The MRI parameter F/V at baseline was a remarkably strong predictor of both histopathologic tumour response and 5-year PFS in patients with LARC.

I n 2018, rectal cancer was the eighth most common cancer in the world (1). Survival rates have increased in the past decade mainly because of total mesorectal excision surgery and neoadjuvant treatment, when indicated. However, patients with metastatic disease remain a challenge. Norwegian patients with metastatic rectal cancer have a 5-year survival rate of 18.3% for men and 20.6% for women (2). To enable a more adapted treatment, there is a need to assess individual tumor characteristics that can be used to identify patients who will respond poorly to conventional therapies and have higher risk of metastatic disease. Anatomic MRI is important for staging rectal cancer. Many studies have also examined the predictive and prognostic value of functional MRI, especially dynamic contrast-enhanced (DCE) MRI that can be analyzed qualitatively, semiquantitatively, or quantitatively. Recently, Dijkhoff et al (3) demonstrated value for DCE MRI in rectal cancer, despite large variability in the performed studies, and called for larger studies to be undertaken.

Background Dynamic contrast‐based MRI and intravoxel incoherent motion imaging (IVIM) MRI are both methods showing promise as diagnostic and prognostic tools in rectal cancer. Both methods aim at measuring perfusion‐related parameters, but the relationship between them is unclear. Purpose To investigate the relationship between perfusion‐ and permeability‐related parameters obtained by IVIM‐MRI, T1‐weighted dynamic contrast‐enhanced (DCE)‐MRI and T2*‐weighted dynamic susceptibility contrast (DSC)‐MRI. Study Type Prospective. Subjects In all, 94 patients with histologically confirmed rectal cancer. Field Strength/Sequence Subjects underwent pretreatment 1.5T clinical procedure MRI, and in addition a study‐specific diffusion‐weighted sequence (b = 0, 25, 50, 100, 500, 1000, 1300 s/mm2) and a multiecho dynamic contrast‐based echo‐planer imaging sequence. Assessment Median tumor values were obtained from IVIM (perfusion fraction [f], pseudodiffusion [D*], diffusion [D]), from the extended Tofts model applied to DCE data (Ktrans, kep, vp, ve) and from model free deconvolution of DSC (blood flow [BF] and area under curve). A subgroup of the excised tumors underwent immunohistochemistry with quantification of microvessel density and vessel size. Statistical Test Spearman's rank correlation test. Results D* was correlated with BF (rs = 0.47, P < 0.001), and f was negatively correlated with kep (rs = –0.31, P = 0.002). BF was correlated with Ktrans (rs = 0.29, P = 0.004), but this correlation varied extensively when separating tumors into groups of low (rs = 0.62, P < 0.001) and high (rs = –0.06, P = 0.68) BF. Ktrans was negatively correlated with vessel size (rs = –0.82, P = 0.004) in the subgroup of tumors with high BF. Data Conclusion We found an association between D* from IVIM and BF estimated from DSC‐MRI. The relationship between IVIM and DCE‐MRI was less clear. Comparing parameters from DSC‐MRI and DCE‐MRI highlights the importance of the underlying biology for the interpretation of these parameters. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1114–1124.

The liver is the most frequent metastatic site in colorectal cancer (CRC), and relevant orthotopic in vivo models are needed to study the efficacy of anticancer drugs in the metastatic setting. A challenge when utilizing such models is monitoring tumor growth during the experiments. In this study, experimental liver metastases were established in nude mice by splenic injection of the CRC cell lines HT29 and HCT116, and the mice were treated with the antiangiogenic drug aflibercept. Tumor growth was monitored using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). Aflibercept treatment was well tolerated and resulted in increased animal survival in HCT116, but not in HT29, while inhibited tumor growth was observed in both models. Treatment efficacy was monitored with high precision using MRI, while BLI detected small-volume disease with high sensitivity, but was less accurate in end-stage disease. Apparent diffusion coefficient (ADC) values obtained by diffusion weighted MRI (DW-MRI) were highly predictive of treatment response, with increased ADC corresponding well with areas of necrosis observed by histological evaluation of aflibercept-treated xenografts. The results showed that the efficacy of the antiangiogenic drug aflibercept varied between the two models, possibly reflecting unique growth patterns in the liver that may be representative of human disease. Non-invasive imaging, especially MRI and DW-MRI, can be used to effectively monitor tumor growth and treatment response in orthotopic liver metastasis models.

