scispace - formally typeset
Search or ask a question
Author

Sophie E Heethuis

Bio: Sophie E Heethuis is an academic researcher from Utrecht University. The author has contributed to research in topics: Chemoradiotherapy & Standardized uptake value. The author has an hindex of 6, co-authored 9 publications receiving 124 citations.

Papers
More filters
Journal ArticleDOI
TL;DR: This study demonstrates that changes in AUC throughout treatment are promising for prediction of histopathologic response to nCRT for oesophageal cancer.

51 citations

Journal ArticleDOI
TL;DR: Both DW-MRI and DCE-MRI are promising in predicting response to nCRT in esophageal cancer, and combining both modalities provides complementary information, resulting in a higher predictive value.
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) ...

40 citations

Journal ArticleDOI
TL;DR: Changes on 18F-FDG PET/CT after nCRT and early changes on DW-MRI during nCRt can help identify pCR to n CRT in esophageal cancer.
Abstract: 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,post P = .016, and Δ total lesion glycolysis post P = .024), as well as changes in DW-MRI parameters during nCRT (Δ apparent diffusion coefficient [ADC]during P = .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.

38 citations

Journal ArticleDOI
TL;DR: DW-MRI during the second week of neoadjuvant chemoradiotherapy is the most predictive for pathologic complete response in esophageal cancer patients.
Abstract: 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. 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. 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). 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. • DW-MRI during the second week of neoadjuvant chemoradiotherapy is most predictive for pathologic complete response in esophageal cancer. • A model including ΔADC week 2 was 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.

21 citations

Journal ArticleDOI
TL;DR: It is indicated 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.
Abstract: Objective Both the apparent diffusion coefficient (ADC) acquired by diffusion-weighted magnetic resonance imaging (DW-MRI) and the standardized uptake value (SUV), acquired by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 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 18 F-FDG PET/CT examinations before treatment. The minimum and mean ADC values (ADC min and ADC mean) of the primary tumor were assessed on MRI. Similarly, the glucose metabolism was evaluated by the maximum and mean SUV (SUV max and SUV mean) in the same lesions on 18 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 (ADC min vs. SUV max: r=-0.087, P=0.457; ADC min vs. SUV mean: r=-0.105, P=0.369; ADC mean vs. SUV max: r=-0.099, P=0.349; ADC mean vs. SUV mean: 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 18 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.

15 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: The correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens was shown, as shown by the proportion of tumour regression grade (TRG) 3 or 4 residual tumours that was missed duringclinical response evaluations.
Abstract: Summary Background After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations. Methods The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m 2 of body-surface area] combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4–6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET–CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12–14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed. Findings Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% [95% CI 17–50]) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% [95% CI 4–23]) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% [95% CI 17–44]). PET–CT missed six of 41 TRG3 or TRG4 tumours (15% [95% CI 7–28]). PET–CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas). Interpretation After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET–CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). Funding Dutch Cancer Society.

168 citations

Journal ArticleDOI
TL;DR: The current and future perspectives in the surgical treatment of patients with esophageal cancer are described in the context of the available literature.
Abstract: Over the last decades, the treatment of resectable esophageal cancer has evolved into a multidisciplinary process in which all players are essential for treatment to be successful Medical oncologists and radiation oncologists have been increasingly involved since the implementation of neoadjuvant therapy, which has been shown to improve survival Although esophagectomy is still considered the cornerstone of curative treatment for locally advanced esophageal cancer, it remains associated with considerable postoperative morbidity, despite promising results of minimally invasive techniques In this light, both physical status and response to neoadjuvant therapy may be important factors for selecting patients who will benefit from surgery Furthermore, it is important to optimize the entire perioperative trajectory: from the initial outpatient clinic visit to postoperative discharge Enhanced recovery after surgery is increasingly recognized for esophagectomy and emphasizes perioperative aspects, such as nutrition, physiotherapy, and pain management To date, several facets of esophageal cancer treatment remain topics of debate, such as the preferred neoadjuvant treatment, anastomotic technique, extent of lymphadenectomy, organization of postoperative care, and the role of surgery beyond locally advanced disease Here, we describe the current and future perspectives in the surgical treatment of patients with esophageal cancer in the context of the available literature

76 citations

Journal ArticleDOI
TL;DR: Current imaging modalities such as CT, PET-CT, and EUS seem to be insufficiently accurate to identify complete responders and more accurate diagnostic tests are needed to improve restaging accuracy for patients with esophageal cancer.

74 citations

Journal ArticleDOI
TL;DR: How the integration of existing and novel forms of computed tomography, magnetic resonance imaging and positron emission tomography have transformed tumour delineation in the radiotherapy planning process is reviewed and how these advances have the potential to allow a more individualised approach to the cancer therapy is outlined.
Abstract: Imaging has an essential role in the planning and delivery of radiotherapy. Recent advances in imaging have led to the development of advanced radiotherapy techniques-including image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy and proton beam therapy. The optimal use of imaging might enable higher doses of radiation to be delivered to the tumour, while sparing normal surrounding tissues. In this article, we review how the integration of existing and novel forms of computed tomography, magnetic resonance imaging and positron emission tomography have transformed tumour delineation in the radiotherapy planning process, and how these advances have the potential to allow a more individualised approach to the cancer therapy. Recent data suggest that imaging biomarkers that assess underlying tumour heterogeneity can identify areas within a tumour that are at higher risk of radio-resistance, and therefore potentially allow for biologically focussed dose escalation. The rapidly evolving concept of adaptive radiotherapy, including artificial intelligence, requires imaging during treatment to be used to modify radiotherapy on a daily basis. These advances have the potential to improve clinical outcomes and reduce radiation-related long-term toxicities. We outline how recent technological advances in both imaging and radiotherapy delivery can be combined to shape the future of precision radiation oncology.

65 citations

Journal ArticleDOI
TL;DR: This study demonstrates that changes in AUC throughout treatment are promising for prediction of histopathologic response to nCRT for oesophageal cancer.

51 citations