Radiology: DOS tomography may inform individualized chemo

Prechemotherapy axial MR image shows an irregularly shaped enhancing mass with spiculated margins that measures 5.8 cm in its greatest transverse diameter (between arrows). Source: Radiology.

Diffuse optical spectroscopic (DOS) tomography imaging may help differentiate complete and partial responses to neoadjuvant chemotherapy among women with invasive breast cancer, according to a small pilot study published in this month's Radiology.

Recently developed imaging modalities, such as DOS tomography which provides 2D information about the intrinsic and ultrastructural biophysical composition of the breast, offer the capability to image biologic markers that reflect tissue function and may improve the ability to predict response to therapy, and thus, help individualize treatment, explained Marius G. Pakalniskis, MD, of the department of pathology at Dartmouth Medical School in Hanover, N.H., and colleagues.

The ability to predict response to therapy is critical in breast cancer as a complete pathologic response (pCR) is associated with a 10-year survival rate of more than 90 percent among neoadjuvant chemotherapy patients. In contrast, patients with a partial pathologic response (pPR) have a corresponding survival rate of 60 percent or less.

The researchers designed the pilot study to determine whether changes in tumor angiogenesis associated with pCR or pPR can be detected via DOS tomography and specifically attempted to uncover a relationship between the DOS measure of total tissue hemoglobin (Hb_T) with quantitative angiogenesis measured before and after chemotherapy.

The authors measured HB_T and mean vessel density (MVD) and mean vessel area (MVA) of tumor-induced endoglin-expressing vessels in a cohort of 11 women referred for neoadjuvant chemotherapy. The datasets included Hb_T inside and outside the tumor region of interest and an average for contralateral breast.

The researchers acquired MR images of the diseased breast and DOS tomographic images before biopsy, before and during neoadjuvant chemotherapy and two to three days prior to final mastectomy.

Pakalniskis et al reported no significant differences in pretreatment MVD or MVA that could be used to predict clinical outcome following chemotherapy. However, “there was a significant difference in the MVD of pre-existing CD31-expressing vessels between pre-treatment core tumor and post-treatment normal tissue in both women with pCR (decrease from 1.47 percent to 0.4 percent) and women with pPR (decrease from 1.56 percent to 0.22 percent).”

In addition, the researchers found significant differences in MVD and MVA of endoglin-expressing vessels when they compared pre-treatment and post-treatment tissues of women with pCR and pPR, except between pretreatment tumor and posttreatment residual tumor in women with pPR.

The seven complete responders demonstrated a significant correlation between the MVD of endoglin-expressing vessels in pretreatment biopsy specimens and pretreatment Hb_T. When the researchers analyzed MVD of preexisting and tumor-induced endoglin-expressing vessels, they detected significant differences between pretreatment tumor tissue and posttreatment normal and treated tissue in women with pCR.

Pakalniskis and colleagues acknowledged several limitations to the study, particularly its small sample size, and emphasized the need for multi-institutional studies.

They concluded, “[O]ur study results show a correlation between changes in Hb_T at DOS tomography and tumor angiogenesis and demonstrate how this noninvasive modality might allow individualization and optimization of neoadjuvant chemotherapy regimens.”