Breast tumour volume and blood flow measured by MRI after one cycle of epirubicin and cyclophosphamide-based neoadjuvant chemotherapy as predictors of pathological response

Objectives: Better markers of early response to neoadjuvant chemotherapy (NACT) in patients with breast cancer are required to enable the timely identification of non-responders and reduce unnecessary treatment side-effects. Early functional imaging may better predict response to treatment than conventional measures of tumour size. The purpose of this study was to test the hypothesis that the change in tumour blood flow after one cycle of NACT would predict pathological response. Methods: In this prospective cohort study, dynamic contrast-enhanced MRI was performed in 35 females with breast cancer before and after one cycle of epirubicin and cyclophosphamide-based NACT (EC90). Estimates of tumour blood flow and tumour volume were compared with pathological response obtained at surgery following completion of NACT. Results: Tumour blood flow at baseline (mean ± SD; 0.32 ± 0.17 ml/min/ml) reduced slightly after one cycle of NACT (0.28 ± 0.18 ml/min/ml). Following treatment 15 patients were identified as pathological responders and 20 as non-responders. There were no relationships found between tumour blood flow and pathological response. Conversely, tumour volume was found to be a good predictor of pathological response (smaller tumours did better) at both baseline (area under the receiver operating characteristic curve 0.80) and after one cycle of NACT (area under the receiver operating characteristic curve 0.81). Conclusion & advances in knowledge: The change in breast tumour blood flow following one cycle of EC90 did not predict pathological response. Tumour volume may be a better early marker of response with such agents.

Potential synergy between PSMA uptake and tumour blood flow for prediction of human prostate cancer aggressiveness

Background Both prostate-specific membrane antigen (PSMA) uptake and tumour blood flow (TBF) correlate with International Society of Urological Pathology (ISUP) Grade Group (GG) and hence prostate cancer (PCa) aggressiveness. The aim of the present study was to evaluate the potential synergistic benefit of combining the two physiologic parameters for separating significant PCa from insignificant findings. Methods From previous studies of [82Rb]Rb positron emission tomography (PET) TBF in PCa, the 43 patients that underwent clinical [68Ga]Ga-PSMA-11 PET were selected for this retrospective study. Tumours were delineated on [68Ga]Ga-PSMA-11 PET or magnetic resonance imaging. ISUP GG was recorded from 52 lesions. Results [68Ga]Ga-PSMA-11 maximum standardized uptake value (SUVmax) and [82Rb]Rb SUVmax correlated moderately with ISUP GG (rho = 0.59 and rho = 0.56, both p < 0.001) and with each other (r = 0.65, p < 0.001). A combined model of [68Ga]Ga-PSMA-11 and [82Rb]Rb SUVmax separated ISUP GG > 2 from ISUP GG 1–2 and benign with an area-under-the-curve of 0.85, 96% sensitivity, 74% specificity, and 95% negative predictive value. The combined model performed significantly better than either tracer alone did (p < 0.001), primarily by reducing false negatives from five or six to one (p ≤ 0.025). Conclusion PSMA uptake and TBF provide complementary information about tumour aggressiveness. We suggest that a combined analysis of PSMA uptake and TBF could significantly improve the negative predictive value and allow non-invasive separation of significant from insignificant PCa.

15O-Water Dynamic Positron Emission Tomography in Patients with Non-Small Cell Lung Cancer: Early Decrease in Blood Flow After Anti-Angiogenic Treatment is Correlated with a Shorter Time to Tumour Progression

Purpose: To evaluate tumour blood flow in patients with non-small cell lung cancer (NSCLC) who underwent chemotherapy with bevacizumab before and after administration of chemotherapy using 15O-water positron emission tomography (PET), and to investigate the effects of bevacizumab on tumour blood flow changes and progression-free survival (PFS).Methods: Twelve patients with NSCLC were enrolled. Six patients had chemotherapy with bevacizumab, and the other six had chemotherapy without bevacizumab. 15O-water dynamic PET scans were performed within 1week before the start of chemotherapy and within 1 week after the first day of chemotherapy. Tumour blood flow was analysed quantitatively using a single one‑tissue compartment model with the correction of pulmonary circulation blood volume and arterial blood volume via an image-derived input function. Results: In the bevacizumab group mean tumour blood flow had reduced statistically significantly post-chemotherapy (pre-chemotherapy 0.27 ± 0.14 mL/cm3/min, post‑chemotherapy 0.18 ± 0.12 mL/cm3/min). In the no bevacizumab group there was no significant difference between mean tumour perfusion pre-chemotherapy (0.42 ± 0.42 mL/cm3/min) and post-chemotherapy (0.40 ± 0.27 mL/cm3/min). In the bevacizumab group there was a positive correlation between the blood flow ratio (tumour blood flow post-chemotherapy/tumour blood flow pre-chemotherapy) and PFS (correlation coefficient 0.94).Conclusion: Mean tumour blood flow decreases within 1–2 days after bevacizumab administration. Greater reductions in blood flow were associated with shorter PFS.

