18F-FDG-PET guided vs whole tumour radiotherapy dose escalation in patients with locally advanced non-small cell lung cancer (PET-Boost): Results from a randomised clinical trial.

BACKGROUND AND PURPOSE: We aimed to assess if radiation dose escalation to either the whole primary tumour, or to an 18F-FDG-PET defined subvolume within the primary tumour known to be at high risk of local relapse, could improve local control in patients with locally advanced non-small-cell lung cancer. MATERIALS AND METHODS: Patients with inoperable, stage II-III NSCLC were randomised (1:1) to receive dose-escalated radiotherapy to the whole primary tumour or a PET-defined subvolume, in 24 fractions. The primary endpoint was freedom from local failure (FFLF), assessed by central review of CT-imaging. A phase II 'pick-the-winner' design (alpha = 0.05; beta = 0.80) was applied to detect a 15 % increase in FFLF at 1-year. CLINICALTRIALS: gov:NCT01024829. RESULTS: 150 patients were enrolled. 54 patients were randomised to the whole tumour group and 53 to the PET-subvolume group. The trial was closed early due to slow accrual. Median dose/fraction to the boosted volume was 3.30 Gy in the whole tumour group, and 3.50 Gy in the PET-subvolume group. The 1-year FFLF rate was 97 % (95 %CI 91-100) in whole tumour group, and 91 % (95 %CI 82-100) in the PET-subvolume group. Acute grade ≥ 3 adverse events occurred in 23 (43 %) and 20 (38 %) patients, and late grade ≥ 3 in 12 (22 %) and 17 (32 %), respectively. Grade 5 events occurred in 19 (18 %) patients in total, of which before disease progression in 4 (7 %) in the whole tumour group, and 5 (9 %) in the PET-subvolume group. CONCLUSION: Both strategies met the primary objective to improve local control with 1-year rates. However, both strategies led to unexpected high rates of grade 5 toxicity. Dose differentiation, improved patient selection and better sparing of central structures are proposed to improve dose-escalation strategies.

Reduction of systematic dosimetric uncertainties in volumetric modulated arc therapy triggered by patient-specific quality assurance.

BACKGROUND AND PURPOSE: Dosimetric patient-Specific Quality Assurance (PSQA) data contain in addition to cases with alerts, many cases without alerts. The aim of this study was to present a procedure to investigate long-term trend analysis of the complete set of PSQA data for the presence of site-specific deviations to reduce underlying systematic dose uncertainties. MATERIALS AND METHODS: The procedure started by analysing a large set of prostate Volumetric Modulated Arc Therapy (VMAT) PSQA data obtained by comparing 3D electronic portal image device (EPID)_based in vivo dosimetry measurements with dose values predicted by the Treatment Planning System (TPS). If systematic deviations were present, several actions were required. These included confirmation of these deviations with an independent dose verification system for which a 2D detector array in a phantom was used, and analysing calculated with measured PSQA data, or delivery machine characteristics. Further analysis revealed that the under-dosage correlated with plan complexity and coincided with changes in clinically applied planning techniques. RESULTS: Prostate VMAT PSQA data showed an under-dosage gradual increasing to about 2% in 3 years, which was confirmed by the measurements with the 2D detector array in a phantom. The implementation of new beam fits in the TPS led to a reduction of the observed deviations. CONCLUSION: Long-term analysis of site-specific PSQA data is a useful method to monitor incremental changes in a radiotherapy department due to various changes in the treatment planning and delivery of prostate VMAT, and may lead to a reduction of systematic dose uncertainties in complex treatments.

The impact of anatomical changes during photon or proton based radiation treatment on tumor dose in glioblastoma dose escalation trials.

