S. Petillion

Breathing adapted radiation therapy in comparison with prone position to reduce the doses to the heart, left anterior descending coronary artery, and contralateral breast in whole breast radiation therapy.

PURPOSE To compare 3 different treatment positions in whole breast radiation therapy in terms of target volume coverage and doses to the organs at risk (OAR). METHODS AND MATERIALS Thirty-four breast cancer (BC) patients (17 right-sided and 17 left-sided) were included in this dosimetric planning study. They all underwent a computed tomography (CT) scan in standard supine position in free-breathing (FB), supine position with gating in deep inspiratory breath hold (DIBH)(G), and prone position (P). Three-dimensional treatment plans were made for all 3 CTs. Target coverage and OAR sparing were evaluated. RESULTS Breast volumes varied between 209 and 2814 cm(3). The target coverage, expressed as the mean volume of the breast receiving at least 95% of the prescription dose, was similar for the 3 treatment positions. The mean lung dose and the volume of the lungs receiving >20 Gy were significantly lower in P (1.7 Gy; 2.3%) compared with G (3.4 Gy; 5.6%; P < .0001) and FB (4 Gy; 7.3%; P < .0001). The volume of the contralateral breast receiving >5 Gy was significantly lower in G (P = .001) or FB (P = .004) versus prone. The supine position with gating in DIBH significantly reduced the volume of the heart receiving >30 Gy (V30(heart)), the mean heart (D(heart)), and mean left anterior descending coronary artery (LAD) dose (D(LAD)) for left-sided BC patients (V30(heart) 0.9%, D(heart) 1.6 Gy, DLAD 22.4 Gy) with respect to FB (V30(heart) 4.3%, D(heart) 3.5 Gy, DLAD 30.9 Gy)(V30(heart) and mean D(heart): P ≤ .0001; mean D(LAD): P = .008) and P (V30(heart) 7.9%, D(heart) 5.4 Gy, D(LAD) 36.4 Gy)(V30(heart) and mean D(heart): P = .0004; mean D(LAD): P = .01). CONCLUSIONS The coverage of the planning target volume breast was equal for the 3 treatment positions. The lowest doses to the lungs were achieved in prone. The heart, LAD, and contralateral breast were best spared in the supine position with gating in DIBH.

The photon dose calculation algorithm used in breast radiotherapy has significant impact on the parameters of radiobiological models.

The comparison of the pencil beam dose calculation algorithm with modified Batho heterogeneity correction (PBC‐MB) and the analytical anisotropic algorithm (AAA) and the mutual comparison of advanced dose calculation algorithms used in breast radiotherapy have focused on the differences between the physical dose distributions. Studies on the radiobiological impact of the algorithm (both on the tumor control and the moderate breast fibrosis prediction) are lacking. We, therefore, investigated the radiobiological impact of the dose calculation algorithm in whole breast radiotherapy. The clinical dose distributions of 30 breast cancer patients, calculated with PBC‐MB, were recalculated with fixed monitor units using more advanced algorithms: AAA and Acuros XB. For the latter, both dose reporting modes were used (i.e., dose‐to‐medium and dose‐to‐water). Next, the tumor control probability (TCP) and the normal tissue complication probability (NTCP) of each dose distribution were calculated with the Poisson model and with the relative seriality model, respectively. The endpoint for the NTCP calculation was moderate breast fibrosis five years post treatment. The differences were checked for significance with the paired t‐test. The more advanced algorithms predicted a significantly lower TCP and NTCP of moderate breast fibrosis then found during the corresponding clinical follow‐up study based on PBC calculations. The differences varied between 1% and 2.1% for the TCP and between 2.9% and 5.5% for the NTCP of moderate breast fibrosis. The significant differences were eliminated by determination of algorithm‐specific model parameters using least square fitting. Application of the new parameters on a second group of 30 breast cancer patients proved their appropriateness. In this study, we assessed the impact of the dose calculation algorithms used in whole breast radiotherapy on the parameters of the radiobiological models. The radiobiological impact was eliminated by determination of algorithm specific model parameters. PACS numbers: 87.55.dh, 87.55.dkThe comparison of the pencil beam dose calculation algorithm with modified Batho heterogeneity correction (PBC-MB) and the analytical anisotropic algorithm (AAA) and the mutual comparison of advanced dose calculation algorithms used in breast radiotherapy have focused on the differences between the physical dose distributions. Studies on the radiobiological impact of the algorithm (both on the tumor control and the moderate breast fibrosis prediction) are lacking. We, therefore, investigated the radiobiological impact of the dose calculation algorithm in whole breast radiotherapy. The clinical dose distributions of 30 breast cancer patients, calculated with PBC-MB, were recalculated with fixed monitor units using more advanced algorithms: AAA and Acuros XB. For the latter, both dose reporting modes were used (i.e., dose-to-medium and dose-to-water). Next, the tumor control probability (TCP) and the normal tissue complication probability (NTCP) of each dose distribution were calculated with the Poisson model and with the relative seriality model, respectively. The endpoint for the NTCP calculation was moderate breast fibrosis five years post treatment. The differences were checked for significance with the paired t-test. The more advanced algorithms predicted a significantly lower TCP and NTCP of moderate breast fibrosis then found during the corresponding clinical follow-up study based on PBC calculations. The differences varied between 1% and 2.1% for the TCP and between 2.9% and 5.5% for the NTCP of moderate breast fibrosis. The significant differences were eliminated by determination of algorithm-specific model parameters using least square fitting. Application of the new parameters on a second group of 30 breast cancer patients proved their appropriateness. In this study, we assessed the impact of the dose calculation algorithms used in whole breast radiotherapy on the parameters of the radiobiological models. The radiobiological impact was eliminated by determination of algorithm specific model parameters. PACS numbers: 87.55.dh, 87.55.dk.

CONFORMAL LOCOREGIONAL BREAST IRRADIATION WITH AN OBLIQUE PARASTERNAL PHOTON FIELD TECHNIQUE

We evaluated an isocentric technique for conformal irradiation of the breast, internal mammary, and medial supra-clavicular lymph nodes (IM-MS LN) using the oblique parasternal photon (OPP) technique. For 20 breast cancer patients, the OPP technique was compared with a conventional mixed-beam technique (2D) and a conformal partly wide tangential (PWT) technique, using dose-volume histogram analysis and normal tissue complication probabilities (NTCPs). The 3D techniques resulted in a better target coverage and homogeneity than did the 2D technique. The homogeneity index for the IM-MS PTV increased from 0.57 for 2D to 0.90 for PWT and 0.91 for OPP (both p < 0.001). The OPP technique was able to reduce the volume of heart receiving more than 30 Gy (V(30)), the cardiac NTCP, and the volume of contralateral breast receiving 5 Gy (V(5)) compared with the PWT plans (all p < 0.05). There is no significant difference in mean lung dose or lung NTCP between both 3D techniques. Compared with the PWT technique, the volume of lung receiving more than 20 Gy (V(20)) was increased with the OPP technique, whereas the volume of lung receiving more than 40 Gy (V(40)) was decreased (both p < 0.05). Compared with the PWT technique, the OPP technique can reduce doses to the contralateral breast and heart at the expense of an increased lung V(20).

Is the use of a preoperative computed tomography beneficial to reduce the interobserver variability of the CTVboost delineation for breast radiation therapy

