Marc Coghe

Adaptive Dose Painting by Numbers for Head-and-Neck Cancer

PURPOSE To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. METHODS AND MATERIALS Each patients treatment used three separate treatment plans: fractions 1-10 used a DPBN ([(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography [(18)F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment (18)F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a (18)F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gy to the high-dose clinical target volume (CTV(high_dose)) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. RESULTS All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second (18)F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV(high_dose) (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV(high_dose) and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. CONCLUSION To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.

Whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy (IMAT): First clinical experience

PURPOSE Whole abdominopelvic radiation therapy (WAPRT) is a treatment option in the palliation of patients with relapsed ovarian cancer. With conventional techniques, kidneys and liver are the dose- and homogeneity-limiting organs. We developed a planning strategy for intensity-modulated arc therapy (IMAT) and report on the treatment plans of the first 5 treated patients. METHODS AND MATERIALS Five consecutive patients with histologically proven relapsed ovarian cancer were sent to our department for WAPRT. The target volumes and organs at risk (OAR) were delineated on 0.5-cm-thick CT slices. The clinical target volume (CTV) was defined as the total peritoneal cavity. CTV and kidneys were expanded with 0.5 cm. In a preset range of 8 degrees interspaced gantry angles, machine states were generated with an anatomy-based segmentation tool. Machine states of the same class were stratified in arcs. The optimization of IMAT was done in several steps, using a biophysical objective function. These steps included weight optimization of machine states, leaf position optimization adapted to meet the maximal leaf speed constraint, and planner-interactive optimization of the start and stop angles. The final control points (machine states plus associated cumulative monitor unit counts) were calculated using a collapsed cone convolution/superposition algorithm. For comparison, two conventional plans (CONV) were made, one with two fields (CONV2), and one with four fields (CONV4). In these CONV plans, dose to the kidneys was limited by cerrobend blocks. The IMAT and the CONV plans were normalized to a median dose of 33 Gy to the planning target volume (PTV). Monomer/polymer gel dosimetry was used to assess the dosimetric accuracy of the IMAT planning and delivery method. RESULTS The median volume of the PTV was 8306 cc. The mean treatment delivery time over 4 patients was 13.8 min. A mean of 444 monitor units was needed for a fraction dose of 150 cGy. The fraction of the PTV volume receiving more than 90% of the prescribed dose (V(90)) was 9% higher for the IMAT plan than for the CONV4 plan (89.9% vs. 82.5%). Outside a build-up region of 0.8 cm and 1 cm away from both kidneys, the inhomogeneity in the PTV was 15.1% for the IMAT plans and 24.9% for the CONV4 plans (for CONV2 plans, this was 34.9%). The median dose to the kidneys in the IMAT plans was lower for all patients. The 95th percentile dose for the kidneys was significantly higher for the IMAT plans than for the CONV4 and CONV2 plans (28.2 Gy vs. 22.2 Gy and 22.6 Gy for left kidney, respectively). No relevant differences were found for liver. The gel-measured dose was within clinical planning constraints. CONCLUSION IMAT was shown to be deliverable in an acceptable time slot and to produce dose distributions that are more homogeneous than those obtained with a CONV plan, with at least equal sparing of the OARs.

Maximum tolerated dose in a phase I trial on adaptive dose painting by numbers for head and neck cancer

PURPOSE To determine the maximum tolerated dose (MTD) in a phase I trial on adaptive dose-painting-by-numbers (DPBN) for non-metastatic head and neck cancer. MATERIALS AND METHODS Adaptive intensity-modulated radiotherapy was based on voxel intensity of pre-treatment and per-treatment [(18)F]fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) scans. Dose was escalated to a median total dose of 80.9 Gy in the high-dose clinical target volume (dose level I) and 85.9 Gy in the gross tumor volume (dose level II). The MTD would be reached, if ≥ 33% of patients developed any grade ≥ 4 toxicity (DLT) up to 3 months follow-up. RESULTS Between February 2007 and August 2009, seven patients at dose level I and 14 at dose level II were treated. All patients completed treatment without interruption. At a median follow-up for surviving patients of 38 (dose level I) and 22 months (dose level II) there was no grade ≥ 4 toxicity during treatment and follow-up but six cases of mucosal ulcers at latency of 4-10 months, of which five (36%) were observed at dose level II. Mucosal ulcers healed spontaneously in four patients. CONCLUSIONS Considering late mucosal ulcers as DLT, the MTD of a median dose of 80.9 Gy has been reached in our trial.

