A dosimetric evaluation of IGART strategies for cervix cancer treatment

PurposeImage guided adaptive radiotherapy (IGART) strategies can be used to include the temporal aspects of radiotherapy treatment. A dosimetric evaluation of on- and off-line adaptive strategies are done in this study.MethodsA library of equivalent uniform dose (EUD)-based Intensity Modulated Radiotherapy Treatment plans with incrementally increasing clinical target volume (CTV)-to-planning target volume (PTV) margins were developed for 10 patients. Utilizing daily computed tomography (CT) images an on-line strategy using a margin-of-the-day (MOD) concept that selects the best plan from the library was employed. This was compared to an off-line strategy with full analysis of accumulated dose between fractions where dosimetric deviations from the treatment intent triggered plan adaptation. A fixed margin treatment approach was used as benchmark.ResultsUsing fixed margins of <15 mm lead to under-dosages of more than 5 Gy in total delivered dose. The average CTV EUD for the off-line and on-line strategy was 50.0 ± 5.0 Gy and 50.4 ± 2.0 Gy respectively and OAR doses were comparable.ConclusionA fixed margin treatment approach yields a significant probability of CTV under-dosage. Using EUD dose metrics CTV coverage can be restored in both the off-line and on-line adaptive strategies at acceptable OAR dose levels. Considering the workload and time on the treatment machine, the off-line strategy proves to be sufficient and more practical.     

Proton or photon radiosurgery for cardiac ablation of ventricular tachycardia? Breath and ECG gated robust optimization

PurposeVentricular tachycardia (VT) is a life-threatening heart disorder. The aim of this preliminary study is to assess the feasibility of stereotactic body radiation therapy (SBRT) photon and proton therapy (PT) plans for the treatment of VT, adopting robust optimization technique for both irradiation techniques.MethodsECG gated CT images (in breath hold) were acquired for one patient. Conventional planning target volume (PTV) and robust optimized plans (25GyE in single fraction) were simulated for both photon (IMRT, 5 and 9 beams) and proton (SFO, 2 beams) plans. Robust optimized plans were obtained both for protons and photons considering in the optimization setup errors (5 mm in the three orthogonal directions), range (±3.5%) and the clinical target volume (CTV) motion due to heartbeat and breath-hold variability.ResultsThe photon robust optimization method, compared to PTV-based plans, showed a reduction in the average dose to the heart by about 25%; robust optimization allowed also reducing the mean dose to the left lung from 3.4. to 2.8 Gy for 9-beams configuration and from 4.1 to 2.9 Gy for 5-beams configuration. Robust optimization with protons, allowed further reducing the OAR doses: average dose to the heart and to the left lung decreased from 7.3 Gy to 5.2 GyE and from 2.9 Gy to 2.2 GyE, respectively.ConclusionsOur study demonstrates the importance of the optimization technique adopted in the treatment planning system for VT treatment. It has been shown that robust optimization can significantly reduce the dose to healthy cardiac tissues and that PT further increases this gain.     

Prediction of multi-criteria optimization (MCO) parameter efficiency in volumetric modulated arc therapy (VMAT) treatment planning using machine learning (ML)

PurposeTo predict the impact of optimization parameter changes on dosimetric plan quality criteria in multi-criteria optimized volumetric-modulated-arc therapy (VMAT) planning prior to optimization using machine learning (ML).MethodsA data base comprising a total of 21,266 VMAT treatment plans for 44 cranial and 18 spinal patient geometries was generated. The underlying optimization algorithm is governed by three highly composite parameters which model a combination of important aspects of the solution. Patient geometries were parametrized via volume- and shape properties of the voxel objects and overlap-volume histograms (OVH) of the planning-target-volume (PTV) and a relevant organ-at-risk (OAR). The impact of changes in one of the three optimization parameters on the maximally achievable value range of five dosimetric properties of the resulting dose distributions was studied. To predict the extent of this impact based on patient geometry, treatment site, and current parameter settings prior to optimization, three different ML-models were trained and tested. Precision-recall curves, as well as the area-under-curve (AUC) of the resulting receiver-operator-characteristic (ROC) curves were analyzed for model assessment.ResultsSuccessful identification of parameter regions resulting in a high variability of dosimetric plan properties depended on the choice of geometry features, the treatment indication and the plan property under investigation. AUC values between 0.82 and 0.99 could be achieved. The best average-precision (AP) values obtained from the corresponding precision/recall curves ranged from 0.71 to 0.99.ConclusionsMachine learning models trained on a database of pre-optimized treatment plans can help finding relevant optimization parameter ranges prior to optimization.     

