2017 Section 7 Green Book

treatment have consistently found that the accuracy of the scans

varies with timing, with a longer time interval associated with a

greater accuracy.

48-51

Our study confirms these findings, with

scans for local or regional disease performed after 12 weeks

having a greater specificity (

= .009 and

= .004, respec-

tively), but no difference in sensitivity, when compared with

those performed before 12 weeks. These results are slightly dif-

ferent from 2 previous meta-analyses that demonstrated an

improvement in sensitivity, rather than specificity, with a delay

of 10 to 12 weeks after the completion of treatment before scan-

ning. However, both of these meta-analyses included retrospec-

tive as well as prospective studies in their analysis.

The lower specificity in the immediate posttreatment

period found in our review is likely related to the increased

vascularity, edema, and inflammatory changes at the pri-

mary site and in the neck after (chemo)radiation, which

results in an increased physiological uptake of FDG

and

hence more false-positive readings. However, a deliberate

delay before the first posttherapy scan is not without conse-

quences; a prolonged period between the completion of che-

motherapy and salvage surgery allows time for extensive

postradiation fibrosis to develop, leading to an increased fre-

quency and severity of surgical complications.

In deter-

mining the optimal time for the initial scan, we must

therefore balance the need for prompt diagnosis and man-

agement of disease against the risk of misleading results if

scans are performed too early. However, the timing of the

first posttreatment scan remains somewhat controversial

despite numerous diagnostic accuracy studies. Based on the

results of our review, we would support a delay of 12 weeks

after (chemo)radiotherapy before imaging because of the

improvement in diagnostic accuracy seen with a later scan.

Strengths and Limitations

There are several strengths of this meta-analysis. We included

only prospective studies in our review, thus reducing the

number of articles included in our study compared with previ-

ous meta-analyses. However, this inclusion may help reduce

the risk of bias that may be found with retrospective studies.

Because studies with positive results are more likely to be pub-

lished, there is always the risk of publication bias with sys-

tematic reviews. We attempted to minimize the potential for

such bias by using a comprehensive search strategy with no

language restrictions. Our exclusion of conference abstracts,

letters, editorials, and gray literature may affect the results;

however, we believe that this would have minimal impact

overall. Publication bias was detected for the nodal sites only,

and based on the large fail-safe number (

1000), we believe

it is highly unlikely that these studies would have not been

found using our comprehensive search strategy.

The studies identified in our review had some limitations.

Most notably, the reference standard was not consistent

across all studies; histopathology was performed in every

patient in only 4 of the 27 included studies. In most cases,

histopathological confirmation was used only in patients

with a positive PET or PET/CT because of the invasive

nature of biopsies and neck dissections. Clinical follow-up,

with and without conventional imaging, formed the basis of

the reference standard in those with negative PET scans.

This may potentially result in the overestimation of test sen-

sitivity and underestimation of test specificity.

There was also substantial variability in the sensitivity and

specificity estimates among studies. Although the difference in

imaging modality and timing explained this to some extent,

some heterogeneity remained despite subgroup analysis. Other

variables such as the stage and location of the tumor at initial

diagnosis, the reference standard used, and the clinical presen-

tation at recurrence may have contributed to the heterogeneity

among studies. We could not assess the impact of these factors

on test accuracy because of inconsistent reporting of data.

Conclusion

This is a meta-analysis focused on the diagnostic accuracy

of PET and PET/CT for the detection of residual and/or

recurrent local and regional disease and distant metastases

in patients with HNSCCs using only prospective data. We

found that both modalities had a good overall diagnostic

accuracy for detection of residual and/or recurrent disease at

local, nodal, and distant sites, with PET/CT being more

specific than PET alone for the detection of disease at the

primary site. The accuracy of visual assessment and semi-

quantitative analysis of images were comparable at local,

nodal, and distant sites. The timing of the scan had an

impact on accuracy, with later scans being more specific

than earlier scans. This study has determined that the most

ideal strategy for follow-up scans is after 12 weeks post-

treatment with the use of combined PET and CT.

Author Contributions

Phylannie K. F. Cheung

, study concept and design, acquisition of

data, analysis and interpretation of data, drafting of the manuscript,

critical revision of the manuscript for important intellectual con-

tent, and statistical analysis;

Ronald Y. Chin

, study concept and

design, analysis and interpretation of data, drafting of the manu-

script, critical revision of the manuscript for important intellectual

content, and study supervision;

Guy D. Eslick

, study concept and

design, analysis and interpretation of data, drafting of the manu-

script, critical revision of the manuscript for important intellectual

content, statistical analysis, and study supervision.

Disclosures

Competing interests:

None.

Sponsorships:

None.

Funding source:

None.

Supplemental Material

Additional supporting information may be found at

http://otojournal .org/supplemental

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Otolaryngology–Head and Neck Surgery 154(3)