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Dynamic Diffuse Optical Tomography for Monitoring Neoadjuvant Chemotherapy in Patients with Breast Cancer.

ABSTRACT: Purpose To identify dynamic optical imaging features that associate with the degree of pathologic response in patients with breast cancer during neoadjuvant chemotherapy (NAC). Materials and Methods Of 40 patients with breast cancer who participated in a longitudinal study between June 2011 and March 2016, 34 completed the study. There were 13 patients who obtained a pathologic complete response (pCR) and 21 patients who did not obtain a pCR. Imaging data from six subjects were excluded from the study because either the patients dropped out of the study before it was finished or there was an instrumentation malfunction. Two weeks into the treatment regimen, three-dimensional images of both breasts during a breath hold were acquired by using dynamic diffuse optical tomography. Features from the breath-hold traces were used to distinguish between response groups. Receiver operating characteristic (ROC) curves and sensitivity analysis were used to determine the degree of association with 5-month treatment outcome. Results An ROC curve analysis showed that this method could identify patients with a pCR with a positive predictive value of 70.6% (12 of 17), a negative predictive value of 94.1% (16 of 17), a sensitivity of 92.3% (12 of 13), a specificity of 76.2% (16 of 21), and an area under the ROC curve of 0.85. Conclusion Several dynamic optical imaging features obtained within 2 weeks of NAC initiation were identified that showed statistically significant differences between patients with pCR and patients without pCR as determined 5 months after treatment initiation. If confirmed in a larger cohort prospective study, these dynamic imaging features may be used to predict treatment outcome as early as 2 weeks after treatment initiation. © RSNA, 2018 Online supplemental material is available for this article.

SUBMITTER: Gunther JE

PROVIDER: S-EPMC5978455 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Dynamic Diffuse Optical Tomography for Monitoring Neoadjuvant Chemotherapy in Patients with Breast Cancer.

Gunther Jacqueline E JE Lim Emerson A EA Kim Hyun K HK Flexman Molly M Altoé Mirella M Campbell Jessica A JA Hibshoosh Hanina H Crew Katherine D KD Kalinsky Kevin K Hershman Dawn L DL Hielscher Andreas H AH

Radiology 20180212 3

Purpose To identify dynamic optical imaging features that associate with the degree of pathologic response in patients with breast cancer during neoadjuvant chemotherapy (NAC). Materials and Methods Of 40 patients with breast cancer who participated in a longitudinal study between June 2011 and March 2016, 34 completed the study. There were 13 patients who obtained a pathologic complete response (pCR) and 21 patients who did not obtain a pCR. Imaging data from six subjects were excluded from the ...[more]

PMID: 29431574

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Project description:PurposeThe purpose of the study was to assess the utility of tumor biomarkers, ultrasound (US) and US-guided diffuse optical tomography (DOT) in early prediction of breast cancer response to neoadjuvant therapy (NAT).MethodsThis prospective HIPAA compliant study was approved by the institutional review board. Forty one patients were imaged with US and US-guided DOT prior to NAT, at completion of the first three treatment cycles, and prior to definitive surgery from February 2017 to January 2020. Miller-Payne grading was used to assess pathologic response. Receiver operating characteristic curves (ROCs) were derived from logistic regression using independent variables, including: tumor biomarkers, US maximum diameter, percentage reduction of the diameter (%US), pretreatment maximum total hemoglobin concentration (HbT) and percentage reduction in HbT (%HbT) at different treatment time points. Resulting ROCs were compared using area under the curve (AUC). Statistical significance was tested using two-sided two-sample student t-test with P < 0.05 considered statistically significant. Logistic regression was used for ROC analysis.ResultsThirty-eight patients (mean age = 47, range 24-71 years) successfully completed the study, including 15 HER2 + of which 11 were ER + ; 12 ER + or PR + /HER2-, and 11 triple negative. The combination of HER2 and ER biomarkers, %HbT at the end of cycle 1 (EOC1) and %US (EOC1) provided the best early prediction, AUC = 0.941 (95% CI 0.869-1.0). Similarly an AUC of 0.910 (95% CI 0.810-1.0) with %US (EOC1) and %HbT (EOC1) can be achieved independent of HER2 and ER status. The most accurate prediction, AUC = 0.974 (95% CI 0.933-1.0), was achieved with %US at EOC1 and %HbT (EOC3) independent of biomarker status.ConclusionThe combined use of tumor HER2 and ER status, US, and US-guided DOT may provide accurate prediction of NAT response as early as the completion of the first treatment cycle.Clinical trial registration numberNCT02891681. https://clinicaltrials.gov/ct2/show/NCT02891681 , Registration time: September 7, 2016.

Project description:To investigate if changes in tumor angiogenesis associated with complete pathologic response (pCR) or partial pathologic response (pPR) to treatment can be demonstrated by using diffuse optical spectroscopic (DOS) tomography.All participants in this prospective, HIPAA-compliant, institutional review board-approved study provided written informed consent. Eleven women with invasive breast carcinoma were imaged with DOS tomography prior to, during, and at completion of neoadjuvant chemotherapeutic regimens. By using region of interest (ROI) analysis, the DOS measure of total tissue hemoglobin (Hb(T)) was temporally correlated with quantitative measures of existing (CD31-expressing) and tumor-induced (CD105-expressing) vessels, in pretreatment and posttreatment tissue specimens, to assess change.Quantified angiogenesis alone in pretreatment core biopsy specimens did not predict treatment response, but mean vessel density (MVD) and mean vessel area (MVA) of CD105-expressing vessels were significantly decreased in women with pCR (n = 7) (P < .001 and P = .003, respectively). MVA of CD105-expressing vessels was also significantly reduced at comparison of pre- and posttreatment residual tumor for women with pPR (n = 4) (P = .033). A longitudinal analysis showed significant decreases (P = .001) in mean Hb(T) levels during neoadjuvant chemotherapy in breast abnormality ROIs for women with pCR but not women with pPR. For women with pCR, but not women with pPR, pretreatment MVD of CD105-expressing vessels correlated with pretreatment Hb(T) (P ≤ .001).DOS tomographic examinations in women with breast cancer who are receiving neoadjuvant chemotherapy show a mean decrease in Hb(T) with time in patients with pCR only. Observed pretreatment and posttreatment correlates with quantified angiogenesis markers confirm the likely biologic origin for this DOS signature and support its potential to predict angiogenic tissue response early in the treatment cycle.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11100699/-/DC1.

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Dynamic Diffuse Optical Tomography for Monitoring Neoadjuvant Chemotherapy in Patients with Breast Cancer.

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Dynamic Diffuse Optical Tomography for Monitoring Neoadjuvant Chemotherapy in Patients with Breast Cancer.

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