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CompletedNCT01217385ACRIN6691Updated Jan 17, 2023Results posted

Monitoring and Predicting Chemotherapy Response Using DOSI

An interventional study of DOSI in Breast Cancer, sponsored by American College of Radiology Imaging Network. Completed at 2 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-01-17.

Sponsored by American College of Radiology Imaging Network · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
60
Allocation
Not applicable
Ages
18 Years and older
Sex
Female
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Study summary

RATIONALE: New imaging procedures, such as diffuse optical spectroscopy imaging, may help measure a patient's response and allow doctors to plan better treatment.

PURPOSE: This clinical trial studies diffuse optical spectroscopy imaging in monitoring and predicting response in patients with locally advanced breast cancer undergoing chemotherapy before surgery.

Read the detailed description

OBJECTIVES:

Primary

  • To determine whether the percentage change in the diffuse optical spectroscopy imaging (DOSI) measurement of the tumor/normal (T/N) tissue optical index (TOI) from baseline to mid-therapy is predictive of the final pathologic response of the primary tumor in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy.

Secondary

  • To investigate whether change of TOI measurements from baseline to post-therapy are predictive of the final pathologic response in these patients treated with this regimen.
  • To investigate whether baseline TOI measurements are associated with final pathologic response in patients treated with this regimen.
  • To investigate whether TOI measurements at baseline, change from baseline to mid-therapy, and change from baseline to post-therapy correlate with available MRI volumetric imaging measurements.
  • To investigate whether changes on TOI measurements from baseline to mid-therapy, and from baseline to post-therapy, correlate with other standard-of-care imaging and/or any MRI-imaging measurements.
  • To explore whether additional optical endpoints and indices obtained during DOSI measurements can be used to predict final pathologic response in patients treated with this regimen.
  • To determine a cutpoint for the percent change of TOI from baseline to mid-therapy that is predictive of pathological complete response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients undergo diffuse optical spectroscopy imaging (DOSI) at baseline, 5-10 days after initiation of neoadjuvant chemotherapy, during early- and mid-neoadjuvant therapy, and within 21 days after completion of neoadjuvant therapy. Results are compared to standard-of-care imaging (e.g., MRI, ultrasound, mammography). Patients then undergo surgery.

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Conditions studied

  • Breast Cancer

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Keywords

  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
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In context

Breast Neoplasms

12,543 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 60 is below the median of 72 across 9,302 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

American College of Radiology Imaging Network is the lead sponsor of 21 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  1. Pathologically confirmed diagnosis of invasive breast cancer, determined to be a candidate for primary systemic (neoadjuvant) therapy and for surgical resection of residual primary tumor following completion of neoadjuvant therapy;
  2. Tumor size >2cm, measured on imaging or estimated by physical exam;
  3. No contraindications for primary chemotherapy;
  4. Planned definitive breast surgery (mastectomy or lumpectomy/breast conservation) following completion of neoadjuvant therapy;
  5. Age 18 years or older;
  6. ECOG Performance Status ≤ 2 (Karnofsky ≥ 60%; see Appendix II);

  7. Normal organ and marrow function as follows:

    • leukocytes ≥ 3,000/μl;
    • absolute neutrophil count ≥ 1,500/μl;
    • platelets ≥ 100,000/μl;
    • total bilirubin within normal institutional limits;
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 times the institutional upper limit of normal;
    • creatinine within normal institutional limits; OR
    • creatinine clearance ≥ 30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal;
  8. If female, postmenopausal for a minimum of one year, OR surgically sterile, OR not pregnant, confirmed by a pregnancy test as per institutional Standard of Care (SOC), and willing to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation;
  9. Able to understand and willing to sign a written informed consent document and a HIPAA authorization in accordance with institutional guidelines;

Exclusion criteria

Exclusion Criteria

  1. Previous treatment (chemotherapy, radiation, or surgery) to involved breast; including hormone therapy;
  2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements;
  3. Medically unstable;
  4. Under age 18;
  5. Pregnant or nursing;
  6. Previous malignancy, other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, from which the patient has been disease free for less than 5 years.
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Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
60 participants (actual)

Study arms

  • Experimental
    DOSI Pre-Surgery

    Participants undergo approximately four assessments of breast health using the DOSI technology during treatment and prior to surgery for breast cancer.

    Procedure: DOSI

Interventions

  • ProcedureDOSI

    Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO2), water (ctH2O), lipid, tissue oxygen saturation (StO2), and TOI (ctHHb x tH2O/lipid) were acquired on both breasts up to four times during neoadjuvant chemotherapy (NAC) treatment.

