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K. Yoshida
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-082 - The Feasibility of Cell-Free DNA Sequencing for Mutation Detection in Non–Small Cell Lung Cancer Was Detemined by Tumor Volume (ID 6001)
14:30 - 14:30 | Author(s): K. Yoshida
- Abstract
Background:
Targeted therapeutics such as tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) have recently been introduced into clinical practice for individuals with NSCLC positive for actionable mutations of EGFR or ALK fusions, respectively. Molecular profiling that is able to predict the response to such drugs has thus become an important therapeutic strategy, allowing selection of the most appropriate treatment for individual patients.
Methods:
Matched lung cancer tissue and serum specimens were collected from 150 patients who underwent surgery at Tokyo Medical University Hospital from January 2013 to July 2014. All tissue samples were stored at –80°C until analysis. Tumor DNA and cfDNA samples were subjected to analysis with next-generation sequencing (NGS) panels for mutation detection.
Results:
All tumor DNA samples were successfully sequenced with the Ion Proton platform. The median read number per amplicon was 15,632. We identified TP53 mutations in 58 cases (38.7%); EGFR mutations in 56 (37.3%); KRAS mutations in 15 (10.0%); CTNNB1 mutations in 7 (4.7%); ERBB2, PIK3CA, BRAF, and PTEN mutations in 3 each (2.0%); and ERBB4, MET, ALK, FGFR2, NRAS, AKT1, and FBXW7 mutations in 1 each (0.7%). No mutation was detected in 22.0% (33/150) of the samples. Serum cfDNA was extracted for all 150 patients, with a median yield (copy number) of 4936 (range, 572 to 373,658). A total of 149 of the 150 (99.3%) cfDNA samples were successfully sequenced with the Ion Proton platform, with sequencing failure being due to an insufficient read number per amplicon in the one unsuccessful case. The median read number per amplicon for the 149 successfully sequenced cfDNA samples was 33,982.
Conclusion:
These results suggested that detection of mutations in cfDNA of patients with disease at stage IA or IB or at T2a or lower is difficult, and that the feasibility of mutation detection with cfDNA may depend on the T factor rather than the N factor. Tumor volume in the cfDNA mutation–positive group was significantly greater than that in the cfDNA mutation–negative group (159.1 ± 58.0 versus 52.5 ± 9.9 cm[3], p = 0.014). The maximum tumor diameter calculated at diagnosis was also larger in the cfDNA mutation–positive group than in the cfDNA mutation–negative group (5.3 ± 0.7 versus 4.1 ± 0.3 cm, p = 0.050). These results suggested that tumor volume is a determining factor for the feasibility of mutation detection with cfDNA.
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P1.08 - Poster Session with Presenters Present (ID 460)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.08-034 - Prognostic Impact of EGFR Mutation in Patients with Surgically Resected Lung Adenocarcinoma; Analysis about Subtypes of EGFR Mutations (ID 6031)
14:30 - 14:30 | Author(s): K. Yoshida
- Abstract
Background:
Epidermal growth factor receptor (EGFR) gene mutations have an important role for predicting the prognosis in advanced or recurrent lung cancer patients. However, the significance of EGFR mutation as a prognostic factor for survival after complete resection remains controversial. The aim of this study is to evaluate the impact of mutational status in patients with surgically resected lung adenocarcinoma.
Methods:
We retrospectively investigated the data of 414 patients (pts) with p-stage I-IIIA adenocarcinoma who underwent completely tumor resection in our hospital from 2009 to 2013. Overall survival (OS), disease-free survival (DFS) , and clinico-pathological factors affecting these factors were evaluated.
