Ebbe Laugaard Lorenzen

Delineation of target volumes and organs at risk in adjuvant radiotherapy of early breast cancer: National guidelines and contouring atlas by the Danish Breast Cancer Cooperative Group

Abstract During the past decade planning of adjuvant radiotherapy (RT) of early breast cancer has changed from two-dimensional (2D) to 3D conformal techniques. In the planning computerised tomography (CT) scan both the targets for RT and the organs at risk (OARs) are visualised, enabling an increased focus on target dose coverage and homogeneity with only minimal dose to the OARs. To ensure uniform RT in the national prospective trials of the Danish Breast Cancer Cooperative Group (DBCG), a national consensus for the delineation of clinical target volumes (CTVs) and OARs was required. Material and methods. A CT scan of a breast cancer patient after surgical breast conservation and axillary lymph node (LN) dissection was used for delineation. During multiple dummy-runs seven experienced radiation oncologists contoured all CTVs and OARs of interest in adjuvant breast RT. Two meetings were held in the DBCG Radiotherapy Committee to discuss the contouring and to approve a final consensus. The Dice similarity coefficient (DSC) was used to evaluate the delineation agreement before and after the consensus. Results. The consensus delineations of CTVs and OARs are available online and a table is presented with a contouring description of the individual volumes. The consensus provides recommendations for target delineation in a standard patient both in case of breast conservation or mastectomy. Before the consensus, the average value of the DSC was modest for most volumes, but high for the breast CTV and the heart. After the consensus, the DSC increased for all volumes. Conclusion. The DBCG has provided the first national guidelines and a contouring atlas of CTVs and OARs definition for RT of early breast cancer. The DSC is a useful tool in quantifying the effect of the introduction of guidelines indicating improved inter-delineator agreement. This consensus will be used by the DBCG in our prospective trials.

Inter-observer variation in delineation of the heart and left anterior descending coronary artery in radiotherapy for breast cancer: A multi-centre study from Denmark and the UK

BACKGROUND AND PURPOSE To determine the extent of inter-observer variation in delineation of the heart and left anterior descending coronary artery (LADCA) and its impact on estimated doses. METHODS AND MATERIALS Nine observers from five centres delineated the heart and LADCA on fifteen patients receiving left breast radiotherapy. The delineations were carried out twice, first without guidelines and then with a set of common guidelines. RESULTS For the heart, most spatial variation in delineation was near the base of the heart whereas for the LADCA most variation was in its length at the apex of the heart. Common guidelines reduced the spatial variation for the heart and the length of the LAD, but increased the variation in the anterior-posterior/right-left plane. The coefficients of variation (CV) in the estimated doses to the heart were: mean dose 7.5% without and 3.6% with guidelines, maximum dose 8.7% without and 4.0% with guidelines. The CVs in the estimated doses to the LADCA were: mean dose 27% without and 29% with guidelines, maximum dose 39% without and 31% with guidelines. CONCLUSIONS For the heart, there was little inter-observer variation in the estimated dose, especially when guidelines were used. In contrast, for the LADCA there was substantial variation in the estimated dose, which was not reduced with guidelines.

Validation of a new control system for Elekta accelerators facilitating continuously variable dose rate