PURPOSE To determine whether the use of a preoperative (preop) computed tomography (CT) reduces (1) the clinical target volume boost (CTVboost) and (2) the interobserver variability (IOV) of the delineated CTVboost in breast radiation therapy. METHODS AND MATERIALS In patients treated with breast-conserving therapy, 3 CT scans in treatment position were performed: (1) preop; (2) after surgery, prechemotherapy (postop); and (3) postchemotherapy (postchemo). Six radiation-oncologists delineated the tumor bed and CTVboost before and after fusion of the preop CT. To assess the IOV, the Jaccard index was used. Linear mixed models were performedfor all analyses. RESULTS Eighty-two lumpectomy cavities were evaluated in 22 patients. No difference in CTVboost using the fusion of the preop CT (50.0 cm3; 95% confidence interval [CI], 35.6-64.4) compared with no fusion (49.0 cm3; 95% CI, 34.6-63.4) (P = .6) was observed. A significant increase in IOV was shown with the fusion of the preop CT; the mean Jaccard index of the CTVboost delineation of postop and postchemo CT together without the fusion of the preop CT was 0.53 (95% CI, 0.49-0.57) versus 0.50 (95% CI, 0.46-0.53) with fusion (P < .0001). CONCLUSIONS There is no benefit of using a preop CT to reduce the volume or the interobserver variability of the delineated CTVboost for breast radiation therapy.

Efficacy and workload analysis of a fixed vertical couch position technique and a fixed-action–level protocol in whole-breast radiotherapy

Quantification of the setup errors is vital to define appropriate setup margins preventing geographical misses. The no‐action–level (NAL) correction protocol reduces the systematic setup errors and, hence, the setup margins. The manual entry of the setup corrections in the record‐and‐verify software, however, increases the susceptibility of the NAL protocol to human errors. Moreover, the impact of the skin mobility on the anteroposterior patient setup reproducibility in whole‐breast radiotherapy (WBRT) is unknown. In this study, we therefore investigated the potential of fixed vertical couch position‐based patient setup in WBRT. The possibility to introduce a threshold for correction of the systematic setup errors was also explored. We measured the anteroposterior, mediolateral, and superior–inferior setup errors during fractions 1–12 and weekly thereafter with tangential angled single modality paired imaging. These setup data were used to simulate the residual setup errors of the NAL protocol, the fixed vertical couch position protocol, and the fixed‐action–level protocol with different correction thresholds. Population statistics of the setup errors of 20 breast cancer patients and 20 breast cancer patients with additional regional lymph node (LN) irradiation were calculated to determine the setup margins of each off‐line correction protocol. Our data showed the potential of the fixed vertical couch position protocol to restrict the systematic and random anteroposterior residual setup errors to 1.8 mm and 2.2 mm, respectively. Compared to the NAL protocol, a correction threshold of 2.5 mm reduced the frequency of mediolateral and superior–inferior setup corrections with 40% and 63%, respectively. The implementation of the correction threshold did not deteriorate the accuracy of the off‐line setup correction compared to the NAL protocol. The combination of the fixed vertical couch position protocol, for correction of the anteroposterior setup error, and the fixed‐action–level protocol with 2.5 mm correction threshold, for correction of the mediolateral and the superior–inferior setup errors, was proved to provide adequate and comparable patient setup accuracy in WBRT and WBRT with additional LN irradiation. PACS numbers: 87.53.Kn, 87.57.‐s

Accuracy of a new paired imaging technique for position correction in whole breast radiotherapy.

Image‐guided position verification in breast radiotherapy is accurately performed with kilovoltage cone beam CT (kV‐CBCT). The technique is, however, time‐consuming and there is a risk for patient collision. Online position verification performed with orthogonal‐angled mixed modality paired imaging is less time‐consuming at the expense of inferior accuracy compared to kV‐CBCT. We therefore investigated whether a new tangential‐angled single modality paired imaging technique can reduce the residual error (RE) of orthogonal‐angled mixed modality paired imaging. The latter was applied to 20 breast cancer patients. Tangential‐angled single modality paired imaging was investigated in 20 breast and 20 breast cancer patients with locoregional lymph node irradiation. The central lung distance (CLD) residual error and the longitudinal residual error were determined during the first 5 treatment fractions. Off‐line matching of the tangential breast field images, acquired after online position correction, was used. The mean, systematic, and random REs of each patient group were calculated. The systematic REs were checked for significant differences using the F‐test. Tangential‐angled single modality paired imaging significantly reduced the systematic CLD residual error of orthogonal‐angled mixed modality paired imaging for the breast cancer patients, from 2.3 mm to 1.0 mm, and also significantly decreased the systematic longitudinal RE from 2.4 mm to 1.3 mm. PTV margins, which account for the residual error (PTVRE), were also calculated. The PTVRE margin needed to account for the RE of orthogonal‐angled mixed modality paired imaging (i.e., 8 mm) was halved by tangential‐angled single modality paired imaging. The differences between the systematic REs of tangential‐angled single modality paired imaging of the breast cancer patients and the breast cancer patients with locoregional lymph node irradiation were not significant, yielding comparable PTVRE margins. In this study, we showed that tangential‐angled single modality paired imaging is superior to orthogonal‐angled mixed modality paired imaging to correct the position errors in whole breast radiotherapy. PACS numbers: 87.57N‐, 87.56Da, 87.53Kn

