Impact of solitary pulmonary nodule size on qualitative and quantitative assessment using 18F-fluorodeoxyglucose PET/CT: the SPUTNIK trial

J R Weir-McCall, S Harris, K A Miles, N R Qureshi, R C Rintoul, S Dizdarevic, L Pike, Heok K Cheow, Fiona J Gilbert, SPUtNIk investigators, Anindo Banerjee, Lucy Brindle, Matthew Callister, Andrew Clegg, Andrew Cook, Kelly Cozens, Philip Crosbie, Sabina Dizdarevic, Rosemary Eaton, Kathrin Eichhorst, Anthony Frew, Fergus Gleeson, Ashley Groves, Sai Han, Jeremy Jones, Osie Kankam, Kavitasagary Karunasaagarar, Lutfi Kurban, Louisa Little, Jackie Madden, Clare McClement, Ken Miles, Patricia Moate, Charles Peebles, Lucy Pike, Fat-Wui Poon, Donald Sinclair, Andrew Shah, Luke Vale, Steve George, Richard Riley, Andrea Lodge, John Buscombe, Theresa Green, Amanda Stone, Neal Navani, Robert Shortman, Gabriella Azzopardi, Sarah Doffman, Janice Bush, Jane Lyttle, Kenneth Jacob, Joris van der Horst, Joseph Sarvesvaran, Barbara McLaren, Lesley Gomersall, Ravi Sharma, Kathleen Collie, Steve O'Hickey, Jayne Tyler, Sue King, John O'Brien, Rajiv Srivastava, Hugh Lloyd-Jones, Sandra Beech, Andrew Scarsbrook, Victoria Ashford-Turner, Elaine Smith, Susan Mbale, Nick Adams, Gail Pottinger, J R Weir-McCall, S Harris, K A Miles, N R Qureshi, R C Rintoul, S Dizdarevic, L Pike, Heok K Cheow, Fiona J Gilbert, SPUtNIk investigators, Anindo Banerjee, Lucy Brindle, Matthew Callister, Andrew Clegg, Andrew Cook, Kelly Cozens, Philip Crosbie, Sabina Dizdarevic, Rosemary Eaton, Kathrin Eichhorst, Anthony Frew, Fergus Gleeson, Ashley Groves, Sai Han, Jeremy Jones, Osie Kankam, Kavitasagary Karunasaagarar, Lutfi Kurban, Louisa Little, Jackie Madden, Clare McClement, Ken Miles, Patricia Moate, Charles Peebles, Lucy Pike, Fat-Wui Poon, Donald Sinclair, Andrew Shah, Luke Vale, Steve George, Richard Riley, Andrea Lodge, John Buscombe, Theresa Green, Amanda Stone, Neal Navani, Robert Shortman, Gabriella Azzopardi, Sarah Doffman, Janice Bush, Jane Lyttle, Kenneth Jacob, Joris van der Horst, Joseph Sarvesvaran, Barbara McLaren, Lesley Gomersall, Ravi Sharma, Kathleen Collie, Steve O'Hickey, Jayne Tyler, Sue King, John O'Brien, Rajiv Srivastava, Hugh Lloyd-Jones, Sandra Beech, Andrew Scarsbrook, Victoria Ashford-Turner, Elaine Smith, Susan Mbale, Nick Adams, Gail Pottinger

Abstract

Purpose: To compare qualitative and semi-quantitative PET/CT criteria, and the impact of nodule size on the diagnosis of solitary pulmonary nodules in a prospective multicentre trial.

Methods: Patients with an SPN on CT ≥ 8 and ≤ 30 mm were recruited to the SPUTNIK trial at 16 sites accredited by the UK PET Core Lab. Qualitative assessment used a five-point ordinal PET-grade compared to the mediastinal blood pool, and a combined PET/CT grade using the CT features. Semi-quantitative measures included SUVmax of the nodule, and as an uptake ratio to the mediastinal blood pool (SURBLOOD) or liver (SURLIVER). The endpoints were diagnosis of lung cancer via biopsy/histology or completion of 2-year follow-up. Impact of nodule size was analysed by comparison between nodule size tertiles.

Results: Three hundred fifty-five participants completed PET/CT and 2-year follow-up, with 59% (209/355) malignant nodules. The AUCs of the three techniques were SUVmax 0.87 (95% CI 0.83;0.91); SURBLOOD 0.87 (95% CI 0.83; 0.91, p = 0.30 versus SUVmax); and SURLIVER 0.87 (95% CI 0.83; 0.91, p = 0.09 vs. SUVmax). The AUCs for all techniques remained stable across size tertiles (p > 0.1 for difference), although the optimal diagnostic threshold varied by size. For nodules < 12 mm, an SUVmax of 1.75 or visual uptake equal to the mediastinum yielded the highest accuracy. For nodules > 16 mm, an SUVmax ≥ 3.6 or visual PET uptake greater than the mediastinum was the most accurate.

Conclusion: In this multicentre trial, SUVmax was the most accurate technique for the diagnosis of solitary pulmonary nodules. Diagnostic thresholds should be altered according to nodule size.

Trial registration: ISRCTN - ISRCTN30784948. ClinicalTrials.gov - NCT02013063.

Keywords: Cost-effectiveness; DCE-CT; Diagnostic accuracy trial; Diagnostic imaging; Lung cancer; PET/CT; Solitary pulmonary nodule (SPN).

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
STARD flow diagram of the study recruitment and follow-up. CT—computed tomography; DCE-CT—dynamic contrast enhanced computed tomography; PET—positron emission tomography
Fig. 2
Fig. 2
Receiver operator characteristic curve for the diagnosis of malignancy by SUVmax, SURBLOOD, SURLIVER and PET grade
Fig. 3
Fig. 3
Box and whisker plot of SUVmax by nodule size tertile and malignancy status. B = Benign, M = Malignant. Thick central band = median; upper and lower bound of box = 75th and 25th centiles respectively, whiskers reflecting upper and lower limits, with dots reflecting outliers

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