Emerging treatment strategies for thymoma with pleural dissemination or recurrence: surgery combined with hyperthermic intrathoracic chemotherapy

Wang Shuai, Ao Yongqiang, Ding Jianyong

Abstract: Thymoma is the most common tumor type in the anterior mediastinum. The pleura is a hotspot for thymoma metastasis, known as the "host site"; pleural implantation metastasis is a special mode of thymoma metastasis. Pleural metastasis of thymoma may already exist at the initial diagnosis, representing stage M1a thymoma; or it may appear during the follow-up period after treatment, representing pleural recurrence (TPR). Surgery is an important treatment method for patients with thymoma with pleural dissemination or TPR. Currently, there is no unified opinion on surgical approaches and methods. Simple surgery is difficult to achieve truly complete resection of thymoma with pleural dissemination or TPR. Hyperthermic intrathoracic chemotherapy (HITOC) is an effective supplementary treatment, but the selection of HITOC regimens and setting of conditions are still in the exploratory stage internationally; previous studies were mainly small-sample, retrospective, and non-controlled studies with many confounding factors and limited clinical experience. This article summarizes and analyzes the diagnosis and treatment progress of thymoma with pleural dissemination or TPR combined with surgery and HITOC, providing a theoretical basis for selecting reasonable treatment methods and developing individualized treatment strategies.

Keywords: Thymoma; Pleural dissemination; Hyperthermic intrathoracic chemotherapy; Complete resection; Pleural recurrence

Treatment strategies for thymoma with pleural dissemination or pleural recurrence Wang Shuai ， Ao Yongqiang ， Ding Jianyong . Department of Thoracic Surgery ， Zhongshan Hospital Fudan University ， Shanghai 230032 ， China

Corresponding author: Ding Jianyong ， Email: ding.jianyong@zs–hospital.sh.cn

【 Abstract Thymoma is the most common pathological type of tumor in the anterior mediastinum. The pleura is the hotspot for thymoma metastasis, known as the “host site”, and pleural implantation metastasis is a special mode of thymoma metastasis. Pleural metastasis of thymoma may already exist in the initial diagnosis, representing stage M1a thymoma; or it may occur during the follow-up period after treatment, indicating pleural recurrence. Surgery is an important treatment for thymoma with pleural dissemination or pleural recurrence. Currently, there is no international expert consensus on the approach, method selection, and other aspects of surgical resection of thymoma. Surgery alone is difficult to achieve complete resection of thymoma with pleural dissemination or pleural recurrence. Thoracic hyperthermic perfusion chemotherapy is an effective supplementary treatment method. However, the selection and condition settings for thoracic hyperthermic perfusion chemotherapy are still in the exploratory period. Previous studies were mainly small-size, retrospective, and uncontrolled studies, with many confounding factors and limited clinical experience. This article summarizes and analyzes the diagnosis of thymoma with pleural dissemination or pleural recurrence and treatment progress of the combination of surgery and thoracic hyperthermic perfusion chemotherapy, providing a theoretical basis for reasonable treatment selection and developing personalized treatment strategies.

【 Key words Thymoma； Pleural dissemination； Hyperthermic intrathoracic chemotherapy； Complete resection； Pleural recurrence

DOI ：10.3877/cma.j.issn.2095-8773.2024.04.05

Funding: National Key Research and Development Program of China (2023YFC3402703); Excellent Youth Fund of Zhongshan Hospital, Fudan University (2021ZSYQ28)

Author's Affiliation: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 230032, China

Corresponding author: Ding Jianyong, Email: ding.jianyong@zs-hospital.sh.cn

The incidence of thymoma is relatively low, but it has been gradually increasing in recent years. Compared with other thoracic tumors, thymoma is easily overlooked by clinicians due to its rarity and diversity. Thymoma not only manifests as local compression or invasion symptoms but is often accompanied by autoimmune diseases such as myasthenia gravis, pure red cell aplasia, psoriasis, autoimmune hepatitis, and myocarditis. Previous scholars classified thymoma types A and AB as benign tumors, type B1 as low-grade malignant, type B2 as moderate malignant, and type B3 as high-grade malignant. However, unlike other tumors, the malignancy of thymoma cannot be completely determined based on cytology and needs to be judged based on the presence or absence of invasion of surrounding tissues or distant metastasis. Therefore, some scholars have simply proposed the concept of invasive and non-invasive thymoma. Currently, the latest evidence suggests that all thymomas are potentially malignant, and even type A thymomas can undergo invasion and metastasis. The classic thymoma staging system was developed by Japanese scholars Masaoka and Koga, known as the Masaoka staging system. The International Thymic Malignancy Interest Group (ITMIG) and the International Association for the Study of Lung Cancer (IASLC) jointly developed the TNM staging system, and the ninth edition of the TNM staging system was published in 2023 [1].

