Single Pulmonary Nodule Investigation (SPUtNIk)

Accuracy and Cost-Effectiveness of Dynamic Contrast Enhanced Computed Tomography in the Characterisation of Solitary Pulmonary Nodules

A small proportion of patients with lung cancer present with a solitary pulmonary nodule (SPN). This is an important group of patients because if it is lung cancer, presentation as a SPN represents early disease, which following surgery has a high 5 year survival rate. However as not all SPNs are lung cancer it would be unethical to biopsy every case. Clinical guidelines recommend that SPNs should undergo an initial (FDG)-PET/CT scan, which may give more information about the SPN and may indicate if it is likely to be lung cancer. However in many cases it does not and current practice is to monitor the SPN with a series of CT scans over 2 years to look for changes or growth which may/ but not always indicate lung cancer. If no changes are observed over 2 years the SPN is considered not lung cancer. This is both expensive for the National Health Service (NHS) and worrying for the patient in terms of monitoring CT costs and delayed treatment due to length of time to diagnosis.

This study examines the diagnostic capacity of using a different CT scan. Dynamic Contrast Enhanced -CT(DCE-CT). DCE-CT and FDG-PET/CT scans give different information about the SPN and the investigators will look to see if information from either scan or combined information from both scans may be better in the diagnosis of early stage lung cancer. The investigators will also undertake a review of previous studies that have used these scans and use data from both the review and the trial to look at the cost effectiveness of using DCE-CT in the diagnosis of SPN.

The trial will recruit 375 people who have a SPN detected by a normal CT scan which requires a FDG-PET/CT scan. In addition they will receive a DCE-CT scan either on the same day or within three weeks of the FDG-PET/CT scan. This is the only extra procedure that will take place to normal NHS care, however we will collect clinical and outcome data over the next two years.

The study is coordinated by Southampton University clinical trials unit. Recruitment between January 2013 - April 2016, from up to 14 UK sites. Data analysis and conclusions are expected by the end of 2018.

The study is funded by the NIHR-HTA

Study Overview

• Status: Unknown
• Conditions: Malignant Neoplasm of Lung

Detailed Description

Indication: Lung Cancer

Primary Objectives:

• To determine with high precision, the diagnostic performances of DCE-CT and 18FDG-PET/CT in the NHS for the characterisation of solitary pulmonary nodules (SPNs).
• To use decision analytic modelling to assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs.

Secondary Objectives:

• To assess, within an NHS setting, the incremental value of incorporating the CT appearances of a SPN into the interpretation of integrated PET/CT examinations.
• To assess whether combining DCE-CT with 18FDG-PET/CT is more accurate and/or cost-effective, in the characterisation of SPNs, than either test used alone or in series.
• To document the nature and incidence of incidental extra-thoracic findings on 18FDG-PET/CT undertaken for the characterisation of SPNs and model their impact on cost-effectiveness.

Rationale:

A small proportion of patients with lung cancer present with a solitary pulmonary nodule (SPN) on diagnostic imaging tests. This is an important group of patients because presentation as a SPN represents early disease with high 5 year survival rates following surgical resection. However, not all SPNs are due to lung cancer and the accurate characterisation of SPNs for diagnosis of early stage lung cancer is a diagnostic challenge with significant associated health costs.

Widely adopted clinical guidelines for the subsequent investigation of SPNs recommend serial CT scans to look for subsequent growth with biopsy to confirm diagnosis. UK, National Institute for Health and Clinical Excellence (NICE) guidelines recommend 18FDG-PET for the assessment of SPN in cases where a biopsy is not possible or has failed.

DCE-CT and 18FDG-PET scans give different information about the SPN. Information from either scan or combined information from both scans may be better in the diagnosis of early stage lung cancer.

Trial Design: Prospective Observational

Sample size: 375

Non-CTIMP:Non interventional trial

Concomitant Therapy: As per local practice

Primary Trial Endpoints:

Primary outcome measures will include diagnostic test characteristics (sensitivity, specificity, accuracy) for 18FDG-PET/CT and DCE-CT in relation to a subsequent clinical diagnosis of lung cancer. The outcome measures used in the economic model will include accuracy, estimated life expectancy, and quality adjusted life years (QALYs). Costs will be estimated from an NHS perspective. Incremental cost-effectiveness ratios will compare management strategies with DCE-CT to strategies without DCE-CT.

