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Background Cure- and toxicity rates after intensity-modulated radiotherapy (IMRT) of prostate cancer are dose-and volume dependent. We prospectively studied the potential for organ at risk (OAR) sparing and compensation of tumor movement with the coverage probability (CovP) concept. Patients and methods Twenty-eight prostate cancer patients (median age 70) with localized disease (cT1c–2c, N0, M0) and intermediate risk features (prostate-specific antigen [PSA] < 20, Gleason score ≤ 7b) were treated in a prospective study with the CovP concept. Planning-CTs were performed on three subsequent days to capture form changes and movement of prostate and OARs. The clinical target volume (CTV) prostate and the OARs (bladder and rectum) were contoured in each CT. The union of CTV1–3 was encompassed by an isotropic margin of 7 mm to define the internal target volume (ITV). Dose prescription/escalation depended on coverage of all CTVs within the ITV. IMRT was given in 39 fractions to 78 Gy using the Monte-Carlo algorithm. Short-term androgen deprivation was recommended and given in 78.6% of patients. Results Long-term toxicity was evaluated in 26/28 patients after a median follow-up of 7.1 years. At last follow-up, late bladder toxicity (Radiation Therapy Oncology Group, RTOG) G1 was observed in 14.3% of patients and late rectal toxicities (RTOG) of G1 (7.1%) and of G2 (3.6%) were observed. No higher graded toxicity occurred. After 7.1 years, biochemical control (biochemically no evidence of disease, bNED) was 95.5%, prostate cancer-specific survival and the distant metastasis-free survival after 7.1 years were 100% each. Conclusions CovP-based IMRT was feasible in a clinical study. Dose escalation with the CovP concept was associated by a low rate of toxicity and a high efficacy regarding local and distant control.

Background: Lung cancer patients struggle with high toxicity rates. This study investigates if IMRT plans with individually set beam angles or uni-lateral VMAT plans results in dose reduction to OARs. We investigate if introduction of a RapidPlan model leads to reduced dose to OARs. Finally, the model is validated prospectively. Material and methods: Seventy-four consecutive lung cancer patients treated with IMRT were included. For all patients, new IMRT plans were made by an experienced dose planner re-tuning beam angles aiming for minimized dose to the lungs and heart. Additionally, VMAT plans were made. The IMRT plans were selected as input for a RapidPlan model, which was used to generate 74 new IMRT plans. The new IMRT plans were used as input for a second RapidPlan model. This model was clinically implemented and used for generation of clinical treatment plans. Dosimetric parameters were compared using a Wilcoxon signed rank test or a 1-sided student’s t-test. p

Purpose Magnetic resonance-guided radiotherapy (MRgRT) has recently been introduced in our institution. As MRgRT requires high patient compliance compared to conventional techniques and can be associated with prolonged treatment times, feasibility and patient tolerance were prospectively assessed using patient-reported outcome questionnaires (PRO-Q). Materials and methods Forty-three patients were enrolled in a prospective observational study and treated with MRgRT on a low-field hybrid Magnetic Resonance Linear Accelerator system (MR-Linac) between April 2018 and April 2019. For assistance in gated breath-hold delivery using cine-MRI, a video feedback system was installed. PRO-Qs consisted of questions on MR-related complaints and also assessed aspects of active patient participation. Results The most commonly treated anatomic sites were nodal metastases and liver lesions. The mean treatment time was 34 min with a mean beam-on time of 2:17 min. Gated stereotactic body radiotherapy (SBRT) was applied in 47% of all patients. Overall, patients scored MRgRT as positive or at least tolerable in the PRO‑Q. Almost two thirds of patients (65%) complained about at least one item of the PRO‑Q (score ≥4), mainly concerning coldness, paresthesia, and uncomfortable positioning. All patients reported high levels of satisfaction with their active role using the video feedback system in breath-hold delivery. Conclusion MRgRT was successfully implemented in our clinic and well tolerated by all patients, despite MR-related complaints and complaints about uncomfortable immobilization. Prospective clinical studies are in development for further evaluation of MRgRT and for quantification of the benefit of MR-guided on-table adaptive radiotherapy.

Purpose The need for four-dimensional (4D) treatment planning becomes indispensable when it comes to radiation therapy for moving tumors in the thoracic and abdominal regions. The primary purpose of this study is to combine the actual breathing trace during each individual treatment fraction with the Linac's log file information and Monte Carlo 4D dose calculations. We investigated this workflow on multiple computed tomography (CT) datasets in a clinical environment for stereotactic body radiation therapy (SBRT) treatment planning. Methods We have developed a workflow, which allows us to recalculate absorbed dose to a 4DCT dataset using Monte Carlo calculation methods and accumulate all 4D doses in order to compare them to the planned dose using the Linac's log file, a 4DCT dataset, and the patient's actual breathing curve for each individual fraction. For five lung patients, three-dimensional-conformal radiation therapy (3D-CRT) and volumetric modulated arc treatment (VMAT) treatment plans were generated on four different CT image datasets: a native free-breathing 3DCT, an average intensity projection (AIP) and a maximum intensity projection (MIP) CT both obtained from a 4DCT, and a 3DCT with density overrides based on the 3DCT (DO). The Monte Carlo 4D dose has been calculated on each 4DCT phase using the Linac's log file and the patient's breathing trace as a surrogate for tumor motion and dose was accumulated to the gross tumor volume (GTV) at the 50% breathing phase (end of exhale) using deformable image registration. Results Δ D 98 % and Δ D 2 % between 4D dose and planned dose differed largely for 3DCT-based planning and also for DO in three patients. Least dose differences between planned and recalculated dose have been found for AIP and MIP treatment planning which both tend to be superior to DO, but the results indicate a dependency on the breathing variability, tumor motion, and size. An interplay effect has not been observed in the small patient cohort. Conclusions We have developed a workflow which, to our best knowledge, is the first incorporation of the patient breathing trace over the course of all individual treatment fractions with the Linac's log file information and 4D Monte Carlo recalculations of the actual treated dose. Due to the small patient cohort, no clear recommendation on which CT can be used for SBRT treatment planning can be given, but the developed workflow, after adaption for clinical use, could be used to enhance a priori 4D Monte Carlo treatment planning in the future and help with the decision on which CT dataset treatment planning should be carried out.

