Evaluation of breast tumor response to neoadjuvant chemotherapy with tomographic diffuse optical spectroscopy: case studies of tumor region-of-interest changes

Abstract

Purpose: To evaluate two methods of summarizing tomographic diffuse optical spectroscopic (DOS) data through region-of-interest (ROI) analysis to differentiate complete from incomplete responses in patients with locally advanced breast cancer undergoing neoadjuvant treatment and to estimate the standard deviations of these methods for power analysis of larger study designs in the future.

Materials and methods: Subjects participating in the HIPAA-compliant imaging study, approved by the institutional review board, provided written informed consent and were compensated for their examination participation. Seven of 16 cases in women with complete study data were analyzed by using both fixed- and variable-size (full-width-at-half-maximum) ROI measures of the DOS total hemoglobin concentration (Hb(T)), blood oxygen saturation, water fraction, optical scattering amplitude, and scattering power in the ipsilateral and contralateral breasts. Postsurgical histopathologic analysis was used to categorize patients as having a complete or incomplete treatment response.

Results: Average normalized change in Hb(T) was the only DOS parameter to show significant differences (P < or = .05) in the pathologic complete response (pCR) and pathologic incomplete response (pIR) outcomes in seven patients. Mean values of the changes for fixed-size ROIs were -64.2% +/- 50.8 (standard deviation) and 16.9% +/- 38.2 for the pCR and pIR groups, respectively, and those for variable-size ROIs were -96.7% +/- 91.8, and 14.1% +/- 26.7 for the pCR and pIR groups, respectively.

Conclusion: Tomographic DOS may provide findings predictive of therapeutic response, which could lead to superior individualized patient treatment.

Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1.

Figure 1a:

Images from 36-year-old patient show radiologic findings and pCR. (a) Full-field digital mediolateral oblique mammogram demonstrates linear and pleomorphic calcifications in segmental distribution involving lower central and entire lower inner quadrant (arrows) with overlying skin thickening (visible in lower area). Postcontrast T1-weighted MR images obtained in the axial imaging plane through the lower half of the breast (b) prior to initiation and (c) after completion of neoadjuvant chemotherapy showed linear and clumped segmental parencyhmal enhancement (arrows), as well as skin thickening corresponding to mammographic findings. During treatment, peak intensity of enhancement diminished and kinetics changed from a washout and plateau dynamic enhancement curve to a persistent pattern; after treatment, enhancement resolved. Patient had pCR (Figs E1–E3 [ http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1 ]). (d, e) DOS images of Hb_T (in micromoles per liter), SO₂ (S_tO₂) (as percentage), and H₂O (as percentage) obtained prior to initiation of treatment, on first day of cycle 2 (C2, D1), and after therapy (3 days before surgery) are shown for (d) abnormal ipsilateral and (e) normal contralateral breasts, respectively. Arrows indicate ROI on d. Because Hb_T values from pretreatment DOS image of cancerous right breast were higher than those from images in following sessions, display scale with maximum of 35 μmol/L was used, although maximum value in tumor was initially 100 μmol/L. DOS values indicate that Hb_T decreased in tumor ROI after first treatment cycle (arrows), to extent that no contrast in ROI relative to surrounding tissue in Hb_T and H₂O was detectable during final visit before surgery.

Figure 1b:

Images from 36-year-old patient show radiologic findings and pCR. (a) Full-field digital mediolateral oblique mammogram demonstrates linear and pleomorphic calcifications in segmental distribution involving lower central and entire lower inner quadrant (arrows) with overlying skin thickening (visible in lower area). Postcontrast T1-weighted MR images obtained in the axial imaging plane through the lower half of the breast (b) prior to initiation and (c) after completion of neoadjuvant chemotherapy showed linear and clumped segmental parencyhmal enhancement (arrows), as well as skin thickening corresponding to mammographic findings. During treatment, peak intensity of enhancement diminished and kinetics changed from a washout and plateau dynamic enhancement curve to a persistent pattern; after treatment, enhancement resolved. Patient had pCR (Figs E1–E3 [ http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1 ]). (d, e) DOS images of Hb_T (in micromoles per liter), SO₂ (S_tO₂) (as percentage), and H₂O (as percentage) obtained prior to initiation of treatment, on first day of cycle 2 (C2, D1), and after therapy (3 days before surgery) are shown for (d) abnormal ipsilateral and (e) normal contralateral breasts, respectively. Arrows indicate ROI on d. Because Hb_T values from pretreatment DOS image of cancerous right breast were higher than those from images in following sessions, display scale with maximum of 35 μmol/L was used, although maximum value in tumor was initially 100 μmol/L. DOS values indicate that Hb_T decreased in tumor ROI after first treatment cycle (arrows), to extent that no contrast in ROI relative to surrounding tissue in Hb_T and H₂O was detectable during final visit before surgery.

