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Cardiotoxicity of the Association Trastuzumab–Locoregional Breast Radiation Therapy: A Prospective Monocentric Study
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International Journal of Radiation Oncology Biology Physics
related to BCS (p Z 0.63) or OS (p Z 0.71). Patients who had not received chemotherapy had a borderline better BCS and OS (p Z 0.0549). In the univariate analyses there were no differences between the boost and the no boost group in regards to molecular subtype or age. Further, there was no difference for the use of a radiation boost in inflammatory breast cancer. In multivariate analysis, where each variable was studied while controlling for all other variables, there were no differences in BCS for those who did and did not receive a radiation boost (HR, 1.053; 95% CI, 0.86-1.29; p Z 0.62) or OS (HR, 1.017; 95% CI, 0.86-1.20; p Z 0.84). In these models, variables related to poor survival after controlling for potential confounders were ER- vs ER+; PR- vs PR+; advanced stage vs stage 1; presence of positive nodes; and not receiving systemic chemotherapy (most significant at p < 0.0001). Conclusions: In an era of comparative effectiveness in oncology, we found no difference in BCS or OS with the addition of a radiation boost following PMRT in our large database. There was a trend for improved BCS and OS for those patients not treated with chemotherapy in the radiation boost group in comparison to the no boost group, suggesting an increased role of local therapy in this setting. Author Disclosure: J.S. Mayadev: None. K. Fish: None. A. Chen: None. M. Brown: None. S.R. Martinez: None. R. Valicenti: None. D. West: None. T. Phillips: None.
months) following the completion of RT. Trastuzumab was interrupted in 18 patients (5.8%) due to a LVEF alteration. Congestive heart failure was reported in 3 patients (1.0%). No death of cardiologic origin was observed. In univariate analysis, no significant statistical association was found between the occurrence of a LVEF alteration and the following factors: age (p Z 0.59), smoking (p Z 0.63), treated breast side (p Z 0.65), anthracycline-based chemotherapy (p Z 0.34) and RT of the IMN (p Z 0.21). Conclusions: With a median follow-up of more than four years, the cardiotoxicity of concurrent trastuzumab to locoregional breast RT remained mild. Longer follow-up is warranted to confirm these results. Author Disclosure: J. Jacob: None. L. Belin: None. J. Pierga: None. A. Gobillion: None. R. Dendale: None. P. Beuzeboc: None. F. Campana: None. A. Fourquet: None. Y.M. Kirova: None.
2021 Cardiotoxicity of the Association TrastuzumabeLocoregional Breast Radiation Therapy: A Prospective Monocentric Study J. Jacob,1 L. Belin,2 J. Pierga,3 A. Gobillion,2 R. Dendale,1 P. Beuzeboc,3 F. Campana,1 A. Fourquet,1 and Y.M. Kirova1; 1Institut Curie, Department of Radiation Oncology, Paris, France, 2Institut Curie, Department of Biostatistics, Paris, France, 3Institut Curie, Department of Medical Oncology, Paris, France Purpose/Objective(s): Postoperative breast radiation therapy (RT) and trastuzumab present a significant oncologic efficacy, in terms of local control and disease-free survival. However, both treatments expose to an increased risk of cardio-vascular events. The aim of our study is to assess the cardiotoxicity of the concurrent administration of trastuzumab to adjuvant locoregional breast RT. Materials/Methods: Prospective study of 308 patients treated between 2000 and 2009 by concurrent trastuzumab to normofractionated locoregional RT for localized breast cancer. Trastuzumab was delivered every three weeks for one year (8 mg/kg at the first infusion then 6 mg/ kg). The Left Ventricular Ejection Fraction (LVEF) was measured by echocardiography or myocardic scintigraphy at baseline, before and after RT, every three months for one year, then annually. The LVEF was assessed according to the Common Terminology Criteria for Adverse Effects version 3.0, and considered as altered when strictly below to 55%. Results: Median follow-up was 50 months (range, 13-126 months). Median age at diagnosis was 52 years (range, 25-83 years). The breast tumor was left-sided in 155 patients (50.3%). Anthracycline-, taxane-, and 5-fluorouracil-based chemotherapy regimens were administered to 280 (90.9%), 293 (95.1%), and 242 patients (78.6%), respectively. Median dose of trastuzumab was 6145 mg (1845-29,180). RT was performed to the mammary gland and to the chest wall in 193 (62.7%) and 115 patients (37.3%), respectively. The internal mammary nodes (IMN) were irradiated in 227 patients (73.7%), among them 114 (37.0%) in the left side. Median delivered doses were: 50 Gy (range, 41-55 Gy) to the breast, 50 Gy (range, 43-52 Gy) to the chest wall, 66 Gy (range, 41-77 Gy) to the tumor bed, and 46 Gy (range, 40-52 Gy) to the IMN. At the initiation of RT, 19 patients (6.2%) presented an altered LVEF. During the follow-up, an alteration of the LVEF occurred in 26 patients (8.4%): 17 (5.5%) grade 1, 7 (2.3%) grade 2, and 2 (0.6%) grade 3. Recovery of a normal LVEF was observed in 20 patients (76.9%) with a median time of 13.1 months (range, 0.7-43.4
2022 Adjuvant Hypofractionated Radiation Therapy With Simultaneous Boost After Breast-Conserving Therapy: First Results of a Multicentric Phase 2 Study J. Dunst,1 A. Schreiber,2 J. Zimmer,2 S. Dinges,3 A. Boicev,4 P. Andreas,5 M. Klug,6 C. Winkler,7 K. Krockenberger,8 and K. Dellas9; 1University of Luebeck, Luebeck, Germany, 2Department. of Radiotherapy, DresdenFriedrichstadt, Germany, 3Department of Radiotherapy, Lueneburg, Germany, 4Department of Radiotherapy, Zwickau, Germany, 5Department of Radiotherapy, Buchholz, Germany, 6Department of Radiotherapy, Deggendorf, Germany, 7Technical University, Department of Radiotherapy, Munich, Germany, 8Center for Clinical Studies, University of Luebeck, Luebeck, Germany, 9Department of Radiation Oncology, University Clinic, Kiel, Germany Purpose/Objective(s): ARO-2010-01, a prospective phase-II-study of the German Radiation Oncology Group ARO, investigated the feasibility of a hypofractionated regimen with integrated boost in a multicentric setting. Materials/Methods: The study was approved by the local ethical committee of the university. Patient with indication for breast irradiation (without nodal irradiation) after breast-conserving surgery were eligible. The tumor bed had to be clearly identified, preferably by clips. Patients with large seroma were to be excluded. The whole breast was irradiated with 16 fractions of 2.5 Gy; the tumor bed received a simultaneous boost of 0.5 Gy up to a total dose of 48 Gy in 16 fractions in an overall treatment time (per protocol) of 22 days. Dose constraints for lung, heart, left coronary artery, and contralateral breast were to be kept. The primary endpoint was feasibility. Results: From July 2011 through October 2012, 151 patients (mean age 62 years) were recruited from seven centers (two academic centers, three major hospital-based radiation therapy departments, and two private practices). The mean tumor diameter was 16 +/- 9 mm with 77% pT1-, 20% pT2-, and 3% pT3-tumors. Axillary staging was performed in 99% of patients (SN-biopsy in 81%); 92% of patients were nodalnegative. Eight patients were excluded from protocol treatment due to withdrawal of informant consent and missing ethical vote (N Z 4), extensive seroma in the tumor bed (N Z 2) or inability to clearly identify the tumor bed (N Z 2). In patients treated according to the protocol, radiation therapy was completed in all cases within less than 4 weeks. During radiation therapy, 11 unexpected events (UEs) were recorded in 10 patients (7%). UEs were hot flushes due to antihormonal therapy (5x), orthostatic hypotension (1x), hospital admission due to chest pain (1x), breast edema in the tumor bed (1x), sleeping disorders (1x), allergic reaction to adhesive plaster (1x), fatigue (1x). In two cases, a causal association with radiation therapy was expected (1x fatigue, 1x orthostatic hypotension). Severe unexpected events or local toxicities were not reported. Conclusions: The results of this prospective phase-II study support that hypofractionation with integrated boost is feasible in a multicentric setting with strict quality criteria. The treatment regimen was associated with minimal, if any, radiation-related toxicity. Unexpected events were mainly caused by hormonal therapy.
