The adverse impact of surveillance intervals on the sensitivity of FDG-PET/CT for the detection of distant metastases in head and neck cancer patients.

The presence of distant metastases at initial evaluation influences treatment selection, since no effective systemic treatment for disseminated head and neck squamous cell carcinoma (HNSCC) is currently available. The reported sensitivity for the detection of distant metastases by contrast-enhanced (ce)CT and FDG-PET(/CT) differs substantially between studies. We hypothesized that these sensitivity values are highly dependent on the reference standard use, e.g., follow-up term. Therefore, we analyze our results of FDG-PET/CT (including chest ceCT) with long-term follow-up and compare these findings with data from the literature, with particular interest in the different reference standards. Forty-six HNSCC patients with high-risk factors underwent pretreatment screening for distant metastases by FDG-PET/CT (including chest ceCT). In 16 (35%) patients, distant metastases were detected during screening (6 patients) or during a mean follow-up of 39.4 months after screening (10 patients). The sensitivity and negative predictive value were 83.3 and 97.2% when 6 months, 60.0 and 89.9% when 12 months, and 37.5 and 72.2% when 30 months follow-up were used as reference standard, respectively. This is comparable with reported studies with similar reference standards. This critical appraisal on the reference standards used in our and reported studies shows room for improvement for the detection of distant metastases to refrain more patients from unnecessary extensive locoregional treatment for occult metastatic HNSCC.

Screening for distant metastases in head and neck cancer patients using FDG-PET and chest CT: validation of an algorithm.

In patients with head and neck squamous cell carcinoma and high-risk factors, the combination of whole body FDG-PET and contrast-enhanced chest CT has the highest sensitivity and accuracy when screening for distant metastases. The aim of the present study was to retrospectively validate an earlier developed algorithm for interpreting the combination of screening PET and CT. The test cohort consisted of 47 consecutive HNSCC patients with high-risk factors for distant metastases, who had previously undergone FDG-PET and CT and had a minimum 12 months of follow-up. In 12 (26 %) patients, distant metastases were detected during screening or within 12-month follow-up. In patients with locoregional control during follow-up, the sensitivity and specificity were 55 % (95 % CI 23-83 %) and 97 % (95 % CI 82-99 %), respectively, for chest CT, 55 % (95 % CI 23-83 %) and 100 % (95 % CI 88-100 %), respectively, for PET and 73 % (95 % CI 39-94 %) and 100 % (95 % CI 88-100 %), respectively, for the combination of PET and CT. The proposed algorithm was considered to have been validated. In this algorithm, all FDG-PET positive scans for distant metastases (regardless of interpretation of a solid lung lesion on CT) and CT scans with suspicious pulmonary lesions of less than 5-mm diameter (regardless of FDG-PET findings) are considered positive for distant metastases.

Pretreatment screening for distant metastases in the Dutch head and neck centers: 10 years later.

To evaluate the current practice and change in practice concerning screening for distant metastases in head and neck squamous cell carcinoma patients, we performed a survey with the same questionnaire as 10 years ago among the eight centers of the Dutch Head and Neck Society treating head and neck cancer in The Netherlands. Factors related to extensive lymph node metastases are the most frequent indication for screening for distant metastases. The combinations of whole body PET-CT and contrast-enhanced chest CT are nowadays the diagnostic techniques for routinely screening for distant metastases. Screening for distant metastases is performed more frequently than 10 years ago. Although the sensitivity of the diagnostic pathway needs to be improved, most centers are satisfied with the current diagnostic pathway. A reduction of variation in indications and diagnostic techniques used for screening for distant metastases is observed during the last 10 years. In future guidelines patients' selection and diagnostic tests need to be specified in more detail.

Screening for distant metastases in head and neck cancer patients by chest CT or whole body FDG-PET: a prospective multicenter trial.