Figure 1c:

Images from 36-year-old patient show radiologic findings and pCR. (a) Full-field digital mediolateral oblique mammogram demonstrates linear and pleomorphic calcifications in segmental distribution involving lower central and entire lower inner quadrant (arrows) with overlying skin thickening (visible in lower area). Postcontrast T1-weighted MR images obtained in the axial imaging plane through the lower half of the breast (b) prior to initiation and (c) after completion of neoadjuvant chemotherapy showed linear and clumped segmental parencyhmal enhancement (arrows), as well as skin thickening corresponding to mammographic findings. During treatment, peak intensity of enhancement diminished and kinetics changed from a washout and plateau dynamic enhancement curve to a persistent pattern; after treatment, enhancement resolved. Patient had pCR (Figs E1–E3 [ http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1 ]). (d, e) DOS images of Hb_T (in micromoles per liter), SO₂ (S_tO₂) (as percentage), and H₂O (as percentage) obtained prior to initiation of treatment, on first day of cycle 2 (C2, D1), and after therapy (3 days before surgery) are shown for (d) abnormal ipsilateral and (e) normal contralateral breasts, respectively. Arrows indicate ROI on d. Because Hb_T values from pretreatment DOS image of cancerous right breast were higher than those from images in following sessions, display scale with maximum of 35 μmol/L was used, although maximum value in tumor was initially 100 μmol/L. DOS values indicate that Hb_T decreased in tumor ROI after first treatment cycle (arrows), to extent that no contrast in ROI relative to surrounding tissue in Hb_T and H₂O was detectable during final visit before surgery.

Figure 1d:

Images from 36-year-old patient show radiologic findings and pCR. (a) Full-field digital mediolateral oblique mammogram demonstrates linear and pleomorphic calcifications in segmental distribution involving lower central and entire lower inner quadrant (arrows) with overlying skin thickening (visible in lower area). Postcontrast T1-weighted MR images obtained in the axial imaging plane through the lower half of the breast (b) prior to initiation and (c) after completion of neoadjuvant chemotherapy showed linear and clumped segmental parencyhmal enhancement (arrows), as well as skin thickening corresponding to mammographic findings. During treatment, peak intensity of enhancement diminished and kinetics changed from a washout and plateau dynamic enhancement curve to a persistent pattern; after treatment, enhancement resolved. Patient had pCR (Figs E1–E3 [ http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1 ]). (d, e) DOS images of Hb_T (in micromoles per liter), SO₂ (S_tO₂) (as percentage), and H₂O (as percentage) obtained prior to initiation of treatment, on first day of cycle 2 (C2, D1), and after therapy (3 days before surgery) are shown for (d) abnormal ipsilateral and (e) normal contralateral breasts, respectively. Arrows indicate ROI on d. Because Hb_T values from pretreatment DOS image of cancerous right breast were higher than those from images in following sessions, display scale with maximum of 35 μmol/L was used, although maximum value in tumor was initially 100 μmol/L. DOS values indicate that Hb_T decreased in tumor ROI after first treatment cycle (arrows), to extent that no contrast in ROI relative to surrounding tissue in Hb_T and H₂O was detectable during final visit before surgery.

Figure 1e:

Images from 36-year-old patient show radiologic findings and pCR. (a) Full-field digital mediolateral oblique mammogram demonstrates linear and pleomorphic calcifications in segmental distribution involving lower central and entire lower inner quadrant (arrows) with overlying skin thickening (visible in lower area). Postcontrast T1-weighted MR images obtained in the axial imaging plane through the lower half of the breast (b) prior to initiation and (c) after completion of neoadjuvant chemotherapy showed linear and clumped segmental parencyhmal enhancement (arrows), as well as skin thickening corresponding to mammographic findings. During treatment, peak intensity of enhancement diminished and kinetics changed from a washout and plateau dynamic enhancement curve to a persistent pattern; after treatment, enhancement resolved. Patient had pCR (Figs E1–E3 [ http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1 ]). (d, e) DOS images of Hb_T (in micromoles per liter), SO₂ (S_tO₂) (as percentage), and H₂O (as percentage) obtained prior to initiation of treatment, on first day of cycle 2 (C2, D1), and after therapy (3 days before surgery) are shown for (d) abnormal ipsilateral and (e) normal contralateral breasts, respectively. Arrows indicate ROI on d. Because Hb_T values from pretreatment DOS image of cancerous right breast were higher than those from images in following sessions, display scale with maximum of 35 μmol/L was used, although maximum value in tumor was initially 100 μmol/L. DOS values indicate that Hb_T decreased in tumor ROI after first treatment cycle (arrows), to extent that no contrast in ROI relative to surrounding tissue in Hb_T and H₂O was detectable during final visit before surgery.