Underdosage of the upper-airway mucosa for small fields as used in intensity-modulated radiation therapy: A comparison between radiochromic film measurements, Monte Carlo simulations, and collapsed cone convolution calculations

Head-and-neck tumors are often situated at an air-tissue interface what may result in an underdosage of part of the tumor in radiotherapy treatments using megavoltage photons, especially for small fields. In addition to effects of transient electronic disequilibrium, for these small fields, an increased lateral electron range in air will result in an important extra reduction of the central axis dose beyond the cavity. Therefore dose calculation algorithms need to model electron transport accurately. We simulated the trachea by a 2 cm diameter cylindrical air cavity with the rim situated 2 cm beneath the phantom surface. A 6 MV photon beam from an Elekta SLiplus linear accelerator, equipped with the standard multileaf collimator (MLC), was assessed. A 10 x 2 cm2 and a 10 x 1 cm2 field, both widthwise collimated by the MLC, were applied with their long side parallel to the cylinder axis. Central axis dose rebuild-up was studied. Radiochromic film measurements were performed in an in-house manufactured polystyrene phantom with the films oriented either along or perpendicular to the beam axis. Monte Carlo simulations were performed with BEAM and EGSnrc. Calculations were also performed using the pencil beam (PB) algorithm and the collapsed cone convolution (CCC) algorithm of Helax-TMS (MDS Nordion, Kanata, Cahada) version 6.0.2 and using the CCC algorithm of Pinnacle (ADAC Laboratories, Milpitas, CA, USA) version 4.2. A very good agreement between the film measurements and the Monte Carlo simulations was found. The CCC algorithms were not able to predict the interface dose accurately when lateral electronic disequilibrium occurs, but were shown to be a considerable improvement compared to the PB algorithm. The CCC algorithms overestimate the dose in the rebuild-up region. The interface dose was overestimated by a maximum of 31% or 54%, depending on the implementation of the CCC algorithm. At a depth of 1 mm, the maximum dose overestimation was 14% or 24%.

Design of and technical challenges involved in a framework for multicentric radiotherapy treatment planning studies

This report introduces a framework for comparing radiotherapy treatment planning in multicentric in silico clinical trials. Quality assurance, data incompatibility, transfer and storage issues, and uniform analysis of results are discussed. The solutions that are given provide a useful guide for the set-up of future multicentric planning studies or public repositories of high quality data.

MCDE: a new Monte Carlo dose engine for IMRT

A new accurate Monte Carlo code for IMRT dose computations, MCDE (Monte Carlo dose engine), is introduced. MCDE is based on BEAMnrc/DOSXYZnrc and consequently the accurate EGSnrc electron transport. DOSXYZnrc is reprogrammed as a component module for BEAMnrc. In this way both codes are interconnected elegantly, while maintaining the BEAM structure and only minimal changes to BEAMnrc.mortran are necessary. The treatment head of the Elekta SLiplus linear accelerator is modelled in detail. CT grids consisting of up to 200 slices of 512 x 512 voxels can be introduced and up to 100 beams can be handled simultaneously. The beams and CT data are imported from the treatment planning system GRATIS via a DICOM interface. To enable the handling of up to 50 x 10(6) voxels the system was programmed in Fortran95 to enable dynamic memory management. All region-dependent arrays (dose, statistics, transport arrays) were redefined. A scoring grid was introduced and superimposed on the geometry grid, to be able to limit the number of scoring voxels. The whole system uses approximately 200 MB of RAM and runs on a PC cluster consisting of 38 1.0 GHz processors. A set of in-house made scripts handle the parallellization and the centralization of the Monte Carlo calculations on a server. As an illustration of MCDE, a clinical example is discussed and compared with collapsed cone convolution calculations. At present, the system is still rather slow and is intended to be a tool for reliable verification of IMRT treatment planning in the case of the presence of tissue inhomogeneities such as air cavities.