Secondary Trial Endpoints:

Secondary outcome measures will include diagnostic test characteristics for 18FDG-PET/CT with incorporation of CT appearances and combined DCE-CT/18FDG-PET. The incidence of incidental extra-thoracic findings on 18FDG-PET/CT, subsequent investigations and costs will also be determined.

Total Number of Sites: up to 14

• Study Type: Observational
• Enrollment (Anticipated): 375

Contacts and Locations

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Recruiting
    • NHS Grampian
    • Principal Investigator: Lesley Gomersall, MD
  • Brighton, United Kingdom, BN2 5BE
    • Recruiting
    • Brighton and Sussex University Hospitals NHS Trust
    • Principal Investigator: Sabina Dr Dizdarevic, MD
  • Cambridge, United Kingdom, CB23 3RE
    • Recruiting
    • Papworth Hospital NHS Foundation Trust
    • Principal Investigator: Nagmi Dr Qureshi, M.B.
  • Glasgow, United Kingdom, G116NT
    • Recruiting
    • NHS Greater Glasgow and Clyde
    • Principal Investigator: Sai Han, MBChB
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • Leeds Teaching Hospitals NHS Trust
    • Principal Investigator: Mathhew Dr Callister, BM PhD
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • University College London Hospitals Nhs Foundation Trust
    • Principal Investigator: Ashley Dr Groves, MBBS
  • Manchester, United Kingdom, M23 9LT
    • Recruiting
    • University Hospital of South Manchester NHS Foundation Trust
    • Principal Investigator: Philip Dr Crosbie, PhD
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Recruiting
      • Southampton University Hospitals NHS Trust
      • Principal Investigator: Anindo Dr Banerjee, PhD
  • Sussex
    • Worthing, Sussex, United Kingdom, BN112DH
      • Recruiting
      • Western Sussex Hospitals NHS Foundation Trust
      • Contact: Nick Adams, MD FRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Hospital Chest Clinics PET referal centres

Description

Inclusion Criteria:

• A soft tissue solitary dominant pulmonary nodule of ≥ 8mm and ≤30mm on axial plane

  • Measured on lung window using conventional CT scan
  • No other ancillary evidence strongly indicative of malignancy (e.g. distant metastases or unequivocal local invasion).
• If clinicians and reporting radiologists believe the patient is being treated as having a single pulmonary nodule and there are other small lesions <4mm that would normally be disregarded, the patient should be included in the trial.
• Nodules already under surveillance can be included provided they have a recent or scheduled FDG-PET/CT18 years of age or over at time of providing consent
• Able and willing to consent to study

Exclusion Criteria:

• Pregnancy
• History of malignancy within the past 2 years
• Confirmed aetiology of the nodule at the time of qualifying CT scan - As this is a diagnostic study, should the aetiology of the nodule be confirmed by investigation such as FDG-PET/CT or bronchoscopy prior to consent the patient remains eligible as the intention to include is made on the analysis of the qualifying CT scan.
• Biopsy of nodule prior to DCE-CT scan
• Contra-indication to potential radiotherapy or surgery
• Contra indication to scans (assessed by local procedures)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of DCE-CT scans and FDG-PET scans to diagnose early lung cancer in SPN	Primary outcome measures will include diagnostic test characteristics (sensitivity, specificity, accuracy) for 18FDG-PET/CT and DCE-CT in relation to a subsequent clinical diagnosis of lung cancer.	2 years
cost effectiveness of using DCE-CT scans in the diagnosis of early lung cancer in SPN	The outcome measures used in the economic model will include accuracy, estimated life expectancy, and quality adjusted life years (QALYs). Costs will be estimated from an NHS perspective. Incremental cost-effectiveness ratios will compare management strategies with DCE-CT to strategies without DCE-CT.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of DCE-CT scans combined with FDG-PET scans to diagnose early lung cancer in SPN	Diagnostic test characteristics combined DCE-CT/18FDG-PET in relation to a subsequent clinical diagnosis of lung cancer.	2 years
Effectiveness of using analysis of the CT image from the FDG-PET/CT in conjunction with data from the FDG incorporation to diagnose early lung cancer in SPN	Diagnostic test characteristics for 18FDG-PET/CT with incorporation of CT appearances in relation to a subsequent clinical diagnosis of lung cancer.	2 years

