As no studies have investigated the use of NBCA for BAE in patients with haemoptysis from primary lung cancer, this retrospective study compared the safety and efficacy of BAE performed using NBCA and PVA particles in patients with primary lung cancer. In this retrospective cohort, BAE using NBCA showed superior initial hemostasis (P = 0.002) with longer HFS (P < 0.001), shorter procedure time (P < 0.001), and reduced radiation dose (P < 0.001) than that using PVA particles. The use of PVA and the presence of coagulopathy were independent predictors of recurrent haemoptysis.
Compared with the clinical outcomes of BAE for benign diseases, those for lung malignancy are low (58.3%–89%); recurrence rates are also higher (20%–75%) [2, 5, 6, 10,11,12, 19]. Thus, BAE is considered a second-line option in lung cancer when bronchoscopy or conservative treatment is of limited efficacy [20]. Differences in the pathogenesis of haemoptysis may explain this discrepancy. In benign diseases, chronic inflammation or longstanding pulmonary ischaemia cause enlargement of the bronchial arteries [1, 7, 21]. Thus, cardiac output to the bronchial arteries can increase by up to 30% [22]. However, lung malignancy is characterised by fine neovascularisation in and adjacent to the neoplasm, tumour necrosis without a hypervascular environment, and early recruitment of feeders due to tumour angiogenesis [20, 23]. Tumour-feeding arteries are generally small, multiple, and have slow flow [4, 24]. Therefore, new embolic materials are required to overcome these limitations.
In this study, NBCA was superior to PVA in terms of immediate haemostasis (81.0% vs. 53.1%, P = 0.002). NBCA is semifluid, enabling advancement into small vessels to achieve complete occlusion [1, 3, 7]. The penetration of NBCA can be controlled according to the size and flow rate of target vessels by adjusting the mixing ratio of NBCA and lipiodol. PVA particles can easily aggregate, possibly resulting in incomplete embolisation proximal to the intended level [3]; appropriate delivery can be challenging owing to the unique target vessel characteristics in lung cancer that include multiple fine feeders with slow flow rates.
HFS was longer in the NBCA group than in the PVA group (median survival, 176.0 vs. 16.5 days; P < 0.001). Multivariable analysis also revealed that the use of PVA was an independent risk factor for haemoptysis recurrence (adjusted hazard ratio 3.452, confidence interval 1.994–5.974; P < 0.001). Most recurrent haemoptysis cases in the PVA group (81.8%) occurred within 1 month after BAE, suggesting that recanalisation is the primary mechanism of rebleeding in the PVA group [7]. Studies have consistently reported the occurrence of recanalisation after BAE using PVA [1, 7, 25, 26]. As intravascular polymerisation of NBCA inhibits recanalisation, the more durable embolic effect of NBCA may explain the superior long-term outcomes.
Coagulopathy is a well-known cause of haemoptysis [10, 27, 28]. Cancer-associated coagulopathy often occurs in lung cancer, and the consumption of platelets and clotting factors can induce life-threatening haemorrhage such as pulmonary bleeding [29]. In coagulopathic conditions, particulate embolisation is less likely to achieve complete haemostasis [30]. Studies on uterine artery embolisation for patients with coagulopathy showed superior durability of NBCA over PVA or gelatin sponge particles [31, 32]. These results may be attributed to the fact that polymerisation by NBCA is independent of the patients’ coagulation status [33]. Although not significant because of the small sample size, the hemostasis success rate in the NBCA group (four of six) was twice that of the PVA group (one of three) in coagulopathic patients.
The NBCA group had a 65% shorter procedure time and 75% less dose–area product than the PVA group. BAE procedures are time-consuming, as multiple feeding vessels must be selected and embolised completely to achieve a successful outcome. In addition, particulate embolisation requires continuous fluoroscopic monitoring of the injected particle/contrast mixture until complete embolisation is achieved. By contrast, the NBCA/lipiodol mixture is radio-opaque and quickly polymerises within a few seconds according to the mixing ratio. An operator can easily notice the exact extent of embolisation and determine the endpoint of the embolisation. No data regarding procedure time or radiation dose of BAE is available in the literature [2]; however, reducing the radiation dose to the patients and operators while maintaining clinical performance is mandatory [34]. Thus, the use of NBCA for BAE may have advantages over PVA in reducing procedure time and radiation exposure.
In this study, no grade 3–5 adverse events were observed in either group. There have been concerns that liquid embolic agents, such as NBCA, may increase the risk of non-target embolisation and tissue necrosis. A study performed a histological analysis of the lung lesion after BAE using NBCA [35]. The authors found that NBCA did not cause necrosis of the bronchial wall or lung parenchyma and only filled the lumen of the bronchial arteries. In this study, no patient experienced bronchial wall abnormalities or pulmonary infarction, which was confirmed on subsequent CT and/or bronchoscopy after BAE. However, the wedged position of the microcatheter tip hinders the antegrade flow of NBCA and may cause early backflow, possibly leading to unintended reflux of NBCA [3]. In addition, polymerised NBCA that adhered to the microcatheter tip could be a source of non-target embolisation [7]. Such complications were not observed in this study; however, care must be taken during the procedure using NBCA.
This study has several limitations. This was a single-centre retrospective study with inherent selection bias, and the embolic material was determined at the interventional radiologists’ discretion. However, the baseline characteristics, angiographic findings, and the number of embolised vessels were well balanced between the groups. Thus, randomised controlled trials are needed to validate the benefits of NBCA over conventional embolic agents. Moreover, the clinical outcomes of the PVA group were relatively poor (initial haemostasis rate: 53.1%) compared with those in previous studies (63%–77.5%) [5, 6, 12]. This may be explained by the finding that previous investigations included patients with malignancy and concomitant benign lung diseases. Many lung cancer patients may have benign diseases, causing haemoptysis and leading to an overestimation of BAE effects. Five patients with concomitant benign lung lesions in this study were excluded. Therefore, the actual results of BAE using PVA particles for haemoptysis in patients with primary lung cancer alone may be worse than those reported in previous studies. Lastly, although this study possibly had the largest cohort of this study type, the sample size was small.
Interpretation
BAE using NBCA in patients with primary lung cancer showed superior initial haemostasis with longer HFS, shorter procedure times, and reduced radiation dose than PVA particles. No significant complications were observed in both groups, and the use of PVA and the presence of coagulopathy were independent risk factors of shortened HFS.