Barbara Vanderstraeten

Accuracy of patient dose calculation for lung IMRT: A comparison of Monte Carlo, convolution/superposition, and pencil beam computations

The accuracy of dose computation within the lungs depends strongly on the performance of the calculation algorithm in regions of electronic disequilibrium that arise near tissue inhomogeneities with large density variations. There is a lack of data evaluating the performance of highly developed analytical dose calculation algorithms compared to Monte Carlo computations in a clinical setting. We compared full Monte Carlo calculations (performed by our Monte Carlo dose engine MCDE) with two different commercial convolution/superposition (CS) implementations (Pinnacle-CS and Helax-TMSs collapsed cone model Helax-CC) and one pencil beam algorithm (Helax-TMSs pencil beam model Helax-PB) for 10 intensity modulated radiation therapy (IMRT) lung cancer patients. Treatment plans were created for two photon beam qualities (6 and 18 MV). For each dose calculation algorithm, patient, and beam quality, the following set of clinically relevant dose-volume values was reported: (i) minimal, median, and maximal dose (Dmin, D50, and Dmax) for the gross tumor and planning target volumes (GTV and PTV); (ii) the volume of the lungs (excluding the GTV) receiving at least 20 and 30 Gy (V20 and V30) and the mean lung dose; (iii) the 33rd percentile dose (D33) and Dmax delivered to the heart and the expanded esophagus; and (iv) Dmax for the expanded spinal cord. Statistical analysis was performed by means of one-way analysis of variance for repeated measurements and Tukey pairwise comparison of means. Pinnacle-CS showed an excellent agreement with MCDE within the target structures, whereas the best correspondence for the organs at risk (OARs) was found between Helax-CC and MCDE. Results from Helax-PB were unsatisfying for both targets and OARs. Additionally, individual patient results were analyzed. Within the target structures, deviations above 5% were found in one patient for the comparison of MCDE and Helax-CC, while all differences between MCDE and Pinnacle-CS were below 5%. For both Pinnacle-CS and Helax-CC, deviations from MCDE above 5% were found within the OARs: within the lungs for two (6 MV) and six (18 MV) patients for Pinnacle-CS, and within other OARs for two patients for Helax-CC (for Dmax of the heart and D33 of the expanded esophagus) but only for 6 MV. For one patient, all four algorithms were used to recompute the dose after replacing all computed tomography voxels within the patients skin contour by water. This made all differences above 5% between MCDE and the other dose calculation algorithms disappear. Thus, the observed deviations mainly arose from differences in particle transport modeling within the lungs, and the commissioning of the algorithms was adequately performed (or the commissioning was less important for this type of treatment). In conclusion, not one pair of the dose calculation algorithms we investigated could provide results that were consistent within 5% for all 10 patients for the set of clinically relevant dose-volume indices studied. As the results from both CS algorithms differed significantly, care should be taken when evaluating treatment plans as the choice of dose calculation algorithm may influence clinical results. Full Monte Carlo provides a great benchmarking tool for evaluating the performance of other algorithms for patient dose computations.

Conversion of CT numbers into tissue parameters for Monte Carlo dose calculations: a multi-centre study.

The conversion of computed tomography (CT) numbers into material composition and mass density data influences the accuracy of patient dose calculations in Monte Carlo treatment planning (MCTP). The aim of our work was to develop a CT conversion scheme by performing a stoichiometric CT calibration. Fourteen dosimetrically equivalent tissue subsets (bins), of which ten bone bins, were created. After validating the proposed CT conversion scheme on phantoms, it was compared to a conventional five bin scheme with only one bone bin. This resulted in dose distributions D(14) and D(5) for nine clinical patient cases in a European multi-centre study. The observed local relative differences in dose to medium were mostly smaller than 5%. The dose-volume histograms of both targets and organs at risk were comparable, although within bony structures D(14) was found to be slightly but systematically higher than D(5). Converting dose to medium to dose to water (D(14) to D(14wat) and D(5) to D(5wat)) resulted in larger local differences as D(5wat) became up to 10% higher than D(14wat). In conclusion, multiple bone bins need to be introduced when Monte Carlo (MC) calculations of patient dose distributions are converted to dose to water.

