Diagnosing peRipheral Lung Lesions With CRYO Biopsies

Background:

Lung cancer is currently the leading cause of cancer related deaths world-wide \[1\]. Approximately 5000 people are diagnosed with lung cancer each year in Denmark \[2\]. Lung cancer is often detected in late stages of the disease, which are rarely curable and have a poor prognosis \[3\]. Currently, early stages of lung cancer are often detected incidentally on a computed tomography (CT) scan as a solitary lung lesion \[4\]. Screening for lung cancer has the possibility to reduce lung cancer mortality, however a screening program will produce a large increase in CT scans with lung lesions \[5, 6\]. Tissue sampling is one of the corner stones for correctly diagnosing cancer in a patient. Obtaining tissue from the lungs is challenging since the lungs are difficult to access and biopsies comes with risk of complications.

Tissue samples can be acquired either by removing part of the lung surgically, by performing a needle biopsy through the chest wall or by using a bronchoscope (i.e. by endoscopy)-. The latter has the lowest risk of complications, but currently the diagnostic yield is lower than the other two methods. The low risk profile is an advantage in an increasing elderly population, where improvements in the diagnostic capabilities would be of great value to the patients.

Cryo freezing probes enable sampling from the lung parenchyma by freezing a small tissue area which is then extracted via the bronchoscope. The technology was initially invented to provide larger tissue samples for the diagnosis of interstitial lung disease, but may also be of great value for collecting tissue from cancerous disease since cryo biopsies are generally larger and less crushed than traditional biopsies.

Few studies regarding cryo biopsy for sampling cancer in the lungs exists, however initial trials demonstrates higher diagnostic yield and an increase in sufficient material for tumor marker analysis\[9, 10\].

Hypothesis:

1. Larger biopsies (i.e., cryo biopsies) will increase the diagnostic yield by allowing for sub-optimal sampling position 2. Cryo biopsies are larger and less crushed than forceps biopsies and could therefore increase benign yield to rule out cancer in patients with cancer suspected lesions 3. Using the 1.1 freezing probe for diagnosing malignancy is safe and feasible under conscious sedation.

Objectives:

1. Compare the diagnostic yield of cryo biopsies with forceps biopsies in lesions suspected of malignancy 2. Compare the benign yield/ malignant yield of cryo biopsies with forceps biopsies 3. Compare the number of samples with sufficient material for Next Generation Sequencing (NGS) testing 4. Assess the safety of using the 1.1 mm freezing probe without general anesthesia, tracheal tube or endobronchial blocker. 5. Develop a grading system for endoscopic biopsies to ensure standardized and reproducible assessment.

Method:

This study will be conducted as a randomized clinical trial according to CONSORT guidelines (multicenter) study at Center for Lung Cancer at Odense University Hospital, Bispebjerg Hospital, and Næstved Hospital in collaboration with the Department of Pathology at Odense University Hospital \[11\] .

• Malignant yield [Time frame: One year after initial study procedure]
• Benign yield [Time frame: One year after initial study procedure]
• NGS testing [Time frame: One week after initial study procedure]
• Complications [Time frame: One week after bronchoscopy]
• Serious procedure complications [Time frame: One week after bronchoscopy]
• Feasibility of procedure [Time frame: Same day as the study procedure]
• tissue grading score [Time frame: One week after initial study procedure]