Management of hemoptysis with bronchial artery embolization: Benign versus malignant indications

INTRODUCTION

Bronchial artery embolization (BAE) is an accepted treatment for the control of moderate-to-massive hemoptysis and has proven to be safe and efficacious.^[1-3] Viamonte was the first physician to perform a selective bronchial arteriogram in 1963, and Rémy et al. produced the first thorough description of embolization of the bronchial arteries for the treatment of hemoptysis in 1974.^[4,5] The most common indication for BAE world-wide is tuberculosis and post-tubercular inflammation.^[1] In the United States, benign conditions such as cystic fibrosis, bronchiectasis, sarcoidosis, and COPD are the most common indications for BAE.^[3]

Patients with lung cancer represent about 25% of those presenting with hemoptysis in the United States, and these patients have a high mortality rate without prompt treatment.^[6,7] Although the literature has not found a significant difference in the hemoptysis volume and imaging characteristics in patients with malignant or benign etiologies, the pathophysiology driving hemoptysis due to malignancy is unique and due to a combination of increased angiogenesis in addition to local necrosis and inflammation.^[8-12] The general approach to hemoptysis in patients with lung cancer is to secure and/or maintain an open airway, ensure hemodynamic stability, and further evaluate the underlying cause with subsequent bronchoscopy and/or computed tomography (CT).^[1,13] A variety of approaches have been studied in the palliation of hemoptysis, such as laser photocoagulation, endobronchial stenting, external radiotherapy, and BAE.^[1,14-16]

Although the safety and efficacy of BAE in patients with hemoptysis secondary to benign etiologies is well established, there is a relative paucity of data on outcomes in patients with hemoptysis due to underlying malignancy. The reported data on short- and long-term efficacy of BAE in patients with malignancy is variable, although several sources suggest poor outcomes in patients presenting with hemoptysis due to pulmonary neoplasm.^[17] In this study, we describe our experience with BAE, analyzing outcomes in patients with hemoptysis secondary to benign and malignant etiologies.

MATERIAL AND METHODS

Management of hemoptysis and technique of BAE

Patients presenting with hemoptysis were managed by an interdisciplinary subsection of interventional radiology, medicine, and surgery. The indication criteria for BAE and re-embolization are illustrated in [Figure 1].

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Figure 1:

Indication criteria for bronchial artery embolization and re-embolization.

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Before performing each procedure, the risks, benefits, and alternatives of BAE were discussed with the patient, and informed consent was obtained. Briefly, the patient was brought to the angiography suite, and the right groin was prepared for right common femoral artery access. A 5 French vascular sheath was placed over a wire under fluoroscopic guidance. Selective right common femoral arteriography was performed to confirm puncture site within the common femoral artery. A 5 French catheter was then advanced over a wire into the aorta, and selection of the bronchial arteries was performed. If bleeding had been localized by CT or bronchoscopy to a lung laterality, only the bronchial arteries supplying that lung were embolized. Selective angiography was then performed of the bronchial arteries with a microcatheter to confirm catheter position and identify hypervascularity, vascular irregularity, and the presence of contrast extravasation, if any. Selected arteries were then embolized until radiographic stasis was achieved.

RESULTS

Overall outcomes

There were 150 total BAE procedures performed over this period, with 114 procedures performed on 93 unique patients who had sufficiently documented hospital and procedural notes from which the variables for this study could be drawn. There were 80 procedures among 64 unique patients with benign indications and 34 procedures in 29 unique patients with malignant indications. Overall patient characteristics are summarized in [Table 1]. The mean age was 54.8 years (± 17.9 years), and 47 (50.5%) patients were female. Of the 114 procedures, 71 were preceded by bronchoscopy (62.3%), and 38 (33.3%) were followed by further bronchoscopic evaluation. Upon angiographic evaluation, two patients were found to have a pseudoaneurysm, one found to have an arteriovenous malformation, and three found to have an arterio-venous shunt. The majority of procedures used Embosphere^® microspheres as the embolization agent (68.4%), followed by coil (8.8%), polyvinyl alcohol (9.6%), and gel foam (3.5%) as the next most common embolization materials. The most common indications among individual patients for BAE within the benign and malignant groups were cystic fibrosis (16/64, 25%) and primary pulmonary malignancy (21/29, 72.4%), respectively. Patient and procedural details are summarized in [Tables 1 and 2].

