Managing stage IV thymic carcinoma—a narrative review of radiation therapy strategies and options
Review Article

Managing stage IV thymic carcinoma—a narrative review of radiation therapy strategies and options

Annemarie F. Shepherd

Division of Radiation Oncology, University of Washington School of Medicine, Seattle, WA, USA

Correspondence to: Annemarie F. Shepherd, MD. Division of Radiation Oncology, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356043, Seattle, WA 98195-6043, USA. Email: ashepher@uw.edu.

Background and Objective: Thymic carcinoma is a type of thymic epithelial tumor that is rare and aggressive. Compared to patients with thymoma, patients with thymic carcinoma experience worse overall survival, progression-free survival and earlier relapses. Patients with stage IV thymic carcinoma most commonly have disease involving the pleural or pericardium, but distant spread outside the thorax is also possible. The purpose of this review is to describe radiation therapy strategies and options for patients with stage IV thymic carcinoma.

Methods: Due to the rare nature of thymic tumors, the literature on stage IV thymic carcinoma is limited. As a result, most of the data on stage IV thymic carcinoma is based on retrospective reviews and heterogenous populations.

Key Content and Findings: The management of stage IV thymic carcinoma is multidisciplinary and depends on many factors including the patient’s performance status, extent of disease, biology of the disease and intent of treatment. Systemic therapy, surgical resection, observation, and radiation therapy are often considered. Radiation can be used for palliation of symptoms, prevention of impending symptoms, and potentially for prolongation of disease control particularly in patients with oligometastatic or oligoprogressive disease. The type of radiation used in patients with stage IV thymic carcinoma depends on the intent of treatment, location of the disease, size of the target, and proximity to organs that are sensitive to radiation. Various techniques such as 3D conformal radiation therapy (3DCRT), stereotactic body radiation therapy (SBRT), intensity modulated radiation therapy (IMRT), proton beam therapy, and hemi-thoracic intensity-modulated pleural radiation therapy (IMPRINT) may be considered depending on these factors.

Conclusions: In patients with stage IV thymic carcinoma, radiation therapy is an effective modality for palliation of symptoms, prevention of impending symptoms, and potentially for prolongation of disease control. Due to the rare nature of the disease, additional data and research are required to better understand the impact and appropriateness of various treatment approaches in patients with thymic carcinoma. Because the management of stage IV thymic carcinoma can involve multiple different modalities depending on the patient’s individual case, a multidisciplinary approach is critical for optimal patient care.

Keywords: Thymic carcinoma; pleural recurrence; pleural radiation; intensity-modulated pleural radiation therapy (IMPRINT); proton therapy

Received: 05 March 2025; Accepted: 09 December 2025; Published online: 24 December 2025.

doi: 10.21037/med-25-14

Introduction

Although thymic tumors are the most common tumor originating from the anterior mediastinum, they are rare with an incidence in the United States of 0.13–0.15 per 100,000 population at risk (1). Thymic tumors are typically comprised of thymomas, thymic carcinomas and thymic neuroendocrine neoplasms. The prognosis of thymic malignancies is complex and based on staging as well as histologic subtype. While thymic carcinomas are rarer than thymomas, they have been shown to be more aggressive than thymoma with worse overall survival, progression-free survival (PFS) and earlier relapses (2,3). According to the American Joint Committee on Cancer (AJCC) 9th edition tumor-node-metastasis (TNM) Staging System, patients are considered to have stage IV thymic tumors if they have involvement of perithymic lymph nodes (N1, stage IVA), the pleura/pericardium (M1a/stage IVA), deep intrathoracic or cervical lymph nodes (N2, stage IVB) or distant organ metastases (including the lung, M1b, stage IVB) (4). Two studies of patients with thymic tumors treated with resection and postoperative radiotherapy (PORT) indicate that the majority of local-regional failures occur in the pleura (5,6). Patients with thymic carcinoma tend to relapse at distant sites more frequently than patients with thymoma. The most common sites of distant relapse include the bone, lung, and liver (2,7).

This narrative review provides information on radiation therapy strategies and options for patients with stage IV thymic carcinoma. I present this article in accordance with the Narrative Review reporting checklist (available at https://med.amegroups.com/article/view/10.21037/med-25-14/rc).

Methods

Our search was conducted on the MEDLINE databases. This narrative review is not a systematic review and therefore some available evidence may be inadvertently excluded from the review. Articles including original full-length articles, meta-analyses, review articles and case reports were included. Table 1 outlines the search strategy summary.

Table 1

The search strategy summary

Items Specification
Date of search 9/1/2024–2/26/2025
Databases and other sources searched PubMed/MEDLINE; known sentinel manuscripts
Search terms used Not limited to: “radiation therapy thymic”, “thymic carcinoma”, “radiotherapy thymic”, “PORT thymic”, “patterns of failure thymic”, “proton therapy thymic”, or any combination thereof
Timeframe Up to February 2025
Inclusion criteria English only
Selection process Selection conducted by the author: A.F.S.