Implementation of biologically conformal radiation therapy (BCRT) in an algorithmic segmentation-based inverse planning approach

The development of new biological imaging technologies offers the opportunity to further individualize radiotherapy. Biologically conformal radiation therapy (BCRT) implies the use of the spatial distribution of one or more radiobiological parameters to guide the IMRT dose prescription. Our aim was to implement BCRT in an algorithmic segmentation-based planning approach. A biology-based segmentation tool was developed to generate initial beam segments that reflect the biological signal intensity pattern. The weights and shapes of the initial segments are optimized by means of an objective function that minimizes the root mean square deviation between the actual and intended dose values within the PTV. As proof of principle, [(18)F]FDG-PET-guided BCRT plans for two different levels of dose escalation were created for an oropharyngeal cancer patient. Both plans proved to be dosimetrically feasible without violating the planning constraints for the expanded spinal cord and the contralateral parotid gland as organs at risk. The obtained biological conformity was better for the first (2.5 Gy per fraction) than for the second (3 Gy per fraction) dose escalation level.

The importance of accurate linear accelerator head modelling for IMRT Monte Carlo calculations

Two Monte Carlo dose engines for radiotherapy treatment planning, namely a beta release of Peregrine and MCDE (Monte Carlo dose engine), were compared with Helax-TMS (collapsed cone superposition convolution) for a head and neck patient for the Elekta SLi plus linear accelerator. Deviations between the beta release of Peregrine and MCDE up to 10% were obtained in the dose volume histogram of the optical chiasm. It was illustrated that the differences are not caused by the particle transport in the patient, but by the modelling of the Elekta SLi plus accelerator head and more specifically the multileaf collimator (MLC). In MCDE two MLC modules (MLCQ and MLCE) were introduced to study the influence of the tongue-and-groove geometry, leaf bank tilt and leakage on the actual dose volume histograms. Differences in integral dose in the optical chiasm up to 3% between the two modules have been obtained. For single small offset beams though the FWHM of lateral profiles obtained with MLCE can differ by more than 1.5 mm from profiles obtained with MLCQ. Therefore, and because the recent version of MLCE is as fast as MLCQ, we advise to use MLCE for modelling the Elekta MLC. Nevertheless there still remains a large difference (up to 10%) between Peregrine and MCDE. By studying small offset beams we have shown that the profiles obtained with Peregrine are shifted, too wide and too flat compared with MCDE and phantom measurements. The overestimated integral doses for small beam segments explain the deviations observed in the dose volume histograms. The Helax-TMS results are in better agreement with MCDE, although deviations exceeding 5% have been observed in the optical chiasm. Monte Carlo dose deviations of more than 10% as found with Peregrine are unacceptable as an influence on the clinical outcome is possible and as the purpose of Monte Carlo treatment planning is to obtain an accuracy of 2%. We would like to emphasize that only the Elekta MLC has been tested in this work, so it is certainly possible that alpha releases of Peregrine provide more accurate results for other accelerators.

Investigation of geometrical and scoring grid resolution for Monte Carlo dose calculations for IMRT

