ABSTRACT
BACKGROUND: Should early response imaging predict tumor response to therapy, personalized treatment adaptations could be feasible to improve outcome or reduce the risk of adverse events. This prospective single-center observational study on 2-fluorine-18-fluoro-deoxy-glucose (2-[18F]FDG) positron-emission tomography/magnetic resonance imaging (PET/MRI) features aims to investigate the association between semantic 2-[18F]FDG-PET/MRI imaging parameters and outcome prediction in uterine cervical squamous cell carcinoma (CSCC) treated with radiotherapy. RESULTS: Eleven study participants with previously untreated CSCC were examined with 2-[18F]FDG-PET/MRI at baseline and approximately one week after start of curative radiotherapy. All study participants had at least 24 months clinical follow-up. Two patients relapsed during the follow-up period. Reduced tumor size according to visual assessment was present in 9/11 participants (median change in sum of largest diameters (SLD) - 10.4%; range - 2.5 to - 24.6%). The size reduction was less pronounced in the relapse group compared to the no relapse group, with median change in SLD - 4.9%, versus - 10.4%. None of the reductions qualified as significantly reduced or increased in size according to RECIST 1.1., hence all participants were at this stage classified as non-responders/stable disease. Median baseline functional tumor volume (FTV) for the relapse group was 126 cm3, while for the no relapse group 9.3 cm3. Median delta FTV in the relapse group was 50.7 cm3, representing an actual increase in metabolically active volume, while median delta FTV in the no relapse group was - 2.0 cm3. Median delta apparent diffusion coefficient (ADC) was lower in the relapse group versus the no relapse group (- 3.5 mm2/s vs. 71 mm2/s). CONCLUSIONS: Early response assessment with 2-[18F]FDG-PET/MRI identified potentially predictive functional imaging biomarkers for prediction of radiotherapy outcome in CSCC, that could not be recognized with tumor measurements according to RECIST 1.1. These biomarkers (delta FTV and delta ADC) should be further evaluated. Trial registration Clinical Trials, NCT02379039. Registered 4 March 2015-Retrospectively registered, https://classic. CLINICALTRIALS: gov/ct2/show/study/NCT02379039 .
ABSTRACT
OBJECTIVE: Matrix metalloproteinases (MMPs) have been linked to aggressive behavior in several malignancies. Gelatinases (MMP-2 and MMP-9) in particular are prognostic factors in many adeno- and epithelial cancers. However, no conclusive data exist concerning the role of gelatinases in endometrial cancer. METHODS: Eighty-eight patients with endometrial cancer, treated between 1988 and 1993 in Umeå University Hospital, were included. MMP-2 and MMP-9 proteins were analyzed immunohistochemically from paraffin-embedded tissues by using specific monoclonal antibodies. The staining results were compared to the clinical data. RESULTS: Fifty-two percent of the cases were positive for MMP-9 and 72% for MMP-2. The overexpression of the proteins of either MMP-2 or MMP-9 was associated with poor survival. The predictive value of MMP-2 expression was most distinct in stage I cancers. An association was found between the positivity of MMP-2 and MMP-9. Only 3% of the cases were highly positive for both gelatinases and 18% of the cases were negative for both MMPs. Both gelatinases correlated to the histological grade. MMP-9 also correlated to the clinical stage of the disease, whereas MMP-2 did not. There was no apparent association with either depth of invasion, menopausal status, or the age of the patient. CONCLUSION: MMP-2 and MMP-9 could serve as markers for the clinical behavior of endometrial cancer. They may further be linked to a tendency to cancer relapse. Thus, these gelatinases may turn out to be potentially useful in decision making about the need for an adjuvant treatment.
