2017 Section 7 Green Book

I.S. Ryu et al. / European Journal of Cancer 63 (2016) 88 e 96

Fig. 1. Kaplan e Meier curves of progression-free survival (PFS) (A) and overall survival (OS) (B) according to the effect of PET/CT- induced changes in conventional workup (CWU) stage of the 248 eligible patients. Patients with upstaged diseases had worse PFS and OS than those whose CWU stage did not change after PET/CT (3-year PFS Z 56.8% versus 74.5%, P Z 0.043; 3-year OS Z 61.3% versus 85.3%, P Z 0.006).

in other human malignancies [26 e 28] . Interestingly, we found that patients whose management plan was highly impacted by PET/CT had significantly worse PFS and OS than the patients with low/no impact; in contrast, patients with moderate impact did not differ from pa- tients with no/low impact in terms of PFS or OS. Notably, the survival curves of the patients with mod- erate and no/low impact converged toward the end of follow-up. This suggests that despite nodal upstaging, PET/CT appropriately modified the treatment plan in the patients with moderate impact. However, the pa- tients whose management was highly impacted by PET/ CT failed to obtain a survival benefit because PET/CT detected distant metastasis and SPCs. Detection of these lesions in patients with HNSCC generally leads to palliative treatment and death [20] . The current clinical guidelines recommend perform- ing PET/CT as an optional imaging modality in advanced stage disease because of a low diagnostic yield of PET/CT in patients with stage I or II disease [17,29] . Indeed, we observed that PET/CT failed to detect the lesion in 14.8% of patients with T1 tumours, due to limitations of PET/CT in assessment of the early T1 stage [30] . However, we also found that PET/CT could upstage several of our patients with CWU stage I e II disease into stages III and IV; after these restaging, significant differences in stage-related prognosis were found, whereas the CWU stage I and II patients did not differ in terms of prognosis. These PET/CT-induced changes also changed the management of 9.8% of the CWU stage I and II patients. The number of these pa- tients is relatively small and results should be interpreted carefully. Nevertheless, our findings suggest that PET/ CT may need to be implemented in the routine imaging

workup for initial staging in all patients with HNSCC, not only those with advanced stage disease. In this study, PET/CT staging was significantly more accurate than CWU staging: it improved the staging accuracy in 16.1% (40/248) of the patients. Our data are similar with previous studies, which show that most PET/CT-induced stage migration is the result of nodal upstaging [10,11,18] . However, contrary to a previous meta-analysis [31] , we did not find that CWU and PET/ CT differ significantly in terms of the accuracy with which they detect SPCs. This may reflect the failure of PET/CT to detect synchronous oesophageal cancer. This was also observed by two recent studies [29,32] . Thus, PET/CT may detect early oesophageal cancer in HNSCC with particularly low sensitivity. Our study had several limitations. First, the CWU and PET/CT results were only validated in the patients with discordant PET/CT and CWU stages and in those in whom PET/CT changed the management plan. Because changes of management were not ex- pected in patients with identical PET/CT and CWU stages, we did not evaluate these patients further. We believe that this reflects the clinical practice of HNSCC staging workup and does not alter our findings. Second, our study cohort included heterogeneous tumour sites, although they were histologically identical (HNSCC). The disparities in T staging, natural courses, and clinical behaviour in HNSCC patients may exist according to the primary tumour location. Third, histopathological confirmation was unavailable in some of the patients. Fourth, this study was not designed to assess the cost- effectiveness of PET/CT in initial routine imaging workup. A randomised trial that addresses this issue is warranted. Nevertheless, our results are valuable as they

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