Efficacy and safety of high-dose prednisone for patients with advanced thymoma: a retrospective study

Introduction

Thymoma, a rare neoplasm arising from thymic epithelial cells (TECs), is the most common anterior mediastinal tumor in adults. Complete surgical resection provides the best chance of cure and is one of the most important prognostic factors (1). However, locally advanced and advanced thymomas often involve extensive invasion and tumor burden, making surgical resection highly challenging. Conventional therapies, including chemotherapy and radiation, often produce suboptimal outcomes, underscoring the need for the development of novel therapeutic strategies.

Glucocorticoids (GCs), synthetic analogs of adrenal corticosteroids, have garnered attention by virtue of their dual anti-inflammatory and potential antitumor effects (2). Preclinical studies suggest that GCs may inhibit thymoma cell proliferation by modulating apoptosis pathways and suppressing pro-survival signals, particularly in lymphocyte-rich thymomas. Clinically, GCs are empirically used to manage autoimmune comorbidities such as myasthenia gravis, yet emerging evidence suggests that they may also exert direct antitumor activity. Retrospective reviews and case reports indicate the occurrence of tumor regression in selected patients receiving high-dose GC monotherapy (3-7).

However, the therapeutic role of GCs for patients with thymoma has not been extensively investigated. Critical knowledge gaps include the molecular mechanisms underlying GC sensitivity, the optimal dosing regimens, and long-term survival outcomes. Additionally, the interplay between GC-induced immunosuppression and tumor progression warrants more in-depth examination, especially given thymoma’s relatively indolent features. This study thus aimed to retrospectively analyze the safety and efficacy of high-dose prednisone in the treatment of potentially unresectable advanced thymoma. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1352/rc).

Methods

This retrospective study was conducted at Shanghai Chest Hospital and analyzed the efficacy and safety of high-dose prednisone in the treatment of patients with advanced thymoma. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of Shanghai Chest Hospital (No. KS1970), which waived the requirement for patient consent due to the de-identification of retrospective information.

Patient selection

Patients with previously treated potentially unresectable tumor-node-metastasis (TNM) (8^th edition) stage III–IV (8) histologically confirmed thymoma were initially included in this study. Patients with primary unresectable stage III–IV disease, those with recurrent pleural stage IV disease, and those who received high-dose prednisone (0.5–1 mg/kg/day) for the purpose of reducing tumor burden were considered eligible for inclusion. Patients enrolled would receive a monthly computed tomography (CT) scan to evaluate the response as well as the resectability of the tumor. When the tumor became resectable, surgery would be scheduled if it was suitable for the patient. If the tumor was deemed unresectable or progressed after prednisone treatment, long-term prednisone maintenance or alternative treatments would be given after multidisciplinary discussion. Clinical tumor staging was performed by an experienced radiologist (Y.S.) from our multidisciplinary team based on contrast-enhanced chest CT with or without chest magnetic resonance imaging (MRI). Tumor resectability was evaluated jointly by two experienced thoracic surgeons (T.M. and Z.G.) before and after prednisone treatment. Potentially unresectable tumors were defined as those unable to be completely resected initially due to extensive tumor burden or invasion into adjacent structures, especially the great vessels. Evaluation of histological types via biopsy and surgically removed samples was performed by an experienced pathologist (L.Z.) according to the 5^th edition of the World Health Organization (WHO) classification (9).

Endpoints

The primary endpoint was objective response rate (ORR) to high-dose prednisone. This was evaluated through chest CT scans and classified according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) recommended by the International Thymic Malignancy Interest Group (ITMIG) (10). Time to response (TTR) was defined as the time from initiation of treatment to the first occurrence of a complete response (CR) or partial response (PR) as per the modified RECIST.

