Oxford Pleural Embolisation Trial

Background and existing literature Image guided thermal ablation is an established treatment for lung malignancy including early stage primary cancer and oligometastases. It is a minimally invasive technique associated with rapid clinical recovery and its efficacy and safety are comparable to surgical resection and radiotherapy. It is also repeatable and feasible for patients contraindicated to other therapies, such as those with impaired lung function or interstitial fibrosis.

One of the most common side effects of lung ablation is pneumothorax, occurring in up to 67% of patients depending on definition. Clinically significant pneumothorax, typically defined as requiring perioperative insertion of chest drain, occurs in up to 58% of patients. In a local audit at Oxford University Hospitals last year, 31.7% of lung ablation patients required a chest drain.

Pleural or parenchymal tract embolisation using autologous blood (pleural blood patch/ PBP) is a recognized technique in pneumothorax prevention in image guided lung biopsies. In a meta-analysis including more than 4000 patients, drawing on mainly retrospective studies, this reduces the risk of pneumothorax by 35% and risks of chest drain by 55%.

A study using prophylactic gelfoam torpedo embolisation for radiofrequency ablation showed significant reduction in chest drain rates.

Rationale and necessity of the OxPET trial

A literature search demonstrates lack of any study examining the prophylactic use of PBP in lung ablation. There are important differences between lung biopsy and ablation that dedicated evaluation rather than direct extrapolation of results:

1. The ablation applicator is larger (at least 16G) than the biopsy needle (usually 20G).
2. The PBP technique in biopsies employ a coaxial technique which involves injection of blood along the same needle after the sample has been taken, which is not possible for ablations.
3. Ablation causes damage not just along the needle tract but a zone of destruction by thermal energy, which may render PBP ineffective.
4. Existing study using gelfoam torpedoes studied patients undergoing radiofrequency ablation and in coaxial application of embolisation agent. The majority of cases performed in OUH are with microwave technology and non coaxial application.
5. Lung ablations are performed under general anaesthesia and ventilation whereas biopsies are performed with local anaesthesia and this may cause a difference in pneumothorax formation.

The tandem needle technique is modified for PBP in the setting of ablation. This involves intraoperative CT guided insertion of a 21G needle to a position within 5mm of the parietal pleural entry of the ablation applicator. This is followed by autologous blood injection upon withdrawal of the ablation applicator. This has been evaluated clinically in selected patients at high risk of pneumothorax at OUH with promising preliminary results. We plan to publish the data as a pilot study of OxPET.

The investigation is performed at the Oxford Thermal Ablation Service, a tertiary centre performing around 200 ablations a year.

Potential clinical impact The potential clinical impact of this study is highly significant. At OUH, lung ablations are inpatient procedures requiring overnight stay, with planned discharge on the subsequent morning. Patients who require a perioperative chest drain will attempt weaning the next day, and a significant portion will fail and thus prolong discharge. A further 3.5% of patients develop drain-related complications requiring invasive management such as infection, empyema and persistent air leak, requiring further invasive management.

Significant reduction in pneumothorax rates will reduce the rate of chest drain insertion and its associated morbidities, shorten patient stay and hasten recovery. Positive trial results may shift the clinical pathway of lung ablation into a day procedure, which is increasingly the case for ablation of other organs such as the kidney.

Safety profile The PBP technique is extremely safe and no negative effects have been identified in previous meta-analysis involving more than 4000 patients. The ablation procedure would induce variable degrees of haemorrhage per se, therefore patients undergoing PBP only differs in the amount and location that the patient's blood is distributed.

There are theoretical risks of introducing infection and pneumothorax during the PBP procedure. In our protocol, a strict aseptic technique is adopted both for blood taking and ablation/ PBP procedure. A sterile surgical field is maintained and it is routine clinical practice to give a dose of prophylactic antibiotics to all ablation patients. The development of infection (pleural or pulmonary) will be monitored in our study.

With regards to pneumothorax induced by the PBP procedure, this would be immediately detected and remedied (by chest drain insertion if appropriate) as the procedure is performed under CT scanning. This complication would be recorded within the safety outcome session of the trial.

The PBP procedure is also associated with a small additional radiation exposure (0.3mSv) to intervention arm patients. The annual background radiation dose in the UK is 2.7 mSv in comparison. This has been assessed by independent medical physics and clinical radiation expert at the local institution. Opinion of the physics expert is that the additional radiation for interventional trial participants would cause a \<0.01% increase in lifetime cancer risk. The opinion from the clinical radiation expert is that there is no increase in radiation exposure on a clinical level.