Predictive Value of Early Post-Treatment Diffusion-Weighted MRI for Recurrence or Tumor Progression of Head and Neck Squamous Cell Carcinoma Treated with Chemo-Radiotherapy

Abstract

Aims: To investigate the predictive capacity of early post-treatment diffusion-weighted magnetic resonance imaging (MRI) for recurrence or tumor progression in patients with no tumor residue after chemo-radiotherapy (CRT) for head and neck squamous cell carcinoma, and, to assess the predictive capacity of pre-treatment diffusion-weighted MRI for persistent tumor residue post-CRT. Materials and Method: A single center cohort study was performed in one French hospital. All patients with squamous cell carcinoma receiving CRT (no surgical indication) were included. Two diffusion-weighted MRI were performed: one within 8 days before CRT and one 3 months after completing CRT with determination of median tumor apparent diffusion coefficient (ADC). Main outcome: The primary endpoint was progression-free survival. Results: 59 patients were included prior to CRT and 46 (78.0%) completed CRT. A post-CRT tumor residue was found in 19/46 (41.3%) patients. In univariate analysis, initial ADC was significantly lower in patients with residue post CRT (0.56 ± 0.11 versus 0.79 ± 0.13; p < 0.001). When initial ADC was dichotomized at the median, initial ADC lower than 0.7 was significantly more frequent in patients with residue post CRT (73.7% versus 11.1%, p < 0.0001). In multivariate analysis, only initial ADC lower than 0.7 was significantly associated with tumor residue (OR = 22.6; IC [4.9–103.6], p < 0.0001). Among 26 patients without tumor residue after CRT and followed up until 12 months, 6 (23.1%) presented recurrence or progression. Only univariate analysis was performed due to a small number of events. The only factor significantly associated with disease progression or early recurrence was the delta ADC (p = 0.0009). When ADC variation was dichotomized at the median, patients with ADC variation greater than 0.7 had time of disease-free survival significantly longer than patients with ADC variation lower than 0.7 (377.5 [286–402] days versus 253 [198–370], p < 0.0001). Conclusion and relevance: Diffusion-weighted MRI could be a technique that enables differentiation of patients with high potential for early recurrence for whom intensive post-CRT monitoring is mandatory. Prospective studies with more inclusions would be necessary to validate our results.

The ability of post-chemoradiotherapy DWI ADCmean and 18F-FDG SUVmax to predict treatment outcomes in head and neck cancer: impact of human papilloma virus oropharyngeal cancer status

“…It is speculated that the favourable outcomes with decreased absolute ADC mean in our cohort actually reflects a post-treatment fibrotic response, since densely packed benign collagen may result in decreased ADC (Ailianou et al 2018). Whilst other previous researchers have found interval changes in ADC mean post treatment to have prognostic potential (Vandecaveye et al 2012;Brenet et al 2020) there were different methodologies and study populations.…”

“…5 Kaplan-Meier plots illustrate the impact of lymph node absolute ADC mean at 6 weeks (a) and primary tumour absolute ADC mean at 12 weeks (b) on DFS. For the purposes of illustration of the results, the patients were split into two equal-sized groups by the median ADC value for each parameter which have applied this to the post-treatment setting (King et al 2010;Vandecaveye et al 2012;Brenet et al 2020). Our finding of decreased absolute ADC mean in patients with successful treatment differs from that observed in previous post-treatment studies (King et al 2010) when an increased ADC mean in primary tumours or lymph nodes (n = 20) was able to predict 6 month outcomes.…”

“…The percentage interval changes were not predictive of DFS overall or within HPV-OPC subgroups. It could therefore be argued that, without multivariate analysis to account for HPV-OPC status, the larger interval changes in treatment responders reported in previous studies (Kim et al 2009;Berrak et al 2011;Vandecaveye et al 2012;King et al 2013a, b;Matoba et al 2014;Marzi et al 2017;Brenet et al 2020) may be related to the predominance of prognostically favourable HPV-OPC.…”

“…Quantitative DW-MRI has been proposed as an alternative prognostic biomarker for the assessment of early HNSCC treatment response to CRT. ADC mean values or their interval changes from pre-treatment baseline studies have been evaluated from both intra-treatment (Kim et al 2009;King et al 2010;Berrak et al 2011;Vandecaveye et al 2012;King et al 2013a, b;Matoba et al 2014;Schouten et al 2014;Ding et al 2015;Galbán et al 2015;Wong et al 2016;Marzi et al 2017;Paudyal et al 2017) and post-treatment (King et al 2010;Vandecaveye et al 2012;Kim et al 2014;Schouten et al 2014;Marzi et al 2017;Brenet et al 2020) DW-MRI studies, in an attempt to predict CRT outcomes. The majority of studies have found that increased absolute ADC mean values or a greater rise in ADC mean from pre-treatment to either intra-treatment values (Kim et al 2009;Berrak et al 2011;King et al 2013a, b;Matoba et al 2014;Ding et al 2015;Marzi et al 2017;Cao et al 2019) are predictive of treatment success, however, this is not a universal finding (Galbán et al 2015;Wong et al 2016;Paudyal et al 2017).…”

“…Cellular tumour impedes diffusion of water molecules, resulting in lower ADC values (Chawla et al 2009), and it has been hypothesised that a reduction in cellularity and progressive necrosis with successful treatment leads to a greater rise in ADC values. A number of studies have evaluated post-treatment tumour ADC mean as a biomarker (Kim et al 2009;King et al 2010;Vandecaveye et al 2012;Schouten et al 2014;Marzi et al 2017;Brenet et al 2020) with increased absolute ADC mean , or a greater percentage interval increase in ADC mean from pre-treatment values, being associated with the disease control (King et al 2010;Vandecaveye et al 2012;Brenet et al 2020). Since DW-MRI probes a different biological process to 18 F-FDG PET-CT, the two modalities may be complementary in stratifying the risk of residual or recurrent disease (Preda et al 2016).…”