Katrien Erven

Acute Radiation Effects on Cardiac Function Detected By Strain Rate Imaging in Breast Cancer Patients

PURPOSE To investigate the occurrence of early radiation-induced changes in regional cardiac function using strain rate imaging (SRI) by tissue Doppler echocardiography. METHODS AND MATERIALS We included 20 left-sided and 10 right-sided breast cancer patients receiving radiotherapy (RT) to the breast or chest wall. Standard echocardiography and SRI were performed before RT (baseline), immediately after RT (post-RT), and at 2 months follow-up (FUP) after RT. Regional strain (S) and strain rate (SR) values were obtained from all 18 left ventricular (LV) segments. Data were compared to the regional radiation dose. RESULTS A reduction in S was observed post-RT and at FUP in left-sided patients (S(post-RT): -17.6 ± 1.5%, and S(FUP): -17.4 ± 2.3%, vs. S(baseline): -19.5 ± 2.1%, p < 0.001) but not in right-sided patients. Within the left-sided patient group, S and SR were significantly reduced after RT in apical LV segments (S(post-RT): -15.3 ± 2.5%, and S(FUP): -14.3 ± 3.7%, vs. S(baseline): -19.3 ± 3.0%, p < 0.01; and SR(post-RT): -1.06 ± 0.15 s(-1), and SR(FUP): -1.16 ± 0.28 s(-1), vs. SR(baseline): -1.29 ± 0.27 s(-1), p = 0.01), but not in mid- or basal segments. Furthermore, we observed that segments exposed to more than 3 Gy showed a significant decrease in S after RT (S(post-RT): -16.1 ± 1.6%, and S(FUP): -15.8 ± 3.4%, vs. S(baseline): -18.9 ± 2.6%, p < 0.001). This could not be observed in segments receiving less than 3 Gy. CONCLUSIONS SRI shows a dose-related regional decrease in myocardial function after RT. It might be a useful tool in the evaluation of modern RT techniques, with respect to cardiac toxicity.

Subclinical cardiotoxicity detected by strain rate imaging up to 14 months after breast radiation therapy.

PURPOSE Strain rate imaging (SRI) is a new echocardiographic modality that enables accurate measurement of regional myocardial function. We investigated the role of SRI and troponin I (TnI) in the detection of subclinical radiation therapy (RT)-induced cardiotoxicity in breast cancer patients. METHODS AND MATERIALS This study prospectively included 75 women (51 left-sided and 24 right-sided) receiving adjuvant RT to the breast/chest wall and regional lymph nodes. Sequential echocardiographs with SRI were obtained before RT, immediately after RT, and 8 and 14 months after RT. TnI levels were measured on the first and last day of RT. RESULTS Mean heart and left ventricle (LV) doses were both 9 ± 4 Gy for the left-sided patients and 4 ± 4 Gy and 1 ± 0.4 Gy, respectively, for the right-sided patients. A decrease in strain was observed at all post-RT time points for left-sided patients (-17.5% ± 1.9% immediately after RT, -16.6% ± 1.4% at 8 months, and -17.7% ± 1.9% at 14 months vs -19.4% ± 2.4% before RT, P<.01) but not for right-sided patients. When we considered left-sided patients only, the highest mean dose was given to the anterior left ventricular (LV) wall (25 ± 14 Gy) and the lowest to the inferior LV wall (3 ± 3 Gy). Strain of the anterior wall was reduced after RT (-16.6% ± 2.3% immediately after RT, -16% ± 2.6% at 8 months, and -16.8% ± 3% at 14 months vs -19% ± 3.5% before RT, P<.05), whereas strain of the inferior wall showed no significant change. No changes were observed with conventional echocardiography. Furthermore, mean TnI levels for the left-sided patients were significantly elevated after RT compared with before RT, whereas TnI levels of the right-sided patients remained unaffected. CONCLUSIONS In contrast to conventional echocardiography, SRI detected a regional, subclinical decline in cardiac function up to 14 months after breast RT. It remains to be determined whether these changes are related to clinical outcome. In the meantime, we encourage the use of radiation techniques that minimize the exposure of the anterior LV wall in left-sided patients.

