18F FDG-PET/CT evaluation of histological response after neoadjuvant treatment in patients with cancer of the esophagus or gastroesophageal junction

Abstract

Background

In most parts of the world, curatively intended treatment for esophageal cancer includes neoadjuvant therapy, either with chemoradiotherapy or chemotherapy alone, followed by esophagectomy. Currently 18F-FDG positron emission tomography/computed tomography (PET/CT) is used for preoperative disease staging, but is not well established in the evaluation of neoadjuvant treatment.

Purpose

To evaluate changes in PET parameters in relation to the histological primary tumor response in the surgical specimen in patients randomized to neoadjuvant chemoradiotherapy or chemotherapy.

Material and Methods

Patients were randomized between either neoadjuvant chemotherapy or chemoradiotherapy followed by esophagectomy.18F-FDG PET/CT exams were conducted at baseline and following neoadjuvant treatment. Standardized uptake ratio (SUR) values were measured in the primary tumor and compared as regards histological responders and non-responders as well as different treatment arms.

Results

Seventy-nine patients were enrolled and 51 were available for analysis. A significant rate of SUR reduction was observed (P = 0.02) in the primary tumor in histological responders compared to non-responders. Changes in SUR were significantly greater in responders following chemoradiotherapy (P = 0.02), but not following chemotherapy alone (P = 0.49). There was no statistically significant difference in SUR in patients with a complete histological response compared to those with a subtotal response.

Conclusion

Our results are similar to those of previous studies and show that changes in the rate of SUR can be used reliably to differentiate histological responders from non-responders after neoadjuvant treatment with either chemoradiotherapy or chemotherapy. Limitations of current PET technology are likely to restrict the possibility of accurately ruling out limited residual disease.

Keywords

Esophageal cancer neoadjuvant therapy histological response PET/CT 18F-FDG standardized uptake ratio

Get full access to this article

View all access options for this article.

References

Herszényi

Tulassay

. Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci 2010; 14: 249–258.

Lambert

Hainaut

. Epidemiology of oesophagogastric cancer. Best Pract Res Clin Gastroenterol 2007; 21: 921–945.

van Hagen

Hulshof

MCCM

van Lanschot

JJB

et al.

Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074–2084.

Ychou

Boige

Pignon

J-P

et al.

Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011; 29: 1715–1721.

Sjoquist

Burmeister

Smithers

et al.

Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 2011; 12: 681–692.

Donohoe

Reynolds

. Neoadjuvant treatment of locally advanced esophageal and junctional cancer: the evidence-base, current key questions and clinical trials. J Thorac Dis 2017; 9: S697–S704.

Chirieac

Swisher

Ajani

et al.

Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer 2005; 103: 1347–1355.

Davies

Gossage

Zylstra

et al.

Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction. J Clin Oncol 2014; 32: 2983–2990.

Langer

Ott

Feith

et al.

Prognostic significance of histopathological tumor regression after neoadjuvant chemotherapy in esophageal adenocarcinomas. Mod Pathol 2009; 22: 1555–1563.

10.

Klevebro F, Alexandersson von Döbeln G, Wang N, Johnsen G, Jacobsen A-B, Friesland S, et al. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol 2016; 27(4): 660–7.

11.

Bollschweiler

Hölscher

Metzger

. Histologic tumor type and the rate of complete response after neoadjuvant therapy for esophageal cancer. Future Oncol 2010; 6: 25–35.

12.

Bedenne L, Mariette C. Comparison of systematic surgery versus surveillance and rescue surgery in operable oesophageal cancer with a complete clinical response to radiochemotherapy (Esostrate). Available at: ClinicalTrials.gov Identifier: NCT02551458. 2015.

13.

van Vliet

EPM

Heijenbrok-Kal

Hunink

MGM

et al.

Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer 2008; 98: 547–557.

14.

Lordick

Ott

Krause

B-J

et al.

PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol 2007; 8: 797–805.

15.

Baksh

Prithviraj

Kim

et al.

Correlation between standardized uptake value in preneoadjuvant and postneoadjuvant chemoradiotherapy and tumor regression grade in patients with locally advanced esophageal cancer. Am J Clin Oncol 2018; 41: 254–258.

16.

Cerfolio

Bryant

Talati

et al.

Change in maximum standardized uptake value on repeat positron emission tomography after chemoradiotherapy in patients with esophageal cancer identifies complete responders. J Thorac Cardiovasc Surg 2009; 137: 605–609.

17.

Arnett

ALH

Merrell

Macintosh

et al.

Utility of 18F-FDG PET for predicting histopathologic response in esophageal carcinoma following chemoradiation. J Thorac Oncol 2017; 12: 121–128.

18.

Weber

Ott

Becker

et al.

Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 2001; 19: 3058–3065.

19.

Butof

Hofheinz

Zophel

et al.

Prognostic value of pretherapeutic tumor-to-blood standardized uptake ratio in patients with esophageal carcinoma. J Nucl Med 2015; 56: 1150–1156.

20.

Schmidt

Lordick

Herrmann

et al.

Value of functional imaging by PET in esophageal cancer. J Natl Compr Canc Netw 2015; 13: 239–247.

21.

Siewert

Stein

. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg 1998; 85: 1457–1459.

22.

van den Hoff

Oehme

Schramm

et al.

The PET-derived tumor-to-blood standard uptake ratio (SUR) is superior to tumor SUV as a surrogate parameter of the metabolic rate of FDG. EJNMMI Res 2013; 3: 77–77.

23.

Kauppi

Oksala

Salo

et al.

Locally advanced esophageal adenocarcinoma: Response to neoadjuvant chemotherapy and survival predicted by ^[18F]FDG-PET/CT. Acta Oncol 2012; 51: 636–644.

24.

Molena

Sun

Badr

et al.

Clinical tools do not predict pathological complete response in patients with esophageal squamous cell cancer treated with definitive chemoradiotherapy: Retrospective review at one institution. Dis Esophagus 2014; 27: 355–359.

25.

Swisher

Erasmus

Maish

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: 1776–1785.

26.

Yen

T-J

Chung

C-S

Y-W

et al.

Comparative study between endoscopic ultrasonography and positron emission tomography-computed tomography in staging patients with esophageal squamous cell carcinoma: Accuracy of preoperative esophageal cancer staging. Dis Esophagus 2012; 25: 40–47.