Publications by authors named "Eugène Damen"

34 Publications

Characterization of automatic treatment planning approaches in radiotherapy.

Phys Imaging Radiat Oncol 2021 Jul 13;19:60-65. Epub 2021 Jul 13.

Department of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.phro.2021.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295841PMC
July 2021

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

Radiother Oncol 2020 01 17;142:224-229. Epub 2019 Aug 17.

Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address:

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 EQD 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 D 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.
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http://dx.doi.org/10.1016/j.radonc.2019.07.015DOI Listing
January 2020

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

Radiother Oncol 2020 01 17;142:175-179. Epub 2019 Aug 17.

Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands. Electronic address:

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 (fSRS) and 19 patients (20 lesions) receiving fSRS postoperatively (fSRS), 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 fSRS patients. For fSRS 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 (fSRS; -2.7 Gy (-16.5 to 2.3 Gy), fSRS; -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.
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http://dx.doi.org/10.1016/j.radonc.2019.07.011DOI Listing
January 2020

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

Phys Imaging Radiat Oncol 2019 Apr 24;10:7-13. Epub 2019 Apr 24.

Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark.

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 Pinnacle® 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.
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http://dx.doi.org/10.1016/j.phro.2019.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807573PMC
April 2019

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

Radiother Oncol 2019 04 15;133:198-204. Epub 2018 Nov 15.

Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Radiation Oncology, Radboud University, Nijmegen, The Netherlands; Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.radonc.2018.10.035DOI Listing
April 2019

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

Radiother Oncol 2019 02 13;131:166-173. Epub 2018 Oct 13.

Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address:

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.
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http://dx.doi.org/10.1016/j.radonc.2018.09.019DOI Listing
February 2019

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

Med Dosim 2019 Summer;44(2):183-189. Epub 2018 Aug 19.

Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.meddos.2018.06.001DOI Listing
December 2019

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

Radiother Oncol 2017 10 19;125(1):62-65. Epub 2017 Sep 19.

Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address:

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_V:HR=1.007% (95% CI:1.002-1.013; p=0.006), age:HR=1.026year (1.011-1.042; p=0.001) and GTV volume:HR=1.001cc (1.000-1.002; p=0.006) with overall survival.
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http://dx.doi.org/10.1016/j.radonc.2017.09.004DOI Listing
October 2017

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

Int J Radiat Oncol Biol Phys 2016 11 21;96(3):653-60. Epub 2016 Jul 21.

Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ijrobp.2016.07.011DOI Listing
November 2016

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

Radiother Oncol 2014 Nov 25;113(2):230-4. Epub 2014 Nov 25.

Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.radonc.2014.11.003DOI Listing
November 2014

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

Int J Radiat Oncol Biol Phys 2014 Jan;88(1):224-8

Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address:

Purpose: To estimate the α/β 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/β ratios from 0 Gy to ∞ Gy. To test for which α/β ratio both treatments have equal biological effect, a 5-parameter logistic model was optimized for both dose-effect relationships simultaneously. Beside the α/β 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/β 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/β ratio equal to 1.3 Gy (0.5-2.1 Gy).
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http://dx.doi.org/10.1016/j.ijrobp.2013.10.015DOI Listing
January 2014

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

Radiother Oncol 2013 Jun 23;107(3):398-402. Epub 2013 Apr 23.

Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

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/β=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.
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http://dx.doi.org/10.1016/j.radonc.2013.04.003DOI Listing
June 2013

Pareto fronts in clinical practice for pinnacle.

Int J Radiat Oncol Biol Phys 2013 Mar 15;85(3):873-80. Epub 2012 Aug 15.

Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.ijrobp.2012.05.045DOI Listing
March 2013

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

Radiother Oncol 2012 Jul 6;104(1):67-71. Epub 2012 Apr 6.

Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.radonc.2012.03.005DOI Listing
July 2012

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

Radiother Oncol 2012 Feb 20;102(2):225-7. Epub 2011 Dec 20.

Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

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%.
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http://dx.doi.org/10.1016/j.radonc.2011.09.023DOI Listing
February 2012

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

Int J Radiat Oncol Biol Phys 2011 Dec 6;81(5):1560-7. Epub 2011 Feb 6.

Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.ijrobp.2010.09.014DOI Listing
December 2011

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

Int J Radiat Oncol Biol Phys 2009 Jul;74(4):1266-75

Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.ijrobp.2009.02.073DOI Listing
July 2009

Frameless stereotactic body radiotherapy for lung cancer using four-dimensional cone beam CT guidance.

Int J Radiat Oncol Biol Phys 2009 Jun 27;74(2):567-74. Epub 2008 Nov 27.

Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Purpose: To quantify the localization accuracy and intrafraction stability of lung cancer patients treated with frameless, four-dimensional (4D) cone beam computed tomography (CBCT)-guided stereotactic body radiotherapy (SBRT) and to calculate and validate planning target volume (PTV) margins to account for the residual geometric uncertainties.

Materials And Methods: Sixty-five patients with small peripheral lung tumors were treated with SBRT without a body frame to 54 Gy in three fractions. For each fraction, three 4D-CBCT scans were acquired: before treatment to measure and correct the time-weighted mean tumor position, after correction to validate the correction applied, and after treatment to estimate the intrafraction stability. Patient-specific PTV margins were computed and subsequently validated using Monte Carlo error simulations.

Results: Systematic tumor localization inaccuracies (1 SD) were 0.8, 0.8, and 0.9 mm for the left-right, craniocaudal, and anteroposterior direction, respectively. Random localization inaccuracies were 1.1, 1.1, and 1.4 mm. Baseline variations were 1.8, 2.9, and 3.0 mm (systematic) and 1.1, 1.5, and 2.0 mm (random), indicating the importance of image guidance. Intrafraction stability of the target was 1.2, 1.2, and 1.8 mm (systematic) and 1.3, 1.5, and 1.8 mm (random). Monte Carlo error simulations showed that patient-specific PTV margins (5.8-10.5 mm) were adequate for 94% of the evaluated cases (2-28 mm peak-to-peak breathing amplitude).

Conclusions: Frameless SBRT can be safely administered using 4D-CBCT guidance. Even with considerable breathing motion, the PTV margins can safely be kept small, allowing patients with larger tumors to benefit from the advantages of SBRT. In case bony anatomy would be used as a surrogate for tumor position, considerably larger PTV margins would be required.
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http://dx.doi.org/10.1016/j.ijrobp.2008.08.004DOI Listing
June 2009

Comparison of different strategies to use four-dimensional computed tomography in treatment planning for lung cancer patients.

Int J Radiat Oncol Biol Phys 2008 Mar;70(4):1229-38

Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Purpose: To discuss planning target volumes (PTVs) based on internal target volume (PTVITV), exhale-gated radiotherapy (PTVGating), and a new proposed midposition (PTVMidP; time-weighted mean tumor position) and compare them with the conventional free-breathing CT scan PTV (PTVConv).

Methods And Materials: Respiratory motion induces systematic and random geometric uncertainties. Their contribution to the clinical target volume (CTV)-to-PTV margins differs for each PTV approach. The uncertainty margins were calculated using a dose-probability-based margin recipe (based on patient statistics). Tumor motion in four-dimensional CT scans was determined using a local rigid registration of the tumor. Geometric uncertainties for interfractional setup errors and tumor baseline variation were included. For PTVGating, the residual motion within a 30% gating (time) window was determined. The concepts were evaluated in terms of required CTV-to-PTV margin and PTV volume for 45 patients.

Results: Over the patient group, the PTVITV was on average larger (+6%) and the PTVGating and PTVMidP smaller (-10%) than the PTVConv using an off-line (bony anatomy) setup correction protocol. With an on-line (soft tissue) protocol the differences in PTV compared with PTVConv were +33%, -4%, and 0, respectively.