The probability of hematogenous metastasis of thymoma is relatively low, but pleural metastasis (thymoma with pleural metastasis, TPM) can occur during the initial diagnosis or follow-up. Literature data show that TPM often occurs after thymectomy, and even patients with completely resected encapsulated thymomas may develop TPM years later. Treatment methods for TPM include surgery, hyperthermic intrathoracic treatment, radiotherapy, and chemotherapy. Various treatment methods have been reported in the past, which on the one hand illustrates the complexity of treatment choices, and on the other hand, confirms that the clinical efficacy of treatment needs further improvement. This article summarizes the latest medical literature and combines the experience of our team to comprehensively analyze the diagnosis and treatment strategies of thymoma with pleural dissemination or recurrence (thymoma with pleural recurrence, TPR) combined with surgery and HITOC.

I. Definition and diagnosis of thymoma with pleural dissemination or TPR

Thymomas with new pleural tumor lesions that appear during follow-up after radical treatment are defined as TPR. Pleural metastases present at the initial diagnosis and treatment of thymoma are called pleural dissemination, also known as de novo stage Ⅳa thymoma (DNT). TPM includes both TPR and DNT. The following issues must be considered when treating TPM: whether the initial thymoma surgery was palliative, whether pleural lesions were missed; whether tumor rupture during surgery caused iatrogenic seeding; and whether the TPR incidence is lower than that of in-situ tumor recurrence. Only after excluding these issues can the pleural lesions be defined as TPR or DNT. The probability of tumor recurrence in thymoma patients after complete resection and long-term follow-up is 10%～30%, the incidence of hematogenous distant metastasis is low, at 0～5%, and most patients relapse as TPR, accounting for 70%～90% of recurrences; or mediastinal recurrence, accounting for about 10%, or both [2]. The incidence of isolated DNT without lymph node or hematogenous metastasis is relatively low, with a previously reported incidence of 3%～15% [3]. For TPM in general, TPR is more common than DNT, which is also consistent with real-world clinical practice.

The overall disease-free survival (DFS) after thymoma surgery is 60～80 months, and TPR may even appear more than ten years after surgery, so lifelong follow-up is recommended for thymoma. If the patient has myasthenia gravis and other thymoma-related syndromes, it may improve the detection time and probability of TPR. TPR is usually asymptomatic and is incidentally discovered during follow-up. A small number of patients have representative symptoms such as pleural effusion, chest pain, or dyspnea. However, the positive rate of exfoliated cytology in pleural effusion is extremely low. Thin-slice plain computed tomography (CT) of the chest is the main diagnostic tool, and patients should undergo chest imaging at least once a year during follow-up after surgery. TPR can occur anywhere in the visceral or parietal pleura of the pleural cavity. Due to gravity and body position, TPR is most common at the bottom of the chest cavity and the posterior mediastinum, especially the costophrenic angle, cardiophrenic angle, and fissure surface. Similar to primary thymoma, TPR is usually homogeneous and mildly enhances in the venous phase, occasionally showing calcification, cystic, and necrotic areas. Thin-slice chest CT can show the number, location, and size of TPR as well as the location of the primary tumor. It is worth emphasizing that chest imaging often underestimates TPR because TPR is too small or in a hidden anatomical area. Therefore, the pleural cavity should be carefully explored in all areas during surgery. The WHO histological classification is consistent with the biological behavior of thymoma, with a higher incidence of TPR in type B3 thymoma than in type A thymoma, but the prognostic significance of histological classification in TPR has not been confirmed. TPR usually maintains the same histological characteristics as the primary thymoma, or even without difference. Therefore, in patients with TPR after complete resection, thin-slice chest CT can clinically diagnose TPR, and histological diagnosis is not necessary, especially when clinicians judge that TPR is resectable. Conversely, histological confirmation is needed in the following situations: for unresectable TPR, or when extensive surgery is required; when induction therapy or radiotherapy/chemotherapy is needed. CT-guided fine-needle aspiration or thoracoscopic biopsy is a feasible and easy-to-implement diagnostic method.