Our purpose was to evaluate an imaging parameter–response relationship between the extent of tumor hypoxia quantified by dynamic 18F-fluoromisonidazole (18F-FMISO) PET/CT and the risk of relapse after radiotherapy in patients with head and neck cancer. Methods: Before a prospective cohort of 25 head and neck cancer patients started radiotherapy, they were examined with dynamic 18F-FMISO PET/CT 0–240 min after tracer injection. 18F-FMISO image parameters, including a hypoxia metric, MFMISO, derived from pharmacokinetic modeling of dynamic 18F-FMISO and maximum tumor-to-muscle ratio (TMRmax) at 4 h after injection, gross tumor volume (GTV), relative hypoxic volume based on MFMISO, and a logistic regression model combining GTV and TMRmax, were assessed and compared with a previous training cohort (n = 15). Dynamic 18F-FMISO was used to validate a tumor control probability model based on MFMISO. The prognostic potential with respect to local control of all potential parameters was validated using the concordance index for univariate Cox regression models determined from the training cohort, in addition to Kaplan–Meier analysis including the log-rank test. Results: The tumor control probability model was confirmed, indicating that dynamic 18F-FMISO allows stratification of patients into different risk groups according to radiotherapy outcome. In this study, MFMISO was the only parameter that was confirmed as prognostic in the independent validation cohort (concordance index, 0.71; P = 0.004). All other investigated parameters, such as TMRmax, GTV, relative hypoxic volume, and the combination of GTV and TMRmax, were not able to stratify patient groups according to outcome in this validation cohort (P = not statistically significant). Conclusion: In this study, the relationship between MFMISO and the risk of relapse was prospectively validated. The data support further evaluation and external validation of dynamic 18F-FMISO PET/CT as a promising method for patient stratification and hypoxia-based radiotherapy personalization, including dose painting.

A novel risk model has recently been proposed for the occurrence of late contrast-enhancing brain lesions (CEBLs) after proton irradiation of low-grade glioma (LGG) patients. It predicts a strong dependence on dose-weighted linear-energy transfer (LETd effect) and an increased radiosensitivity of the ventricular proximity, a 4-mm fringe surrounding the ventricular system (VP4mm effect). On this basis, we investigated (A) how these two risk factors and patient-specific anatomical and treatment plan (TP) features contribute to normal tissue complication probability (NTCP) and (B) if conventional LETd -reduction techniques like multiple-field TP are able to reduce NTCP. (A) The LGG model cohort (N = 110) was stratified with respect to prescribed dose, tumor grade, and treatment field configuration. NTCP predictions and CEBL occurrence rates per strata were analyzed. (B) The effect of multiple-field TP was investigated in two patient groups: (i) nine high-risk subjects with extended lateral target volumes who had developed CEBLs after single-beam treatments were retrospectively replanned with a clinical standard two-field setting using almost orthogonal fields and strictly opposing fields, (ii) single-field treatments were simulated for seven low-risk patients with small central target volumes clinically treated with two strictly opposing fields. (A) In the model cohort, we identified the exposure of the radiosensitive VP4mm fringe with proton field components of increased biological effectiveness as dominant NTCP driving factor. We observed that larger target volumes and location lateral to the main ventricles, both being characteristic for WHO°II tumors, presented with the highest complication risks. Among subjects of an equal dose prescription of 54 Gy(RBE), the highest median NTCP was obtained for the WHO°II group treated with two fields using sharp angles. (B) Regarding the effect of multiple-field plans, we found that an NTCP reduction was only achievable in the low-risk group where the LETd effect dominates and the VP4mm effect is small. NTCP of the single-field plans was 23% higher compared to the clinical opposing field plan. In the high-risk group, where the VP4mm effect dominates the risk, both two-field scenarios yielded 44% higher NTCP predictions compared to the clinical single-field plans. The interplay of an increased radiosensitivity in the VP4mm fringe with proton field components of increased biological effectiveness creates a geometric complexity that can hardly be managed by current clinical TP. Our results underline that advanced biologically guided TP approaches become crucial for an effective risk minimization in proton therapy of LGG.

Highlights • No statistically significant difference between the high- and low dose arm in risk of RP. • Identified risk factors for RP: target volume, infection, dyspnea at baseline, and increase of cough during RT. • number of patients was too small to establish a statistically sound multivariable model., Purpose Prospectively scored radiation pneumonitis (RP) observed in a national, randomized phase II dose-escalation trial for patients with locally advanced non-small cell lung cancer (NSCLC) was investigated. Methods Patients with stage IIB-IIIB histologically proven NSCLC were treated with concomitant chemo-radiotherapy (oral Vinorelbine 3times/week) at 60 Gy/30fx (A–59pts) and 66 Gy/33fx (B–58pts) from 2009 to 2013 at five Danish RT centers. Grade 2 RP (CTCAEv3.0) was investigated with univariate analysis for association with clinical and dosimetric parameters, including dyspnea and cough at baseline and during RT. Multivariable logistic regression and Cox regression with regularization were used to find a multivariable model for RP ≥ G2. Results Despite a tendency of higher mean lung dose in the high-dose arm (median[range] A = 14.9 Gy[5.8,23.1], B = 17.5 Gy[8.6,24.8], p = 0.075), pulmonary toxicities were not significantly different (RP ≥ G2 41%(A) and 52%(B), p = 0.231). A Kaplan Meier analysis of the time to RP ≥ G2 between the two arms did not reach statistical significance (p = 0.180). Statistically significant risk factors for RP ≥ G2 were GTV size (OR = 2.091/100 cm3, p = 0.002), infection at baseline or during RT (OR = 8.087, p = 0.026), dyspnea at baseline (OR = 2.184, p = 0.044) and increase of cough during RT (OR = 2.787, p = 0.008). In the multivariable logistic regression and the Cox regression analysis, the deviances of the most predictive models were within one standard deviation of the null model. Conclusion No statistical difference between the high- and low dose arm was found in the risk of developing RP. The univariate analysis identified target volume, infection, dyspnea at baseline, and increase of cough during RT as risk factors for RP. The number of patients was too small to establish a statistically sound multivariable model.

Background This work addresses a basic inconsistency in the way dose is accumulated in radiotherapy when predicting the biological effect based on the linear quadratic model (LQM). To overcome this inconsistency, we introduce and evaluate the concept of the total biological dose, bEQDd. Methods Daily computed tomography imaging of nine patients treated for prostate carcinoma with intensity-modulated radiotherapy was used to compute the delivered deformed dose on the basis of deformable image registration (DIR). We compared conventional dose accumulation (DA) with the newly introduced bEQDd, a new method of accumulating biological dose that considers each fraction dose and tissue radiobiology. We investigated the impact of the applied fractionation scheme (conventional/hypofractionated), uncertainties induced by the DIR and by the assigned α/β-value. Results bEQDd was systematically higher than the conventionally accumulated dose with difference hot spots of 3.3–4.9 Gy detected in six out of nine patients in regions of high dose gradient in the bladder and rectum. For hypofractionation, differences are up to 8.4 Gy. The difference amplitude was found to be in a similar range to worst-case uncertainties induced by DIR and was higher than that induced by α/β. Conclusion Using bEQDd for dose accumulation overcomes a potential systematic inaccuracy in biological effect prediction based on accumulated dose. Highest impact is found for serial-type late responding organs at risk in dose gradient regions and for hypofractionation. Although hot spot differences are in the order of several Gray, in dose-volume parameters there is little difference compared with using conventional or biological DA. However, when local dose information is used, e.g. dose surface maps, difference hot spots can potentially change outcomes of dose-response modelling and adaptive treatment strategies.

