Dominique Huyskens

The impact of 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) lymph node staging on the radiation treatment volumes in patients with non-small cell lung cancer

Abstract Purpose : 18 F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) combined with computer tomography (PET-CT) is superior to CT alone in mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). We studied the potential impact of this non-invasive LN staging procedure on the radiation treatment plan of patients with NSCLC. Patients and methods : The imaging and surgical pathology data from 105 patients included in two previously published prospective LN staging protocols form the basis for the present analysis. For 73 of these patients, with positive LNs on CT and/or on PET, a theoretical study was performed in which for each patient the gross tumour volume (GTV) was defined based on CT and on PET-CT data. For each GTV, the completeness of tumour coverage was assessed, using the available surgical pathology data as gold standard. A more detailed analysis was done for the first ten consecutive patients in whom the PET-CT-GTV was smaller than the CT-GTV. Theoretical radiation treatment plans were constructed based on both CT-GTV and PET-CT-GTV. Dose-volume histograms for the planning target volume (PTV), for the total lung volume and the lung volume receiving more than 20 Gy ( V lung(20) ), were calculated. Results : Data from 988 assessed LN stations were available. In the subgroup of 73 patients with CT or PET positive LNs, tumour coverage improved from 75% when the CT-GTV was used to 89% with the PET-CT-GTV ( P =0.005). In 45 patients (62%) the information obtained from PET would have led to a change of the treatment volumes. For the ten patients in the dosimetry study, the use of PET-CT to define the GTV, resulted in an average reduction of the PTV by 29±18% (±1 SD) ( P =0.002) and of the V lung(20) of 27±18% (±1 SD) ( P =0.001). Conclusion : In patients with NSCLC considered for curative radiation treatment, assessment of locoregional LN tumour extension by PET will improve tumour coverage, and in selected patients, will reduce the volume of normal tissues irradiated, and thus toxicity. This subgroup of patients could then become candidates for treatment intensification.

Testing of the analytical anisotropic algorithm for photon dose calculation

The analytical anisotropic algorithm (AAA) was implemented in the Eclipse (Varian Medical Systems) treatment planning system to replace the single pencil beam (SPB) algorithm for the calculation of dose distributions for photon beams. AAA was developed to improve the dose calculation accuracy, especially in heterogeneous media. The total dose deposition is calculated as the superposition of the dose deposited by two photon sources (primary and secondary) and by an electron contamination source. The photon dose is calculated as a three-dimensional convolution of Monte-Carlo precalculated scatter kernels, scaled according to the electron density matrix. For the configuration of AAA, an optimization algorithm determines the parameters characterizing the multiple source model by optimizing the agreement between the calculated and measured depth dose curves and profiles for the basic beam data. We have combined the acceptance tests obtained in three different departments for 6, 15, and 18MV photon beams. The accuracy of AAA was tested for different field sizes (symmetric and asymmetric) for open fields, wedged fields, and static and dynamic multileaf collimation fields. Depth dose behavior at different source-to-phantom distances was investigated. Measurements were performed on homogeneous, water equivalent phantoms, on simple phantoms containing cork inhomogeneities, and on the thorax of an anthropomorphic phantom. Comparisons were made among measurements, AAA, and SPB calculations. The optimization procedure for the configuration of the algorithm was successful in reproducing the basic beam data with an overall accuracy of 3%, 1mm in the build-up region, and 1%, 1mm elsewhere. Testing of the algorithm in more clinical setups showed comparable results for depth dose curves, profiles, and monitor units of symmetric open and wedged beams below dmax. The electron contamination model was found to be suboptimal to model the dose around dmax, especially for physical wedges at smaller source to phantom distances. For the asymmetric field verification, absolute dose difference of up to 4% were observed for the most extreme asymmetries. Compared to the SPB, the penumbra modeling is considerably improved (1%, 1mm). At the interface between solid water and cork, profiles show a better agreement with AAA. Depth dose curves in the cork are substantially better with AAA than with SPB. Improvements are more pronounced for 18MV than for 6MV. Point dose measurements in the thoracic phantom are mostly within 5%. In general, we can conclude that, compared to SPB, AAA improves the accuracy of dose calculations. Particular progress was made with respect to the penumbra and low dose regions. In heterogeneous materials, improvements are substantial and more pronounced for high (18MV) than for low (6MV) energies.