Dose-escalated volumetric modulated arc therapy for total marrow irradiation: A feasibility dosimetric study with 4DCT planning and simultaneous integrated boost

PurposeTo evaluate the planning feasibility of dose-escalated total marrow irradiation (TMI) with simultaneous integrated boost (SIB) to the active bone marrow (ABM) using volumetric modulated arc therapy (VMAT), and to assess the impact of using planning organs at risk (OAR) volumes (PRV) accounting for breathing motion in the optimization.MethodsFive patients underwent whole-body CT and thoraco-abdominal 4DCT. A planning target volume (PTV) including all bones and ABM was contoured on each whole-body CT. PRV of selected OAR (liver, heart, kidneys, lungs, spleen, stomach) were determined with 4DCT. Planning consisted of 9–10 full 6 MV photon VMAT arcs. Four plans were created for each patient with 12 Gy prescribed to the PTV, with or without an additional 4 Gy SIB to the ABM. Planning dose constraints were set on the OAR or on the PRV. Planning objective was a PTV D_mean < 110% of the prescribed dose, a PTV V_110% < 50%, and OAR D_mean ≤ 50–60%.ResultsPTV D_mean < 110% was accomplished for most plans (n = 18/20), while all achieved V_110%<50%. SIB plans succeeded to optimally cover the boost volume (median ABM D_mean = 16.3 Gy) and resulted in similar OAR sparing compared to plans without SIB (median OAR D_mean = 40–54% of the ABM prescribed dose). No statistically significant differences between plans optimized with constraints on OAR or PRV were found.ConclusionsAdding a 4 Gy SIB to the ABM for TMI is feasible with VMAT technique, and results in OAR sparing similar to plans without SIB. Setting dose constraints on PRV does not impair PTV dosimetric parameters.     

Patient-specific quality assurance and plan dose errors on breast intensity-modulated proton therapy

PurposeTo investigate, in proton therapy, whether the Gamma passing rate (GPR) is related to the patient dose error and whether MU scaling can improve dose accuracy.MethodsAmong 20 consecutively treated breast patients selected for analysis, two IMPT plans were retrospectively generated: (1) the pencil-beam (PB) plan and (2) the Monte Carlo (MC) plan. Patient-specific QA was performed. A 3%/3-mm Gamma analysis was conducted to compare the TPS-calculated PB algorithm dose distribution with the measured 2D dose. Dose errors were compared between the plans that passed the Gamma testing and those that failed. The MU was then scaled to obtain a better GPR. MU-scaled PB plan dose errors were compared to the original PB plan.ResultsOf the 20 PB plans, 8 were passed Gamma testing (G_pass_group) and 12 failed (G_fail_group). Surprisingly, the G_pass_group had a greater dose error than the G_fail_group. The median (range) of the PTV DVH RMSE and PTV ΔDmean were 1.36 (1.00–1.91) Gy vs 1.18 (1.02–1.80) Gy and 1.23 (0.92–1.71) Gy vs 1.10 (0.87–1.49) Gy for the G_pass_group and the G_fail_group, respectively. MU scaling reduced overall dose error. However, for PTV D99 and D95, MU scaling worsened some cases.ConclusionFor breast IMPT, the PB plans that passed the Gamma testing did not show smaller dose errors compared to the plans that failed. For individual plans, the MU scaling technique leads to overall smaller dose errors. However, we do not suggest use of the MU scaling technique to replace the MC plans when the MC algorithm is available.     