Purpose: To report on the commissioning and clinical validation of the first commercially available independent Monte Carlo (MC) three-dimensional (3D) dose calculation for CyberKnife robotic radiosurgery system® (Accuray, Sunnyvale, CA). Methods: The independent dose calculation (IDC) by SciMoCa® (Scientific RT, Munich, Germany) was validated based on water measurements of output factors and dose profiles (unshielded diode, field-size dependent corrections). A set of 84 patient-specific quality assurance (QA) measurements for multi-leaf collimator (MLC) plans, using an Octavius two-dimensional SRS1000 array (PTW, Freiburg, Germany), was compared to results of respective calculations. Statistical process control (SPC) was used to detect plans outside action levels. Results: Of all output factors for the three collimator systems of the CyberKnife, 99% agreed within 2% and 81% within 1%, with a maximum deviation of 3.2% for a 5-mm fixed cone. The profiles were compared using a one-dimensional gamma evaluation with 2% dose difference and 0.5 mm distance-to-agreement (Γ(2,0.5)). The off-centre ratios showed an average pass rate >99% (92–100%). The agreement of the depth dose profiles depended on field size, with lowest pass rates for the smallest MLC field sizes. The average depth dose pass rate was 88% (35–99%). The IDCs showed a Γ(2,1) pass rate of 98%. Statistical process control detected six plans outside tolerance levels in the measurements, all of which could be attributed the measurement setup. Independent dose calculations showed problems in five plans, all due to differences in the algorithm between TPS and IDC. Based on these results changes were made in the class solution for treatment plans. Conclusion: The first commercially available MC 3D dose IDC was successfully commissioned and validated for the CyberKnife and replaced all routine patientspecific QA measurements in our clinic.

PURPOSE: The two distinct dose computation paradigms of Boltzmann equation solvers and Monte Carlo simulation both promise in principle maximum accuracy. In practice, clinically acceptable calculation times demand approximations and numerical short-cuts on one hand, and modeling the beam characteristics of a real linear accelerator to the required accuracy on the other. A thorough benchmark of both algorithm types therefore needs to start with beam modeling, and needs to include a number of clinically challenging treatment plans.METHODS: The Acuros XB (v 13.7, Varian Medical Systems) and SciMoCa (v 1.0, Scientific RT) algorithms were commissioned for the same Varian Clinac accelerator for beam qualities 6 and 15 MV. Beam models were established with water phantom measurements and MLC calibration protocols. In total, 25 patients of five case classes (lung/three-dimensional (3D) conformal, lung/IMRT, head and neck/VMAT, cervix/IMRT, and rectum/VMAT) were randomly selected from the clinical database and computed with both algorithms. Statistics of 3D gamma analysis for various dose/distance-to-agreement (DTA) criteria and differences in selected DVH parameters were analyzed.RESULTS: The percentage of points fulfilling a gamma evaluation was scored as the gamma agreement index (GAI), denoted as G(ΔD, DTA). G(3,3), G(2,2), and G(1,1) were evaluated for the full body, PTV, and selected organs at risk (OARs). For all patients, G(3,3) ≥ 99.9% and G(2,2) > 97% for the body. G(1,1) varied among the patients. However, for all patients, G(1,1) > 70% and G(1,1) > 80% for 68% of the patients. For each patient, the mean dose deviation was ΔD < 1% for the body, PTV, and all evaluated OARs, respectively. In dense bone and at off-axis distance > 10 cm, the Acuros algorithm yielded slightly higher doses. In the first layer of voxels of the patient surface, the calculated doses deviated between the algorithms. However, at the second voxel, good agreement was observed. The differences in D(98%PTV) were CONCLUSIONS: Overall, an outstanding agreement was found between the Boltzmann equation solver and Monte Carlo. High-accuracy dose computation algorithms have matured to a level that their differences are below common experimental detection thresholds for clinical treatment plans. Aside from residual differences which could be traced back to implementation details and fundamental cross-section data, both algorithms arrive at identical dose distributions.

PURPOSE: In image-guided adaptive brachytherapy (IGABT), dose distributions are optimized for each fraction. Optimum fractional dose can be constant or adapted to previous fractions and a conjecture about the future ones. We evaluate the efficacy of different fraction size schemes, derived from total IGABT dose constraints, against constant per-fraction constraints.METHODS AND MATERIALS: This retrospective planning study included 20 IGABT patients where four different fractionation schedules were compared based on modern planning recommendations. A total high-risk clinical target volume D-90 (minimum dose in 90% of the volume) dose aim of 90.0 Gy with constant per-fraction organs at risk (OARs) dose constraint planning (CONST) was compared with conservative and aggressive fractionation compensation (COMP) techniques. COMP allows variations in the per-fraction dose constraints. Dose accumulation was performed through dose summation at a given volume and equivalent uniform dose (EUD) worst-case dose estimates.RESULTS: No significant differences were identifiable between dose metrics of CONST and COMP in the total patient population. However, a subgroup of patients with alternating dose limiting OARs had significant benefit from COMP. Median high-risk clinical target volume dose escalation ranged from 5% to 12%, whereas OAR dose increases were lower and ranged from 3% to 8%. EUD-based planning delivered similar tumor doses, although slightly lower OAR doses. By distributing the treatment aim over an increased number of treatment fractions, median tumor dose could be increased by a further 8% per additional treatment fraction at the same OAR dose levels for both CONST and COMP.CONCLUSIONS: COMP is effective in patients with alternating dose-limiting OARs and is enhanced using more treatment fractions and EUD constraints. (C) 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Purpose Late radiation-induced contrast-enhancing brain lesions (CEBLs) on magnetic resonance imaging (MRI) after proton therapy of brain tumors have been observed to occur frequently in regions of high linear energy transfer (LET) and in proximity to the ventricular system. We analyzed 110 patients with low-grade glioma treated with proton therapy to determine whether the risk for CEBLs is increased in proximity to the ventricular system and if there is a relationship between relative biological effectiveness (RBE) and LET. Methods and Materials We contoured CEBLs identified on follow-up T1-MRI scans and computed dose and dose-averaged LET (LETd) distributions for all patients using the Monte Carlo method. We then performed cross-validated voxel-level logistic regression to predict local risks for image change and to extract model parameters, such as the RBE. From the voxel-level model, we derived a model for patient-level risk prediction based on the treatment plan. Results Of 110 patients, 23 exhibited 1 or several CEBLs on follow-up MRI scans. The voxel-level logistic model has an accuracy as follows: area under the curve of 0.94 and Brier score of 2.6 × 10-5. Model predictions are a 3-fold increased risk in the 4 mm region around the ventricular system and an LETd-dependent RBE of, for example, 1.20 for LETd = 2 keV/μm and 1.50 for LETd = 5 keV/μm. The patient-level risk model has an accuracy as follows: area under the curve of 0.78 and Brier score of 0.13. Conclusions Our findings present clinical evidence for an increased risk in ventricular proximity and for a proton RBE that increases significantly with increasing LET. We present a voxel-level model that accurately predicts the localization of late MRI contrast change and extrapolate a patient-level model that allows treatment plan–based risk prediction.

