Title: Randomised controlled trial to compare the diagnostic yield of Positron Emission Tomography Computerised Tomography (PET-CT) guided pleural biopsy versus CT-guided pleural biopsy in suspected pleural malignancy. (PET-biopsy trial)
Funder: Department of Health and Social Care

Abstract: Background Asbestos was a commonly used material in the building industry in the 1950s. Due to the unknown deleterious effects to humans from asbestos exposure, it was used without any health and safety protection at the time. There was an increasing emergence of lung disease that was later found to be attributable to asbestos exposure. Malignant pleural mesothelioma is cancer of the lung lining occurring as a consequence of asbestos exposure. It is an aggressive and fatal tumour that is still on the increase in many parts of the world. Due to its long latency period from exposure, patients may not develop mesothelioma up to 30 to 40 years from exposure. Unfortunately, once diagnosed the average life expectancy is 9 to 15 months, as no curative treatments are available for mesothelioma. Diagnosis of mesothelioma can be challenging in the absence of pleural fluid (fluid in the chest cavity), to perform a thoracoscopy for direct visualisation and biopsy of the pleura. Computed Tomography (CT) or Ultrasound (US) guided biopsy of the pleura are two of the commonest techniques used in this situation but the diagnostic rate is low. Diagnostic imaging in pleural malignancy remains a significant challenge. PET scanning has proved itself a useful tool in diagnosing and staging lung cancer. It identifies areas of high metabolic activity, which is a feature of malignant disease, by highlighting areas of uptake of the radio labelled glucose analogue Fluorodeoxyglucose (FDG). We hypothesise that targeting the CT guided biopsy to these highlighted areas on PET may increase the diagnostic yield. Aims This study will assess whether a PET-CT guided biopsy is superior to a standard CT guided biopsy when obtaining pleural tissue in suspected pleural malignancy, in patients who have already undergone one non-diagnostic pleural biopsy. At present there are no studies comparing the two approaches. Pilot data from our institution has shown a 66% sensitivity with PET for repeat biopsies as opposed to 20% sensitivity with a repeat CT guided biopsy. Plan of investigation This multi-centre randomised controlled study will recruit patients from 6 respiratory departments over a 24 month period or until 78 patients have been recruited. Patients will be randomised either to receive a PET targeted biopsy or a standard CT guided biopsy using an online randomisation tool provided by the Bristol Clinical Trial Evaluation Unit (CTEU). The experimental group will undergo a PET scan which will be reviewed by a local radiologist to identify the most suitable area for biopsy, then a CT guided biopsy targeted to the afore highlighted area. The standard CT group will have a repeat CT and a biopsy from a site identified as per the local radiologist. Standard Operating Procedures (SOP) will be in place to minimise variation. The diagnostic yield for the two biopsy methods in identifying malignancy will be compared using the chi-squared test for proportions. Final analysis will occur once all recruited patients have undergone a second pleural biopsy and a tissue diagnosis confirmed or 12 months follow-up occurred. Potential impact If this superiority study is proven successful, it would shorten the patient s cancer journey and reduce the number of invasive investigations they undergo. An early diagnosis may allow more patients to have life prolonging chemotherapy that they may not be able to have at a later stage in disease if they are too unwell. Mesothelioma patients have a very poor survival and often some of this time may be spent in hospital. An early diagnosis would allow patients more time to enjoy the financial benefits of the compensations they receive following a diagnosis of mesothelioma.

Lay abstract: Many patients with a history of asbestos exposure can develop irregular thickening of the lung lining (the pleura). Although in many cases the pleural thickening is not serious a small proportion of patients can develop cancer of the lung lining (mesothelioma). Chest X-rays and CT (computed tomography) scans of these patients can indicate a suspicion of mesothelioma but the only way to confirm the diagnosis is by obtaining a sample of the lung lining and examining the cells. Unfortunately, in a subgroup of patients, it can take a considerable time to confirm the diagnosis of mesothelioma with a tissue sample. This is due to the difficulty of obtaining a sample containing cancerous cells in some patients. These patients will often require repeated samples to be taken until a definitive diagnosis can be made. A rapid diagnosis is important as, although mesothelioma is incurable, life-extending treatments started early can be effective and diagnosis allows patients with confirmed mesothelioma to apply for compensation. Currently, pleural tissue samples are taken with guidance from a CT scan of the lungs. We believe that another type of scan (Positron Emission Tomography 'PET scan' is a whole body scan where radio-labelled glucose is taken up more avidly by cancerous cells) may be better at identifying the location of the cancerous tissue allowing a more targeted biopsy to occur, thus improving the diagnostic accuracy. PET scanners are expensive and in high demand so good evidence is required before they can be used routinely for this purpose. This study aims to determine how effective PET-scan targeted tissue sampling is compared to the conventional CT targeted sampling in patients requiring a second biopsy. We intend to conduct a clinical study comparing the results in two groups of patients who have been randomly allocated to one or the other method.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS