ReviewUsefulness of F-18-fluorodeoxyglucose positron emission tomography to confirm suspected pancreatic cancer: A meta-analysis
Introduction
Pancreatic cancer is among the five most lethal malignancies in the world1 and survival has not increased substantially in the past 30 years.2 Its overall 5-year survival rate is 6%,2 increasing to 10%–25% after intentionally curative resection.3, 4, 5, 6, 7, 8 Unfortunately, at the time of diagnosis over 80% of all tumors are unresectable.9 Therefore, an early diagnosis of pancreatic cancer is crucial.
Overlooking a malignant tumor is a great concern to both physician and patient, as it may withhold early and live-extending treatment. The ideal diagnostic tool should be able to identify every malignant tumor, but keep the number of false positive results to a minimum. Surgeons are dealing with this dilemma of false negative and false positive results on a daily base. However, it is often beneficial to perform surgery in patients with suspicious pancreatic head lesions, despite the risk of performing an unnecessary pancreaticoduodenectomy.10 Besides, the impairment of quality of life after pancreaticoduodenectomy is not per definition irreversible.11 From a clinical and social point of view, lowering the risk of missing a malignant pancreatic tumor is more valuable than the risk of overtreatment. Against this background, clinicians would be willing to accept 95% sensitivity and 80% specificity. Thus allowing for four times more false positive results than false negative results.
Helical computed tomography (CT) and magnetic resonance imaging (MRI) are still the primary diagnostic tools, with sensitivity 91% and 84%, respectively, and specificity 85% and 82%, respectively.12 This means that with the use of these imaging techniques 10%–20% of all malignant tumors may be missed (false negatives). Therefore, it would be desirable to have a diagnostic tool with higher sensitivity and specificity, thereby, most important that would enable to identify a higher percentage of malignant pancreatic tumors.
One candidate is positron emission tomography (PET) with F-18-fluorodeoxyglucose (18FDG), which has been proven to be of clinical value in several gastrointestinal malignancies.13, 14It is based on the principle that photons resulting from the annihilation of the positrons emitted by specific radioisotopes (e.g. 18Fluorine) are detected by the PET-scanner and subsequently computed to a tomogram. A more recent tool, the 18FDG-PET/CT, combines in a single gantry both 18FDG-PET and CT and produces one combined image,15 see Supplement 1. Currently, 18FDG-PET/CT is quickly replacing stand-alone PET in clinical practice. Various studies have examined the ability of 18FDG-PET to diagnose pancreatic cancer. The reported sensitivity and specificity of 18FDG-PET is up to 95% and 100%, respectively.16 Furthermore, multiple studies showed that the sensitivity and specificity of 18FDG-PET is superior to CT alone.17, 18, 19, 20 The 18FDG-PET/CT is stated to be more sensitive than conventional imaging techniques regarding the detection of pancreatic cancer.21 Nonetheless, the clinical usefulness of both 18FDG-PET and 18FDG-PET/CT in patients with suspected pancreatic cancer is yet to be determined.
Main objective of this study is to review the relevant literature and to determine from these sources the usefulness of 18FDG-PET and 18FDG-PET/CT to confirm suspected pancreatic cancer. The focus is on identifying malignant tumors and limiting the number of false negative results to a minimum. Secondary objective is to evaluate the extent to which 18FDG-PET(/CT) can differentiate between pancreatic cancer and chronic pancreatitis.
Section snippets
Methods
Relevant literature was searched in Medline via OvidSP 350, PubMed not MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. The search period was from January first 1990 to April 10th 2013. Main keywords for the search-queries were: pancreatic neoplasm or cancer, pancreas, tumor and fluorodeoxyglucose. Studies, written in English, which fulfilled our search query and investigated the diagnostic accuracy of 18FDG-PET(/CT) in patients with primary pancreatic cancer were
Results
The search strategy applied on April 10th 2013 yielded 1541 citations. A total of 178 studies were excluded in first instance because they were either not written in English or had been published before 1990. Next, we excluded 423 duplicates. Thereafter, 862 studies were excluded based on title or abstract for not meeting the selection criteria as writing in the method section of this meta-analysis. Leaving 78 studies eligible for inclusion. However, in 39 of these 78 studies the sensitivity
Discussion
This meta-analysis revealed that both 18FDG-PET and 18FDG-PET/CT have a pooled sensitivity of around 90% and a pooled specificity of around 80% to diagnose pancreatic cancer in patients with suspected pancreatic cancer. As mentioned in the introduction, missing a malignant tumor is a great concern for both physician and patient. Unfortunately, 10% of all patients with a malignant tumor are not classified as such by 18FDG-PET. We also suggested that we are willing to allow four times more false
Methods and limitations
The broad search strategy in all major search engines was aimed not only at minimizing selection bias, but also on analyzing the ability of 18FDG-PET to: (i) Detect metastasis. (ii) Determine resectability. (iii) Determine survival. (iv) Evaluate treatment response. Unfortunately, the studies were too heterogeneous in study design and outcome measures to properly perform meta-analyses on these outcomes. A broad search strategy is disadvantageous in that many studies have to be evaluated for
Additional utilities
18FDG-PET and 18FDG-PET/CT are also used to detect metastatic disease in patients with pancreatic cancer but studies and subsequent data are limited. Accuracy to diagnose metastasis varied per metastatic site. For bone metastasis it ranged from 24%65–100%.66 Additionally, all studies which compared the detection rate of bone metastasis between 18FDG-PET (/CT) and CT reported that 18FDG-PET (/CT) was superior over CT.65, 66, 67, 68, 69, 70 The detection rate for liver metastasis widely ranged
Conclusion
Despite the technical development of 18FDG-PET(/CT) its diagnostic performance in patients with suspected pancreatic cancer has not improved over time. The results of our meta-analysis suggest that rather the biological behavior of pancreatic cancer and inflammation mainly limit the diagnostic performance of 18FDG-PET. Another pitfall of 18FDG-PET is the absence of anatomical information. However, 18FDG-PET/CT has become the state of the art and is quickly replacing stand-alone PET in clinical
Conflict of interest
None.
