Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia.

In the Netherlands, head and neck cancer (HNC) patients qualify for intensity modulated proton therapy (IMPT) based on model-based selection (MBS). The aim of this study was to evaluate the first experience in MBS of HNC patients. Methods: Patients who were subjected to MBS (Jan 2018-Sep 2019) were evaluated. A VMAT plan was created for all patients with optimal sparing of organ at risks (OARs) in normal tissue complication probability (NTCP) models for a number of toxicities. An IMPT plan was created only for those with NTCP difference (DNTCP) between VMAT and best-case scenario for proton (assuming 0 Gy dose for all OARs in IMPT plan) that exceeded any DNTCP-thresholds defined in Dutch National Indication Protocol. These patients qualified for a robust IMPT-plan creation with similar target doses and subsequent plan comparison. Results: Of 227 patients, 141 (62%) qualified for plan comparison, of which 80 (35%) were eventually selected for proton therapy. Most patients were selected based on the DNTCP for dysphagia-related toxicities. The selection rate was higher among patients with advanced disease, pharyngeal tumors, and/or baseline complaints. A significant reduction in all OAR doses and NTCP values was obtained with IMPT compared with VMAT in both selected and non-selected patients, but more pronounced in patients selected for protons. Conclusion: Model-based selection of patients with HNC for proton therapy is clinically feasible. Approximately one third of HNC patients qualify for protons and these patients have the highest probability to benefit from protons in terms of toxicity prevention.

a b s t r a c tBackground and purpose: A planning target volume (PTV) in photon treatments aims to ensure that the clinical target volume (CTV) receives adequate dose despite treatment uncertainties. The underlying static dose cloud approximation (the assumption that the dose distribution is invariant to errors) is problematic in intensity modulated proton treatments where range errors should be taken into account as well. The purpose of this work is to introduce a robustness evaluation method that is applicable to photon and proton treatments and is consistent with (historic) PTV-based treatment plan evaluations. Materials and methods: The limitation of the static dose cloud approximation was solved in a multiscenario simulation by explicitly calculating doses for various treatment scenarios that describe possible errors in the treatment course. Setup errors were the same as the CTV-PTV margin and the underlying theory of 3D probability density distributions was extended to 4D to include range errors, maintaining a 90% confidence level. Scenario dose distributions were reduced to voxel-wise minimum and maximum dose distributions; the first to evaluate CTV coverage and the second for hot spots. Acceptance criteria for CTV D98 and D2 were calibrated against PTV-based criteria from historic photon treatment plans. Results: CTV D98 in worst case scenario dose and voxel-wise minimum dose showed a very strong correlation with scenario average D98 (R 2 > 0.99). The voxel-wise minimum dose visualised CTV dose conformity and coverage in 3D in agreement with PTV-based evaluation in photon therapy. Criteria for CTV D98 and D2 of the voxel-wise minimum and maximum dose showed very strong correlations to PTV D98 and D2 (R 2 > 0.99) and on average needed corrections of À0.9% and +2.3%, respectively. Conclusions: A practical approach to robustness evaluation was provided and clinically implemented for PTV-less photon and proton treatment planning, consistent with PTV evaluations but without its static dose cloud approximation. Ó 2019 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 141 (2019) 267-274 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).The use of margins in photon radiotherapy is a long established and universally adopted method to provide adequate target coverage under the presence of uncertainties. The CTV-PTV margin provides a geometrical buffer zone around the target within which the desired dose is achieved for the majority of treatments; criteria of 95% of the prescription dose in 90% of the patient population has found general appeal [1,2]. The suitability of a geometricallyexpanded buffer zone arises from the (relative) insensitivity of megavoltage photon dose distributions to density changes in the beam path. By and large, the biggest risk to a photon dose distribution is a geometrical miss -a translation of the CTV relative to the beam. Therefore, the static dose cloud approximation (dose distribution is invariant to errors)...

The presented method to select patients for ART pre-treatment reduces the labour of ART, contributing to a more effective allocation of the department resources.

