부산대학교 도서관

Proton therapy for cancer reduces the integral radiation dose to the patient compared to conventional photon treatments.1 The number of proton therapy centers globally has been growing rapidly as a result, but uncertainties in the in vivo proton range remain a considerable hurdle.2,3 A variety of different approaches to reduce proton range uncertainties are therefore currently being pursued.4,5,6,7,8,9,10 The associated benefits have been quantified previously but depend on clinical practices, including the number of gantry angles from which the tumor is irradiated.11,12,13,14 For conventional proton therapy techniques like intensity-modulated proton therapy (IMPT), the target is irradiated from only a few directions, but proton arc therapy (PAT), for which the target is irradiated from hundreds of angles, may see clinical implementation by the time considerable range uncertainty reductions are achieved.15,16,17,18,19 It is therefore crucial to determine the impact of PAT implementation on the importance of range uncertainty reductions. Five head-and-neck cancer patients were randomly selected from The Radiotherapy Optimization Test Set (TROTS).20 For each patient, four different radiotherapy treatment plans were created in Version 6.0 of RayStation (RaySearch Laboratories, Stockholm, Sweden): an IMPT and a PAT treatment plan assuming current clinical range uncertainties of 3.5% (IMPT3.5% and PAT3.5%), and an IMPT and a PAT treatment plan assuming that range uncertainties can be reduced to 1% (IMPT1% and PAT1%). Treatment plans were evaluated with respect to target coverage and organ-at-risk (OAR) doses as well as normal tissue complication probabilities (NTCPs) resulting from organ irradiation during radiotherapy delivery. NTCPs were determined for both parotid glands (endpoint: parotid gland flow < 25% compared to pre-treatment after one year (grade 4 xerostomia)) and the larynx (endpoint: grade ≥ 2 larynx edema).21,22,23 In accordance with clinical practice, radiotherapy treatment planning assumed a patient setup uncertainty of 3 mm, and dose calculations applied a constant relative biological effectiveness (RBE) value of 1.1 to account for differences between proton and photon irradiation.12 For all four types of treatment plans and all delineated organs, OAR doses are shown in Table 1. Values are given in the nominal delivery scenario (in which neither patient setup nor proton range errors occur) as well as in the worst-case scenario (in which errors in patient setup and/or the proton range do occur during treatment delivery) and constitute average values over all five patients. On average, implementation of PAT (IMPT 3.5% -PAT 3.5%) reduced NTCPs in the nominal and worst-case scenario by 2.51 percentage points (pp) and 3.96 pp, respectively. In comparison, reducing range uncertainties from 3.5% to 1% during continued use of IMPT (IMPT 3.5% -IMPT 1%) reduced evaluated NTCPs by 0.64 pp and 1.27 pp, respectively. Average benefits of range uncertainty reductions subsequently to PAT implementation (PAT 3.5% - PAT 1%) were 0.81 pp in the nominal and 1.78 pp in the worst-case scenario. Table 1 Organ-at-risk doses for all four types of treatment plans averaged over all five patients. Nom and WC refer to the nominal and the worst-case delivery scenario, respectively. All values are in units of Gy(RBE) and concern the mean dose within the organ in question, with the exception of the brainstem and the spinal cord, for which the maximum value within the organ is given. SMG refers to the submandibular glands while other abbreviations indicate swallowing muscles. [Display omitted] The average clinical benefit of implementing PAT was approximately three times higher than the benefit of a 3.5% to 1% range uncertainty reduction during continued use of IMPT. Reducing range uncertainties provided a similar clinical benefit for PAT and IMPT. Range uncertainty reductions are therefore expected to remain beneficial even when achieved subsequently to or in tandem with PAT implementation. [ABSTRACT FROM AUTHOR]