Conclusions: The internal target volume method resulted in a significantly larger PTV than conventional CT scanning. The exhale-gated and mid-position approaches were comparable in terms of PTV. However, mid-position (or mid-ventilation) is easier to use in the clinic because it only affects the planning part of treatment and not the delivery.
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http://dx.doi.org/10.1016/j.ijrobp.2007.11.042DOI Listing
March 2008

Mid-ventilation CT scan construction from four-dimensional respiration-correlated CT scans for radiotherapy planning of lung cancer patients.

Int J Radiat Oncol Biol Phys 2006 Aug;65(5):1560-71

Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Purpose: Four-dimensional (4D) respiration-correlated imaging techniques can be used to obtain (respiration) artifact-free computed tomography (CT) images of the thorax. Current radiotherapy planning systems, however, do not accommodate 4D-CT data. The purpose of this study was to develop a simple, new concept to incorporate patient-specific motion information, using 4D-CT scans, in the radiotherapy planning process of lung cancer patients to enable smaller error margins.

Methods And Materials: A single CT scan was selected from the 4D-CT data set. This scan represented the tumor in its time-averaged position over the respiratory cycle (the mid-ventilation CT scan). To select the appropriate CT scan, two methods were used. First, the three-dimensional tumor motion was analyzed semiautomatically to calculate the mean tumor position and the corresponding respiration phase. An alternative automated method was developed to select the correct CT scan using the diaphragm motion.

Results: Owing to hysteresis, mid-ventilation selection using the three-dimensional tumor motion had a tumor position accuracy (with respect to the mean tumor position) better than 1.1 +/- 1.1 mm for all three directions (inhalation and exhalation). The accuracy in the diaphragm motion method was better than 1.1 +/- 1.1 mm. Conventional free-breathing CT scanning had an accuracy better than 0 +/- 3.9 mm. The mid-ventilation concept can result in an average irradiated volume reduction of 20% for tumors with a diameter of 40 mm.

Conclusion: Tumor motion and the diaphragm motion method can be used to select the (artifact-free) mid-ventilation CT scan, enabling a significant reduction of the irradiated volume.
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http://dx.doi.org/10.1016/j.ijrobp.2006.04.031DOI Listing
August 2006

Impact of geometrical uncertainties on 3D CRT and IMRT dose distributions for lung cancer treatment.

Int J Radiat Oncol Biol Phys 2006 Jul;65(4):1260-9

Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Purpose: To quantify the effect of set-up errors and respiratory motion on dose distributions for non-small cell lung cancer (NSCLC) treatment.

Methods And Materials: Irradiations of 5 NSCLC patients were planned with 3 techniques, two (conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT1)) with a homogeneous dose in the planning target volume (PTV) and a third (IMRT2) with dose heterogeneity. Set-up errors were simulated for gross target volume (GTV) and organs at risk (OARs). For the GTV, the respiration was also simulated with a periodical motion around a varying average. Two configurations were studied for the breathing motion, to describe the situations of free-breathing (FB) and respiration-correlated (RC) CT scans, each with 2 amplitudes (5 and 10 mm), thus resulting in 4 scenarios (FB_5, FB_10, RC_5 and RC_10). Five thousand treatment courses were simulated, producing probability distributions for the dosimetric parameters.

Results: For CRT and IMRT1, RC_5, RC_10 and FB_5 were associated with a small degradation of the GTV coverage. IMRT2 with FB_10 showed the largest deterioration of the GTV dosimetric indices, reaching 7% for Dmin at the 95% probability level. Removing the systematic error due to the periodic breathing motion was advantageous for a 10 mm respiration amplitude. The estimated probability of radiation pneumonitis and acute complication for the esophagus showed limited sensitivity to geometrical uncertainties. Dmax in the spinal cord and the parameters predicting the risk of late esophageal toxicity were associated to a probability up to 50% of violating the dose tolerances.

Conclusions: Simulating the effect of geometrical uncertainties on the individual patient plan should become part of the standard pre-treatment verification procedure.
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http://dx.doi.org/10.1016/j.ijrobp.2006.03.035DOI Listing
July 2006

Intensity-modulated radiotherapy of breast cancer using direct aperture optimization.

Radiother Oncol 2006 May 18;79(2):162-9. Epub 2006 May 18.

Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background And Purpose: To design a clinically reliable and efficient step-and-shoot IMRT delivery technique for the treatment of breast cancer using direct aperture optimization (DAO). Using DAO, segments are created and optimized within the same optimization process.

Patients And Methods: The DAO technique implemented in the Pinnacle treatment planning system, which is called direct machine parameter optimization (DMPO), was used to generate IMRT plans for twelve breast cancer patients. The prescribed dose was 50 Gy. Two DMPO plans were generated. The first approach uses DMPO only; the second technique combines DMPO with two predefined segments (DMPO(segm)), having shapes identical to the conventional tangential fields. The weight of these predefined segments is optimized simultaneously with DMPO. The DMPO plans were compared with normal two-step (TS) IMRT, creating segments after optimizing the intensity.

Results: Dose homogeneity within the target volume was 4.8+/-0.6, 4.3+/-0.5 and 3.8+/-0.5 Gy for the TS, DMPO and DMPO(segm) plans, respectively. Comparing the IMRT plans with an idealized dose distribution obtained using only beamlet optimization, the degradation of the dose distribution was less for the DMPO plans compared with the two-step IMRT approach. Furthermore, this degradation was similar for all patients, while for the two-step IMRT approach it was patient specific.

Conclusions: An efficient step-and-shoot IMRT solution was developed for the treatment of breast cancer using DMPO combined with two predefined segments.
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http://dx.doi.org/10.1016/j.radonc.2006.04.010DOI Listing
May 2006

The sensitivity of dose distributions for organ motion and set-up uncertainties in prostate IMRT.

Radiother Oncol 2005 Jul;76(1):18-26

Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background And Purpose: To determine the effect of organ motion and set-up uncertainties on IMRT dose distributions for prostate.

Methods: For five patients, IMRT techniques were designed to irradiate the CTV (prostate plus seminal vesicles). Technique I delivered 78 Gy to PTV1 (CTV+10 mm margin). Technique II delivered 68 Gy to PTV1, and a 10 Gy boost to PTV2 (CTV+an anisotropic margin of 0 to 5 mm). Technique III delivered 68 Gy to PTV1 and simultaneously 78 Gy to PTV2. Uncertainties were simulated using population statistics of organ motion and set-up accuracy. The average TCP (TCPpop) of the CTV and average NTCP (NTCPpop) of the rectal wall were calculated.

Results: The planning TCP was a good predictor for TCPpop for Techniques I and II. Technique III was sensitive for geometrical uncertainties, reducing TCPpop by 0.8 to 2.4% compared to planning. NTCPpop was reduced for Technique III by a factor 2.6 compared to Technique I. For all plans, the planning NTCP was strongly correlated with NTCPpop.

Conclusions: Dose distributions created with Techniques I and II are insensitive for geometrical uncertainties, while Technique III resulted in a reduction of TCPpop. This reduction can be compensated by a small dose escalation, while still resulting in an NTCPpop of the rectal wall that is lower or comparable to Technique I.
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http://dx.doi.org/10.1016/j.radonc.2005.06.010DOI Listing
July 2005

Dose heterogeneity in the target volume and intensity-modulated radiotherapy to escalate the dose in the treatment of non-small-cell lung cancer.

Int J Radiat Oncol Biol Phys 2005 Jun;62(2):561-70

Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Purpose: To quantify the dose escalation achievable in the treatment of non-small-cell lung cancer (NSCLC) by allowing dose heterogeneity in the target volume or using intensity-modulated radiotherapy (IMRT), or both.

Methods And Materials: Computed tomography data and contours of 10 NSCLC patients with limited movements of the tumor and representing a broad spectrum of clinical cases were selected for this study. Four irradiation techniques were compared: two conformal (CRT) and two IMRT techniques, either prescribing a homogeneous dose in the planning target volume (PTV) (CRT(hom) and IMRT(hom)) or allowing dose heterogeneity (CRT(inhom) and IMRT(inhom)). The dose heterogeneity was allowed only toward high doses, i.e., the minimum dose in the target for CRT(inhom) and IMRT(inhom) could not be lower than for the corresponding homogeneous plan. The dose in the PTV was escalated (fraction size of 2.25 Gy) until either an organ at risk reached the maximum allowed dose or the mean PTV dose reached a maximum level set at 101.25 Gy.