PORT, post-operative radiation therapy.

Key content and findings

While radiotherapy is a standard consideration in the management of locally-advanced thymic carcinoma, the objective for radiation therapy in patients with stage IV thymic carcinoma depends on the patient’s condition, location of the target, the extent of metastatic disease and the intent of treatment (8-15). Typical objectives for radiation of stage IV disease include palliation of symptoms, prevention of impending symptoms, and prolongation of disease control particularly in patients with limited extent of disease. The type of radiation used in patients with stage IV thymic carcinoma depends on the intent of treatment, site of metastases, size of the target, and proximity to organs that are sensitive to radiation (Table 2).

Table 2

Radiation techniques for stage IV thymic carcinoma

Technique Common dose regimens Clinical indications   Benefits   Limitations
Conventional/3DCRT Palliative regimens: 8 Gy × 1 fraction; 4 Gy × 5 fractions; 3 Gy × 10–15 fractions Palliation   Quick and easy to plan   Poor conformality, which limits the ability to treat to high doses
  Covers a wide region
IMRT PORT/definitive regimens: 1.8–2 Gy × 25–30 fractions PORT   Conformal, which results in lower exposure of normal organs to radiation   Complex planning requiring more resources
Hypofractionated palliation: 3–4 Gy × 10–15 fractions Definitive RT   Longer time required for radiation planning
Hypofractionated palliation   Occasional insurance issues
SBRT 6–10 Gy × 3–5 fractions Oligometastatic/oligoprogressive disease   Highly conformal allowing for dose escalation and lower exposure of normal organs to radiation   Best suited for small, well-defined targets
Aggressive palliation (e.g., spine SBRT)   Requires strict immobilization, which can be uncomfortable
  Complex planning requiring more resources
  Longer time required for radiation planning
  Occasional insurance issues
IMPRINT 1.8–2 Gy × 25–30 fractions Clinical trial for control of pleural disease   Conformal technique using IMRT or proton therapy to target the whole ipsilateral pleural space   Complex planning
  Large target
  High risk of pneumonitis
  Only being done on a clinical trial
Proton therapy PORT/definitive regimens: 1.8–2 CGE × 25–30 fractions PORT   Radiation beam can stop at the target, eliminating exit dose which results in lower exposure of normal organs to radiation   Complex planning requiring more resources
Hypofractionated palliation: 3–4 CGE × 10–15 fractions Definitive RT   Longer time required for radiation planning
Hypofractionated palliation   Insurance issues
  Limited access to proton therapy centers
Carbon ion therapy Under investigation; current trial uses 4 GyE × 18 fractions Under investigation   Radiation beam with larger particles that may more effectively kill tumor cells and also spare normal organs   Not available in most countries (including USA)
  Under investigation
  High cost

3DCRT, 3D conformal radiation therapy; CGE, cobalt Gray equivalent; Gy, Gray (unit of radiation); GyE, Gray equivalent; IMPRINT, intensity-modulated pleural radiation therapy; IMRT, intensity modulated radiation therapy; PORT, post-operative radiation therapy; RT, radiation therapy; SBRT, stereotactic body radiation therapy.

Radiation therapy for stage IV thymic carcinoma by site of metastases

Lymph node metastases

In thymic malignancies, thoracic lymph node metastases (N1 or N2) are staged as stage IVA or stage IVB. Compared to thymoma patients, patients with thymic carcinoma are more likely to have lymph node involvement (16,17). From a radiation therapy perspective, patients with lymph node involvement without other sites of metastases like the pleura/pericardium or extrathoracic sites are treated definitively with either post-operative radiation therapy (PORT) if they underwent surgery or definitive radiation therapy with or without chemotherapy.

Pleural metastases

The management of pleural metastases typically requires a multidisciplinary approach and treatment recommendations depend on the patient’s performance status and co-morbidities, the extent of disease and how quickly the disease appears to be progressing. Options include systemic therapy, surgical resection, radiotherapy, and close monitoring with interval imaging. For thymoma cases, if there is a limited extent of indolent, resectable pleural disease in a fit patient, surgical resection is usually considered as a primary treatment (18,19). Upon progression, patients may undergo repeat surgery until further surgical resection is no longer recommended. Choe et al. found that after surgical resection of pleural metastases, the 5-year PFS rate was 29%. Among the 15 patients with thymic carcinoma in this study, however, the 5-year PFS was 0%. The authors conclude that “it is less clear that aggressive surgical intervention benefits patients with stage IV thymic carcinoma” (18).

