Asato Hashinokuchi1, Shinkichi Takamori2, Junjia Zhu3, Kyoto Matsudo1, Fumihiko Kinoshita1, Takaki Akamine1, Miyuki Abe2, Mikihiro Kohno1, Keigo Ozono4, Tomoyoshi Takenaka1, Atsushi Osoegawa2, Tomoharu Yoshizumi1, Takefumi Komiya5
1Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
2Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan;
3Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA;
4Division of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
5Division of Hematology Oncology, Penn State College of Medicine, Hershey, PA, USA
Correspondence to: Shinkichi Takamori, MD, PhD. Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu 879-5593, Japan. Email: shinkichi.takamori@gmail.com.
Background: Staging for thymic epithelial tumor (TET) has commonly been based on Masaoka-Koga systems or the 8thedition of the tumor-node-metastasis (TNM) classification that do not use tumor size for T descriptor. However, American Joint Committee on Cancer (AJCC) and International Association for the Study of Lung Cancer (IASLC) have recently published 9th edition of the TNM classification in 2024 that incorporated size of tumor (5 cm or smaller vs. larger); however, its role has not been well validated in US patients due to under representation (only 4.4% from North America). We aimed to investigate the prognostic impact of primary tumor size in patients with TETs using data from an American database. Furthermore, we validated the results with data from our facilities.
Methods: Using National Cancer Database (NCDB), we analyzed patients with surgically resected TETs diagnosed between 2004 and 2020. Survival analysis was performed using Kaplan-Meier method and multivariate Cox regression analyses, and propensity-score matching (PSM) analyses was also performed. Data of thymoma from our facilities (n=166) were used for validation.
Results: Of 4,151 and 647 patients with thymoma and thymic carcinoma, we identified 1618 (39.0%) and 268 patients (41.4%) as the small tumor group (primary tumor size ≤5 cm), respectively. In thymoma patients, the small tumor group had a statistically significantly longer overall survival (OS) than the large group (>5 cm) [median OS 193.2 vs. 161.4 months, respectively, P<0.001, hazard ratio (HR) 0.72, 95% confidence interval (CI): 0.64–0.82]. After PSM adjusting age, sex, and World Health Organization (WHO) histological type, multivariate Cox model showed that primary tumor size ≤5 cm was an independent prognostic factor for long OS (HR 0.65, 95% CI: 0.56–0.74, P<0.001) similarly to younger age, female, CD score (0–1), year of diagnosis >2009, WHO histological type (type A, AB and B1), adjuvant radiotherapy, and complete resection. The validation cohort analysis supported these findings. In patients with thymic carcinoma, tumor size did not have significant impact on OS (P=0.099).
Conclusions: Our retrospective analysis using NCDB demonstrated that tumor size of thymoma was an important prognostic factor in the US population, but not for thymic carcinoma. The large US cases and data from two facilities in Japan validated the forthcoming 9th edition of the TNM classification.
Keywords: Thymic epithelial tumor; thymoma; National Cancer Database (NCDB)
