Abstract
ObjectiveTo assess the optimal timing and predictive value of early intra-treatment changes in multimodality functional and molecular imaging (FMI) parameters as biomarkers for clinical remission in patients receiving chemoradiation for head and neck squamous cell carcinoma (HNSCC).MethodsThirty-five patients with stage III-IVb (AJCC 7th edition) HNSCC prospectively underwent 18F–FDG-PET/CT, and diffusion-weighted (DW), dynamic contrast-enhanced (DCE) and susceptibility-weighted MRI at baseline, week 1 and week 2 of chemoradiation. Patients with evidence of persistent or recurrent disease during follow-up were classed as non-responders. Changes in FMI parameters at week 1 and week 2 were compared between responders and non-responders with the Mann–Whitney U test. The significance threshold was set at a p value of <0.05.ResultsThere were 27 responders and 8 non-responders. Responders showed a greater reduction in PET-derived tumor total lesion glycolysis (TLG40%; p = 0.007) and maximum standardized uptake value (SUVmax; p = 0.034) after week 1 than non-responders but these differences were absent by week 2. In contrast, it was not until week 2 that MRI-derived parameters were able to discriminate between the two groups: larger fractional increases in primary tumor apparent diffusion coefficient (ADC; p < 0.001), volume transfer constant (Ktrans; p = 0.012) and interstitial space volume fraction (Ve; p = 0.047) were observed in responders versus non-responders. ADC was the most powerful predictor (∆ >17%, AUC 0.937).ConclusionEarly intra-treatment changes in FDG-PET, DW and DCE MRI-derived parameters are predictive of ultimate response to chemoradiation in HNSCC. However, the optimal timing for assessment with FDG-PET parameters (week 1) differed from MRI parameters (week 2). This highlighted the importance of scanning time points for the design of FMI risk-stratified interventional studies.
Highlights
Radical chemoradiation (CRT) is widely accepted as the standard of care for organ-sparing treatment of locally advanced head and neck squamous cell carcinoma (HNSCC)
Another possible confounding factor is the influence of radiotherapy-induced peritumoral inflammation on FDG uptake with cumulative fractions, which may affect Regions of interest (ROIs) segmentation (Fig. 3), but this phenomenon is typically observed during the latter part of radiotherapy [2, 16]
We investigated the role of SW-derived R2* as a predictive biomarker in HNSCC
Summary
Radical chemoradiation (CRT) is widely accepted as the standard of care for organ-sparing treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). It is evident that locally advanced HNSCC represents a disease spectrum rather than a single entity, with variable response to standard CRT. Clinical variables such as tumor, node and metastases (TNM) staging and smoking history are prognostically robust but predictively deficient. Functional and molecular imaging (FMI) can characterize tumor phenotypes by providing quantitative parameters with radiobiological relevance. Several correlation studies in HNSCC have demonstrated varied, but complementary, biological information from different FMI parameters [1, 2]. Most FMI biomarker studies in HNSCC have concentrated only on pre-treatment time points.
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