PURPOSE/OBJECTIVE: Most dose-escalation trials in glioblastoma patients integrate the escalated dose throughout the standard course by targeting a specific subvolume. We hypothesize that anatomical changes during irradiation may affect the dose coverage of this subvolume for both proton- and photon-based radiotherapy. MATERIAL AND METHODS: For 24 glioblastoma patients a photon- and proton-based dose escalation treatment plan (of 75 Gy/30 fr) was simulated on the dedicated radiotherapy planning MRI obtained before treatment. The escalated dose was planned to cover the resection cavity and/or contrast enhancing lesion on the T1w post-gadolinium MRI sequence. To analyze the effect of anatomical changes during treatment, we evaluated on an additional MRI that was obtained during treatment the changes of the dose distribution on this specific high dose region. RESULTS: The median time between the planning MRI and additional MRI was 26 days (range 16-37 days). The median time between the planning MRI and start of radiotherapy was relatively short (7 days, range 3-11 days). In 3 patients (12.5%) changes were observed which resulted in a substantial deterioration of both the photon and proton treatment plans. All these patients underwent a subtotal resection, and a decrease in dose coverage of more than 5% and 10% was observed for the photon- and proton-based treatment plans, respectively. CONCLUSION: Our study showed that only for a limited number of patients anatomical changes during photon or proton based radiotherapy resulted in a potentially clinically relevant underdosage in the subvolume. Therefore, volume changes during treatment are unlikely to be responsible for the negative outcome of dose-escalation studies.

Characterization of automatic treatment planning approaches in radiotherapy.

BACKGROUND AND PURPOSE: Automatic approaches are widely implemented to automate dose optimization in radiotherapy treatment planning. This study systematically investigates how to configure automatic planning in order to create the best possible plans. MATERIALS AND METHODS: Automatic plans were generated using protocol based automatic iterative optimization. Starting from a simple automation protocol which consisted of the constraints for targets and organs at risk (OAR), the performance of the automatic approach was evaluated in terms of target coverage, OAR sparing, conformity, beam complexity, and plan quality. More complex protocols were systematically explored to improve the quality of the automatic plans. The protocols could be improved by adding a dose goal on the outer 2 mm of the PTV, by setting goals on strategically chosen subparts of OARs, by adding goals for conformity, and by limiting the leaf motion. For prostate plans, development of an automated post-optimization procedure was required to achieve precise control over the dose distribution. Automatic and manually optimized plans were compared for 20 head and neck (H&N), 20 prostate, and 20 rectum cancer patients. RESULTS: Based on simple automation protocols, the automatic optimizer was not always able to generate adequate treatment plans. For the improved final configurations for the three sites, the dose was lower in automatic plans compared to the manual plans in 12 out of 13 considered OARs. In blind tests, the automatic plans were preferred in 80% of cases. CONCLUSIONS: With adequate, advanced, protocols the automatic planning approach is able to create high-quality treatment plans.

Predicting and implications of target volume changes of brain metastases during fractionated stereotactic radiosurgery.

OBJECTIVE: To study the impact of target volume changes in brain metastases during fractionated stereotactic radiosurgery (fSRS) and identify patients that benefit from MRI guidance. MATERIAL AND METHODS: For 15 patients (18 lesions) receiving fSRS only (fSRSonly) and 19 patients (20 lesions) receiving fSRS postoperatively (fSRSpostop), a treatment planning MRI (MR0) and repeated MRI during treatment (MR1) were acquired. The impact of target volume changes on the target coverage was analyzed by evaluating the planned dose distribution (based on MR0) on the planning target volume (PTV) during treatment as defined on MR1. The predictive value of target volume changes before treatment (using the diagnostic MRI (MRD)) was studied to identify patients that experienced the largest changes during treatment. RESULTS: Target volume changes during fSRS did result in large declines of the PTV dose coverage up to -34.8% (median = 3.2%) for fSRSonly patients. For fSRSpostop the variation and declines were smaller (median PTV dose coverage change = -0.5% (-4.5% to 1.9%)). Target volumes changes did also impact the minimum dose in the PTV (fSRSonly; -2.7 Gy (-16.5 to 2.3 Gy), fSRSpostop; -0.4 Gy (-4.2 to 2.5 Gy)). Changes in target volume before treatment (i.e. seen between the MRD and MR0) predicted which patients experienced the largest dose coverage declines during treatment. CONCLUSION: Target volume changes in brain metastases during fSRS can result in worsening of the target dose coverage. Patients benefiting the most from a repeated MRI during treatment could be identified before treatment.

SBRT combined with concurrent chemoradiation in stage III NSCLC: Feasibility study of the phase I Hybrid trial.

