Predicting pathologic response to neoadjuvant chemotherapy in breast cancer by using MR imaging and quantitative 1H MR spectroscopy

Abstract

Purpose: To compare changes in the concentration of choline-containing compounds (tCho) and in tumor size at follow-up after neoadjuvant chemotherapy (NAC) between patients who achieved pathologic complete response (pCR) and those who did not (non-pCR).

Materials and methods: This study was approved by the institutional review board and was compliant with HIPAA; each patient gave informed consent. Thirty-five patients (mean age, 48 years +/- 11 [standard deviation]; range, 29-75 years) with breast cancer were included. Treatment included doxorubicin and cyclophosphamide followed by a taxane-based regimen. Changes in tCho and tumor size in pCR versus non-pCR groups were compared by using the two-way Mann-Whitney nonparametric test. Receiver operating characteristic (ROC) analysis was performed to differentiate between them and the area under the ROC curve (AUC) was compared.

Results: In the pCR group, the tCho level change was greater compared with change in tumor size (P = .003 at first follow-up, P = .01 at second follow-up), but they were not significantly different in the non-pCR group. Changes in tumor size and tCho level at the first follow-up study were not significantly different between the pCR and non-pCR groups but reached significance at the second follow-up. In ROC analysis, the magnetic resonance (MR) imaging and MR spectroscopic parameters had AUCs of 0.65-0.68 at first follow-up; at second follow-up, AUC for change in tumor size was 0.9, AUC for change in tCho was 0.73.

Conclusion: Patients who show greater reduction in tCho compared with changes in tumor size are more likely to achieve pCR. The change in tumor size halfway through therapy was the most accurate predictor of pCR.

Figure 1a:

Box plot shows comparison of percentage of changes in tumor size and tCho (a) in follow-up study after one to two AC cycles and (b) in follow-up study after four AC cycles or two AC cycles followed by one of taxane regimen in pCR versus non-pCR groups. In both follow-up studies, there were significantly higher reductions in tCho level compared with tumor size in pCR group only.

Figure 1b:

Box plot shows comparison of percentage of changes in tumor size and tCho (a) in follow-up study after one to two AC cycles and (b) in follow-up study after four AC cycles or two AC cycles followed by one of taxane regimen in pCR versus non-pCR groups. In both follow-up studies, there were significantly higher reductions in tCho level compared with tumor size in pCR group only.

Figure 2a:

Plots of changes in (a) normalized tCho and (b) tumor size with treatment in pCR patients. First follow-up study after one to two AC cycles and second follow-up study after four AC cycles or two of AC followed by first cycle of taxane regimen. Five patients did not have detectable tCho at baseline. Of 12 patients who had positive tCho before treatment, seven had detectable tCho at first follow-up. At second follow-up, all patients had substantially smaller tumor sizes and none had detectable tCho.

Figure 2b:

Plots of changes in (a) normalized tCho and (b) tumor size with treatment in pCR patients. First follow-up study after one to two AC cycles and second follow-up study after four AC cycles or two of AC followed by first cycle of taxane regimen. Five patients did not have detectable tCho at baseline. Of 12 patients who had positive tCho before treatment, seven had detectable tCho at first follow-up. At second follow-up, all patients had substantially smaller tumor sizes and none had detectable tCho.

Figure 3:

Maximum intensity projection MR images (left) and corresponding MR spectra (right) from 40-year-old patient (patient 12) who achieved pCR. (A) Before treatment, 3.4-cm lesion (arrow) shows heterogeneous enhancing pattern. Elevated total tCho peak (right) is visible at 3.23 ppm in water-fat suppressed spectrum. Gaussian model fitting of tCho peak, 2.33 mmol/kg ± 0.54. (B) Enhancing lesion (white arrow) and water-fat suppressed spectrum (black arrow) acquired after one AC cycle. Lesion size is reduced to 2.6 cm, tCho peak is visible at 3.22 ppm, and tCho = 1.15 mmol/kg ± 0.25. Change of tCho level shows 51% reduction, tumor size shows 23% reduction. (C) At second follow-up after two AC cycles and one of taxane regimen, lesion (white arrow) further shrank to 1.3 cm, indicating good response. (D) After all chemotherapy, breast lesion completely regressed. In water-fat suppressed spectrum, tCho peak (arrow) was no longer detectable (100% reduction).

Figure 4a:

Plots of changes in (a) normalized tCho and (b) tumor size with treatment in non-pCR patients. One patient did not have detectable tCho at baseline. Of 16 patients who had positive tCho before treatment, 13 had detectable tCho levels at first follow-up. At second follow-up, seven patients had detectable tCho and two had increased tCho (higher than baseline). Patients show wide range of changes in tumor size compared with changes in pCR group in Figure 2.

Figure 4b:

Plots of changes in (a) normalized tCho and (b) tumor size with treatment in non-pCR patients. One patient did not have detectable tCho at baseline. Of 16 patients who had positive tCho before treatment, 13 had detectable tCho levels at first follow-up. At second follow-up, seven patients had detectable tCho and two had increased tCho (higher than baseline). Patients show wide range of changes in tumor size compared with changes in pCR group in Figure 2.

Figure 5:

Maximum intensity projection MR images of 29-year-old woman (patient 24) who had residual invasive cancer after completing NAC. (A) Before treatment, lesion is 8.4 cm (arrow); tCho peak is visible at 3.22 ppm in water-fat suppressed spectrum (right), and tCho = 0.77 ± 0.11 mmol/kg. (B) After one AC cycle, enhanced lesion (white arrow) shrank to 7.4 cm (12% reduction), tCho level (black arrow) decreased to 0.21 mmol/kg (73% reduction). (C) At second follow-up after four AC cycles, lesion (white arrow) further shrank to 4.6 cm but tCho concentration increased to 1.01 mmol/kg (black arrow). (D) In third follow-up after completing all chemotherapy, tumor increased to 5.5 cm (white arrow). Increase in tCho level (black arrow) at second follow-up seems to predict disease progression at third follow-up.