled in the pathologic evaluation of CTV-T. The median range of CTV-T in patients received or did not receive neoadjuvant chemotherapy were 0.4mm and 1.7mm respectively, a margin of 1.4mm and 10.2mm could cover 95% of microscopic nidus extension respectively (p=0.00).
8eea62084ca7e541d918e823422bd82e Conclusion
Irradiating post-chemotherapy tumour extent and applicant of IFRT didn't increase local/regional failure, and the OS difference wasn't statistically significant between the two arms. TRT could be limited to post-chemotherapy tumour extent, while IFRT could be routinely applied for limited-stage SCLC patients.
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-43 - Next-Generation Sequencing in the Exploration of Genetic Heterogeneity for Lung Adenocarcinoma Patients with EGFR Activating Mutations (ID 11194)
16:45 - 18:00 | Author(s): Ming Chen
- Abstract
Background
Increasing evidence leads to a ratiocination that genetic heterogeneity of the lung adenocarcinoma patients with sensitive EGFR mutations may impact clinical responses and outcomes to EGFR-TKIs.
a9ded1e5ce5d75814730bb4caaf49419 Method
We performed targeted NGS with a gene panel covering 416 cancer-related genes to profile genetic characteristics of 69 lung adenocarcinoma patients with activating EGFR mutations and assessed the contribution of targeted NGS to exploration of genetic heterogeneity of such cohort.
4c3880bb027f159e801041b1021e88e8 Result
We detected total 200 actionable genetic alterations (mean 2.9 variations per patient, range: 1-7 variations) in tumor DNA and 140 actionable genetic alterations (mean 2.0 variations per patient, range: 0-5 variations) in matched plasma ctDNA, respectively. The concurrent genes with the highest mutation rate were TP53 (observed in 72.5% patients), other uncommon EGFR mutations (observed in 21.7% patients), EGFR amplification (observed in 20.3% patients), RB1 (observed in 10.1% patients), PIK3CA (observed in 7.2% patients), and MYC (observed in 5.8% patients). NGS provides EGFR mutation detection in plasma with a test sensitivity of 88.2% and specificity of 100.0%. Novel mutations potentially related to primary drug resistance were identified including: CDC73, SMAD4, and CTNNB1 missense mutations; RB1, ARID1A, ARID2, DNMT3A, STK11, and ATR frameshift indel; CDKN2B-PATA31D1, NFKBIA-OR11H12 fusion gene; PRKCI, CCNE1, MCL1, ARAF copy number gain; RB1 loss. The pathways analysis showed that unique pathways in the primary resistant cohort included: 1) immune related pathways: Toll-like receptor signaling pathway, T cell receptor signaling pathway; 2) epithelial-mesenchymal transition (EMT) related pathways: TGF-beta signaling pathway; 3) downstream pathway of EGFR: PIK3CA/AKT/mTOR signaling pathway; 4) cell function related pathways: Mismatch repair pathway, AMPK signaling pathway, TNF signaling pathway, Notch signaling pathway, and Transcriptional misregulation in cancer.
8eea62084ca7e541d918e823422bd82e Conclusion
In conclusion, we note the complexity and heterogeneity of activating EGFR-mutant lung adenocarcinoma that may confer primary resistance to EGFR TKI using NGS platform. This study highlights the advantage of the NGS than traditional methods on testing EGFR mutations, enabling further refinement in sub-classification for the improved personalization of lung cancer treatment.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 961)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.12-18 - Interstitial Lung Abnormalities are a Risk Factor for Radiation Pneumonitis in Patients with Limited-Stage Small-Cell Lung Cancer (ID 11923)
16:45 - 18:00 | Author(s): Ming Chen
- Abstract
Background
Previous studies reported that patients wth preexisting radiological interstitial lung abnormalities (ILAs) were more susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy (TRT). The present study aimed to evaluate the incidence and predictors of RP after TRT in patients with limited-stage small-cell lung cancer (LS-SCLC) with or without preexisting radiological ILAs.
a9ded1e5ce5d75814730bb4caaf49419 Method
A total of 183 consecutive patients with LS-SCLC between January 2015 and December 2016, who were treated with thoracic intensity-modulated radiation therapy at our institution, were analyzed. The diagnosis of ILAs was reviewed by two experienced thoracic radiologists based on the pretreatment high-resolution computed tomography(CT) imaging, such as honeycombing, subpleural reticular opacities, ground-glass opacity, and traction bronchiectasis. Univariate and multivariate analyses were used to assess the correlation of clinical factors, preexisting radiological ILAs, and dose-volume histogram-based dosimetric parameters with RP. The correlation between the preexisting ILAs score on CT findings and the grade of RP was analyzed by Pearson Correlation.
4c3880bb027f159e801041b1021e88e8 Result
Twenty (10.9%) patients had preexisting radiological ILAs. The median follow-up time was 10.9 months. RP was observed in 75 (41.0%), 35 (19.1%), 11 (6.0%), and 0 (0%) patients with grades 1, 2, 3, and ≥4 RP, respectively. The incidence of ≥ grade 2 and 3 RP at 1 year was 26.3% and 6.2% in the entire cohort, respectively. Preexisting radiological ILAs were associated with an increased risk of ≥grade 2 RP (84.1% in ILAs + vs 18.7% in ILAs-, P＜0.001) and ≥ grade 3 RP (27.7% in ILAs + vs 3.8% in ILAs-, P ＜0.001) at 1 year. Preexisting radiological ILAs was a significant predictors of ≥grade 2 RP and ≥grade 3 RP in multivariate analysis (P ＜0.001, P = 0.004, respectively). Lower forced expiratory volume in 1 second was a significant predictor of ≥grade 2 RP in multivariate analysis (P = 0.043). The ratio of CD4 and CD8 cells has a tendency to predict ≥grade 3 RP in multivariate analysis (P = 0.053).There was a moderate correlation between the preexisting ILAs score on CT findings and the grade of RP (Pearson Correlation Coefficient = 0.364, P ＜0.001).
8eea62084ca7e541d918e823422bd82e Conclusion
Preexisting radiological ILAs is associated with an increased risk of ≥grade 2 RP and ≥grade 3 RP after TRT in patients with LS-SCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
