title: Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging.
abstract: The prospective multicenter ACRIN 6691 trial was designed to evaluate whether changes from baseline to mid-therapy in a diffuse optical spectroscopic imaging (DOSI)-derived imaging endpoint, the tissue optical index (TOI), predict pathologic complete response (pCR) in women undergoing breast cancer neoadjuvant chemotherapy (NAC). DOSI instruments were constructed at the University of California, Irvine (Irvine, CA), and delivered to six institutions where 60 subjects with newly diagnosed breast tumors (at least 2 cm in the longest dimension) were enrolled over a 2-year period. Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO2), water (ctH2O), lipid, and TOI (ctHHb × ctH2O/lipid) were acquired on both breasts up to four times during NAC treatment: baseline, 1-week, mid-point, and completion. Of the 34 subjects (mean age 48.4 ± 10.7 years) with complete, evaluable data from both normal and tumor-containing breast, 10 (29%) achieved pCR as determined by central pathology review. The percent change in tumor-to-normal TOI ratio (%TOITN) from baseline to mid-therapy ranged from -82% to 321%, with a median of -36%. Using pCR as the reference standard and ROC curve methodology, %TOITNAUC was 0.60 (95% CI, 0.39-0.81). In the cohort of 17 patients with baseline tumor oxygen saturation (%StO2) greater than the 77% population median, %TOITNAUC improved to 0.83 (95% CI, 0.63-1.00). We conclude that the combination of baseline functional properties and dynamic optical response shows promise for clinical outcome prediction. Cancer Res; 76(20); 5933-44. ©2016 AACR.
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, California. bjtrombe@uci.edu.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Tromberg
authors.affiliation: Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, California.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Leproux
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, California.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: O'Sullivan
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, California.
authors.forename: Albert E
authors.initials: AE
authors.lastname: Cerussi
authors.affiliation: Department of Pathology, University of Southern California, California.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Carpenter
authors.affiliation: Department of Medicine, University of California Irvine, Irvine, California.
authors.forename: Rita S
authors.initials: RS
authors.lastname: Mehta
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Darren
authors.initials: D
authors.lastname: Roblyer
authors.affiliation: Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Paulsen
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
authors.forename: Shudong
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Section of Hematology and Oncology, Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, New Hampshire.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kaufman
authors.affiliation: Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Arjun G
authors.initials: AG
authors.lastname: Yodh
authors.affiliation: Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: So Hyun
authors.initials: SH
authors.lastname: Chung
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Schnall
authors.affiliation: Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Snyder
authors.affiliation: Department of Radiology, University of California, San Francisco, California.
authors.forename: Nola
authors.initials: N
authors.lastname: Hylton
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: David A
authors.initials: DA
authors.lastname: Boas
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Carp
authors.affiliation: Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Isakoff
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Mankoff
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D012372:ROC Curve; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D006454:Hemoglobins