Results: When small and convex tumors were irradiated, CRT(hom) could achieve the maximum dose of 101.25 Gy, whereas for bigger and/or concave PTVs the dose level achievable with CRT(hom) was significantly lower, in 1 case even below 60 Gy. The CRT(inhom) allowed on average a 6% dose escalation with respect to CRT(hom). The IMRT(hom) achieved in all except 1 case a mean PTV dose of at least 75 Gy. The gain in mean PTV dose of IMRT(hom) with respect to CRT(hom) ranged from 7.7 to 14.8 Gy and the IMRT(hom) plans were always more conformal than the corresponding CRT(hom) plans. The IMRT(inhom) provided an additional advantage over IMRT(hom) of at least 5 Gy. For all CRT plans the achievable dose was determined by the lung dose threshold, whereas for more than half of the IMRT plans the esophagus was the dose-limiting organ. The IMRT plans were deliverable with 10-12 segments per beam and did not produce an increase of lung volume irradiated at low doses (<20 Gy).

Conclusions: The dose in NSCLC treatments can be escalated by loosening the constraints on maximum dose in the target volume or using IMRT, or both. For large and concave tumors, an average dose escalation of 6% and 17% was possible when dose heterogeneity and IMRT were applied alone. When they were combined, the average dose increase was as high as 35%. Intensity-modulated RT delivered in a static mode can produce homogeneous dose distributions in the target and does not lead to an increase of lung volume receiving (very) low doses, even down to 5 Gy.
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http://dx.doi.org/10.1016/j.ijrobp.2005.02.011DOI Listing
June 2005

Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT?

Int J Radiat Oncol Biol Phys 2004 Dec;60(5):1425-39

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.

Purpose: To identify the anatomic structures whose damage or malfunction cause late dysphagia and aspiration after intensive chemotherapy and radiotherapy (RT) for head-and-neck cancer, and to explore whether they can be spared by intensity-modulated RT (IMRT) without compromising target RT.

Methods And Materials: A total of 26 patients receiving RT concurrent with gemcitabine, a regimen associated with a high rate of late dysphagia and aspiration, underwent prospective evaluation of swallowing with videofluoroscopy (VF), direct endoscopy, and CT. To assess whether the VF abnormalities were regimen specific, they were compared with the VF findings of 6 patients presenting with dysphagia after RT concurrent with high-dose intra-arterial cisplatin. The anatomic structures whose malfunction was likely to cause each of the VF abnormalities common to both regimens were determined by literature review. Pre- and posttherapy CT scans were reviewed for evidence of posttherapy damage to each of these structures, and those demonstrating posttherapy changes were deemed dysphagia/aspiration-related structures (DARS). Standard three-dimensional (3D) RT, standard IMRT (stIMRT), and dysphagia-optimized IMRT (doIMRT) plans in which sparing of the DARS was included in the optimization cost function, were produced for each of 20 consecutive patients with advanced head-and-neck cancer.

