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. 2018 Sep;45(10):1742-1751.
doi: 10.1007/s00259-018-4011-6. Epub 2018 Apr 16.

Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT

Lucas Goense  1   2   3 , Jelle P Ruurda  4 , Brett W Carter  5 , Penny Fang  6 , Linus Ho  7 , Gert J Meijer  8 , Richard van Hillegersberg  4 , Wayne L Hofstetter  9 , Steven H Lin  10
Affiliations

Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT

Lucas Goense et al. Eur J Nucl Med Mol Imaging. 2018 Sep.

Abstract

Objective: During neoadjuvant chemoradiotherapy for oesophageal cancer, or in the interval prior to surgery, some patients develop systemic metastasis. This study aimed to evaluate the diagnostic performance of 18F-FDG PET/CT for the detection of interval metastasis and to identify predictors of interval metastases in a large cohort of oesophageal cancer patients.

Methods: In total, 783 consecutive patients with potentially resectable oesophageal cancer who underwent chemoradiotherapy and pre- and post-treatment 18F-FDG PET/CT between 2006 and 2015 were analyzed from a prospectively maintained database. Diagnostic accuracy measures were calculated on a per-patient basis using histological verification or clinical follow-up as a reference standard. Multivariable logistic regression analysis was performed to determine pre-treatment predictors of interval metastasis. A prediction score was developed to predict the probability of interval metastasis.

Results: Of 783 patients that underwent 18F-FDG PET/CT restaging, 65 (8.3%) were found to have interval metastasis and 44 (5.6%) were deemed to have false positive lesions. The resulting sensitivity and specificity was 74.7% (95% CI: 64.3-83.4%) and 93.7% (95% CI: 91.6-95.4%), respectively. Multivariable analysis revealed that tumor length, cN status, squamous cell tumor histology, and baseline SUVmax were associated with interval metastasis. Based on these criteria, a prediction score was developed with an optimism adjusted C-index of 0.67 that demonstrated accurate calibration.

Conclusions: 18F-FDG PET/CT restaging detects distant interval metastases in 8.3% of patients after chemoradiotherapy for oesophageal cancer. The provided prediction score may stratify risk of developing interval metastasis, and could be used to prioritize additional restaging modalities for patients most likely to benefit.

Keywords: 18F-FDG PET/CT; Cancer staging; Chemoradiotherapy; Esophagectomy; Oesophageal cancer.

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Conflict of interest statement

Conflict of interest

Steven H. Lin received research funding from STCube Pharmaceuticals, Genetech, Peregrine Pharmaceuticals, Hitachi Chemical, and honorarium from AstraZeneca. All other authors have no conflict of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

This retrospective study was approved by our Institutional Review Board, and the need for written informed consent was waived.

Figures

Fig. 1
Fig. 1
Flowchart of the study
Fig. 2
Fig. 2
Examples of true positive metastatic lesions detected by 18F-FDG PET/CT restaging. (a/c): 80-year-old woman with adenocarcinoma of the distal esophagus treated with chemoradiation. The maximum intensity projection PET image shows multiple hypermetabolic foci of the liver and multiple soft tissue lesions that were confirmed malignant with follow-up scans. (b): 65-year-old male with squamous cell carcinoma of the distal esophagus who had undergone chemoradiotherapy. The PET/CT image showed 18F-FDG accumulation in the liver and in the thoracic spine at T5. Follow-up CT showed disease progression
Fig. 3
Fig. 3
Examples of new non-malignant 18F-FDG avid lesions detected by 18F-FDG PET/CT restaging. (a): 78-year-old woman with squamous cell carcinoma of the esophagus treated with chemoradiation. The PET/CT image shows new opacities within the left lower lobe with corresponding areas of 18F-FDG activity. The new lesion was within the presumed radiation field (b) and the appearance was most compatible with radiation-induced pneumonitis (scan was regarded as ‘true negative’ for new metastatic disease). (c): 42-year-old female with adenocarcinoma of the distal esophagus who had undergone chemoradiotherapy. The PET/CT images show linear 18F-FDG accumulation within the lateral aspect of the left hepatic lobe. The new lesion was within the presumed radiation field (d) and was thought to be related to radiation therapy changes, which was confirmed with an MRI scan (scan was regarded as ‘false positive’ as additional imaging was required to exclude metastatic disease)
Fig. 4
Fig. 4
Calibration curve for predicted probability of interval metastasis for each unit of the risk score versus the observed frequency of interval metastasis
Fig. 5
Fig. 5
Risk prediction model for interval metastasis predicts overall survival in patients without interval metastasis after 18F-FDG PET/CT restaging
See this image and copyright information in PMC

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