Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial.

BACKGROUND AND PURPOSE: Partial breast irradiation (PBI)has beenthe Danish Breast Cancer Group(DBCG) standard for selected breast cancer patients since 2016 based onearlyresults from the DBCG PBI trial.During trial accrual, respiratory-gated radiotherapy was introduced in Denmark. This study aims to investigate the effect of respiratory-gating on mean heart dose (MHD). PATIENTS AND METHODS: From 2009 to 2016 the DBCG PBI trial included 230 patientswith left-sided breast cancer receiving external beam PBI, 40 Gy/15 fractions/3 weeks.Localization of the tumor bed on the planning CT scan, the use of respiratory-gating, coverage of the clinical target volume (CTV), and doses to organs at risk were collected. RESULTS: Respiratory-gating was used in 123 patients (53 %). In 176 patients (77 %) the tumor bed was in the upper and in 54 patients (23 %) in the lower breast quadrants. The median MHD was 0.37 Gy (interquartile range 0.26-0.57 Gy), 0.33 Gy (0.23-0.49 Gy) for respiratory-gating, and 0.49 Gy (0.31-0.70 Gy) for free breathing, p < 0.0001. MHD was < 1 Gy in 206 patients (90 %) and < 2 Gy in 221 patients (96 %). Respiratory-gating led to significantly lower MHD for upper-located, but not for lower-located tumor beds, however, all MHD were low irrespective of respiratory-gating. Respiratory-gating did not improve CTV coverage or lower lung doses. CONCLUSIONS: PBI ensured a low MHD for most patients. Adding respiratory-gating further reduced MHD for upper-located but not for lower-located tumor beds but did not influence target coverage or lung doses. Respiratory-gating is no longer DBCG standard for left-sided PBI.

Volume matters: Breast induration is associated with irradiated breast volume in the Danish Breast Cancer Group phase III randomized Partial Breast Irradiation trial.

PURPOSE: The relation between breast induration grade 2-3 at 3 years after radiation therapy and irradiated breast volume was investigated for patients in the Danish Breast Cancer Group (DBCG) Partial Breast Irradiation (PBI) trial. METHODS Treatment plan data was obtained from the Danish radiotherapy plan database. Dosimetric parameters for breast and organs at risk were determined. Breast induration data was obtained from the DBCG database. The volume of the whole breast (CTVp_breast) treated to various dose levels was determined for treatment plans in both arms. Logistic regression was used to assess the frequency of induration on breast volume irradiated to ≥40 Gy. RESULTS PBI and WBI was given to 433 and 432 patients, respectively. Median and interquartile ranges (IQR) for CTVp_breast were 710 mL (467-963 mL; PBI) and 666 mL (443-1012 mL; WBI) (p = 0.98). Median and IQR for CTVp_breast treated to ≥40 Gy was 24.9% (18.6-32.6%; PBI) and 59.8% (53.6-68.5%; WBI). Grade 2-3 induration was observed in 5% (PBI) and 10% (WBI) of the patients. A dose-response relationship was established between irradiated breast volume and frequency of breast induration. From the model, 5% and 10% risks of breast induration were observed for ≥40 Gy delivered to CTVp_breast volumes of 177 mL (95%CI, 94-260 mL) and 426 mL (95%CI, 286-567 mL), respectively. CONCLUSION The frequency of breast induration increased significantly with increasing irradiated breast volume, strongly favouring small volumes and PBI. Thus, treated breast volume - not the breast size itself - is the risk factor for induration. This is the first report directly linking the 40 Gy irradiated breast volume to breast induration.

Partial Breast Irradiation Versus Whole Breast Irradiation for Early Breast Cancer Patients in a Randomized Phase III Trial: The Danish Breast Cancer Group Partial Breast Irradiation Trial.

PURPOSE: On the basis of low risk of local recurrence in elderly patients with breast cancer after conservative surgery followed by whole breast irradiation (WBI), the Danish Breast Cancer Group initiated the noninferiority external-beam partial breast irradiation (PBI) trial (ClinicalTrials.gov identifier: NCT00892814). We hypothesized that PBI was noninferior to WBI regarding breast induration. METHODS: Patients operated with breast conservation for relatively low-risk breast cancer were randomly assigned to WBI versus PBI, and all had 40 Gy/15 fractions. The primary end point was 3-year grade 2-3 breast induration. RESULTS: In total, 865 evaluable patients (434 WBI and 431 PBI) were enrolled between 2009 and 2016. Median follow-up was 5.0 years (morbidity) and 7.6 years (locoregional recurrence). The 3-year rate of induration was 9.7% for WBI and 5.1% for PBI (P = .014). Large breast size was significantly associated with induration with a 3-year incidence of 13% (WBI) and 6% (PBI) for large-breasted patients versus 6% (WBI) and 5% (PBI) for small-breasted patients. PBI showed no increased risk of dyspigmentation, telangiectasia, edema, or pain, and patient satisfaction was high. Letrozole and smoking did not increase the risk of radiation-associated morbidity. Sixteen patients had a locoregional recurrence (six WBI and 10 PBI; P = .28), 20 patients had a contralateral breast cancer, and eight patients had distant failure (five WBI and three PBI). A nonbreast second cancer was detected in 73 patients (8.4%), and there was no difference between groups. CONCLUSION: External-beam PBI for patients with low-risk breast cancer was noninferior to WBI in terms of breast induration. Large breast size was a risk factor for radiation-associated induration. Few recurrences were detected and unrelated to PBI.