Advanced optimization methods for whole pelvic and local prostate external beam therapy

PurposeRadiation treatment planning inherently involves multiple conflicting planning goals, which makes it a suitable application for multicriteria optimization (MCO). This study investigates a MCO algorithm for VMAT planning (VMAT–MCO) for prostate cancer treatments including pelvic lymph nodes and uses standard inverse VMAT optimization (sVMAT) and Tomotherapy planning as benchmarks.MethodsFor each of ten prostate cancer patients, a two stage plan was generated, consisting of a stage 1 plan delivering 22 Gy to the prostate, and a stage 2 plan delivering 50.4 Gy to the lymph nodes and 56 Gy to the prostate with a simultaneous integrated boost. The single plans were generated by three planning techniques (VMAT–MCO, sVMAT, Tomotherapy) and subsequently compared with respect to plan quality and planning time efficiency.ResultsPlan quality was similar for all techniques, but sVMAT showed slightly better rectum (on average D_mean −7%) and bowel sparing (D_mean −17%) compared to VMAT–MCO in the whole pelvic treatments. Tomotherapy plans exhibited higher bladder dose (D_mean +42%) in stage 1 and lower rectum dose (D_mean −6%) in stage 2 than VMAT–MCO. Compared to manual planning, the planning time with MCO was reduced up to 12 and 38 min for stage 1 and 2 plans, respectively.ConclusionMCO can generate highly conformal prostate VMAT plans with minimal workload in the settings of prostate-only treatments and prostate plus lymph nodes irradiation. In the whole pelvic plan manual VMAT optimization led to slightly improved OAR sparing over VMAT–MCO, whereas for the primary prostate treatment plan quality was equal.     

Dosimetric impact of statistical uncertainty on Monte Carlo dose calculation algorithm in volumetric modulated arc therapy using Monaco TPS for three different clinical cases

AimTo study the dosimetric impact of statistical uncertainty (SU) per plan on Monte Carlo (MC) calculation in Monaco? treatment planning system (TPS) during volumetric modulated arc therapy (VMAT) for three different clinical cases.BackgroundDuring MC calculation SU is an important factor to decide dose calculation accuracy and calculation time. It is necessary to evaluate optimal acceptance of SU for quality plan with reduced calculation time.Materials and methodsThree different clinical cases as the lung, larynx, and prostate treated using VMAT technique were chosen. Plans were generated with Monaco? V5.11 TPS with 2% statistical uncertainty. By keeping all other parameters constant, plans were recalculated by varying SU, 0.5%, 1%, 2%, 3%, 4%, and 5%. For plan evaluation, conformity index (CI), homogeneity index (HI), dose coverage to PTV, organ at risk (OAR) dose, normal tissue receiving dose ≥5 Gy and ≥10 Gy, integral dose (NTID), calculation time, gamma pass rate, calculation reproducibility and energy dependency were analyzed.ResultsCI and HI improve as SU increases from 0.5% to 5%. No significant dose difference was observed in dose coverage to PTV, OAR doses, normal tissue receiving dose ≥5 Gy and ≥10 Gy and NTID. Increase of SU showed decrease in calculation time, gamma pass rate and increase in PTV max dose. No dose difference was seen in calculation reproducibility and dependent on energy.ConclusionFor VMAT plans, SU can be accepted from 1% to 3% per plan with reduced calculation time without compromising plan quality and deliverability by accepting variations in point dose within the target.     