Table 1: Summary of unique patient characteristics (unique patients, n=93).

Characteristics	All patients (n=93)	Benign (n=64)	Malignancy (n=29)	P-valuea (Benign vs. Malignant)
Mean age, years	54.8±17.9	53.6	57.4	0.364
Sex, n (%)
Male	46 (49.5)	29 (45.3)	17 (58.7)	0.234
Female	47 (50.5)	35 (54.7)	12 (41.3)	-
ASA Score	3.21	3.3	3.04	0.067
Indications, n (%)
Any pulmonary neoplasm	29 (31.2)	-	29 (100)	-
Primary pulmonary neoplasm	21 (22.6)	-	21 (72.4)	-
Metastatic lung malignancy	8 (8.6)	-	8 (27.6)	-
Cystic fibrosis	16 (17.2)	16 (25.0)	-	-
Pneumonia	9 (9.7)	9 (14.1)	-	-
Idiopathic	6 (6.5)	6 (9.4)	-	-
MAC	5 (5.4)	5 (7.8)	-	-
Tuberculosis	2 (2.2)	2 (3.1)	-	-
Aspergillosis	5 (5.4)	5 (7.8)	-	-
COPD	3 (3.2)	3 (4.7)	-	-
Vascular abnormality	2 (2.2)	2 (3.1)	-	-
Vasculitis	2 (2.2)	2 (3.1)	-	-
Coagulopathy/ITP	2 (2.2)	2 (3.1)	-	-
Berylliosis	1 (1.1)	1 (1.6)	-	-
Other	11 (11.8)	11 (17.2)	-	-
Overall clinical outcomes
Survival (days)	1074.8	1359.0	447.4	0.005
Overall mortality	51 (54.8)	31 (48.4)	20 (69.0)	0.065

^aPearson’s Chi²; Two-sample t-test, ASA: American society of anesthesiologists, ITP: Idiopathic thrombocytopenic purpura, MAC: Mycobacterium avium complex

Table 2: Procedure characteristics (procedures, n=114).

Procedure characteristic	All procedures (n=114)	Benign (n=80)	Malignancy (n=34)	P-valuea (Benign vs. Malignant)
Total # of arteries embolized**	181	140	41	0.009
Mean # of arteries embolized/procedure**	1.59	1.75	1.21	0.009
Radiation exposure/procedure
Fluoroscopy time (min) (mean)	30.8	30.9	30.5	0.936
Dose (440mGym)	889.1	784.5	1132.4	0.099
DAP (440uGym2)	7461.4	6325.3	10101	0.098
Embolization Material c, n (%)
Single embolization agent	90 (78.9)	66 (82.5)	23 (67.6)	0.080
Multiple embolization agents	20 (17.5)	12 (15.0)	8 (23.5)	0.287
None	4 (3.5)	1 (1.3)	3 (8.8)	0.044
Additional procedures, n (%)
Pre-procedure bronchoscopy	71 (62.3)	47 (58.8)	24 (70.6)	0.233
Post-procedure bronchoscopy	38 (33.3)	22 (27.5)	16 (47.1)	0.047
Post-procedure surgery	7 (6.1)	3 (3.8)	4 (11.8)	0.103
Clinical outcomes per procedure, n (%)
Technical success	105 (92.1)	74 (92.5)	31 (91.2)	0.811
Clinical success	91 (79.8)	66 (82.5)	25 (73.5)	0.275
ICU admission	73 (64.0)	47 (58.8)	26 (76.5)	0.071
30 day readmission	14 (12.3)	9 (11.3)	5 (14.7)	0.607
Mean length of stay (days)	23.2	19.3	32.3	0.373
bNeed for reembolization	23 (20.2)	18 (22.5)	5 (14.7)	0.343
bTime to reembolization (days)	679.5	861.3	25.0	0.160