Density calibrated cone beam CT as a tool for adaptive radiotherapy.

BACKGROUND: Visual inspections of anatomical changes observed on daily cone-beam CT (CBCT) images are often used as triggers for radiotherapy plan adaptation to avoid unacceptable dose levels to the target or OARs. Direct CBCT dose calculations would improve the ability to adapt only those plans where dosimetric changes are observed. This study investigates the accuracy of dose calculations on CBCTs. MATERIALS AND METHODS: Calibration curves were obtained for CBCT imagers at nine identical accelerators. CBCT scans of a phantom with different density inserts were recorded for two scan modes (Head-Neck and Pelvis) and mean calibration curves were calculated. Subsequently, CBCT scans of the phantom with six different density inserts were recorded, the dose distributions on the CBCTs were calculated and compared to dose on the planning CT (pCT). The uncertainty was quantified by the dosimetric difference between the pCT and the CBCT. The two mean calibration curves were used to calculate the daily delivered CBCT dose for ten Head-Neck-, eleven Lung-, and ten pelvic patients. Additional patient calculations were performed using low-HU empirically corrected calibration curves. Patient doses were compared on target coverage and mean dose, and D1cc for OARs. RESULTS: The dose differences between pCT and CBCT for phantom data were small for all DVH parameters, with mean deviations below ±0.6% for both CBCT modes. For patient data, it was found that low-HU corrected calibration curves performed the best. The mean deviations for the mean dose and coverage of the target were 0.2%±0.7% and 0.1%±0.6%, across all patient groups. CONCLUSION: Dose calculation on CBCT images results in target coverage and mean dose with an accuracy of the order of 1%, which makes this acceptable for clinical use. The CBCT mode specific calibration curves can be used at all identical imaging devices and for all patient groups.

The potential benefits from respiratory gating for breast cancer patients regarding target coverage and dose to organs at risk when applying strict dose limits to the heart: results from the DBCG HYPO trial.

PURPOSE: The potential benefits from respiratory gating (RG) compared to free-breathing (FB) regarding target coverage and dose to organs at risk for breast cancer patients receiving post-operative radiotherapy (RT) in the DBCG HYPO multicentre trial are reported. MATERIAL AND METHODS: Patients included in the DBCG HYPO trial were randomized between 50 Gy in 25 fractions (normofractionated) versus 40 Gy in 15 fractions (hypofractionated). A tangential forward field-in-field dose planning technique was used to cover the clinical target volume (CTV) with the intent to limit dose to the left anterior descending coronary artery (LADCA) to 20 Gy and 17 Gy in the normo- and hypofractionated arms, respectively. Treatment plan data for 1327 patients from four Danish centres was retrospectively analyzed. FB right-sided patients served as control group for the left-sided patients regarding CTV V95% (relative volume receiving at least 95% of the prescribed dose), mean heart dose (MHD) and mean lung dose (MLD). RESULTS: Median CTV V95% was for FB right-sided, FB left-sided and RG left-sided patients 94.6, 92.6 and 94.7% for normofractionated therapy, respectively, and 94.6, 91.8 and 94.4% for hypofractionated therapy and did not differ significantly for RG left-sided plans compared to FB right-sided in either study arm. CTV V95% was significantly lower for FB versus RG for left-sided plans in both arms. Median MHD was 0.7, 1.8 and 1.5 Gy (normofractionated therapy) versus 0.6, 1.5 and 1.2 Gy (hypofractionated therapy), respectively. The corresponding median MLD was 9.0, 8.3 and 7.3 Gy versus 7.3, 6.4 and 5.8 Gy, respectively. CONCLUSIONS: RG for left-sided breast cancer patients ensured similar CTV V95% as for FB right-sided patients. MLD was lower for RG due to the increased lung volume. MHD was generally low due to strict protocol-defined maximum dose to LADCA, but for left-sided patients RG led to significantly lower MHD.

Quality assessment of delineation and dose planning of early breast cancer patients included in the randomized Skagen Trial 1.