The secondary endpoints included the rates of surgical resection, pathological features, treatment-related toxicity, tumor recurrence, and survival. Pathological evaluation following prednisone treatment was carried out by an experienced pathologist (L.Z.). Oncological outcomes were assessed in terms of overall survival (OS) and progression-free survival (PFS). OS was defined as the period from the start of treatment to death from any cause. PFS was defined as the period from treatment initiation to the first occurrence of any of the following events: disease recurrence, disease progression, or death from any cause.

Statistical analysis

For the statistical analysis, continuous variables that followed a normal distribution are reported as the mean ± standard deviation, and intergroup comparisons were performed via the Student t-test. Categorical data are summarized as percentages and were analyzed with either the Chi-squared test or Fisher’s exact test, as appropriate. Survival distributions were compared with the Kaplan-Meier method and the log-rank test. Statistics were carried out via SPSS version 23.0 software (IBM Corporation, Armonk, NY, USA), and figures were drawn with GraphPad Prism 7.0 software (Dotmatics, Boston, MA, USA). P values less than 0.05 were considered statistically significant.

Results

Patient and tumor characteristics

From December 2016 to March 2024, a total of 26 patients were included in this study. The clinical features of the enrolled patients are shown in Table 1. Most patients (22/26, 84.6%) had pleural metastatic stage IV diseases. Fifteen (57.7%) patients had primary stage III–IV diseases, and 11 (42.3%) had recurrent pleural stage IV disease. All patients had type B thymomas according to biopsy or previously surgically resected primary tumors. Of the 15 patients with primary stage III–IV thymomas, 14 (93.3%) had received induction platinum-based chemotherapy and 1 (6.7%) had received induction chemoradiotherapy. For the rest 11 patients with recurrent pleural diseases after previous surgery and peri-operative treatments, 5 (45.5%) received radiotherapy for the recurrent diseases, 2 (18.1%) received chemotherapy, and 4 (36.4%) with no other treatment before prednisone treatment.

Clinical response and toxicity

The ORR of prednisone was 57.7% (15/26), with 2 cases of CR and 13 cases of PR. Ten (38.5%) patients had stable disease (SD), and 1 (3.8%) had progressive disease (PD) (Figure 1). The median TTR was 2 [interquartile range (IQR), 1–3] months. According to biopsy, there were more thymomas containing type B1 component in patients with CR or PR than in those with SD or PD (76.9% vs. 44.4%, P=0.19) (Table 2). The two patients with CR had recurrent pleural type B1+2 thymomas. The patient with PD had a biopsy-proven type B2 thymoma but ultimately had a mixed-type B2 (70%) and B3 (30%) thymoma according to pathological examination after surgical resection. The proportion of myasthenia gravis was comparable between patients with CR or PR and those with SD or PD (33.3% vs. 18.2%, P=0.66) (Table 2).

Figure 1 Change in tumor size from baseline in each patient. CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.

During treatment with high-dose prednisone, three patients experienced pneumonia and recovered after antibiotic treatment. One patient had new-onset hypertension and diabetes. None of the patients died from treatment.

Surgical and pathological results

Of the 26 patients, 16 (61.5%) received subsequent surgery (Table 3). The median duration of prednisone treatment before surgery was 2 (IQR, 1–3) months. Among the 16 patients, 10 (62.5%) achieved PR after prednisone treatment. One patient experienced disease progression but still received surgery, as most lesions were pleural and surgical resection was technically feasible. Resection of lung tissue was recorded in 14 (87.5%) patients and was followed by partial resection of the pericardium in 11 (68.8%) patients. Two patients had tumors invading the left innominate vein. Thirteen (81.3%) patients had pleural metastases and received pleurectomy with complete resection of the visible lesions. One patient developed severe postoperative complications, including dyspnea necessitating noninvasive ventilation and air leak resulting in prolonged chest tube drainage.

Pathological examination revealed that the degrees of decrease in the percentage of terminal deoxynucleotidyl transferase (TdT)⁺ immature T cells differed between surgical samples and biopsy samples, which could account for the change in histological type before and after prednisone treatment (Figure 2, Table 3).