Range optimization for target and organs at risk in dynamic adaptive passive scattering proton beam therapy – A proof of concept

PurposeThe purpose of this study was to design and develop a new range optimization for target and organs at risk (OARs) in dynamic adaptive proton beam therapy (PBT).MethodsThe new range optimization for target and OARs (RO-TO) was optimized to maintain target dose coverage but not to increase the dose exposure of OARs, while the other procedure, range optimization for target (RO-T), only focused on target dose coverage. A retrospective analysis of a patient who received PBT for abdominal lymph node metastases was performed to show the effectiveness of our new approach. The original plan (OP), which had a total dose of 60 Gy (relative biological effectiveness; RBE), was generated using six treatment fields. Bone-based registration (BR) and tumor-based registration (TR) were performed on each pretreatment daily CT image dataset acquired once every four fractions, to align the isocenter.ResultsBoth range adaptive approaches achieved better coverage (D_95%) and homogeneity (D_5%−D_95%) than BR and TR only. However, RO-T showed the greatest increases in D_2cc and D_mean values of the small intestine and stomach and exceeded the limitations of dose exposure for those OARs. RO-TO showed comparable or superior dose sparing compared with the OP for all OARs.ConclusionsOur results suggest that BR and TR alone may reduce target dose coverage, and that RO-T may increase the dose exposure to the OARs. RO-TO may achieve the planned dose delivery to the target and OARs more efficiently than the OP. The technique requires testing on a large clinical dataset.     

In silico comparison of photons versus carbon ions in single fraction therapy of lung cancer

PurposeStereotactic body image guided radiation therapy (SBRT) shows good results for lung cancer treatment. Better normal tissue sparing might be achieved with scanned carbon ion therapy (PT). Therefore an in silico trial was conducted to find potential advantages of and patients suited for PT.MethodsFor 19 patients treated with SBRT, PT plans were calculated on 4D-CTs with simulated breathing motion. Prescribed single fraction dose was 24 Gy and OAR constraints used for photon planning were respected. Motion was mitigated by rescanning and range-adapted ITVs. Doses were compared to the original SBRT plans.ResultsCTV coverage was the same in SBRT and PT. The field-specific PTV including range margins for PT was 1.5 (median, 25–75% 1.3–2.1) times larger than for SBRT. Nevertheless, maximum point dose and mean dose in OARs were higher in SBRT by 2.8 (1.6–3.7) Gy and 0.7 (0.3–1.6) Gy, respectively. Patients with a CTV >2.5 cc or with multiple lung lesions showed larger differences in OAR doses in favor of PT.ConclusionsPatients receive less dose in critical OARs such as heart, spinal cord, esophagus, trachea and aorta with PT, while maintaining the same target coverage. Patients with multiple or larger lesions are particularly suited for PT.     

Assessment of monitor unit limiting strategy using volumetric modulated arc therapy for cancer of hypopharynx

PurposeTo quantify relative merit of MU deprived plans against freely optimized plans in terms of plan quality and report changes induced by progressive resolution optimizer algorithm (PRO3) to the dynamic parameters of RapidArc.Materials and methodsTen cases of carcinoma hypopharynx were retrospectively planned in three phases without using MU tool. Replicas of these baseline plans were reoptimized using “Intermediate dose” feature and “MU tool” to reduce MUs by 20%, 35%, and 50%. Overall quality indices for target and OAR, integral dose, dose-volume spread were assessed. All plans were appraised for changes induced in RapidArc dynamic parameters and pre-treatment quality assurance (QA).ResultsWith increasing MU reduction strength (MURS), MU/Gy values reduced, for all phases with an overall range of 8.6–34.7%; mean dose rate decreased among plans of each phase, phase3 plans recorded greater reductions. MURS20% showed good trade-off between MUs and plan quality. Dose-volume spread below 5 Gy was higher for baseline plans while lower between 20 and 35 Gy. Integral dose was lower for MURS0%, not exceeding 1.0%, compared against restrained plans. Mean leaf aperture and control point areas increased systematically, correlated negatively with increasing MURS. Absolute delta dose rate variations were least for MURS0%. MU deprived plans exhibited GAI (>93%), better than MURS0% plans.ConclusionBaseline plans are superior to MU restrained plans. However, MURS20% offers equivalent and acceptable plan quality with mileage of MUs, improved GAI for complex cases. MU tool may be adopted to tailor treatment plans using PRO3.     