PURPOSE: To assess the technical and clinical feasibility of the phase I Hybrid trial (NCT01933568), combining SBRT of the primary tumor (PT) and fractionated radiotherapy (FRT) to the lymph nodes (LN). MATERIALS AND METHODS: Ten patients with stage III NSCLC with a peripheral PT < 5 cm were prospectively selected. The EQD2 corrected normal tissue dose parameters of the FRT plan of 24×2.75 Gy to PT and 24×2.42 Gy to LN (IMRT) was compared with 3×18 Gy on the PT and 24×2.42 Gy on the LN (VMAT) using a Wilcoxon signed-rank test. To anticipate differential motion between PT and LN, worst-case scenarios for OAR were calculated. Electronic portal imaging device (EPID) dosimetry analysis was performed to rule out dosimetric errors during delivery. RESULTS: The Hybrid plans revealed a significant decrease of esophagus EUD n = 0.13, lung V5 and V20 and a significant increase in Dmax of the PRV of the mediastinal envelope. Plans were robust against differential motion of 5 mm between PT and LN in 8 patients and failed in 2 patients due to spinal cord constraints. Average pass rates were ≥87% for EPID dosimetry. CONCLUSIONS: SBRT and FRT could be combined within the given OAR constraints. Safety will be assessed in the Hybrid trial.

The acute and late toxicity results of a randomized phase II dose-escalation trial in non-small cell lung cancer (PET-boost trial).

BACKGROUND AND PURPOSE: The PET-boost randomized phase II trial (NCT01024829) investigated dose-escalation to the entire primary tumour or redistributed to regions of high pre-treatment FDG-uptake in inoperable non-small cell lung cancer (NSCLC) patients. We present a toxicity analysis of the 107 patients randomized in the study. MATERIALS AND METHODS: Patients with stage II-III NSCLC were treated with an isotoxic integrated boost of ≥72 Gy in 24 fractions, with/without chemotherapy and strict dose limits. Toxicity was scored until death according to the CTCAEv3.0. RESULTS: 77 (72%) patients were treated with concurrent chemoradiotherapy. Acute and late ≥G3 occurred in 41% and 25%. For concurrent (C) and sequential or radiotherapy alone (S), the most common acute ≥G3 toxicities were: dysphagia in 14.3% (C) and 3.3% (S), dyspnoea in 2.6% (C) and 6.7% (S), pneumonitis in 0% (C) and 6.7% (S), cardiac toxicity in 6.5% (C) and 3.3% (S). Seventeen patients died of which in 13 patients a possible relation to treatment could not be excluded. In 10 of these 13 patients progressive disease was scored. Fatal pulmonary haemorrhages and oesophageal fistulae were observed in 9 patients. CONCLUSION: Personalized dose-escalation in inoperable NSCLC patients results in higher acute and late toxicity compared to conventional chemoradiotherapy. The toxicity, however, was within the boundaries of the pre-defined stopping rules.

Independent knowledge-based treatment planning QA to audit Pinnacle autoplanning.

BACKGROUND AND PURPOSE: With the advent of automatic treatment planning options like Pinnacle's Autoplanning (PAP), the challenge arises how to assess the quality of a plan that no dosimetrist did work on. The aim of this study was to assess plan quality consistency of PAP prostate cancer patients in clinical practice. MATERIALS AND METHODS: 100 prostate cancer patients were included from NKI and 129 from RadboudUMC (RUMC). Per institute a previously developed [1] treatment planning QA model, based on overlap volume histograms, was trained on PAP plans to predict achievable dose metrics which were then compared to the clinical PAP plans. A threshold of 3 Gy (DVH dose parameters)/3% (DVH volume parameters) was used to detect outliers. For the outlier plans, the PAP technique was adjusted with the aim of meeting the threshold. RESULTS: The average difference between the prediction and the clinically achieved value was <0.5 Gy (mean dose parameters) and <1.2% (volume parameters), with standard deviation of 1.9 Gy/1.5% respectively. We found 8% (NKI)/25% (RUMC) of patients to exceed the 3 Gy/3% threshold, with deviations up to 6.7 Gy (mean dose rectum) and 6% (rectal wall V64Gy). In all cases the plans could be improved to fall within the thresholds, without compromising the other dose metrics. CONCLUSION: Independent treatment planning QA was used successfully to assess the quality of clinical PAP in a multi-institutional setting. Respectively 8% and 25% suboptimal clinical PAP plans were detected that all could be improved with replanning. Therefore we recommend the use of independent treatment plan QA in combination with PAP for prostate cancer patients.

A robust volumetric arc therapy planning approach for breast cancer involving the axillary nodes.