ObjectivesTo demonstrate that novice dosimetry planners efficiently create clinically acceptable IMRT plans for head and neck cancer (HNC) patients using a commercially available multicriteria optimization (MCO) system.MethodsTwenty HNC patients were enrolled in this in-silico comparative planning study. Per patient, novice planners with less experience in dosimetry planning created an IMRT plan using an MCO system (RayStation). Furthermore, a conventionally planned clinical IMRT plan was available (Pinnacle3). All conventional IMRT and MCO-plans were blind-rated by two expert radiation-oncologists in HNC, using a 5-point scale (1–5 with 5 the highest score) assessment form comprising 10 questions. Additionally, plan quality was reported in terms of planning time, dosimetric and normal tissue complication probability (NTCP) comparisons. Inter-rater reliability was derived using the intra-class correlation coefficient (ICC).ResultsIn total, the radiation-oncologists rated 800 items on plan quality. The overall plan score indicated no differences between both planning techniques (conventional IMRT: 3.8 ± 1.2 vs. MCO: 3.6 ± 1.1, p = 0.29). The inter-rater reliability of all ratings was 0.65 (95% CI: 0.57–0.71), indicating substantial agreement between the radiation-oncologists. In 93% of cases, the scoring difference of the conventional IMRT and MCO-plans was one point or less. Furthermore, MCO-plans led to slightly higher dose uniformity in the therapeutic planning target volume, to a lower integral body dose (13.9 ± 4.5 Gy vs. 12.9 ± 4.0 Gy, p < 0.001), and to reduced dose to the contra-lateral parotid gland (28.1 ± 11.8 Gy vs. 23.0 ± 11.2 Gy, p < 0.002). Consequently, NTCP estimates for xerostomia reduced by 8.4 ± 7.4% (p < 0.003). The hands-on time of the conventional IMRT planning was approximately 205 min. The time to create an MCO-plan was on average 43 ± 12 min.ConclusionsMCO planning enables novice treatment planners to create high quality IMRT plans for HNC patients. Plans were created with vastly reduced planning times, requiring less resources and a short learning curve.

A prerequisite for adaptive dose-tracking in radiotherapy is the assessment of the deformable image registration (DIR) quality. In this work, various metrics that quantify DIR uncertainties are investigated using realistic deformation fields of 26 head and neck and 12 lung cancer patients. Metrics related to the physiologically feasibility (the Jacobian determinant, harmonic energy (HE), and octahedral shear strain (OSS)) and numerically robustness of the deformation (the inverse consistency error (ICE), transitivity error (TE), and distance discordance metric (DDM)) were investigated. The deformable registrations were performed using a B-spline transformation model. The DIR error metrics were log-transformed and correlated (Pearson) against the log-transformed ground-truth error on a voxel level. Correlations of r  ⩾  0.5 were found for the DDM and HE. Given a DIR tolerance threshold of 2.0 mm and a negative predictive value of 0.90, the DDM and HE thresholds were 0.49 mm and 0.014, respectively. In conclusion, the log-transformed DDM and HE can be used to identify voxels at risk for large DIR errors with a large negative predictive value. The HE and/or DDM can therefore be used to perform automated quality assurance of each CT-based DIR for head and neck and lung cancer patients.

Hypofractionated radiotherapy of rectal cancer leads to an increased tumor perfusion as reflected by an elevated K(trans), possibly improving the bioavailability of cytotoxic agents in rectal tumors, often administered early after radiotherapy treatment.

Objective: To establish optimal robust optimization uncertainty settings for clinical head and neck cancer (HNC) patients undergoing 3D image-guided pencil beam scanning (PBS) proton therapy. Methods: We analyzed ten consecutive HNC patients treated with 70 and 54.25 Gy RBE to the primary and prophylactic clinical target volumes (CTV) respectively using intensity-modulated proton therapy (IMPT). Clinical plans were generated using robust optimization with 5 mm/3% setup/range uncertainties (RayStation v6.1). Additional plans were created for 4, 3, 2 and 1 mm setup and 3% range uncertainty and for 3 mm setup and 3%, 2% and 1% range uncertainty. Systematic and random error distributions were determined for setup and range uncertainties based on our quality assurance program. From these, 25 treatment scenarios were sampled for each plan, each consisting of a systematic setup and range error and daily random setup errors. Fraction doses were calculated on the weekly verification CT closest to the date of treatment as this was considered representative of the daily patient anatomy. Results: Plans with a 2 mm/3% setup/range uncertainty setting adequately covered the primary and prophylactic CTV (V 95 ! 99% in 98.8% and 90.8% of the treatment scenarios respectively). The average organat-risk dose decreased with 1.1 Gy RBE /mm setup uncertainty reduction and 0.5 Gy RBE /1% range uncertainty reduction. Normal tissue complication probabilities decreased by 2.0%/mm setup uncertainty reduction and by 0.9%/1% range uncertainty reduction. Conclusion: The results of this study indicate that margin reduction below 3 mm/3% is possible but requires a larger cohort to substantiate clinical introduction.