Results:
There were 202 males and 212 females (median age, 67 years). In total, 270 (65%), 66 (16%) and 78 pts (19%) had p-stageI, II and IIIA disease respectively. In all 210 pts (51%) with EGFR mutation were detected. Eighty-six pts (21%) had exon 19 deletion (19 del) and 113 pts (27%), exon 21 mutation (L858R). Among 414 pts, 131 pts (31%) had lung cancer recurrence. The median follow-up period was 38.6 months. p-stageI mutant/wild:145/125, II:24/42, and IIIA:41/37. The 3-year survival rates of p-I-II and IIIA mutant/wild were 96.8%/92.1% and 81.6%/61.8% respectively. The median survival time of p-stageIIIA mutant was 80.5 months, and those of others were not reached. The 3-year DFS of p-I-II and IIIA mutant/wild were 78.3%/69.2% and 27.1%/45.1%, respectively. There were no significant difference in OS and DFS at each p-stage despite the EGFR mutational status. Compared to the wild type, the p-IIIA mutant group had a poor DFS. conversely, compared to wild type, the p-I mutant group showed a favorable DFS. According to the subtypes of EGFR mutation, there were no significant differences among EGFR subtypes, but pts with 19del tended to have the worst DFS. In subgroup analysis of 131 pts with recurrence, 3-year survival rate of p-I-II and IIIA mutant/wild were 92.0%/75.8% and 80.8%/45.6% respectively. Pts with p-IIIA mutant showed significantly favorable OS than those of wild type (p=0.014) as well as with p-I-II wild type. Although OS was not significantly different among the subtypes of EGFR mutation, pts with 19del showed statistically better prognosis than shown by the wild type (p=0.038).
Conclusion:
EGFR status was an independent prognostic factor in pts with surgically resected lung adenocarcinoma. Particularly, EGFR exon 19 deletion might be the strongest predictive factor of poor DFS and good OS in resected lung adenocarcinoma.
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-017 - A Clinical Outcome of Resected Small-Sized Non-Small Cell Lung Cancer 1 cm or Less in Diameter with N2 Lymph Node Metastasis (ID 5573)
14:30 - 14:30 | Author(s): K. Yoshida
- Abstract
Background:
The detection of small-sized (≤ 1cm) non-small cell lung cancer (NSCLC) has increased with the development of high-resolution computed tomography. The reported 5-year survival rate of T1a (≤ 2cm) N0M0 patients is more than 80%, and that of p-T1a (≤ 2cm) N2M0 patients has also steadily improved.
Methods:
Between 1991 and 2011, a total of 917 patients with small-sized (≤ 2cm) NSCLC underwent curative pulmonary resection with systematic lymph node dissection at Tokyo Medical University Hospital and Tokyo Medical University Ibaraki Medical Center. We retrospectively evaluated their postoperative clinical outcomes and survival rates. Survival was analyzed using the Kaplan-Meier method and log-rank test.
Results:
There were 46 (5.0%) patients with mediastinal lymph node metastasis in pT1a (≤ 2cm). And there were 6 (0.6%) patients with pT1a (≤ 1cm) N2M0. The histological types were 3 cases of adenocarcinoma, 2 case of squamous cell carcinoma, and one large cell carcinoma. The respectively status of lymph node metastasis was single station in 2 cases and multiple station in 4 cases. Skip lymph node metastasis was observed in 2 cases. There were 26 cases (56.5%) that were upstaged from clinical diagnosis in pT1a (≤ 2 cm) N2M0 patients. There was one upstaging case from cT1a (≤ 1 cm) N0M0 to pT1a (≤ 2 cm) N2M0. The median overall survival period and 5-year survival of patients in pT1 (≤ 2 cm) N2M0 was 52.1 months and 45%. And patients with pT1a (≤ 1 cm) N2M0 has 29.8 months and 0% (3 year overall survival rate was 33.3%). The recurrence rate was 71.7% (5/6) and disease free survival was 13.2 months.
Conclusion:
This study showed that 5.0% of small-sized (≤ 2 cm) NSCLC had N2 disease and 0.6% of T1a (≤ 1 cm) NSCLC has pN2. Moreover, 56.5% of small-sized (≤ 2 cm) NSCLC was upstaged from clinical diagnosis to pathological diagnosis. The patients with pT1a (≤ 1 cm) N2M0 had worse survival data than the patients with pT1a (≤ 2 cm) N2M0. We recommend systematic lymph node dissection for local treatment as well as accurate diagnosis. As multiple mediastinal node metastases showed an unfavorable prognosis, surgery combined with systematic treatment is recommended.