We quantify the robustness of a proposed volumetric-modulated arc therapy (VMAT) planning and treatment technique for radiotherapy of breast cancer involving the axillary nodes. The proposed VMAT technique is expected to be more robust to breast shape changes and setup errors, yet maintain the improved conformity of VMAT compared to our current standard technique that uses tangential intensity-modulated radiation therapy (IMRT) fields. Treatment plans were created for 10 patients. To account for anatomical variation, planning was carried out on a computed tomography (CT) with an expanded breast, followed by segment weight optimization (SWO) on the original planning CT (VMAT + SWO). For comparison purposes, tangential field IMRT plans and conventional VMAT (cVMAT) plans were also created. Anatomical changes (expansion and contraction of the breast) and setup errors were simulated to quantify changes in target coverage, target maximum, and organ-at-risk (OAR) doses. Finally, robustness was assessed by calculating the actual delivered dose for each fraction using cone-beam CT images acquired during treatment. Target coverage of VMAT + SWO was shown to be significantly more robust compared to cVMAT technique, against anatomical variations and setup errors. Sensitivity of the clinical target volume (CTV) V95% is -5%/cm of expansion for the proposed technique, which is identical to the IMRT technique and much lower than the -22%/cm for cVMAT. Results are similar for setup errors. OAR doses are mostly insensitive to anatomical variations and the OAR sensitivity to setup variations does not depend on the planning technique. The results are confirmed by dose distributions recalculated on cone-beam CT, showing that for VMAT + SWO the CTV V95% remains within 2.5% of the planned value, whereas it deviates by up to 7% for cVMAT. A practical VMAT planning technique is developed, which is robust to daily anatomical variations and setup errors.

Adapting automated treatment planning configurations across international centres for prostate radiotherapy.

BACKGROUND AND PURPOSE: Automated configurations are increasingly utilised for radiotherapy treatment planning. This study investigates whether automated treatment planning configurations are adaptable across clinics with different treatment planning protocols for prostate radiotherapy. MATERIAL AND METHODS: The study comprised three participating centres, each with pre-existing locally developed prostate AutoPlanning configurations using the Pinnacle3® treatment planning system. Using a three-patient training dataset circulated from each centre, centres modified local prostate configurations to generate protocol compliant treatment plans for the other two centres. Each centre applied modified configurations on validation datasets distributed from each centre (10 patients from 3 centres). Plan quality was assessed through DVH analysis and protocol compliance. RESULTS: All treatment plans were clinically acceptable, based off relevant treatment protocol. Automated planning configurations from Centre's A and B recorded 2 and 18 constraint and high priority deviations respectively. Centre C configurations recorded no high priority deviations. Centre A configurations produced treatment plans with superior dose conformity across all patient PTVs (mean = 1.14) compared with Centre's B and C (mean = 1.24 and 1.22). Dose homogeneity was consistent between all centre's configurations (mean = 0.083, 0.077, and 0.083 respectively). CONCLUSIONS: This study demonstrates that automated treatment planning configurations can be shared and implemented across multiple centres with simple adaptations to local protocols.

Heart dose associated with overall survival in locally advanced NSCLC patients treated with hypofractionated chemoradiotherapy.

Association of heart dose and overall survival was investigated in a cohort including 469 locally-advanced NSCLC patients receiving daily low-dose hypofractionated chemo-radiotherapy. Significant associations were found over a range of dose parameters. Multivariate analysis showed significant associations of heart_V2Gy:HR=1.007%-1 (95% CI:1.002-1.013; p=0.006), age:HR=1.026year-1 (1.011-1.042; p=0.001) and GTV volume:HR=1.001cc-1 (1.000-1.002; p=0.006) with overall survival.

Head and Neck Margin Reduction With Adaptive Radiation Therapy: Robustness of Treatment Plans Against Anatomy Changes.