Boost delineation in breast radiation therapy: Isotropic versus anisotropic margin expansion

PURPOSE The purpose of this article is to compare isotropic and anisotropic margin expansion with regard to the size of the clinical target volume boost (CTVboost) and the interobserver variability (IOV). METHODS AND MATERIALS Lumpectomy cavities marked with 3 or more surgical clips were delineated by 6 radiation oncologists who specialized in breast radiation therapy. CTVboost anisotropic was created by manually expanding the tumor bed with an anisotropic margin of 15 mm (20 mm in case of extensive intraductal component) minus the surgical free margins in 6 directions (anteroposterior, craniocaudal, and superoinferior). For the CTVboost isotropic, the tumor bed was enlarged with an isotropic margin of 15 mm (20 mm in case of extensive intraductal component) minus the minimal surgical free margin. The volumes of the delineated CTVboost (cm3) were measured. To assess the IOV, the Jaccard index (JI), defined as the intersection divided by the size of the union of the sample sets, was used (ideal value = 1). The JI was calculated for each case and each observer pair. Linear mixed models were used for all analyses. RESULTS A total of 444 delineated tumor beds were evaluated. The mean volume of the CTVboost almost doubled by expanding the tumor bed with an isotropic margin compared with anisotropic margins (CTVboost isotropic 94 mL [12.5-331.0] vs CTVboost anisotropic 50 mL [3.2-332.7]; P = .0006). The IOV, assessed by the JI, significantly decreased by using isotropic versus anisotropic margin expansion (JICTV boost isotropic 0.73 [0.02-0.92] vs JICTV boost anisotropic 0.51 [0.0-0.8]; P< .0001). Because of the known positive correlation of the IOV and larger volumes, we corrected for CTVboost volumes. With this correction, the difference in IOV remains highly significant (P < .0001) in favor of isotropic margin expansion. CONCLUSIONS The use of anisotropic margin expansion from tumorbed to CTVboost isotropic significantly reduced the volume of the delineated CTVboost with a factor of 1.9 compared with isotropic margin expansion, but it substantially increased the interobserver variability.

SU-FF-T-162: Does the Implementation of Electron Monte Carlo Simulation Based Treatment Planning Have Radiobiologically Significant Ramifications?

Purpose: To quantify differences in dosedeposition between three different methodologies determining the dose delivered by electrons in the treatment of breast carcinoma. The quantification is performed using radio‐biological models and we determine whether the difference is significant on radio‐biological level. Methods: Twenty patients to be treated with chestwall irradiation are planned in a conventional way using electron fields. The treatments are planned using a pencil beam algorithm, a monte carlo simulation based TPS, and manual hand calcs. Using a dose volumes histogram decomposition technique we calculate tumor control probability for the chest wall, the medial supraclavicular‐, and the intra‐mammary lymph nodes. Normal tissue complication probabilities are calculated using different models, including Burman‐Kutcher effective volume and relative seriality Poisson based models. Endpoints are excess of cardiac mortality risk and radiation pneumonitis. Results: We find that there is a significant difference for PB based compared to MC‐based dose calculation for TCP—values. Both methods are lower than the “ideal” case where we assume homogeneous irradiation of the target structure to the prescribed dose level. The TCP for PB calculation is on average 3% (1SD = 1%) higher than the TCP calculated with a MC‐based TPS. Levels of TCP with respect to the ideal case for IM‐MS irradiation are 7%, resp. 10% for PB resp. MC. For NTCP an overall decrease is noted although not significant with the data available at the submission time. Cases with an inverse shift in NTCP are found (i.e. NTCP‐PB < NTCP‐MC). Conclusions: The outcome predicted from the radio‐biological models is dependent on the algorithm used to determine the dosedeposition. This implies that the use of patient data to fit radio‐biological models needs to be accompanied with the type of dose calculation used. Preferably, all such studies should be performed with a gold standard methodology.