Figure 2 Comparison of histological types before and after the treatment of prednisone in patients receiving surgery (excluding three patients with type B thymomas that were unable to be further subtyped by biopsy).

Survival outcomes

After a median follow-up of 29.5 (IQR, 11.9–34.5) months, 4 patients experienced disease recurrence in the pleura among the 16 patients who received surgery. None of the patients died, and the median PFS was not reached.

Moreover, 10 (38.5%) of the 26 patients did not receive surgery. Among them, 7 (70%) had recurrent pleural disease (stage IVa), and 3 (30%) had unresectable stage III tumors. The ORR was 50%, with two cases of CR, three cases of PR, and five cases of SD. Five patients received subsequent radiotherapy, two received long-term treatment of prednisone, and three were scheduled for follow-up. During a median follow-up of 28.2 (IQR, 15.4–35.6) months, four patients had disease progression in the pleura. One patient experienced disease progression during prednisone dose tapering and had tumor shrinkage after prednisone reloading. The median PFS was 17.5 (IQR, 16.2–18.9) months.

Importantly, the patients with CR or PR to prednisone had better PFS than did those with SD or PD after prednisone treatment (P=0.045; Figure 3). Moreover, patients receiving surgery after prednisone treatment did not have better PFS than did those not receiving surgery (P=0.53; Figure 4).

Figure 3 Kaplan-Meier plots of PFS comparing patients with SD/PD and patients with PR/CR (P=0.045). CR, complete response; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.

Figure 4 Kaplan-Meier plots of PFS comparing patients who did and did not undergo surgery (P=0.53). PFS, progression-free survival.

Discussion

We conducted a retrospective study of patients with advanced thymoma receiving high-dose prednisone. In this study, 26 patients with previously treated but still potentially unresectable TNM (8^th edition) stage III–IV thymoma were included. After treatment with prednisone, the ORR was 57.7% (15/26), with 2 cases of CR and 13 cases of PR. The ORR was relatively higher in thymomas containing type B1 component than in those without B1 component (69.2% vs. 37.5%, P=0.20). Of the 26 patients, 16 (61.5%) received complete resection of the visible tumors. The PFS was significantly longer in patients with PR or CR than in those with SD or PD (P=0.045).

The use of high-dose prednisone exhibited good safety in this study. Of the 16 patients receiving surgery, the median duration of prednisone treatment before surgery was 2 (IQR, 1–3) months. Only minor adverse events, such as weight gain, were observed. In 10 patients that did not receive surgery, 3 patients had pneumonia at 1, 3, and 38 months of treatment with prednisone and recovered after antibiotic therapy. One patient experienced new-onset hypertension and diabetes, which were well controlled. None of the patients died due to the treatment. Overall, the treatment of short-term high-dose prednisone was safe in our study, but the long-term administration of high-dose prednisone remains to be further examined and should be applied with caution.

According to the European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) guidelines, chemotherapy is preferred as induction therapy for locally advanced thymoma (11,12), while for unresectable thymomas, systemic therapy or chemoradiotherapy is recommended. However, due to the limited efficacy and high rate of adverse events, there is a need for improved treatment. For example, the NCCN panel decided that the preferred regimen for thymoma is cisplatin + doxorubicin + cyclophosphamide (CAP) because it appears to provide the best outcomes, with a response rate of approximately 44% (13). A high rate of major response (77%) for induction chemotherapy was reported by Kim et al. (14). However, this could have partly been due to the use of high-dosage prednisone in their regimen. In our study, the ORR was 57.7% for high-dose prednisone, which not only provides an opportunity for surgery but also for the administration of radiotherapy in unresectable tumors. For those who cannot tolerate further antitumor therapy, long-term prednisone is recommended.

