Adaptive Radiation Therapy for Intact Thymoma: An Illustrative Report

Discussion

The concept of ART was first formally introduced by Yan et al. in 1997 (6). A recent review article by Badley et al. in 2019 provides an overview of current ART strategies (7). The overall objective of this technological advancement is to improve the quality of a patient’s treatment by maintaining prescribed dose to the target while reducing dose to healthy tissue (8). Because re-planning radiotherapy treatment takes time, ART is only worthwhile in tumors that have significant shrinkage early in the treatment course. For this reason, ART has predominantly been utilized for head and neck and lung tumors (7, 9-10). A recent review of 29 articles regarding ART for head and neck cancer suggested that ART may decrease toxicity and improve local control for locally advanced head and neck cancer (9). A recent phase 2 clinical trial evaluated ART for non-small-cell lung cancer and demonstrated favorable local-regional tumor control (10). While many types of malignancies shrink very slowly and thus are not amenable to ART, thymoma is known to be a radiosensitive tumor (11). Although ART is certainly being used for thymoma at many institutions, there are no prior publications illustrating the impact of ART for thymoma.

While induction therapy is standard of care for patients with initially unresectable thymoma, induction chemotherapy is more common than induction chemoradiation because these tumors are often very large and thus would require large radiotherapy fields (4, 12). However, there are notable benefits of concurrent chemoradiation including the synergistic effects of combining chemotherapy with radiation and the increased ability to obtain an R0 resection (12). A retrospective review of 10 patients with locally advanced thymic tumors treated with induction chemoradiation consisting of cisplatin and etoposide resulted in 8 patients receiving an R0 resection and 2 patients receiving an R1 resection (12). Since large radiotherapy fields is the major disadvantage of induction chemoradiotherapy relative to induction chemotherapy, one method to obtain the benefits of induction chemoradiotherapy while minimizing the detrimental effects of large radiotherapy fields is the utilization of ART.

This patient had a very large tumor that showed significant radiographic response early in the chemoradiation course. Therefore, he was the ideal candidate for ART. Table II depicts the lung dosimetry for his case and compares it to both the hypothetical lung dosimetry had he not received ART and the hypothetical lung dosimetry if ART treatment could have been initiated the same day the adaptive 4DCT simulation was performed. This highlights not only the benefit of ART but also the added value of rapid re-planning.

The histological classification of his thymoma may be responsible for his rapid radiographic response to chemoradiation. While all thymomas are known to be radiosensitive, WHO type B2 thymoma has abundant immature T cells so theoretically it should be even more sensitive to chemoradiation (1). Unfortunately, due to the low incidence of thymoma in general, there are no published studies demonstrating different levels of radiosensitivity for different thymoma histologies.

The patient has done very well without any recurrence or treatment-related toxicity. Concurrent induction chemoradiotherapy with ART successfully down-staged the disease allowing for optimal surgical resection while minimizing the irradiation volume of normal tissues. Therefore, ART appears to be feasible, safe, and efficacious for locally advanced intact thymoma.