Interlaced proton grid therapy – Linear energy transfer and relative biological effectiveness distributions

PurposeInterlaced beams have previously been proposed for delivering proton grid therapy. This study aims to assess dose-averaged LET (LET_d) and RBE-weighted dose (D_RBE) distributions of such beam geometries, and compare them with conventional intensity modulated proton therapy (IMPT).MethodsIMPT plans and four different interlaced proton grid therapy plans were generated for five patient cases (esophagus, lung, liver, prostate, anus). The constant RBE = 1.1 was assumed for optimization. The LET_d was subsequently Monte Carlo calculated for each plan and used as input for two LET-dependent variable RBE models. The fulfilment of clinical goals, along with DVH and spatial distribution evaluations, were then assessed and compared.ResultsAll plans fulfilled the clinical target goals assuming RBE = 1.1. The target coverage was slightly compromised for some grid plans when assuming the variable RBE models. All IMPT plans, and 18 of 20 grid plans, fulfilled all clinical goals for the organs at risk when assuming RBE = 1.1, whereas most plans failed at least one goal when assuming the variable RBE models. Compared with the IMPT plans, the grid plans demonstrated substantially different LET_d distributions due to the fundamentally different beam geometries. However, D_RBE distributions in the target were similar.ConclusionsDespite the unconventional beam geometries of interlaced proton grid plans, with resulting alternating dose and LET_d patterns, the fulfillment of realistic clinical goals seems to be comparable to regular IMPT plans, both assuming RBE = 1.1 and variable RBE models. In addition, the alternating grid patterns do not seem to give rise to unexpected D_RBE hot-spots.     

Variance-based sensitivity analysis of biological uncertainties in carbon ion therapy

PurposeBiological models to estimate the relative biological effectiveness (RBE) or the equivalent dose in 2 Gy fractions (EQD2) are needed for treatment planning and plan evaluation in carbon ion therapy. We present a model-independent, Monte Carlo based sensitivity analysis (SA) approach to quantify the impact of different uncertainties on the biological models.Methods and materialsThe Monte Carlo based SA is used for the evaluation of variations in biological parameters. The key property of this SA is the high number of simulation runs, each with randomized input parameters, allowing for a statistical variance-based ranking of the input variations. The potential of this SA is shown in a simplified one-dimensional treatment plan optimization. Physical properties of carbon ion beams (e.g. fragmentation) are simulated using the Monte Carlo code FLUKA. To estimate biological effects of ion beams compared to X-rays, we use the Local Effect Model (LEM) in the framework of the linear-quadratic (LQ) model. Currently, only uncertainties in the output of the biological models are taken into account.Results/conclusionsThe presented SA is suitable for evaluation of the impact of variations in biological parameters. Major advantages are the possibility to access and display the sensitivity of the evaluated quantity on several parameter variations at the same time. Main challenges for later use in three-dimensional treatment plan evaluation are computational time and memory usage. The presented SA can be performed with any analytical or numerical function and hence be applied to any biological model used in carbon ion therapy.     

NTCP modeling analysis of acute hematologic toxicity in whole pelvic radiation therapy for gynecologic malignancies – A dosimetric comparison of IMRT and spot-scanning proton therapy (SSPT)

PurposeThis treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade ⩾3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT).Methods and materialsThe normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45 Gy(RBE) in 1.8 Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared.ResultsThe bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP = 0.04 ± 0.01 and 0.19 ± 0.03, p = 0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI = 0.97 ± 0.01 and 0.96 ± 0.02, p = 0.3177, and HI = 1.24 ± 0.11 and 1.27 ± 0.05, p = 0.8473, respectively).ConclusionThe SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT.     