PURPOSE: We set out to investigate loss of target coverage from anatomy changes in head and neck cancer patients as a function of applied safety margins and to verify a cone beam computed tomography (CBCT)-based adaptive strategy with an average patient anatomy to overcome possible target underdosage. METHODS AND MATERIALS: For 19 oropharyngeal cancer patients, volumetric modulated arc therapy treatment plans (2 arcs; simultaneous integrated boost, 70 and 54.25 Gy; 35 fractions) were automatically optimized with uniform clinical target volume (CTV)-to-planning target volume margins of 5, 3, and 0 mm. We applied b-spline CBCT-to-computed tomography (CT) deformable registration to allow recalculation of the dose on modified CT scans (planning CT deformed to daily CBCT following online positioning) and dose accumulation in the planning CT scan. Patients with deviations in primary or elective CTV coverage >2 Gy were identified as candidates for adaptive replanning. For these patients, a single adaptive intervention was simulated with an average anatomy from the first 10 fractions. RESULTS: Margin reduction from 5 mm to 3 mm to 0 mm generally led to an organ-at-risk (OAR) mean dose (Dmean) sparing of approximately 1 Gy/mm. CTV shrinkage was mainly seen in the elective volumes (up to 10%), likely related to weight loss. Despite online repositioning, substantial systematic errors were present (>3 mm) in lymph node CTV, the parotid glands, and the larynx. Nevertheless, the average increase in OAR dose was small: maximum of 1.2 Gy (parotid glands, Dmean) for all applied margins. Loss of CTV coverage >2 Gy was found in 1, 3, and 7 of 73 CTVs, respectively. Adaptive intervention in 0-mm plans substantially improved coverage: in 5 of 7 CTVs (in 6 patients) to <2 Gy of initially planned. CONCLUSIONS: Volumetric modulated arc therapy head and neck cancer treatment plans with 5-mm margins are robust for anatomy changes and show a modest increase in OAR dose. Margin reduction improves OAR sparing with approximately 1 Gy/mm at the expense of target coverage in a subgroup of patients. Patients at risk of CTV underdosage >2 Gy in 0-mm plans may be identified early in treatment using dose accumulation. A single intervention with an average anatomy derived from CBCT effectively mitigates discrepancies.

Reproducibility of the MRI-defined spinal cord position in stereotactic radiotherapy for spinal oligometastases.

PURPOSE: To establish the reproducibility of the MRI-defined spinal cord position within the spinal canal. MATERIALS AND METHODS: We acquired T1- and T2-weighted MRI scans of 15 volunteers on spine levels C7, T8 or L2. The scan protocol was repeated several times for different postures and time intervals. We determined the spinal cord shift (LR, AP, CC) using a rigid, grey value, vertebral body registration, followed by a spinal cord registration. We tested the sensitivity of our method, introducing artificial spinal cord shifts by varying the size and direction of the water-fat-shift (WFS) of the MR sequences. RESULTS: The spinal cord position on MRI is reproducible within approximately 0.2mm SD (LR, AP) and 0.7mm SD (CC) when reproducing the posture on the same day, as well as several weeks later. However, when comparing different postures, shifts of ∼1.5mm were found. Varying the WFS difference between scans (0.6-3.0mm) induced equivalent virtual spinal cord shifts (0.5-2.5mm). CONCLUSIONS: Displacement of the spinal cord inside the spinal canal may occur as a result of posture change. Considering the total geometric accuracy of spine SBRT, MRI-defined spinal cord position is sufficiently reproducible and requires no addition to the typical setup-and-intrafraction motion PRV margin if posture is identical throughout the RT process.

Alpha/beta ratio for normal lung tissue as estimated from lung cancer patients treated with stereotactic body and conventionally fractionated radiation therapy.

PURPOSE: To estimate the α/ß ratio for which the dose-dependent lung perfusion reductions for stereotactic body radiation therapy (SBRT) and conventionally fractionated radiation therapy (CFRT) are biologically equivalent. METHODS AND MATERIALS: The relations between local dose and perfusion reduction 4 months after treatment in lung cancer patients treated with SBRT and CFRT were scaled according to the linear-quadratic model using α/ß ratios from 0 Gy to ∞ Gy. To test for which α/ß ratio both treatments have equal biological effect, a 5-parameter logistic model was optimized for both dose-effect relationships simultaneously. Beside the α/ß ratio, the other 4 parameters were d50, the steepness parameter k, and 2 parameters (MSBRT and MCFRT) representing the maximal perfusion reduction at high doses for SBRT and CFRT, respectively. RESULTS: The optimal fitted model resulted in an α/ß ratio of 1.3 Gy (0.5-2.1 Gy), MSBRT=42.6% (40.4%-44.9%), MCFRT=66.9% (61.6%-72.1%), d50=35.4 Gy (31.5-9.2 Gy), and k=2.0 (1.7-2.3). CONCLUSIONS: An equal reduction of lung perfusion in lung cancer was observed in SBRT and CFRT if local doses were converted by the linear-quadratic model with an α/ß ratio equal to 1.3 Gy (0.5-2.1 Gy).