BACKGROUND AND PURPOSE: The aim of the study was to define the added value of whole body FDG-PET in screening for distant metastases in patients with head and neck squamous cell carcinoma and risk factors. MATERIALS AND METHODS: In a multi-center prospective study between 1998 and 2003, 145 consecutive HNSCC patients with risk factors for distant metastases underwent chest CT and whole body FDG-PET for screening of distant metastases. The data of 92 evaluable patients who developed distant metastases or who had a follow-up of at least 12 months were analyzed. Besides their performance in clinical practice, the operational characteristics of PET and CT using ROC analyses were investigated. RESULTS: Pretreatment screening identified distant metastases in 19 patients (21%). FDG-PET had a higher sensitivity (53% vs. 37%) and positive predictive value (80% vs. 75%) than CT. The combination of CT and FDG-PET had the highest sensitivity (63%). The ROC analyses of the five point ordinal scales revealed that the "area under the curve" (AUC) of FDG-PET was significantly higher as compared to CT. CONCLUSION: In HNSCC patients with risk factors, pretreatment screening for distant metastases by chest CT is improved by FDG-PET.

Detection of Distant Metastases in Head and Neck Cancer: Changing Landscape.

As head and neck squamous cell carcinoma (HNSCC) patients with distant metastases (DM) were generally treated only palliatively, the value of screening for DM was usually limited to attempts to avoid extensive locoregional treatment when DM were present pretreatment. Recently, the concept of treating oligometastases, e.g., by metastatectomy or stereotactic body radiotherapy, has been reintroduced for HNSCC and may cause a change in the treatment paradigm. Although whole body 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) combined with computed tomography (CT; WB-FDG-PET/CT) is still the mainstay diagnostic technique, there is a growing body of evidence supporting implementation of whole body magnetic resonance imaging (WB-MRI) as an important diagnostic technique for screening for DM. Also, FDG-PET/MRI may become a valuable technique for the detection of DM in HNSCC patients. Because the yield of examinations for detection of DM is too low to warrant routine screening of all HNSCC patients, only patients with high risk factors should be selected for intense screening for DM. Clinical and histopathological risk factors are mainly related to the extent of lymph node metastases. Risk for development of DM may also be assessed by molecular characterization of the primary tumor using genomic and proteomic technologies and radiomics. More research is needed to develop a new protocol for screening for DM after introduction of the concept of treating oligometastases in HNSCC.

Screening for distant metastases in patients with head and neck cancer: is there a role for (18)FDG-PET?

The detection of distant metastases and second primary tumours at the time of initial evaluation changes the prognosis and influences the selection of treatment modality in patients with HNSCC. Until recently chest CT was the single most effective test to screen for distant metastases in HNSCC patients. In this observational cohort study we prospectively compared the yield of whole body (18)FDG-PET and chest CT to detect distant metastases and synchronous primary tumours. The results of whole body (18)FDG-PET and chest CT were analysed in 34 consecutive HNSCC patients with previously established risk factors for the presence of distant metastases. Four patients were diagnosed with distant metastases or second primary tumours: CT as well as (18)FDG-PET identified one patient with lung metastases and another with primary lung cancer. In addition, (18)FDG-PET detected second primary tumours in two patients (hepatocellular carcinoma and abdominal adenocarcinoma). However increased uptake sites at (18)FDG-PET in lung, liver and pelvis in five patients were not confirmed by other imaging modalities. The added value of whole body (18)FDG-PET versus chest CT was to identify unknown malignancy in 6% of the patients. Confirmation of positive (18)FDG-PET findings is feasible and necessary.

Pretreatment screening on distant metastases and head and neck cancer patients: Validation of risk factors and influence on survival.