Background and purposeWe investigated how features relating to pelvic cavity anatomy and tumor hemodynamic factors may influence systemic failure in rectal cancer.Materials and methodsRectal cancer patients (207 women, 343 men), who had been prospectively enrolled onto six cohorts and given curative-intent therapy, were analyzed for the first metastatic event. In one of the cohorts, the diameter of the inferior mesenteric vein (IMV) was assessed on diagnostic abdominal computed tomography images (n = 113). Tumor volume (n = 193) and histologic response to neoadjuvant therapy (n = 445) were recorded from diagnostic magnetic resonance images and surgical specimens, respectively.ResultsMore women than men developed lung metastasis (p = 0.037), while the opposite was the case for liver metastasis (p = 0.040). Wider IMV diameter correlated with larger tumor volume (r = 0.481, p < 0.001) and male sex (p < 0.001). Female sex was the only adverse prognostic factor for lung metastasis. When sex, tumor volume, and histologic response were taken into consideration, poor tumor response remained the only determinant for liver metastasis (p = 0.002).ConclusionsIn a diverse rectal cancer population given curative-intent treatment, women and men had different outcome with regard to the primary metastatic site. Tumor hemodynamic factors should be considered in rectal cancer risk stratification.

Background In colorectal cancer, the inflamed tumour microenvironment with its angiogenic activities is immune- tolerant and incites progression to liver metastasis. We hypothesised that angiogenic and inflammatory factors in serum samples from patients with non-metastatic rectal cancer could inform on liver metastasis risk. Methods We measured 84 angiogenic and inflammatory markers in serum sampled at the time of diagnosis within the population-based cohort of 122 stage I–III patients. In a stepwise manner, the statistically strongest proteins associated with time to development of liver metastasis were analysed in the corresponding serum samples from 273 stage II–III rectal cancer patients in three independent cohorts. Results We identified the soluble form of the costimulatory immune checkpoint receptor cluster of differentiation molecule 40 (sCD40) as a marker of liver metastasis risk across all patient cohorts—the higher the sCD40 level, the shorter time to liver metastasis. In patients receiving neoadjuvant treatment, the sCD40 value remained an independent variable associated with progression to liver metastasis along with the local treatment response. Of note, serum sCD40 was not associated with progression to lung metastasis. Conclusions Circulating sCD40 is a marker of liver metastasis risk in rectal cancer and may be developed for use in clinical practice.

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BackgroundDynamic contrast enhanced magnetic resonance imaging (DCE-MRI) may be used to depict tumour vascular structure and for therapy response assessment in various tumour sites. The purpose of the current work is to examine whether ultra-early changes in tumour physiology following cytotoxic treatment with doxorubicin and liver X receptor (LXR) agonist GW3965 are detectable by DCE-MRI.Methods36 female, athymic nude foxn1nu mice with bilaterally implanted breast cancer xenografts (17 with ER-positive HBCx34, 19 with triple-negative HBCx39) were randomised in the following treatment groups; control, GW3965 (40 mg/kg p.o.), doxorubicin (8 mg/kg i.v.) and a combination therapy of GW3965 and doxorubicin. DCE-MRI (3D FLASH on a 7 T preclinical scanner) was performed at baseline and one and six days after onset of treatment. Wash-in (30 s p.i.) and wash-out (300 s p.i.) enhancement were quantified from dynamic uptake curves, before voxel-by-voxel fitting to the pharmacokinetic Tofts model and generation of maps for the resulting parameters Ktrans, νe and νB. Treatment effect was evaluated by univariate repeated measures mixed-effects maximum likelihood regression models applied to median tumour data.ResultsWe found no effects of any treatment 24 h post treatment. After 6 days, doxorubicin given as both mono- and combination therapy gave significant increases of ~ 30% in wash-in enhancement (p < 0.011) and Ktrans (p < 0.017), and 40–50% in νB (p < 0.024) for HBCx34, but not for HBCx39. No effects of GW3965 were observed at any time (p > 0.1).ConclusionsTwenty-four h after onset of treatment was too early to evaluate treatment effects by DCE-MRI. Early enhancement and Ktrans were approximately equally sensitive metrics to capture treatment effects six days pt. Pharmacokinetic modelling however allowed us to attribute the observed effect to changes in tumour perfusion rather than increased retention.