Erik W. Korevaar

The potential of intensity-modulated proton radiotherapy to reduce swallowing dysfunction in the treatment of head and neck cancer: A planning comparative study.

Abstract Background. Predictive models for swallowing dysfunction were developed previously and showed the potential of improved intensity-modulated radiotherapy to reduce the risk of swallowing dysfunction. Still the risk is high. The aim of this study was to determine the potential of swallowing-sparing (SW) intensity-modulated proton therapy (IMPT) in head and neck cancer (HNC) for reducing the risk of swallowing dysfunction relative to currently used photon therapy. Material and methods. Twenty-five patients with oropharyngeal (n = 21) and hypopharyngeal (n = 4) cancer received primary radiotherapy, including bilateral neck irradiation, using standard (ST) intensity-modulated photon therapy (IMRT). Prophylactic (54 Gy) and therapeutic (70 Gy) target volumes were defined. The dose to the parotid and submandibular glands was reduced as much as possible. Four additional radiotherapy plans were created for each patient: SW-IMRT, ST-IMPT, 3-beam SW-IMPT (3B-SW-IMPT) and 7-beam SW-IMPT (7B-SW-IMPT). All plans were optimized similarly, with additional attempts to spare the swallowing organs at risk (SWOARs) in the SW plans. Probabilities of swallowing dysfunction were calculated with recently developed predictive models. Results. All plans complied with standard HNC radiotherapy objectives. The mean parotid gland doses were similar for the ST and SW photon plans, but clearly lower in all IMPT plans (ipsilateral parotid gland ST-IMRT: 46 Gy, 7B-SW-IMPT: 29 Gy). The mean dose in the SWOARs was lowest with SW-IMPT, in particular with 7B-SW-IMPT (supraglottic larynx ST-IMRT: 60 Gy, 7B-SW-IMPT: 40 Gy). The observed dose reductions to the SWOARs translated into substantial overall reductions in normal tissue complication risks for different swallowing dysfunction endpoints. Compared with ST-IMRT, the risk of physician-rated grade 2–4 swallowing dysfunction was reduced on average by 8.8% (95% CI 6.5–11.1%) with SW-IMRT, and by 17.2% (95% CI: 12.7–21.7%) with 7B-SW-IMPT. Conclusion. SWOAR-sparing with proton therapy has the potential to substantially reduce the risk of swallowing dysfunction compared to similar treatment with photons.

Reconstruction of high-resolution 3D dose from matrix measurements: error detection capability of the COMPASS correction kernel method

The COMPASS system (IBA Dosimetry) is a quality assurance (QA) tool which reconstructs 3D doses inside a phantom or a patient CT. The dose is predicted according to the RT plan with a correction derived from 2D measurements of a matrix detector. This correction method is necessary since a direct reconstruction of the fluence with a high resolution is not possible because of the limited resolution of the matrix used, but it comes with a blurring of the dose which creates inaccuracies in the dose reconstruction. This paper describes the method and verifies its capability to detect errors in the positioning of a MLC with 10 mm leaf width in a phantom geometry. Dose reconstruction was performed for MLC position errors of various sizes at various locations for both rectangular and intensity-modulated radiotherapy (IMRT) fields and compared to a reference dose. It was found that the accuracy with which an error in MLC position is detected depends on the location of the error relative to the detectors in the matrix. The reconstructed dose in an individual rectangular field for leaf positioning errors up to 5 mm was correct within 5% in 50% of the locations. At the remaining locations, the reconstruction of leaf position errors larger than 3 mm can show inaccuracies, even though these errors were detectable in the dose reconstruction. Errors larger than 9 mm created inaccuracies up to 17% in a small area close to the penumbra. The QA capability of the system was tested through gamma evaluation. Our results indicate that the mean gamma provided by the system is slightly increased and that the number of points above gamma 1 ensures error detection for QA purposes. Overall, the correction kernel method used by the COMPASS system is adequate to perform QA of IMRT treatment plans with a regular MLC, despite local inaccuracies in the dose reconstruction.