TPR still uses the staging system for DNT thymoma. We recommend the 9th edition TNM staging system developed by ITMIG to evaluate TPR. TPR may occur after surgery for any stage of thymoma, but the incidence of TPR and recurrence interval vary with the progression of the initial TNM stage of thymoma. In 1996, Haniuda et al. [4] proposed a pathology-based method to evaluate the relationship between thymoma and pleura (pleural factors, p) and pericardium (pericardial factors, c): p0/c0, the tumor has no adhesion or invasion to the mediastinal pleura and pericardium; p1/c1, the tumor is significantly adhered to the mediastinal pleura and pericardium, but without microscopic invasion; p2/c2, the tumor invades the mediastinal pleura and pericardium. Studies have shown that the probability of TPR after surgery for p2/c2 thymoma is significantly higher than that for p1/c1 and p0/c0 patients.

II. Surgical Treatment

Except for widely metastatic diseases, surgery is the cornerstone of TPM treatment for thymoma. Complete surgical resection is a key factor for long-term survival of TPM. For resectable patients, although the surgical approach is controversial, the survival benefit of surgery has been recognized by experts at home and abroad [5]. Even partial resection improves survival compared to biopsy. The surgical benefit of TPR needs to be strictly evaluated, especially for surgeries with great trauma and extremely high risk of complications. Not only DFS, but also overall survival (OS) and quality of life should be evaluated.

To date, no clinical randomized controlled trials have confirmed that surgery alone is superior to chemotherapy, or combined radiotherapy and chemotherapy. Previous retrospective studies have shown that progression-free survival is better in patients receiving combined surgical and drug treatment than in those receiving radiotherapy and chemotherapy alone. However, in studies led by surgical teams, surgery is limited to patients in good clinical condition, those who are preoperatively judged to have potential for complete resection, and those with completely resectable recurrent tumors. This clinical selection bias leads to a lower statistical value of the superiority of surgical treatment.

Theoretically, complete resection of TPM thymoma should provide the best long-term survival, but whether complete resection can be achieved may be "philosophical." Surgeons are more inclined to radical surgical approaches than physicians. When there are few TPM nodules, usually in the costophrenic recess or diaphragm, TPM resection is easy, and can even be achieved through minimally invasive surgery. Video-assisted thoracoscopic surgery has been maturely applied in thoracic surgery and can provide better observation angles. Open thoracotomy or sternotomy is suitable for the following situations: TPM with in-situ mediastinal recurrence, large pleural mass, widespread pleural or pericardial dissemination, diaphragmatic involvement, and invasion of the hilum or chest wall. We recommend combined open surgery and thoracoscopic techniques for the treatment of TPM. With the cooperation of thoracoscopy, all corners of the chest cavity can be explored, making it easier to achieve the greatest extent of tumor resection.

至今尚未有临床随机对照试验证实单纯手术优 于化疗，或者联合放化疗。既往回顾性研究数据表 明外科手术联合药物治疗患者的无进展生存优于单 纯放化疗。然而，在外科团队主导的研究中，手术 仅限于临床状态良好的患者，术前判断潜在完全切 除的患者和可完全切除的复发性肿瘤。这种临床选 择偏差导致手术治疗优越性的统计学价值较低。

理论上， T PM胸腺瘤的完全切除应该提供最 佳的长期生存，但是否能完全切除的判断可能是 “哲学性的”，外科医生相比内科医生更倾向激 进的外科方法。当T PM结节很少时，通常在肋膈 隐窝或横膈膜上， T PM切除很容易，甚至通过微 创手术即可实现。电视胸腔镜手术在胸外科已经 成熟应用，并且可以提供更佳的观察角度。直接 开胸或者胸骨劈开手术适用于以下情况： T PM伴 有纵隔原位复发，大块胸膜占位，胸膜或者心包 的广泛播散，膈肌受累，侵及肺门或胸壁。推荐 开放手术联合胸腔镜技术治疗T PM ，在胸腔镜的 配合下，可以探查胸腔的各个角落，更易实现最

