The ROCOCO performance scoring system translates dosimetric differences into clinically relevant endpoints: Comparing IMPT to VMAT in an example pilocytic astrocytoma dataset.

BACKGROUND AND PURPOSE: Proton therapy is expected to outperform photon-based treatment regarding organs at risk (OAR) sparing but to date there is no method to practically measure clinical benefit. Here, we introduce the novel ROCOCO Performance Scoring System (RPSS) translating dose differences into clinically relevant endpoints and apply this to a treatment plan comparison of volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in 20 pilocytic astrocytoma patients. MATERIAL AND METHODS: The RPSS was developed on the basis of expert-based weighting factors and toxicity scores per OAR. The imaging datasets of 20 pilocytic astrocytoma patients having undergone radiotherapy were included in this in silico dosimetric comparison trial as proof of principle. For each of these patients, treatment plans to a total dose of 54 Gy (RBE) were generated for VMAT and IMPT and these were compared regarding radiation dose to the clinical target volume (CTV) and OARs. The RPSS was calculated for each treatment plan comparing VMAT and IMPT. RESULTS: In 40 analysed treatment plans, the average and low dose volumes to various OARs were significantly reduced when using IMPT compared to VMAT (p < 0.05). Using the RPSS, a significant difference between both treatment modalities was found, with 85% of the patients having a lower RPSS in favour of the IMPT plan. CONCLUSION: There are dosimetric differences between IMPT and VMAT in pilocytic astrocytoma patients. In absence of clinically validated NTCP models we introduce the RPSS model in order to objectively compare treatment modalities by translating dosimetric differences in potential clinical differences.

Quantification of plan robustness against different uncertainty sources for classical and anatomical robust optimized treatment plans in head and neck cancer proton therapy.

OBJECTIVE: Classical robust optimization (cRO) in intensity-modulated proton therapy (IMPT) considers isocenter position and particle range uncertainties; anatomical robust optimization (aRO) aims to consider additional non-rigid positioning variations. This work compares the influence of different uncertainty sources on the robustness of cRO and aRO IMPT plans for head and neck squamous cell carcinoma (HNSCC). METHODS: Two IMPT plans were optimized for 20 HNSCC patients who received weekly control CTs (cCT): cRO, using solely the planning CT, and aRO, including 2 additional cCTs. The robustness of the plans in terms of clinical target volume (CTV) coverage and organ at risk (OAR) sparing was analyzed considering stepwise the influence of (1) non-rigid anatomical variations given by the weekly cCT, (2) with fraction-wise added rigid random setup errors and (3) additional systematic proton range uncertainties. RESULTS: cRO plans presented significantly higher nominal CTV coverage but are outperformed by aRO plans when considering non-rigid anatomical variations only, as cRO and aRO plans presented a median target coverage (D98%) decrease for the low-risk/high-risk CTV of 1.8/1.1 percentage points (pp) and -0.2 pp/-0.3 pp, respectively. Setup and range uncertainties had larger influence on cRO CTV coverage, but led to similar OAR dose changes in both plans. Considering all error sources, 10/2 cRO/aRO patients missed the CTV coverage and a limited number exceeded some OAR constraints in both plans. CONCLUSION: Non-rigid anatomical variations are mainly responsible for critical target coverage loss of cRO plans, whereas the aRO approach was robust against such variations. Both plans provide similar robustness of OAR parameters. ADVANCES IN KNOWLEDGE: The influence of different uncertainty sources was quantified for robust IMPT HNSCC plans.

Including anatomical variations in robust optimization for head and neck proton therapy can reduce the need of adaptation.

BACKGROUND AND PURPOSE: Classical robust optimization considers uncertainties in patient setup and particle range. However, anatomical changes occurring during the treatment are neglected. Our aim was to compare classical robust optimization (cRO) with anatomical robust optimization (aRO), to quantify the influence of anatomical variations during the treatment course, and to assess the need of adaptation. MATERIALS AND METHODS: Planning CT and weekly control CTs (cCTs) from 20 head and neck patients were analysed. Three intensity-modulated proton therapy (IMPT) plans were compared: conventional PTV-based plan; cRO, using solely the planning CT, and aRO, including additionally the first 2 cCTs in the optimization. Weekly and total cumulative doses, considering anatomical variations during the treatment, were calculated and compared with the nominal plans. RESULTS: Nominal plans fulfilled clinical specifications for target coverage (D98% ≥95% of prescribed dose). The PTV-based and cRO approaches were not sufficient to account for anatomical changes during the treatment in 10 and 5 patients, respectively, resulting in the need of plan adaptation. With the aRO approach, in all except one patient the target coverage was conserved, and no adaptations were necessary. CONCLUSION: In 25% of the investigated cases, classical robust optimization is not sufficient to account for anatomical changes during the treatment. Adding additional information of random anatomical variations in the optimization improves plan robustness.

Intensity-modulated proton therapy decreases dose to organs at risk in low-grade glioma patients: results of a multicentric in silico ROCOCO trial.

