Angela Lamarca1, Jorge Barriuso2, Amarjot Chander3, Mairéad G McNamara2, Richard A Hubner2, Derek ÓReilly4, Prakash Manoharan3, Juan W Valle5. 1. Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, UK. Electronic address: angela.lamarca@christie.nhs.uk. 2. Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, UK. 3. Radiology and Nuclear Medicine Department, The Christie NHS Foundation Trust, Manchester, UK. 4. HPB Surgery Department, Manchester Royal Infirmary, Central Manchester University Hospitals, Manchester, UK. 5. Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, UK. Electronic address: juan.valle@christie.nhs.uk.
Abstract
BACKGROUND & AIMS: The role of 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) in the diagnosis and staging of patients with biliary tract cancers (BTCs) remains controversial, so we aimed to provide robust information on the utility of 18FDG-PET in the diagnosis and management of BTC. METHODS: This systematic review and meta-analysis explored the diagnostic test accuracy of 18FDG-PET as a diagnostic tool for diagnosis of primary tumour, lymph node invasion, distant metastases and relapsed disease. Subgroup analysis by study quality and BTC subtype were performed. Changes in management based on 18FDG-PET and impact of maximum standardised uptake values (SUVmax) on prognosis were also assessed. A random effects model was used for meta-analyses. RESULTS: A total of 2,125 patients were included from 47 eligible studies. The sensitivity (Se) and specificity (Sp) of 18FDG-PET for the diagnosis of primary tumour were 91.7% (95% CI 89.8-93.2) and 51.3% (95% CI 46.4-56.2), respectively, with an area under the curve (AUC) of 0.8668. For lymph node invasion, Se was 88.4% (95% CI82.6-92.8) and Sp was 69.1% (95% CI 63.8-74.1); AUC 0.8519. For distant metastases, Se was 85.4% (95% CI 79.5-90.2) and Sp was 89.7% (95% CI86.0-92.7); AUC 0.9253. For relapse, Se was 90.1% (95% CI 84.4-94.3) and Sp was 83.5% (95% CI 74.4-90.4); AUC 0.9592. No diagnostic threshold effect was identified. Meta-regression did not identify significant sources of heterogeneity. Sensitivity analysis revealed no change in results when analyses were limited to studies with low risk of bias/concern. The pooled proportion of change in management was 15% (95% CI 11-20); the majority (78%) due to disease upstaging. Baseline high SUVmax was associated with worse survival (pooled hazard ratio of 1.79; 95% CI 1.37-2.33; p <0.001). CONCLUSIONS: There is evidence to support the incorporation of 18FDG-PET into the current standard of care for the staging (lymph node and distant metastases) and identification of relapse in patients with BTC to guide treatment selection; especially if the identification of occult sites of disease would change management, or if diagnosis of relapse remains unclear following standard of care imaging. The role for diagnosis of the primary tumour remains controversial due to low sensitivity and 18FDG-PET should not be considered as a replacement for pathological confirmation in this setting. LAY SUMMARY: A positron emission tomography (PET scan), using 18F-fluorodeoxyglucose (18FDG), can help doctors identify areas of cancer in the body by highlighting "hot spots". These hotspots may be cancerous (true positive) but may also be non-cancerous, like inflammation (false positive). We show that PET scans are useful to assess how far advanced the cancer is (by assessing spread to lymph glands and to other organs) and also to identify if the cancer has recurred (for example after surgery), thus helping doctors to make treatment decisions. However, a biopsy is still needed for the initial diagnosis of a biliary tract cancer, because of the high chance of a "false positive" with PET scans.
