Prognostic value of volumetric PET parameters in unresectable and metastatic esophageal cancer

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Abstract

Purpose

To assess the prognostic value of volumetric parameters measured with PET/CT in patients with advanced or metastatic esophageal cancer (EC).

Materials and methods

We identified 71 patients (33 adenocarcinoma [AC] and 38 squamous cell carcinoma [ESCC]) with unresectable or metastatic EC who had PET/CT prior to palliative treatment. Volumetric parameters (metabolic tumor volume [MTV], total lesion glycolysis [TLG], tumor length [TL]) as well as maximum and mean standardized uptake (SUVmax, SUVmean) were obtained from 18F-FDG PET/CT studies. The correlation between overall survival (OS) and established clinical parameters was assessed using a Cox proportional hazards model.

Results

ESCC patients had higher SUVmax and SUVmean compared to AC (p = 0.002 and p < 0.001, respectively). There was an association of lower SUVmax and SUVmean with metastatic compared to locally advanced tumors (e.g., median SUVmax stage IV: 14.9, 95% confidence interval [95% CI 4.4–35.5] vs. stage IIIA-C: 23.3 [9.2–40.6], p = 0.017). TL, MTV and TLG showed an association to OS for all patients and for the subgroup of AC patients (AC; TL: Hazard ratio [HR] 3.23, [95% CI 1.03–10.11], p = 0.044; MTV: HR 3.16, [95% CI 1.08-9.23], p = 0.035). There was no correlation between PET parameters and survival in ESCC patients. Clinical nodal status was the only clinical variable associated to OS (HR 2.45 [95% CI 1.26–4.75], p = 0.008) in AC patients. In a multivariate analysis, nodal status and MTV remained as independent factors associated to OS (N: HR 9.98, [95% CI 1.28–78.11], p = 0.028; MTV: HR 1.02, [95% CI 1.01–1.03], p = 0.003).

Conclusions

MTV predicted poor OS in patients with advanced AC. No PET parameters were associated to OS in ESCC patients.

Introduction

Among cancers of the gastrointestinal tract, esophageal squamous cell carcinoma (ESCC) and adenocarcinoma of the esophago-gastric junction (AEG, here AC) as defined by Siewert and Stein [1] still represent tumors with poorest prognosis and outcome. With the prevalence of this condition increasing over the last 25 years [2], [3], more than 18,000 cases are expected to occur in the United States every year with a yearly mortality of about 15,000 [4], [5].

Since up to 65% of patients are metastatic or inoperable at the time of diagnosis [4], many patients will be directed to non-surgical treatment which consists mainly of radiochemotherapy (RCHT) or chemotherapy (CHT) alone, with an expected 5-year survival of 15% [4]. Besides several established clinical prognostic factors for long-term survival [6], only few imaging features exist, which are accepted markers for poor prognosis [7]. In order to better plan which patients might benefit from intensified treatment, the establishment of novel markers to correctly predict prognosis is required.

F18-FDG PET/CT has become the standard in the evaluation of patients with EC, since it has been shown that significantly more distant metastases can be detected compared to CT alone [8]. Most commonly, maximum standardized uptake value (SUVmax) is used to predict outcome in localized or metastatic EC. However, over the last years, the concept of volumetric parameters has emerged that have the potential to better mirror the true tumor biology [9]. With the use of both the metabolic tumor volume (MTV) as well as total lesion glycolysis (TLG; derived from MTV and mean SUV of the entire mass), not only the tumor volume, but also the FDG avidity of the entire tumor is displayed [10]. In several reports this has been shown to correlate with survival [9], [10], [11], [12], [13]. However, in many of these studies, the intent to treat is not clearly defined, hence patients with both curative and palliative intent were included. This leads to sometimes-conflicting results between studies, and it is yet unclear, if volumetric parameters can be used to assess prognosis in patients with advanced EC.

Thus, the purpose of this study was to determine the value of volumetric PET-CT parameters on survival in comparison to SUVmax and clinical parameters in patients with advanced or metastatic EC.

Section snippets

Patients

The local institutional review board approved the study (blinded), and written informed consent was obtained for PET/CT exams.

From our PET/CT database, we identified 364 patients who were examined for an esophageal or gastro-esophageal junction tumor staging between 2008 and 2012 (for semantic purposes, those two groups will be referred to as EC from now on). After exclusion of all patients with a different pathology other than esophageal adeno- or squamous cell carcinoma, exclusion of all

Patient characteristics

Of 71 patients that were amenable for this analysis, 41 died during the observation period. The median survival was 14.1 months (95% CI 8.6–19.6). The 1-, 2- and estimated 3- year survival was 66.0%, 37.2% and 31.7%, respectively. Median follow up was 31.5 months (95% CI 13.9–48.8).

Patient demographic details, with respect to tumor histology, are depicted in Table 1. Patients with ESCC were older (p = 0.011), and were more likely to present with locally advanced disease (AJCC stage IIIA-C 47% vs.

Discussion

In this study of patients with advanced or metastatic esophageal cancer, we could show that metabolic tumor volume is associated with poor survival in the subgroup of patients with adenocarcinoma. SUVmax and SUVmean were correlated with clinical features of the tumors like grading and AJCC stage, but not with OS.

The results from the PET parameter analysis go along well with the clinical observation that patients with ESCC are more often locally advanced due to the anatomical predilection of

References (21)

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