Normal tissue sparing potential of scanned proton beams with and without respiratory gating for the treatment of internal mammary nodes in breast cancer radiotherapy

Proton therapy has shown potential for reducing doses to normal tissues in breast cancer radiotherapy. However data on the impact of protons when including internal mammary nodes (IMN) in the target for breast radiotherapy is comparatively scarce. This study aimed to evaluate normal tissue doses when including the IMN in regional RT with scanned proton beams, with and without respiratory gating. The study cohort was composed of ten left-sided breast patients CT-scanned during enhanced inspiration gating (EIG) and free-breathing (FB). Proton plans were designed for the target including or excluding the IMN. Targets and organs-at-risk were delineated according to RTOG guidelines. Comparison was performed between dosimetric parameters characterizing target coverage and OAR radiation burden. Statistical significance of differences was tested using a paired, two-tailed Student’s t-test. Inclusion of the IMN in the target volume led to a small increase of the cardiopulmonary burden. The largest differences were seen for the ipsilateral lung where the mean dose increased from 6.1 to 6.6 Gy (RBE) (P < 0.0001) in FB plans and from 6.9 to 7.4 Gy (RBE) (P = 0.003) in EIG plans. Target coverage parameters were very little affected by the inclusion of IMN into the treatment target. Radiotherapy with scanned proton beams has the potential of maintaining low cardiovascular burden when including the IMN into the target, irrespective of whether respiratory gating is used or not.     

Gated carbon-ion scanning treatment for pancreatic tumour with field specific target volume and organs at risk

ObjectiveTo assess the feasibility of treatment planning for pancreatic tumours subject to respiratory motion using field-specific target volumes (FTV) and field-specific organs at risk (FOAR) using four-dimensional computed tomography (4DCT).MethodsFourteen pancreatic cancer patients underwent 4DCT. Radiation oncologists contoured the gross tumour volume (GTV), clinical target volume (CTV), spinal cord, duodenum, kidneys, and stomach. The gating duty cycle was set to 30 % around exhalation. FTV and FOAR were calculated using the 4DCT dataset. Planning target volumes (PTV) and planning organs at risk volumes (PRV) were defined as equal to FTV and FOAR, respectively. A dose of 55.2 Gy relative biological effectiveness (RBE) was planned to target the PTV from four beam angles. A single field uniform dose (SFUD) plan was selected. The dose distribution, including intrafractional motion changes, was generated.ResultsThe mean volume of target receiving 95 % of the planned doses was 96.4 ± 4.1 % to the GTV and 94.7 ± 0.9 % to the CTV. The highest dose to 2 cc of duodenal volume was 27.5 Gy (RBE). The volume of the stomach receiving ⩾30 Gy (RBE) was <7.0 cc in all patients. All metrics for OARs satisfied dose constraints.ConclusionDose to the CTV was covered sufficiently by the 4DCT-generated FTV, and dose to OARs was reduced by 4DCT-generated FOAR. This methodology may prevent adverse reactions while preserving local tumour control.     

Feasibility of intensity-modulated radiotherapy to treat gastric cancer

AimTo present a proposed gastric cancer intensity-modulated radiotherapy (IMRT) treatment planning protocol for an institution that have not introduced volumetric modulated arc therapy in clinical practice. A secondary aim was to determine the impact of 2DkV set-up corrections on target coverage and organ at risk (OAR).Methods and MaterialsTwenty consecutive patients were treated with a specially-designed non-coplanar 7-field IMRT technique. The isocenter-shift method was used to estimate the impact of 2DkV-based set-up corrections on the original base plan (BP) coverage. An alternative plan was simulated (SP) by taking into account isocenter shifts. The SP and BP were compared using dose-volume histogram (DVH) plots calculated for the internal target volume (ITV) and OARs.ResultsBoth plans delivered a similar mean dose to the ITV (100.32 vs. 100.40%), with no significant differences between the plans in internal target coverage (5.37 vs. 4.96%). Similarly, no significant differences were observed between the maximal dose to the spinal cord (67.70 and 67.09%, respectively) and volume received 50% of the prescribed dose of: the liver (62.11 vs. 59.84%), the right (17.62 vs. 18.58%) and left kidney (29.40 vs. 30.48%). Set-up margins (SM) were computed as 7.80 mm, 10.17 mm and 6.71 mm in the left-right, cranio-caudal and anterior-posterior directions, respectively.ConclusionPresented IMRT protocol (OAR dose constraints with selected SM verified by 2DkV verification) for stomach treatment provided optimal dose distribution for the target and the critical organs. Comparison of DVH for the base and the modified plan (which considered set-up uncertainties) showed no significant differences.     

