Robustness assessment of clinical adaptive proton and photon radiotherapy for oesophageal cancer in the model-based approach

Purpose In the Netherlands, oesophageal cancer (EC) patients are selected for intensity modulated proton therapy (IMPT) using the expected normal tissue complication probability reduction (ΔNTCP) when treating with IMPT compared to volumetric modulated arc therapy (VMAT). In this study, we evaluate the robustness of the first EC patients treated with IMPT in our clinic in terms of target and organs-at-risk (OAR) dose with corresponding NTCP, as compared to VMAT. Materials and Methods For 20 consecutive EC patients, clinical IMPT and VMAT plans were created on the average planning 4DCT. Both plans were robustly evaluated on weekly repeated 4DCTs and if target coverage degraded, replanning was performed. Target coverage was evaluated for complete treatment trajectories with and without replanning. The planned and accumulated mean lung dose (MLD) and mean heart dose (MHD) were additionally evaluated and translated into NTCP. Results Replanning in the clinic was performed more often for IMPT (15x) than would have been needed for VMAT (8x) (p = 0.11). Both adaptive treatments would have resulted in adequate accumulated target dose coverage. Replanning in the first week of treatment had most clinical impact, as anatomical changes resulting in insufficient accumulated target coverage were already observed at this stage. No differences were found in MLD between the planned dose and the accumulated dose. Accumulated MHD differed from the planned dose (p < 0.001), but since these differences were similar for VMAT and IMPT (1.0 and 1.5 Gy, respectively), the ΔNTCP remained unchanged. Conclusion Following an adaptive clinical workflow, adequate target dose coverage and stable OAR doses with corresponding NTCPs was assured for both IMPT and VMAT

Towards the clinical implementation of intensity-modulated proton therapy for thoracic indications with moderate motion:Robust optimised plan evaluation by means of patient and machine specific information

PURPOSE: Compared to volumetric modulated arc therapy (VMAT), clinical benefits are anticipated when treating thoracic tumours with intensity-modulated proton therapy (IMPT). However, the current concern of plan robustness as a result of motion hampers its wide clinical implementation. To define an optimal protocol to treat lung and oesophageal cancers, we present a comprehensive evaluation of IMPT planning strategies, based on patient 4DCTs and machine log files. MATERIALS AND METHODS: For ten lung and ten oesophageal cancer patients, a planning 4DCT and weekly repeated 4DCTs were collected. For these twenty patients, the CTV volume and motion were assessed based on the 4DCTs. In addition to clinical VMAT plans, layered rescanned 3D and 4D robust optimised IMPT plans (IMPT_3D and IMPT_4D respectively) were generated, and approved clinically, for all patients. The IMPT plans were then delivered in dry runs at our proton facility to obtain log files, and subsequently evaluated through our 4D robustness evaluation method (4DREM). With this method, for each evaluated plan, fourteen 4D accumulated scenario doses were obtained, representing 14 possible fractionated treatment courses. RESULTS: From VMAT to IMPT_3D, nominal Dmean(lungs-GTV) decreased 2.75 ± 0.56 GyRBE and 3.76 ± 0.92 GyRBE over all lung and oesophageal cancer patients, respectively. A more pronounced reduction was verified for Dmean(heart): 5.38 ± 7.36 GyRBE (lung cases) and 9.51 ± 2.25 GyRBE (oesophagus cases). Target coverage robustness of IMPT_3D was sufficient for 18/20 patients. Averaged dose in critical structures over all 4DREM scenarios changed only slightly for both IMPT_3D and IMPT_4D. Relative to IMPT_3D, no gain in IMPT_4D was observed. CONCLUSION: The dosimetric superiority of IMPT over VMAT has been established. For most thoracic tumours, our IMPT_3D planning protocol showed to be robust and clinically suitable. Nevertheless, accurate patient positioning and adapting to anatomical variations over the course of treatment remain compulsory

A comprehensive motion analysis - consequences for high precision image-guided radiotherapy of esophageal cancer patients