A thermoporoelastic model for fluid transport in tumour tissues

In this paper, the effect of coupled thermal dilation and stress on interstitial fluid transport in tumour tissues is evaluated. The tumour is modelled as a spherical deformable poroelastic medium embedded with interstitial fluid, while the transvascular fluid flow is modelled as a uniform distribution of fluid sink and source points. A hyperbolic-decay radial function is used to model the heat source generation along with a rapid decay of tumour blood flow. Governing equations for displacement, fluid flow and temperature are first scaled and then solved with a finite-element scheme. Results are compared with analytical solutions from the literature, while results are presented for different scaling parameters to analyse the various physical phenomena. Results show that temperature affects pressure and velocity fields through the deformable medium. Finally, simulations are performed by assuming that the heat source is periodic, in order to assess the extent to which this condition affects the velocity field. It is reported that in some cases, especially for periodic heating, the combination of thermoelastic and poroelastic deformation led to no monotonic pressure distribution, which can be interesting for applications such as macromolecule drug delivery, in which the advective contribution is very important owing to the low diffusivity.

Sensitivity of Multiphase Pseudocontinuous Arterial Spin Labelling (MP pCASL) Magnetic Resonance Imaging for Measuring Brain and Tumour Blood Flow in Mice

Brain and tumour blood flow can be measured noninvasively using arterial spin labelling (ASL) magnetic resonance imaging (MRI), but reliable quantification in mouse models remains difficult. Pseudocontinuous ASL (pCASL) is recommended as the clinical standard for ASL and can be improved using multiphase labelling (MP pCASL). The aim of this study was to optimise and validate MP pCASL MRI for cerebral blood flow (CBF) measurement in mice and to assess its sensitivity to tumour perfusion. Following optimization of the MP pCASL sequence, CBF data were compared with gold-standard autoradiography, showing close agreement. Subsequently, MP pCASL data were acquired at weekly intervals in models of primary and secondary brain tumours, and tumour microvessel density was determined histologically. MP pCASL measurements in a secondary brain tumour model revealed a significant reduction in blood flow at day 35 after induction, despite a higher density of blood vessels. Tumour core regions also showed reduced blood flow compared with the tumour rim. Similarly, significant reductions in CBF were found in a model of glioma 28 days after tumour induction, together with an increased density of blood vessels. These findings indicate that MP pCASL MRI provides accurate and robust measurements of cerebral blood flow in naïve mice and is sensitive to changes in tumour perfusion.

Arterial spin labelling and diffusion-weighted magnetic resonance imaging in differentiation of recurrent head and neck cancer from post-radiation changes

ObjectiveTo assess arterial spin labelling and diffusion-weighted imaging in the differentiation of recurrent head and neck cancer from post-radiation changes.MethodsA retrospective study was conducted of 47 patients with head and neck cancer, treated with radiotherapy, who underwent magnetic resonance arterial spin labelling and diffusion-weighted magnetic resonance imaging. Tumour blood flow and apparent diffusion co-efficient of the lesion were calculated.ResultsThere was significant difference (p= 0.001) in tumour blood flow between patients with recurrent head and neck cancer (n= 31) (47.37 ± 16.3 ml/100 g/minute) and those with post-radiation changes (n= 16) (18.80 ± 2.9 ml/100 g/minute). The thresholds of tumour blood flow and apparent diffusion co-efficient used for differentiating recurrence from post-radiation changes were more than 24.0 ml/100 g/minute and 1.21 × 10−3mm2/second or less, with area under the curve values of 0.94 and 0.90, and accuracy rates of 88.2 per cent and 88.2 per cent, respectively. The combined tumour blood flow and apparent diffusion co-efficient values used for differentiating recurrence from post-radiation changes had an area under the curve of 0.96 and an accuracy of 90.2 per cent.ConclusionCombined tumour blood flow and apparent diffusion co-efficient can differentiate recurrence from post-radiation changes.