International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationPreoperative Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients With Esophageal Cancer Using 18F-FDG PET/CT and DW-MRI: A Prospective Multicenter Study
Introduction
Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the preferred curative-intent treatment for patients with locally advanced esophageal cancer.1 Through tumor downsizing and downstaging, nCRT improves locoregional control and overall survival rates compared with surgery alone.2, 3, 4 Many studies have reported that the degree of tumor regression in response to nCRT is directly related to long-term survival, with pathologic complete responders having the most favorable long-term prognosis.3,5 The absence of viable tumor cells at the site of the primary tumor in pathologic complete responders raises the question of whether surgical resection is of benefit for patients who might have already been cured locoregionally by nCRT alone.6 Accurate prediction of pathologic complete response (pCR) before surgery could potentially allow patients to forgo surgery and would enable researchers to study the feasibility and outcome of an organ-preserving strategy after chemoradiotherapy. Conversely, patients with a poor response to nCRT are likely to benefit less or not at all from nCRT but are exposed to its side effects. Reliable identification of poor responders during nCRT may thus also be beneficial because ineffective therapy could be stopped or alternative treatment strategies (eg, additional neoadjuvant treatment or upfront surgery) could be explored.
Unfortunately, most studied modalities—including endoscopic biopsy, endoscopic ultrasonography, and computed tomography (CT)—yield unsatisfactory results for the evaluation of tumor response to nCRT.7, 8, 9, 10, 11 Metabolic and functional imaging modalities such as 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) may be more promising because they allow biological and microstructural characterization of tumors and visualization of treatment-induced changes before volumetric changes become apparent.9,12, 13, 14, 15, 16, 17, 18 However, the discriminatory ability of 18F-FDG PET/CT alone has been shown in a multitude of studies to be insufficient to guide clinical decision-making.14,19,20 The performance of DW-MRI and the quantitative apparent diffusion coefficient (ADC) are promising in predicting response to nCRT, although they have been demonstrated only in 2 small single-center pilot studies.16,17
A multimodality imaging approach, in comparison to single modality, may provide complementary value for predicting pathologic response, with the ultimate goal of optimally guiding individualized treatment decision-making. Therefore, the aim of this prospective multicenter study was to evaluate the individual and combined value of 18F-FDG PET/CT and DW-MRI during and after nCRT to predict pathologic response in patients who undergo nCRT for esophageal cancer, as well as to validate these findings for the prediction of survival.
Section snippets
Methods and Materials
Three high-volume institutions participated in this multicenter prospective study, including the University Medical Center Utrecht, the University of Texas MD Anderson Cancer Center, and the Netherlands Cancer Institute. The study has been approved by the institutional review board of each institution separately, and all patients provided their written informed consent. The study was registered with ClinicalTrials.gov, number NCT02125448.
Study population
Between October 2013 and July 2017, a total of 82 consecutive patients with newly diagnosed esophageal cancer who underwent standard diagnostic workup signed informed consent forms. A total of 13 patients were excluded from the analysis (withdrawal from study participation [n = 4], unexpected distant metastatic disease [n = 3], no tumor signal on the baseline 18F-FDG PET/CT or DW-MRI [n = 3], small tumor volume [<2 mL, n = 2], and refusal of surgery [n = 1]). The remaining 69 patients, with a
Discussion
This international, multicenter, prospective study was designed to assess the predictive value of quantitative changes on 18F-FDG PET/CT and DW-MRI scans acquired during and after nCRT in patients with esophageal cancer. Changes in 18F-FDG PET/CT parameters after nCRT (ΔSUVmean,post and ΔTLGpost) and changes in DW-MRI parameters during nCRT (ΔADCduring) discriminate well between pathologic complete responders (TRG 1) and non-pCR (TRG 2-4) in esophageal cancer. Moreover, 18F-FDG PET/CT and
Conclusions
Our study shows that quantitative ADC changes from baseline to interim DW-MRI scans and SUVmean changes from baseline to follow-up 18F-FDG PET/CT scans can help identify pCR to nCRT in patients with esophageal cancer. However, additional larger prospective studies, as well as other combined multimodal approaches, are needed to validate these results, especially regarding the potentially complementary value of 18F-FDG PET/CT and DW-MRI imaging parameters.
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Alicia S. Borggreve Lucas Goense made equal contributions to this study.
This research was partially funded by Elekta Inc and by National Institutes of Health/National Cancer Institute Cancer Center support grant P30CA016672.
Research data are stored in an institutional repository and will be shared upon request to the corresponding author.
Disclosures: R.v.H. and J.P.R. are proctoring surgeons for Intuitive Surgical Inc and train other surgeons in robot-assisted minimally invasive esophagectomy. J.J.W. receives research funding from Elekta Inc. S.H.L. receives research funding from Elekta Inc, Genentech, Hitachi Chemicals, New River Labs, and Beyond Spring Pharmaceuticals and is a member of the Advisory Board of AstraZeneca. All of the above are not in conflict with the research in question. All other authors have nothing to disclose.