Monte Carlo based treatment planning of two different patient groups treated with step-and-shoot IMRT (head-and-neck and lung treatments) with different CT resolutions and scoring methods is performed to determine the effect of geometrical and scoring voxel sizes on DVHs and calculation times. Dose scoring is performed in two different ways: directly into geometrical voxels (or in a number of grouped geometrical voxels) or into scoring voxels defined by a separate scoring grid superimposed on the geometrical grid. For the head-and-neck cancer patients, more than 2% difference is noted in the right optical nerve when using voxel dimensions of 4 x 4 x 4 mm3 compared to the reference calculation with 1 x 1 x 2 mm3 voxel dimensions. For the lung cancer patients, 2% difference is noted in the spinal cord when using voxel dimensions of 4 x 4 x 10 mm3 compared to the 1 x 1 x 5 mm3 calculation. An independent scoring grid introduces several advantages. In cases where a relatively high geometrical resolution is required and where the scoring resolution is less important, the number of scoring voxels can be limited while maintaining a high geometrical resolution. This can be achieved either by grouping several geometrical voxels together into scoring voxels or by superimposing a separate scoring grid of spherical voxels with a user-defined radius on the geometrical grid. For the studied lung cancer cases, both methods produce accurate results and introduce a speed increase by a factor of 10-36. In cases where a low geometrical resolution is allowed, but where a high scoring resolution is required, superimposing a separate scoring grid on the geometrical grid allows a reduction in geometrical voxels while maintaining a high scoring resolution. For the studied head-and-neck cancer cases, calculations performed with a geometrical resolution of 2 x 2 x 2 mm3 and a separate scoring grid containing spherical scoring voxels with a radius of 2 mm produce accurate results and introduce a speed increase by a factor of 13. The scoring grid provides an additional degree of freedom for limiting calculation time and memory requirements by selecting optimized scoring and geometrical voxel dimensions in an independent way.

In Search of the Economic Sustainability of Hadron Therapy: The Real Cost of Setting Up and Operating a Hadron Facility

PURPOSE To determine the treatment cost and required reimbursement for a new hadron therapy facility, considering different technical solutions and financing methods. METHODS AND MATERIALS The 3 technical solutions analyzed are a carbon only (COC), proton only (POC), and combined (CC) center, each operating 2 treatment rooms and assumed to function at full capacity. A business model defines the required reimbursement and analyzes the financial implications of setting up a facility over time; activity-based costing (ABC) calculates the treatment costs per type of patient for a center in a steady state of operation. Both models compare a private, full-cost approach with public sponsoring, only taking into account operational costs. RESULTS Yearly operational costs range between €10.0M (M = million) for a publicly sponsored POC to €24.8M for a CC with private financing. Disregarding inflation, the average treatment cost calculated with ABC (COC: €29,450; POC: €46,342; CC: €46,443 for private financing; respectively €16,059, €28,296, and €23,956 for public sponsoring) is slightly lower than the required reimbursement based on the business model (between €51,200 in a privately funded POC and €18,400 in COC with public sponsoring). Reimbursement for privately financed centers is very sensitive to a delay in commissioning and to the interest rate. Higher throughput and hypofractionation have a positive impact on the treatment costs. CONCLUSIONS Both calculation methods are valid and complementary. The financially most attractive option of a publicly sponsored COC should be balanced to the clinical necessities and the sociopolitical context.

OC-0079: Automated instead of manual planning for lung SBRT? Aplan comparison based on dose-volume statistics

Material and Methods: Between March 2012 and May 2015, 55 lung cancer patients were treated with SBRT at our institution. A total dose of 60 Gy in 3 fractions was prescribed to the PTV (D95). For each patient, an IMRT plan was created using in-house developed optimization software by manually tweaking a set of optimization objectives during several iterations. Final dose calculation was performed in Pinnacle 9.8 (Philips Medical Systems Inc, USA). These plans are further referred to as the manual plans (MP). For each patient, an additional plan was created retrospectively using the Pinnacle 9.10 Auto-Planning software with a template representing the clinical objectives for the following structures: GTV, PTV, lungs minus GTV, spinal cord, esophagus, heart, aorta, trachea, main stem bronchus and chest wall. Using automatic optimization tuning methods, an automated plan (AP) was created for each patient using the same IMRT beam directions as for the MP. No additional manual tweaking whatsoever was performed. For all of the above-mentioned structures the following DVH parameters were included in our analysis: D99, D98, D95, D90, D50, D5, D2 (in which xx% of the PTV volume receives a dose of at least Dxx) and Dmean. For the organs at risk (OAR) V5, V10 and V20 were also included (in which Vxx is the volume receiving at least xx Gy). The acceptability of each plan was judged against our clinical objectives (result: pass, minor deviation or fail). Additionally, pairwise comparisons of the DVH parameters were performed using paired, two-sided t-tests between the MPs and APs.