大程度切除肿瘤。

Pleurectomy/decortication (P/D), extended pleurectomy/decortication (eP/D), and extrapleural pneumonectomy (EPP) are common surgical methods for treating TPM. EPP can achieve radical resection of TPM by resecting the diaphragm if necessary, especially suitable for patients with widespread dissemination. However, according to data from a retrospective multicenter study in Japan, among 136 patients with stage IVA thymoma, 8 patients underwent EPP, and the 5-year OS was only 70%. Foreign scholars reported that the perioperative complication rate of EPP is 20%~47%, and the perioperative mortality rate is 0~17% [6]. Therefore, EPP is suitable for experienced surgical teams for "superselected patients". Wright summarized the selection criteria for EPP: extensive pleural disease with phrenic nerve palsy, young patients with good cardiopulmonary function, and well-controlled myasthenia gravis [7]. EPP is often used for malignant pleural mesothelioma and is favored by some surgeons, but for thymoma, a slow-progressing indolent tumor, the therapeutic value of EPP needs further confirmation. Our clinical team prefers P/D or eP/D, removing visible pleural dissemination lesions and invaded tissues as much as possible. eP/D includes partial lung resection, partial diaphragm resection with repair, partial pericardium resection with repair, partial phrenic nerve resection, chest wall resection, and partial azygos vein resection; it focuses not only on the extent of tumor resection but also on perioperative mortality and complications. P/D or eP/D adopts a lung-preserving procedure, which can reduce postoperative complications and mortality and improve patients' postoperative quality of life. For patients judged preoperatively as not completely resectable, surgical treatment should be cautiously selected first, and the choice between cytoreductive surgery and extended resection during surgery still requires careful selection by the surgeon.

III. HITOC

Body cavity hyperthermic intraperitoneal chemotherapy (HIPEC) is a new adjuvant cancer therapy method that involves heating a large volume of perfusate or a perfusate containing chemotherapeutic drugs to a certain temperature, continuously circulating and maintaining a constant temperature into the patient's body cavity (thoracic cavity, abdominopelvic cavity, bladder) for a certain period of time. Through the synergistic sensitization effect of hyperthermia and chemotherapy and the flushing effect of large-volume perfusate circulation, it effectively kills and removes residual cancer cells and micrometastases in the body cavity. It is particularly effective in preventing and treating thoracic and abdominal cavity implantation metastasis, especially malignant pleural and ascites.

The application principles of HITOC include the following aspects: ① Thermal effect, normal tissues can tolerate 47 ℃ for 1 h, while tumor tissues are heat-intolerant due to their unique biological characteristics and begin to die at 43 ℃ for 1 h; therefore, the commonly used perfusion temperature and duration are 43 ℃ (thoracic cavity) and 60 min, which can effectively kill tumor cells.

② Local chemotherapy, this utilizes the natural barrier effect of the "pleura-plasma barrier" on chemotherapeutic drugs, concentrating chemotherapeutic drugs at higher concentrations and for longer periods in the thoracic cavity, thus directly killing residual micrometastases and tumor cells in the body cavity; at the same time, the drug concentration entering the systemic circulation is low, which can reduce the occurrence of systemic toxic side effects. ③ Synergistic sensitization effect of heat and chemotherapy, this utilizes the fact that chemotherapeutic drugs can have stronger pharmacological activity and deeper tissue penetration at high temperatures. Under the action of heat, some chemotherapeutic drugs can penetrate into tumor tissue 3-5 mm below, playing a 1+1 > 2 role. ④ Mechanical flushing effect, large-volume perfusate can fill the entire body cavity, and the physical action of circulatory flushing washes away free cancer cells, micrometastases, blood clots, and necrotic substances in the body cavity. Body cavity hyperthermic intraperitoneal chemotherapy uses these principles comprehensively to achieve a "one method, multiple levels" therapeutic effect.

After thoracic drainage tube placement, it can be used multiple times, with the advantage of repeatability, that is, after the patient has a drainage tube placed, multiple treatments can be performed according to the condition. This treatment model has been clinically applied in bladder perfusion and abdominal cavity perfusion. HITOC can also be perfused multiple times, and the chemotherapy regimen and dosage for each treatment can be adjusted according to the patient's condition; even without chemotherapy drugs, simple liquid hyperthermia perfusion or gas hyperthermia perfusion can be chosen. However, for TPM thymoma treatment with HITOC, it is still under exploration, and the safety and oncological effects of multiple treatments still need further verification.

