Andreas M. Hötker

Multiparametric MRI of rectal cancer in the assessment of response to therapy: a systematic review.

BACKGROUND: Conventional MRI is limited in the assessment of nodal status and T status after neoadjuvant chemoradiotherapy. Multiparametric MRI strives to overcome these issues by directly measuring the local microcirculation and cellular environment, thus possibly allowing for a more reliable evaluation of response to therapy. OBJECTIVE: We assessed the available literature for the value of multiparametric MRI sequences (diffusion-weighted and dynamic contrast-enhanced imaging) in determining the response to neoadjuvant chemoradiotherapy in patients with rectal cancer. DATA SOURCES: We conducted a systematic literature research in the PubMed database. STUDY SELECTION: English-language publications of the years 2000–2013 that applied multiparametric MRI in the neoadjuvant setting were included in this study. INTERVENTION: Patients received neoadjuvant chemoradiotherapy and MRI examinations for staging and assessment of response. MAIN OUTCOME MEASURES: Accuracy, specificity, and sensitivity of MRI in prediction/assessment of response to therapy were the included measures. RESULTS: Forty-three studies were included in this review; 30 of them included diffusion-weighted imaging sequences, and 13 included dynamic contrast-enhanced MRI. Conventional MRI is limited in the accuracy of both T and N stages and response assessment. Diffusion-weighted imaging and dynamic contrast-enhanced MRIs showed additional value in both the prediction and detection of (complete) response to therapy compared with conventional sequences alone, as well as in correct N staging along with new experimental contrast agents. LIMITATIONS: The lack of standardization represents an important technical limitation. Most studies are conducted in an experimental setting; therefore, larger multicenter prospective studies are needed to verify the present findings. CONCLUSIONS: Advanced, functional MRI techniques allow for the quantification of tumor biological processes, such as microcirculation, vascular permeability, and tissue cellularity. This new technology has begun to show potential advantages over standard morphologic imaging in the restaging of rectal cancer, allowing for more accurate prognostication of response and potentially introducing an era allowing earlier treatment alteration and more accurate noninvasive surveillance, which could improve patient outcomes.

Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

PURPOSE To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). METHODS AND MATERIALS A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgical specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). RESULTS A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p ≤ 0.001). Positive resection margins (ypCRM ≤ 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p ≤ 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). CONCLUSION Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.

Use of DWI in the Differentiation of Renal Cortical Tumors

OBJECTIVE The purpose of this study was to differentiate clear cell renal cell carcinoma (RCC) from other common renal cortical tumors by use of DWI. MATERIALS AND METHODS The study included 117 patients (mean age, 60 years) with 122 histopathologically confirmed renal cortical tumors who underwent 1.5-T MRI that included DWI before they underwent nephrectomy between 2006 and 2013. For each tumor, two radiologists independently evaluated apparent diffusion coefficient (ADC) values on the basis of a single ROI in a nonnecrotic area of the tumor and also by assessment of the whole tumor. The concordance correlation coefficient (CCC) was calculated to assess interreader agreement. The mean ADC values of clear cell RCC and every other tumor subtype were compared using an exact Wilcoxon rank sum test. RESULTS Interreader agreement was excellent and higher in whole-tumor assessment (CCC, 0.982) than in single-ROI analysis (CCC, 0.756). For both readers, ADC values for clear cell RCC found on single-ROI assessment (2.19 and 2.08 × 10(-3) mm(2)/s) and whole-tumor assessment (2.30 and 2.32 × 10(-3) mm(2)/s) were statistically significantly higher than those for chromophobe, papillary, or unclassified RCC (p < 0.05) but were similar to those for oncocytoma found on single-ROI assessment (2.14 and 2.32 × 10(-3) mm(2)/s) and whole-tumor assessment (2.38 and 2.24 × 10(-3) mm(2)/s). ADC values were also higher for clear cell RCC than for angiomyolipoma, but the difference was statistically significant only in whole-tumor assessment (p < 0.03). CONCLUSION ADC values were statistically significantly higher for clear cell RCC than for chromophobe, papillary, or unclassified RCC subtypes; however, differentiating clear cell RCC from oncocytoma by use of DWI remains especially challenging, because similar ADC values have been shown for these two tumor types.

