Early Repeated ¹⁸F-FDG PET Scans During Neoadjuvant Chemoradiation Fail to Predict Histopathologic Response or Survival Benefit in Adenocarcinoma of the Esophagus

Abstract

This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response to neoadjuvant chemoradiotherapy and overall survival in patients with adenocarcinoma of the esophagus undergoing multimodal therapy. Methods: Thirty-seven patients with locally advanced adenocarcinoma of the esophagus underwent pretreatment and an intratreatment 18 F-FDG PET scan in the second week of a 6-wk regimen of neoadjuvant chemoradiotherapy. Histopathologic response and overall survival were correlated with percentage change in 18 F-FDG uptake (%Dmax-imum standardized uptake value [%DSUVmax]). Results: In 16 patients (43%), treatment induced a histopathologic response (,10% viable tumor cells), which was associated with a significant (P , 0.05) survival benefit. The optimal reduction in 18 F-FDG uptake, which separated histopathologic responders and nonresponders, was a 226.4% DSUVmax (receiver-operating-characteristic curve analysis). At this separation, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (area under the receiver operating characteristic curve) were 62.5%, 71.4%, 62.5%, 71.4%, and 67.4%, respectively, for intratreatment 18 F-FDG PET scans. Kaplan-Meier survival analysis of 18 F-FDG PET responders (.26.4% reduction in SUVmax), compared with 18 F-FDG PET nonresponders (,26.4% reduction in SUVmax), revealed no survival benefit for responders (P 5 0.6812). Conclusion: The %DSUVmax during the second week of induction chemoradiation did not correlate either with histopathologic response or with survival. Our results show that, in contrast to published reports on neoadjuvant chemotherapy, combined chemoradiotherapy in patients with adenocarcinoma of the esophagus lowers the predictive accuracy of early repeated 18 F-FDG PET in identifying histopathologic responders and those with chances for increased survival below clinically applicable levels.

Predicting tumour response to chemoradiotherapy in oesophageal cancer by early interim 18F-FDG PET: where do we stand and where should we go?

“…The study by Wieder et al [7], in 38 patients with squamous cell carcinoma, also found an association between metabolic tumour response and OS. In contrast, the study by Malik et al [8], in 37 patients with adenocarcinoma, did not find a significant association.…”

“…Increased 18 F-FDG uptake caused by radiation-induced inflammation may limit the use of 18 F-FDG PET, because 18 F-FDG PET is unable to distinguish whether tracer uptake is associated with inflammatory cells or residual viable tumour cells [7,8]. To our knowledge, there are only three published prospective studies [7][8][9] in which the predictive value of early interim 18 F-FDG PET in patients who received concurrent neoadjuvant chemoradiotherapy has been investigated. These studies all demonstrated an association between a decrease in tumour standardized uptake value (SUV) 14 days after start of neoadjuvant treatment and histopathological tumour response [7][8][9].…”

“…To our knowledge, there are only three published prospective studies [7][8][9] in which the predictive value of early interim 18 F-FDG PET in patients who received concurrent neoadjuvant chemoradiotherapy has been investigated. These studies all demonstrated an association between a decrease in tumour standardized uptake value (SUV) 14 days after start of neoadjuvant treatment and histopathological tumour response [7][8][9]. The study by Wieder et al [7], in 38 patients with squamous cell carcinoma, also found an association between metabolic tumour response and OS.…”

“…Much research work still needs to be done. The studies published so far were all single-centre studies with relatively small sample sizes, comprising patients with squamous cell and adenocarcinoma, and there were differences in the chemoradiotherapy regimen [7][8][9]. In addition, PET acquisition methods and ways of image analysis were not uniform.…”

“…However, these studies [5,6] were performed in patients who only received neoadjuvant chemotherapy, whereas concurrent chemoradiotherapy is now considered the standard neoadjuvant treatment [2]. Increased 18 F-FDG uptake caused by radiation-induced inflammation may limit the use of 18 F-FDG PET, because 18 F-FDG PET is unable to distinguish whether tracer uptake is associated with inflammatory cells or residual viable tumour cells [7,8]. To our knowledge, there are only three published prospective studies [7][8][9] in which the predictive value of early interim 18 F-FDG PET in patients who received concurrent neoadjuvant chemoradiotherapy has been investigated.…”