Acceptance tests and quality control (QC) procedures for the clinical implementation of intensity modulated radiotherapy (IMRT) using inverse planning and the sliding window technique: experience from five radiotherapy departments

BACKGROUND AND PURPOSE An increasing number of radiotherapy centres is now aiming for clinical implementation of intensity modulated radiotherapy (IMRT), but--in contrast to conventional treatment--no national or international guidelines for commissioning of the treatment planning system (TPS) and acceptance tests of treatment equipment have yet been developed. This paper bundles the experience of five radiotherapy departments that have introduced IMRT into their clinical routine. METHODS AND MATERIALS The five radiotherapy departments are using similar configurations since they adopted the commercially available Varian solution for IMRT, regarding treatment planning as well as treatment delivery. All are using the sliding window technique. Different approaches towards the derivation of the multileaf collimator (MLC) parameters required for the configuration of the TPS are described. A description of the quality control procedures for the dynamic MLC, including their respective frequencies, is given. For the acceptance of the TPS for IMRT multiple quality control plans were developed on a variety of phantoms, testing the flexibility of the inverse planning modules to produce the desired dose pattern as well as assessing the accuracy of the dose calculation. Regarding patient treatment verification, all five centres perform dosimetric pre-treatment verification of the treatment fields, be it on a single field or on a total plan procedure. During the actual treatment, the primary focus is on patient positioning rather than dosimetry. Intracavitary in vivo measurements were performed in special cases. RESULT AND CONCLUSION The configurational MLC parameters obtained through different methods are not identical for all centres, but the observed variations have shown to be of no significant clinical relevance. The quality control (QC) procedures for the dMLC have not detected any discrepancies since their initiation, demonstrating the reliability of the MLC controller. The development of geometrically simple QC plans to test the inverse planning, the dynamic MLC modules and the final dose calculation has proven to be useful in pointing out the need to remodel the single pencil beam scatter kernels in some centres. The final correspondence between calculated and measured dose was found to be satisfactory by all centres, for QC test plans as well as for pre-treatment verification of clinical IMRT fields. An intercomparison of the man hours needed per patient plan verification reveals a substantial variation depending on the type of measurements performed.

On-line quality assurance of rotational radiotherapy treatment delivery by means of a 2D ion chamber array and the Octavius phantom

For routine pretreatment verification of innovative treatment techniques such as (intensity modulated) dynamic arc therapy and helical TomoTherapy, an on-line and reliable method would be highly desirable. The present solution proposed by TomoTherapy, Inc. (Madison, WI) relies on film dosimetry in combination with up to two simultaneous ion chamber point dose measurements. A new method is proposed using a 2D ion chamber array (Seven29, PTW, Freiburg, Germany) inserted in a dedicated octagonal phantom, called Octavius. The octagonal shape allows easy positioning for measurements in multiple planes. The directional dependence of the response of the detector was primarily investigated on a dual energy (6 and 18 MV) Clinac 21EX (Varian Medical Systems, Palo Alto, CA) as no fixed angle incidences can be calculated in the Hi-Art TPS of TomoTherapy. The array was irradiated from different gantry angles and with different arc deliveries, and the dose distributions at the level of the detector were calculated with the AAA (Analytical Anisotropic Algorithm) photon dose calculation algorithm implemented in Eclipse (Varian). For validation on the 6 MV TomoTherapy unit, rotational treatments were generated, and dose distributions were calculated with the Hi-Art TPS. Multiple cylindrical ion chamber measurements were used to cross-check the dose calculation and dose delivery in Octavius in the absence of the 2D array. To compensate for the directional dependence of the 2D array, additional prototypes of Octavius were manufactured with built-in cylindrically symmetric compensation cavities. When using the Octavius phantom with a 2 cm compensation cavity, measurements with an accuracy comparable to that of single ion chambers can be achieved. The complete Octavius solution for quality assurance of rotational treatments consists of: The 2D array, two octagonal phantoms (with and without compensation layer), an insert for nine cylindrical ion chambers, and a set of inserts of various tissue equivalent materials of different densities. The combination of the 2D array with the Octavius phantom proved to be a fast and reliable method for pretreatment verification of rotational treatments. Quality control of TomoTherapy patients was reduced to a total of approximately 25 min per patient.

Automatic segmentation of thoracic and pelvic CT images for radiotherapy planning using implicit anatomic knowledge and organ-specific segmentation strategies

Automatic segmentation of anatomical structures in medical images is a valuable tool for efficient computer-aided radiotherapy and surgery planning and an enabling technology for dynamic adaptive radiotherapy. This paper presents the design, algorithms and validation of new software for the automatic segmentation of CT images used for radiotherapy treatment planning. A coarse to fine approach is followed that consists of presegmentation, anatomic orientation and structure segmentation. No user input or a priori information about the image content is required. In presegmentation, the body outline, the bones and lung equivalent tissue are detected. Anatomic orientation recognizes the patients position, orientation and gender and creates an elastic mapping of the slice positions to a reference scale. Structure segmentation is divided into localization, outlining and refinement, performed by procedures with implicit anatomic knowledge using standard image processing operations. The presented version of algorithms automatically segments the body outline and bones in any gender and patient position, the prostate, bladder and femoral heads for male pelvis in supine position, and the spinal canal, lungs, heart and trachea in supine position. The software was developed and tested on a collection of over 600 clinical radiotherapy planning CT stacks. In a qualitative validation on this test collection, anatomic orientation correctly detected gender, patient position and body region in 98% of the cases, a correct mapping was produced for 89% of thorax and 94% of pelvis cases. The average processing time for the entire segmentation of a CT stack was less than 1 min on a standard personal computer. Two independent retrospective studies were carried out for clinical validation. Study I was performed on 66 cases (30 pelvis, 36 thorax) with dosimetrists, study II on 52 cases (39 pelvis, 13 thorax) with radio-oncologists as experts. The experts rated the automatically produced structures on the scale 1-excellent (no corrections necessary, maximum time saving), 2-good (corrections necessary for up to 1/3 of slices), 3-acceptable (major corrections necessary, but still time saving), 4-not acceptable (manual redrawing more efficient, no time saving). A rating<or=3 indicates a time saving in the treatment planning process and was given for pelvis segmentation in 70% (I) and 68% (II) of the cases, with average ratings 2.9 (I) and 2.6 (II). For the thorax, a rating<or=3 was given in 94% and 91% of the cases, with average ratings 2.1 and 1.9, respectively. For quantitative validation, automatically generated structures were compared geometrically in 2D and 3D to manually drawn structures created by experts on seven randomly selected cases. The quantitative validation was limited to pelvis structures. The results indicate that the accuracy of the algorithms is within the bandwidth of manual segmentation by experts, except for specific erroneous situations. Even though manual review and corrections of automatically segmented structures are still mandatory, it can be expected that due to the speed of the presented software and the quality of its results, its introduction in the radiotherapy treatment planning process will lead to a considerable amount of time being saved.

The potential impact of treatment variations on the results of radiotherapy of the internal mammary lymph node chain: a quality-assurance report on the dummy run of EORTC Phase III randomized trial 22922/10925 in Stage I–III breast cancer

PURPOSE To present the results of the dummy run of the European Organization for Research and Treatment of Cancer (EORTC) trial investigating the role of adjuvant internal mammary and medial supraclavicular (IM-MS) irradiation in Stage I--III breast cancer. METHODS AND MATERIALS All participating institutions were asked to produce a treatment plan without (Arm 1) and with (Arm 2) simultaneous IM-MS irradiation of 1 patient after mastectomy and of 1 patient after lumpectomy. Thirty-two dummy runs have been evaluated for compliance to protocol guidelines, with respect to treatment technique and dose prescription. RESULTS A number of more or less important deviations in treatment setup and prescription have been found. The dose in the IM-MS region deviated significantly from the prescribed dose in 10% of the cases for Arm 1, and in 21% for Arm 2. Assuming a true 5% 10-year survival benefit from optimal IM-MS irradiation, an increase of only 3.8% will be found due to this suboptimal dose distribution. CONCLUSION In the dummy run, a number of potential systematic protocol deviations that might lead to false-negative results were detected. By providing recommendations to the participating institutions, we expect to improve the interinstitutional consistency and to promote a high quality irradiation in all institutions participating in the trial.

