Changes in multimodality functional imaging parameters early during chemoradiation predict treatment response in patients with locally advanced head and neck cancer

Abstract

Objective: To 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).

Methods: Thirty-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.

Results: There were 27 responders and 8 non-responders. Responders showed a greater reduction in PET-derived tumor total lesion glycolysis (TLG_40%; p = 0.007) and maximum standardized uptake value (SUV_max; 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 (K^trans; p = 0.012) and interstitial space volume fraction (V_e; p = 0.047) were observed in responders versus non-responders. ADC was the most powerful predictor (∆ >17%, AUC 0.937).

Conclusion: Early 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.

Keywords: Biomarker; Chemoradiation; Head and neck squamous cell carcinoma; MRI; PET/CT.

Fig. 1

Serial ADC maps (tumor ROI displayed in jet color scale) in the first 2 weeks of CRT for A (non-responder) and B (responder). Patient B showed a large treatment-induced increase in PT ADC (+51.3% post-week 2) in contrast to patient A (+2.8% post-week 2)

Fig. 2

Overlay K^trans and V_e maps demonstrating the differences in longitudinal changes between responder and non-responder after week 2 of CRT. The responder showed a significantly larger increase in median K^trans and V_e, in comparison to the non-responder

Fig. 3

An example of a responder having a paradoxical increase in primary tumor SUV at week 2 (highlighted by the blue arrow, cyan contour = MTV_40%) despite a marked initial decrease at week 1. This phenomenon was observed in a few other responders, which may be confounded by radiotherapy-induced peritumoral inflammation with cumulative fractions