Results: The posttherapy VF abnormalities common to both regimens included weakness of the posterior motion of the base of tongue, prolonged pharyngeal transit time, lack of coordination between the swallowing phases, reduced elevation of the larynx, and reduced laryngeal closure and epiglottic inversion, contributing to a high rate of aspiration. The anatomic structures whose malfunction was the likely cause of each of these abnormalities, and that also demonstrated anatomic changes after RT concurrent with gemcitabine doses associated with dysphagia and aspiration, were the pharyngeal constrictor muscles (median thickness near midline 2.5 mm before therapy vs. 7 mm after therapy; p = 0.001), the supraglottic larynx (median thickness, 2 mm before therapy vs. 4 mm after therapy; p < 0.001), and, similarly, the glottic larynx. The constrictors and the glottic and supraglottic larynx were, therefore, deemed the DARS. The lowest maximal dose delivered to a stricture volume was 50 Gy. Reducing the volumes of the DARS receiving > or =50 Gy (V(50)) was, therefore, a planning and evaluation goal. Compared with the 3D plans, stIMRT reduced the V(50) of the pharyngeal constrictors by 10% on average (range, 0-36%, p < 0.001), and doIMRT reduced these volumes further, by an additional 10% on average (range, 0-38%; p <0.001). The V(50) of the larynx (glottic + supraglottic) was reduced marginally by stIMRT compared with 3D (by 7% on average, range, 0-56%; p = 0.054), and doIMRT reduced these volumes by an additional 11%, on average (range, 0-41%; p = 0.002). doIMRT reduced laryngeal V(50) compared with 3D, by 18% on average (range 0-61%; p = 0.001). Certain target delineation rules facilitated sparing of the DARS by IMRT. The maximal DARS doses were not reduced by IMRT because of their partial overlap with the targets. stIMRT and doIMRT did not differ in target doses, parotid gland mean dose, spinal cord, or nonspecified tissue maximal dose.

Conclusions: The structures whose damage may cause dysphagia and aspiration after intensive chemotherapy and RT are the pharyngeal constrictors and the glottic and supraglottic larynx. Compared with 3D-RT, moderate sparing of these structures was achieved by stIMRT, and an additional benefit, whose extent varied among the patients, was gained by doIMRT, without compromising target doses. Clinical validation is required to determine whether the dosimetric gains are translated into clinical ones.
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http://dx.doi.org/10.1016/j.ijrobp.2004.05.050DOI Listing
December 2004

Sensitivity of treatment plan optimisation for prostate cancer using the equivalent uniform dose (EUD) with respect to the rectal wall volume parameter.

Radiother Oncol 2004 Nov;73(2):209-18

Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Background And Purpose: To analyse the sensitivity of plan optimisation of prostate cancer treatments with respect to changes in the volume parameter (n), when the EUD is used to control the dose in the rectal wall.

Patients And Methods: A series of plans was defined, by varying n over a range between 0.08 and 1, and testing different cost functions and beam arrangements. In all cases, the aim was to minimise the EUD in the rectal wall, while ensuring specific dose coverage of the PTV, and limiting the dose in the other OARs. The results were evaluated in terms of 3-D dose distribution and with respect to the current clinical knowledge about late rectal toxicity after irradiation.

Results: Different values of n lead to very similar dose distributions over the PTV (differences in mean dose < 1 Gy, differences in dose given to 99% of the volume < 1%). For the rectal wall, the following observations were made: (a) all cumulative DVH curves crossed each other around 60 Gy; (b) the rectal wall volume receiving doses between 30 and 45 Gy could change by 45 and 30%, respectively, depending on the value of n; (c) for doses higher than 70Gy the differences were typically within 5%. Different values of n also affected the position of isodose surfaces. The distance between the 70 and the 30 Gy isodose curves changed in the AP direction by a factor of 3 when n decreased from 1 to 0.08. High values of n were associated with less dose conformity and a larger volume (at least 20%) of normal tissues receiving 50 Gy or more. All DVHs for the rectal wall were below published dose toxicity thresholds except when the prescribed dose was escalated up to 86 Gy.

Conclusions: In most cases, the solutions associated with n values up to 0.25 produced similar dose distribution in the rectal wall for doses above 45 Gy, complying with the dose-toxicity thresholds we analysed. The choice of a specific value of n in the optimisation requires an analysis of its effects on the dose distribution for the rectal wall, but also on other aspects, such as the value of the dose to the non-involved normal tissues.
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http://dx.doi.org/10.1016/j.radonc.2004.08.016DOI Listing
November 2004

Comparison between manual and automatic segment generation in step-and-shoot IMRT of prostate cancer.

Med Phys 2004 Jan;31(1):122-30

Radiotherapy Department, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Purpose: To compare two methods to generate treatment plans for intensity-modulated radiotherapy (IMRT) of prostate cancer, delivered in a step-and-shoot mode. The first method uses fluence optimization (inverse planning) followed by conversion of the fluence weight map into a limited number of segments. In the second method, segments are manually assigned using a class solution (forward planning), followed by computer optimization of the segment weights.