BACKGROUND AND PURPOSE: To report on a Quality assessment (QA) of Skagen Trial 1, exploring hypofractionation for breast cancer patients with indication for regional nodal radiotherapy. MATERIAL AND METHODS: Deviations from protocol regarding target volume delineations and dose parameters (Dmin, Dmax, D98%, D95% and D2%) from randomly selected dose plans were assessed. Target volume delineation according to ESTRO guidelines was obtained through atlas based automated segmentation and centrally approved as gold standard (GS). Dice similarity scores (DSC) with original delineations were measured. Dose parameters measured in the two delineations were reported to assess their dosimetric outcome. RESULTS: Assessment included 88 plans from 12 centres in 4 countries. DSC showed high agreement in contouring, 99% and 96% of the patients had a complete delineation of target volumes and organs at risk. No deviations in the dosimetric outcome were found in 76% of the patients, 82% and 95% of the patients had successful coverage of breast/chestwall and CTVn_L2-4-interpectoral. Dosimetric outcomes of original delineation and GS were comparable. CONCLUSIONS: QA showed high protocol compliance and adequate dose coverage in most patients. Inter-observer variability in contouring was low. Dose parameters were in harmony with protocol regardless original or GS segmentation.

Dosimetric assessment of an Atlas based automated segmentation for loco-regional radiation therapy of early breast cancer in the Skagen Trial 1: A multi-institutional study.

The effect of Atlas-based automated segmentation (ABAS) on dose volume histogram (DVH) parameters compared to manual segmentation (MS) in loco-regional radiotherapy (RT) of early breast cancer was investigated in patients included in the Skagen Trial 1. This analysis supports implementation of ABAS in clinical practice and multi-institutional trials.

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.

CT-planned internal mammary node radiotherapy in the DBCG-IMN study: benefit versus potentially harmful effects.

BACKGROUND: The DBCG-IMN is a nationwide population-based cohort study on the effect of internal mammary node radiotherapy (IMN-RT) in patients with node positive early breast cancer. Due to the risk of RT-induced heart disease, only patients with right-sided breast cancer received IMN-RT, whereas patients with left-sided breast cancer did not. At seven-year median follow-up, a 3% gain in overall survival with IMN-RT has been reported. This study estimates IMN doses and doses to organs at risk (OAR) in patients from the DBCG-IMN. Numbers needed to harm (NNH) if patients with left-sided breast cancer had received IMN-RT are compared to the number needed to treat (NNT). MATERIAL AND METHODS: Ten percent of CT-guided treatment plans from the DBCG-IMN patients were selected randomly. IMNs and OAR were contoured in 68 planning CT scans. Dose distributions were re-calculated. IMNs and OAR dose estimates were compared in right-sided versus left-sided breast cancer patients. In six left-sided patients, IMN-RT was simulated, and OAR doses were compared to those in the original plan. The NNH resulting from the change in mean heart dose (MHD) was calculated using a published model for risk of RT-related ischemic heart death. RESULTS: In original plans, the absolute difference between right- and left-sided V90% to the IMNs was 38.0% [95% confidence interval (5.5%; 70.5%), p < 0.05]. Heart doses were higher in left-sided plans. With IMN-RT simulation without regard to OAR constraints, MHD increased 4.8 Gy (0.9 Gy; 8.7 Gy), p < 0.05. Resulting NNHs from ischemic heart death were consistently larger than the NNT with IMN-RT. CONCLUSION: Refraining from IMN-RT on the left side may have spared some ischemic heart deaths. Assuming left-sided patients benefit as much from IMN-RT as right-sided patients, the benefits from IMN-RT outweigh the costs in terms of ischemic heart death.

Inter- and intra-fraction geometric errors in daily image-guided radiotherapy of free-breathing breast cancer patients measured with continuous portal imaging.

BACKGROUND: Daily image-guided radiotherapy (IGRT) using two orthogonal setup images may be inaccurate for breast cancer patients treated in free breathing because the setup images may capture the patient in a breathing phase that is not representative of the mean anatomy. The aim of this study was to quantify the setup errors in breast radiotherapy after image-guided setup correction based on two orthogonal setup images acquired in free breathing. METHODS AND MATERIALS: For 16 breast cancer patients with daily image-pair based IGRT, continuous portal imaging (7.5 Hz) were acquired at each treatment fraction during the delivery of the two tangential fields. For each portal image, the chest wall position relative to the planned position was determined in the imager direction orthogonal to the cranio-caudal direction. It yielded the time resolved setup error in this direction throughout the 16 treatment courses. RESULTS: The mean absolute setup error exceeded 5 mm in 0.9% (first field) and 1.8% (last field) of the treatments. The group mean error (M) and the standard deviations of the random (σ) and systematic (Σ) setup errors were M=-0.7 mm, Σ=1.1 mm, σ=1.5 mm (first field) and M=-0.2 mm, Σ=1.4 mm, σ=1.7 mm (last field). The negative sign of M indicates that less lung than planned was included in the treatment fields. Intra-field peak-to-peak chest wall motion amplitudes were patient dependent with patient mean values of 2.0±0.7 mm [range 1.1-3.2 mm]. The largest observed intra-field motion amplitude was 8 mm. CONCLUSION: Image-guided setup based on orthogonal planar images acquired in free breathing without synchronization with the respiratory phase was found to result in accurate tangential breast radiotherapy with only few outliers.