For pleural metastases in patients with stage IV thymic carcinoma, radiation therapy may be used for palliation. The typical objective of palliative radiotherapy is to palliate symptoms caused by the tumor and prevent impending symptoms when pleural metastases are radiologically encroaching upon critical structures. Examples of symptoms that can be caused by pleural metastases include chest wall or back pain when the tumor is invading the chest wall or vertebral body, respectively, superior vena cava (SVC) syndrome caused by compression of the SVC, brachial plexopathy from compression of the neural plexus, or neurologic deficits caused by neural foramen involvement or spinal cord compression. Additionally, compression of the bronchial airway or vasculature can cause shortness of breath, palpitations, or chest pain. In these cases, radiotherapy can shrink the metastases away from the critical structures to alleviate symptoms and prevent future local progression.

Patients with extensive pleural involvement are at risk for disease progression throughout the pleura. A phase II study by Wang et al. treated thymoma patients with unresectable pleural metastases that progressed on chemotherapy with intensity modulated radiation therapy (IMRT) to 30–50 Gy in 2 Gy/fractions (20). This regimen was safe when one course of radiation was delivered and the control rates were optimal with 50 Gy. The median PFS was 19 months. Unfortunately, 93.5% of patients developed out-of-field failures, indicating that only targeting areas of known pleural metastases is not sufficient in preventing future progression. While this study was done in patients with thymoma, there is likely less of an indication for this approach for extensive pleural involvement in patients with thymic carcinoma, who have more aggressive disease.

With advancing radiation technologies, such as IMRT with photons and pencil beam scanning with proton therapy, it is now feasible to safely deliver higher radiation doses to the hemithoracic pleura with two intact lungs. Hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) is a radiation technique that has been studied in pleural mesothelioma and may be an option in select thymic patients to delay or prevent progression of pleural metastases from thymic malignancies (21-23). The technique targets the entire pleural space and could eradicate microscopic pleural disease prior to developing into an out-of-field failure when targeting only known sites of disease. Due to the large radiation field, however, patients could be at risk for radiation pneumonitis and fibrosis. To better understand the role of this radiation technique in thymic patients, hemithoracic IMPRINT is currently under investigation as a treatment for patients with pleural metastases from thymic malignancies, including thymic carcinoma (Clinicaltrials.gov ID: NCT05354570).

Distant extrathoracic metastases

For distant extrathoracic metastases in the bone, lung and liver, systemic therapy is typically the mainstay of treatment. Radiation therapy can be used for palliation. Toxicities related to treatment of distant extrathoracic metastases are determined by the normal organs near the radiation field and the doses to these organs. Organs that are sensitive to radiation tend to be the mucosal organs (e.g., oral cavity, gastrointestinal tract), skin, lung. However, each organ has a different tolerance for radiation.

For patients with a limited extent of metastatic disease (oligometastatic or oligoprogressive disease) and good performance status, radiation can potentially be used to prolong disease control. Highly-effective local therapies, such as surgical resection or stereotactic body radiation therapy (SBRT), for the treatment of oligometastases (limited number of metastatic sites of disease) or oligoprogression (limited number of progressive sites of disease) is a relatively newer treatment approach for metastatic disease. For patients with small metastases, SBRT can deliver high doses of radiation in few treatments using a highly conformal approach to maximize the dose of radiation delivered to the target and avoid sensitive organs. Data from other disease sites, such as lung cancer, have demonstrated improvements in progression-free and overall survival with this aggressive treatment approach (24-29). In these studies, oligometastases/oligoprogression was defined as either 5 or fewer or 3 or fewer sites. While the data for definitively treating thymic-specific patients with oligometastatic/oligoprogressive disease is limited to case reports and small series, SBRT or surgery may be options for select patients (30-34). The ability of highly effective local therapies to eradicate all macroscopically appreciable disease makes this an attractive approach. Due to the more aggressive nature of thymic carcinoma compared to thymoma, however, it is unclear how this approach would potentially benefit different thymic histologies. Because thymic carcinoma is more aggressive, it is possible that patients with thymic carcinoma may not benefit as much from an aggressive approach for oligometastatic/oligoprogressive disease. In the series by Chiappetta et al., which reported outcomes after surgery in patients with distant recurrence from thymic tumors, patients with more aggressive histology like thymic carcinoma had worse overall survival compared to patients with type A, B1 and B2 thymoma (34). Despite this, however, because lung cancer patients seem to benefit from an aggressive approach to oligometastatic/oligoprogressive disease and the prognosis of lung cancer is more similar to thymic carcinoma rather than thymoma, it is possible that patients with thymic carcinoma may benefit from this approach. Additional data on this topic is warranted to understand the best approach for oligometastatic or oligoprogressive disease in patients with stage IV thymic carcinoma.