PURPOSE Elekta accelerators controlled by the current clinically used accelerator control system, Desktop 7.01 (D7), uses binned variable dose rate (BVDR) for volumetric modulated arc therapy (VMAT). The next version of the treatment control system (Integrity) supports continuously variable dose rate (CVDR) as well as BVDR. Using CVDR opposed to BVDR for VMAT has the potential of reducing the treatment time but may lead to lower dosimetric accuracy due to faster moving accelerator parts. Using D7 and a test version of Integrity, differences in ability to control the accelerator, treatment efficiency, and dosimetric accuracy between the two systems were investigated. METHODS Single parameter tests were designed to expose differences in the way the two systems control the movements of the accelerator. In these tests, either the jaws, multi leaf collimators (MLCs), or gantry moved at constant speed while the dose rate was changed in discrete steps. The positional errors of the moving component and dose rate were recorded using the control systems with a sampling frequency of 4 Hz. The clinical applicability of Integrity was tested using 15 clinically used VMAT plans (5 prostate, 5 H&N, and 5 lung) generated by the SmartArc algorithm in PINNACLE. The treatment time was measured from beam-on to beam-off and the accuracy of the dose delivery was assessed by comparing DELTA4 measurements and PINNACLE calculated doses using gamma evaluation. RESULTS The single parameter tests showed that Integrity had an improved feedback between gantry motion and dose rate at the slight expense of MLC control compared to D7. The single parameter test did not reveal any significant differences in the control of either jaws or backup jaws between the two systems. These differences in gantry and MLC control together with the use of CVDR gives a smoother Integrity VMAT delivery compared to D7 with less abrupt changes in accelerator motion. Gamma evaluation (2% of 2 Gy and 2 mm) of the calculated doses and DELTA4 measured doses corrected for systematic errors showed an average pass rate of more than 97.8% for both D7, Integrity BVDR, and Integrity CVDR deliveries. Direct comparisons between the measured doses using strict gamma criteria of 0.5% and 0.5 mm showed excellent agreement between D7 and Integrity delivered doses with average pass rates above 95.7%. Finally, the Integrity control system resulted in a significant 35% (55 +/- 13 s) reduction in treatment time, on average. CONCLUSIONS Single parameter tests showed that the two control systems differed in their feedbac loops between MLC, gantry, and dose rate. These differences made the VMAT deliveries more smooth using the new Integrity treatment control system, compared to the current Desktop 7.01. Together with the use of CVDR, which results in less abrupt changes in dose rate, this further increases the smoothness of the delivery. The use of CVDR for VMAT with the Integrity desktop results in a significant reduction in treatment time compared to BVDR with an average reduction of 35%. This decrease in delivery time was achieved without compromising the dosimetric accuracy.

A cardiac contouring atlas for radiotherapy.

Background and purpose The heart is a complex anatomical organ and contouring the cardiac substructures is challenging. This study presents a reproducible method for contouring left ventricular and coronary arterial segments on radiotherapy CT-planning scans. Material and methods Segments were defined from cardiology models and agreed by two cardiologists. Reference atlas contours were delineated and written guidelines prepared. Six radiation oncologists tested the atlas. Spatial variation was assessed using the DICE similarity coefficient (DSC) and the directed Hausdorff average distance (d→H,avg). The effect of spatial variation on doses was assessed using six different breast cancer regimens. Results The atlas enabled contouring of 15 cardiac segments. Inter-observer contour overlap (mean DSC) was 0.60–0.73 for five left ventricular segments and 0.10–0.53 for ten coronary arterial segments. Inter-observer contour separation (mean d→H,avg) was 1.5–2.2 mm for left ventricular segments and 1.3–5.1 mm for coronary artery segments. This spatial variation resulted in <1 Gy dose variation for most regimens and segments, but 1.2–21.8 Gy variation for segments close to a field edge. Conclusions This cardiac atlas enables reproducible contouring of segments of the left ventricle and main coronary arteries to facilitate future studies relating cardiac radiation doses to clinical outcomes.

Risk of heart disease in relation to radiotherapy and chemotherapy with anthracyclines among 19,464 breast cancer patients in Denmark, 1977–2005