Image-guided IMRT for localized prostate cancer with daily repositioning: Inferring the difference between planned dose and delivered dose distribution

IntroductionTo investigate the dosimetric impact of daily on-line repositioning during a full course of IMRT for prostate cancer.Materials and methodsTwenty patients were treated with image-guided IMRT. Each pre-treatment plan (Plan A) was compared with a post-treatment plan sum (Plan B) based on couch shifts measured. The delivered dose to the prostate without a daily repositioning was inferred by considering each daily couch shift during the whole course of image-guided IMRT (i.e. plan B). Dose metrics were compared for prostate CTV (P-CTV) and PTV (P-PTV) and for organs at risk. Ten patients were treated with a 5 mm margin and 10 patients with a 10 mm margin.ResultsFor plan A vs plan B: the average D95, D98, D50, D mean and EUD were: 76.4 Gy vs 73.9 Gy (p = 0.0007), 75.4 Gy vs 72.3 Gy (p = 0.001), 78.9 Gy vs 78.4 Gy (p = 0.014), 78.7 Gy vs 77.8 Gy (p = 0.003) and 78.1 Gy vs 75.9 Gy (p = 0.002), respectively for P-CTV, and 73.2 Gy vs 69.3 Gy (p = 0.0006), 70.7 Gy vs 66.0 Gy (p = 0.0008), 78.3 Gy vs 77.5 Gy (p = 0.001), 77.8 Gy vs 76.4 Gy (p = 0.0002) and 74.4 Gy vs 69.2 Gy (p = 0.003), respectively for P-PTV. Margin comparison showed no differences in dose metrics between the two plans except for D98 of the rectum in plan B which was significantly higher with a 10 mm margin.ConclusionsThe absence of daily image-guided IMRT resulted in a significantly less uniform and less homogeneous dose distribution to the prostate. A reduction in PTV margin showed neither a lower target coverage nor a better spare of OAR with and without daily image-guided IMRT.     

The FLUKA Monte Carlo code coupled with an OER model for biologically weighted dose calculations in proton therapy of hypoxic tumors

IntroductionThe increased radioresistance of hypoxic cells compared to well-oxygenated cells is quantified by the oxygen enhancement ratio (OER). In this study we created a FLUKA Monte Carlo based tool for inclusion of both OER and relative biological effectiveness (RBE) in biologically weighted dose (ROWD) calculations in proton therapy and applied this to explore the impact of hypoxia.MethodsThe RBE-weighted dose was adapted for hypoxia by making RBE model parameters dependent on the OER, in addition to the linear energy transfer (LET). The OER depends on the partial oxygen pressure (pO₂) and LET. To demonstrate model performance, calculations were done with spread-out Bragg peaks (SOBP) in water phantoms with pO₂ ranging from strongly hypoxic to normoxic (0.01–30 mmHg) and with a head and neck cancer proton plan optimized with an RBE of 1.1 and pO₂ estimated voxel-by-voxel using [¹⁸F]-EF5 PET. An RBE of 1.1 and the Rørvik RBE model were used for the ROWD calculations.ResultsThe SOBP in water had decreasing ROWD with decreasing pO₂. In the plans accounting for oxygenation, the median target doses were approximately a factor 1.1 lower than the corresponding plans which did not consider the OER. Hypoxia adapted target ROWDs were considerably more heterogeneous than the RBE_1.1-weighted doses.ConclusionWe realized a Monte Carlo based tool for calculating the ROWD. Read-in of patient pO₂ and estimation of ROWD with flexibility in choice of RBE model was achieved, giving a tool that may be useful in future clinical applications of hypoxia-guided particle therapy.