Multiparametric MRI in the assessment of response of rectal cancer to neoadjuvant chemoradiotherapy: A comparison of morphological, volumetric and functional MRI parameters

AbstractPurposeTo compare morphological and functional MRI metrics and determine which ones perform best in assessing response to neoadjuvant chemoradiotherapy (CRT) in rectal cancer.Materials and methodsThis retrospective study included 24 uniformly-treated patients with biopsy-proven rectal adenocarcinoma who underwent MRI, including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after completion of CRT. On all MRI exams, two experienced readers independently measured longest and perpendicular tumour diameters, tumour volume, tumour regression grade (TRG) and tumour signal intensity ratio on T2-weighted imaging, as well as tumour volume and apparent diffusion coefficient on DW-MRI and tumour volume and transfer constant Ktrans on DCE-MRI. These metrics were correlated with histopathological percent tumour regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC).ResultsFor both readers, post-treatment DW-MRI and DCE-MRI volumetric tumour assessments were significantly associated with %TR; DCE-MRI volumetry showed better inter-reader agreement (CCC=0.700) than DW-MRI volumetry (CCC=0.292). For one reader, mrTRG, post-treatment T2 tumour volumetry and assessments of volume change made with T2, DW-MRI and DCE-MRI were also significantly associated with %TR.ConclusionTumour volumetry on post-treatment DCE-MRI and DW-MRI correlated well with %TR, with DCE-MRI volumetry demonstrating better inter-reader agreement.Key Points• Volumetry on post-treatment DCE-/DW-MRI sequences correlated well with histopathological tumour regression. • DCE-MRI volumetry demonstrated good inter-reader agreement. • Inter-reader agreement was higher for DCE-MRI volumetry than for DW-MRI volumetry. • DCE-MRI volumetry merits further investigation as a metric for evaluating treatment response.

Assessment of Prostate Cancer Aggressiveness by Use of the Combination of Quantitative DWI and Dynamic Contrast-Enhanced MRI.

OBJECTIVE The objective of this study was to investigate whether the apparent diffusion coefficient (ADC) value from DWI and the forward volume transfer constant (K(trans)) value from dynamic contrast-enhanced MRI independently predict prostate cancer aggressiveness, and to determine whether the combination of both parameters performs better than either parameter alone in assessing tumor aggressiveness before treatment. MATERIALS AND METHODS This retrospective study included 158 men with histopathologically confirmed prostate cancer who underwent 3-T MRI before undergoing prostatectomy in 2011. Whole-mount step-section pathologic maps identified 195 prostate cancer foci that were 0.5 mL or larger; these foci were then volumetrically assessed to calculate the per-tumor ADC and K(trans) values. Associations between MRI and histopathologic parameters were assessed using Spearman correlation coefficients, univariate and multivariable logistic regression, and AUCs. RESULTS The median ADC and K(trans) values showed moderate correlation only for tumors for which the Gleason score (GS) was 4 + 4 or higher (ρ = 0.547; p = 0.042). The tumor ADC value was statistically significantly associated with all dichotomized GSs (p < 0.005), including a GS of 3 + 3 versus a GS of 3 + 4 or higher (AUC, 0.693; p = 0.001). The tumor K(trans) value differed statistically significantly only between tumors with a GS of 3 + 3 and those with a primary Gleason grade of 4 (p ≤ 0.015), and it made a statistically significant contribution only in differentiating tumors with a GS of 4 + 3 or higher (AUC, 0.711; p < 0.001) and those with a GS of 4 + 4 or higher (AUC, 0.788; p < 0.001) from lower-grade tumors. Combining ADC and K(trans) values improved diagnostic performance in characterizing tumors with a GS of 4 + 3 or higher and those with a GS of 4 + 4 or higher (AUC, 0.739 and 0.856, respectively; p < 0.01). CONCLUSION Although the ADC value helped to differentiate between all GSs, the K(trans) value was only a benefit in characterizing more aggressive tumors. Combining these parameters improves their performance in identifying patients with aggressive tumors who may require radical treatment.

