Radiological evaluation of response to treatment: application to metastatic renal cancers receiving anti-angiogenic treatment.

Targeted therapies have considerably improved the prognosis of patients with metastatic renal cancer (mRCC) but there are no reliable response assessment criteria reflecting the clinical benefits, because there is no regression in size, or it is delayed. Such criteria would help early identification of non-responders, who would then benefit from a change of treatment, and would avoid their being subjected to unnecessary side effects related to the treatment. We will review the imaging techniques currently available for evaluating tumour response in mRCC patients, including the response evaluation criteria in solid tumours (RECIST), the Choi criteria, the modified Choi criteria, and the CT size and attenuation criteria (SACT). We will also discuss functional imaging techniques, which are based on the physiological characteristics of the tumours, such as perfusion CT, magnetic resonance imaging or ultrasound (DCE-CT, DCE-MRI, DCE-US), diffusion MRI, BOLD MRI and new positron emission tomography (PET) tracers. It is not possible at present to propose a unanimously acknowledged criterion for evaluating tumour response to targeted therapy. However, there is a real need for this according to oncologists and the pharmaceutical industry, and radiologists need to be involved in reflecting on the subject.

Imaging criteria for assessing tumour response: RECIST, mRECIST, Cheson.

Most methods define a limited number of "target" lesions to be measured and other "non-target" lesions to be evaluated qualitatively. RECIST criteria are the most widely used although other criteria have been proposed that are derived from them based on size alone, or size and attenuation. Modified RECIST (mRECIST) criteria only concern hepatocellular carcinoma and only take into account the viable portion (enhanced after injection during the arterial phase). Cheson criteria are more complex as target lesions are defined differently depending on the organ (lymph nodes, liver or spleen, other organs), and involve both CT and PET scans, as well as the clinical examination and bone marrow biopsy.

In vivo MRI assessment of placental and foetal oxygenation changes in a rat model of growth restriction using blood oxygen level-dependent (BOLD) magnetic resonance imaging.

OBJECTIVES: To evaluate whether changes in BOLD signal intensities following hyperoxygenation are related to intrauterine growth restriction (IUGR) in a rat model. METHODS: IUGR was induced in pregnant rats by ligating the left vascular uterine pedicle at day 16 of gestation. BOLD MR imaging using a balanced steady-state free-precession (balanced-SSFP) sequence on a 1.5-T system was performed on day 19. Signal intensities (SI) before and after maternal hyperoxygenation were compared in the maternal liver and in control and growth-restricted foetoplacental units (FPUs). RESULTS: Maternal hyperoxygenation resulted in a significant increase in SI in all regions of interest (P < 0.05) in the 18 rats. In the control group, the SI (mean ± SD) increased by 21 % ± 15 in placentas (n = 74) and 13 % ± 8.5 in foetuses (n = 53). In the IUGR group, the increase was significantly lower: 6.5 % ± 4 in placentas (n = 36) and 7 %± 5.5 in foetuses (n = 34) (P < 0.05). CONCLUSION: BOLD MRI allows non-invasive assessment of the foetoplacental response to maternal hyperoxygenation in the rat and demonstrates its alteration in an IUGR model. This imaging method may provide a useful adjunct for the early diagnosis, evaluation, and management of human IUGR. KEY POINTS: • Intra-uterine growth restriction is an important cause of perinatal morbidity and mortality. • Blood oxygen level-dependent MRI non-invasively assesses foetoplacental response to maternal hyperoxygenation. • In the rat, foetoplacental response to maternal hyperoxygenation is altered in IUGR. • Functional MRI may help to assess human IUGR.

SPIO-enhanced magnetic resonance imaging study of placental perfusion in a rat model of intrauterine growth restriction.

OBJECTIVE: To assess placental perfusion with magnetic resonance imaging (MRI) and superparamagnetic iron oxide (SPIO) in a rat model of intrauterine growth restriction (IUGR). DESIGN: Experimental animal study. SETTING: The study complied with US National Institutes of Health recommendations for animal care. POPULATION: Thirty-two rats at day 16 of gestation underwent surgical ligation of the left uterine vessel to induce IUGR. METHODS: Eighteen rats were examined by MRI 3 days later, after bolus injection of ferucarbotran. MAIN OUTCOME MEASURE: Signal intensities were measured in the maternal left ventricle and in the placentas of the two horns. Quantitative microcirculation parameters were calculated and compared between the placentas of the two horns. RESULTS: Fifty-four kinetic curves of placental perfusion were obtained in 11 rats. The mean placental blood flow was significantly lower in the ligated horns than in the normal horns (108.1 versus 159.4 ml/minute/100 ml, p = 0.0004). The mean fractional volume of the maternal vascular placental compartment did not differ significantly between the pathological (42.8%) and normal placentas (39.2%). CONCLUSIONS: Placental perfusion, including changes during experimental IUGR, can be measured in rats by using MRI with SPIO. These findings could have implications for human studies of placental microcirculation and for the management of disorders related to placental dysfunction.

Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib.

BACKGROUND: In metastatic renal cell carcinoma (mRCC), antiangiogenic treatments rarely achieve a reduction of -30% in the sum of longest diameters (SLD) of target lesions required by RECIST for an 'objective response', although they objectively improve progression-free survival (PFS). We sought to determine a threshold for the computed tomography evaluation of these patients' best reflecting patient outcome. PATIENTS AND METHODS: In 334 mRCC patients treated with sunitinib, we tested thresholds from -45% to +10%. We classified patients as 'responders' when the best relative variation of the sum of longest diameters (DeltaSLD) reached the tested threshold and as 'nonresponders' otherwise. For each tested threshold, the median PFS of the two groups were compared. Receiver operating characteristic (ROC) analysis was also carried out among the 103 patients that progressed during follow-up. Finally, the 'optimal' threshold was retested on an independent cohort of 39 patients. RESULTS: The DeltaSLD threshold of -10% gave the most significant difference. It divided patients into 256 responders and 78 nonresponders (median PFS 11.1 and 5.6 months). The same -10% threshold was found using the ROC analysis. Results were confirmed on the external validation cohort. CONCLUSION: A variation of -10% in the SLD accurately and rapidly identifies mRCC patients benefiting from sunitinib.