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Table 2 Comparison of diagnostic accuracy of staging by conventional workups with and without 18 F-FDG PET/CT in discordant cases. Imaging TP FP FN TN Sensitivity (%) Specificity (%) Accuracy (%) PPV (%) NPV (%) TNM staging a ( n Z 71) CWU 16 12 31 12 34.0 (22.9 e 45.0) 50.0 (38.3 e 61.6) 39.4 (28.0 e 50.7) 57.1 (45.5 e 68.6) 27.9 (17.4 e 38.3) CWU þ PET/CT 29 14 17 11 63.0 (51.7 e 74.2) 44.0 (32.4 e 55.5) 56.3 (44.7 e 67.8) 67.4 (56.5 e 78.3) 39.2 (27.8 e 50.5) P value b < 0.001 0.500 < 0.001 Abbreviations: CWU, conventional work-ups; 18 F-FDG, fluorine 18-fluorodeoxyglucose; FN, false negative; FP, false positive; NPV, negative predictive value; PET, positron emission tomography; PPV, positive predictive value; TN, true negative; TP, true positive. a TNM staging represented as T þ N þ M, according to discrepancies. b P values were determined by McNemar’s test. Values in bold indicate P < 0.05.

the CWU staging. Three (1.2%) patients were classified as no impact because the PET/CT results were ignored in the management decision making. Patients in whom PET/CT had a high impact on the management plan had significantly worse PFS and OS than those in whom PET/CT had low/no impact (both P < 0.001; Fig. 2 ). The Kaplan e Meier estimates of 3-year PFS and OS rates in all patients were 72.8% and 83.0%, respectively. Univariate analyses for PFS showed that CWU stage, PET/CT stage, and SPC associated significantly with lower PFS (all P < 0.05). Multivariate analysis revealed that PET/CT stage III e IV (HR Z 2.05, 95% CI Z 1.25 e 3.44; P Z 0.007) and SPCs (HR Z 2.30, 95% CI Z 1.16 e 4.54; P Z 0.016) independently pre- dicted PFS. Univariate analyses for OS showed that CWU stage, PET/CT stage, and SPC associated signif- icantly with lower OS (all P < 0.05). Multivariate analysis demonstrated that PET/CT stage III e IV (HR Z 4.70, 95% CI Z 2.08 e 10.60; P < 0.001) and SPCs (HR Z 3.07, 95% CI Z 1.51 e 6.23; P Z 0.002) independently predicted reduced OS ( Table 3 ). Subset analyses showed that the 3-year OS of the 122 patients with CWU stages I e II disease was 92.3% and the patients with CWU stages I and II did not differ in terms of OS ( P Z 0.317, Fig. 3 A). However, after PET/ CT, 98, 13, 7, and 4 of these 122 patients were re-staged as stage I, II, III, and IV, respectively. This PET/CT re- staging was of prognostic significance as the 3-year OS rates of these four groups were 94.8%, 92.3%, 85.7%, and 50.0%, respectively ( P Z 0.002, Fig. 3 B). The current study evaluated the impact of incorporating PET/CT findings into the initial staging process on the management and prognostic stratification of patients with newly diagnosed HNSCC. A few prospective studies have investigated the management impact of PET alone or PET/CT in a subset of patients (17 e 40%) and assessed only specific focus [10,11,18,19] . 3.2. Secondary outcome 4. Discussion

Moreover, there was no research to present relevant follow-up data for patients with HNSCC in regard to the prognostic stratification of PET/CT staging. To our knowledge, the current study is the first to prospectively evaluate the incremental clinical impact of PET/CT for the above topic. PET/CT altered the management of 15.7% of our patients. This is slightly higher than the rate reported previously: Lonneux et al. showed that PET altered the management of 13.7% of 233 patients [10] . This differ- ence may be associated with superiority of PET/CT in detecting regional or distant metastases and SPCs that are critical for selecting treatment [14 e 16] . Further, in terms of the primary tumour, hybrid imaging using PET/CT has been shown to improve both anatomic localisation and extent of 18 F-FDG-avid lesions compared with PET alone [23,24] . All our patients un- derwent PET/CT scan, while 83% of patients were assessed by PET in the latter report [10] . However, two other prospective studies found that PET/CT had a much greater impact on the management of HNSCC: PET/CT changed the management of 26 e 33.8% of the patients, including those with only stage III e IV or considerable proportion of cervical metastasis of an unknown primary (CUP). And they regarded major impact on management in whom PET/CT detected the primary tumour in CUP [11,18] . The possible explana- tion for different impact rates is that we included the patients at all stage of HNSCC with known primary site. Further, the result of Cacicedo et al. [18] are similar with those of our patients staged as III e IV by CWU. Our recent study already demonstrated that PET/CT lead to improved therapeutic planning in CUP [25] . The main finding of the present study was that PET/ CT staging has a prognostic role in HNSCC. PET/CT staging separated the HRs for both PFS and OS better than CWU staging, regardless of which treatment was employed. Multivariate analysis revealed that PET/CT staging independently predicted worse PFS and OS. In addition, patients whose CWU-determined disease was upstaged by PET/CT had significantly poorer PFS and OS than those whose clinical stage was unchanged. Thus, PET/CT staging can reveal disease extent better than CWU staging. Our results are in line with findings

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