Feasibility study of individualized optimal positioning selection for left‐sided whole breast radiotherapy: DIBH or prone

Abstract The deep inspiration breath hold (DIBH) and prone (P) position are two common heart‐sparing techniques for external‐beam radiation treatment of left‐sided breast cancer patients. Clinicians select the position that is deemed to be better for tissue sparing based on their experience. This approach, however, is not always optimum and consistent. In response to this, we develop a quantitative tool that predicts the optimal positioning for the sake of organs at risk (OAR) sparing. Sixteen left‐sided breast cancer patients were considered in the study, each received CT scans in the supine free breathing, supine DIBH, and prone positions. Treatment plans were generated for all positions. A patient was classified as DIBH or P using two different criteria: if that position yielded (1) lower heart dose, or (2) lower weighted OAR dose. Ten anatomical features were extracted from each patients data, followed by the principal component analysis. Sequential forward feature selection was implemented to identify features that give the best classification performance. Nine statistical models were then applied to predict the optimal positioning and were evaluated using stratified k‐fold cross‐validation, predictive accuracy and receiver operating characteristic (AUROC). For heart toxicity‐based classification, the support vector machine with radial basis function kernel yielded the highest accuracy (0.88) and AUROC (0.80). For OAR overall toxicities‐based classification, the quadratic discriminant analysis achieved the highest accuracy (0.90) and AUROC (0.84). For heart toxicity‐based classification, Breast volume and the distance between Heart and Breast were the most frequently selected features. For OAR overall toxicities‐based classification, Heart volume, Breast volume and the distance between ipsilateral lung and breast were frequently selected. Given the patient data considered in this study, the proposed statistical model is feasible to provide predictions for DIBH and prone position selection as well as indicate important clinical features that affect the position selection.

Development of a normal tissue complication probability model for late unfavourable aesthetic outcome after breast-conserving therapy

Abstract Purpose/Objectives: To develop a normal tissue complication probability (NTCP) model for late unfavourable aesthetic outcome (AO) after breast-conserving therapy. Material and Methods: The BCCT.core software evaluated the AO using standardized photographs of patients treated between 2009 and 2014. Dose maps in 2 Gy equivalents were calculated assuming α/β = 3.6 Gy. Uni- and multivariable logistic regression analysis was performed to study the predictive value of clinicopathological and dosimetric variables for unfavourable AO. The Lyman Kutcher Burman (LKB) model was fit to the data with dose modifying factors (dmf). Model performance was assessed with the area under the curve (AUC) of the receiver operating characteristic curve and bootstrap sampling. Results: Forty-four of the 121 analysed patients (36%) developed unfavourable AO. In the optimal multivariable logistic regression model, a larger breast volume receiving ≥55 Gy (V55), a seroma and an axillary lymph node dissection (ALND) were independently associated with an unfavourable AO, AUC = 0.75 (95%CI 0.64;0.85). Beta-estimates were −2.68 for β0, 0.057 for V55, 1.55 for seroma and 1.20 for ALND. The optimal LKB model parameters were EUD3.6(50) = 63.3 Gy, n = 1.00, m = 0.23, dmf(seroma) = 0.83 and dmf(ALND) = 0.84, AUC = 0.74 (95%CI 0.61;0.83). Conclusions: An NTCP model for late unfavourable AO after breast-conserving therapy was developed including seroma, axillary lymphadenectomy and V55.