Methods: Treatment plans for IMRT, utilizing a simultaneous integrated boost, were created. Plans comprise a five-field technique to deliver 78 Gy to the prostate plus seminal vesicles. Five patients were evaluated. Optimization objectives of both planning approaches concerned dose coverage of the target volumes and the dose distribution in the rectal wall. The two methods were evaluated by comparing dose distributions, the complexity of the resulting plan and the time expenditure to generate and to deliver the plan.

Results: For both planning approaches 99% of the target volumes received 95% of the prescribed dose, which complies with our planning objectives. Inverse planning resulted in more conformal dose distributions than forward planning (conformity index: 1.37 versus 1.51). Inverse planning reduced the dose to the rectal wall compared to a manually designed plan, albeit to a small extent. The theoretical probability of severe rectal proctitis and/or stenosis was reduced on average by 1.9% with inverse planning. Maximal sparing of the rectal wall was achieved with inverse planning for a patient whose target volume was partly wrapped around the rectum. The number of segments generated with inverse planning ranged between 33 and 52, and between 9 and 13 segments for manually created segments.

Conclusion: Dose coverage of the planning target volumes is adequate for both approaches of planning. Inverse planning results in slightly better dose distributions with respect to the rectal wall compared to manual planning, at the cost of an increase of the number of segments by a factor of 3.
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http://dx.doi.org/10.1118/1.1634481DOI Listing
January 2004

Importance of accurate dose calculations outside segment edges in intensity modulated radiotherapy treatment planning.

Radiother Oncol 2003 Dec;69(3):305-14

Radiotherapy Division, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.

Background And Purpose: To assess the effect of differences in the calculation of the dose outside segment edges on the overall dose distribution and the optimisation process of intensity modulated radiation therapy (IMRT) treatment plans.

Patients And Methods: Accuracy of dose calculations of two treatment planning systems (TPS1 and TPS2) was assessed, to ensure that they are both suitable for IMRT treatment planning according to published guidelines. Successively, 10 treatment plans for patients with prostate and head and neck tumours were calculated in both systems. The calculations were compared in selected points as well as in combination with volumetric parameters concerning the planning target volume (PTV) and organs at risk.

Results: For both planning systems, the calculations agree within 2.0% or 3 mm with the measurements in the high-dose region for single and multiple segment dose distributions. The accuracy of the dose calculation is within the tolerances proposed by recent recommendations. Below 35% of the prescribed dose, TPS1 overestimates and TPS2 underestimates the measured dose values, TPS2 being closer to the experimental data. The differences between TPS1 and TPS2 in the calculation of the dose outside segments explain the differences (up to 50% of the local value) found in point dose comparisons. For the prostate plans, the discrepancies between the TPS do not translate into differences in PTV coverage, normal tissue complication probability (NTCP) values and results of the plan optimisation process. The dose-volume histograms (DVH) of the rectal wall differ below 60 Gy, thus affecting the plan optimisation if a cost function would operate in this dose region. For the head and neck cases, the two systems give different evaluations of the DVH points for the PTV (up to 22% differences in target coverage) and the parotid mean dose (1.0-3.0 Gy). Also the results of the optimisation are influenced by the choice of the dose calculation algorithm.

Conclusions: In IMRT, the accuracy of the dose calculation outside segment edges is important for the determination of the dose to both organs at risks and target volumes and for a correct outcome of the optimisation process. This aspect should therefore be of major concern in the commissioning of a TPS intended for use in IMRT. Fulfilment of the accuracy criteria valid for conformal radiotherapy is not sufficient. Three-dimensional evaluation of the dose distribution is needed in order to assess the impact of dose calculation accuracy outside the segment edges on the total dose delivered to patients treated with IMRT.
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http://dx.doi.org/10.1016/j.radonc.2003.09.002DOI Listing
December 2003

A comparison of forward and inverse treatment planning for intensity-modulated radiotherapy of head and neck cancer.