GCs have been occasionally used since the 20^th century as a palliative treatment of thymomas that failed to respond to conventional treatments (3-7). There were also studies reporting the combined treatment of GCs and octreotide for thymomas (15,16). Although the courses and doses varied among different reported cases, the response rate of GCs is promising. In addition, the duration of response could be as long as 48 months without severe side effects in these cases. Kobayashi et al. reported using GCs as an induction therapy before surgery for advanced thymomas (17). In their study, the ORR of steroid pulse therapy was 47.1% (8 of 17). The reduction in tumor size was most prominent in type B1 thymomas, and there were significant differences between type AB and type B1 thymomas (20% vs. 68%) and between type B1 and type B3 thymomas (68% vs. 8.3%). This is consistent with our finding that type B1 encapsulated thymomas had a higher ORR (69.2%) than did the other tumor types. In the study by Kobayashi et al. (17), the reduction in tumor size was accompanied with a marked reduction in the CD4-CD8 double-positive immature thymocytes that expressed higher levels of GC receptor (GR). In our study, pathological examination also revealed varying degrees of decrease in immature T-cell proportion in surgically removed samples.

However, the mechanism underlying the effect of GCs in treating thymoma remains unclear. GC-induced growth arrest or apoptosis in lymphocytes has established GCs as a key agent in lymphoid cancer therapy (2). However, certain cases appear resistant to GC treatment; for example, it was found that patients with acute lymphocytic leukemia and higher expression levels of the antiapoptotic genes BCL2 and MCL1 experienced treatment resistance due to the blunting of the apoptotic signal induced by GCs (2). As it relates to thymoma, Kobayashi et al. (17) reported that CD4⁺CD8⁺ lymphocytes in thymoma were highly sensitive to GC-induced apoptosis, which was consistent with the high level of GR expression in these cells. Moreover, there was a greater proportion of CD4⁺CD8⁺ immature lymphocytes in type B1 than in type AB or B3 thymomas; this resulted in B1 thymomas responding better to GC therapy than type AB/B3 thymomas. In addition, Funakoshi et al. (18) found that GR was expressed intracellularly in neoplastic TECs and that GCs could induce apoptosis and G1 cell cycle arrest in TECs. While these studies focused on the effect of GCs on thymomas, Mimae et al. (19) examined patients with thymic carcinoma and detected GR expression in 75.7% (28/37) of these cases. In a recent study, Yu et al. (20) observed that the percentage of IL-8⁺ T effector memory-expressing CD45RA (TEMRA) cells decreased in B1 and B2 thymoma tissues after prednisone treatment, which might be associated with the good response of type B1 or B2 thymomas to prednisone. Overall, further research is needed to clarify the underlying mechanism of GCs on thymic tumors.

Despite the encouraging ORR encountered in our study, there were certain limitations that should be addressed. First, we employed a retrospective design with a limited sample size. Prospective studies with larger sample size are thus needed to further verify the efficacy and safety of high-dose prednisone in treating patients with thymoma. Second, we conducted a single-arm study, and thus a controlled study is needed to compare the efficacy of chemotherapy and GCs. This would generate more reliable clinical evidence to inform the selection of treatment for patients with advanced thymoma. Our center has initiated a randomized controlled phase II trial to compare neoadjuvant GC with chemotherapy in the treatment of patients with advanced type B thymoma (ChiCTR2500110661). Finally, the safety and optimal dosage of long-term prednisone administration remain unclear and should be determined in further work.

Conclusions

In conclusion, high-dose prednisone is effective in patients with advanced thymomas, especially those containing type B1 component. Selected patients with potentially unresectable tumors might gain the opportunity for surgery after induction therapy with prednisone. Long-term, high-dose administration of prednisone may be effective but should be applied with caution.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1352/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1352/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1352/prf

