PET/CT-guided percutaneous biopsy of FDG-avid metastatic bone lesions in patients with advanced lung cancer: a safe and effective technique

Lung cancer has replaced liver cancer as the primary cause of death among patients with malignancies in China [8]. During the last three decades, the registered lung cancer mortality rate has increased by 464.84 %, which is a heavy burden on patients, health-care professionals, and society [8, 9]. The prognosis of patients with advanced lung cancer is poor, with a 5-year survival rate of 5 % or less. Recent developments in cancer genomics and molecular targeted therapy have caused a major paradigm shift in the management of advanced-stage lung cancer [10]. Precise staging of patients with lung cancer now plays a significant role in determining treatment strategy and prognosis. The accurate definition of tumour stage is a prerequisite for an individualized, risk-adapted therapy for lung cancer. Since ¹⁸F-FDG PET/CT combines the metabolic information of PET with the anatomic information of CT, it is of significant value in the diagnosis and staging of lung cancer patients [11]. An additional advantage is that it can be used for whole-body scanning with the potential to detect local and distant metastases in a single examination [12].

¹⁸F-FDG PET/CT has shown excellent diagnostic accuracy in the staging and restaging of a majority of malignant tumours including NSCLC, lymphoma, breast cancer, and liver cancer. When patients with an advanced-stage tumour are accurately staged using¹⁸F-FDG PET/CT, inappropriate surgery is avoided [13]. However, positive ¹⁸F-FDG PET/CT findings for distant disease also require pathological or radiological confirmation. Histological examination remains the “gold standard” for definitive diagnosis of lung nodules or lung metastasis. In order to obtain tissue for a histological diagnosis in patients with suspected lung cancer, CT-guided lung biopsy is commonly used [14]. But this invasive procedure is associated with the risk of complications including pain, haemoptysis (1 % to 10 %), pneumothorax (4 % to about 25 %), pneumothorax requiring a chest tube (1 % to about 4 %), air embolism, and atrial fibrillation [14‐18]. The elderly with poor pulmonary function are especially at risk of complications. Besides a biopsy of the primary focus, a biopsy of a lung metastasis can usually provide a diagnosis in lung cancer patients. Furthermore, any findings of distant disease can be confirmed by tissue biopsy to ensure accurate staging of the disease [19].

According to the 2015 NCCN guidelines regarding NSCLC, the choice of biopsy should be based on the clinical suspicion of lung cancer, location of the lesion, and patient preferences. Patients suspected of having a solitary site of metastasis should have the disease confirmed in tissue from that site, if feasible. If it is technically difficult or risky to biopsy a particular metastatic site, patients who may have multiple sites of metastatic disease should undergo biopsy of the primary lung lesion or mediastinal lymph nodes. The latest guidelines emphasize the importance of biopsying the site of metastasis as it is preferable to biopsy the pathology that would confer the highest stage (i.e. it is preferable to biopsy a suspected metastasis or mediastinal lymph node rather than a pulmonary lesion [20]).

The optimal puncture site should be selected on the basis of integrated factors, such as target location, optimal needle path and shortest skin-to-target distance. First, when selecting the target location, the most reliably identified focus should be selected. As mentioned above, selecting metastatic tumour rather than the primary lung tumour as the target location may minimize the occurrence of complications. Second, the optimal needle path is very important, because the biopsy process needs avoid nearby blood vessels, the spinal nerve trunk and vital organs. Third, selecting the shortest skin-to-target distance can simplify the biopsy procedure, save time and reduce pain. The aim of all these considerations is to ensure security, feasibility and effectiveness of the procedure. In general, biopsy of FDG-avid bone metastasis was found to meet all these factors simultaneously and it should be considered the best choice for obtaining tumour tissue.

PET imaging is frequently best performed before a diagnostic biopsy site is chosen in patients with a high clinical suspicion of aggressive, advanced-stage tumours. In contrast to a conventional CT-guided biopsy, ¹⁸F-FDG PET/CT guidance allows targeting of the metabolically active mass or the metabolically active portion of a mass [21]. This novel method can reduce the false-negative rate and is a relatively safe and effective way to obtain a pathological diagnosis. Transoesophageal endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high sensitivity and specificity for staging mediastinal and hilar lymph nodes in patients with NSCLC. EBUS-TBNA is of particular value for the biopsy of PET-positive hilar lymph nodes [20, 22].

Since lung cancer patients often have bone metastases, it is important to choose a hypermetabolic bone lesion that is suspected to be a metastasis from lung cancer as the biopsy target after the whole-body ¹⁸F-FDG PET/CT scan. In the current study, 51 patients underwent PET/CT-guided percutaneous biopsy of ¹⁸F-FDG-avid metastatic bone lesions. Bone metastases from lung cancer were confirmed pathologically in 48 of the 51 patients, and of the other three patients two were diagnosed as having NHL and one metastatic RCC. Even though two patients underwent a second biopsy since the pathological diagnosis was unclear from the first biopsy, the overall sensitivity was 100 % with a 100 % success rate. In all the patients in this study, the bone biopsy was successful, i.e. the biopsy needle was positioned correctly in the lesion of interest, and a clinically useful histological result was obtained in all 51 patients. Compared with biopsy of pulmonary nodules, bone biopsy avoids hazardous complications such as haemoptysis and pneumothorax. Despite a small amount of bleeding and pain, most patients tolerated the procedure well. Thus, this biopsy method is safe, effective, and feasible as it minimizes the risks while ensuring that an adequate amount of tissue is obtained.

An adequate amount of tissue is required for molecular diagnosis (EGFR or ALK mutation testing), which plays an important role in the treatment of advanced NSCLC [23]. Conventional methods for obtaining tissue samples such as CT-guided fine needle aspiration, bronchoalveolar aspirate, bronchial alveolar lavage or sampling of pleural effusions provide insufficient material for molecular analysis in a significant proportion of patients [23]. Targeted therapy is of significant value in patients with unresectable lung cancer. EGFR inhibitors, such as erlotinib and gefitinib, are of significant benefit in EGFR mutation-positive malignancies, which are primarily adenocarcinomas [24].

In our study, all lung cancer samples were sufficient to perform H&E staining or immunohistochemical tests. EGFR mutation status was determined in 23 of the 51 biopsies of bone metastases, and the total mutation rate was 30.4 % (7/23). ALK mutation status was determined in 19 biopsies, and the mutation rate was 31.6 % (6/19). Molecular testing of the biopsies from the remaining lung cancer patients was not performed due to lack of funds or the subsequent cost of the targeted treatment. The three other patients had either NHL or metastatic RCC.

In summary, PET/CT-guided biopsy of bone tissue solved the problem of insufficient tissue obtained on biopsy. Our samples from PET/CT-guided biopsy were ample for our needs and enabled us to do more studies with less tissue, i.e. the adequate amount of tissue obtained guaranteed a successful molecular test result.