title: Potential impact of cardiac dose-volume on acute cardiac toxicity following concurrent trastuzumab and radiotherapy.
abstract: OBJECTIVE
  To analyse the risk factors associated with acute cardiotoxicity in HER2-positive breast cancer patients receiving concurrent trastuzumab and radiotherapy.
  
  
  METHODS
  Medical records of 45 breast cancer patients treated between 02/2009 and 02/2011 by concurrent trastuzumab and radiotherapy were collected. Radiation was delivered to the conserved breast or chest wall with or without regional nodes. Dose prescription was 50Gy in 25 fractions over five weeks with a tumor bed boost of 10Gy in 5 fractions in breast conservation. Acute cardiotoxicity (grade≥1) was defined using NCI-CTC v2.0. Doses to the heart and left ventricle were quantified.
  
  
  RESULTS
  Median follow-up of left ventricular ejection fraction and clinical assessment from the completion of radiotherapy was 10 months (range: 3-27 months) and 25 months (range: 13-40 months), respectively. Ten (22.2%) and one (2.2%) of the 45 patients developed grade 1 and grade 2 cardiotoxicity, respectively. For 24 left-sided patients, the mean heart dose was significantly higher in those with cardiac events compared to those without (10.14 and 6.27Gy, respectively; P<0.05). A continuous increase of D17-D57 and V10-V15 of the heart and increase of D40-D80 and V5-V7 of the left ventricle were statistically significant in left-sided patients who developed cardiotoxicity compared with those who did not (P<0.05). No significant relationship of dosimetric parameters of cardiac structures and cardiac events was found in right-sided patients.
  
  
  CONCLUSIONS
  Left-sided irradiation with increased low dose-volume and mean heart dose were associated with increased but reversible low-grade early cardiac toxicity after use of concurrent trastuzumab.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270, Dong An Road, 200032 Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270, Dong An Road, 200032 Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: W G
authors.initials: WG
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Institut Curie, Paris, France.
authors.forename: Y M
authors.initials: YM
authors.lastname: Kirova
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270, Dong An Road, 200032 Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270, Dong An Road, 200032 Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Cai
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270, Dong An Road, 200032 Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: X L
authors.initials: XL
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270, Dong An Road, 200032 Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: J L
authors.initials: JL
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270, Dong An Road, 200032 Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: X M
authors.initials: XM
authors.lastname: Guo
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Shao
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270, Dong An Road, 200032 Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: chenjiayi0188@gmail.com.
authors.forename: J Y
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects* / Q000528:radiation effects*; D014057:Tomography, X-Ray Computed; D000068878:Trastuzumab; D016277:Ventricular Function, Left / Q000187:drug effects / Q000528:radiation effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Breast cancer; Cancer du sein; Cardiac toxicity; Concurrent trastuzumab; Radiation therapy; Radiothérapie; Toxicité cardiaque; Trastuzumab concomitant