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Hirotsugu Notsuda



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    EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.18-13 - Review of Preoperative Examination (Now Available) (ID 1351)

      08:00 - 18:00  |  Author(s): Hirotsugu Notsuda

      • Abstract
      • Slides

      Background

      Before lung resection, it is necessary to perform various preoperative examinations to determine the indication for surgery. In our department, lung blood flow scintigraphy is performed on all cases scheduled for lung resection, and predicted post operation (ppo)%FEV1 and ppo%DLCO, are calculated based on lung function tests and scheduled surgery. Both have a cut-off value of 40%, and if the case has less than 40%, change to surgery with less lung volume loss.

      However, the large number of cases have no difference between left and right lung blood flow ratios. Even if the difference is large, almost all cases have organic lung abnormalities which are detected by CT easily. In addition, even if there is a large dissociation in the left-right difference in pulmonary blood flow, it is very rare that the predicted value after surgery is less than 40% in normal respiratory function patients. In recent years, most institutions do not perform pulmonary blood flow scintigraphy as preoperative examination, and it may be necessary to examine the significance of lung blood flow scintigraphy as preoperative examination.

      Method

      Of the cases in which lung blood flow scintigraphy was performed as a preoperative examination for lung resection in our department from January 2010 to December 2018, we selected the cases who has the blood flow ratio between the left and right lungs has more than doubled difference and doesn’t have detectable organic abnormality and history of lung resection.

      Result

      Nineteen out of 1570 cases were extracted. The blood flow of the right lung was more than twice that of the left lung in 18 cases. 19 cases have 12 men and the average age is 73.6 ± 6.9. There were 13 cases undergoing planned surgery, 3 cases that could not be resected due to the progress of the tumor, 1 case refusing the operation, and only 2 cases changed treatment based on the result of scintigraphy. One case treated by radiation therapy and another was treated by PDT.

      Conclusion

      It is suggested that lung blood flow scintigraphy may not be necessary in cases who have normal pulmonary function and have no organic abnormalities.

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    OA08 - Advanced Models and "Omics" for Therapeutic Development (ID 133)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Biology
    • Presentations: 1
    • Now Available
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      OA08.01 - Organoid Cultures as Novel Preclinical Models of Non-Small Cell Lung Cancer (Now Available) (ID 2115)

      11:00 - 12:30  |  Author(s): Hirotsugu Notsuda

      • Abstract
      • Presentation
      • Slides

      Background

      There is an unmet need to develop novel clinically relevant models of NSCLC to accelerate identification of drug targets and our understanding of the disease. Organoids, which are cells grown in three-dimensional environments in Matrigel, have emerged as novel preclinical models of cancer. Recently protocols for generating NSCLC organoids have been reported, but the growth, and molecular features of organoids as compared to their matching primary patient tumor or patient-derived xenografts (PDX) remain vague.

      Method

      Thirty surgically resected NSCLC patient tumor and 35 PDX tissue of lung adenocarcinoma and squamous cell carcinoma subtypes were processed for organoid establishment. Organoids and matching tumor tissues were characterized by histology and immunohistochemistry, and molecularly profiled by whole exome and RNA-sequencing. Subcutaneous injection of organoids in vivo was performed to confirm tumorgenicity. Organoids were subjected to drug testing and drug response was verified in the matched PDX.

      Result

      Using a novel culture condition that our laboratory developed, we have collected tumor samples from 16 primary and 13 PDX samples of adenocarcinoma (n=29) and 14 primary and 22 PDX samples of squamous cell carcinoma (n=36). Over 85% (57/65) of our patient and PDX tumor tissues formed organoids that exhibited a wide range of short-term (<3 months) and long-term (>3 months) growth. Specifically, the success rate of establishing short-term and long-term models are 74% (48/65) and 14% (9/65), respectively. The long-term propagable organoids recapitulated the histology of the patient and PDX tumor. They also retained the ability to form xenograft in NOD-SCID mice. The organoids preserved mutation, copy number aberrations and global gene expression profile of the parental tumors. We additionally showed the utility of short-term and long-term organoids for identifying biomarkers of sensitivity to drugs and combinational targeted therapies.

      Conclusion

      NSCLC organoids are novel patient-derived ex-vivo tumor models for anti-cancer drug screening and biomarker discovery, thus could be incorporated into novel drug discovery pipelines. Further efforts are ongoing to increase the success rate of establishing long-term organoid lines.

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    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.09-09 - EGFR Is Highly Mutated in Lung Adenocarcinoma Patients with History of Breast Cancer (ID 2210)

      10:15 - 18:15  |  Author(s): Hirotsugu Notsuda

      • Abstract

      Background

      EGFR gene mutation has been reported to be frequent in the patients with specific clinical features such as female, adenocarcinoma, and East-Asian ethnicity. The mutation rate in lung adenocarcinoma is approximately 50% in Japan. Currently, the molecular mechanism which cause EGFR mutation has not been clarified. If the EGFR mutation in lung adenocarcinoma correlates with specific type of malignancy in the other organ, it could be a clue to find a mechanism which promote carcinogenesis of lung adenocarcinoma. In the current study, we focused on breast cancer.

      Method

      Patients with lung adenocarcinoma who underwent pulmonary resection in our hospital from January 2011 to December 2018 were analyzed. We retrospectively reviewed clinical information such as past illness, radiological findings, pathological diagnosis, and EGFR mutation status. Correlation was tested by chi-square test and p value of less than 0.05 was regarded as statistically significant.

      Result

      A total of 21 patients of lung adenocarcinoma had history of treatment for breast cancer. All patients were female. Among them, EGFR mutation was detected in 20 patients (95%). One patient who were negative for EGFR mutation had history of not only breast cancer but also cervical cancer of uterus and gastrointestinal stromal tumor, and developed angiosarcoma of the skin. Detected EGFR mutation types in 20 patients were as follows; deletion in exon 19 for 9 patients, L858R for 7 patients G719X for two patients, and L861Q for one patient. One patient showed multiple mutation (G719X and L861). In the same period, among 203 lung adenocarcinoma patients without other organ malignancy, 115 showed EGFR mutation (56.7%). There was significant difference in EGFR mutation rate between breast cancer group and no malignancy group (p=0.00058).

      Conclusion

      Patients of lung adenocarcinoma with history of breast cancer showed extremely high positive rate for EGFR mutation in Japan, suggesting underlying common oncogenic molecular mechanism between lung adenocarcinoma and breast cancer. Elucidation of the mechanism may contribute to the diagnosis and treatment of carcinogenesis of breast cancer and lung cancer.