BACKGROUND AND PURPOSE: Previously identified high risk factors for development of distant metastases are: three or more lymph node metastases, bilateral lymph node metastases, lymph nodes larger than 6cm, low jugular lymph node metastases, locoregional tumor recurrence and second primary tumors. The aims of this study were to validate these specific risk factors and to investigate the impact of time (i.e. during screening or follow-up) of detection of distant metastases on survival. MATERIAL AND METHODS: From a total of 301 HNSCC patients with high risk factors who were scheduled for extensive treatment and underwent pretreatment screening on distant metastases using chest CT and/or whole body PET(-CT) (in some patients combined with whole body MRI), the high risk factors, the development and time point of distant metastases and survival were analyzed. RESULTS: Forty-four percent developed distant metastases. Multivariate analysis revealed that bilateral lymph node metastases is the strongest predictive factor. Locoregional recurrence and second primary tumor were the risk factors associated with the lowest cumulative incidence. However, if the risk factor locoregional recurrence was split into local and regional recurrences, regional recurrence became a high risk factor. The more high risk factors a patient had the lower the 5-year distant metastases free survival was. Patients with distant metastases detected pretreatment has a significant worse survival (corrected for lead time bias) compared to patients with distant metastases diagnosed during follow-up. CONCLUSIONS: The validity of three or more lymph node metastases, bilateral lymph node metastases, lymph nodes larger than 6cm, low jugular lymph node metastases and regional recurrence as high risk factors for the development of distant metastases was confirmed. If more high risk factors are present the cumulative incidence of distant metastases increases significantly. The detection of distant metastases by pretreatment screening worsens the overall survival as compared to distant metastases detected during follow-up.

Interobserver variability in chest CT and whole body FDG-PET screening for distant metastases in head and neck cancer patients.

PURPOSE: The aim of the study was to assess the interobserver variability in chest computed tomography (CT) and whole body 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) screening for distant metastases in head and neck squamous cell carcinoma (HNSCC) patients. PROCEDURE: Chest CT and whole body FDG-PET of 69 HNSCC patients with high-risk factors who underwent screening for distant metastases were analyzed. All scans were independently read by two experienced radiologists or nuclear physicians who were blinded to the other examinations and follow-up results. RESULTS: A kappa of 0.516 was found for assessment of size on CT. Kappa values for origin and susceptibility of 0.406 and 0.512 for CT and 0.834 and 0.939 for PET were found, respectively. The overall conclusions had a kappa of 0.517-0.634 for CT and 0.820-1.000 for PET. CONCLUSIONS: In screening for distant metastases in HNSCC patients with high-risk factors, chest CT readings had a reasonable to substantial agreement, while PET readings showed an almost perfect agreement. These findings suggest that for optimal assessment in clinical practice, PET most often can be scored by one observer, but CT should probably more often be scored by different observers in consensus or combined with PET.

Chest CT and whole-body 18F-FDG PET are cost-effective in screening for distant metastases in head and neck cancer patients.

UNLABELLED: The aim of the study was to define the cost-effectiveness of whole-body (18)F-FDG PET, as compared with chest CT, in screening for distant metastases in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: In a multicenter prospective study, 145 consecutive patients with high risk factors for distant metastases and scheduled for extensive treatment underwent chest CT and whole-body (18)F-FDG PET for screening of distant metastases. The cost data of 80 patients in whom distant metastases developed or who had a follow-up of at least 12 mo were analyzed. Cost-effectiveness analysis, including sensitivity analysis, was performed to compare the results of (18)F-FDG PET, CT, and a combination of CT and (18)F-FDG PET (CT + (18)F-FDG PET). RESULTS: Pretreatment screening identified distant metastases in 21% of patients. (18)F-FDG PET had a higher sensitivity (53% vs. 37%) and positive predictive value (80% vs. 75%) than did CT. CT + (18)F-FDG PET had the highest sensitivity (63%). The average costs in the CT, (18)F-FDG PET, and CT + (18)F-FDG PET groups amounted to euro38,558 (approximately $57,705), euro38,355 (approximately $57,402), and euro37,954 (approximately $56,801), respectively, in the first year after screening. CT + (18)F-FDG PET resulted in savings between euro203 (approximately $303) and euro604 (approximately $903). Sensitivity analysis showed that the dominance of CT + (18)F-FDG PET was robust. CONCLUSION: In HNSCC patients with risk factors, pretreatment screening for distant metastases by chest CT is improved by (18)F-FDG PET. The combination of (18)F-FDG PET with CT is the most effective, without leading to additional costs.