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

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

Relations of image quality in on-line portal images and individual patient parameters for pelvic field radiotherapy

AbstractWe have previously demonstrated that on-line portal imaging (OPI) can detect and correct significant errors in field set-up. Such errors occurred very frequently when irradiating the pelvic region and were typically detected after 10% of the field dose was delivered. The image quality on pelvic fields was, however, disappointing. The aims of the present study involving 566 pelvic fields on 13 patients were: 1.To study the machine- and patient-related factors influencing image quality.2.To study the factors related to machine, patient and patient set-up, influencing the errors of field set-up.3.To develop a method for predicting the camera settings. The OPI device consisted of a fluorescent screen scanned by a video camera. An image quality score on a scale 0–5 was given for 546/566 fields. In a univariate analysis, open field subtraction adversely affected the score (P < 0.001). The image score of anterior fields was significantly better than that of posterior fields (P < 0.001). Multivariate stepwise logistic regression showed that, in addition to anterior or posterior field (P < 0.001) and subtraction (P = 0.003), gender (P = 0.02) was also a significant predictor of image score. Errors requiring field adjustments were detected on 289/530 (54.5%) evaluable fields or 229/278 (82.4%) evaluable patient set-ups. Multivariate logistic regression showed that the probability of performing an adjustment was significantly related to gender (P < 0.001), image quality (P = 0.001) and AP-PA diameter (P = 0.04). The magnitude of adjustments made in the lateral direction correlated significantly (P < 0.0001) with patient bulk. The camera kV level with gain held constant showed an exponential dependency on dose rate at the image detector plate and can thus be predicted by treatment planning.

Automatic generation of a plan optimization volume for tangential field breast cancer radiation therapy.

Background and Purpose:Dose homogeneity is one of the objectives during computer planning of postoperative radiotherapy of the conserved breast. For three-dimensional (3-D) optimization of the dose distribution using serial CT scan images, suitable volumes have to be delineated. The purpose of this study was to develop a computer-generated delineation of a plan optimization volume (POV) and an irradiated volume (IV) and to automate their use in a fast dose homogeneity optimization engine.Patients and Methods:Simulation was performed according to our standard procedure which involves the positioning of a lead collar around the palpable breast to facilitate the definition of gantry angle, collimator angle and field aperture for tangential wedged photon beams. In a change to the standard procedure an anterolateral radiograph was taken with its axis orthogonal to the central plane of the two tangential half-beams. Images from a serial CT scan were acquired in treatment position, and the geometric data of the three simulated beams were used by a computer program to generate the POV and IV. For each patient, weights of wedged and unwedged beams were optimized by either human heuristics using only the central slice (2-D), the whole set of CT slices (3-D), or by a computer algorithm using the POV, IV and lung volume with constrained matrix inversion (CMI) as optimization method. The resulting dose distributions were compared.Results:The total planning procedure took, on average, 44 min of which < 7 min were needed for human interactions, compared to about 52 min for the standard planning at Ghent University Hospital, Belgium. The simulation time is increased by 2–3 min. The method provides 3-D information of the dose distribution. Dose homogeneity and minimum dose inside the POV and maximum dose inside the IV were not significantly different for the three optimization techniques.Conclusion:This automated planning method is capable of replacing the contouring of the clinical target volume as well as the trial-and-error procedure of assigning weights of wedged and unwedged beams by an experienced planner.Hintergrund und Ziel:Dosishomogenitität ist eines der Ziele bei der Planung für die Strahlentherapie nach brusterhaltender Operation. Für die dreidimensionale (3-D) Optimierung der Dosisverteilung mit Hilfe serieller CT-Schnitte müssen passende Volumina ermittelt werden. Ziel dieser Studie war, eine computergesteuerte Erstellung des optimierten Planungszielvolumens (POV) und des bestrahlten Volumens (IV) zu entwickeln und ihren Einsatz in einem schnellen Rechner zur Optimierung der Dosishomogenität zu automatisieren.Patienten und Methoden:Die Simulation wurde nach unserem Standardverfahren durchgeführt, bei dem eine Bleikette um die tastbare Brust gelegt wird, um die Festlegung von Gantry-Winkel, Kollimatorwinkel und Feldgrößen für tangentiale Keilfilterfelder zu erleichtern. In einer Abwandlung des Standardverfahrens wurde ein anterolaterales Röntgenbild aufgenommen, dessen Achse orthogonal zur Zentralebene der beiden tangentialen Strahlen verläuft. Serielle CT-Schnitte wurden in Behandlungsposition aufgenommen, und mit den geometrischen Daten der drei simulierten Felder erstellte ein Computerprogramm POV und IV. Für jede Patientin wurde die Wichtung für die Strahlenfelder mit und ohne Keilfilter optimiert, indem manuell nach menschlichem Ermessen nur die zentrale Schicht (2-D) bzw. alle CT-Schichten herangezogen wurden (3-D). Alternativ wurde ein Computeralgorithmus eingesetzt, der POV, IV und das bestrahlte Lungenvolumen nach der Methode der Constrained Matrix Inversion (CMI) optimiert. Die so erzielten Dosisverteilungen wurden verglichen.Ergebnisse:Das gesamte Planungsverfahren dauerte durchschnittlich 44 min, von denen < 7 min für menschliche Interaktion benötigt wurden, im Vergleich zu rund 52 Minuten beim Standardverfahren der Universitätsklinik Gent/Belgien. Die Simulationszeit ist um 2–3 min länger. Das Verfahren liefert 3-D-Information über die Dosisverteilung. Dosishomogenität und minimale Dosis innerhalb des POV und maximale Dosis innerhalb des IV unterschieden sich bei den drei Optimierungstechniken nicht signifikant.Schlussfolgerung:Dieses automatisierte Planungsverfahren kann sowohl das Festlegen des klinischen Zielvolumens ersetzen als auch Näherungsmethoden erfahrener Planer.

