Virtual Library
Start Your Search
T. Ohira
Author of
-
+
MA08 - Treatment Monitoring in Advanced NSCLC (ID 386)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:R. Perez-Soler, T. Reungwetwattana
- Coordinates: 12/06/2016, 11:00 - 12:30, Lehar 3-4
-
+
MA08.10 - Detection of the T790M Mutation of EGFR in Plasma of Advanced NSCLC Patients with Acquired Resistance to EGFR-TKI (WJOG8014LTR) (ID 5377)
12:06 - 12:12 | Author(s): T. Ohira
- Abstract
- Presentation
Background:
NSCLC patients with activating mutations of the EGFR initially respond well to TKIs, but about half such patients develop TKI resistance through acquisition of a secondary T790M mutation. Whereas next-generation EGFR-TKIs have been developed to overcome T790M-mediated resistance, performance of a second tumor biopsy to assess T790M mutation status can be problematic.
Methods:
We developed and evaluated liquid biopsy assays for detection of TKI-sensitizing and T790M mutations of EGFR by droplet digital PCR (ddPCR) in EGFR mutation–positive patients with acquired EGFR-TKI resistance.
Results:
A total of 260 patients was enrolled between November 2014 and March 2015 at 29 centers for this West Japan Oncology Group (WJOG 8014LTR) study. Plasma specimens from all subjects as well as tumor tissue or malignant pleural effusion or ascites from 41 patients were collected after the development of EGFR-TKI resistance. All plasma samples were genotyped successfully and the results were reported to physicians within 14 days. TKI-sensitizing and T790M mutations were detected in plasma of 120 (46.2%) and 75 (28.8%) patients, respectively. T790M was detected in 56.7% of patients with plasma positive for TKI-sensitizing mutations. For the 41 patients with paired samples obtained after acquisition of EGFR-TKI resistance, the concordance for mutation detection by ddPCR in plasma compared with tumor tissue or malignant fluid specimens was 78.0% for TKI-sensitizing mutations and 65.9% for T790M.
Conclusion:
Noninvasive genotyping by ddPCR with cell-free DNA extracted from plasma is a promising approach to the detection of gene mutations during targeted treatment.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
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)
-
+
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): T. Ohira
- 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.
-
+
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)
-
+
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): T. Ohira
- 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.
-
+
P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.01-024 - Drastic Morphological and Molecular Differences between Lymph Node Micrometastatic Tumors and Macrometastatic Tumors of Lung Adenocarcinoma (ID 5894)
14:30 - 14:30 | Author(s): T. Ohira
- Abstract
Background:
The expansion of micrometastatic tumors to macrometastatic ones is thought to be tightly regulated by several microenvironmental factors. The aim of this study was to elucidate the morphological and phenotypical differences between micrometastatic and macrometastatic tumors.
Methods:
We first examined the morphological characteristics of 66 lymph node (LN) micrometastatic tumors (less than 2 mm in size) and 51 macrometastatic tumors (more than 10 mm in size) in 42 lung adenocarcinoma cases. Then, we evaluated the expression level of E-cadherin, S100A4, ALDH1, and Geminin in cancer cells and the number of smooth muscle actin (SMA), CD34, and CD204 (+) stromal cells in the primary tumors, matched micrometastatic tumors, and macrometastatic tumors (n = 34, each).
Results:
Tumor budding reflects the process of EMT, and stromal reactions were observed more frequently in macrometastatic tumors (P < 0.001). E-cadherin staining score for the micrometastatic tumors was significantly higher than that for the primary tumors (P < 0.001). In contrast, the E-cadherin staining score for the macrometastatic tumors was significantly lower than that for the micrometastatic tumors (P = 0.017). As for the stromal cells, the numbers of SMA (+) fibroblasts, CD34 (+) microvessels, and CD204 (+) macrophages were significantly higher for the macrometastatic tumors and primary tumors than for the micrometastatic tumors (P < 0.001, all).
Conclusion:
The present study clearly showed that dynamic microenvironmental changes (e.g., EMT-related changes incancer cells and structural changes in stromal cells) occur during the growth of micrometastases into macrometastases.
-
+
P3.01-028 - Comparison of Touch Imprint Cytology and Section Histopathology in the Diagnostic of the Small Peripheral Lung Tumors (ID 5997)
14:30 - 14:30 | Author(s): T. Ohira
- Abstract
Background:
There have been some reports on transbronchial biopsy (TBB) through endobronchial ultrasonography with a guide sheath (EBUS-GS) for diagnostic sampling of small-sized tumors which showing ground-glass opacity (GGO) on chest CT. However, technique such as EBUS-GS is limited in their ability to diagnose such small lung tumors. The discussion about the cytological features of small tumors with GGO in detail is necessary. We evaluated about the association of the cytological features with the histological examination using the surgically resected specimen. 140 patients, age between 23–86 years old, who showed clinical and radiological signs of peripheral lung tumors below 3.0cm in diameter, underwent surgical resection at our institution between 2013 and 2015.
Methods:
Imprints or touch preparation and squash smears preparation were prepared from the unfixed, fresh sample in 140 cases. Papanicolaou's stain was employed in all cases. To make the squash smears preparation, the slides are drawn apart away from each other, in the direction of the long axis of the slide. Tissue fragments taken from surgical specimen were fixed with 10% neutral buffered formalin and stained with hematoxylin and eosin (H&E).
Results:
By histological examination (in the 140 cases), the diagnostic of lung cancer was given with the establishing of the histological type. In 110 cases (78.6%) of the cases diagnosed as adenocarcinoma, in 21 cases (15%) squamous cell carcinoma, in 4cases (2.9%) was neuroendocrine tumors, and one case each of adenosquamous carcinoma, pleomorphic carcinoma and pleomorphic sarcoma. In 84 of the 110cases (76.3%), the result of imprint cytological examination was adenocarcinoma. In the 110 pathological diagnosed as adenocarcinoma cases, 52 patients (47.2%) are below 2.0cm in size. Tumor stamps of small sized adenocarcinoma are characterized by moderate cellularity and are composed of atypical cells arranged in small flat sheets. The nuclei are generally round, slightly hyperchromatic with small nucleoli.
Conclusion:
Our data indicate the fact that the cytological examination on stamps from surgical material offers a very high percentage of positive results, close to the histological one. But in the tumor size less than 1.0cm, the establishing of the histological type of lung cancer is more difficult by cytological examination. Despite this, the cytology may be extremely useful in diagnose of the small peripheral tumors. The cytological characteristics of small peripheral adenocarcinoma were little reference to the differentiation at the cellular level. Our findings indicated that the presence of several nucleoli and granular chromatin densely are the factors of adenocarcinoma.