BACKGROUND AND PURPOSE: Patients with low-grade glioma (LGG) have a prolonged survival expectancy due to better discriminative tumor classification and multimodal treatment. Consequently, long-term treatment toxicity gains importance. Contemporary radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO) and intensity-modulated proton therapy (IMPT) enable high-dose irradiation of the target but they differ regarding delivered dose to organs at risk (OARs). The aim of this comparative in silico study was to determine these dosimetric differences in delivered doses. MATERIAL AND METHODS: Imaging datasets of 25 LGG patients having undergone postoperative radiotherapy were included. For each of these patients, in silico treatment plans to a total dose of 50.4 Gy to the target volume were generated for the four treatment modalities investigated (i.e., IMRT, VMAT, TOMO, IMPT). Resulting treatment plans were analyzed regarding dose to target and surrounding OARs comparing IMRT, TOMO and IMPT to VMAT. RESULTS: In total, 100 treatment plans (four per patient) were analyzed. Compared to VMAT, the IMPT mean dose (Dmean) for nine out of 10 (90%) OARs was statistically significantly (p < .02) reduced, for TOMO this was true in 3/10 (30%) patients and for 1/10 (10%) patients for IMRT. IMPT was the prime modality reducing dose to the OARs followed by TOMO. DISCUSSION: The low dose volume to the majority of OARs was significantly reduced when using IMPT compared to VMAT. Whether this will lead to a significant reduction in neurocognitive decline and improved quality of life is to be determined in carefully designed future clinical trials.

Impact of robust treatment planning on single- and multi-field optimized plans for proton beam therapy of unilateral head and neck target volumes.

BACKGROUND: Proton beam therapy is promising for the treatment of head and neck cancer (HNC), but it is sensitive to uncertainties in patient positioning and particle range. Studies have shown that the planning target volume (PTV) concept may not be sufficient to ensure robustness of the target coverage. A few planning studies have considered irradiation of unilateral HNC targets with protons, but they have only taken into account the dose on the nominal plan, without considering anatomy changes occurring during the treatment course. METHODS: Four pencil beam scanning (PBS) proton therapy plans were calculated for 8 HNC patients with unilateral target volumes: single-field (SFO) and multi-field optimized (MFO) plans, either using the PTV concept or clinical target volume (CTV)-based robust optimization. The dose was recalculated on computed tomography (CT) scans acquired during the treatment course. Doses to target volumes and organs at risk (OARs) were compared for the nominal plans, cumulative doses considering anatomical changes, and additional setup and range errors in each fraction. If required, the treatment plan was adapted, and the dose was compared with the non-adapted plan. RESULTS: All nominal plans fulfilled the clinical specifications for target coverage, but significantly higher doses on the ipsilateral parotid gland were found for both SFO approaches. MFO PTV-based plans had the lowest robustness against range and setup errors. During the treatment course, the influence of the anatomical variation on the dose has shown to be patient specific, mostly independent of the chosen planning approach. Nine plans in four patients required adaptation, which led to a significant improvement of the target coverage and a slight reduction in the OAR dose in comparison to the cumulative dose without adaptation. CONCLUSIONS: The use of robust MFO optimization is recommended for ensuring plan robustness and reduced doses in the ipsilateral parotid gland. Anatomical changes occurring during the treatment course might degrade the target coverage and increase the dose in the OARs, independent of the chosen planning approach. For some patients, a plan adaptation may be required.

Quantification and Assessment of Interfraction Setup Errors Based on Cone Beam CT and Determination of Safety Margins for Radiotherapy.

INTRODUCTION: To quantify interfraction patient setup-errors for radiotherapy based on cone-beam computed tomography and suggest safety margins accordingly. MATERIAL AND METHODS: Positioning vectors of pre-treatment cone-beam computed tomography for different treatment sites were collected (n = 9504). For each patient group the total average and standard deviation were calculated and the overall mean, systematic and random errors as well as safety margins were determined. RESULTS: The systematic (and random errors) in the superior-inferior, left-right and anterior-posterior directions were: for prostate, 2.5(3.0), 2.6(3.9) and 2.9(3.9)mm; for prostate bed, 1.7(2.0), 2.2(3.6) and 2.6(3.1)mm; for cervix, 2.8(3.4), 2.3(4.6) and 3.2(3.9)mm; for rectum, 1.6(3.1), 2.1(2.9) and 2.5(3.8)mm; for anal, 1.7(3.7), 2.1(5.1) and 2.5(4.8)mm; for head and neck, 1.9(2.3), 1.4(2.0) and 1.7(2.2)mm; for brain, 1.0(1.5), 1.1(1.4) and 1.0(1.1)mm; and for mediastinum, 3.3(4.6), 2.6(3.7) and 3.5(4.0)mm. The CTV-to-PTV margins had the smallest value for brain (3.6, 3.7 and 3.3mm) and the largest for mediastinum (11.5, 9.1 and 11.6mm). For pelvic treatments the means (and standard deviations) were 7.3 (1.6), 8.5 (0.8) and 9.6 (0.8)mm. CONCLUSIONS: Systematic and random setup-errors were smaller than 5mm. The largest errors were found for organs with higher motion probability. The suggested safety margins were comparable to published values in previous but often smaller studies.