Satoru Okada1,2, Shunta Ishihara3, Chiaki Nakazono1, Yasuo Ueshima3, Masashi Yanada4, Tsunehiro Ii5, Kenji Kameyama1,5, Satoshi Ikebe6, Hiroaki Tsunezuka7, Motohiro Nishimura8, Shinya Ito9, Kunihiko Terauchi10, Kazuhiro Ito11, Daishiro Kato12, Hiroyuki Izumi13, Hirofumi Suzuki8,14, Yoshiaki Matsuura14, Masanori Shimomura1, Tatsuo Furuya1, Masayoshi Inoue1
1Division of Thoracic Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan;
2Department of Thoracic Surgery, Kyoto Chubu Medical Center, Nantan, Japan;
3Department of General Thoracic Surgery, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan;
4Department of General Thoracic Surgery, Japanese Red Cross Kyoto Daiini Hospital, Kyoto, Japan;
5Department of General Thoracic Surgery, Ayabe City Hospital, Ayabe, Japan;
6Department of Thoracic Surgery, Fukuchiyama City Hospital, Fukuchiyama, Japan;
7Department of Thoracic Surgery, Otsu City Hospital, Otsu, Japan;
8Department of Thoracic Surgery, Saiseikai Suita Hospital, Suita, Japan;
9Department of Thoracic Surgery, Uji-Tokushukai Medical Center, Uji, Japan;
10Department of Chest Surgery, Nara City Hospital, Nara, Japan;
11Department of Thoracic Surgery, Kyoto Yamashiro Medical Center, Kizugawa, Japan;
12Department of Thoracic Surgery, Saiseikai Shiga Hospital, Ritto, Japan;
13Department of Thoracic Surgery, Matsushita Memorial Hospital, Moriguchi, Japan;
14Department of Thoracic Surgery, Osaka General Hospital of West Japan Railway Company, Osaka, Japan
Correspondence to: Satoru Okada, MD, PhD. Division of Thoracic Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 6028566, Japan; Department of Thoracic Surgery, Kyoto Chubu Medical Center, Nantan, Japan. Email: s-okada@koto.kpu-m.ac.jp.
Background: Thymic epithelial tumors (TETs) are rare and heterogeneous malignancies. Because they are surrounded by vital mediastinal structures, achieving complete (R0) resection and determining the extent of lymph node dissection are often challenging in advanced cases. Therefore, accurate preoperative assessment of tumor invasiveness is of critical importance for treatment planning. The maximum standardized uptake value (SUVmax) has been reported to correlate with biological aggressiveness and tumor progression in various malignancies. However, its clinical significance in TETs remains insufficiently clarified, and the association with tumor size has also been scarcely investigated. This study aimed to evaluate the clinical utility of SUVmax as a predictor of pathological invasion and a prognostic factor in advanced TETs requiring combined resection of adjacent organs or management of dissemination.
Methods: A multicenter retrospective study was conducted, comprising 102 patients with TETs, requiring combined resections of adjacent organs or pleural disseminations, from January 2000 to November 2024. Among these, 53 patients with available SUVmax data were included. Receiver operating characteristic (ROC) curves were used to determine optimal SUVmax and tumor size cut-offs for predicting advanced pathological stage (Masaoka stage III/IV) and nodal metastasis. Logistic regression identified factors associated with pathological invasion. Progression-free survival (PFS) was analyzed using Kaplan-Meier methods (log-rank test) and Cox hazard model.
Results: Twenty-five thymomas and 27 thymic carcinomas or thymic neuroendocrine tumors were analyzed. The median SUVmax and tumor size were 5.3 [interquartile range (IQR), 3.8–8.4] and 5.5 (IQR, 5.5–8.0) cm, respectively. Pathological staging revealed 2 stage I, 9 stage II, 29 stage III, 4 stage IVa, and 9 stage IVb cases. Both SUVmax and tumor size were significant predictors of advanced stage and nodal involvement. ROC analysis identified SUVmax cut-offs of 4.7 for advanced disease [area under the curve (AUC) =0.685, sensitivity 71.4%, specificity 63.6%] and 6.1 for nodal involvement (AUC =0.765, sensitivity 77.8%, specificity 68.2%). Tumor size cut-offs were 5.6 cm for both events. Combination of SUVmax (≥4.7 or ≥6.1) and tumor size (≥5.6 cm) stratified risk: rates of advanced disease were 45.5%, 80.0%, and 100% (P<0.001) and nodal involvement rates were 0%, 15.0%, and 46.2% (P=0.001) for patients with 0, 1, and 2 risk factors, respectively. During a median follow-up of 34 months, 15 disease progressions/relapses were observed. High SUVmax (≥6.1) was associated with significantly worse PFS compared to low SUVmax (<6.1) (P<0.001; 5-year PFS, 41.9% vs. 77.5%; hazard ratio 4.53, 95% confidence interval: 1.53–13.4). No significant interactions were found between SUVmax and tumor size, stage, or histology.
Conclusions: SUVmax is a valuable indicator of pathological invasion along with tumor size and may guide surgical decision-making and nodal dissection strategy. Furthermore, SUVmax serves as a prognostic factor in advanced TETs.
Keywords: Thymic epithelial tumor (TET); maximum standardized uptake value (SUVmax); pathological invasion; nodal metastasis; prognostic factor