Purpose To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.

To investigate a new automatic template-based replanning approach combined with constrained optimization, which may be highly useful for a rapid plan transfer for planned or unplanned machine breakdowns. This approach was tested for prostate cancer (PC) and head-and-neck cancer (HNC) cases. The constraints of a previously optimized volumetric modulated arc therapy (VMAT) plan were used as a template for automatic plan reoptimization for different accelerator head models. All plans were generated using the treatment planning system (TPS) Hyperion. Automatic replanning was performed for 16 PC cases, initially planned for MLC1 (4 mm MLC) and reoptimized for MLC2 (5 mm) and MLC3 (10 mm) and for 19 HNC cases, replanned from MLC2 to MLC3. EUD, Dmean, D2%, and D98% were evaluated for targets; for OARs EUD and D2% were analyzed. Replanning was considered successful if both plans fulfilled equal constraints. All prostate cases were successfully replanned. The mean relative target EUD deviation was −0.15% and −0.57% for replanning to MLC2 and MLC3, respectively. OAR sparing was successful in all cases. Replanning of HNC cases from MLC2 to MLC3 was successful in 16/19 patients with a mean decrease of −0.64% in PTV60 EUD. In three cases target doses were substantially decreased by up to −2.58% (PTV60) and −3.44% (PTV54), respectively. Nevertheless, OAR sparing was always achieved as planned. Automatic replanning of VMAT plans for a different treatment machine by using pre-existing constraints as a template for a reoptimization is feasible and successful in terms of equal constraints.

Treatment planning for radiotherapy has become unthinkable without computer algorithms for dose optimization. Although the need for optimization algorithms originated from the complexity of treatment delivery technology such as intensity-modulated radiotherapy, volumetric-modulated arc therapy, and robotic stereotactic radiotherapy, the focus has shifted to refining goals and methods of optimization itself. Dose optimization chiefly advances in 3 directions: human interface and automation, compensation of changing patient geometries, and diversification/individualization of radiation dose prescription. Traditionally, dose optimization requires the definition of numerical treatment goals, followed by an interactive trial-and-error process to adjust the correct, patient-specific balance of these goals. Being both operator dependent and time consuming, methods are needed that produce high-quality treatments efficiently, with the long-term objective of autonomous dose optimization. Expedient treatment planning is also key to treatment adaptation to changes in patient geometry. Despite all efforts to image and adapt at treatment time, some residual uncertainties remain and must be compensated via treatment planning. Reformulations of the dose optimization problem are joined with various image-based 4D patient models to ensure treatment robustness against geometric uncertainties. Robust optimization leads to a deviation from customary dose prescription in favour of more predictable dose delivery. The dose distribution can be individualized further by additional functional image information, aiming to guide the dose towards undertreated volumes and away from overtreated ones, also known as dose-painting. Multimodal imaging is increasingly integrated into treatment planning, making it a natural consequence to supplant computed tomography by magnetic resonance imaging to establish MR-based radiotherapy.

Purpose: Helium ions (4He) may supplement current particle beam therapy strategies as they possess advantages in physical dose distribution over protons. To assess potential clinical advantages, a dose calculation module accounting for relative biological effectiveness (RBE) was developed and integrated into the treatment planning system Hyperion. Methods: Current knowledge on RBE of 4He together with linear energy transfer considerations motivated an empirical depth-dependent “zonal” RBE model. In the plateau region, a RBE of 1.0 was assumed, followed by an increasing RBE up to 2.8 at the Bragg-peak region, which was then kept constant over the fragmentation tail. To account for a variable proton RBE, the same model concept was also applied to protons with a maximum RBE of 1.6. Both RBE models were added to a previously developed pencil beam algorithm for physical dose calculation and included into the treatment planning system Hyperion. The implementation was validated against Monte Carlo simulations within a water phantom using γ-index evaluation. The potential benefits of 4He based treatment plans were explored in a preliminary treatment planning comparison (against protons) for four treatment sites, i.e., a prostate, a base-of-skull, a pediatric, and a head-and-neck tumor case. Separate treatment plans taking into account physical dose calculation only or using biological modeling were created for protons and 4He. Results: Comparison of Monte Carlo and Hyperion calculated doses resulted in a γ mean of 0.3, with 3.4% of the values above 1 and γ 1% of 1.5 and better. Treatment plan evaluation showed comparable planning target volume coverage for both particles, with slightly increased coverage for 4He. Organ at risk (OAR) doses were generally reduced using 4He, some by more than to 30%. Improvements of 4He over protons were more pronounced for treatment plans taking biological effects into account. All OAR doses were within tolerances specified in the QUANTEC report. Conclusions: The biological 4He model proposed above is a first approach matching biological data published so far. The advantage of 4He seems to lie in the reduction of dose to surrounding tissue and to OARs. Nevertheless, additional biological experiments and treatment planning studies with larger patient numbers and more tumor indications are necessary to study the possible benefits of helium ion beam therapy in detail.

Volumetric modulated arc therapy (VMAT) has found widespread clinical application in recent years. A large number of treatment planning studies have evaluated the potential for VMAT for different disease sites based on the currently available commercial implementations of VMAT planning. In contrast, literature on the underlying mathematical optimization methods used in treatment planning is scarce. VMAT planning represents a challenging large scale optimization problem. In contrast to fluence map optimization in intensity-modulated radiotherapy planning for static beams, VMAT planning represents a nonconvex optimization problem. In this paper, the authors review the state-of-the-art in VMAT planning from an algorithmic perspective. Different approaches to VMAT optimization, including arc sequencing methods, extensions of direct aperture optimization, and direct optimization of leaf trajectories are reviewed. Their advantages and limitations are outlined and recommendations for improvements are discussed.

