Torgeir Mo

Objectives: To explore if MRI can monitor treatment and predict outcome in patients with human epidermal growth factor 2 (HER2)-negative breast cancer receiving neoadjuvant chemotherapy (NACT) with or without bevacizumab. Methods: Multiparametric MRI was performed at baseline and after 12 and 25 weeks of NACT. MRI assessment included tumour size, apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI), and signal intensity–time curves and vascular volume transfer constant (K^TRANS) from dynamic contrast-enhanced MRI (DCE). The reference standards were pathological complete response (pCR) at the time of surgery, and 10-year recurrence-free survival. Receiver operating characteristics analyses were performed to assess the predictive value of the MRI parameters. MRI findings and outcomes were compared between the treatment groups. Results: Seventy women were included from November 2008 to July 2012, with a median age of 49.5 years and median tumour diameter of 47 mm. Fourteen patients (20.0%) achieved pCR, while eleven (15.7%) had recurrence during the 10-year follow-up. The treatment significantly reduced tumour size, increased ADC, decreased K^TRANS, and shifted the signal intensity–time curves towards more benign shapes. The DCE parameters changed significantly more in the bevacizumab group. In the bevacizumab group, baseline K^TRANS predicted pCR (Area under curve (AUC) = 0.73), but the difference in pCR-rates between the treatment groups was not significant (p = 0.07). Only tumour size and shrinkage at 12 weeks predicted pCR (AUC = 0.71–0.85) regardless of size measuring method. No MRI parameters predicted survival. Conclusions: All MRI parameters reflected treatment response, but no parameter predicted survival or benefit from adding bevacizumab to chemotherapy.

Anti-VEGF (vascular endothelial growth factor) treatment improves response rates, but not progression-free or overall survival in advanced breast cancer. It has been suggested that subgroups of patients may benefit from this treatment; however, the effects of adding anti-VEGF treatment to a standard chemotherapy regimen in breast cancer patients are not well studied. Understanding the effects of the anti-vascular treatment on tumor vasculature may provide a selection of patients that can benefit. The aim of this study was to study the vascular effect of bevacizumab using clinical dynamic contrast-enhanced MRI (DCE-MRI). A total of 70 women were randomized to receive either chemotherapy alone or chemotherapy with bevacizumab for 25 weeks. DCE-MRI was performed at baseline and at 12 and 25 weeks, and in addition 25 of 70 patients agreed to participate in an early MRI after one week. Voxel-wise pharmacokinetic analysis was performed using semi-quantitative methods and the extended Tofts model. Vascular architecture was assessed by calculating the fractal dimension of the contrast-enhanced images. Changes during treatment were compared with baseline and between the treatment groups. There was no significant difference in tumor volume at any point; however, DCE-MRI parameters revealed differences in vascular function and vessel architecture. Adding bevacizumab to chemotherapy led to a pronounced reduction in vascular DCE-MRI parameters, indicating decreased vascularity. At 12 and 25 weeks, the difference between the treatment groups is severely reduced.

The purpose of the present study is to investigate if consumption and supply hypoxia (CSH) MR-imaging can depict breast cancer hypoxia, using the CSH-method initially developed for prostate cancer. Furthermore, to develop a generalized pan-cancer application of the CSH-method that doesn’t require a hypoxia reference standard for training the CSH-parameters. In a cohort of 69 breast cancer patients, we generated, based on the principles of intravoxel incoherent motion modelling, images reflecting cellular density (apparent diffusion coefficient; ADC) and vascular density (perfusion fraction; fp). Combinations of the information in these images were compared to a molecular hypoxia score made from gene expression data, aiming to identify a way to apply the CSH-methodology in breast cancer. Attempts to adapt previously proposed models for prostate cancer included direct transfers and model parameter rescaling. A novel approach, based on rescaling ADC and fp data to give more nuanced response in the relevant physiologic range, was also introduced. The new CSH-method was validated in a prostate cancer cohort with known hypoxia status. The proposed CSH-method gave estimates of hypoxia that was strongly correlated to the molecular hypoxia score in breast cancer, and hypoxia as measured in pathology slices stained with pimonidazole in prostate cancer. The generalized approach to CSH-imaging depicted hypoxia in both breast and prostate cancers and requires no model training. It is easy to implement using readily available technology and encourages further investigation of CSH-imaging in other cancer entities and in other settings, with the goal being to overcome hypoxia-induced resistance to treatment.