The optimal management strategy for how to combine SBRT with systemic therapy regimens is also not known. In general, because SBRT is typically given in 3–5 fractions, the SBRT treatments are coordinated in between systemic therapy cycles to avoid concurrent administration of SBRT on the same days as systemic therapy, especially if there are overlapping toxicity profiles of the systemic agent and radiation or if there is concern for radiosensitization and additive toxicity with concurrent administration. For example, systemic agents with VEGF inhibition are avoided with central thoracic radiation therapy given the concern for vascular toxicity (35). Similarly, anthracycline-based therapy with thoracic radiation is avoided given the concern for cardiac toxicity (36).

Radiation therapy techniques for patients with thymic carcinoma with lymph node metastases requiring PORT or definitive thoracic radiation therapy include IMRT or proton therapy. Both IMRT and proton therapy are highly conformal radiation therapy techniques that can spare normal organs. Because reducing the risk of cardiopulmonary toxicity is a priority when treating patient with PORT or definitive radiation therapy, these modalities are preferred over 3D conformal radiation therapy when feasible to limit radiation exposure to the heart and lungs (37-39). Proton therapy is currently being studied by the Swedish Lung Cancer Study Group in a phase II study called PROTHYM, which includes patients with stage IVA thymic carcinoma (Clinicaltrials.gov ID: NCT04822077).

An emerging advancement in radiation therapy, carbon ion radiotherapy, is currently being explored as an option for patients with thymic carcinoma through a Prospective Phase II Clinical Study of Carbon Ion Radiotherapy Combined with Chemotherapy for Thymic Epithelial Tumors being conducted in China (Clinicaltrials.gov ID: NCT06186726). While carbon ion therapy is currently not available in the United States, there are plans to develop a center in Florida. Similar to proton therapy, carbon ion therapy using high energy particles to precisely target tumors. The risks and benefits of this new technology are under exploration.

The radiation technique for the palliation of symptoms varies based on the prognosis of the patient, the size of the radiation target and the location of the target. For patients with poor prognoses, conventional radiation techniques that deliver low doses of radiation using comprehensive, non-conformal fields, may be adequate to provide palliation for a short duration of time. Patients with more favorable prognoses may benefit from more durable local tumor control with higher biologically effective doses of radiation. Higher biologically effective doses are more feasible to achieve with techniques like SBRT and IMRT.

Patients undergoing radiation therapy for oligometastatic/oligoprogressive disease typically have targets that are small and well-defined. In these cases, SBRT is often considered to safely deliver very high doses of radiation. More extensive radiation targets and targets abutting critical organs may not be appropriate for SBRT. In these cases, spreading the radiation treatment out over a longer period of time with alternative highly-conformal techniques such as intensity-modulated radiation therapy or proton beam therapy may be appropriate.

Conclusions

In summary, radiotherapy should be considered as part of a multidisciplinary approach to the management of metastases from thymic malignancies, including thymic carcinoma. Because thymic carcinoma is more aggressive than thymoma, high-risk treatment approaches may not be indicated to spare patients unnecessary toxicity. Radiotherapy can be used to palliate symptoms and can be considered to maximize disease control, particularly in patients with limited sites of disease. Additionally, hemithoracic IMPRINT is a radiotherapy technique that may benefit thymic patients with pleural involvement. While this technique has been established to be safe in patients with pleural mesothelioma, at centers of excellence with significant experience, the safety and efficacy data of IMPRINT in thymic patients needs to be established. Due to the rare nature of the disease, additional data and research are required to better understand the impact and appropriateness of various treatment approaches in patients with thymic carcinoma.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Malgorzata Szolkowska) for “The Series Dedicated to the 14th International Thymic Malignancy Interest Group Annual Meeting (ITMIG 2024)” published in Mediastinum. The article has undergone external peer review.

Reporting Checklist: The author has completed the Narrative Review reporting checklist. Available at https://med.amegroups.com/article/view/10.21037/med-25-14/rc

Peer Review File: Available at https://med.amegroups.com/article/view/10.21037/med-25-14/prf

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-25-14/coif). “The Series Dedicated to the 14th International Thymic Malignancy Interest Group Annual Meeting (ITMIG 2024)” was commissioned by the editorial office without any funding or sponsorship. A.F.S. serves as an unpaid editorial board member of Mediastinum from January 2025 to December 2026. A.F.S. also declares honoraria from the Binaytara Foundation for speaking at the Seattle Lung Cancer Conference, travel reimbursement from IASLC, leadership position in ITMIG as treasurer and stock with ARCELLX. The author has no other conflicts of interest to declare.

Ethical Statement: The author is 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.

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/.

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doi: 10.21037/med-25-14
Cite this article as: Shepherd AF. Managing stage IV thymic carcinoma—a narrative review of radiation therapy strategies and options. Mediastinum 2025;9:33.

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