Background and purpose The risk of heart disease subsequent to breast cancer radiotherapy was examined with particular focus on women receiving anthracycline-containing chemotherapy. Material and methods Women diagnosed with early-stage breast cancer in Denmark, 1977–2005, were identified from the register of the Danish Breast Cancer Cooperative Group, as was information on cancer-directed treatment. Information on heart disease was sought from the Danish National Patient and Cause of Death Registries. Incidence rate ratios were estimated comparing left-sided with right-sided cancer (IRR, LvR), stratified by calendar year, age, and time since breast cancer radiotherapy. Results Among 19,464 women receiving radiotherapy, the IRR, LvR, was 1.11 (95% CI 1.03–1.20, p = 0.005) for all heart disease and among those also receiving anthracyclines the IRR, LvR, was 1.32 (95% CI 1.02–1.70, p = 0.03). This risk was highest if the treatment was given before the age of 50 years (IRR, LvR, 1.44, (95% CI 1.04–2.01) but there was no significant trend with age or time since treatment. Conclusions Radiotherapy for left-sided breast cancer is associated with a higher risk of heart disease than for right-sided with the largest increases seen in women who also received anthracycline-containing chemotherapy.

Internal and external validation of an ESTRO delineation guideline – dependent automated segmentation tool for loco-regional radiation therapy of early breast cancer

BACKGROUND AND PURPOSE To internally and externally validate an atlas based automated segmentation (ABAS) in loco-regional radiation therapy of breast cancer. MATERIALS AND METHODS Structures of 60 patients delineated according to the ESTRO consensus guideline were included in four categorized multi-atlas libraries using MIM Maestro™ software. These libraries were used for auto-segmentation in two different patient groups (50 patients from the local institution and 40 patients from other institutions). Dice Similarity Coefficient, Average Hausdorff Distance, difference in volume and time were computed to compare ABAS before and after correction against a gold standard manual segmentation (MS). RESULTS ABAS reduced the time of MS before and after correction by 93% and 32%, respectively. ABAS showed high agreement for lung, heart, breast and humeral head, moderate agreement for chest wall and axillary nodal levels and poor agreement for interpectoral, internal mammary nodal regions and LADCA. Correcting ABAS significantly improved all the results. External validation of ABAS showed comparable results. CONCLUSIONS ABAS is a clinically useful tool for segmenting structures in breast cancer loco-regional radiation therapy in a multi-institutional setting. However, manual correction of some structures is important before clinical use. The ABAS is now available for routine clinical use in Danish patients.

Uncertainties in estimating heart doses from 2D-tangential breast cancer radiotherapy.

Background and purpose We evaluated the accuracy of three methods of estimating radiation dose to the heart from two-dimensional tangential radiotherapy for breast cancer, as used in Denmark during 1982–2002. Material and methods Three tangential radiotherapy regimens were reconstructed using CT-based planning scans for 40 patients with left-sided and 10 with right-sided breast cancer. Setup errors and organ motion were simulated using estimated uncertainties. For left-sided patients, mean heart dose was related to maximum heart distance in the medial field. Results For left-sided breast cancer, mean heart dose estimated from individual CT-scans varied from <1 Gy to >8 Gy, and maximum dose from 5 to 50 Gy for all three regimens, so that estimates based only on regimen had substantial uncertainty. When maximum heart distance was taken into account, the uncertainty was reduced and was comparable to the uncertainty of estimates based on individual CT-scans. For right-sided breast cancer patients, mean heart dose based on individual CT-scans was always <1 Gy and maximum dose always <5 Gy for all three regimens. Conclusions The use of stored individual simulator films provides a method for estimating heart doses in left-tangential radiotherapy for breast cancer that is almost as accurate as estimates based on individual CT-scans.

Contouring and dose calculation in head and neck cancer radiotherapy after reduction of metal artifacts in CT images