Clinical introduction of a linac head-mounted 2D detector array based quality assurance system in head and neck IMRT

BACKGROUND AND PURPOSE IMRT QA is commonly performed in a phantom geometry but the clinical interpretation of the results in a 2D phantom plane is difficult. The main objective of our work is to move from film measurement based QA to 3D dose reconstruction in a patient CT scan. In principle, this could be achieved using a dose reconstruction method from 2D detector array measurements as available in the COMPASS system (IBA Dosimetry). The first step in the clinical introduction of this system instead of the currently used film QA procedures is to test the reliability of the dose reconstruction. In this paper we investigated the validation of the method in a homogeneous phantom with the film QA procedure as a reference. We tested whether COMPASS QA results correctly identified treatment plans that did or did not fulfil QA requirements in head and neck (H&N) IMRT. MATERIALS AND METHODS A total number of 24 treatments were selected from an existing database with more than 100 film based H&N IMRT QA results. The QA results were classified as either good, just acceptable or clinically rejected (mean gamma index <0.4, 0.4-0.5 or >0.5, respectively with 3%/3mm criteria). Film QA was repeated and compared to COMPASS QA with a MatriXX detector measurement performed on the same day. RESULTS Good agreement was found between COMPASS reconstructed dose and film measured dose in a phantom (mean gamma 0.83±0.09, 1SD with 1%/1mm criteria, 0.33±0.04 with 3%/3mm criteria). COMPASS QA results correlated well with film QA, identifying the same patients with less good QA results. Repeated measurements with film and COMPASS showed changes in delivery after a modified MLC calibration, also visible in a standard MLC check in COMPASS. The time required for QA reduced by half by using COMPASS instead of film. CONCLUSIONS Agreement of COMPASS QA results with film based QA supports its clinical introduction for a phantom geometry. A standard MLC calibration check is sensitive to <1mm changes that could be significant in H&N IMRT. These findings offer opportunities to further investigate the method based on a 2D detector array to 3D dose reconstruction in a patient anatomy.

Development and evaluation of an online three-level proton vs photon decision support prototype for head and neck cancer – Comparison of dose, toxicity and cost-effectiveness

To quantitatively assess the effectiveness of proton therapy for individual patients, we developed a prototype for an online platform for proton decision support (PRODECIS) comparing photon and proton treatments on dose metric, toxicity and cost-effectiveness levels. An evaluation was performed with 23 head and neck cancer datasets.

Swallowing-sparing intensity-modulated radiotherapy for head and neck cancer patients: treatment planning optimization and clinical introduction.

PURPOSE To report on the potential benefits of swallowing-sparing intensity-modulated radiation therapy (SW-IMRT) in the first 100 SW-IMRT treated patients, as well as on the factors that influence the potential benefit of SW-IMRT relative to standard parotid sparing (ST)-IMRT. MATERIAL AND METHODS One hundred consecutive head and neck cancer patients, scheduled for primary radiotherapy, were included in this prospective cohort study. For each patient, ST-IMRT and SW-IMRT treatment plans were created. All patients were eventually treated with SW-IMRT. Objectives for SW-IMRT were identical to those with ST-IMRT, with additional objectives to spare the swallowing organs at risk (SWOARs). After 20 patients, interim results were evaluated by a multidisciplinary committee. RESULTS The mean gain of SW-IMRT relative to ST-IMRT in the first 20 patients was less than expected based on our previous planning comparative study. A critical review of all plans revealed that the results with SW-IMRT could be improved by: (1) gaining experience and attempting to reduce SWOAR dose as much as possible; (2) accepting a moderate shift of dose to unspecified tissues; (3) maximizing SWOAR sparing while keeping PTV coverage exactly according to protocol. In the additional 80 patients, the mean dose to the various SWOARs was further reduced significantly compared to ST-IMRT. Dose reductions with SW-IMRT were largest for patients who received neck irradiation, had a tumour located in the larynx, oropharynx, nasopharynx or oral cavity, and had <75% overlap between SWOARs and PTVs. The mean absolute reduction in predicted physician-rated RTOG grade 2-4 swallowing dysfunction for patients numbered 21-100 was 6.1%, ranging from 0.0% to 17.2%. CONCLUSIONS The benefit of SW-IMRT depends significantly on neck radiotherapy, tumour site and the amount of overlap between SWOARs and PTVs. Optimal clinical introduction requires a detailed evaluation and comparison between the standard (ST-IMRT) and new technique (SW-IMRT) in order to fully exploit the potential benefits.