Purpose A treatment planning/delivery QA tool using linac log files (LF) and Monte Carlo (MC) dose calculation is investigated as a standalone alternative to phantom-based patient-specific QA (ArcCHECK (AC)). Methods Delivering a variety of fields onto MapCHECK2 and ArcCHECK, diode sensitivity dependence on dose rate (in-field) and energy (primarily out-of-field) was quantified. AC and LF QAs were analyzed with respect to delivery complexity by delivering 12 × 12 cm static fields/arcs comprised of varying numbers of abutting sub-fields onto ArcCHECK. About 11 clinical dual-arc VMAT patients planned using Pinnacle's convolution-superposition (CS) were delivered on ArcCHECK and log file dose (LF-CS and LF-MC) calculated. To minimize calculation time, reduced LF-CS sampling (1/2/3/4° control point spacing) was investigated. Planned ("Plan") and LF-reconstructed CS and MC doses were compared with each other and AC measurement via statistical [mean ± StdDev(σ)] and gamma analyses to isolate dosimetric uncertainties and quantify the relative accuracies of AC QA and MC-based LF QA. Results Calculation and ArcCHECK measurement differed by up to 1.5% in-field due to variation in dose rate and up to 5% out-of-field. For the experimental segment-varying plans, despite CS calculation deviating by as much as 13% from measurement, Plan-MC and LF-MC doses generally matched AC measurement within 3%. Utilizing 1° control point spacing, 2%/2 mm LF-CS vs AC pass rates (97%) were slightly lower than Plan-CS vs AC pass rates (97.5%). Utilizing all log file samples, 2%/2 mm LF-MC vs AC pass rates (97.3%) were higher than Plan-MC vs AC (96.5%). Phantom-dependent, calculation algorithm-dependent (MC vs CS), and delivery error-dependent dose uncertainties were 0.8 ± 1.2%, 0.2 ± 1.1%, and 0.1 ± 0.9% respectively. Conclusion Reconstructing every log file sample with no increase in computational cost, MC-based LF QA is faster and more accurate than CS-based LF QA. Offering similar dosimetric accuracy compared to AC measurement, MC-based log files can be used for treatment planning QA.

INTRODUCTION: More than 50% of patients with locally advanced cervical cancer (LACC) have pathological nodes. Coverage probability (CovP) is a new planning technique allowing for relaxed dose at the boost periphery minimising collateral irradiation. The aim was to report the first early clinical outcome data for CovP based simultaneous integrated boost (SIB) in LACC. MATERIAL AND METHODS: Twenty-three consecutive node positive patients were analysed. FIGO stage IB2/IIB/IIIB/IVA/IVB was 1/14/3/1/4. Treatment was radio(chemo)therapy (RT) delivering 45 Gy/25 fx whole pelvis ± para-aortic region (PAN) using volumetric arc therapy (VMAT) followed by magnetic resonance imaging (MRI) guided brachytherapy. PAN RT (13 pts) was given if >2 nodes or if node(s) were present at the common iliac vessels or PAN. Nodal gross tumour volumes (GTV-N) were contoured on both PET-CT and MRI. Clinical target volume (CTV-N) was formed by fusion of GTV-NCT and GTV-NMRI. A 5-mm isotropic margin was used for planning target volume (PTV-N). Nodes in the small pelvis were boosted to 55.0 Gy/25 fx. Common iliac and para-aortic nodes received 57.5 Gy/25 fx. Planning aims for CovP were PTV-N D98 ≥ 90%, CTV-N D98 ≥ 100% and CTV-N D50 ≥ 101.5%. RESULTS: Seventy-four nodes were boosted. A consistent 5.0 ± 0.7 Gy dose reduction from CTV-N D98 to PTV-N D98 was obtained. In total, 73/74 nodes were in complete remission at 3 months PET-CT and MRI. Pelvic control was obtained in 21/23 patients. One patient (IB2, clear cell) had salvageable local disease, while another (IIB) failed in a boosted node. Two patients failed in un-irradiated PAN. One patient age 88 (IIIB) did not receive PAN RT, despite a common iliac node. The other (IIB) recurred above L1. Two further patients (IVB) failed systemically. CONCLUSION: Since complete remission at 3 months is predictive for favourable long-term nodal control, our study indicates that CovP for SIB is promising. INTRODUCTION: More than 50% of patients with locally advanced cervical cancer (LACC) have pathological nodes. Coverage probability (CovP) is a new planning technique allowing for relaxed dose at the boost periphery minimising collateral irradiation. The aim was to report the first early clinical outcome data for CovP based simultaneous integrated boost (SIB) in LACC. MATERIAL AND METHODS: Twenty-three consecutive node positive patients were analysed. FIGO stage IB2/IIB/IIIB/IVA/IVB was 1/14/3/1/4. Treatment was radio(chemo)therapy (RT) delivering 45 Gy/25 fx whole pelvis ± para-aortic region (PAN) using volumetric arc therapy (VMAT) followed by magnetic resonance imaging (MRI) guided brachytherapy. PAN RT (13 pts) was given if >2 nodes or if node(s) were present at the common iliac vessels or PAN. Nodal gross tumour volumes (GTV-N) were contoured on both PET-CT and MRI. Clinical target volume (CTV-N) was formed by fusion of GTV-NCT and GTV-NMRI. A 5-mm isotropic margin was used for planning target volume (PTV-N). Nodes in the small pelvis were boosted to 55.0 Gy/25 fx. Common iliac and para-aortic nodes received 57.5 Gy/25 fx. Planning aims for CovP were PTV-N D98 ≥ 90%, CTV-N D98 ≥ 100% and CTV-N D50 ≥ 101.5%. RESULTS: Seventy-four nodes were boosted. A consistent 5.0 ± 0.7 Gy dose reduction from CTV-N D98 to PTV-N D98 was obtained. In total, 73/74 nodes were in complete remission at 3 months PET-CT and MRI. Pelvic control was obtained in 21/23 patients. One patient (IB2, clear cell) had salvageable local disease, while another (IIB) failed in a boosted node. Two patients failed in un-irradiated PAN. One patient age 88 (IIIB) did not receive PAN RT, despite a common iliac node. The other (IIB) recurred above L1. Two further patients (IVB) failed systemically. CONCLUSION: Since complete remission at 3 months is predictive for favourable long-term nodal control, our study indicates that CovP for SIB is promising.

Purpose: The consistency between the AAA and XVMC algorithm in the treatment planning for RapidArc is investigated. While the majority of the radiation field is blocked by the MLC system, multiple small dose islands with MLC opened only slightly can be observed in one control point. This raises questions on how accurate the clinically used AAA algorithm in Eclipse is able to calculate RapidArc dose distributions. The fast Monte Carlo Code XVMC was used as a benchmark to test the AAA algorithm. Methods: RadpidArc plans of 25 patients were calculated with AAA and XVMC. The patient cohort consisted of 4 different cancer sites (H&N, upper abdominal, lung, prostate). Dose distributions, PTV and OAR coverage were compared looking at the PTV mean dose Dmean, the volume V95% of the PTV receiving 95% of the prescribed dose, the dose D95% delivered to 95% of the PTV Volume, the percentage PTV mean dose with respect to the prescribed dose Dmean/prescr and OAR mean dose.Results: The recalculation of RapidArc plans yielded good agreement of both calculation algorithms for treatment plans of all four cancer sites. PTV mean dose differences of AAA and XVMC were found to be in between −0.11% and 4.89% of the prescribed dose. The mean dose difference found was 0.48±0.77 Gy. Local dose differences were found when comparing dose distributions in regions of big mass density differences and in high dose regions. One head and neck plan and one prostate plan revealed significant differences in PTV coverage (ΔDmean=3.25 Gy) and OAR mean dose (prostate mean dose −13.71 Gy) respectively. Conclusions: The vast majority of treatment plans calculated with the AAA algorithm were found to agree within the expected and acceptable tolerances compared to XVMC results. Nevertheless in some cases dose differences were observed that could be of clinical significance. This work was funded by a Varian grant. Wolfram Laub is working in the physics group of CMS.

