PROSPERO

International prospective register of systematic reviews

Diagnostic performance of 18F-FDG PET and 18F-FDG PET/CT for the detection of
interval metastases after neoadjuvant therapy for esophageal cancer: a systematic review
and meta-analysis
Lucas Goense, Tiuri E. Kroese, Peter S. N. van Rossum, Jelle P. Ruurda, Richard van Hilligersberg

Citation
Lucas Goense, Tiuri E. Kroese, Peter S. N. van Rossum, Jelle P. Ruurda, Richard van
Hilligersberg. Diagnostic performance of 18F-FDG PET and 18F-FDG PET/CT for the detection of
interval metastases after neoadjuvant therapy for esophageal cancer: a systematic review and
meta-analysis. PROSPERO 2016 CRD42016050592 Available from:
http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42016050592

Review question
What is the value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) or 18F-FDG
PET with integrated computerized tomography (CT) for the detection of interval metastases after
neoadjuvant therapy in patients with esophageal cancer?

Searches
A systematic search will be performed in three databases:
1. MEDLINE (via PubMed),
2. EMBASE, and
3. the Cochrane library using the search terms: ‘cancer’ and ‘PET and ‘esophageal’ or there synonyms to
identify all diagnostic studies that reported on the detection of interval metastases after neoadjuvant therapy
(either chemotherapy or chemoradiotherapy) with 18F-FDG PET or 18F-FDG PET with integrated CT in
humans with esophageal cancer.

Types of study to be included

Diagnostic studies that compared the specified index test and specified reference standard.

Condition or domain being studied

Human patients with esophageal cancer who received neoadjuvant therapy (either chemotherapy or
chemoradiotherapy)

Participants/population
Inclusion: *Diagnostic studies on performance of 18F-FDG PET or 18F-FDG PET/CT after neoadjuvant
chemo(radio)therapy * In humans with esophageal cancer.
Exclusion: * No baseline 18F-FDG PET or 18F-FDG PET/CT * Review * Poster abstract * Language other
than English language * Complete overlap of study population * Reference standard other than histology or
follow-up

Intervention(s), exposure(s)
Inclusion criteria Index test: detection of interval metastases with 18F-FDG PET or 18F-FDG PET/CT after
neoadjuvant treatment.

Comparator(s)/control
Not applicable.

Primary outcome(s)
Our primary outcome measure is the proportion of patients who developed interval metastases after
neoadjuvant therapy, detected with 18F-FDG PET or 18F-FDG PET/CT imaging.

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International prospective register of systematic reviews

Timing and effect measures

It is impossible to calculate specificity for distant metastases because the number of true negatives are
impossible to calculate.

Secondary outcome(s)
The proportion of patients where 18F-FDG PET or 18F-FDG PET/CT imaging was falsely suggestive of
interval metastases

Data extraction (selection and coding)

Two authors (P.S.N.v.R. and T.E.K.), independently, will screen titles and abstracts for eligibility, after
removal of duplicates. Subsequently, the same two authors will independently elevate full texts of potentially
relevant articles for inclusion

Risk of bias (quality) assessment

Two authors (P.S.N.v.R. and T.E.K), independently, will critically appraise the risk of bias and applicability
concern (‘low’, ‘high’ and ‘unclear’) on four key domains (patient selection, index test, reference standard
and flow and timing) of the included studies using the revised Quality Assessment of Diagnostic Accuracy
Studies (QUADAS-2) tool. Disagreements will be resolved by consensus. Regarding the applicability of the
index test, specific expertise will be acquired from a nuclear physician.

Strategy for data synthesis

Study- and patient characteristics will be extracted from each included study. A quantitative synthesis is
planned using a random-effects meta-analysis.
The I-squared test will be used to test for heterogeneity. We will consider an I square value greater than 50%
indicative of substantial heterogeneity.
Pooled and per study primary- and secondary outcomes measures will be calculated with 95% confidence
intervals. This will be depicted in a forest plot. Subgroup analysis will be performed to explore potential
causes heterogeneity (see analysis of subgroups). Statistically significant differences between groups are
defined by p = 0,05 using a random effect model.

Analysis of subgroups or subsets

Subgroup analysis only on primary outcome: -neoadjuvant treatment: chemotherapy vs chemoradiotherapy
-imaging: PET vs PET/CT -histology: adeno vs mixed Risk Of Bias (ROB) on primary outcome regarding
-patient selection: low vs high/unclear -index test: low vs high/unclear -reference standard: low vs
high/unclear On secondary outcome no subgroup analysis will be performed.

Contact details for further information

Dr Goense
l.goense-2@umcutrecht.nl

Organisational affiliation of the review

University Medical Center Utrecht, The Netherlands
www.umcutrecht.nl

Review team members and their organisational affiliations

Dr Lucas Goense. University Medical Center Utrecht, The Netherlands
Mr Tiuri E. Kroese. University Medical Center Utrecht, The Netherlands
Dr Peter S. N. van Rossum. University Medical Center Utrecht, The Netherlands
Dr Jelle P. Ruurda. University Medical Center Utrecht, The Netherlands
Professor Richard van Hilligersberg. University Medical Center Utrecht, The Netherlands

Anticipated or actual start date

07 November 2016

Anticipated completion date

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International prospective register of systematic reviews

19 December 2016

Funding sources/sponsors
No external funding will be involved in this investigation.

Conflicts of interest
None known

Language
English

Country
Netherlands

Stage of review
Review_Ongoing

Subject index terms status

Subject indexing assigned by CRD

Subject index terms

Esophageal Neoplasms; Fluorodeoxyglucose F18; Humans; Neoadjuvant Therapy; Neoplasms, Second
Primary; Tomography, X-Ray Computed

Date of registration in PROSPERO

03 November 2016

Date of publication of this version

03 November 2016

Details of any existing review of the same topic by the same authors
Stage of review at time of this submission
The review has not started

Stage Started Completed

Preliminary searches No No

Piloting of the study selection process No No

Formal screening of search results against eligibility criteria No No

Data extraction No No

Risk of bias (quality) assessment No No

Data analysis No No

Versions
03 November 2016

PROSPERO
This information has been provided by the named contact for this review. CRD has accepted this information in good
faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration
record, any associated files or external websites.

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International prospective register of systematic reviews

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