Dosimetric consequences of the shift towards computed tomography guided target definition and planning for breast conserving radiotherapy

BackgroundThe shift from conventional two-dimensional (2D) to three-dimensional (3D)-conformal target definition and dose-planning seems to have introduced volumetric as well as geometric changes. The purpose of this study was to compare coverage of computed tomography (CT)-based breast and boost planning target volumes (PTV), absolute volumes irradiated, and dose delivered to the organs at risk with conventional 2D and 3D-conformal breast conserving radiotherapy.MethodsTwenty-five patients with left-sided breast cancer were subject of CT-guided target definition and 3D-conformal dose-planning, and conventionally defined target volumes and treatment plans were reconstructed on the planning CT. Accumulated dose-distributions were calculated for the conventional and 3D-conformal dose-plans, taking into account a prescribed dose of 50 Gy for the breast plans and 16 Gy for the boost plans.ResultsWith conventional treatment plans, CT-based breast and boost PTVs received the intended dose in 78% and 32% of the patients, respectively, and smaller volumes received the prescribed breast and boost doses compared with 3D-conformal dose-planning. The mean lung dose, the volume of the lungs receiving > 20 Gy, the mean heart dose, and volume of the heart receiving > 30 Gy were significantly less with conventional treatment plans. Specific areas within the breast and boost PTVs systematically received a lower than intended dose with conventional treatment plans.ConclusionThe shift towards CT-guided target definition and planning as the golden standard for breast conserving radiotherapy has resulted in improved target coverage at the cost of larger irradiated volumes and an increased dose delivered to organs at risk. Tissue is now included into the breast and boost target volumes that was never explicitly defined or included with conventional treatment. Therefore, a coherent definition of the breast and boost target volumes is needed, based on clinical data confirming tumour control probability and normal tissue complication probability with the use of 3D-conformal radiotherapy.

Minimising contralateral breast dose in post-mastectomy intensity-modulated radiotherapy by incorporating conformal electron irradiation

PURPOSE To assess the potential benefit of incorporating conformal electron irradiation in intensity-modulated radiotherapy (IMRT) for loco-regional post-mastectomy RT. PATIENTS AND METHODS Ten consecutive patients that underwent left-sided mastectomy were selected for this comparative planning study. Three-dimensional conformal radiotherapy (3D-CRT) photon-electron dose plans were compared to photon-only IMRT (IMRT(p)) and photon IMRT with conformal electron irradiation (IMRT(p/e)). The planning target volume (PTV) was prescribed 50 Gy and included the chest wall and the internal mammary and supra-clavicular lymph node regions. It was attempted to minimise dose delivered to heart, lungs and contralateral breast (CB), while maintaining adequate PTV coverage. RESULTS All plans complied with objectives for PTV coverage. IMRT(p/e) eliminated volumes receiving 70 Gy (V70) that were present in 3D-CRT at the junction of photon and electron beams. Both IMRT strategies reduced heart V30 significantly below 3D-CRT levels. Mean heart dose with IMRT(p/e) was the lowest and was equal to that with 3D-CRT. Minimising heart dose with IMRT(p) resulted in irradiated CB volumes much larger than that with 3D-CRT. With IMRT(p/e), CB dose was only slightly increased when compared to 3D-CRT. Mean lung dose values were similar for IMRT and 3D-CRT. With IMRT, lung V20 was smaller, whereas V5 values for heart, lung and CB were higher than those with 3D-CRT. CONCLUSIONS Incorporation of conformal electron irradiation in post-mastectomy IMRT(p/e) enables a heart dose reduction which can only be obtained with IMRT(p) when allowing large irradiated volumes in the contralateral breast.