BACKGROUND AND PURPOSE:Large anatomical changes during radiotherapy are seen for a large proportion of lung cancer patients. We investigate the applicability of a decision support protocol for photon therapy in a proton therapy setting.MATERIAL AND METHODS:Twenty-three consecutive NSCLC patients treated with adaptive photon therapy were retrospectively planned using IMPT. The adaptive protocol was based on geometrical measures of target positioning and large anatomical changes as shown on daily CBCT scans. Two surveillance CT-scans were acquired during the treatment course. The consequences of anatomical changes were evaluated by recalculating the proton plans on the surveillance scans. The CTV receiving 95% of the prescribed dose was analysed.RESULTS:Fourteen (61%) patients needed adaptations when treated with protons, given that 95% of the CTV must be covered by 95% of the dose. In comparison, no patients needed adaptation when treated with photons using this criterion. The adaptive protocol was found to identify patients with large target under-dosage for proton therapy (six patients). Additionally, target under-dosage was observed for eight patients with non-rigid changes up to 15mm in the positioning of the bones.CONCLUSIONS:Proton therapy for loco-regional lung cancer demands daily imaging and therapy adaptation for a high proportion of patients. BACKGROUND AND PURPOSE: Large anatomical changes during radiotherapy are seen for a large proportion of lung cancer patients. We investigate the applicability of a decision support protocol for photon therapy in a proton therapy setting.MATERIAL AND METHODS: Twenty-three consecutive NSCLC patients treated with adaptive photon therapy were retrospectively planned using IMPT. The adaptive protocol was based on geometrical measures of target positioning and large anatomical changes as shown on daily CBCT scans. Two surveillance CT-scans were acquired during the treatment course. The consequences of anatomical changes were evaluated by recalculating the proton plans on the surveillance scans. The CTV receiving 95% of the prescribed dose was analysed.RESULTS: Fourteen (61%) patients needed adaptations when treated with protons, given that 95% of the CTV must be covered by 95% of the dose. In comparison, no patients needed adaptation when treated with photons using this criterion. The adaptive protocol was found to identify patients with large target under-dosage for proton therapy (six patients). Additionally, target under-dosage was observed for eight patients with non-rigid changes up to 15mm in the positioning of the bones.CONCLUSIONS: Proton therapy for loco-regional lung cancer demands daily imaging and therapy adaptation for a high proportion of patients.

Background and purpose To prospectively assess the prognostic value of tumour hypoxia determined by dynamic [ 18 F]Fluoromisonidazole (dynFMISO) PET/CT, and to evaluate both feasibility and toxicity in patients with locally advanced squamous cell carcinomas of the head and neck (LASCCHN) treated with dynFMISO image-guided dose escalation (DE) using dose-painting by contours. Patients and methods We present a planned interim analysis of a randomized phase II trial. N =25 patients with LASCCHN received baseline dynFMISO PET/CT to derive hypoxic volumes (HV). Patients with tumour hypoxia were randomized into standard radiochemotherapy (stdRT) (70Gy/35 fractions) or DE (77Gy/35 fractions) to the HV. Patients with non-hypoxic tumours were treated with stdRT. Loco-regional control (LRC) in hypoxic patients randomized to stdRT was compared to non-hypoxic patients. Feasibility and toxicity were analysed for patients in the DE arm and compared to stdRT. Results With a mean follow-up of 27months, LRC in hypoxic patients receiving stdRT ( n =10) was significantly worse compared to the non-hypoxic group ( n =5) (2y-LRC 44.4% versus 100%, p =0.048). The respective LRC for the DE group ( n =10) was 70.0%. Treatment compliance as well as acute and late toxicity did not show significant differences between the DE and the standard dose arms. Conclusion Tumour hypoxia determined by baseline dynFMISO PET/CT is associated with a high risk of local failure in patients with LASCCHN. First data suggest that DE to HV is feasible without excess toxicity.

