Pilot study of serial FLT and FDG-PET/CT imaging to monitor response to neoadjuvant chemoradiotherapy of esophageal adenocarcinoma: correlation with histopathologic response
The aim of this prospective pilot study was to investigate the potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early indication of esophageal cancer response to concurrent neoadjuvant chemoradiation therapy.
Five patients with biopsy-proven esophageal adenocarcinomas underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive esophagectomy. The presence of residual tumor was classified histologically using the Mandard et al. criteria, categorizing patients as pathologic responders and non-responders. Participants underwent PET/CT imaging 1 h after intravenous administration of FDG and of FLT on two separate days within 48 h of each other. Each patient underwent a total of 3 scan “pairs”: (1) pre-treatment, (2) during treatment, and (3) post-treatment. Image-based response to therapy was measured in terms of changes in SUVmax (ΔSUV) between pre- and post-therapeutic FLT- and FDG-PET scans. The PET imaging findings were correlated with the pathology results after surgery.
All tumors were FDG and FLT avid at baseline. Lesion FLT uptake was lower than with FDG. Neoadjuvant chemoradiation resulted in a reduction of tumor uptake of both radiotracers in pathological responders (n = 3) and non-responders (n = 2). While the difference in the reduction in mean tumor FLT uptake during Tx between responders (ΔSUV = − 55%) and non-responders (ΔSUV = − 29%) was significant (P = 0.007), for FDG it was not, [responders had a mean ΔSUV = − 39 vs. − 31% for non-responders (P = 0.74)]. The difference in the reduction in tumor FLT uptake at the end of treatment between responders (ΔSUV = − 62%) and non-responders (ΔSUV = − 57%) was not significant (P = 0.54), while for FDG there was a trend toward significance [ΔSUV of responders = − 74 vs. − 52% in non-responders (P = 0.06)].
The results of this prospective pilot study suggest that early changes in tumor FLT uptake may be better than FDG in predicting response of esophageal adenocarcinomas to neoadjuvant chemoradiation. These preliminary results support the need to corroborate the value of FLT-PET/CT in a larger cohort.
KeywordsFDG FLT PET/CT Esophageal cancer Radiation therapy Response to treatment Neoadjuvant chemoradiotherapy
Technology and Innovation Grant from the Kaye Scholar Award at Brigham and Women’s Hospital, Boston, MA.
Compliance with ethical standards
Conflict of interest
No potential conflicts of interest were disclosed.
- 1.Siegel RL, Miller KD, Jemal A. Cancer statistics 2017. CA: A Cancer J Clin. 2017;67:7–30.Google Scholar
- 3.Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V. Australasian Gastro-Intestinal Trials Group. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.CrossRefPubMedGoogle Scholar
- 4.Ronellenfitsch U, Schwarzbach M, Hofheinz R, Kienle P, Kieser M, Slanger TE, et al. Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer. 2013;49:3149 – 3148.CrossRefPubMedGoogle Scholar
- 8.Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, Zaninotto G, et al. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001;91:2165–74.CrossRefPubMedGoogle Scholar
- 12.Goodman KA, Niedzwiecki D, Hall N, et al. Initial results of CALGB 80803 (Alliance): a randomized phase II trial of PET scan-directed combined modality therapy for esophageal cancer. Presented at: 2017 Gastrointestinal Cancers Symposium. January 19–21, 2017; San Francisco, California; Abstract 1.Google Scholar
- 15.Swisher SG, Erasmus J, Maish M, Correa AM, Macapinlac H, Ajani JA, et al. 2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma. Cancer. 2004;101:1776–85.CrossRefPubMedGoogle Scholar
- 19.Mamede M, Abreu-E-Lima P, Oliva MR, Nosé V, Mamon H, Gerbaudo VH. FDG-PET/CT tumor segmentation-derived indices of metabolic activity to assess response to neoadjuvant therapy and progression-free survival in esophageal cancer: correlation with histopathology results. Am J Clin Oncol. 2007;30:377–88.CrossRefPubMedGoogle Scholar
- 21.Toyohara J, Waki A, Takamatsu S, Yonekura Y, Magata Y, Fujibayashi Y. Basis of FLT as a cell proliferation marker: comparative uptake studies with [3H]thymidine and [3H]arabinothymidine, and cell analysis in 22 asynchronously growing tumor cell lines. Nucl Med Biol. 2002;29:281–7.CrossRefPubMedGoogle Scholar
- 28.Park SH, Ryu JS, Oh SJ, Park SI, Kim YH, Jung HY, et al. The feasibility of (18)F-Fluorothymidine PET for prediction of tumor response after induction chemotherapy followed by chemoradiotherapy with S-1/oxaliplatin in patients with resectable esophageal cancer. Nucl Med Mol Imaging. 2012;46:57–64.CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Edge SB, Byrd DR, Compton CC et al, editors Esophagus and esophagogastric junction. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010: pp. 103–15.Google Scholar