An in silico planning study comparing doses and estimated risk of toxicity in 3D-CRT, IMRT and proton beam therapy of patients with thymic tumours
Introduction
Thymic tumours, i.e. thymoma and thymic carcinoma, derive from the epithelial cells of the thymus gland. Thymic tumours may be non-invasive (WHO Type A thymoma) or show loco regional invasive, or even metastatic traits (WHO Type B thymomas and Type C thymic carcinomas, respectively) [1]. Thymectomy is the main, and sometimes definitive, treatment. Patients (pts) with positive surgical margins, gross residual disease, tumour recurrence or unresectable tumours, may be treated with radiotherapy (RT), in a neo-/adjuvant, salvage or definitive setting. Prescribed doses depend on the clinical indication, with lower doses given to pts with minimal or positive surgical margins (45–60 Gy) and higher doses to patients with gross residual disease or unresectable tumours (60–70 Gy) [2]. Radiotherapy is often combined with platinum-based chemotherapy [2].
Due to its location in the anterior mediastinum, the thymus is closely adjacent to several critical organs, such as heart, lungs, oesophagus and spinal cord. Several studies on RT in thoracic tumours, e.g. breast cancer, lymphoma, lung-, and oesophageal cancer, have shown a wide range of acute and long-term toxicities, e.g., pneumonitis, pericarditis, esophagitis, myelitis and cardiovascular events [3], [4], [5], [6]. As the long-term survival for many thymoma pts is excellent, avoidance of severe RT-related side effects is vital.
A small number of studies have shown dosimetric advantages when using proton beam therapy (PBT) in the treatment of thymic tumours as compared to photon RT, especially with regard to doses to the organs at risk (OAR) [7], [8]. In the present study, we evaluate the dosimetric- and NTCP-outcomes for 12 patients treated for thymoma, or thymic carcinoma, comparing spot-scanning PBT implemented with the single-field uniform dose (SFUD) technique and photon beam RT performed with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT). Multi-field optimization was not used due to uncertainties in the produced dose distributions, caused by possible organ movement, associated with this method.
Section snippets
Material and methods
The Regional Medical Ethics Committee has approved this study.
Dosimetric comparison
For all pts, the robustness criteria set for the CTV and spinal cord were met with the SFUD plans. The planning objective for the PTV (3D-CRT plans) and the constraints for the OARs (3D-CRT and SFUD plans) were also respected. Typical dose distributions obtained with 3D-CRT and SFUD plans are shown in Fig. 1, for a representative patient case. The obtained DVHs for the CTV and the OARs with the 3D-CRT and the SFUD plans are also presented for this patient (Fig. 2).
For the 3D-CRT, IMRT and the
Discussion
In the present study, we demonstrate dosimetric advantages of using SFUD delivered with scanned proton beams in the treatment of thymic tumours, as compared to photon 3D-CRT and IMRT. The probability of observing different toxicities was also evaluated for the three treatment modalities. A good CTV dose-coverage was obtained with both the SFUD plans and the clinically used photon plans. The dose-volume values for several OARs were significantly lower with the SFUD plans, than in the
Conclusion
The present study confirms the dosimetric advantage of using PBT in the treatment of thymic tumours, as compared to 3D-CRT and IMRT, in regard to lower doses to OARs, and in reducing the risk of toxicity, especially to the lung and oesophagus. Randomized, prospective studies, comparing PBT with photon radiotherapy, should be performed to confirm PBT as a feasible alternative in the treatment of thymic tumours.
Acknowledgements
Declarations of interest: None.
Funding: this research did not receive any specific grant from funding agencies in the public, commercial, or not-for profit sectors. Gracinda Mondlane and Albert Siegbahn would like to acknowledge the support of the cancer research funds of Radiumhemmet.
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