Background and purpose When treating patients for esophageal cancer (EC) with photon or proton radiotherapy (RT), breathing motion of the target and neighboring organs may result in deviations from the planned dose distribution. The aim of this study was to evaluate the magnitude and dosimetric impact of breathing motion. Results were based on comparing weekly 4D computed tomography (4D CT) scans with the planning CT, using the diaphragm as an anatomical landmark for EC. Material and methods A total of 20 EC patients were included in this study. Diaphragm breathing amplitudes and off-sets (changes in position with respect to the planning CT) were determined from delineated left diaphragm structures in weekly 4D CT-scans. The potential dosimetric impact of respiratory motion was shown in several example patients for photon and proton radiotherapy. Results Variation in diaphragm amplitudes were relatively small and ranged from 0 to 0.8 cm. However, the measured off-sets were larger, ranging from -2.1 to 1.9 cm. Of the 70 repeat CT-scans, the off-set exceeded the ITV-PTV margin of 0.8 cm during expiration in 4 CT-scans (5.7%) and during inspiration in 13 CT-scans (18.6%). The dosimetric validation revealed under- and overdosages in the VMAT and IMPT plans. Conclusions Despite relatively constant breathing amplitudes, the variation in the diaphragm position (off-set), and consequently tumor position, was clinically relevant. These motion effects may result in either treatments that miss the target volume, or dose deviations in the form of highly localized over- or underdosed regions

Organ sparing potential and inter-fraction robustness of adaptive intensity modulated proton therapy for lung cancer

Background: The aim of this study was to compare adaptive intensity modulated proton therapy (IMPT) robustness and organ sparing capabilities with that of adaptive volumetric arc photon therapy (VMAT). Material and methods: Eighteen lung cancer patients underwent a planning 4DCT (p4DCT) and 5 weekly repeated 4DCT (r4DCT) scans. Target volumes and organs at risk were manually delineated on the three-dimensional (3D) average scans of the p4DCT (av_p4DCT) and of the r4DCT scans (av_r4DCT). Planning target volume (PTV)-based VMAT plans and internal clinical target volume (ICTV)-based robust IMPT plans were optimized in 3D on the av_p4DCT and re-calculated on the av_r4DCTs. Re-planning on av_r4DCTs was performed when indicated and accumulated doses were evaluated on the av_p4DCT. Results: Adaptive VMAT and IMPT resulted in adequate ICTV coverage on av_r4DCT in all patients and adequate accumulated-dose ICTV coverage on av_p4DCT in 17/18 patients (due to a shrinking target in one patient). More frequent re-planning was needed for IMPT than for VMAT. The average mean heart dose reduction with IMPT compared with VMAT was 4.6 Gy (p = .001) and it was >5 Gy for five patients (6, 7, 8, 15, and 22 Gy). The average mean lung dose reduction was 3.2 Gy (p < .001). Significant reductions in heart and lung V5 Gy were observed with IMPT. Conclusion: Robust-planned IMPT required re-planning more often than VMAT but resulted in similar accumulated ICTV coverage. With IMPT, heart and lung mean dose values and low dose regions were significantly reduced. Substantial cardiac sparing was obtained in a subgroup of five patients (28%)

Proton-based RT enables target dose escalation in oesophageal cancer with limited impact on OAR dose

Purpose or ObjectiveOesophageal cancer (EC) patients with a clinical complete response after neo-adjuvant chemoradiotherapy (nCRT) might be candidates for organ preservation. Thomas et al. (2019) demonstrated that higher radiation dose improves the rate of major pathologic response. The ARTDECO trial (2021) showed a trend towards better local control in the high dose arm in definitive setting. However, dose escalation using photon-based RT failed to result in improved overall survival. This might be related to higher normal tissue dose and consequently higher toxicity risks. The aim of this in silico planning study was to evaluate the impact of dose escalation to the tumour regarding organs at risk (OARs) dose in nCRT for EC patients.Material and MethodsFor this study, we used the planning CT scans of 16 EC patients, who were treated with proton nCRT between April and July 2022 and who provided informed consent for the use of their data. The target dose was escalated from 41.4 Gy (current standard) to a total dose of 50.4 Gy by re-scaling the original clinical treatment plan. We investigated the impact of dose escalation on OARs dose for both the proton (IMPT) and the back-up photon (VMAT) plans, and differences in OARs dose were tested using the Wilcoxon signed rank test.ResultsFor both PhRT and PRT, the OARs dose increased significantly by escalating the dose to the target. In the escalated PhRT plans, the mean heart dose (MHD) and Lung V5 exceeded the constraints in 6 (37.5%) and 4 (25%) patients. None of the escalated PRT plans exceeded the normal tissue constraints. Only the left kidney dose was relatively high in 3 patients (mean 10-17 Gy). The absolute differences in OARs dose between the escalated and standard treatment plans were significantly higher in the PhRT plans as compared to the PRT plans. The MHD increased on average by 4.3 Gy, while in PRT the increase was only 1.9 Gy on average (Table 1). Moreover, the mean dose to heart and lungs remained significantly lower in the escalated proton plans compared to the non-escalated photon plans.ConclusionFrom a dosimetric point of view, it seems feasible to escalate the dose to the target from 41.4 Gy to 50.4 Gy using PRT. In the escalated PRT plans, the MHD and MLD dose remained on average significantly lower than the current standard PhRT plans and did not exceed any OARs constraints. Re-optimisation of the escalated treatment plans might reduce the OARs dose slightly. However, in PhRT the optimisation is restricted by the relatively high heart- and lung dose and its constraints

