title: Multiparametric monitoring of chemotherapy treatment response in locally advanced breast cancer using quantitative ultrasound and diffuse optical spectroscopy.
abstract: OBJECTIVE
  This study evaluated pathological response to neoadjuvant chemotherapy using quantitative ultrasound (QUS) and diffuse optical spectroscopy imaging (DOSI) biomarkers in locally advanced breast cancer (LABC).
  
  
  METHODS
  The institution's ethics review board approved this study. Subjects (n = 22) gave written informed consent prior to participating. US and DOSI data were acquired, relative to the start of neoadjuvant chemotherapy, at weeks 0, 1, 4, 8 and preoperatively. QUS parameters including the mid-band fit (MBF), 0-MHz intercept (SI), and the spectral slope (SS) were determined from tumor ultrasound data using spectral analysis. In the same patients, DOSI was used to measure parameters relating to tumor hemoglobin and composition. Discriminant analysis and receiver-operating characteristic (ROC) analysis was used to classify clinical and pathological response during treatment and to estimate the area under the curve (AUC). Additionally, multivariate analysis was carried out for pairwise QUS/DOSI parameter combinations using a logistic regression model.
  
  
  RESULTS
  Individual QUS and DOSI parameters, including the (SI), oxy-hemoglobin (HbO2), and total hemoglobin (HbT) were significant markers for response after one week of treatment (p < 0.01). Multivariate (pairwise) combinations increased the sensitivity, specificity and AUC at this time; the SI + HbO2 showed a sensitivity/specificity of 100%, and an AUC of 1.0.
  
  
  CONCLUSIONS
  QUS and DOSI demonstrated potential as coincident markers for treatment response and may potentially facilitate response-guided therapies. Multivariate QUS and DOSI parameters increased the sensitivity and specificity of classifying LABC patients as early as one week after treatment.
authors.affiliation: Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada.|Centre for Health and Social Care Research, Sheffield Hallam University, Sheffield, UK.
authors.forename: William T
authors.initials: WT
authors.lastname: Tran
authors.affiliation: Centre for Health and Social Care Research, Sheffield Hallam University, Sheffield, UK.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Childs
authors.affiliation: Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada.
authors.forename: Lee
authors.initials: L
authors.lastname: Chin
authors.affiliation: Division of Anatomic Pathology, Sunnybrook Hospital, Toronto, Canada.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Slodkowska
authors.affiliation: Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Sannachi
authors.affiliation: Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Hadi
authors.initials: H
authors.lastname: Tadayyon
authors.affiliation: Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada.
authors.forename: Elyse
authors.initials: E
authors.lastname: Watkins
authors.affiliation: Department of Nursing, Sunnybrook Hospital, Toronto, Canada.
authors.forename: Sharon Lemon
authors.initials: SL
authors.lastname: Wong
authors.affiliation: Division of Radiology, Sunnybrook Hospital, Toronto, Canada.
authors.forename: Belinda
authors.initials: B
authors.lastname: Curpen
authors.affiliation: Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El Kaffas
authors.affiliation: Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada.
authors.forename: Azza
authors.initials: A
authors.lastname: Al-Mahrouki
authors.affiliation: Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Sadeghi-Naini
authors.affiliation: Department of Radiation Oncology, University of Toronto, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Czarnota
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D015999:Multivariate Analysis; D061848:Optical Imaging / Q000379:methods; D017063:Outcome Assessment, Health Care / Q000379:methods*; D012372:ROC Curve; D015203:Reproducibility of Results; D013057:Spectrum Analysis / Q000379:methods; D014463:Ultrasonography / Q000379:methods
chemical_list: D006454:Hemoglobins
keywords: diffuse optical spectroscopy; locally advanced breast cancer; neoadjuvant chemotherapy; quantitative ultrasound; treatment monitoring