Abstract

Thymic carcinoma is a rare malignancy with peak incidence in the 4th-6th decade. In contrast to thymoma, it is commonly associated with higher rates of both lymph node and distant metastatic spread and also with shorter disease free survival. For localized or locally advanced disease, surgical resection, with the intention of complete disease extirpation, remains the standard of care. Due to its rarity however, definitive clinical trial data regarding optimal and appropriate addition of adjuvant therapy is lacking. Thus, decision making for post-operative patients is guided by data from large institutional, national or international retrospective series or databases (evidence level IV or V). Recommendations for adjuvant therapy for thymic carcinoma are influenced principally by stage and adequacy of resection (R0 vs R1 vs R2). Thymic carcinoma is classically staged us the Masaoka-Koga (MK) system but, based on recommendation to the AJCC by the IASLC Staging Prognostic Factors Committee and the International Thymic Malignancy Interest Group (ITMIG), using a database of more than 10 000 patients (Detterbeck et al 2014), a TNM-based system has now been incorporated into the 8th Edition of the AJCC/UICC TNM Classification of Malignant Tumours. However, since much of the published data regarding thymic malignancies is based on the Masaoka-Koga system, at present this remains commonly used for clinical decision-making but, as data continues to accumulate, will likely be superseded by the TNM system over time. Post-operative radiotherapy is routinely recommended for patients with MK stage III (TNM Stage I – T1bN0, Stage II, IIIA/B) thymic carcinoma following R0 resection. Similarly, adjuvant radiation is recommended following R1 resection, regardless of stage, with adjuvant chemoradiation recommended following R2 resection. Adjuvant radiotherapy is not recommended for MK I or IIA (TNM Stage 1 T1aN0 with no extension to mediastinal fat) disease. Controversy exists regarding the utility of adjuvant radiotherapy in the management of MK IIB (TNM Stage I – T1aN0 with extension to mediastinal fat) disease but can be considered for this group of patients. The optimal adjuvant radiotherapy dose remains undefined for thymic carcinoma patients but typical doses reported in the literature for patients in the above recommended groups range from 45-50 Gy in 1.8-2 Gy per fraction daily. Following R1 resection, 50-54 Gy in 1.8-2 Gy per fraction is typically recommended. Following R2 resection, 60-70 Gy (with or without concurrent chemotherapy) is considered standard. Nodal involvement is much more frequent in patients with thymic carcinoma compared with thymoma. Resected, unexpectedly N+ patients are typically recommended to receive adjuvant RT to 45-60 Gy if complete resection was obtained or 60-70 Gy (with or without concurrent chemotherapy) if residual nodal disease is suspected/documented. Under the TNM staging system, N1 nodes are defined as those in the anterior mediastinal compartment (IASLC levels 1, 3a, 6 and/or supradiaphragmatic/inferior phrenics/pericardial) and N2 nodes are defined as deep intrathoracic or cervical nodes (IASLC levels 2, 4, 5, 7, 10 and/or internal mammary nodes). Whether inclusion of N1 or N2 nodal compartments in adjuvant RT target volumes is of benefit for N0 or completely resected N1 or N2 patients remains unknown but may be prudent to consider during radiotherapy planning based on clinical factors. Radiotherapy should conform to modern standards with CT-based simulation with photon-based 3D conformal or beam-modulated treatment delivery, motion management and image guidance to reduce margins and dose to organs at risk. The utility of adjuvant proton-based RT for patients with resected thymic malignancy remains the focus of ongoing study but may offer some dosimetric advantages with respect to OAR dose (e.g. lung or heart). Selected

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