Proton-based RT enables target dose escalation in oesophageal cancer with limited impact on OAR dose

Purpose or ObjectiveOesophageal cancer (EC) patients with a clinical complete response after neo-adjuvant chemoradiotherapy (nCRT) might be candidates for organ preservation. Thomas et al. (2019) demonstrated that higher radiation dose improves the rate of major pathologic response. The ARTDECO trial (2021) showed a trend towards better local control in the high dose arm in definitive setting. However, dose escalation using photon-based RT failed to result in improved overall survival. This might be related to higher normal tissue dose and consequently higher toxicity risks. The aim of this in silico planning study was to evaluate the impact of dose escalation to the tumour regarding organs at risk (OARs) dose in nCRT for EC patients.Material and MethodsFor this study, we used the planning CT scans of 16 EC patients, who were treated with proton nCRT between April and July 2022 and who provided informed consent for the use of their data. The target dose was escalated from 41.4 Gy (current standard) to a total dose of 50.4 Gy by re-scaling the original clinical treatment plan. We investigated the impact of dose escalation on OARs dose for both the proton (IMPT) and the back-up photon (VMAT) plans, and differences in OARs dose were tested using the Wilcoxon signed rank test.ResultsFor both PhRT and PRT, the OARs dose increased significantly by escalating the dose to the target. In the escalated PhRT plans, the mean heart dose (MHD) and Lung V5 exceeded the constraints in 6 (37.5%) and 4 (25%) patients. None of the escalated PRT plans exceeded the normal tissue constraints. Only the left kidney dose was relatively high in 3 patients (mean 10-17 Gy). The absolute differences in OARs dose between the escalated and standard treatment plans were significantly higher in the PhRT plans as compared to the PRT plans. The MHD increased on average by 4.3 Gy, while in PRT the increase was only 1.9 Gy on average (Table 1). Moreover, the mean dose to heart and lungs remained significantly lower in the escalated proton plans compared to the non-escalated photon plans.ConclusionFrom a dosimetric point of view, it seems feasible to escalate the dose to the target from 41.4 Gy to 50.4 Gy using PRT. In the escalated PRT plans, the MHD and MLD dose remained on average significantly lower than the current standard PhRT plans and did not exceed any OARs constraints. Re-optimisation of the escalated treatment plans might reduce the OARs dose slightly. However, in PhRT the optimisation is restricted by the relatively high heart- and lung dose and its constraints

Proton-based RT enables target dose escalation in oesophageal cancer with limited impact on OAR dose

Purpose or ObjectiveOesophageal cancer (EC) patients with a clinical complete response after neo-adjuvant chemoradiotherapy (nCRT) might be candidates for organ preservation. Thomas et al. (2019) demonstrated that higher radiation dose improves the rate of major pathologic response. The ARTDECO trial (2021) showed a trend towards better local control in the high dose arm in definitive setting. However, dose escalation using photon-based RT failed to result in improved overall survival. This might be related to higher normal tissue dose and consequently higher toxicity risks. The aim of this in silico planning study was to evaluate the impact of dose escalation to the tumour regarding organs at risk (OARs) dose in nCRT for EC patients.Material and MethodsFor this study, we used the planning CT scans of 16 EC patients, who were treated with proton nCRT between April and July 2022 and who provided informed consent for the use of their data. The target dose was escalated from 41.4 Gy (current standard) to a total dose of 50.4 Gy by re-scaling the original clinical treatment plan. We investigated the impact of dose escalation on OARs dose for both the proton (IMPT) and the back-up photon (VMAT) plans, and differences in OARs dose were tested using the Wilcoxon signed rank test.ResultsFor both PhRT and PRT, the OARs dose increased significantly by escalating the dose to the target. In the escalated PhRT plans, the mean heart dose (MHD) and Lung V5 exceeded the constraints in 6 (37.5%) and 4 (25%) patients. None of the escalated PRT plans exceeded the normal tissue constraints. Only the left kidney dose was relatively high in 3 patients (mean 10-17 Gy). The absolute differences in OARs dose between the escalated and standard treatment plans were significantly higher in the PhRT plans as compared to the PRT plans. The MHD increased on average by 4.3 Gy, while in PRT the increase was only 1.9 Gy on average (Table 1). Moreover, the mean dose to heart and lungs remained significantly lower in the escalated proton plans compared to the non-escalated photon plans.ConclusionFrom a dosimetric point of view, it seems feasible to escalate the dose to the target from 41.4 Gy to 50.4 Gy using PRT. In the escalated PRT plans, the MHD and MLD dose remained on average significantly lower than the current standard PhRT plans and did not exceed any OARs constraints. Re-optimisation of the escalated treatment plans might reduce the OARs dose slightly. However, in PhRT the optimisation is restricted by the relatively high heart- and lung dose and its constraints