CommentIn Reply to de Ruysscher et al

To the Editor: We thank the authors for their comments and appreciate their interest in our research (1, 2). Our cost calculations were part of a feasibility study that also consisted of eligible indications for hadron therapy, technical specifications, current fractionation schedules, and a health economic evaluation (1). An epidemiologic and literature analysis resulted in standard and “model” indications including lung, liver, and pancreatic cancer. Technical specifications envisioned a state-of-the-art installation, which implied the use of a gantry for protons. Average numbers of fractions were based on current clinical practice, including treatment protocols of the International Society of Paediatric Oncology (SIOP), and on data derived from the systematic literature search, and clinical study protocols applied in proton and carbon ion centers. The references provided do not support the claim that hypofractionated protons have produced outcomes similar to those with carbon ions in the selected indications of liver, pancreatic, and lung cancer. At the National Institute of Radiological Science (NIRS)-MedAustron meeting (December 5-7, 2013,Wiener-Neustadt, Austria), Yasuda et al reported 1and 3-year local control rates of 98% and 83%, respectively, for hepatocellular carcinoma treated with twofraction carbon ion therapy (3). High local control rates have also been reported with 10to 20-fraction proton therapy (47), but we have no knowledge of extremely hypofractionated proton studies reporting similar outcome data. In locally advanced unresectable pancreatic cancer, outcomes gradually improved during a dose-escalation study using carbon ion therapy and gemcitabine (8). Twoyear local control and overall survival rates of 58% and 54% were reported (9). The statement of the authors that similar results can be obtained using proton therapy remains speculative. In early-stage non-small cell lung cancer (NSCLC), hypofractionation is the novel standard in proton, carbon ion, and stereotactic body radiation therapy (SBRT) photon therapy alike (10), but both carbon ions and SBRT were found to be superior to protons, as they provide better outcome at a lower cost (11). For locally advanced NSCLC, the existing clinical evidence was obtained with mostly conventionally fractionated proton therapy (12). In a specific situation of limited resources regarding the initial investment and in the absence of a strong project group allowing considerable technical development, the most attractive option probably remains a proton center. However, hadron facilities are long-term investments, typically for several decades. It may be risky to make assumptions with regard to the long-term clinical competitiveness of protons relative to the wealth of heavier ions such as carbon, helium, or oxygen, with superior physical characteristics and well-known Linear Energy Transfer (LET)-advantages. This legitimizes our suggestion of a combined modality. Barbara Vanderstraeten, PhD Wilfried De Neve, PhD Yolande Lievens, PhD Department of Radiotherapy Ghent University Hospital Gent, Belgium

