Changes in the tumor oxygenation but not in the tumor volume and tumor vascularization reflect early response of breast cancer to neoadjuvant chemotherapy

Abstract

Background Breast cancer neoadjuvant chemotherapy (NACT) allows for assessing tumor sensitivity to systemic treatment, planning adjuvant treatment and follow-up. However, a sufficiently large number of patients fail to achieve the desired level of pathological tumor response while optimal early response assessment methods have not been established now. In our study, we simultaneously assessed the early chemotherapy-induced changes in the tumor volume by ultrasound (US), the tumor oxygenation by diffuse optical spectroscopy imaging (DOSI), and the state of the tumor vascular bed by Doppler US to elaborate the predictive criteria of breast tumor response to treatment. Methods A total of 133 patients with a confirmed diagnosis of invasive breast cancer stage II to III admitted to NACT following definitive breast surgery were enrolled, of those 103 were included in the final analysis. Tumor oxygenation by DOSI, tumor volume by US, and tumor vascularization by Doppler US were determined before the first and second cycle of NACT. After NACT completion, patients underwent surgery followed by pathological examination and assessment of the pathological tumor response. On the basis of these, data regression predictive models were created. Results We observed changes in all three parameters 3 weeks after the start of the treatment. However, a high predictive potential for early assessment of tumor sensitivity to NACT demonstrated only the level of oxygenation, ΔStO2, (ρ = 0.802, p ≤ 0.01). The regression model predicts the tumor response with a high probability of a correct conclusion (89.3%). The “Tumor volume” model and the “Vascularization index” model did not accurately predict the absence of a pathological tumor response to treatment (60.9% and 58.7%, respectively), while predicting a positive response to treatment was relatively better (78.9% and 75.4%, respectively). Conclusions Diffuse optical spectroscopy imaging appeared to be a robust tool for early predicting breast cancer response to chemotherapy. It may help identify patients who need additional molecular genetic study of the tumor in order to find the source of resistance to treatment, as well as to correct the treatment regimen.

Ultrasound and clinicopathologic feature based model for early prediction of pathologic response to neoadjuvant chemotherapy in breast cancer: A case-control study

“…In terms of US characteristics, the presence of lateral acoustic shadowing, absence of calcifications or presence of coarse calcifications, absence of crab foot-like changes, low blood flow score, and greater shrinkage rate of post 2 nd course of NAC were established as independent predictors associated with PCR after NAC of breast cancer. ΔD is the rate of change of the maximum diameter of the lesion, and dynamic changes in tumor volume are a simple and effective marker [26], This study found that the rate of tumor shrinkage post 2 nd course of NAC was an independent predictor of PCR acquisition in breast cancer, which is the same as previous studies [27,28],Tumors with greater shrinkage rate post 2 nd course of NAC are more likely to get PCR. it has been suggested [29]that the method of assessing PCR based on detecting tumor size has significant limitations; morphologic changes in breast cancer after NAC lag behind changes in metabolic response and are influenced by the pattern of lesion regression; the size of lesions that show centripetal regression is easily measured, whereas some of the lesions that show non-centripetal regression have insignificant morphologic changes but reduced density of tumor cells and proliferating fibrous tissue separating the lesions into a "honeycomb" [30],These tumors are still susceptible to PCR although the rate of maximum diameter reduction is small, so the sensitivity of using the rate of change of the maximum tumor diameter alone is not high and needs to be combined with other indicators.…”

Towards detection of early response in neoadjuvant chemotherapy of breast cancer using Bayesian intravoxel incoherent motion

“…The results of the study suggest that perfusion fraction might be a sensitive biomarker of NACT to improve treatment planning, reduce side effects, and expedite precision medicine. Mammography and breast ultrasound have been proposed at the halfway point of NACT to measure the residual tumour size using the RECIST criteria ( 55 ); however, tumour regression is not an accurate predictor of response at the first ( 56 ) or second ( 34 ) cycle of NACT. There was no correlation in size reduction with tumour grade decrease after two cycles of NACT ( 50 ), and a reduction in size of the tumours was seen in both small and large tumours ( 57 ), potentially due to the formation of islands of nonviable tumour cells subsequent to NACT ( 50 ).…”

Functional hemodynamic imaging markers for the prediction of pathological outcomes in breast cancer patients treated with neoadjuvant chemotherapy

“…The secondary aims of this study were to explore if compression-induced changes in DOT-derived metrics were predictive of pCR and if the prediction could be made at an earlier time, such as pre-cycle 2. These exploratory aims were motivated by findings from prior studies that reported tissue oxygenation as an early indicator of pCR 23 – 25 and that hemodynamic changes during mammographic compression are correlated with pathologic outcomes. 45 To this end, we explored other possible imaging markers which consisted of a full combination of the normalized HbT and values at either a single imaging time point (i.e., pre-cycle 2 and pre-cycle 3) or changes across two imaging time points (i.e., baseline versus pre-cycle 2, and baseline versus pre-cycle 3) using either absolute normalized values at each compression period (i.e., periods 1 to 3) or cross-period changes (i.e., period 1 versus period 2, and period 2 versus period 3).…”

“… 18 , 19 DOT-derived markers, such as total hemoglobin concentration (HbT = HbO + HbR) and tissue oxygenation ( ), can offer insights into tumor oxygen metabolism, perfusion, and proliferation. 20 Over the years, several NIRS/DOT studies, either using standalone optical imaging devices 21 – 31 or hybrid systems with breast ultrasound, 32 – 34 have reported statistically significant differences between responders versus non-responders as early as after the first cycle of therapy. The consensus from these studies generally indicates early decreases in tumor HbT, a surrogate marker of blood volume and hence angiogenesis, correlate with favorable treatment outcomes, more so in tumors with higher tissue oxygenation levels.…”