Quality assurance in the 22991 EORTC ROG trial in localized prostate cancer: Dummy run and individual case review

INTRODUCTION EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. MATERIALS AND METHODS CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. RESULTS Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. CONCLUSIONS Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques.

Quality assurance of EORTC trial 22922/10925 investigating the role of internal mammary—medial supraclavicular irradiation in stage I-III breast cancer: the individual case review

To assess consistency among participants in an European Organisation for Research and Treatment of Cancer (EORTC) phase III trial randomising between irradiation and no irradiation of the internal mammary and medial supraclavicular (IM-MS) lymph nodes, all participating institutes were invited to send data from 3 patients in each arm as soon as they started accrual. The evaluation focused on eligibility, compliance with the radiotherapy guidelines, treatment techniques and dose prescription to the IM-MS region. Nineteen radiotherapy departments provided a total of 111 cases, all being eligible. Minor discrepancies were found in the surgery and pathology data in almost half the patients. Major radiotherapy protocol deviations were very limited: 2 cases of unwarranted irradiation of the supraclavicular region and a significant dose deviation to the internal mammary region in 5 patients. The most frequently observed minor protocol deviation was the absence of delineation of the target volumes in 80% of the patients. By detecting systematic protocol deviations in an early phase of the trial, recommendations made to all the participating institutes should improve the interinstitutional consistency and promote a high-quality treatment.

Quality control in interstitial brachytherapy of the breast using pulsed dose rate: treatment planning and dose delivery with an Ir-192 afterloading system.

BACKGROUND AND PURPOSE In the Radiotherapy Department of Leuven, about 20% of all breast cancer patients treated with breast conserving surgery and external radiotherapy receive an additional boost with pulsed dose rate (PDR) Ir-192 brachytherapy. An investigation was performed to assess the accuracy of the delivered PDR brachytherapy treatment. Secondly, the feasibility of in vivo measurements during PDR dose delivery was investigated. MATERIALS AND METHODS Two phantoms are manufactured to mimic a breast, one for thermoluminescent dosimetry (TLD) measurements, and one for dosimetry using radiochromic films. The TLD phantom allows measurements at 34 dose points in three planes including the basal dose points. The film phantom is designed in such a way that films can be positioned in a plane parallel and orthogonal to the needles. RESULTS The dose distributions calculated with the TPS are in good agreement with both TLD and radiochromic film measurements (average deviations of point doses <+/-5%). However, close to the interface tissue-air the dose is overestimated by the TPS since it neglects the finite size of a breast and the associated lack of backscatter (average deviations of point doses -14%). CONCLUSION Most deviations between measured and calculated doses, are in the order of magnitude of the uncertainty associated with the source strength specification, except for the point doses measured close to the skin. In vivo dosimetry during PDR brachytherapy treatment was found to be a valuable procedure to detect large errors, e.g. errors caused by an incorrect data transfer.

Midplane dose determination using in vivo dose measurements in combination with portal imaging.

The possibility of using portal films in combination with semiconductor in vivo measurements for midplane dose distribution is investigated. A general algorithm, using measured entrance and exit doses and available beam data of the Linac, is proposed to derive the midplane dose for symmetrical inhomogeneities. Experimental verification of the algorithm with phantom measurements is performed for different kinds of inhomogeneities (Al, air and cork) and phantom thicknesses from 13 cm to 30 cm. When using only the entrance dose and the exit dose, provided by the diodes on the beam axis, the algorithm predicts for the different inhomogeneities midplane doses in all cases within 1% of the midplane doses measured with an ionization chamber. When using the portal film in combination with entrance and exit dose measurements to estimate the midplane dose in an off-axis position, the calculated midplane doses are within 3% of the midplane doses measured with an ionization chamber. The midplane doses calculated with the algorithm are compared to the midplane doses obtained with simplified calculation methods, i.e. the arithmetical mean and the geometrical mean of the measured entrance and exit doses. The geometrical mean especially seems to give acceptable results (within 5%) and can as such be used as an easy rule of thumb to estimate roughly the midplane dose. Finally, critical considerations on the validity and the precision of the proposed algorithm are given. The present results confirm the possibility of using the portal film for midplane dose distribution determination at the patient level.