Local dose-effect relations for lung perfusion post stereotactic body radiotherapy.

PURPOSE: To model the local dose-effect relation for lung perfusion reduction in lung cancer patients treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Forty-two patients having upper-lobe peripheral tumours <5 cm treated with SBRT (3×18 Gy) underwent single-photon emission computed-tomography (SPECT) scans to measure the lung perfusion 2 weeks pre-SBRT, 4-months post-SBRT, and for 8 patients 15-months post-SBRT. The relation between the calculated relative local perfusion reduction and the normalised total dose (α/ß=3 Gy) at 4-months post-SBRT was modeled by 3-parameter logistic model and 2-parameter linear-maximum model. RESULTS: The relation between local dose and perfusion reduction at 4-months post-SBRT showed a maximum effect of 42.6% at doses >100 Gy and was best described by the logistic model with parameters (95% CI): M=42.6% (40.7-44.6), D50=28.7 Gy (26.3-31.1) and k=2.2 (1.8-2.5). A significant increase of this maximum effect to 65.2% was found at 15-months post-SBRT. CONCLUSIONS: The relation between local dose and perfusion reduction in patients treated with SBRT can be modeled by a 3-parameter logistic model. This demonstrated relationship 4-months post-SBRT approaches a plateau for doses >100 Gy, where 90% of the maximum lung-perfusion reduction is observed at NTD=78 Gy. A further perfusion reduction compared to 4-months post-SBRT was observed fifteen months post-SBRT.

Pareto fronts in clinical practice for pinnacle.

PURPOSE: Our aim was to develop a framework to objectively perform treatment planning studies using Pareto fronts. The Pareto front represents all optimal possible tradeoffs among several conflicting criteria and is an ideal tool with which to study the possibilities of a given treatment technique. The framework should require minimal user interaction and should resemble and be applicable to daily clinical practice. METHODS AND MATERIALS: To generate the Pareto fronts, we used the native scripting language of Pinnacle(3) (Philips Healthcare, Andover, MA). The framework generates thousands of plans automatically from which the Pareto front is generated. As an example, the framework is applied to compare intensity modulated radiation therapy (IMRT) with volumetric modulated arc therapy (VMAT) for prostate cancer patients. For each patient and each technique, 3000 plans are generated, resulting in a total of 60,000 plans. The comparison is based on 5-dimensional Pareto fronts. RESULTS: Generating 3000 plans for 10 patients in parallel requires on average 96 h for IMRT and 483 hours for VMAT. Using VMAT, compared to IMRT, the maximum dose of the boost PTV was reduced by 0.4 Gy (P=.074), the mean dose in the anal sphincter by 1.6 Gy (P=.055), the conformity index of the 95% isodose (CI(95%)) by 0.02 (P=.005), and the rectal wall V(65 Gy) by 1.1% (P=.008). CONCLUSIONS: We showed the feasibility of automatically generating Pareto fronts with Pinnacle(3). Pareto fronts provide a valuable tool for performing objective comparative treatment planning studies. We compared VMAT with IMRT in prostate patients and found VMAT had a dosimetric advantage over IMRT.

The PET-boost randomised phase II dose-escalation trial in non-small cell lung cancer.

PURPOSE: The local site of relapse in non-small cell lung cancer (NSCLC) is primarily located in the high FDG uptake region of the primary tumour prior to treatment. A phase II PET-boost trial (NCT01024829) randomises patients between dose-escalation of the entire primary tumour (arm A) or to the high FDG uptake region inside the primary tumour (>50% SUV(max)) (arm B), whilst giving 66 Gy in 24 fractions to involved lymph nodes. We analysed the planning results of the first 20 patients for which both arms A and B were planned. METHODS: Boost dose levels were escalated up to predefined normal tissue constraints with an equal mean lung dose in both arms. This also forces an equal mean PTV dose in both arms, hence testing pure dose-redistribution. Actual delivered treatment plans from the ongoing clinical trial were analysed. Patients were randomised between arms A and B if dose-escalation to the primary tumour in arm A of at least 72 Gy in 24 fractions could be safely planned. RESULTS: 15/20 patients could be escalated to at least 72 Gy. Average prescribed fraction dose was 3.27±0.31 Gy [3.01-4.28 Gy] and 3.63±0.54 Gy [3.20-5.40 Gy] for arms A and B, respectively. Average mean total dose inside the PTV of the primary tumour was comparable: 77.3±7.9 Gy vs. 77.5±10.1 Gy. For the boost region dose levels of on average 86.9±14.9 Gy were reached. No significant dose differences between both arms were observed for the organs at risk. Most frequent observed dose-limiting constraints were the mediastinal structures (13/15 and 14/15 for arms A and B, respectively), and the brachial plexus (3/15 for both arms). CONCLUSION: Dose-escalation using an integrated boost could be achieved to the primary tumour or high FDG uptake regions whilst keeping the pre-defined dose constraints.

