Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy

Abstract

Diffuse optical spectroscopy (DOS) and imaging are emerging diagnostic techniques that quantitatively measure the concentration of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctO 2Hb), water (ctH 2O), and lipid in cm-thick tissues. In early-stage clinical studies, diffuse optical imaging and DOS have been used to characterize breast tumor biochemical composition and monitor therapeutic response in stage II/III neoadjuvant chemotherapy patients. We investigated whether DOS measurements obtained before and 1 week into a 3-month adriamycin/cytoxan neoadjuvant chemotherapy regimen can predict final, postsurgical pathological response. Baseline DOS measurements of 11 patients before therapy revealed significant increases in tumor ctHHb, ctO 2Hb, ctH 2O, and spectral scattering slope, and decreases in bulk lipids, relative to normal breast tissue. Tumor concentrations of ctHHb, ctO 2Hb, and ctH2O dropped 27 ؎ 15%, 33 ؎ 7%, and 11 ؎ 15%, respectively, within 1 week (6.5 ؎ 1.4 days) of the first treatment for pathology-confirmed responders (n ‫؍‬ 6), whereas nonresponders (n ‫؍‬ 5) and normal side controls showed no significant changes in these parameters. The best single predictor of therapeutic response 1 week posttreatment was ctHHb (83% sensitivity, 100% specificity), while discrimination analysis based on combined ctHHb and ctH 2O changes classified responders vs. nonresponders with 100% sensitivity and specificity. In addition, the pretreatment tumor-to-normal ctO 2Hb ratio was significantly higher in responders (2.82 ؎ 0.44) vs. nonresponders (1.82 ؎ 0.49). These results highlight DOS sensitivity to tumor cellular metabolism and biochemical composition and demonstrate its potential for predicting and monitoring an individual's response to treatment.diffuse optical imaging ͉ frequency-domain photon migration ͉ near-infrared ͉ tissue spectroscopy ͉ translational research O ptimal management locally advanced breast cancer (LABC) remains a complex therapeutic problem (1). LABC represents 5-20% of all newly diagnosed breast cancers in the United States with a higher incidence in medically underserved areas (2). Treatment for LABC has evolved from radical mastectomy to preoperative neoadjuvant chemotherapy followed by mastectomy or breast conservation therapy (3). Despite aggressive local therapy, long-term patient survival is still poor. LABC remains controversial because of uncertainties in determining the optimal intensity and duration of neoadjuvant chemotherapy and evaluating therapeutic response (2, 4, 5).Neoadjuvant chemotherapy response is determined by serial physical examination, mammography and/or ultrasound. Complete pathological response (cPR) is an important therapeutic endpoint that is a surrogate for eradicating micrometastases, and strongly correlates with patient survival (6). Thus one goal of neoadjuvant chemotherapy monitoring is to determine early when a patient will demonstrate cPR. Many studies revealed significant discrepancies between clinical response assessments and final pathology (7-9).A rece...

Diffuse optical tomography of the breast: preliminary findings of a new prototype and comparison with magnetic resonance imaging

“…Intra-and interobserver agreement were good to excellent, indicating a reproducible method. Our results are in agreement with previously published studies using different techniques [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Detection rates ranging from 0.04 to 1.00 were reported, irrespective of lesion classification (benign/malignant).…”

In Vivo 1H-MRS Lipid Signal: Is it Useful for Tumor Response to Neoadjuvant Chemotherapy?

“…Our study performed on breast cancer treated with chemotherapy showed that in non-pCR group the change in lipids peak signals at the first follow-up (F/U-1, 1-2 cycles AC) was higher, but not significant compared to that of pCR group (P>0.05). The result suggests that the change of lipid peak signals maybe not serve as an early indicator for predicting later clinical response or pathological complete response [6]. However, in previous studies [1][2][3], tCho level has showed significant reduction in the response group but not in non-response group, suggesting an early response predictor.…”

Prognostic imaging in neoadjuvant chemotherapy of locally-advanced breast cancer should be cost-effective

“…Thus, an important conclusion from this study is that the specificity and cost of the systems are not dominant factors in the cost effectiveness. While our initial calculations were looking at near-infrared imaging [16], the results of the study are applicable to a range of possible imaging systems that could be applied in the course of neoadjuvant therapy. This is important, because studies with ultrasound, PET and MRI have all been completed, and the cost and specificity of each of these systems varies considerably, yet each would likely have similarly acceptable cost effectiveness.…”

“…Recent pilot studies in both MRI and Near-Infrared Spectroscopy (NIR) have shown that more global estimates of cancer, such as water content and vascular volume changes, can be good predictors of response in primary breast cancer [14][15][16][17][18]. Total water content and vascular volume are robust signals in that they can be measured with a good signal to noise ratio, and biological variations in these are generally low, except in response to intervention.…”

“…Total water content and vascular volume are robust signals in that they can be measured with a good signal to noise ratio, and biological variations in these are generally low, except in response to intervention. Further, and of great potential interest, in pilot studies there is evidence that these biophysical changes occur within the first cycle of chemotherapy [14][15][16][17][18], which could have considerable prognostic value if confirmed with high specificity. Thus a key factor being tested in multi-center trials now is to determine the sensitivity and specificity of NIR or MRI as a measurement of response within the first cycle of NACT, and if this value is sufficient for a cost-effective test.…”