Radiother Oncol 2003 Dec;69(3):251-8

Medical Physics Division, University Hospital for Radiation Oncology, Hoppe-Seyler-Str. 3, Tübingen 72076, Germany.

Background And Purpose: To compare intensity-modulated treatment plans of patients with head and neck cancer generated by forward and inverse planning.

Materials And Methods: Ten intensity-modulated treatment plans, planned and treated with a step&shoot technique using a forward planning approach, were retrospectively re-planned with an inverse planning algorithm. For this purpose, two strategies were applied. First, inverse planning was performed with the same beam directions as forward planning. In addition, nine equidistant, coplanar incidences were used. The main objective of the optimisation process was the sparing of the parotid glands beside an adequate treatment of the planning target volume (PTV). Inverse planning was performed both with pencil beam and Monte Carlo dose computation to investigate the influence of dose computation on the result of the optimisation.

Results: In most cases, both inverse planning strategies managed to improve the treatment plans distinctly due to a better target coverage, a better sparing of the parotid glands or both. A reduction of the mean dose by 3-11Gy for at least one of the parotid glands could be achieved for most of the patients. For three patients, inverse planning allowed to spare a parotid gland that had to be sacrificed by forward planning. Inverse planning increased the number of segments compared to forward planning by a factor of about 3; from 9-15 to 27-46. No significant differences for PTV and parotid glands between both inverse planning approaches were found. Also, the use of Monte Carlo instead of pencil beam dose computation did not influence the results significantly.

Conclusion: The results demonstrate the potential of inverse planning to improve intensity-modulated treatment plans for head and neck cases compared to forward planning while retaining clinical utility in terms of treatment time and quality assurance.
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http://dx.doi.org/10.1016/j.radonc.2003.08.002DOI Listing
December 2003

Incorporating an improved dose-calculation algorithm in conformal radiotherapy of lung cancer: re-evaluation of dose in normal lung tissue.

Radiother Oncol 2003 Oct;69(1):1-10

Department of Radiotherapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Background And Purpose: The low density of lung tissue causes a reduced attenuation of photons and an increased range of secondary electrons, which is inaccurately predicted by the algorithms incorporated in some commonly available treatment planning systems (TPSs). This study evaluates the differences in dose in normal lung tissue computed using a simple and a more correct algorithm. We also studied the consequences of these differences on the dose-effect relations for radiation-induced lung injury.

Materials And Methods: The treatment plans of 68 lung cancer patients initially produced in a TPS using a calculation model that incorporates the equivalent-path length (EPL) inhomogeneity-correction algorithm, were recalculated in a TPS with the convolution-superposition (CS) algorithm. The higher accuracy of the CS algorithm is well-established. Dose distributions in lung were compared using isodoses, dose-volume histograms (DVHs), the mean lung dose (MLD) and the percentage of lung receiving >20 Gy (V20). Published dose-effect relations for local perfusion changes and radiation pneumonitis were re-evaluated.

Results: Evaluation of isodoses showed a consistent overestimation of the dose at the lung/tumor boundary by the EPL algorithm of about 10%. This overprediction of dose was also reflected in a consistent shift of the EPL DVHs for the lungs towards higher doses. The MLD, as determined by the EPL and CS algorithm, differed on average by 17+/-4.5% (+/-1SD). For V20, the average difference was 12+/-5.7% (+/-1SD). For both parameters, a strong correlation was found between the EPL and CS algorithms yielding a straightforward conversion procedure. Re-evaluation of the dose-effect relations showed that lung complications occur at a 12-14% lower dose. The values of the TD(50) parameter for local perfusion reduction and radiation pneumonitis changed from 60.5 and 34.1 Gy to 51.1 and 29.2 Gy, respectively.

Conclusions: A simple tissue inhomogeneity-correction algorithm like the EPL overestimates the dose to normal lung tissue. Dosimetric parameters for lung injury (e.g. MLD, V20) computed using both algorithms are strongly correlated making an easy conversion feasible. Dose-effect relations should be refitted when more accurate dose data is available.
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http://dx.doi.org/10.1016/s0167-8140(03)00195-6DOI Listing
October 2003
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