References (92)
- et al.
Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators
J Gastrointest Surg
(2000 Nov-Dec) - et al.
Diagnostic ascertainment of suspicious pancreatic mass: a threshold analysis
Clin Gastroenterol Hepatol
(2008 Oct) - et al.
Gastrointestinal malignancies evaluated with (18)F-fluoro-2-deoxyglucose positron emission tomography
Best Pract Res Clin Gastroenterol
(2006 Feb) - et al.
The role of positron emission tomography in the management of pancreatic cancer
Semin Nucl Med
(2006 Jul) Does blinding of readers affect the results of meta-analyses? University of Pennsylvania Meta-analysis Blinding Study Group
Lancet
(1997 Jul 19)- et al.
F-18 fluorodeoxyglucose (FDG) and C-Reactive Protein (CRP)
Clin Positron Imaging
(1999 May) - et al.
EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma
Gastrointest Endosc
(2000 Sep) - et al.
Impact of FDG-PET/MRI image fusion on the detection of pancreatic cancer
Pancreatology
(2006) - et al.
MR imaging versus PET/CT for evaluation of pancreatic lesions
Eur J Radiol
(2012 Oct) - et al.
Bivariate meta-analysis of predictive values of diagnostic tests can be an alternative to bivariate meta-analysis of sensitivity and specificity
J Clin Epidemiol
(2012 Oct)
Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews
J Clin Epidemiol
Impact of 18-fluorodeoxyglucose positron emission tomography on the management of pancreatic cancer
J Gastrointest Surg
Contribution of PET in the detection of liver metastases from pancreatic tumours
Clin Radiol
18Fluorodeoxyglucose pet is prognostic of progression-free and overall survival in locally advanced pancreas cancer treated with stereotactic radiotherapy
Int J Radiat Oncol Biol Phys
18-Fluorodeoxyglucose positron emission tomography in predicting survival of patients with pancreatic carcinoma
J Gastrointest Surg
Use of F-18 fluorodeoxyglucose positron emission tomography with dual-phase imaging to identify intraductal papillary mucinous neoplasm
Clin Gastroenterol Hepatol
Epidemiology of pancreatic cancer: an overview
Nat Rev Gastroenterol Hepatol
Cancer statistics
CA Cancer J Clin
Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group
Ann Surg
Carcinoma of the pancreas and periampullary region: palliation versus cure
Br J Surg
A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer
N Engl J Med
Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial
JAMA
Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma
Br J Surg
Pancreatic cancer
N Engl J Med
Quality of life after curative or palliative surgical treatment of pancreatic and periampullary carcinoma
Br J Surg
Ultrasonography, computed tomography and magnetic resonance imaging for diagnosis and determining resectability of pancreatic adenocarcinoma: a meta-analysis
J Comput Assist Tomogr
Value of contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography in detection and presurgical assessment of pancreatic cancer: a prospective study
J Gastroenterol Hepatol
FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0
Eur J Nucl Med Mol Imaging
The clinical usefulness of 18-fluorodeoxyglucose positron emission tomography in the differential diagnosis, staging, and response evaluation after concurrent chemoradiotherapy for pancreatic cancer
J Clin Gastroenterol
Optimal interpretation of FDG PET in the diagnosis, staging and management of pancreatic carcinoma
J Nucl Med
Evaluation of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose for the differentiation of chronic pancreatitis and pancreatic cancer
Br J Surg
2-(fluorine-18)-fluoro-2-deoxy-D-glucose PET in detection of pancreatic cancer: value of quantitative image interpretation
Radiology
Pancreatic adenocarcinoma
BMJ
The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews
BMC Med Res Methodol
Cochrane handbook for systematic reviews of diagnostic test accuracy version 1.0.0
Measuring inconsistency in meta-analyses
BMJ
F-18 fluorodeoxyglucose PET in vivo evaluation of pancreatic glucose metabolism for detection of pancreatic cancer
Radiology
Dual-head gamma camera coincidence imaging in pancreatic cancer
Rev Esp Med Nucl
FDG-PET evaluation of indeterminate pancreatic masses
J Comput Assist Tomogr
Evaluation of pancreatic tumors with positron emission tomography and F- 18 fluorodeoxyglucose: comparison with CT and US
Radiology
Clinical utility of positron emission tomography in the diagnosis and management of periampullary neoplasms
Ann Surg Oncol
Diagnosis of pancreatic carcinoma: role of FDG PET
Am J Roentgenol
Diagnostic usefulness of FDG PET for pancreatic mass lesions
Ann Nucl Med
Retrospective digital image fusion of multidetector CT and 18F-FDG PET: clinical value in pancreatic lesions - a prospective study with 104 patients
J Nucl Med
Positron emission tomography does not add to computed tomography for the diagnosis and staging of pancreatic cancer
Dig Surg
Delayed 18F-fluoro-2-deoxy-D-glucose positron emission tomography scan for differentiation between malignant and benign lesions in the pancreas
Cancer
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