IV. Surgery combined with HITOC

Visible TPM can be surgically removed, but unfortunately, many micrometastases or free tumor cells are difficult to remove. Due to dose-limiting toxicity and the existence of the pleural-plasma barrier, systemic treatment has limited control over thoracic and abdominal membrane metastasis. Surgery combined with HITOC achieves complementary advantages, surgically removing visible tumors, and HITOC killing residual micrometastases and free tumor cells. Through continuous treatment with surgery and HITOC, the radical cure effect of TPM is maximized.

Previous studies have provided strong evidence for the feasibility of treating TPM thymoma with surgery combined with HITOC (Table 1). Maury et al. [8] collected 19 patients with TPM thymoma who underwent surgery and HITOC. All patients underwent radical resection, including 18 eP/D and 1 EPP. The average maximum perfusion temperature was 42 ℃, with no perioperative deaths and a complication rate of 26%, of which 3 cases (16%) experienced chemotherapy toxic side effects; the median follow-up time was 39 months, and the median DFS time was 42 months. Five patients died during the follow-up period, with a median OS time of 63 months and a 5-year survival rate of 86%. Yellin et al. [9]

This report details 35 thymic epithelial tumor (TET) patients who underwent surgery combined with HITOC treatment. After a median follow-up of 62 months, the results showed: Surgery combined with HITOC had no serious complications; 90-day mortality was 2.5%; surgery-related complication rate was 12%; 5-, 10-, and 15-year overall survival rates were 50%, 26%, and 12%, respectively; and 5-, 10-, and 15-year progression-free survival rates were 35%, 13%, and 9%, respectively. Refaely et al. [10] reported on 15 TET patients who received surgery combined with HITOC treatment. The complete resection rate was 66.7%, R1 resection rate was 20.0%, and R2 resection rate was 13.3%. There were zero perioperative deaths and no serious complications such as perioperative respiratory failure or major bleeding. Four patients survived more than 5 years after treatment. However, like other similar studies, some issues remain. First, the small number of cases in these single-center studies is insufficient for effective assessment of complication rates. Second, the treatment regimens varied across reports, including cisplatin alone, cisplatin combined with doxorubicin, and cisplatin combined with mitomycin. Cisplatin dosages also varied (80–175 mg/m2 body surface area (BSA)). Therefore, the optimal chemotherapy regimen in HITOC treatment is controversial, and no clinical studies have yet analyzed the impact of different HITOC regimens and dosages on the survival prognosis of TPM.

Based on current research progress and past clinical experience, we conducted the world's first prospective clinical study: a prospective single-arm clinical study (CHOICE) [14] of surgery combined with HITOC for the treatment of pleural dissemination or TPR thymic epithelial tumors. This study plans to screen 37 TET patients who meet the inclusion criteria. The overall treatment plan includes a screening phase, a surgery combined with HITOC treatment phase, and a follow-up phase. ① Screening phase: According to the inclusion criteria, patients suitable for surgery combined with HITOC treatment for pleural dissemination or TPR TET are screened by the MDT team.

② Surgery combined with HITOC treatment phase: The surgical approach is selected by the surgeon based on the patient's condition, including minimally invasive thoracoscopic surgery or open-chest surgery. The purpose of surgery is to remove larger tumors and reduce tumor burden, including but not limited to the affected pleura, diaphragm, or lung. Three chest tubes are placed postoperatively:

One inflow tube, placed in the 4th or 5th intercostal space in the anterior axillary line, inserted to a depth of 10–15 cm; and two outflow tubes, placed in the 7th or 8th intercostal space in the mid-axillary or posterior axillary line, inserted to a depth of 8–10 cm. General/combined anesthesia is used. Volume-controlled ventilation is used intraoperatively, with a tidal volume of 6–8 mL/kg. The anesthesiologist determines the extubation time based on clinical results. HITOC treatment can be performed in the operating room, ICU, or general ward. Doxorubicin is infused at 25 mg/m2 on postoperative day 1, and cisplatin at 50 mg/m2 on postoperative day 2. The patient is positioned in a semi-sitting or supine position for HITOC. The lavage fluid and drugs are preheated to 43 ℃ after preparation; pre-lavage is set at 250 mL/min; the infusion rate can be self-adjusted according to body weight, chest size, and oxygen saturation. A new generation of body cavity hyperthermic perfusion system and dedicated disposable treatment tubes are used for HITOC. ③ Follow-up phase: Perioperative indicators and postoperative follow-up are recorded. Patient safety and perioperative outcomes include vital signs; temperature monitoring; blood tests, liver and kidney function, biochemical blood glucose monitoring; chest drainage; pain scores on postoperative days 1, 3, 7, and 30; chest tube removal time and postoperative hospital stay; perioperative complication rates (atelectasis, pneumonia, pneumothorax, chest infection, pleural effusion/hematoma, poor wound healing); and quality of life scores at 1, 3, and 6 months postoperatively. Long-term follow-up is conducted to monitor DFS and OS.

