S.E. Heethuis

Dynamic contrast-enhanced MRI for treatment response assessment in patients with oesophageal cancer receiving neoadjuvant chemoradiotherapy.

PURPOSE To explore and evaluate the potential value of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal cancer. MATERIAL AND METHODS Twenty-six patients underwent DCE-MRI before, during (week 2-3) and after nCRT, but before surgery (pre/per/post, respectively). Histopathologic tumour regression grade (TRG) was assessed after oesophagectomy. Tumour area-under-the-concentration time curve (AUC), time-to-peak (TTP) and slope were calculated. The ability of these DCE-parameters to distinguish good responders (GR, TRG 1-2) from poor responders (noGR, TRG⩾3), and pathologic complete responders (pCR) from no-pCR was assessed. RESULTS Twelve patients (48%) showed GR of which 8 patients (32%) pCR. Analysis of AUC change throughout treatment, AUCper-pre, was most predictive for GR, at a threshold of 22.7% resulting in a sensitivity of 92%, specificity of 77%, PPV of 79%, and a NPV of 91%. AUCpost-pre was most predictive for pCR, at a threshold of -24.6% resulting in a sensitivity of 83%, specificity of 88%, PPV of 71%, and a NPV of 93%. TTP and slope were not associated with pathologic response. CONCLUSIONS This study demonstrates that changes in AUC throughout treatment are promising for prediction of histopathologic response to nCRT for oesophageal cancer.

Correlation between functional imaging markers derived from diffusion-weighted MRI and 18 F-FDG PET/CT in esophageal cancer

Objective Both the apparent diffusion coefficient (ADC) acquired by diffusion-weighted magnetic resonance imaging (DW-MRI) and the standardized uptake value (SUV), acquired by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), are well-established functional parameters in cancer imaging. Currently, it is unclear whether these two markers provide complementary prognostic and predictive information in esophageal cancer. The aim of this study was to evaluate the correlation between ADC and SUV in patients with esophageal cancer. Materials and methods This prospective study included 76 patients with histologically proven esophageal cancer who underwent both DW-MRI and 18F-FDG PET/CT examinations before treatment. The minimum and mean ADC values (ADCmin and ADCmean) of the primary tumor were assessed on MRI. Similarly, the glucose metabolism was evaluated by the maximum and mean SUV (SUVmax and SUVmean) in the same lesions on 18F-FDG PET/CT images. Spearman’s rank correlation coefficients were used to assess the correlation between tumor ADC and SUV values. Results The tumor ADC and SUV values as measures of cell density and glucose metabolism, respectively, showed negligible nonsignificant correlations (ADCmin vs. SUVmax: r=−0.087, P=0.457; ADCmin vs. SUVmean: r=−0.105, P=0.369; ADCmean vs. SUVmax: r=−0.099, P=0.349; ADCmean vs. SUVmean: r=−0.111, P=0.340). No differences in tumor ADC and SUV values were observed between the different histologic tumor types, stages, and differentiation grades. Conclusion This study indicates that tumor cellularity derived from DW-MRI and tumor metabolism measured by 18F-FDG PET/CT are independent cellular phenomena in newly diagnosed esophageal cancer. Therefore, tumor ADC and SUV values may play complementary roles as imaging markers in the prediction of survival and evaluation of response to treatment in esophageal cancer.

Quantification of variations in intra-fraction motion of esophageal tumors over the course of neoadjuvant chemoradiotherapy based on cine-MRI

To noninvasively quantify variation in intra-fraction motion of esophageal tumors over the course of neoadjuvant chemoradiotherapy (nCRT) using 2D cine-magnetic resonance imaging (MRI) series. Patients treated with nCRT for esophageal cancer underwent six MRI scans. Scans were acquired prior to the start of nCRT, followed by weekly MRI scans during nCRT. Cine-MRI series were acquired in the coronal and sagittal plane (≈1.6 Hz). To be able to quantify intra-fraction motion over a longer time period, a second cine-MRI series was performed after 10 min. Tumor motion was assessed in cranio-caudal (CC), anterior-posterior (AP) and left-right (LR) direction. Motion patterns were analyzed for the presence of deep inhales and tumor drift. A total of 232 cine-MRI series of 20 patients were analyzed. The largest tumor motion was found in CC direction, with a mean peak-to-peak motion of 12.7 mm (standard deviation [SD] 5.6), followed by a mean peak-to peak motion in AP direction of 3.8 mm (SD 2.0) and in LR direction of 2.7 mm (SD 1.3). The CC intra-fraction tumor motion can differ extensively between and within patients. Deep inhales were present in six of 232 scans (3%). After exclusion of these scans, mean CC peak-to-peak motion was12.3 mm (SD 5.2). Correction for tumor drift showed a further reduction to 11.0 mm (SD 4.6). Despite correction for tumor drift, a large variation in tumor motion occurred within patients during treatment. Mean tumor drift during the 10 min interval between the two series was 1.5 mm (SD 1.8), with a maximum of 11.6 mm. Intra-fraction tumor motion was found to be highly variable between and within patients with esophageal cancer over the course of nCRT. Correction for deep inhales and tumor drift reduced peak-to-peak motion. The stochastic nature of both deep inhales and tumor drift indicates that real-time tumor motion management during radiotherapy is a prerequisite to safely reduce treatment margins.

