Review
Usefulness of F-18-fluorodeoxyglucose positron emission tomography to confirm suspected pancreatic cancer: A meta-analysis

https://doi.org/10.1016/j.ejso.2014.03.016Get rights and content

Abstract

Introduction

Pancreatic cancer is among the five most lethal malignancies in the world. Unfortunately, many malignant tumors go undetected by the current primary diagnostic tools. 18FDG-PET and 18FDG-PET/CT might be useful to confirm suspected pancreatic cancer.

Methods

A meta-analysis was performed using all major search engines. Methodological quality of included studies was assessed as well as quality of the PET-protocol. The following pooled estimates served as primary outcome measures: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy.

Results

Thirty-five studies were included. Pooled estimates for 18FDG-PET were: sensitivity 90%, specificity 76%, PPV 90%, NPV 76% and accuracy 86%. Pooled estimates for 18FDG-PET/CT were: sensitivity 90%, specificity 76%, PPV 89%, NPV 78% and accuracy 86%. The pooled sensitivity and specificity for 18FDG-PET to differentiate between pancreatic cancer and chronic pancreatitis were 90% and 84%, respectively.

Conclusion

Both 18FDG-PET and 18FDG-PET/CT offer no benefit over the current primary diagnostic tools in diagnosing pancreatic cancer. However, the 18FDG-PET/CT systems are still improving. We should investigate the sensitivity and specificity of these new systems while reevaluating the tradeoff between false positive and false negative results. Yet, 18FDG-PET/CT may have a role in the staging of pancreatic cancer, in survival prediction, and may add to other diagnostic information, like histology.

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.

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