Abstract
PurposeTo investigate clinical and radiological factors predicting worse outcome after (chemo)radiotherapy ([C]RT) in oropharyngeal squamous cell carcinoma (OPSCC) with a focus on apparent diffusion coefficient (ADC).MethodsThis retrospective study included 67 OPSCC patients, treated with (C)RT with curative intent and diagnosed during 2013–2017. Human papilloma virus (HPV) association was detected with p16 immunohistochemistry. Of all 67 tumors, 55 were p16 positive, 9 were p16 negative, and in 3 the p16 status was unknown. Median follow-up time was 38 months. We analyzed pretreatment magnetic resonance imaging (MRI) for factors predicting disease-free survival (DFS) and locoregional recurrence (LRR), including primary tumor volume and the largest metastasis. Crude and p16-adjusted hazard ratios were analyzed using Cox proportional hazards model. Interobserver agreement was evaluated.ResultsDisease recurred in 13 (19.4%) patients. High ADC predicted poor DFS, but not when the analysis was adjusted for p16. A break in RT (hazard ratio, HR = 3.972, 95% confidence interval, CI 1.445–10.917, p = 0.007) and larger metastasis volume (HR = 1.041, 95% CI 1.007–1.077, p = 0.019) were associated with worse DFS. A primary tumor larger than 7 cm3 was associated with increased LRR rate (HR = 4.861, 1.042–22.667, p = 0.044). Among p16-positive tumors, mean ADC was lower in grade 3 tumors compared to lower grade tumors (0.736 vs. 0.883; p = 0.003).ConclusionLow tumor ADC seems to be related to p16 positivity and therefore should not be used independently to evaluate disease prognosis or to choose patients for treatment deintensification.
Highlights
Oropharyngeal squamous cell carcinoma (OPSCC) subdivides into human papilloma virus (HPV)-associated and non-HPV-associated cancer groups
The main clinical outcome measures were disease-free survival (DFS) and locoregional recurrence (LRR) rate, as we found them to be most representative of the treatment effect in our study setting
This finding may be explained by the fact that apparent diffusion coefficient (ADC) correlates with tumor p16 status [21, 22], which in itself is a strong predictor of disease recurrence and survival [31, 32]
Summary
Oropharyngeal squamous cell carcinoma (OPSCC) subdivides into human papilloma virus (HPV)-associated and non-HPV-associated cancer groups. Immunohistochemical (IHC) overexpression of p16 is a surrogate marker for HPV and used in the current TNM classification [1] and the World Health Organization (WHO) classification of head and neck tumors [2]. A HPV-associated OPSCC usually responds well to (chemo)radiation ([C]RT), and treatment deintensification trials are underway to reduce treatment adverse effects [3, 4]. In a small subset of patients, the disease recurs making salvage surgery more demanding. Some radiological features show prognostic impact, such as volume of the primary tumor and metastasis, lymph node cystic or matted morphology, and extra-
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