Proton-based RT enables target dose escalation in oesophageal cancer with limited impact on OAR dose

Purpose or ObjectiveOesophageal cancer (EC) patients with a clinical complete response after neo-adjuvant chemoradiotherapy (nCRT) might be candidates for organ preservation. Thomas et al. (2019) demonstrated that higher radiation dose improves the rate of major pathologic response. The ARTDECO trial (2021) showed a trend towards better local control in the high dose arm in definitive setting. However, dose escalation using photon-based RT failed to result in improved overall survival. This might be related to higher normal tissue dose and consequently higher toxicity risks. The aim of this in silico planning study was to evaluate the impact of dose escalation to the tumour regarding organs at risk (OARs) dose in nCRT for EC patients.Material and MethodsFor this study, we used the planning CT scans of 16 EC patients, who were treated with proton nCRT between April and July 2022 and who provided informed consent for the use of their data. The target dose was escalated from 41.4 Gy (current standard) to a total dose of 50.4 Gy by re-scaling the original clinical treatment plan. We investigated the impact of dose escalation on OARs dose for both the proton (IMPT) and the back-up photon (VMAT) plans, and differences in OARs dose were tested using the Wilcoxon signed rank test.ResultsFor both PhRT and PRT, the OARs dose increased significantly by escalating the dose to the target. In the escalated PhRT plans, the mean heart dose (MHD) and Lung V5 exceeded the constraints in 6 (37.5%) and 4 (25%) patients. None of the escalated PRT plans exceeded the normal tissue constraints. Only the left kidney dose was relatively high in 3 patients (mean 10-17 Gy). The absolute differences in OARs dose between the escalated and standard treatment plans were significantly higher in the PhRT plans as compared to the PRT plans. The MHD increased on average by 4.3 Gy, while in PRT the increase was only 1.9 Gy on average (Table 1). Moreover, the mean dose to heart and lungs remained significantly lower in the escalated proton plans compared to the non-escalated photon plans.ConclusionFrom a dosimetric point of view, it seems feasible to escalate the dose to the target from 41.4 Gy to 50.4 Gy using PRT. In the escalated PRT plans, the MHD and MLD dose remained on average significantly lower than the current standard PhRT plans and did not exceed any OARs constraints. Re-optimisation of the escalated treatment plans might reduce the OARs dose slightly. However, in PhRT the optimisation is restricted by the relatively high heart- and lung dose and its constraints

Necessity of manually adjusting automatic deformed CTVs on repeat CT scan to evaluate CTV coverage in IMPT for lung cancer

Background/Introduction: Manual CTV adjustment after deformable CTV registration on repeat-CT scans (rCT) is time consuming and may delay decisions on whether or not to perform plan adaptations. Our aim was to investigate if omitting such manual CTV adjustments would alter the decisions and/or impact the overall adequacy of treatment. Methodology: Seventeen lung cancer patients underwent a 4D planning-CT (pCT0) and 3-5 weekly 4D rCTs. In total 82 4D-average rCTs were available. Robustly optimized IMPT plans were established on the pCT0 aiming for a CTV D98 ≥ 57 Gy. The plans were evaluated on all rCTs including setup and range error scenarios. CTVs were deformed (intensity based deformable registration) from pCT0 to the rCTs (CTVauto) and manually adjusted by a clinician (CTVman). When rCT CTVauto and/or CTVman D98 &lt; 56.5 Gy (worst case scenario dose) the IMPT plan was adapted. Results: On average, CTVman was smaller than CTVauto (Δ volume in weeks 1-5: -4%, -6%, -9%, -11% and -15% (p &lt; 0.001), respectively. The average CTVauto D98 and CTVman D98 on all rCTs were 55.17 Gy and 55.13 Gy (p = 0.767), respectively. Omitting CTVman on all 82 rCTs would result in 3 ‘unnecessary' plan adjustments and 1 ‘skipped' plan adjustment. In the latter single case, the weekly rCTs dose deformed and summed in the CTV on pCT0 was adequate despite the skipped plan adaptation (58.1 Gy). Conclusions: In 17 lung cancer patients, omitting manual adjustments of deformed CTVs on weekly rCTs did not impact adequate CTV coverage of IMPT treatment