Changes in Pulmonary Function Up to 10 Years After Locoregional Breast Irradiation

PURPOSE To evaluate the long-term impact of locoregional breast radiotherapy (RT) on pulmonary function tests (PFTs). METHODS AND MATERIALS This study included 75 women who underwent postoperative locoregional breast RT. PFTs were performed before RT and 3, 6, and 12 months and 8 to 10 years after RT. By use of univariate and multivariate analyses, the impact of treatment- and patient-related factors on late changes in PFTs was evaluated. RESULTS During the first year after RT, all PFTs significantly worsened at 3 to 6 months after RT (p < 0.05). At 12 months, forced vital capacity (FVC), vital capacity (VC), and forced expiratory volume in 1 second (FEV(1)) recovered almost to baseline values, whereas total lung capacity (TLC) and diffusion capacity of carbon monoxide (DL(CO)) recovered only slightly and were still found to be decreased compared with baseline (p < 0.05). At 8 to 10 years after RT, mean reductions in FEV(1) of 4% (p = 0.03) and in VC, DL(CO), and TLC of 5%, 9%, and 11% (all p < 0.0001), respectively, were observed compared with pre-RT values. On multivariate analysis, tamoxifen use negatively affected TLC at 8 to 10 years after RT (p = 0.033), whereas right-sided irradiation was associated with a late reduction in FEV(1) (p = 0.027). For FEV(1) and DL(CO), an early decrease was predictive for a late decrease (p = 0.003 and p = 0.0009, respectively). CONCLUSIONS The time course of PFT changes after locoregional RT for breast cancer follows a biphasic pattern. An early reduction in PFTs at 3 to 6 months with a partial recovery at 12 months after RT is followed by a late, more important PFT reduction up to 8 to 10 years after RT. Tamoxifen use may have an impact on this late decline in PFTs.

Clinical outcome of coronary stenting after thoracic radiotherapy: a case-control study

Objective Patients with lymphoma, lung or breast neoplasia show significant improvement in their disease-specific survival after radiotherapy (RT), but these benefits may be offset by delayed effects of irradiation of the heart. We compared clinical outcome after coronary stenting in patients with neoplastic disease and previous thoracic RT with matched patients without previous RT. Design Single-centre retrospective case-control study. Patients and methods Each patient with former thoracic RT undergoing coronary stenting between June 1998 and June 2005 was matched to two control patients according to several known prognostic factors (gender, age, available follow-up, stented vessel, drug-eluting stent use, unstable coronary disease, renal insufficiency, diabetes, bifurcational disease, stent length and size and ejection fraction). Main outcome measures Major adverse cardiac events (MACE) were defined as the composite of cardiac death, acute myocardial infarction (AMI) and target lesion revascularisation (TLR) and were assessed at latest follow-up and compared using Cox regression analyses. Results 41 patients underwent coronary stenting at 6±4 years after RT. Clinical outcome at 5±2 years after stenting was compared with outcome in 82 matched patients. For all-cause mortality, the hazard ratio for RT versus no RT was 4.2 (95% CI 1.8 to 9.5; p=0.0006). For cardiac mortality, the estimated hazard ratio was 4.2 (95% CI 1.0 to 17.0; p=0.0451). No significant differences were detected in terms of AMI, TLR, MACE or stent thrombosis. Conclusions Our findings suggest an increased risk of all-cause and cardiac mortality in patients who underwent coronary stent implantation after previous thoracic RT. Verification in larger patient populations is warranted.

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.

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.

WE‐C‐AUD B‐10: Which Patients Benefit From Prospective Gating in Treatment for Loco‐Regional Breast Irradiation — a Radiobiological Assessment

Purpose: To determine a selection procedure based on radiobiological parameters to triage patients that benefit maximally from the use of free breathing gating in inspiration during treatment of the breast, internal mammary and medial supraclavicular lymph nodes. Methodology: Twenty patients undergoing external treatment to the breast were prospectively selected in this study, 10 patients with involvement in the right breast, and 10 in the left‐hand side. All patients underwent a classical non‐gated CT scan, followed by a CT scan using prospective gating with coached breathing. To perform prospective gating a large bore Siemens Sensation Open™ was utilized, adapted to work with the Varian RPM™ gating system, which is also installed on our Varian Linacs. For each patient, dose distributions for the same field setup were calculated on each CT‐scan. Differential DVHs for heart and lung, were analyzed providing an NTCP using a serial model with parameters: s=1, gamma=1.28, and D50=52.3 for the heart (predicting an increased risk of late cardiac mortality), and s=0.06, gamma=0.90, and D50=34.0 for the lung respectively (predicting clinical radiation pneumonitis). Results: The mean NTCP for the heart for all patients was 0.80% for a non‐‐gated treatment and was reduced to 0.26% in gated treatments. This improvement was significant (p=0.0008). Five patients had a reduction of NTCP of 1% or more for heart complications. All of these patients were treated to the left breast, but not all left breast patients seemed to benefit. For lung NTCP overall improvement (p=0.0006) could be shown, reducing mean NTCP from 2.1% to 1.4%. Conclusion: We have shown that it is possible to have an objective criterium to apply free breathing gating for breast cancer patients resulting in an effective and economically acceptable use of machine time for gating.