Increased bone marrow SUVmax on 18F-FDG PET is associated with higher pelvic treatment failure in patients with cervical cancer treated by chemoradiotherapy and brachytherapy

Abstract

The aim of this study was to evaluate if bone marrow (BM) SUVmax measured on pre-treatment 18F-FDG PET/CT predicts the clinical outcome of locally advanced cervical cancer (LACC). We recruited retrospectively patients with LACC who underwent staging 18F-FDG PET/CT and had baseline blood tests, then treated by chemoradiation therapy (CRT), followed by image-guided adaptive brachytherapy (IGABT). BM SUVmax was calculated and correlated to inflammatory blood markers. Tumor size and pelvic lymph node involvement were evaluated on baseline MRI. Prognostic value of SUV uptake and blood markers regarding overall survival (OS), pelvic and extra-pelvic recurrence-free survival (PRFS and EPRFS respectively) was assessed using Cox models with adjusted p-values. 116 patients with FIGO stage Ib-IVa cervical cancer, treated between 2005 and 2014, were analyzed. The median follow-up was 75.5 months. BM SUVmax was significantly correlated to tumor SUVmax. In multivariate analysis, PRFS was significantly poorer in patients with high BM SUVmax (>2.8) and neutrophilia (p < .05). Tumor size (>5 vs ≤5 cm) could predict PRFS, EPRFS and OS (p < .05). In our cohort, FIGO stage (I-II vs III-IV), pelvic lymph node involvement and tumor SUVmax (>12 vs ≤12) were not prognostic for OS or pelvic and extra-pelvic relapses. Patients with LACC and high BM SUVmax on 18F-FDG PET have worse PFRS following CRT plus IGABT. These results can be potentially explained by the pro-inflammatory role of the tumor microenvironment and G-CSF expressed by tumor cells. These data support the role of PET as a potential indicator of disease aggressiveness beyond tumor staging.

Keywords: 18F-FDG bone marrow uptake; Cervical cancer; PET/CT; brachytherapy; chemoradiotherapy; pelvic treatment failure.

Figure 1.

Maximal intensity projection coronal (left) and sagittal (middle) FDG PET* images. Sagittal 18F-FDG PET/CT with bone window CT^† on the spine (right); initial staging for a 44-year-old patient with squamous LACC revealing pelvic and para-aortic lymph node metastasis and showing an increased FDG uptake in the spine hematopoietic BM^‡ tissue (BM SUV_max^§ 3.5). Nearly 3 years after completion of brachytherapy, the patient relapsed locally and finally died one full-year after recurrence. Abbreviations: *FDG PET: fluorodeoxyglucose positron emission tomography. †CT: computed tomography. SUV_max: maximum standardized uptake value. ‡BM: bone marrow. §BM SUV_max: average of maximum standardized uptake values of each vertebral body in bone marrow.

Figure 2.

Kaplan-Meier curves for PRFS* (in the upper left) and OS^§ (in the lower right) in all patients (N = 116). Curves for PRFS* stratified according to BM SUV_max^‡ (in the lower left) and neutrophils count (in the upper right). Abbreviations: *PRFS: pelvic recurrence-free survival. ^§OS: overall survival. ^‡BM SUV_max: average of maximum standardized uptake values of each vertebral body in bone marrow.