Optimal timing for prediction of pathologic complete response to neoadjuvant chemoradiotherapy with diffusion-weighted MRI in patients with esophageal cancer.

OBJECTIVE: This study was conducted in order to determine the optimal timing of diffusion-weighted magnetic resonance imaging (DW-MRI) for prediction of pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. METHODS: Patients with esophageal adenocarcinoma or squamous cell carcinoma who planned to undergo nCRT followed by surgery were enrolled in this prospective study. Patients underwent six DW-MRI scans: one baseline scan before the start of nCRT and weekly scans during 5 weeks of nCRT. Relative changes in mean apparent diffusion coefficient (ADC) values between the baseline scans and the scans during nCRT (ΔADC(%)) were compared between pathologic complete responders (pCR) and non-pCR (tumor regression grades 2-5). The discriminative ability of ΔADC(%) was determined based on the c-statistic. RESULTS: A total of 24 patients with 142 DW-MRI scans were included. pCR was observed in seven patients (29%). ΔADC(%) from baseline to week 2 was significantly higher in patients with pCR versus non-pCR (median [IQR], 36% [30%, 41%] for pCR versus 16% [14%, 29%] for non-pCR, p = 0.004). The ΔADC(%) of the second week in combination with histology resulted in the highest c-statistic for the prediction of pCR versus non-pCR (0.87). The c-statistic of this model increased to 0.97 after additional exclusion of patients with a small tumor volume (< 7 mL, n = 3) and tumor histology of the resection specimen other than adenocarcinoma or squamous cell carcinoma (n = 1). CONCLUSION: The relative change in tumor ADC (ΔADC(%)) during the first 2 weeks of nCRT is the most predictive for pathologic complete response to nCRT in esophageal cancer patients. KEY POINTS: • DW-MRI during the second week of neoadjuvant chemoradiotherapy is most predictive for pathologic complete response in esophageal cancer. • A model including ΔADCweek 2was able to discriminate between pathologic complete responders and non-pathologic complete responders in 87%. • Improvements in future MRI studies for esophageal cancer may be obtained by incorporating motion management techniques.

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

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.

Preoperative Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients With Esophageal Cancer Using 18F-FDG PET/CT and DW-MRI: A Prospective Multicenter Study.

PURPOSE: Accurate preoperative prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer could enable omission of esophagectomy in patients with a pathologic complete response (pCR). This study aimed to evaluate the individual and combined value of 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) during and after nCRT to predict pathologic response in patients with esophageal cancer. METHODS AND MATERIALS: In this multicenter prospective study, patients scheduled to receive nCRT followed by esophagectomy for esophageal cancer underwent 18F-FDG PET/CT and DW-MRI scanning before the start of nCRT, during nCRT, and before esophagectomy. Response to nCRT was based on histopathologic evaluation of the resection specimen. Relative changes in 18F-FDG PET/CT and DW-MRI parameters were compared between patients with pCR and non-pCR groups. Multivariable ridge regression analyses with bootstrapped c-indices were performed to evaluate the individual and combined value of 18F-FDG PET/CT and DW-MRI. RESULTS: pCR was found in 26.1% of 69 patients. Relative changes in 18F-FDG PET/CT parameters after nCRT (Δ standardized uptake value [SUV]mean,postP = .016, and Δ total lesion glycolysis postP = .024), as well as changes in DW-MRI parameters during nCRT (Δ apparent diffusion coefficient [ADC]duringP = .008) were significantly different between pCR and non-pCR. A c-statistic of 0.84 was obtained for a model with ΔADCduring, ΔSUVmean,post, and histology in classifying patients as pCR (versus 0.82 for ΔADCduring and 0.79 for ΔSUVmean,post alone). CONCLUSIONS: Changes on 18F-FDG PET/CT after nCRT and early changes on DW-MRI during nCRT can help identify pCR to nCRT in esophageal cancer. Moreover, 18F-FDG PET/CT and DW-MRI might be of complementary value in the assessment of pCR.

Patient perspectives on repeated MRI and PET/CT examinations during neoadjuvant treatment of esophageal cancer.

OBJECTIVE: The perceived burden of diagnostic tests by patients during the assessment of esophageal cancer warrants attention with the current increase in repeated imaging for purposes of disease monitoring during and after treatment. The purpose of this prospective study was to evaluate the experienced burden associated with repeated MRI and positron emission tomography with integrated CT (PET/CT) examinations during neoadjuvant treatment for esophageal cancer from the perspective of the patient. METHODS: In 27 patients receiving neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer MRI and PET/CT examinations were performed before nCRT, during nCRT and before surgery. The experienced burden during repeated MRI and PET/CT examinations was evaluated with a self-report questionnaire addressing discomfort, pain, anxiety and embarrassment, each measured on a 5-point Likert scale (1 = none; up to 5 = very much). In addition, a comparative assessment was used to rank MRI, PET/CT and baseline endoscopy. RESULTS: All scans were performed without the occurrence of an adverse event. Few patients experienced discomfort (mean score ±SD: 1.9 ± 1.0 for MRI vs 2.0 ± 1.0 for PET/CT, p = 0.586), pain (1.1 ± 0.4 for MRI vs 1.3 ± 0.7 for PET/CT, p = 0.059), anxiety (1.0 ± 0.2 for MRI vs 1.0 ± 0.2 for PET/CT, p = 1.000) and embarrassment (1.0 ± 0 for MRI vs 1.0 ± 0.2 for PET/CT, p = 0.317) during both MRI and PET/CT. Patients preferred MRI over PET/CT (67% vs 22%, respectively, p = 0.023), and MRI over endoscopy (59% vs 19%, respectively, p = 0.027). In the comparison between PET/CT and endoscopy, 59% of patients preferred PET/CT and 26% preferred endoscopy (p = 0.093). CONCLUSION: Repeated imaging with both MRI and PET/CT is generally well-tolerated for the assessment of response to treatment in esophageal cancer patients. Shorter acquisition times and altered body positioning during scanning will likely improve patient experience. Advances in knowledge: This paper demonstrates that MRI and PET/CT are generally well-tolerated imaging procedures for the assessment of response to treatment in esophageal cancer patients. When asked to rank different tests, patients preferred MRI over PET/CT and endoscopy.

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.

Correlation between functional imaging markers derived from diffusion-weighted MRI and 18F-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 F-fluorodeoxyglucose positron emission tomography/computed tomography (F-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 F-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 F-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 F-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.

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.