International Journal of Radiation Oncology Biology Physics
related to BCS (p Z 0.63) or OS (p Z 0.71). Patients who had not received chemotherapy had a borderline better BCS and OS (p Z 0.0549). In the univariate analyses there were no differences between the boost and the no boost group in regards to molecular subtype or age. Further, there was no difference for the use of a radiation boost in inflammatory breast cancer. In multivariate analysis, where each variable was studied while controlling for all other variables, there were no differences in BCS for those who did and did not receive a radiation boost (HR, 1.053; 95% CI, 0.86-1.29; p Z 0.62) or OS (HR, 1.017; 95% CI, 0.86-1.20; p Z 0.84). In these models, variables related to poor survival after controlling for potential confounders were ER- vs ER+; PR- vs PR+; advanced stage vs stage 1; presence of positive nodes; and not receiving systemic chemotherapy (most significant at p < 0.0001). Conclusions: In an era of comparative effectiveness in oncology, we found no difference in BCS or OS with the addition of a radiation boost following PMRT in our large database. There was a trend for improved BCS and OS for those patients not treated with chemotherapy in the radiation boost group in comparison to the no boost group, suggesting an increased role of local therapy in this setting. Author Disclosure: J.S. Mayadev: None. K. Fish: None. A. Chen: None. M. Brown: None. S.R. Martinez: None. R. Valicenti: None. D. West: None. T. Phillips: None.
months) following the completion of RT. Trastuzumab was interrupted in 18 patients (5.8%) due to a LVEF alteration. Congestive heart failure was reported in 3 patients (1.0%). No death of cardiologic origin was observed. In univariate analysis, no significant statistical association was found between the occurrence of a LVEF alteration and the following factors: age (p Z 0.59), smoking (p Z 0.63), treated breast side (p Z 0.65), anthracycline-based chemotherapy (p Z 0.34) and RT of the IMN (p Z 0.21). Conclusions: With a median follow-up of more than four years, the cardiotoxicity of concurrent trastuzumab to locoregional breast RT remained mild. Longer follow-up is warranted to confirm these results. Author Disclosure: J. Jacob: None. L. Belin: None. J. Pierga: None. A. Gobillion: None. R. Dendale: None. P. Beuzeboc: None. F. Campana: None. A. Fourquet: None. Y.M. Kirova: None.
2021 Cardiotoxicity of the Association TrastuzumabeLocoregional Breast Radiation Therapy: A Prospective Monocentric Study J. Jacob,1 L. Belin,2 J. Pierga,3 A. Gobillion,2 R. Dendale,1 P. Beuzeboc,3 F. Campana,1 A. Fourquet,1 and Y.M. Kirova1; 1Institut Curie, Department of Radiation Oncology, Paris, France, 2Institut Curie, Department of Biostatistics, Paris, France, 3Institut Curie, Department of Medical Oncology, Paris, France Purpose/Objective(s): Postoperative breast radiation therapy (RT) and trastuzumab present a significant oncologic efficacy, in terms of local control and disease-free survival. However, both treatments expose to an increased risk of cardio-vascular events. The aim of our study is to assess the cardiotoxicity of the concurrent administration of trastuzumab to adjuvant locoregional breast RT. Materials/Methods: Prospective study of 308 patients treated between 2000 and 2009 by concurrent trastuzumab to normofractionated locoregional RT for localized breast cancer. Trastuzumab was delivered every three weeks for one year (8 mg/kg at the first infusion then 6 mg/ kg). The Left Ventricular Ejection Fraction (LVEF) was measured by echocardiography or myocardic scintigraphy at baseline, before and after RT, every three months for one year, then annually. The LVEF was assessed according to the Common Terminology Criteria for Adverse Effects version 3.0, and considered as altered when strictly below to 55%. Results: Median follow-up was 50 months (range, 13-126 months). Median age at diagnosis was 52 years (range, 25-83 years). The breast tumor was left-sided in 155 patients (50.3%). Anthracycline-, taxane-, and 5-fluorouracil-based chemotherapy regimens were administered to 280 (90.9%), 293 (95.1%), and 242 patients (78.6%), respectively. Median dose of trastuzumab was 6145 mg (1845-29,180). RT was performed to the mammary gland and to the chest wall in 193 (62.7%) and 115 patients (37.3%), respectively. The internal mammary nodes (IMN) were irradiated in 227 patients (73.7%), among them 114 (37.0%) in the left side. Median delivered doses were: 50 Gy (range, 41-55 Gy) to the breast, 50 Gy (range, 43-52 Gy) to the chest wall, 66 Gy (range, 41-77 Gy) to the tumor bed, and 46 Gy (range, 40-52 Gy) to the IMN. At the initiation of RT, 19 patients (6.2%) presented an altered LVEF. During the follow-up, an alteration of the LVEF occurred in 26 patients (8.4%): 17 (5.5%) grade 1, 7 (2.3%) grade 2, and 2 (0.6%) grade 3. Recovery of a normal LVEF was observed in 20 patients (76.9%) with a median time of 13.1 months (range, 0.7-43.4
2022 Adjuvant Hypofractionated Radiation Therapy With Simultaneous Boost After Breast-Conserving Therapy: First Results of a Multicentric Phase 2 Study J. Dunst,1 A. Schreiber,2 J. Zimmer,2 S. Dinges,3 A. Boicev,4 P. Andreas,5 M. Klug,6 C. Winkler,7 K. Krockenberger,8 and K. Dellas9; 1University of Luebeck, Luebeck, Germany, 2Department. of Radiotherapy, DresdenFriedrichstadt, Germany, 3Department of Radiotherapy, Lueneburg, Germany, 4Department of Radiotherapy, Zwickau, Germany, 5Department of Radiotherapy, Buchholz, Germany, 6Department of Radiotherapy, Deggendorf, Germany, 7Technical University, Department of Radiotherapy, Munich, Germany, 8Center for Clinical Studies, University of Luebeck, Luebeck, Germany, 9Department of Radiation Oncology, University Clinic, Kiel, Germany Purpose/Objective(s): ARO-2010-01, a prospective phase-II-study of the German Radiation Oncology Group ARO, investigated the feasibility of a hypofractionated regimen with integrated boost in a multicentric setting. Materials/Methods: The study was approved by the local ethical committee of the university. Patient with indication for breast irradiation (without nodal irradiation) after breast-conserving surgery were eligible. The tumor bed had to be clearly identified, preferably by clips. Patients with large seroma were to be excluded. The whole breast was irradiated with 16 fractions of 2.5 Gy; the tumor bed received a simultaneous boost of 0.5 Gy up to a total dose of 48 Gy in 16 fractions in an overall treatment time (per protocol) of 22 days. Dose constraints for lung, heart, left coronary artery, and contralateral breast were to be kept. The primary endpoint was feasibility. Results: From July 2011 through October 2012, 151 patients (mean age 62 years) were recruited from seven centers (two academic centers, three major hospital-based radiation therapy departments, and two private practices). The mean tumor diameter was 16 +/- 9 mm with 77% pT1-, 20% pT2-, and 3% pT3-tumors. Axillary staging was performed in 99% of patients (SN-biopsy in 81%); 92% of patients were nodalnegative. Eight patients were excluded from protocol treatment due to withdrawal of informant consent and missing ethical vote (N Z 4), extensive seroma in the tumor bed (N Z 2) or inability to clearly identify the tumor bed (N Z 2). In patients treated according to the protocol, radiation therapy was completed in all cases within less than 4 weeks. During radiation therapy, 11 unexpected events (UEs) were recorded in 10 patients (7%). UEs were hot flushes due to antihormonal therapy (5x), orthostatic hypotension (1x), hospital admission due to chest pain (1x), breast edema in the tumor bed (1x), sleeping disorders (1x), allergic reaction to adhesive plaster (1x), fatigue (1x). In two cases, a causal association with radiation therapy was expected (1x fatigue, 1x orthostatic hypotension). Severe unexpected events or local toxicities were not reported. Conclusions: The results of this prospective phase-II study support that hypofractionation with integrated boost is feasible in a multicentric setting with strict quality criteria. The treatment regimen was associated with minimal, if any, radiation-related toxicity. Unexpected events were mainly caused by hormonal therapy.