Early prediction of residual disease after neoadjuvant chemoradiotherapy and cetuximab for locally advanced esophageal cancer using 18F-FDG PET-CT imaging: a prospective cohort study

Baruch Brenner; Yulia Kundel; Zoya Cohen; Hadar Brand; Noa Gordon; Aaron Sulkes; Sara Morgenstern; Nikolai Menasherov; Hanoch Kashtan; David Groshar; Liran Domachevsky; Hanna Bernstine

doi:10.21037/jgo-22-352

Early prediction of residual disease after neoadjuvant chemoradiotherapy and cetuximab for locally advanced esophageal cancer using ¹⁸F-FDG PET-CT imaging: a prospective cohort study

J Gastrointest Oncol. 2022 Dec;13(6):2721-2735. doi: 10.21037/jgo-22-352.

Authors

Baruch Brenner^{1

2}, Yulia Kundel¹, Zoya Cohen³, Hadar Brand¹, Noa Gordon¹, Aaron Sulkes^{1

2}, Sara Morgenstern⁴, Nikolai Menasherov⁵, Hanoch Kashtan^{2

6}, David Groshar^{2

7}, Liran Domachevsky^#^{2

7

8}, Hanna Bernstine^#^{2

7}

Affiliations

¹ Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, Israel.
² Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel.
³ Felsenstein Medical Research Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, Israel.
⁴ Institute of Pathology, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, Israel.
⁵ Department of Surgery A, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, Israel.
⁶ Departments of Surgery A and B, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, Israel.
⁷ Department of Nuclear Medicine, Rabin Medical Center, Beilinson Hospital, Petach Tiqva, Israel.
⁸ Department of Nuclear Medicine, The Chaim Sheba Medical Center, Tel Hashomer, Israel.

^# Contributed equally.

Abstract

Background: Previous studies in locally advanced esophageal cancer (LAEC) suggested that a change in the tumor's metabolic response, i.e., decrease of its interim ¹⁸F-FDG uptake compared with baseline, may predict histopathological response. We evaluated the possible predictive correlation between various PET-CT and histopathological parameters following a neoadjuvant biological-containing chemoradiotherapy (CRT) regimen.

Methods: Patients with resectable LAEC received neoadjuvant cisplatin/5-fluorouracil-based CRT and cetuximab following one cycle of induction chemotherapy and cetuximab. Changes in maximum and mean standardized uptake values (ΔSUV-max and ΔSUV-mean, respectively) and metabolic tumor volume (ΔMTV), measured by PET-CT at baseline and 2 weeks after the onset of treatment, were compared with histopathological findings at surgery. Histopathological response was defined by tumor regression grade (TRG), pathological complete response (pCR) and microscopic or macroscopic residual disease (RD).

Results: Of 18 patients, 13 (72%) with adenocarcinoma (AC) and 5 (28%) with squamous cell carcinoma (SCC), were included. None of the changes in the parameters of PET was associated with pCR; only ΔSUV-mean was associated with TRG in the AC cohort. In contrast, both ΔSUV-mean% and ΔSUV-max% were significantly associated with RD, both in the whole cohort and in the AC cohort. Changes in FDG-uptake predicted RD2 at surgery: only patients with less than 13% decrease in SUV-mean% or less than 29% decrease in SUV-max% had RD2, while all patients with RD0 or RD1 had greater reductions [100% specificity and 100% positive predictive value (PPV)].

Conclusions: Changes in ΔSUV-max and ΔSUV-mean after two weeks of onset of cetuximab-based neoadjuvant chemotherapy for LAEC may predict macroscopic RD but not TRG or pCR at surgery.

Keywords: Locally advanced esophageal cancer (LAEC); PET-CT; cetuximab; induction chemotherapy; neoadjuvant chemoradiotherapy; prediction of response.