^aPearson’s Chi²; Two-sample t-test, ^bRe-embolization analyzed for all procedures, ^cMore than one type per procedure may be used, DAP: Dose area product, ASA: American society of anesthesiologists physical status score, ICU: Intensive care unit

The overall technical and clinical success rates for the benign and malignant groups were 92.1% and 79.8%, respectively. The average length of stay after BAE was 23.2 ± 70.8 days. About 73.0% of all patients were admitted to the ICU, and 12.3% of the patients were readmitted to the hospital within 30 days of being discharged. About 20.2% of patients underwent re-embolization. Of those, 47.8% needed reembolization to the same artery. The mean follow-up time/ survival was 1074.8 ± 1471 days. The Kaplan–Meier survival and re-embolization-free survival curves are shown in [Figure 2]. There were two major adverse events in the entire cohort; one patient had a stroke following their BAE procedure, and another patient died intra-procedurally due to cardiac arrest.

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Figure 2:

(a) Kaplan–Meier Survival Curves. (a) overall survival; (b) overall re-embolization-free survival.

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DISCUSSION

The results of this study support the efficacy of BAE for malignant hemoptysis and provide a unique comparison of outcomes between patients with benign and malignant indications managed at the same institution. The overall technical (92.1%) and clinical (79.8%) success rates are within previously reported ranges for BAE for benign and malignant indications.^[1,10,18,19] The overall re-embolization rate of 20.2% in the present analysis also fell within previously reported values of ~20%, and malignant cases were not found to be at a higher risk of re-embolization relative to benign cases, unlike in other reported series.^[1,10,18] Technical (91.2%) and clinical (73.5%) success and re-embolization rates (14.7%) for the malignant group closely match previously published data on BAE in patients with malignant hemoptysis from Han et al.^[18] Chen et al. performed a similar study finding the overall clinical success rate to be 90.1%, with no significant differences between the malignant and benign groups.^[17]

The analysis identified several post-procedural outcome similarities between the two groups. There were no statistically significant differences in rates of technical success, clinical success, need for re-embolization, ICU admission, 30-day readmission, mean hospital length of stay, or mortality between benign and malignant groups [Table 2]. However, the difference in rate of ICU admission (58.8% vs. 76.5%, P = 0.07) may be interpreted as clinically significant, with lack of power likely accounting for lack of statistical significance. Similarly, a greater number of BAE procedures in the malignant cohort were followed by definitive treatment of hemoptysis in the form of surgery, though this difference did not come out to be statistically significant (3.7% vs. 1.8%, P = 0.10). BAE procedures indicated for a malignant cause of hemoptysis were also more likely to be followed by bronchoscopic evaluation (27.5% vs. 47.1%, P = 0.047), which were performed primarily for diagnostic evaluation and/or suction of remaining blood clots and secretions rather than for further therapeutic management of active hemoptysis. Altogether, the greater rates of ICU admission, post-procedure surgery, and post-procedure bronchoscopy among patients with malignancy suggest that hemoptysis due to malignancy may require additional immediate management in addition to BAE, expanding on Gershman et al.’s conclusion that diagnostic and treatment algorithms for hemoptysis of malignant versus non-malignant etiologies should be applied with care.^[13]