Mixing intensity modulated electron and photon beams: combining a steep dose fall-off at depth with sharp and depth-independent penumbras and flat beam profiles

For application in radiotherapy, intensity modulated high-energy electron and photon beams were mixed to create dose distributions that feature: (a) a steep dose fall-off at larger depths, similar to pure electron beams, (b) flat beam profiles and sharp and depth-independent beam penumbras, as in photon beams, and (c) a selectable skin dose that is lower than for pure electron beams. To determine the required electron and photon beam fluence profiles, an inverse treatment planning algorithm was used. Mixed beams were realized at a MM50 racetrack microtron (Scanditronix Medical AB, Sweden), and evaluated by the dose distributions measured in a water phantom. The multileaf collimator of the MM50 was used in a static mode to shape overlapping electron beam segments, and the dynamic multileaf collimation mode was used to realize the intensity modulated photon beam profiles. Examples of mixed beams were generated at electron energies of up to 40 MeV. The intensity modulated electron beam component consists of two overlapping concentric fields with optimized field sizes, yielding broad, fairly depth-independent overall beam penumbras. The matched intensity modulated photon beam component has high fluence peaks at the field edges to sharpen this penumbra. The combination of the electron and the photon beams yields dose distributions with the characteristics (a)-(c) mentioned above.

Efficient and reliable 3D dose quality assurance for IMRT by combining independent dose calculations with measurements

PURPOSE Advanced radiotherapy treatments require appropriate quality assurance (QA) to verify 3D dose distributions. Moreover, increase in patient numbers demand efficient QA-methods. In this study, a time efficient method that combines model-based QA and measurement-based QA was developed; i.e., the hybrid-QA. The purpose of this study was to determine the reliability of the model-based QA and to evaluate time efficiency of the hybrid-QA method. METHODS Accuracy of the model-based QA was determined by comparison of COMPASS calculated dose with Monte Carlo calculations for heterogeneous media. In total, 330 intensity modulated radiation therapy (IMRT) treatment plans were evaluated based on the mean gamma index (GI) with criteria of 3%∕3mm and classification of PASS (GI ≤ 0.4), EVAL (0.4 < GI > 0.6), and FAIL (GI ≥ 0.6). Agreement between model-based QA and measurement-based QA was determined for 48 treatment plans, and linac stability was verified for 15 months. Finally, time efficiency improvement of the hybrid-QA was quantified for four representative treatment plans. RESULTS COMPASS calculated dose was in agreement with Monte Carlo dose, with a maximum error of 3.2% in heterogeneous media with high density (2.4 g∕cm(3)). Hybrid-QA results for IMRT treatment plans showed an excellent PASS rate of 98% for all cases. Model-based QA was in agreement with measurement-based QA, as shown by a minimal difference in GI of 0.03 ± 0.08. Linac stability was high with an average GI of 0.28 ± 0.04. The hybrid-QA method resulted in a time efficiency improvement of 15 min per treatment plan QA compared to measurement-based QA. CONCLUSIONS The hybrid-QA method is adequate for efficient and accurate 3D dose verification. It combines time efficiency of model-based QA with reliability of measurement-based QA and is suitable for implementation within any radiotherapy department.

Limited benefit of inversely optimised intensity modulation in breast conserving radiotherapy with simultaneously integrated boost

BACKGROUND AND PURPOSE To examine whether in breast-conserving radiotherapy (RT) with simultaneously integrated boost (SIB), application of inversely planned intensity-modulated radiotherapy (IMRT-SIB) instead of three-dimensional RT (3D-CRT-SIB) has benefits that justify the additional costs, and to evaluate whether a potential benefit of IMRT-SIB depends on specific patient characteristics. MATERIAL AND METHODS 3D-CRT-SIB and various IMRT-SIB treatment plans were constructed and optimised for 30 patients with early stage left-sided breast cancer. Coverage of planning target volumes (PTVs) and dose delivered to organs at risk (OARs) were determined for each plan. Overlap between heart and breast PTV (OHB), size of breast and boost PTVs and boost location were examined in their ability to identify patients that might benefit from IMRT-SIB. RESULTS All plans had adequate PTV coverage. IMRT-SIB generally reduced dose levels delivered to heart, lungs, and normal breast tissue relative to 3D-CRT-SIB. However, IMRT-SIB benefit differed per patient. For many patients, comparable results were obtained with 3D-CRT-SIB, while patients with OHB>1.4 cm and a relatively large boost PTV volume (>125 cm(3)) gained most from the use of IMRT-SIB. CONCLUSIONS In breast-conserving RT, results obtained with 3D-CRT-SIB and IMRT-SIB are generally comparable. Patient characteristics could be used to identify patients that are most likely to benefit from IMRT-SIB.