In Reply to de Ruysscher et al

To the Editor: We thank the authors for their comments and appreciate their interest in our research (1, 2). Our cost calculations were part of a feasibility study that also consisted of eligible indications for hadron therapy, technical specifications, current fractionation schedules, and a health economic evaluation (1). An epidemiologic and literature analysis resulted in standard and “model” indications including lung, liver, and pancreatic cancer. Technical specifications envisioned a state-of-the-art installation, which implied the use of a gantry for protons. Average numbers of fractions were based on current clinical practice, including treatment protocols of the International Society of Paediatric Oncology (SIOP), and on data derived from the systematic literature search, and clinical study protocols applied in proton and carbon ion centers. The references provided do not support the claim that hypofractionated protons have produced outcomes similar to those with carbon ions in the selected indications of liver, pancreatic, and lung cancer. At the National Institute of Radiological Science (NIRS)-MedAustron meeting (December 5-7, 2013,Wiener-Neustadt, Austria), Yasuda et al reported 1and 3-year local control rates of 98% and 83%, respectively, for hepatocellular carcinoma treated with twofraction carbon ion therapy (3). High local control rates have also been reported with 10to 20-fraction proton therapy (47), but we have no knowledge of extremely hypofractionated proton studies reporting similar outcome data. In locally advanced unresectable pancreatic cancer, outcomes gradually improved during a dose-escalation study using carbon ion therapy and gemcitabine (8). Twoyear local control and overall survival rates of 58% and 54% were reported (9). The statement of the authors that similar results can be obtained using proton therapy remains speculative. In early-stage non-small cell lung cancer (NSCLC), hypofractionation is the novel standard in proton, carbon ion, and stereotactic body radiation therapy (SBRT) photon therapy alike (10), but both carbon ions and SBRT were found to be superior to protons, as they provide better outcome at a lower cost (11). For locally advanced NSCLC, the existing clinical evidence was obtained with mostly conventionally fractionated proton therapy (12). In a specific situation of limited resources regarding the initial investment and in the absence of a strong project group allowing considerable technical development, the most attractive option probably remains a proton center. However, hadron facilities are long-term investments, typically for several decades. It may be risky to make assumptions with regard to the long-term clinical competitiveness of protons relative to the wealth of heavier ions such as carbon, helium, or oxygen, with superior physical characteristics and well-known Linear Energy Transfer (LET)-advantages. This legitimizes our suggestion of a combined modality. Barbara Vanderstraeten, PhD Wilfried De Neve, PhD Yolande Lievens, PhD Department of Radiotherapy Ghent University Hospital Gent, Belgium

The cost of setting up and operating a hadron facility: reply

To the Editor: We thank the authors for their comments and appreciate their interest in our research (1, 2). Our cost calculations were part of a feasibility study that also consisted of eligible indications for hadron therapy, technical specifications, current fractionation schedules, and a health economic evaluation (1). An epidemiologic and literature analysis resulted in standard and “model” indications including lung, liver, and pancreatic cancer. Technical specifications envisioned a state-of-the-art installation, which implied the use of a gantry for protons. Average numbers of fractions were based on current clinical practice, including treatment protocols of the International Society of Paediatric Oncology (SIOP), and on data derived from the systematic literature search, and clinical study protocols applied in proton and carbon ion centers. The references provided do not support the claim that hypofractionated protons have produced outcomes similar to those with carbon ions in the selected indications of liver, pancreatic, and lung cancer. At the National Institute of Radiological Science (NIRS)-MedAustron meeting (December 5-7, 2013,Wiener-Neustadt, Austria), Yasuda et al reported 1and 3-year local control rates of 98% and 83%, respectively, for hepatocellular carcinoma treated with twofraction carbon ion therapy (3). High local control rates have also been reported with 10to 20-fraction proton therapy (47), but we have no knowledge of extremely hypofractionated proton studies reporting similar outcome data. In locally advanced unresectable pancreatic cancer, outcomes gradually improved during a dose-escalation study using carbon ion therapy and gemcitabine (8). Twoyear local control and overall survival rates of 58% and 54% were reported (9). The statement of the authors that similar results can be obtained using proton therapy remains speculative. In early-stage non-small cell lung cancer (NSCLC), hypofractionation is the novel standard in proton, carbon ion, and stereotactic body radiation therapy (SBRT) photon therapy alike (10), but both carbon ions and SBRT were found to be superior to protons, as they provide better outcome at a lower cost (11). For locally advanced NSCLC, the existing clinical evidence was obtained with mostly conventionally fractionated proton therapy (12). In a specific situation of limited resources regarding the initial investment and in the absence of a strong project group allowing considerable technical development, the most attractive option probably remains a proton center. However, hadron facilities are long-term investments, typically for several decades. It may be risky to make assumptions with regard to the long-term clinical competitiveness of protons relative to the wealth of heavier ions such as carbon, helium, or oxygen, with superior physical characteristics and well-known Linear Energy Transfer (LET)-advantages. This legitimizes our suggestion of a combined modality. Barbara Vanderstraeten, PhD Wilfried De Neve, PhD Yolande Lievens, PhD Department of Radiotherapy Ghent University Hospital Gent, Belgium