DW-MRI and DCE-MRI are of complementary value in predicting pathologic response to neoadjuvant chemoradiotherapy for esophageal cancer

Abstract Purpose: To explore the potential benefit and complementary value of a multiparametric approach using diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) for prediction of response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer. Material and methods: Forty-five patients underwent both DW-MRI and DCE-MRI prior to nCRT (pre), during nCRT (week 2–3) (per) and after completion of nCRT, but prior to esophagectomy (post). Subsequently, histopathologic tumor regression grade (TRG) was assessed. Tumor apparent diffusion coefficient (ADC) and area-under-the-concentration time curve (AUC) were calculated for DW-MRI and DCE-MRI, respectively. The ability of these parameters to predict pathologic complete response (pCR, TRG1) or good response (GR, TRG ≤ 2) to nCRT was assessed. Furthermore the complementary value of DW-MRI and DCE-MRI was investigated. Results: GR was found in 22 (49%) patients, of which 10 (22%) patients showed pCR. For DW-MRI, the 75th percentile (P75) ΔADCpost-pre was most predictive for GR (c-index = 0.75). For DCE-MRI, P90 ΔAUCper-pre was most predictive for pCR (c-index = 0.79). Multivariable logistic regression analyses showed complementary value when combining DW-MRI and DCE-MRI for pCR prediction (c-index = 0.89). Conclusions: Both DW-MRI and DCE-MRI are promising in predicting response to nCRT in esophageal cancer. Combining both modalities provides complementary information, resulting in a higher predictive value.

WE‐G‐18C‐04: Comparison of Image Registration Strategies to Improve DCE‐MRI Uptake Curves in Esophageal Cancer

PURPOSE Neoadjuvant chemoradiotherapy (nCRT) is often used to treat resectable esophageal cancer. In 29% of the patients, nCRT results in a pathologic complete reponse (pCR). pCR is an important prognostic factor and surgery can potentially be omitted in this patient group. We will study the potential of DCE-MRI for accurate response assessment in those patients. In preparation to this study, motion compensation by retrospective image registration strategies of DCE-MRI time series was investigated to enable correct pharmacokinetic analysis required for response assessment. METHODS Five patients with biopsy-proven esophageal cancer received a DCE-MRI scan (62 time-frames, 3 s/frame) prior to neoadjuvant therapy; contrast was injected after the 10th time-frame. Three different registration strategies were reviewed; registration to: (1) 1st time-frame, (2) 41th timeframe, and (3) previous time-frame; rigid or affine transformations were allowed (using Elastix toolbox). We chose these time-points as they occur well before (1) or after (2) contrast uptake. In strategy (3), the registration process is thought to be less susceptible to image intensity variations caused by contrast uptake. The effectiveness of the registration strategies was measured with SSIM (structure component of Structural SIMilarity, 1 = perfect match) metric within the volume encompassing the tumor. The 41th frame was chosen as reference image. RESULTS The average SSIM over all time-frames and patients was: pre-registration: 0.67, post-registration rigid to 1st/41th/previous frame: 0.68/0.70/0.66, affine: 0.68/0.69/0.66. For rigid registration to frame 41, the minimum and maximum SSIM change per time-frame ranged from -0.09 to 0.14. CONCLUSION In this analysis, rigid registration to a time-frame after contrast-enhancement led to the best retrospective motion compensation of DCE-MRI in esophageal cancer measured by SSIM. After verification in a larger patient group, this correction will be used prior to semi-quantitative analysis and pharmacokinetic modeling to assess response to neoadjuvant therapy.