Quality assurance of conventional non-CT-based internal mammary lymph node irradiation in a prospective Danish Breast Cancer Cooperative Group trial: the DBCG-IMN study.

UNLABELLED: In 2003, the Danish Breast Cancer Cooperative Group (DBCG) initiated DBCG-IMN, a prospective study on the effect of adjuvant internal mammary lymph node radiotherapy (IMN-RT) in patients with early lymph node positive breast cancer (BC). In the study, standard DBCG IMN-RT was provided only to patients with right-sided BC. We provide estimates of doses to IMNs and organs at risk (OARs) in patients treated with the non-CT-based RT techniques used during the DBCG-IMN study. MATERIAL AND METHODS: Five DBCG RT regimens were simulated on planning CT scans from 50 consecutively scanned BC patients, 10 in each group. Intended target volumes were chest wall or breast and regional lymph nodes ± IMNs. Field planning was conducted in the Eclipse(TM) RT treatment planning system. Subsequently, IMN clinical target volumes (CTVs) and OARs were delineated. Estimates on doses to the IMN-CTV and OARs were made. RESULTS: IMN dose coverage estimates were consistently higher in right-sided techniques where IMN treatment was intended (p < 0.0001). Estimated doses to cardiac structures were low regardless of whether IMNs were treated or not. Post-lumpectomy patients had the highest estimated lung doses. CONCLUSION: Overall, simulator-based treatment using the DBCG RT techniques resulted in satisfactory coverage of IMNs and acceptable levels of OAR irradiation.

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.

UNLABELLED: 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.

Post-mastectomy radiotherapy in Denmark: from 2D to 3D treatment planning guidelines of The Danish Breast Cancer Cooperative Group.

This paper describes the procedure of changing from 2D to 3D treatment planning guidelines for post-mastectomy radiotherapy in Denmark. The aim of introducing 3D planning for post-mastectomy radiotherapy was to optimize the target coverage and minimize the dose to the normal tissues. Initially, it was investigated whether it was possible to find a treatment technique alternative to the one recommended by the Danish Breast Cancer Cooperative Group (DBCG). A dosimetric comparison of a combined photon/electron 3-field technique (3F) and a partial wide tangent technique (PWT) was carried out on individual planning CT-scans from seven patients selected to represent a wide range of sizes and shapes of chest walls. The heart dose was lower for PWT than for 3F, however, for both techniques the dose was within the accepted constraints. The lung dose was higher but acceptable for six of the seven patients with PWT. The dose to the internal mammary nodes (IMN) was not satisfactory for five of the seven patients for 3F, whereas only two of the seven patients had a minimum dose lower than 95% of the prescribed dose with PWT. Finally, the dose to the contralateral breast was increased when using PWT compared to 3F. It was concluded that PWT was an appropriate choice of technique for future radiation treatment of post-mastectomy patients. A working group was formed and guidelines for 3D planning were developed during a series of workshops where radiation oncologists and physicists from all radiotherapy centres participated. This work also included a definition of the tissue structures needed to be outlined on the planning CT-scan. The work was initiated in 2003 and the guidelines were approved by the DBCG Radiotherapy Committee in 2006. The first of January 2007 the 3D guidelines had been fully implemented in five of the seven radiotherapy centres.

Attenuation of 4-20 MV x rays by a new compensator material of cement.

The properties of a new cement based material for production of compensators are presented. Broad beam attenuation of 4-20 MV x rays by slabs of the material have been measured at various field sizes and depths in a large water phantom. For comparison the attenuation of aluminum was determined at some of the photon energies and it was found that the attenuation properties of the cement based material are very close to those of aluminum. At 6 and 18 MV, a comparison of different phantoms for attenuation measurements was carried out. For this investigation the ionization chamber was placed in a 50x50x50 cm3 water phantom, a 20x20x20 cm3 water equivalent plastic phantom, and a cylindrical mini-phantom. Agreement was obtained between the measurements in the large water phantom and in the water equivalent plastic phantom. The measurements carried out with the mini-phantom in a 6 MV x-ray beam gave a higher transmission versus absorber thickness than the transmission found with the water phantom resulting in a lower value of the effective attenuation coefficient. At 18 MV x rays the difference between the measurements in the water phantom and in the mini-phantom was less. This shows that a water equivalent plastic phantom with an area comparable with the largest field size applied can be used for measurements of effective attenuation coefficients, whereas a mini-phantom cannot be used directly, especially at low photon energies.