Increased FDG uptake on late-treatment PET in non-tumour-affected oesophagus is prognostic for pathological complete response and disease recurrence in patients undergoing neoadjuvant radiochemotherapy
Early side effects including oesophagitis are potential prognostic factors in patients undergoing radiochemotherapy (RCT) for locally advanced oesophageal cancer (LAEC). We assessed the prognostic value of 18F-fluorodeoxyglucose (FDG) uptake within irradiated non-tumour-affected oesophagus (NTO) during restaging positron emission tomography (PET) as a surrogate for inflammation/oesophagitis.
This retrospective evaluation included 64 patients with LAEC who had completed neoadjuvant RCT and had successful oncological resection. All patients underwent FDG PET/CT before and after RCT. In the restaging PET scan maximum and mean standardized uptake values (SUVmax, SUVmean) were determined in the tumour and NTO. Univariate Cox regression with respect to overall survival, local control, distant metastases and treatment failure was performed. Independence of clinically relevant parameters was tested in a multivariate Cox regression analysis.
Increased FDG uptake, measured in terms of SUVmean in NTO during restaging was significantly associated with complete pathological remission (p = 0.002) and did not show a high correlation with FDG response of the tumour (rho < 0.3). In the univariate analysis, increased SUVmax and SUVmean in NTO was associated with improved overall survival (p = 0.011, p = 0.004), better local control (p = 0.051, p = 0.044), a lower rate of treatment failure (p < 0.001 for both) and development of distant metastases (p = 0.012, p = 0.001). In the multivariate analysis, SUVmax and SUVmean in NTO remained a significant prognostic factor for treatment failure (p < 0.001, p = 0.004) and distant metastases (p = 0.040, p = 0.011).
FDG uptake in irradiated normal tissues measured on restaging PET has significant prognostic value in patients undergoing neoadjuvant RCT for LAEC. This effect may potentially be of use in treatment personalization.
KeywordsOesophageal cancer Radiochemotherapy Side effects Inflammation FDG pet
- 4.Rebollo Aguirre AC, Ramos-Font C, Villegas Portero R, Cook GJR, Llamas Elvira JM, Tabares AR. 18F-fluorodeoxiglucose positron emission tomography for the evaluation of neoadjuvant therapy response in esophageal cancer: systematic review of the literature. Ann Surg. 2009;250:247–54.CrossRefPubMedGoogle Scholar
- 5.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
- 7.Elimova E, Wang X, Etchebehere E, Shiozaki H, Shimodaira Y, Wadhwa R, et al. 18-fluorodeoxy-glucose positron emission computed tomography as predictive of response after chemoradiation in oesophageal cancer patients. Eur J Cancer 1990. 2015;51:2545–52.Google Scholar
- 9.Palie O, Michel P, Ménard J-F, Rousseau C, Rio E, Bridji B, et al. The predictive value of treatment response using FDG PET performed on day 21 of chemoradiotherapy in patients with oesophageal squamous cell carcinoma. A prospective, multicentre study (RTEP3). Eur J Nucl Med Mol Imaging. 2013;40:1345–55.Google Scholar
- 10.Lordick F, Ott K, Krause B-J, Weber WA, Becker K, Stein HJ, 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.Google Scholar
- 15.Zschaeck S, Loeck S, Leger S, Haase R, Bandurska-Luque A, et al. FDG uptake in normal tissues assessed by PET during treatment has prognostic value for treatment results in head and neck squamous cell carcinomas undergoing radiochemotherapy. Radiother Oncol. 2017;122(3):437–44.Google Scholar
- 16.Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6.Google Scholar
- 20.R Core Team. R: A Language and Environment for Statistical Computing. The R Foundation.Google Scholar
- 28.Wolff HA, Gaedcke J, Jung K, Hermann RM, Rothe H, Schirmer M, et al. High-grade acute organ toxicity during preoperative radiochemotherapy as positive predictor for complete histopathologic tumor regression in multimodal treatment of locally advanced rectal cancer. Strahlenther Onkol. 2010;186:30–5.CrossRefPubMedGoogle Scholar
- 30.Barber JB, Burrill W, Spreadborough AR, Levine E, Warren C, Kiltie AE, et al. Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer. Radiother Oncol. 2000;55:179–86.CrossRefPubMedGoogle Scholar
- 35.Balermpas P, Rödel F, Rödel C, Krause M, Linge A, Lohaus F, et al. CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: a multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer. 2016;138:171–81.CrossRefPubMedGoogle Scholar
- 39.Yip SS, Coroller TP, Sanford NN, Mamon H, Aerts HJ, Berbeco RI. Relationship between the temporal changes in positron-emission-tomography-imaging-based textural features and pathologic response and survival in esophageal cancer patients. Front Oncol. 2016;6:72.CrossRefPubMedPubMedCentralGoogle Scholar
- 41.Tixier F, Le Rest CC, Hatt M, Albarghach N, Pradier O, Metges JP, et al. Intratumor heterogeneity characterized by textural features on baseline 18F-FDG PET images predicts response to concomitant radiochemotherapy in esophageal cancer. J Nucl Med. 2011;52:369–78.CrossRefPubMedPubMedCentralGoogle Scholar
- 42.van Rossum PSN, Fried DV, Zhang L, Hofstetter WL, van Vulpen M, Meijer GJ, et al. The incremental value of subjective and quantitative assessment of 18F-FDG PET for the prediction of pathologic complete response to preoperative chemoradiotherapy in esophageal cancer. J Nucl Med. 2016;57:691–700.CrossRefPubMedGoogle Scholar