Measurement Techniques, Modeling Strategies and Pitfalls to Avoid when Implementing a Mini MLC in a Non Dedicated Planning System*

Background and Purpose:Ghent University Hospital investigated the feasibility of the Pinnacle® system for planning intracranial stereotactic treatments. The aim was to perform precise dose computation using the collapsed cone engine for treatment delivery with the Moduleaf mini-MLC mounted on an Elekta accelerator.Material and Methods:The Moduleaf® was commissioned using dose rate corrected data recorded by a diamond detector and using data measured by cylindrical chambers each limited to restricted field sizes.Results:Automatic modeling resulted in clinical relevant dose errors up to 10%. Using manual modeling in Pinnacle®, for clinical applicable fields a 2%/2 mm agreement between modeled data and measurements was obtained.Conclusion:The overall accuracy of the collapsed cone algorithm is within tolerances for single fraction stereotactic treatments.Hintergrund und Ziel:Am Universitätsklinikum Gent wurde die Anwendung eines Pinnacle®-Planungssystems für die intrakranielle stereotaktische Bestrahlung untersucht. Das Ziel bestand darin, für die Bestrahlung mit einem Moduleaf-Mini-MLC, der an einem Elekta-Beschleuniger® befestigt ist, mit dem „Collapsed cone“-Rechenalgorithmus eine präzise Dosisberechnung zu erstellen.Material und Methoden:Hierzu wurden Messungen mit einem Diamantdetektor durchgeführt, die bezüglich der Dosisleistung korrigiert wurden, sowie Messungen mit einer zylindrischen Ionisationskammer für kleine Felder.Ergebnisse:Die automatische Modellierung führte zu Fehlern von bis zu 10%, was bereits klinisch relevant ist. Mit der manuellen Modellierung in Pinnacle war es möglich, zwischen modellierten Daten und Messungen eine Übereinstimmung von 2%/2 mm zu erreichen.Schlussfolgerung:Die Gesamtgenauigkeit des „Collapsed-cone“-Algorithmus liegt innerhalb der Toleranzgrenzen für stereotaktische Einzeldosisbehandlungen.