Collaborators and Investigators

• Sponsor: University Hospital Southampton NHS Foundation Trust
• Collaborators: University College London Hospitals; The Leeds Teaching Hospitals NHS Trust; University of Southampton; Manchester University NHS Foundation Trust; Brighton and Sussex University Hospitals NHS Trust; Papworth Hospital NHS Foundation Trust; East and North Hertfordshire NHS Trust; Oxford University Hospitals NHS Trust; NHS Greater Glasgow and Clyde; NHS Grampian; Western Sussex Hospitals NHS Trust
• Investigators: Principal Investigator: Steve George, MD,FRCP, University of Southampton

Publications and helpful links

General Publications

• Gilbert FJ, Harris S, Miles KA, Weir-McCall JR, Qureshi NR, Rintoul RC, Dizdarevic S, Pike L, Sinclair D, Shah A, Eaton R, Clegg A, Benedetto V, Hill JE, Cook A, Tzelis D, Vale L, Brindle L, Madden J, Cozens K, Little LA, Eichhorst K, Moate P, McClement C, Peebles C, Banerjee A, Han S, Poon FW, Groves AM, Kurban L, Frew AJ, Callister ME, Crosbie P, Gleeson FV, Karunasaagarar K, Kankam O, George S. Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules: the SPUtNIk diagnostic accuracy study and economic modelling. Health Technol Assess. 2022 Mar;26(17):1-180. doi: 10.3310/WCEI8321.
• Gilbert FJ, Harris S, Miles KA, Weir-McCall JR, Qureshi NR, Rintoul RC, Dizdarevic S, Pike L, Sinclair D, Shah A, Eaton R, Jones J, Clegg A, Benedetto V, Hill J, Cook A, Tzelis D, Vale L, Brindle L, Madden J, Cozens K, Little L, Eichhorst K, Moate P, McClement C, Peebles C, Banerjee A, Han S, Poon FW, Groves AM, Kurban L, Frew A, Callister MEJ, Crosbie PA, Gleeson FV, Karunasaagarar K, Kankam O, George S. Comparative accuracy and cost-effectiveness of dynamic contrast-enhanced CT and positron emission tomography in the characterisation of solitary pulmonary nodules. Thorax. 2021 Dec 9:thoraxjnl-2021-216948. doi: 10.1136/thoraxjnl-2021-216948. Online ahead of print.
• Weir-McCall JR, Harris S, Miles KA, Qureshi NR, Rintoul RC, Dizdarevic S, Pike L, Cheow HK, Gilbert FJ; SPUtNIk investigators. Impact of solitary pulmonary nodule size on qualitative and quantitative assessment using 18F-fluorodeoxyglucose PET/CT: the SPUTNIK trial. Eur J Nucl Med Mol Imaging. 2021 May;48(5):1560-1569. doi: 10.1007/s00259-020-05089-y. Epub 2020 Nov 1.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): October 1, 2018
• Study Completion (Anticipated): October 1, 2018

Study Registration Dates

• First Submitted: December 11, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 17, 2013

Study Record Updates

• Last Update Posted (Estimate): October 18, 2016
• Last Update Submitted That Met QC Criteria: October 17, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Lung cancer; Diagnostic; Computed Tomography; CT scan; Single Pulmonary Nodule; SPN; FDG-PET scan; Dynamic CT scan; DCE-CT scan; Dynamic contrast enhanced CT scan; soft tissue solitary dominant; ≥ 8mm and ≤30mm
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms; Lung Neoplasms; Multiple Pulmonary Nodules
• Other Study ID Numbers: RHM RAD0030; ISRCTN30784948 (Other Identifier: ISRCTN); project number 09/22/117 (Other Grant/Funding Number: NIHR-HTA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: there is no plan to share individual patient data