Figure 2a:

Clinical images for 29-year-old patient with absence of substantial radiologic response and pIR. Postcontrast T1-weighted axial MR images (a) prior to and (b) after neoadjuvant chemotherapy. Abnormal area of enhancement initially consisted of complex mass with rim enhancement and adjacent nonmasslike enhancement. During treatment, complex mass decreased minimally; adjacent areas of enhancement progressed with both mass and nonmasslike enhancement. Pathologic findings showed pIR to neoadjuvant chemotherapy; more than 50% and less than 90% residual tumor remained (Figs E4–E6 [ http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1 ]). (c) DOS Images of Hb_T (in micromoles per liter), SO₂ (S_tO₂) (as percentage), and H₂O (as percentage) before treatment, on day 10 of cycle 1 (C1, D10), and after therapy (11 days before surgery) are shown for abnormal ipsilateral breast. Arrows indicate ROI. No substantial changes in Hb_T, SO₂, H₂O, and scattering properties were evident in tumor region; Hb_T contrast in ROI relative to surrounding tissue increased during course of treatment. SA = scattering amplitude, SP = scattering power.

Figure 2b:

Clinical images for 29-year-old patient with absence of substantial radiologic response and pIR. Postcontrast T1-weighted axial MR images (a) prior to and (b) after neoadjuvant chemotherapy. Abnormal area of enhancement initially consisted of complex mass with rim enhancement and adjacent nonmasslike enhancement. During treatment, complex mass decreased minimally; adjacent areas of enhancement progressed with both mass and nonmasslike enhancement. Pathologic findings showed pIR to neoadjuvant chemotherapy; more than 50% and less than 90% residual tumor remained (Figs E4–E6 [ http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1 ]). (c) DOS Images of Hb_T (in micromoles per liter), SO₂ (S_tO₂) (as percentage), and H₂O (as percentage) before treatment, on day 10 of cycle 1 (C1, D10), and after therapy (11 days before surgery) are shown for abnormal ipsilateral breast. Arrows indicate ROI. No substantial changes in Hb_T, SO₂, H₂O, and scattering properties were evident in tumor region; Hb_T contrast in ROI relative to surrounding tissue increased during course of treatment. SA = scattering amplitude, SP = scattering power.

Figure 2c:

Clinical images for 29-year-old patient with absence of substantial radiologic response and pIR. Postcontrast T1-weighted axial MR images (a) prior to and (b) after neoadjuvant chemotherapy. Abnormal area of enhancement initially consisted of complex mass with rim enhancement and adjacent nonmasslike enhancement. During treatment, complex mass decreased minimally; adjacent areas of enhancement progressed with both mass and nonmasslike enhancement. Pathologic findings showed pIR to neoadjuvant chemotherapy; more than 50% and less than 90% residual tumor remained (Figs E4–E6 [ http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1 ]). (c) DOS Images of Hb_T (in micromoles per liter), SO₂ (S_tO₂) (as percentage), and H₂O (as percentage) before treatment, on day 10 of cycle 1 (C1, D10), and after therapy (11 days before surgery) are shown for abnormal ipsilateral breast. Arrows indicate ROI. No substantial changes in Hb_T, SO₂, H₂O, and scattering properties were evident in tumor region; Hb_T contrast in ROI relative to surrounding tissue increased during course of treatment. SA = scattering amplitude, SP = scattering power.

Figure 3:

Box plots of normalized change in Hb_T (ΔHb_T%) between pretreatment image and image acquired during last breast examination performed within 4-week period after start of therapy computed on basis of fixed-size ROI or FWHM-ROI definitions for Hb_T. In each box, horizontal lines and circles with crosses indicate median and mean, respectively. Vertical lines extending from the top and bottom of boxes represent range in data in each case. In fixed-size ROI analysis, average Hb_T changes in cases of pCR and pIR were −64.2% and 16.9%, whereas in FWHM-ROI analysis, changes increased to −96.7% and 14.1%, respectively. Standard deviations in each category were ±50.8%, ±38.2%, ±91.8%, and ±26.7%, respectively.