Standardized HITOC procedures are also key to ensuring a smooth and safe treatment process. Strict adherence to operational procedures, rational use of chemotherapeutic drugs, and careful patient selection are crucial for reducing complication rates and improving overall treatment safety and efficacy.

Table

Comparison of Clinical Studies with Different Treatment Regimens 1 Study

BSA: Body surface area; EPP: Extrapleural pneumonectomy; P/D: Pleurectomy; CRS: Cytoreduction surgery; OS: Overall survival.

V. Chemotherapy and radiotherapy

Advanced thymoma can be treated with chemotherapy. Commonly used chemotherapy regimens include cisplatin, doxorubicin, vincristine, and cyclophosphamide (A DOC), cisplatin, doxorubicin, and cyclophosphamide (PAC), and paclitaxel and cisplatin (TP). Early research data showed that T PM thymomas respond poorly to chemotherapy. Of 15 patients with T PM thymoma, only 6 showed a partial response to chemotherapy, 8 were stable, and 1 showed tumor progression; while in 66 thymoma patients without T PM receiving induction therapy based on chemotherapy, 2 developed T PM [15]. Previous research data rarely focused on evaluating the response of TRM to chemotherapy. To date, no clinical trials have confirmed the effectiveness of chemotherapy for T PM thymoma. The current difficulty lies in accurately assessing the response of pleural lesions to chemotherapy. Chemotherapy can be used as a treatment for extensive T PM thymoma. Multicenter studies are currently needed to provide higher-level data to confirm the effectiveness and adverse reactions of chemotherapy for TPM.

More and more innovative radiotherapy techniques are being used in the treatment of thymoma, such as adaptive radiotherapy, tomotherapy, and particle radiotherapy.

The main problem with radiotherapy is the accumulation of dose in surrounding tissues. This problem is more pronounced in radiotherapy for thymoma because surrounding organs, including the heart, lungs, and esophagus, cannot avoid radiation. As reported in the literature, the mass of thymoma can be reduced by 40% to 70% within the first two cycles of initial radiotherapy. The masses of TPR thymomas are often small but extensive, which poses new requirements for radiotherapy. Tomo-radiotherapy has higher dose conformity, more accurate dose intensity modulation, and finer modulation of the dose to normal tissues around the tumor. In our team, Tomo-radiotherapy is widely used in T PM thymoma. In addition to radiotherapy at the primary site, radiation also covers the pleural area. In addition to local treatment of metastatic nodules, Tomo-therapy also considers the entire ipsilateral pleura. Tomo-radiotherapy can maintain the dose coverage rate of tumor and pleural targets while reducing the dose to organs at risk [16].

VI. Conclusion

Surgical resection contributes to the long-term survival of T PM, and surgery should be based on the patient's overall condition, the condition and extent of pleural involvement,

The surgical scope should remove all macroscopically visible lesions as much as possible. The clinical effects of radiotherapy and chemotherapy on T PM still need to be confirmed by well-designed multicenter clinical trials. Tomo-radiotherapy provides innovative radiotherapy technology for the treatment of T PM thymoma, showing great advantages in whole-pleura radiotherapy; the "sandwich" therapy combining surgery, HITOC, and radiotherapy is expected to become a potential treatment strategy for T PM. HITOC provides a new option for T PM thymoma, and our ongoing clinical research will confirm the safety and effectiveness of surgery combined with HITOC for the treatment of T PM thymoma. With the continuous development of multidisciplinary communication, anti-tumor drugs and radiotherapy technologies, and surgical techniques, the treatment of TPM thymoma will surely usher in a new era.

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(Received: 2024-08-06; Revised: 2024-08-28; Accepted: 2024-09-02)

(Edited by: Ding Wei)

Wang Shuai, Ao Yongqiang, Ding Jianyong. Emerging treatment strategies for thymoma with pleural dissemination or recurrence - surgery combined with intrathoracic hyperthermic perfusion chemotherapy ［J/OL］. Chinese Journal of Thoracic Surgery (Electronic Edition), 2024, 11(4): 236-241.