Clinical trial NCT02013063: Single Pulmonary Nodule Investigation
Official title: Accuracy and Cost-Effectiveness of Dynamic Contrast Enhanced Computed Tomography in the Characterisation of Solitary Pulmonary Nodules
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Malignant Neoplasm of Lung
Keywords: Single Pulmonary Nodule
SPN
Lung cancer
Diagnostic
Computed Tomography
CT scan
FDG-PET scan
Dynamic CT scan
DCE-CT scan
Dynamic contrast enhanced CT scan
soft tissue solitary dominant
≥ 8mm and ≤30mm
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University of Southampton
name: Brighton and Sussex University Hospitals NHS Trust
name: University College London Hospitals
name: Oxford University Hospitals NHS Trust
name: Papworth Hospital NHS Foundation Trust
name: The Leeds Teaching Hospitals NHS Trust
name: Manchester University NHS Foundation Trust
name: East and North Hertfordshire NHS Trust
name: NHS Grampian
name: NHS Greater Glasgow and Clyde
name: Western Sussex Hospitals NHS Trust
First posted: 2013-12-17
Enrollment: 375
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Hospital Chest Clinics PET referal centres

Brief summary: 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

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

Eligibility criteria: 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)

Primary outcomes:
measure: Effectiveness of DCE-CT scans and FDG-PET scans to diagnose early lung cancer in SPN
timeFrame: 2 years
measure: cost effectiveness of using DCE-CT scans in the diagnosis of early lung cancer in SPN
timeFrame: 2 years
Secondary outcomes:
measure: Effectiveness of DCE-CT scans combined with FDG-PET scans to diagnose early lung cancer in SPN
timeFrame: 2 years
measure: 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
timeFrame: 2 years
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals Nhs Trust
state: Hampshire
city: Worthing
country: United Kingdom
facility: Western Sussex Hospitals NHS Foundation Trust
state: Sussex
city: Aberdeen
country: United Kingdom
facility: NHS Grampian
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals Nhs Trust
city: Cambridge
country: United Kingdom
facility: Papworth Hospital Nhs Foundation Trust
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals Nhs Trust
city: London
country: United Kingdom
facility: University College London Hospitals Nhs Foundation Trust
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester Nhs Foundation Trust
Study officials:
affiliation: University of Southampton
name: Steve George, MD,FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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. 2022 Oct;77(10):988-996. doi: 10.1136/thoraxjnl-2021-216948. Epub 2021 Dec 9.
citation: 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.