A practical technique to avoid the hippocampus in prophylactic cranial irradiation for lung cancer.

A practical technique is presented to deliver hippocampus avoiding prophylactic cranial irradiation for lung cancer patients, using two lateral fields. For a prescribed dose of 12×2.5 Gy, sparing of the hippocampi to 6.1 Gy was achieved with a V95% of the brain of 81.7%.

Volumetric-modulated arc therapy for stereotactic body radiotherapy of lung tumors: a comparison with intensity-modulated radiotherapy techniques.

PURPOSE: To demonstrate the potential of volumetric-modulated arc therapy (VMAT) compared with intensity-modulated radiotherapy (IMRT) techniques with a limited number of segments for stereotactic body radiotherapy (SBRT) for early-stage lung cancer. METHODS AND MATERIALS: For a random selection of 27 patients eligible for SBRT, coplanar and noncoplanar IMRT and coplanar VMAT (using SmartArc) treatment plans were generated in Pinnacle(3) and compared. In addition, film measurements were performed using an anthropomorphic phantom to evaluate the skin dose for the different treatment techniques. RESULTS: Using VMAT, the delivery times could be reduced to an average of 6.6 min compared with 23.7 min with noncoplanar IMRT. The mean dose to the healthy lung was 4.1 Gy for VMAT and noncoplanar IMRT and 4.2 Gy for coplanar IMRT. The volume of healthy lung receiving>5 Gy and >20 Gy was 18.0% and 5.4% for VMAT, 18.5% and 5.0% for noncoplanar IMRT, and 19.4% and 5.7% for coplanar IMRT, respectively. The dose conformity at 100% and 50% of the prescribed dose of 54 Gy was 1.13 and 5.17 for VMAT, 1.11 and 4.80 for noncoplanar IMRT and 1.12 and 5.31 for coplanar IMRT, respectively. The measured skin doses were comparable for VMAT and noncoplanar IMRT and slightly greater for coplanar IMRT. CONCLUSIONS: Coplanar VMAT for SBRT for early-stage lung cancer achieved plan quality and skin dose levels comparable to those using noncoplanar IMRT and slightly better than those with coplanar IMRT. In addition, the delivery time could be reduced by ≤70% with VMAT.

Effects of respiration-induced density variations on dose distributions in radiotherapy of lung cancer.

PURPOSE: To determine the effect of respiration-induced density variations on the estimated dose delivered to moving structures and, consequently, to evaluate the necessity of using full four-dimensional (4D) treatment plan optimization. METHODS AND MATERIALS: In 10 patients with large tumor motion (median, 1.9 cm; range, 1.1-3.6 cm), the clinical treatment plan, designed using the mid-ventilation ([MidV]; i.e., the 4D-CT frame closest to the time-averaged mean position) CT scan, was recalculated on all 4D-CT frames. The cumulative dose was determined by transforming the doses in all breathing phases to the MidV geometry using deformable registration and then averaging the results. To determine the effect of density variations, this cumulative dose was compared with the accumulated dose after similarly deforming the planned (3D) MidV-dose in each respiratory phase using the same transformation (i.e., "blurring the dose"). RESULTS: The accumulated tumor doses, including and excluding density variations, were almost identical. Relative differences in the minimum gross tumor volume (GTV) dose were less than 2% for all patients. The relative differences were even smaller in the mean lung dose and the V20 (<0.5% and 1%, respectively). CONCLUSIONS: The effect of respiration-induced density variations on the dose accumulated over the respiratory cycle was very small, even in the presence of considerable respiratory motion. A full 4D-dose calculation for treatment planning that takes into account such density variations is therefore not required. Planning using the MidV-CT derived from 4D-CT with an appropriate margin for geometric uncertainties is an accurate and safe method to account for respiration-induced anatomy variations.