Background: Autocontouring improves workflow in computed tomography (CT)-based dose planning, but could also potentially play a role for optimal use of daily cone beam CT (CBCT) in adaptive radiotherapy. This study aims to determine the accuracy of a deformable image registration (DIR) algorithm for organs at risk (OAR) in the neck region, when applied to CBCT. Material and methods: For 30 head and neck cancer (HNC) patients 14 OARs including parotid glands, swallowing structures and spinal cord were delineated. Contours were propagated by DIR from CT to the CBCTs of the first and last treatment fraction. An indirect approach, propagating contours to the first CBCT and from there to the last CBCT was also tested. Propagated contours were compared to manually corrected contours by Dice similarity coefficient (DSC) and Hausdorff distance (HD). Dose was recalculated on CBCTs and dosimetric consequences of uncertainties in DIR were reviewed. Results: Mean DSC values of ≥0.8 were considered adequate and were achieved in tongue base (0.91), esophagus (0.85), glottic (0.81) and supraglottic larynx (0.83), inferior pharyngeal constrictor muscle (0.84), spinal cord (0.89) and all salivary glands in the first CBCT. For the last CBCT by direct propagation, adequate DSC values were achieved for tongue base (0.85), esophagus (0.84), spinal cord (0.87) and all salivary glands. Using indirect propagation only tongue base (0.80) and parotid glands (0.87) were ≥0.8. Mean relative dose difference between automated and corrected contours was within ±2.5% of planed dose except for esophagus inlet (-4.5%) and esophagus (5.0%) for the last CBCT using indirect propagation. Conclusion: Compared to manually corrected contours, the DIR algorithm was accurate for use in CBCT images of HNC patients and the minor inaccuracies had little consequence for mean dose in most clinically relevant OAR. The method can thus enable a more automated segmentation of CBCT for use in adaptive radiotherapy. Radiotherapy is the primary treatment for most patients with squamous cell carcinoma of the head and neck and about 80% of all patients receive radiotherapy either alone or in combination with surgery and chemotherapy. Relatively high loco-regional control rates are obtained, but at the expense of substantial side effects, of which xerostomia and swallowing dysfunction are the most prominent [1–4 Jensen K, Jensen AB, Grau C. A cross sectional quality of life study of 116 recurrence free head and neck cancer patients. The first use of EORTC H&N35 in Danish. Acta Oncol 2006;45:28–37. Jensen K, Lambertsen K, Grau C. Late swallowing dysfunction and dysphagia after radiotherapy for pharynx cancer: frequency, intensity and correlation with dose and volume parameters. Radiother Oncol 2007;85:74–82. Jensen K, Overgaard M, Grau C. Morbidity after ipsilateral radiotherapy for oropharyngeal cancer. Radiother Oncol 2007;85:90–7. Mortensen HR, Overgaard J, Specht L, et al. Prevalence and peak incidence of acute and late normal tissue morbidity in the DAHANCA 6&7 randomised trial with accelerated radiotherapy for head and neck cancer. Radiother Oncol 2012;103:69–75. ]. The observed morbidity is to a large extent due to inadvertent irradiation of normal tissues in the vicinity of the clinical target, including salivary glands and swallowing structures [5 Eisbruch A, Ten Haken RK, Kim HM, et al. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 1999;45:577–87. [CrossRef], [PubMed], [Web of Science ®] ,6 Langendijk JA, Doornaert P, Rietveld DH, et al. A predictive model for swallowing dysfunction after curative radiotherapy in head and neck cancer. Radiother Oncol 2009;90:189–95. [CrossRef], [PubMed], [Web of Science ®] ]. The irradiation of normal structures are in part a result of applied margins around the clinical target to counteract multiple uncertainties, including daily setup errors, target definition, and interfraction changes in the anatomy. Several studies indicate that the anatomical changes in these patients over the course of treatment can be substantial [7–9 Barker JL, Garden AS, Ang KK, et al. Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system. Int J Radiat Oncol Biol Phys 2004;59:960–70. Castadot P, Lee JA, Geets X, et al. Adaptive radiotherapy of head and neck cancer. Semin Radiat Oncol 2010;20:84–93. Ricchetti F, Wu B, McNutt T, et al. Volumetric change of selected organs at risk during IMRT for oropharyngeal cancer. Int J Radiat Oncol Biol Phys 2011;80:161–8. ]. Repeated imaging and replanning, even with a single mid-treatment computed tomography (CT), can significantly improve tumor coverage and normal tissue sparing [10–12 Hansen EK, Bucci MK, Quivey JM, et al. Repeat CT imaging and replanning during the course of IMRT for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2006;64:355–62. Schwartz DL, Garden AS, Thomas J, et al. Adaptive radiotherapy for head-and-neck cancer: initial clinical outcomes from a prospective trial. Int J Radiat Oncol Biol Phys 2012;83:986–93. Schwartz DL, Garden AS, Shah SJ, et al. Adaptive radiotherapy for head and neck cancer-dosimetric results from a prospective clinical trial. Radiother Oncol 2013;106:80–4. ]. Replanning requires repeated contouring of target volumes and normal tissues, which remains a time consuming task, even for experienced clinicians. There is a growing array of commercial software aimed at easing this burden by automatic contouring, utilizing novel deformable image registration (DIR) techniques to propagate one set of contours from an initial CT to fit the anatomy of a second CT [13 Elstrøm UV, Wysocka BA, Muren LP, et al. Daily kV cone-beam CT and deformable image registration as a method for studying dosimetric consequences of anatomic changes in adaptive IMRT of head and neck cancer. Acta Oncol 2010;49:1101–8. [Taylor & Francis Online], [Web of Science ®] ,14 Østergaard Noe K, De Senneville BD, Elstrøm UV, et al. Acceleration and validation of optical flow based deformable registration for image-guided radiotherapy. Acta Oncol 2008;47:1286–93. [Taylor & Francis Online], [Web of Science ®] ]. Such techniques have been found to reduce contouring time considerably [15 La Macchia M, Fellin F, Amichetti M, et al. Systematic evaluation of three different commercial software solutions for automatic segmentation for adaptive therapy in head-and-neck, prostate and pleural cancer. Radiat Oncol 2012;7:160. [CrossRef], [PubMed], [Web of Science ®] ,16 Teguh DN, Levendag PC, Voet PW, et al. Clinical validation of atlas-based auto-segmentation of multiple target volumes and normal tissue (swallowing/mastication) structures in the head and neck. Int J Radiat Oncol Biol Phys 2011;81:950–7. [CrossRef], [PubMed], [Web of Science ®] ]. Today, in-room daily imaging with cone beam CT (CBCT) allows more convenient soft tissue volumetric information to be potentially utilized in an adaptive approach. Previous studies have shown that if the image quality is sufficiently optimized, it is possible to contour soft tissue organs at risk (OAR), including spinal cord, salivary glands and swallowing structures [17 Elstrøm UV, Muren LP, Petersen JB, et al. Evaluation of image quality for different kV cone-beam CT acquisition and reconstruction methods in the head and neck region. Acta Oncol 2011;50:908–17. [Taylor & Francis Online], [Web of Science ®] ]. With Hounsfield unit calibration, the segmented CBCT can subsequently be used for dose calculation, with an overall precision of 2–3% for clinically relevant dose-volume parameters compared to standard CT-based dose planning [18 Elstrøm U, Olsen S, Wysocka B, et al. Cone-beam CT-based radiotherapy planning of head and neck cancer. Radiother Oncol 2012;103. [CrossRef] ]. Combining DIR techniques with the daily CBCT imaging could potentially enable prospective monitoring of volumetric and dosimetric changes over the course of treatment, improving the possibilities for plan adaptation. Few studies concerning this have been published to date [19 Hou J, Guerrero M, Chen W, et al. Deformable planning CT to cone-beam CT image registration in head-and-neck cancer. Med Phys Apr 2011;38:2088–94. [CrossRef], [PubMed], [Web of Science ®] ]. If feasible, this approach may also replace the mid-treatment CT as an added benefit. The purpose of this study was to determine the contouring accuracy of a software solution for unsupervised segmentation of OARs in daily CBCTs of head and neck cancer (HNC) patients.

Background and purpose Advanced lung cancer patients experience anatomical changes during radiotherapy. Uncorrected, these may lead to lower tumor dose, but can be corrected for by adaptive radiotherapy (ART). Material and methods Anatomical changes in 233 patients were monitored online on cone-beam CT-scans used for daily soft-tissue matching. If systematic changes above the pre-defined trigger criteria were observed, a new CT-scan, delineations, and treatment plan were made, restoring the intended dose distribution. Dose distributions with and without adaptation were compared. The first fifty ART patients were given two surveillance CT-scans during radiotherapy. These were used to evaluate delivered dose for patients without adaptation. The first fifty-two patients treated with ART were also compared with 52 pre-ART patients to evaluate the reduction in normal tissue doses. Results Sixty-three patients (27%) were adapted. Seventy-five per cent of all adaptations correctly adjusted for a decrease in tumor dose. Eighty-seven surveillance CT-scans were obtained for the first fifty patients and in only 2% of the cases, a decrease in tumor coverage (ΔV95%CTV > 1%) was observed. With ART we observed a significant decrease in lung dose (MLD reduced from 14.6 Gy to 12.6 Gy on average). Conclusions Implementation of soft-tissue match combined with ART decreased the lung dose. The trigger criteria used correctly identified all but one (98%) of the patients requiring adaptation with a false positive rate of 20%.