Abstract Background: Delineation accuracy of the gross tumor volume (GTV) in radiotherapy planning for head and neck (H&N) cancer is affected by computed tomography (CT) artifacts from metal implants which obscure identification of tumor as well as organs at risk (OAR). This study investigates the impact of metal artifact reduction (MAR) in H&N patients in terms of delineation consistency and dose calculation precision in radiation treatment planning. Material and methods: Tumor and OAR delineations were evaluated in planning CT scans of eleven oropharynx patients with streaking artifacts in the tumor region preceding curative radiotherapy (RT). The GTV-tumor (GTV-T), GTV-node and parotid glands were contoured by four independent observers on standard CT images and MAR images. Dose calculation was evaluated on thirty H&N patients with dental implants near the treated volume. For each patient, the dose derived from the clinical treatment plan using the standard image set was compared with the recalculated dose on the MAR image dataset. Results: Reduction of metal artifacts resulted in larger volumes of all delineated structures compared to standard reconstruction. The GTV-T and the parotids were on average 22% (p < 0.06) and 7% larger (p = 0.005), respectively, in the MAR image plan compared to the standard image plan. Dice index showed reduced inter-observer variations after reduction of metal artifacts for all structures. The average surface distance between contours of different observers improved using the MAR images for GTV and parotids (p = 0.04 and p = 0.01). The median volume receiving a dose difference larger than ±3% was 2.3 cm3 (range 0–32 cm3). Conclusions: Delineation of structures in the head and neck were affected by metal artifacts and volumes were generally larger and more consistent after reduction of metal artifacts, however, only small changes were observed in the dose calculations.

Automatic segmentation of the heart in radiotherapy for breast cancer.

Abstract Background. The aim of this study was to evaluate two fully automatic segmentation methods in comparison with manual delineations for their use in delineating the heart on planning computed tomography (CT) used in radiotherapy for breast cancer. Material and methods. Automatic delineation of heart in 15 breast cancer patients was performed by two different automatic delineation systems. Analysis of accuracy and precision of the differences between manual and automatic delineations were evaluated on volume, mean dose, maximum dose and spatial distance differences. Two sets of manual delineations were used in the evaluation: 1) a set prior to common delineation guidelines; and 2) a second set repeated with a common set of guidelines. Results. Systematic differences between automatic and manual delineations were small for volume as well as dose. The uncertainty of the difference in volume was smaller than or similar to the inter-observer variation in manual delineations. For dose, the uncertainty was similar to manual delineations performed without common guidelines but slightly higher than the variation in manual delineations with common guidelines. Spatial differences between average manual and automatic delineations were largest at the base of the heart, where also large variations are observed in the manual delineations. Both algorithms could be improved slightly at the apex of the heart where the variation of automatic delineation was larger than for the manual delineations. Conclusion. Automatic delineation is an equal alternative to manual delineation when compared to the inter-observer variation. The reduction in precision of measured dose was small compared to other uncertainties affecting the estimated heart dose and would for most applications be outweighed by the benefits of fully automated delineations.

Risk of pacemaker or implantable cardioverter defibrillator after radiotherapy for early-stage breast cancer in Denmark, 1982-2005.

BACKGROUND AND PURPOSE To examine the risk of cardiac conduction abnormalities or severe ventricular arrhythmias requiring implantation of a cardiac implantable electronic device (CIED), either a pacemaker or an implantable cardioverter-defibrillator, subsequent to breast cancer (BC) radiotherapy (RT). MATERIAL AND METHODS All women treated for early-stage BC in Denmark from 1982 to 2005 were identified from the Danish Breast Cancer Cooperative Group. By record linkage to the Danish Pacemaker and ICD Registry information was retrieved on CIED implants subsequent to RT. Standardized incidence ratios (SIR) of CIED implantation were estimated for women receiving RT and compared to women not receiving RT for BC. Uni- and multivariate Poisson regression models were used to estimate incidence rate ratios (IRR) among irradiated women compared to non-irradiated. RESULTS Of 44,423 BC patients, 179 had a CIED implanted among 18,251 women who received RT, and 401 had a CIED in 26,172 who did not receive RT. The unadjusted IRR was 1.09 (0.91-1.30 95% CI) for CIED implants among women receiving RT compared to non-irradiated women and the IRR was 1.13 (0.93-1.38 95% CI) when adjustments were made. CONCLUSIONS BC RT as practiced in Denmark in 1982-2005 did not increase the risk of CIED implants. This indicates that RT for BC does not increase the risk of severe ventricular arrhythmias or cardiac conduction abnormalities.