University of California Irvine/ Tromberg BJ*
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, %TOITN AUC 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, %TOITN AUC 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.
Tromberg BJ1, Zhang Z2, Leproux A3, O'Sullivan TD3, Cerussi AE3, Carpenter PM4, Mehta RS5, Roblyer D6, Yang W7, Paulsen KD8, Pogue BW8, Jiang S8, Kaufman PA9, Yodh AG10, Chung SH10, Schnall M11, Snyder BS12, Hylton N13, Boas DA14, Carp SA14, Isakoff SJ15, Mankoff D11; ACRIN 6691 investigators.
1Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, California. firstname.lastname@example.org.
2Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
3Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, California.
4Department of Pathology, University of Southern California, California.
5Department of Medicine, University of California Irvine, Irvine, California.
6Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
7Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas.
8Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
9Section of Hematology and Oncology, Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, New Hampshire.
10Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, Pennsylvania.
11Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
12Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
13Department of Radiology, University of California, San Francisco, California.
14Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
15Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.