Annals of Nuclear Medicine (2018) 32:165–174
Pilot study of serial FLT and FDG-PET/CT imaging to monitor response
to neoadjuvant chemoradiotherapy of esophageal adenocarcinoma:
correlation with histopathologic response
Victor H. Gerbaudo
· Joseph H. Killoran
· Chun K. Kim
· Jason L. Hornick
· Jonathan A. Nowak
Peter C. Enzinger
· Harvey J. Mamon
Received: 9 December 2017 / Accepted: 4 January 2018 / Published online: 13 January 2018
© The Japanese Society of Nuclear Medicine 2018
Objective 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.
Methods 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.
Results All tumors were FDG and FLT avid at baseline. Lesion FLT uptake was lower than with FDG. Neoadjuvant chemo-
radiation 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)].
Conclusion 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 sup-
port the need to corroborate the value of FLT-PET/CT in a larger cohort.
Keywords FDG · FLT · PET/CT · Esophageal cancer · Radiation therapy · Response to treatment · Neoadjuvant
Esophageal cancer is among the ten most common malig-
nancies worldwide and the seventh most common cause of
cancer-related deaths in developed countries [1, 2]. Most
patients are found to have advanced disease at presentation
with an overall 5-year survival of 12% . Preoperative and
deﬁnitive combined radiation therapies are among the stand-
ard treatment options for locally advanced disease [3–5].
Patients who respond to neoadjuvant treatment have
a better prognosis than those undergoing surgery alone.
Responders have a markedly better prognosis after surgery
* Victor H. Gerbaudo
Division of Nuclear Medicine and Molecular Imaging,
Department of Radiology, Brigham and Women’s
Hospital, Harvard Medical School, 75 Francis Street,
Boston, Massachusetts, USA
Department of Radiation Oncology, Brigham and Women’s
Hospital, Harvard Medical School, Boston, USA
Department of Pathology, Brigham and Women’s Hospital,
Harvard Medical School, Boston, USA
Center for Esophageal and Gastric Cancer, Dana Farber
Cancer Institute, Harvard Medical School, Boston, USA