18F-FDG-PET/CT can be used to predict distant metastasis in hypopharyngeal squamous cell carcinoma

Distant metastases of head and neck cancers are present in approximately 10% of cases at diagnosis, with additional 20%–30% developing metastases throughout their disease [14]. In addition to this clinically recognized occurrence, the incidence of distant metastases in autopsy series is three to four times higher than that in clinical series [15, 16]. Once distant metastasis occurs in head and neck squamous cell carcinoma (HNSCC), the prognosis is relatively poor (approximately ten months), even with the best treatments related to recent drug developments [17]. Thus, approximately 15–20% of patients with HNSCC die of distant metastasis [16].

HPSCC, in particular, has the most frequent incidence of distant metastasis among HNSCC [14, 16], and distant metastasis has occurred in 60% of patients who died of hypopharyngeal cancer [15]. Thus, distant metastasis is a clinically significant problem directly related to HNSCC prognosis, particularly HPSCC. However, it has long been highlighted that the head and neck cancer prognosis can be improved if distant metastasis can be controlled [18].

Recently, following the development of new drugs, particularly immune checkpoint inhibitors, it has become possible to prolong the survival of patients with distant metastasis [19, 20]. Therefore, predicting distant metastasis and performing appropriate treatment early is becoming increasingly important for improving HNSCC progonisis, particularly HPSCC.

This study examined 121 cases of HPSCC and found that the SUVmax in the primary lesion before treatment was an independent predictor of distant metastases. Notably, it was found that the low SUVmax group had few distant metastases, but metastases incidence increased rapidly above the cutoff value, as shown in Fig. 2. Conversely, following the T and N classifications, distant metastases were scattered, even at a relatively early stage (Table 3). Because of these characteristics, SUVmax may have been the only independent predictor of distant metastasis in multivariate analysis.

A higher uptake of FDG shows active tumor metabolism and correlates negatively with tumor oxygenation [21]. Many studies have revealed that poor tumor oxygenation or hypoxia is related to higher tumorigenicity, resulting in a poor clinical prognosis, including distant metastasis [22]. Alternatively, the SUVmax, which is obtained from FDG accumulation, directly reflects the condition inside the primary tumor. Therefore, SUVmax is thought to better judge the nature of the tumor, which is thought to be why SUVmax was considered an independent index of distant metastasis in this study.

In addition to SUVmax, metabolic tumor parameters derived from FDG-PET include metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Many studies have reported the usefulness of these parameters in head and neck cancer [23, 24]. However, among these metabolic parameters, SUVmax is thought to have an advantage over MTV and TLG because, in clinical practice, MTV and TLG are susceptible to fluctuations induced by differences in the definition of areas of interest and adjacent FDG-avid structures [5, 25]. These factors do not affect SUVmax. Therefore, SUVmax has only small differences among observers, is highly reliable and is easy to introduce compared with MTV and TLG [5, 26]. For these reasons, SUVmax is considered the most suitable metabolic tumor parameter derived from FDG-PET.

This study has several limitations. First, a comparatively small number of patients were obtained from only one institution, and a retrospective design was used. Secondly, the presence or absence of chemotherapy combined with radiation or surgery could not be considered. In addition to these limitations, the study included cases in which radiation therapy and surgical treatment was used as the initial treatment. In locally advanced cases, the primary site, the hypopharynx, may have been resected by surgery. In these cases, it is inevitably difficult to assess local recurrence. Therefore, it is possible that SUVmax was not a predictor of locoregional recurrence in this study.

Further large-scale studies that focus on the initial treatment of the target patients, with a prospective design is necessary.

Conclusively, this study highlights the role of SUVmax in pretreatment primary tumors of HPSCC and shows that SUVmax is significantly associated with distant metastasis, distant metastasis-free survival, and overall survival in a retrospective study.

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