The observed survival time for patients with malignant hemoptysis is consistent with previously reported values.^[18,20,21] Cause of death in the present analysis for either group was not explored, though the decreased survival time in the malignant hemoptysis cohort was likely related to their underlying disease process.^[10] As expected, with regard to overall survival time, there was a significant difference of 911.6 days (1359 vs. 447.4 days, P = 0.005) between the benign and malignant groups, corresponding with an increase in overall mortality (48.4% vs. 69.0%, P = 0.07), which is a likely function of the underlying disease process. From the Kaplan– Meier survival curve, there was no short-term difference in mortality within 30 months post-procedure, suggesting no procedure-specific increase in mortality for patients with malignancy. Divergence in between 30 and 33 months is likely secondary to disease progression in the malignant group [Figure 2a]. Of the 14 patients with stage IV NSCLC, the median survival of patients post-BAE (5.7 months) is similar to the data reported in the literature of patients with stage IV NSCLC presenting with hemoptysis.^[22]

Further support for the efficacy of BAE in malignancy is demonstrated by the limited need for endovascular intervention in the form of re-embolization. As demonstrated in [Figure 2b], there was no statistically significant difference in re-embolization-free survival between the benign and malignant cohorts. Only one person with primary pulmonary malignancy required re-embolization of the same artery, comprising of only 4.3% of the cases of re-embolization in our study. Hemoptysis due to metastatic lung malignancy was more likely to undergo re-embolization compared to primary pulmonary neoplasms (33.3% vs. 4.5%). This finding is likely explained by multifocal tumor burden, as all four reinterventions (100%) due to metastatic malignancy were at different arteries, suggesting different tumor sites were being embolized per intervention.^[11] Patients who required re-embolization had similar overall mortality outcomes compared to patients who did not receive re-embolization (57.1% vs. 60.9%, P = 0.746).

Risk factors for re-embolization have been previously described, including presentation with massive hemoptysis, presence of a cavitary mass, and bronchial-pulmonary arterial shunts.^[9,18] Within this study, clinical success, defined as resolution of hemoptysis with no need for endovascular reintervention in the same hospital stay, was protective against all-cause mortality and re-embolization at any time during follow-up, while ASA score, primary pulmonary malignancy, and female sex were associated with significant risk of all-cause mortality. Age, technical success, and ICU admission status were not found to have a significant effect on the risk of death or re-embolization in our model. It is concerning that female sex status was associated with significantly higher risk of death and re-embolization in our study, and further studies are needed to understand the factors that potentially contribute to this disparity.

This retrospective study has multiple limitations, including the modest number of patients, the retrospective nature, and loss to follow-up. The limited number of patients, particularly among the malignant etiology group, reduced the statistical power of our analyses. Therefore, certain clinically significant outcomes, such as increased rates of ICU admission and post-BAE surgery among patients with malignancy, were not statistically significant. Data collection was ended before 2019 to reduce possible confounding caused by the SARS-CoV-2 pandemic, and future studies analyzing how COVID-19 impacted rates of hemoptysis are indicated. Another limitation of this study was that reembolization was used as an objective proxy for clinically significant recurrent hemoptysis, which does not accurately reflect cases in which re-embolization was not indicated despite recurrent hemoptysis. In addition, detailed staging data on all malignant cases were not available, so there may be variable outcomes for different stages of pulmonary malignancy. The exact degree of hemoptysis at presentation was similarly not included, preventing this study from being able to assess differences between major and minor hemoptysis. Furthermore, not all patients had follow-up data available beyond 1 year.

CONCLUSION

Analysis of outcomes after BAE performed in patients with hemoptysis due to various benign and malignant conditions suggests it is a safe and effective technique. There were no differences in periprocedural survival, technical success, clinical success, need for re-embolization, 30-day readmission, or mean hospital length of stay when BAE is performed for a benign or malignant indication. Endovascular intervention in the form of BAE for malignancy appears to be effective as seen by the limited requirement for re-embolization of the same artery and lack of statistically significant difference in re-embolization-free survival. As expected, patients presenting with hemoptysis due to malignancy undergo post-procedural bronchoscopy, surgery, and ICU admission as part of further management of the underlying malignancy.