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Taichiro Goto
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MA 05 - Immuno-Oncology: Novel Biomarker Candidates (ID 658)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Yoichi Nakanishi, P. Mitchell
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 303 + 304
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MA 05.08 - Very Early Response of Circulating Tumor Derived DNA Predict the Efficacy of Treatment by Nivolumab in Patients with Non-small Cell Lung Cancer (ID 8303)
16:30 - 16:35 | Author(s): Taichiro Goto
- Abstract
- Presentation
Background:
Immunotherapy has become one of the options among the treatments of lung cancer. Nivolumab was first proven to have the utility as a second line treatment for non-small cell lung cancer. However, predictive factor of its efficacy is unknown. In recent years, studies have evolved on circulating tumor DNA (ctDNA). Clinical applications expanded and included prediction of prognosis, monitoring treatment effects and acquired resistance of driver genes, and assessment of residual tumor burden of resected cancer. In this study, we took cases in which tumor tissue was surgically resected or obtained by biopsy and the corresponding somatic mutations in plasma were studied. Then, we used these somatic mutations presumably derived from original tumor tissue as “tumor markers”. We took serial blood samples before and after starting nivolumab and examined to see whether early change of the level of ctDNA can predict long term treatment outcomes.
Method:
Fourteen patients who were treated by nivolumab from February 1st to September 30th in 2016 were studied. Peripheral blood samples were collected from the patients before, 1, 2, 4, 6 and 8 weeks after the initiation of nivolumab treatment. To identify somatic mutations in tissue and total plasma DNA, we performed targeted sequencing using “lung cancer panel” spanning whole exons of these 53 genes, and next generation sequencing was performed. Gene mutations detected in both tumor tissue and plasma were defined here as circulating tumor DNA (ctDNA). Early response of the level of ctDNA after starting nivolumab was evaluated to see whether it could predict treatment outcome.
Result:
Of 14 cases, 6 cases were Responders, and 8 Non-responders. ctDNA was detected more often in the serial plasma samples of patients carrying high tumor burden (p=0.02). In addition, basal and serial ctDNA analysis revealed that decrease of allelic frequency (AF) level within 2 weeks correlated with the good durable response, and on the contrary, the increase with no or poor response.
Conclusion:
In patients carrying high tumor burden, plasma analysis of ctDNA which was validated by tumor tissue, revealed the durable good response of nivolumab could be predicted within 2 weeks.
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.15 - Discussant - MA 13.11, MA 13.12, MA 13.13, MA 13.14 (ID 10786)
17:10 - 17:25 | Presenting Author(s): Taichiro Goto
- Abstract
- Presentation
Abstract not provided
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MA 15 - Lung Cancer Biology II (ID 670)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
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MA 15.03 - Distribution of Circulating Tumor DNA in Lung Cancer: Analysis of Primary Lesion, Pulmonary Vein, Bone Marrow and Pripheral Blood (ID 7454)
15:55 - 16:00 | Presenting Author(s): Taichiro Goto
- Abstract
- Presentation
Background:
Circulating tumor DNA (ctDNA), extracted from plasma, is a non-invasive surrogate biomarker. However, the distribution of ctDNA in the body still remains to be elucidated. In this study, resected lung tumors, with simultaneous blood and bone marrow samples, were analyzed to elucidate the distribution of ctDNA.
Method:
Rib bone marrow, pulmonary venous blood (Pul.V) and peripheral blood (Peri.B) were obtained from 30 patients. The liquid samples were divided into cell pellets and supernatant by centrifugation; a total of 212 DNA samples were subjected to massively parallel sequencing.
Result:
ctDNA was detected in 5 patients. Given that the frequency of mutations in the primary tumor was considered to be 100%, those in the other specimens were as follows; Pul.V plasma 20%, Peri.B plasma 11%, and the other samples 0%. Furthermore, ctDNA reflected the predominant mutations in the primary lesion. Clinically, the presence of ctDNA was associated with significantly poorer survival.
Conclusion:
These results suggest ctDNA “spill over” into an immediate outflow tract (Pul.V), and from there is disseminated to the entire body. Thus, it can be inferred that ctDNA reflects the cancer progression and could function as a prognostic marker.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-097h - Mutational Analysis of Multiple Lung Cancers: Discrimination between Primary and Metastatic Lung Cancers by Genomic Profile (ID 7453)
09:30 - 09:30 | Presenting Author(s): Taichiro Goto
- Abstract
Background:
In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature.
Method:
The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed.
Result:
In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic.
Conclusion:
In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.