    Also known as: Diffuse Optical Spectroscopic Imaging, Laser spectroscopy, Optical Breast Imaging

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What researchers measure

Primary outcomes

  1. Accuracy of %Change in TOI Between Baseline and Mid-therapy to Predict Pathologic Response (pCR +/-)

    This measure will look at the Accuracy of % change in DOSI measured Tumor Optical Index (TOI) from baseline to mid therapy to predict pathologic response (pCR+ v pCR-) Pathologic response (dichotomized into responders (pCR+) and non-responders (pCR-) based pathologic assessment) will be used as the reference standard and Accuracy will be determined using receiver operating characteristic (ROC) analysis to determine the ROC Area Under the Curve (AUC).

    Time frame: From baseline to mid-therapy

Secondary outcomes

  1. %Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Progesterone Receptor (PR) Status (Positive, Negative, Unknown )

    Pathologic Complete response vs Non-Complete response, by PR status Progesterone Receptor Status (positive, negative, unknown ) is determined at pathological assessment of the tumor sample. %change in TOI is evaluated from baseline to mid-therapy.

    Time frame: baseline to mid-therapy

  2. Accuracy of %Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Oxygen Saturation (St02)

    subset analysis, subjects were stratified using the median tumor StO2 %change TOI Between Baseline and Mid-therapy dichotomized at -40% stratified by the set evaluable subjects with baseline tumor StO2 dichotomized at 76.9%. (i.e. population median). Accuracy will be determined using ROC analysis to determine the ROC Area Under the Curve (AUC).

    Time frame: baseline to mid-therapy

  3. Estimate the Optimal Cutpoint for %Change in TOI From Baseline to Mid-therapy to Predict pCR

    Determine the optimal cutpoint (aka Youden-index) for %Change in TOI ratio (T/N) to maximize sensitivity and specificity in the predication of pCR

    Time frame: baseline to mid-therapy

07

Results

Posted Jul 23, 2019

Participant flow

Seven institutions were approved to enroll a total of 60 female breast cancer patients: Enrollment began in June 2011 and completed in June 2013. All institutions activated concurrently, except MD Anderson Cancer Center and Boston University, which joined the study in January and May 2013, respectively.

Participant flow — Overall Study
MilestoneDiffuse Optical Spectroscopy Imaging (DOSI)
Started60
Completed34
Not completed26
Withdrew: Withdrawal by subject3
Withdrew: Dosi not performed/not eval12
Withdrew: Central path not available1
Withdrew: Normal breast toi not available10

Outcome measures

PrimaryAccuracy of %Change in TOI Between Baseline and Mid-therapy to Predict Pathologic Response (pCR +/-)

This measure will look at the Accuracy of % change in DOSI measured Tumor Optical Index (TOI) from baseline to mid therapy to predict pathologic response (pCR+ v pCR-) Pathologic response (dichotomized into responders (pCR+) and non-responders (pCR-) based pathologic assessment) will be used as the reference standard and Accuracy will be determined using receiver operating characteristic (ROC) analysis to determine the ROC Area Under the Curve (AUC).

Time frame:
From baseline to mid-therapy
Reported as:
Number · probability
Accuracy of %Change in TOI Between Baseline and Mid-therapy to Predict Pathologic Response (pCR +/-)
probabilityDiffuse Optical Spectroscopy Imaging (DOSI
Accuracy of %Change in TOI Between Baseline and Mid-therapy to Predict Pathologic Response (pCR +/-)0.60 (0.39 to 0.81)
Statistical analysis
  • Diffuse Optical Spectroscopy Imaging (DOSI · Regression, Logistic · p = 0.059 (5% alpha threshold for significance.) · Odds ratio (or): 4.667 · 95% CI 0.95 to 23.04
Secondary%Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Progesterone Receptor (PR) Status (Positive, Negative, Unknown )

Pathologic Complete response vs Non-Complete response, by PR status Progesterone Receptor Status (positive, negative, unknown ) is determined at pathological assessment of the tumor sample. %change in TOI is evaluated from baseline to mid-therapy.

Time frame:
baseline to mid-therapy
Reported as:
Mean · percentage change
%Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Progesterone Receptor (PR) Status (Positive, Negative, Unknown )
percentage changePR+ ParticipantsPR- ParticipantsPR? Participants
%Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Progesterone Receptor (PR) Status (Positive, Negative, Unknown )-29.874 ± 31.349-14.605 ± 107.425-45.701 ± 25.237
Statistical analysis
  • PR+ Participants vs PR- Participants · Regression, Logistic · p = 0.8193 (significance at alpha=0.05) · Slope: 0.4463Multivariate logistic regression model using % change in TOI ratio (T/N) (baseline to mid-therapy) dichotomized at -40%, PR status, and the corresponding interaction.
SecondaryAccuracy of %Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Oxygen Saturation (St02)

subset analysis, subjects were stratified using the median tumor StO2 %change TOI Between Baseline and Mid-therapy dichotomized at -40% stratified by the set evaluable subjects with baseline tumor StO2 dichotomized at 76.9%. (i.e. population median). Accuracy will be determined using ROC analysis to determine the ROC Area Under the Curve (AUC).