Funding: This work was funded by the National Natural Science Foundation of China (No. 82202924 to Ying Yang).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1352/coif). Ying Yang reports that this work was funded by the National Natural Science Foundation of China (No. 82202924). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Institutional Review Board of Shanghai Chest Hospital (No. KS1970), which waived the requirement for patient consent due to the de-identification of retrospective information.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Fang W, Chen W, Chen G, et al. Surgical management of thymic epithelial tumors: a retrospective review of 204 cases. Ann Thorac Surg 2005;80:2002-7. [Crossref] [PubMed]
2. Pufall MA. Glucocorticoids and Cancer. Adv Exp Med Biol 2015;872:315-33. [Crossref] [PubMed]
3. Barratt S, Puthucheary ZA, Plummeridge M. Complete regression of a thymoma to glucocorticoids, commenced for palliation of symptoms. Eur J Cardiothorac Surg 2007;31:1142-3. [Crossref] [PubMed]
4. Termeer A, Visser FJ, Mravunac M. Regression of invasive thymoma following corticosteroid therapy. Neth J Med 2001;58:181-4. [Crossref] [PubMed]
5. Kirkove C, Berghmans J, Noel H, et al. Dramatic response of recurrent invasive thymoma to high doses of corticosteroids. Clin Oncol (R Coll Radiol) 1992;4:64-6. [Crossref] [PubMed]
6. Tandan R, Taylor R, DiCostanzo DP, et al. Metastasizing thymoma and myasthenia gravis. Favorable response to glucocorticoids after failed chemotherapy and radiation therapy. Cancer 1990;65:1286-90.
7. Almog C, Horowitz M, Burke M. Steroid therapy in inappropriate secretion of antidiuretic hormone due to malignant thymoma. Respiration 1983;44:382-6. [Crossref] [PubMed]
8. Detterbeck FC, Stratton K, Giroux D, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol 2014;9:S65-72. [Crossref] [PubMed]
9. Marx A, Chan JKC, Chalabreysse L, et al. The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial, Germ Cell, and Mesenchymal Tumors? J Thorac Oncol 2022;17:200-13. [Crossref] [PubMed]
10. Benveniste MF, Korst RJ, Rajan A, et al. A practical guide from the International Thymic Malignancy Interest Group (ITMIG) regarding the radiographic assessment of treatment response of thymic epithelial tumors using modified RECIST criteria. J Thorac Oncol 2014;9:S119-24. [Crossref] [PubMed]
11. Girard N, Ruffini E, Marx A, et al. Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015;26:v40-55. [Crossref] [PubMed]
12. National Comprehensive Cancer Network. NCCN Guidelines. Thymomas and Thymic Carcinomas. 2021. Available online: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1469
13. Merveilleux du Vignaux C, Dansin E, Mhanna L, et al. Systemic Therapy in Advanced Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort. J Thorac Oncol 2018;13:1762-70. [Crossref] [PubMed]
14. Kim ES, Putnam JB, Komaki R, et al. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer 2004;44:369-79. [Crossref] [PubMed]
15. Loehrer PJ Sr, Wang W, Johnson DH, et al. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol 2004;22:293-9. [Crossref] [PubMed]
16. Kirzinger L, Boy S, Marienhagen J, et al. Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study. PLoS One 2016;11:e0168215. [Crossref] [PubMed]
17. Kobayashi Y, Fujii Y, Yano M, et al. Preoperative steroid pulse therapy for invasive thymoma: clinical experience and mechanism of action. Cancer 2006;106:1901-7. [Crossref] [PubMed]
18. Funakoshi Y, Shiono H, Inoue M, et al. Glucocorticoids induce G1 cell cycle arrest in human neoplastic thymic epithelial cells. J Cancer Res Clin Oncol 2005;131:314-22. [Crossref] [PubMed]
19. Mimae T, Tsuta K, Takahashi F, et al. Steroid receptor expression in thymomas and thymic carcinomas. Cancer 2011;117:4396-405. [Crossref] [PubMed]
20. Yu XT, Cui J, Yang XG, et al. Novel modulation of T effector memory cells-expressing CD45RA by prednisone in inoperable advanced type B thymoma patients. Genes Immun 2025;26:222-8. [Crossref] [PubMed]

(English Language Editor: J. Gray)