Personalized cancer avatars for patients with thymic malignancies: A pilot study with circulating tumor cell-derived organoids

Yuan-Hung Wu; Heng-Sheng Chao; Chi-Lu Chiang; Yung-Hung Luo; Chao-Hua Chiu; Sang-Hue Yen; Chun-Yu Liu; Jeng-Fong Chiou; Thierry Burnouf; Yin-Ju Chen; Peng-Yuan Wang; Tsu-Yi Chao; Shih-Ming Hsu; Long-Sheng Lu

doi:10.1111/1759-7714.15039

Personalized cancer avatars for patients with thymic malignancies: A pilot study with circulating tumor cell-derived organoids

Thorac Cancer. 2023 Sep;14(25):2591-2600. doi: 10.1111/1759-7714.15039. Epub 2023 Jul 20.

Authors

Yuan-Hung Wu^{1

2

3}, Heng-Sheng Chao^{2

4}, Chi-Lu Chiang^{2

4}, Yung-Hung Luo^{2

4}, Chao-Hua Chiu^{4

5}, Sang-Hue Yen^{1

3

6}, Chun-Yu Liu^{1

2}, Jeng-Fong Chiou^{7

8

9}, Thierry Burnouf^{10

11}, Yin-Ju Chen^{9

10

11

12

13}, Peng-Yuan Wang^{14

15}, Tsu-Yi Chao^{16

17

18

19}, Shih-Ming Hsu³, Long-Sheng Lu^{9

10

11

12}

Affiliations

¹ Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
² School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan.
³ Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming Chiao-Tung University, Taipei, Taiwan.
⁴ Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵ Taipei Cancer Center and Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
⁶ Department of Radiation Oncology, Taipei Municipal Wan-Fang Hospital, Taipei, Taiwan.
⁷ Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁸ Department of Radiation Oncology, Taipei Medical University, Taipei, Taiwan.
⁹ TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan.
¹⁰ Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
¹¹ International Ph.D. Program for Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
¹² Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.
¹³ Department of Medical Research, Taipei Medical University, Taipei, Taiwan.
¹⁴ Oujiang Laboratory, Wenzhou, China.
¹⁵ Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, China.
¹⁶ Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
¹⁷ Division of Hematology/Oncology, Department of Medicine, Tri-service General Hospital, National Defense Medical Center, Taipei, Taiwan.
¹⁸ Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
¹⁹ Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.

Abstract

Background: Systemic therapy is the primary treatment for advanced thymic malignancies. However, there is an urgent need to improve clinical outcome. Personalized treatment based on predictive biomarkers is a potential approach to address this requirement. In this study, we aimed to show the correlation between drug sensitivity tests on CTCs-derived organoids and clinical response in patients with thymic malignancies. This approach carries the potential to create personalized cancer avatars and improve treatment outcome for patients.

Methods: We previously reported potential treatment outcome prediction with patient-derived organoids (cancer avatars) in patients with pancreatic ductal adenocarcinoma. To further investigate the feasibility of this approach in advanced thymic malignancies, we conducted a study in which 12 patients were enrolled and 21 liquid biopsies were performed.

Results: Cancer avatars were successfully derived in 16 out of 21 samples (success rate 76.2%). We found a sensitivity of 1.0 and specificity of 0.6 for drug sensitivity tests on the cancer avatars, and a two-tailed Fisher's exact test revealed a significant correlation between drug sensitivity tests and clinical responses (p = 0.0275).

Conclusion: This study supports the potential of circulating tumor cell-derived organoids to inform personalized treatment for advanced thymic malignancies. Further validation of this proof of concept finding is ongoing.

Trial registration: ClinicalTrials.gov NCT04972461.

Keywords: circulating tumor cell; organoid; thymic carcinoma; thymic malignancy; thymoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Neoplastic Cells, Circulating* / pathology
Organoids / pathology
Pancreatic Neoplasms* / pathology
Pilot Projects
Thymus Neoplasms* / pathology

Associated data

ClinicalTrials.gov/NCT04972461