Time frame:
baseline to mid-therapy
Reported as:
Number · probability
Accuracy of %Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Oxygen Saturation (St02)
probabilityStO2 NegativeStO2 Positive
Accuracy of %Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Oxygen Saturation (St02)0.38 (0.08 to 0.68)0.83 (0.63 to 1)
Statistical analysis
  • StO2 Positive · Regression, Logistic · p = 0.043 · Odds ratio (or): 16.5 · 95% CI 1.09 to 250.15
  • StO2 Negative · Regression, Logistic · p = 0.406 · Odds ratio (or): 2.86 · 95% CI 0.24 to 33.90
SecondaryEstimate the Optimal Cutpoint for %Change in TOI From Baseline to Mid-therapy to Predict pCR

Determine the optimal cutpoint (aka Youden-index) for %Change in TOI ratio (T/N) to maximize sensitivity and specificity in the predication of pCR

Time frame:
baseline to mid-therapy
Reported as:
Number · percentage change in TOI
Estimate the Optimal Cutpoint for %Change in TOI From Baseline to Mid-therapy to Predict pCR
percentage change in TOIDiffuse Optical Spectroscopy Imaging (DOSI)
Estimate the Optimal Cutpoint for %Change in TOI From Baseline to Mid-therapy to Predict pCR-32.527

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
DOSI0/34 (0%)0/34 (0%)0/34 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)Diffuse Optical Spectroscopy Imaging (DOSI)
Mean48.4 ± 10.7
Sex: Female, Male
Sex: Female, Male(Participants)Diffuse Optical Spectroscopy Imaging (DOSI)
Female34
Male0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Diffuse Optical Spectroscopy Imaging (DOSI)
Hispanic or Latino5
Not Hispanic or Latino29
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Diffuse Optical Spectroscopy Imaging (DOSI)
American Indian or Alaska Native0
Asian4
Native Hawaiian or Other Pacific Islander0
Black or African American8
White19
More than one race0
Unknown or Not Reported3
Histologic findings
Histologic findings(Participants)Diffuse Optical Spectroscopy Imaging (DOSI)
Invasive (infiltrating) ductal carcinoma (IDC)16
Invasive lobular carcinoma (ILC)3
Ductal Carcinoma In Situ (DCIS)/ILC11
IDC/ILC2
Other/not available2
estrogen receptor (ER) status
estrogen receptor (ER) status(Participants)Diffuse Optical Spectroscopy Imaging (DOSI)
Positive24
Negative7
Unknown3
progesterone receptor (PR) status
progesterone receptor (PR) status(Participants)Diffuse Optical Spectroscopy Imaging (DOSI)
Positive19
Negative12
Unknown3
cell division marker (Ki67) status
cell division marker (Ki67) status(Participants)Diffuse Optical Spectroscopy Imaging (DOSI)
Positive17
Negative2
Unknown15

3 further baseline measures are reported on the registry.

08

Study locations

2 sites
  • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
    Irvine, California 92617, United States
  • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
    Lebanon, New Hampshire 03756-0002, United States
09

References and documents

Publications

  • Tromberg BJ, Butler JA, Mankoff DA, et al.: ACRIN 6691 monitoring and predicting breast cancer neoadjuvant chemotherapy response using diffuse optical spectroscopic imaging (DOSI). [Abstract] J Clin Oncol 29 (Suppl 15): A-TPS249, 2011.
  • Tromberg BJ, Zhang Z, Leproux A, O'Sullivan TD, Cerussi AE, Carpenter PM, Mehta RS, Roblyer D, Yang W, Paulsen KD, Pogue BW, Jiang S, Kaufman PA, Yodh AG, Chung SH, Schnall M, Snyder BS, Hylton N, Boas DA, Carp SA, Isakoff SJ, Mankoff D; ACRIN 6691 investigators. Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging. Cancer Res. 2016 Oct 15;76(20):5933-5944. doi: 10.1158/0008-5472.CAN-16-0346. Epub 2016 Aug 15. PubMed 27527559 ↗

Individual participant data

Plan to share: Yes — See ACRIN data Sharing Policy: Monitoring and Predicting Breast Cancer Neoadjuvant Chemotherapy Response Using Diffuse Optical Spectroscopic Imaging (DOSI)

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 17, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01217385
Lead sponsor
American College of Radiology Imaging Network
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Oct 8, 2010
Start date
Jun 2011
Primary completion
Jun 2013
Completion
Oct 6, 2014
Results posted
Jul 23, 2019
Last update
Jan 17, 2023

Study contacts

Bruce J. Tromberg, MD
principal investigator · Chao Family Comprehensive Cancer Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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