Prostate Cancer: assessing the effects of androgen-deprivation therapy using quantitative diffusion-weighted and dynamic contrast-enhanced MRI

AbstractPurposeTo investigate the effects of androgen-deprivation therapy (ADT) on MRI parameters and evaluate their associations with treatment response measures.Materials and methodsThe study included 30 men with histopathologically confirmed prostate cancer who underwent MRI before and after initiation of ADT. Thirty-four tumours were volumetrically assessed on DW-MRI (n = 32) and DCE-MRI (n = 18), along with regions of interest in benign prostatic tissue, to calculate apparent diffusion coefficient (ADC) and transfer constant (Ktrans) values. Changes in MRI parameters and correlations with clinical parameters (change in prostate-specific antigen [PSA], treatment duration, PSA nadir) were assessed.ResultsProstate volume and PSA values decreased significantly with therapy (p < 0.001). ADC values increased significantly in tumours and decreased in benign prostatic tissue (p < 0.05). Relative changes in ADC and absolute post-therapeutic ADC values differed significantly between tumour and benign tissue (p < 0.001). Ktrans decreased significantly only in tumours (p < 0.001); relative Ktrans changes and post-therapeutic values were not significantly different between tumour and benign tissue. The relative change in tumour ADC correlated significantly with PSA decrease. No changes were associated with treatment duration or PSA nadir.ConclusionsMulti-parametric MRI shows significant measurable changes in tumour and benign prostate caused by ADT and may help in monitoring treatment response.Key Points• Androgen-deprivation therapy caused changes of ADC, Ktransin tumour and benign prostate. • Prostate volume and PSA values decreased significantly with therapy. • ADC values may be helpful for monitoring treatment response.

Subcentimeter Pulmonary Nodules are Not Associated with Disease Progression in Patients with Renal Cell Carcinoma

PURPOSE Renal cell carcinoma most commonly metastasizes to the lung. Indeterminate pulmonary nodules develop preoperatively in half of the patients with localized renal cell carcinoma but clinical significance remains poorly defined. We determined whether the presence of indeterminate pulmonary nodules, or nodule size or number is associated with renal cell carcinoma outcomes. MATERIALS AND METHODS We reviewed data on 1,102 patients with renal cell carcinoma in whom chest computerized tomography was done within 6 months before nephrectomy from 2002 to 2012. Patients with metastatic disease at presentation, benign tumors, pulmonary nodules greater than 2 cm or concurrent pulmonary disease were excluded, leaving 748 available for analysis. Study outcomes included lung metastasis, any distant metastasis or death from renal cell carcinoma. Cox proportional hazards models were used to assess whether the presence of indeterminate pulmonary nodules, or nodule size or number was associated with outcomes. Models were evaluated by comparing discrimination using the Harrell c-index. RESULTS Indeterminate pulmonary nodules were present in 382 of 748 patients (51%). Median followup was 4.1 years (IQR 2.2-6.1). The presence of indeterminate pulmonary nodules was not associated with distant metastasis or death from kidney cancer. However, compared to subcm indeterminate pulmonary nodules the nodules greater than 1 cm were associated with metastatic disease after adjusting for tumor histology, stage and size (HR 2.48, 95% CI 1.08-5.68, p = 0.031). The outcome c-index increased slightly after adding nodule size to a predictive model adjusted for tumor characteristics. CONCLUSIONS No evidence in the current study suggested that indeterminate pulmonary nodules less than 1 cm are associated with renal cell carcinoma progression, although large nodules significantly predicted metastatic disease. Patients with subcm indeterminate pulmonary nodules would be unlikely to benefit from extensive postoperative chest imaging surveillance, which should be reserved for patients with nodules greater than 1 cm.