BACKGROUND & AIMS: The role of 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) in the diagnosis and staging of patients with biliary tract cancers (BTCs) remains controversial, so we aimed to provide robust information on the utility of 18FDG-PET in the diagnosis and management of BTC. METHODS: This systematic review and meta-analysis explored the diagnostic test accuracy of 18FDG-PET as a diagnostic tool for diagnosis of primary tumour, lymph node invasion, distant metastases and relapsed disease. Subgroup analysis by study quality and BTC subtype were performed. Changes in management based on 18FDG-PET and impact of maximum standardised uptake values (SUVmax) on prognosis were also assessed. A random effects model was used for meta-analyses. RESULTS: A total of 2,125 patients were included from 47 eligible studies. The sensitivity (Se) and specificity (Sp) of 18FDG-PET for the diagnosis of primary tumour were 91.7% (95% CI 89.8-93.2) and 51.3% (95% CI 46.4-56.2), respectively, with an area under the curve (AUC) of 0.8668. For lymph node invasion, Se was 88.4% (95% CI82.6-92.8) and Sp was 69.1% (95% CI 63.8-74.1); AUC 0.8519. For distant metastases, Se was 85.4% (95% CI 79.5-90.2) and Sp was 89.7% (95% CI86.0-92.7); AUC 0.9253. For relapse, Se was 90.1% (95% CI 84.4-94.3) and Sp was 83.5% (95% CI 74.4-90.4); AUC 0.9592. No diagnostic threshold effect was identified. Meta-regression did not identify significant sources of heterogeneity. Sensitivity analysis revealed no change in results when analyses were limited to studies with low risk of bias/concern. The pooled proportion of change in management was 15% (95% CI 11-20); the majority (78%) due to disease upstaging. Baseline high SUVmax was associated with worse survival (pooled hazard ratio of 1.79; 95% CI 1.37-2.33; p <0.001). CONCLUSIONS: There is evidence to support the incorporation of 18FDG-PET into the current standard of care for the staging (lymph node and distant metastases) and identification of relapse in patients with BTC to guide treatment selection; especially if the identification of occult sites of disease would change management, or if diagnosis of relapse remains unclear following standard of care imaging. The role for diagnosis of the primary tumour remains controversial due to low sensitivity and 18FDG-PET should not be considered as a replacement for pathological confirmation in this setting. LAY SUMMARY: A positron emission tomography (PET scan), using 18F-fluorodeoxyglucose (18FDG), can help doctors identify areas of cancer in the body by highlighting "hot spots". These hotspots may be cancerous (true positive) but may also be non-cancerous, like inflammation (false positive). We show that PET scans are useful to assess how far advanced the cancer is (by assessing spread to lymph glands and to other organs) and also to identify if the cancer has recurred (for example after surgery), thus helping doctors to make treatment decisions. However, a biopsy is still needed for the initial diagnosis of a biliary tract cancer, because of the high chance of a "false positive" with PET scans.
Authors: Jesus M Banales; Jose J G Marin; Angela Lamarca; Pedro M Rodrigues; Shahid A Khan; Lewis R Roberts; Vincenzo Cardinale; Guido Carpino; Jesper B Andersen; Chiara Braconi; Diego F Calvisi; Maria J Perugorria; Luca Fabris; Luke Boulter; Rocio I R Macias; Eugenio Gaudio; Domenico Alvaro; Sergio A Gradilone; Mario Strazzabosco; Marco Marzioni; Cédric Coulouarn; Laura Fouassier; Chiara Raggi; Pietro Invernizzi; Joachim C Mertens; Anja Moncsek; Sumera Rizvi; Julie Heimbach; Bas Groot Koerkamp; Jordi Bruix; Alejandro Forner; John Bridgewater; Juan W Valle; Gregory J Gores Journal: Nat Rev Gastroenterol Hepatol Date: 2020-06-30 Impact factor: 46.802
Authors: Mohammad Y Zaidi; Ghassan K Abou-Alfa; Cecilia G Ethun; Shailesh V Shrikhande; Mahesh Goel; Bruno Nervi; John Primrose; Juan W Valle; Shishir K Maithel Journal: Chin Clin Oncol Date: 2019-08-05
Authors: T Peter Kingham; Victoria G Aveson; Alice C Wei; Jason A Castellanos; Peter J Allen; Daniel P Nussbaum; Yinin Hu; Michael I D'Angelica Journal: Curr Probl Surg Date: 2020-06-30 Impact factor: 1.909
Authors: Jae Pil Hwang; Jong Ho Moon; Hee Kyung Kim; Min Hee Lee; Chae Hong Lim; Soo Bin Park; Joon-Kee Yoon; Jung Mi Park Journal: Medicine (Baltimore) Date: 2021-05-28 Impact factor: 1.817
Authors: Lukas Müller; Aline Mähringer-Kunz; Simon Johannes Gairing; Friedrich Foerster; Arndt Weinmann; Fabian Bartsch; Lisa-Katharina Heuft; Janine Baumgart; Christoph Düber; Felix Hahn; Roman Kloeckner Journal: J Clin Med Date: 2021-05-12 Impact factor: 4.241