Assessment of therapeutic response of locally advanced breast cancer (LABC) patients undergoing neoadjuvant chemotherapy (NACT) monitored using sequential magnetic resonance spectroscopic imaging (MRSI)

Abstract

The potential of total choline (tCho) signal-to-noise ratio (SNR) (ChoSNR) and tumor volume in the assessment of tumor response in locally advanced breast cancer (LABC) patients (n = 30) undergoing neoadjuvant chemotherapy (NACT) was investigated using magnetic resonance spectroscopic imaging (MRSI) and conventional MRI at 1.5 T. Experiments were carried out sequentially at four time-points: prior to therapy and after I, II and III NACT and ChoSNR, and the tumor volume was measured. The MR response was compared with the clinical response. Sequential data of 25 patients were retrospectively analyzed by classifying them as clinical responders and non-responders. In 14 responders, the pre-therapy ChoSNR was 7.8 +/- 5.1. In 10/14 responders, no choline was observed after III NACT while in the remaining four patients the ChoSNR was reduced to 3.6 +/- 1.1 (p < 0.05). Non-responders showed no statistically significant change in ChoSNR. After III NACT, the tumor volume reduced by 84.0 +/- 14.8% in responders. Using receiver operating curve (ROC) analysis, cut-off values of 53% for ChoSNR and 47.5% for volume were obtained to differentiate responders from non-responders. The sensitivity to detect responders from non-responders using ChoSNR was 85.7% with 91% specificity while 100% sensitivity was observed for volume but with reduced specificity of 73%. Our results indicate that ChoSNR may serve as a useful parameter to predict tumor response to NACT with higher specificity compared to volume, suggesting its potential in effective treatment management.

In vivo MRS of locally advanced breast cancer: characteristics related to negative or positive choline detection and early monitoring of treatment response

“…Many authors report the use of signal to noise as a semiquantitative measure, usually considering SNR > 2 as a positive tCho detection [4,14,42]. This is an easy applicable measure in a clinical setting, and as also shown by our reliability measurements, a stable measure for tCho in breast tumors.…”

“…However, a significant difference in tCho after the 2nd cycle of chemotherapy was proven using an external reference method [33]. Using MRSI and SNR (averaged on positive tCho voxels), a significant reduction in tCho was observed in responders at all timepoints (after NAC cycle 1, 2 and 3), while the reduction in non-responders was not significant [14]. Another important issue in light of previous in vivo 31P MRS studies, showing significantly increased GPC concentrations as response to treatment in breast cancer cells and xenografts [34,35], may however question whether it is reasonable to expect that decreases in tCho really should be observed in all responders.…”

“…Meisamy et al used the RECIST criterion, defining responders based on a reduction in clinically measured tumor size of at least 30% after the 4th cycle of NAC [13]. Danishad et al [14] used a commonly applied modification of RECIST, defining responders as those with at least 50% reduction after the 3rd cycle of NAC, while Tozaki et al [33] used the less common Sataloff grading. Baek et al [11] defined responders as those with no invasive cancer present in the final surgical specimen, i.e.…”

“…It has also been shown that tCho can be detected in lactating women [1], and in benign lesions, especially at higher field strengths [9]. During the last decade, the tCho signal has been extensively investigated as a potential biomarker for response to neoadjuvant chemotherapy (NAC) in breast cancer [10][11][12][13][14]. However, one of the challenges using in vivo MRS in the breast is the fact that even in highly malignant tumours tCho may be below the detection limits.…”

MRI in the evaluation of breast cancer patient response to neoadjuvant chemotherapy: predictive factors for breast conservative surgery

“…The use of the additional MRI techniques like diffusion-weighted imaging, improves the specificity to 80%, according to Fanberget et al (28), although the use of diffusion-weighted imaging in monitoring treatment response has been limited (37). Another technique is magnetic resonance spectroscopic imaging, which improves the specificity up to 91% (44). Based on the higher cut-off value of 83%, which is the tumor volume reduction suggested by Fangberget et al (28), the sensitivity remains high-87% after the completion of NACT-with the accuracy of 77% and precision of 73%.…”