Diffusion weighted imaging to predict nodal status in breast cancer: A systematic review and meta-analysis.

Abstract

Diffusion weighted imaging is a functional imaging modality based upon Brownian water movement in tissues.1-3 This movement can be quantified by apparent diffusion coefficient (ADC). According to the literature, apparent diffusion coefficient (ADC) inversely correlates with histopathological features.1, 2 It was identified that benign breast lesions have significant higher ADC values compared to breast cancer (BC).5 Nodal status is one of the most important prognosis parameters in BC, which is assessed by axillary lymph node dissection.6 Our purpose was to systematically review the published literature regarding ADC values of BC in accordance with nodal status and the ADC values of axillary lymph nodes and perform a meta-analysis to establish, whether ADC values can reliably predict nodal status in BC. The literature was searched for suitable papers investigating the associations between ADC values and nodal status in BC. The meta-analysis was performed as previously described.5 The primary end point of the systematic review was association between nodal status of BC and ADC values of the primary tumor and axillary LN. In total, 23 studies were suitable for the analysis and were included into the present study. The acquired 23 studies comprised overall 1669 BC and 1423 LN. In total, 1025 nodal negative and 548 nodal positive BC were included into the analysis. The mean ADC of the primary tumor of the nodal positive BC was 0.89 × 10− 3 mm2/s [95% CI 0.84–0.94, I2 = 91%], and 0.96 × 10− 3 mm2/s [95% CI 0.91–1.01, I2 = 92%] of the nodal negative BC (Figure 1). In total, 876 benign and 547 malignant LN were included into the analysis. The mean ADC value of the malignant axillary LN was 0.90 × 10− 3 mm2/s [95% CI 0.80–1.01, I2 = 98%] and 1.17 × 10− 3 mm2/s [95% CI 1.02–1.32, I2 = 99%] of the benign LN (Figure 2). Three studies reported data regarding ADC values and LN size in large and short axis with overall 57 lymph nodes. Spearman's correlation coefficient for the large axis was r = −0.143, p = 0.29 and for the short axis was r = 0.024, p = 0.86. The present analysis showed that ADC values of the axillary LN are lower in malignant LN compared to benign LN and might aid in clinical decision-making. Similar findings were identified of the ADC values of primary tumors to predict nodal status in BC. Thus, the present analysis based upon a large sample size corroborates the results of previous single-center studies. Nodal status is one of the most important prognosis factors in BC, which leads to a worse outcome in patients with positive axillary lymph nodes compared to nodal negative patients.6 A precise definition of the status of axillary LN in BC patients is also important to select treatment modality or surgical method. Axillary LN dissection is the reference standard for evaluating nodal involvement. Several imaging modalities were used to predict LN status non-invasively. So, ultrasound was deemed to be unreliable.7 The cost expensive modality with radiation exposure, namely PET-CT, achieved only a pooled sensitivity of 56% in a recent meta-analysis, whereas morphological MRI achieved a sensitivity of 55% only.7 However, both modalities reached a high specificity of 91% and 86%, respectively. Yet, there is definite need for a better diagnostic modality to predict nodal status in BC. The present analysis tried to emphasize that DWI and ADC values might be able to fill this diagnostic gap with measurement of the primary tumor itself as well as with the measurement of the lymph nodes. Interestingly, ADC values are independent of the lymph node size, which is most often used in clinical routine as a sign for malignancy. The present analysis can state that ADC values are not correlated with the short and long axis size of the lymph nodes. Presumably, a primary tumor with nodal involvement has a more aggressive tumor biology with distinctive microstructure, which can be assessed by ADC values. Moreover, there is clear evidence that ADC values can aid in the discrimination between benign and malignant tumors, which was shown in a recent meta-analysis.5 So, the present analysis can harmonize the published results that ADC values of the primary tumor as well as of the axillary lymph nodes can aid to predict nodal status in BC. As a limitation to address, the meta-analysis is based upon published results in the literature. There might be a certain publication bias because there is a trend to report positive or significant results. In conclusion, ADC values of axillary LN and of primary tumors may aid in predict nodal status of BC in clinical routine. These results are based upon a large patient sample and can be considered representative.