Differentiation of Clear Cell Renal Cell Carcinoma From Other Renal Cortical Tumors by Use of a Quantitative Multiparametric MRI Approach

OBJECTIVE The purpose of this study was to develop a quantitative multiparametric MRI approach to differentiating clear cell renal cell carcinoma (RCC) from other renal cortical tumors. MATERIALS AND METHODS This retrospective study included 119 patients with 124 histopathologically confirmed renal cortical tumors who underwent preoperative MRI including DWI, contrast-enhanced, and chemical-shift sequences before nephrectomy. Two radiologists independently assessed each tumor volumetrically, and apparent diffusion coefficient values, parameters from multiphasic contrast-enhanced MRI (peak enhancement, upslope, downslope, AUC), and chemical-shift indexes were calculated. Univariate and multivariable logistic regression analyses were performed to identify parameters associated with clear cell RCC. RESULTS Interreader agreement was excellent (intraclass correlation coefficient, 0.815-0.994). The parameters apparent diffusion coefficient (reader 1 AUC, 0.804; reader 2, 0.807), peak enhancement (reader 1 AUC, 0.629; reader 2, 0.606), and downslope (reader 1 AUC, 0.575; reader 2, 0.561) were significantly associated with discriminating clear cell RCC from other renal cortical tumors. The combination of all three parameters further increased diagnostic accuracy (reader 1 AUC, 0.889; reader 2, 0.907; both p ≤ 0.001), yielding sensitivities of 0.897 for reader 1 and 0.897 for reader 2, and specificities of 0.762 for reader 1 and 0.738 for reader 2 in the identification of clear cell RCC. With maximized sensitivity, specificities of 0.429 and 0.262 were reached for readers 1 and 2, respectively. CONCLUSION A quantitative multiparametric approach statistically significantly improves diagnostic performance in differentiating clear cell RCC from other renal cortical tumors.

Dynamic contrast enhanced‐MRI in rectal cancer: Inter‐ and intraobserver reproducibility and the effect of slice selection on pharmacokinetic analysis

To assess inter‐ and intraobserver reproducibility of DCE‐MRI measurements and possible differences between two directly adjacent slices.

The value of advanced MRI techniques in the assessment of cervical cancer: a review

ObjectivesTo assess the value of new magnetic resonance imaging (MRI) techniques in cervical cancer.MethodsWe searched PubMed and MEDLINE and reviewed articles published from 1990 to 2016 to identify studies that used MRI techniques, such as diffusion weighted imaging (DWI), intravoxel incoherent motion (IVIM) and dynamic contrast enhancement (DCE) MRI, to assess parametric invasion, to detect lymph node metastases, tumour subtype and grading, and to detect and predict tumour recurrence.ResultsSeventy-nine studies were included. The additional use of DWI improved the accuracy and sensitivity of the evaluation of parametrial extension. Most studies reported improved detection of nodal metastases. Functional MRI techniques have the potential to assess tumour subtypes and tumour grade differentiation, and they showed additional value in detecting and predicting treatment response. Limitations included a lack of technical standardisation, which limits reproducibility.ConclusionsNew advanced MRI techniques allow improved analysis of tumour biology and the tumour microenvironment. They can improve TNM staging and show promise for tumour classification and for assessing the risk of tumour recurrence. They may be helpful for developing optimised and personalised therapy for patients with cervical cancer.Teaching points• Conventional MRI plays a key role in the evaluation of cervical cancer.• DWI improves tumour delineation and detection of nodal metastases in cervical cancer.• Advanced MRI techniques show promise regarding histological grading and subtype differentiation.• Tumour ADC is a potential biomarker for response to treatment.