Background The purpose of this study is to investigate the potential to reduce exposure of the contralateral hippocampus in radiotherapy for glioblastoma using volumetric modulated arc therapy (VMAT). Methods Datasets of 27 patients who had received 3D conformal radiotherapy (3D-CRT) for glioblastoma with a prescribed dose of 60Gy in fractions of 2Gy were included in this planning study. VMAT plans were optimized with the aim to reduce the dose to the contralateral hippocampus as much as possible without compromising other parameters. Hippocampal dose and treatment parameters were compared to the 3D-CRT plans using the Wilcoxon signed-rank test. The influence of tumour location and PTV size on the hippocampal dose was investigated with the Mann–Whitney-U-test and Spearman’s rank correlation coefficient. Results The median reduction of the contralateral hippocampus generalized equivalent uniform dose (gEUD) with VMAT was 36 % compared to the original 3D-CRT plans (p

This study reports on the treatment techniques, toxicity, and outcome of pelvic intensity-modulated radiotherapy (IMRT) for lymph node-positive prostate cancer (LNPPC, T1-4, c/pN1 cM0). Pelvic IMRT to 45–50.4 Gy was applied in 39 cases either after previous surgery of involved lymph nodes (n = 18) or with a radiation boost to suspicious nodes (n = 21) with doses of 60–70 Gy, usually combined with androgen deprivation (n = 37). The prostate and seminal vesicles received 70–74 Gy. In cases of previous prostatectomy, prostatic fossa and remnants of seminal vesicles were given 66–70 Gy. Treatment-related acute and late toxicity was graded according to the RTOG criteria. Acute radiation-related toxicity higher than grade 2 occurred in 2 patients (with the need for urinary catheter/subileus related to adhesions after surgery). Late toxicity was mild (grade 1–2) after a median follow-up of 70 months. Over 50% of the patients reported no late morbidity (grade 0). PSA control and cancer-specific survival reached 67% and 97% at over 5 years. Pelvic IMRT after the removal of affected nodes or with a radiation boost to clinically positive nodes led to an acceptable late toxicity (no grade 3/4 events), thus justifying further evaluation of this approach in a larger cohort.

The standard treatment for stage I non-small cell lung cancer (NSCLC) is lobectomy. However, a considerable number of patients are not eligible for standard lung surgery due to poor pulmonary function or comorbidities. We evaluated the efficacy and tolerability of intensity-modulated stereotactic radiotherapy (IMSRT) with moderate hypofractionation for these patients. Twelve patients were selected for IMSRT. 4D-CT planning was performed by gating CT-scanning positioning. The applied doses ranged between 10x4.5 Gy (80% ID) (N=1), 12x4.5 Gy (95% ID) (N=1) and 10x5.5 Gy (95% ID) (N=10). Long-term follow-up was performed including spirometry and CT for evaluation of local, locoregional and distant control. Even in patients with poor pulmonary function IMRST was safe and well tolerated. No severe acute adverse effects were observed. Estimated local control at 2 years was 90%. Moreover, IMSRT does not induce a significant deterioration of pulmonary function. IMRST is safe and feasible even for patients with very poor pulmonary function. The applied dose provides a high local control rate, although the biological equivalent dose (BED) is lower compared to the average of other SRT regimens. Therefore, IMRST may be an efficient alternative for all NSCLC stage I patients with contraindications to standard lobectomy especially in patients with small tumors in high-risk localisations.

We present a method of modeling dosimetric consequences of organ deformation and correlated motion of adjacent organ structures in radiotherapy. Based on a few organ geometry samples and the respective deformation fields as determined by deformable registration, principal component analysis (PCA) is used to create a low-dimensional parametric statistical organ deformation model (Söhn et al 2005 Phys. Med. Biol. 50 5893-908). PCA determines the most important geometric variability in terms of eigenmodes, which represent 3D vector fields of correlated organ deformations around the mean geometry. Weighted sums of a few dominating eigenmodes can be used to simulate synthetic geometries, which are statistically meaningful inter- and extrapolations of the input geometries, and predict their probability of occurrence. We present the use of PCA as a versatile treatment simulation tool, which allows comprehensive dosimetric assessment of the detrimental effects that deformable geometric uncertainties can have on a planned dose distribution. For this, a set of random synthetic geometries is generated by a PCA model for each simulated treatment course, and the dose of a given treatment plan is accumulated in the moving tissue elements via dose warping. This enables the calculation of average voxel doses, local dose variability, dose-volume histogram uncertainties, marginal as well as joint probability distributions of organ equivalent uniform doses and thus of TCP and NTCP, and other dosimetric and biologic endpoints. The method is applied to the example of deformable motion of prostate/bladder/rectum in prostate IMRT. Applications include dosimetric assessment of the adequacy of margin recipes, adaptation schemes, etc, as well as prospective 'virtual' evaluation of the possible benefits of new radiotherapy schemes.

Tumour hypoxia can be assessed by positron emission tomography (PET) using radiotracers like [(18)F]fluoromisonidazole (Fmiso). The purpose of this work was to independently investigate the influence of chronic and acute hypoxia on the retention of Fmiso on the microscale. This was approached by modelling and simulating tissue oxygenation and Fmiso dynamics on the microscale based on tumour histology. Diffusion of oxygen and Fmiso molecules in tissue- and oxygen-dependent Fmiso binding were included in the model. Moreover, a model of fluctuating vascular oxygen tension was incorporated to theoretically predict the effects of acute hypoxia. Simulated tissue oxygen tensions (PO(2)) are strongly influenced by the modelled periodical fluctuations (period 40 min, total amplitude 10 mmHg and mean 35 mmHg). Fluctuations led to variations in mean PO(2) of up to 41% and in the hypoxic fraction (PO(2)?

Treatment planning tools that use biologically related models for plan optimization and/or evaluation are being introduced for clinical use. A variety of dose-response models and quantities along with a series of organ-specific model parameters are included in these tools. However, due to various limitations, such as the limitations of models and available model parameters, the incomplete understanding of dose responses, and the inadequate clinical data, the use of biologically based treatment planning system (BBTPS) represents a paradigm shift and can be potentially dangerous. There will be a steep learning curve for most planners. The purpose of this task group is to address some of these relevant issues before the use of BBTPS becomes widely spread. In this report, the authors (1) discuss strategies, limitations, conditions, and cautions for using biologically based models and parameters in clinical treatment planning; (2) demonstrate the practical use of the three most commonly used commercially available BBTPS and potential dosimetric differences between biologically model based and dose-volume based treatment plan optimization and evaluation; (3) identify the desirable features and future directions in developing BBTPS; and (4) provide general guidelines and methodology for the acceptance testing, commissioning, and routine quality assurance (QA) of BBTPS.