Drug-eluting beads bronchial arterial chemoembolization in advanced and standard treatment-refractory/ineligible NSCLC

Drug-eluting beads bronchial arterial chemoembolization in advanced and standard treatment-refractory/ineligible NSCLC | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Drug-eluting beads bronchial arterial chemoembolization in advanced and standard treatment-refractory/ineligible NSCLC Wei Cui, Jing Li, Jie Tian, Yi Deng, Jingjing Chen, Jinghua Cui, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4612874/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract OBJECTIVES: The treatment strategy for previously standard treated non-small-cell lung cancer (NSCLC) still remained challenge. This study was to evaluate the effectiveness and safety of epirubicin-loaded drug-eluting bead transbronchial artery chemoembolization (D-BACE) plus bronchial artery infusion chemotherapy (BAIC) in patients with refractory advanced NSCLC. METHODS: Between January 2018 and December 2022, 32 patients with refractory advanced NSCLC (26 males; mean age of 64±9.3years [range 41-78]; 19 squamous carcinomas [59.4%]) who had received one or more previous standard treatments and received D-BACE (epirubicin 50mg) plus BAIC (lobaplatin 30 mg/m2) were included in our study. The study evaluated several parameters including local tumor response based on RECIST 1.1 criteria, progression-free survival (PFS), overall survival (OS), and complication rates. To examine the impact of different factors on PFS and OS, Kaplan–Meier and Cox regression analyses were performed. RESULTS: A total of 68 D-BACE plus BAIC sessions (median, 1, range 1-7) were performed. Overall response and disease control rates were 25% and 100%, respectively. The median PFS and median overall survival were 6.0 months (95% confidence interval (CI): 4.1–7.9) and 14.0 months (95% CI: 4.8–23.2), respectively. The number of cycles in the D-BACE plus BAIC treatment was found to be an independent predictor of PFS and OS. There were no instances of severe procedure-related complications or deaths during the study. CONCLUSIONS: The combination of D-BACE and BAIC shows great potential as a treatment choice for patients with refractory advanced NSCLC. Interventional Radiology Chemoembolization Non-Small-Cell Lung Cancer Catheterization Bronchial Artery Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, representing the majority of lung cancer cases. Due to the occult onset of NSCLC, approximately 70% of patients are diagnosed at an advanced stage, resulting in poor 5-year survival rates ranging from 10–20% 1 . Systemic treatments, such as chemotherapy, molecular targeted therapy, and immunotherapy, are commonly used for patients with refractory advanced NSCLC. However, treatment options for NSCLC becomes limited when tumors stop responding to standard therapy. Additionally, patients with poor performance status as a result of cardiovascular and pulmonary ailments may not meet the criteria for receiving systemic therapy. The prognosis for refractory advanced NSCLC is extremely unfavorable, as indicated by a median time for disease progression of approximately 3.4 to 3.8 months. Furthermore, the median overall survival (OS) duration ranges from around 6.5 to 7 months 2 . Transcatheter arterial chemoembolization of the bronchial arteries has emerged as a treatment option for large multifocal lung tumors 3 . Drug-eluting bead bronchial arterial chemoembolization (D-BACE) is an innovative drug delivery system that effectively blocks the arteries supplying nutrients to tumors, while also gradually releasing powerful chemotherapy drugs directly into the tumor tissue 4 . D-BACE is safe, feasible, and well tolerated in patients with advanced lung cancer 4–7 . Bronchial arterial infusion chemotherapy (BAIC) is an effective intra-arterial intervention that efficiently administers concentrated doses of anticancer drugs directly to the tumor tissue. This treatment is commonly employed alongside other therapies, and it has showcased promising outcomes in terms of lung cancer treatment response. 8 . Both D-BACE and BAIC have the capability to effectively enhance drug concentrations in specific organs while simultaneously reducing drug levels in the peripheral areas of the body. 5 . Recently, a combination of embolization and arterial infusion was reported in patients with metastatic lung tumors 9, 10 . D-BACE plus intercostal arterial infusion chemotherapy has shown effectiveness and good tolerance in treating patients with NSCLC and previously treated malignant pleural effusion 8 . However, there have been limited studies investigating the efficacy and tolerability of D-BACE and BAIC in patients with refractory advanced NSCLC. Hence, this study introduces a novel approach termed salvage therapy, which combines D-BACE and BAIC, and aims to evaluate its effectiveness and safety in individuals who have undergone prior treatment for non-small cell lung cancer (NSCLC). Materials and Methods Study design and Patient selection This single-center retrospective study was approved by the Institutional Review Board (IRB) of our hospital(No. KY2024-050-02). The requirement for informed consent was waived by the IRB for retrospective analyses of patient records and imaging data. The study was conducted according to the STROBE guidelines 11 . Between January 2018 and December 2022, 84 consecutive patients diagnosed with non-small cell lung cancer (NSCLC) through histological confirmation were included in this study. The inclusion criteria for patients were as follows: (a) age exceeding 18 years, (b) refractory advanced NSCLC with either local progression or intolerance to systemic therapies after standard treatment, and a (c) willingness to receive interventional therapy. The patient exclusion criteria were as follows: (a) Eastern Cooperative Oncology Group score > 2; (b) incomplete data; (c) untreatable coagulation disorder; and (d) no measurable lung tumor lesions. Patients with refractory advanced NSCLC who underwent D-BACE plus BAIC as first-line therapy were also excluded from this study. A comprehensive flow diagram depicting the process of selecting patients is presented in Fig. 1 . Finally, this study including 32 patients with refractory advanced non-small cell lung cancer (NSCLC) who received treatment with D-BACE plus BAIC was analyzed. The mean age was 64 ± 9.3 years (41–78 years old). Treatment procedures Interventional procedures were performed by one of two interventional radiologists with at least 20 years of experience. Potential tumor-feeding arteries were scrutinized on computed tomography (CT) angiography before endovascular treatment. After successful percutaneous right femoral artery puncture using the modified Seldinger technique under local anesthesia, a 5-Fr Cobra 2-shaped, MIK or RH catheter (Cook, USA) was successively inserted bilaterally in the bronchial and/or non-bronchial systemic arteries to localize the tumor-feeding arteries. Angiography was performed using a catheter to confirm that the tumor-feeding arteries were identified. Superselective angiography and intubation were performed using a 2.7-Fr microcatheter (Progreat, Terumo, Japan). Selective digital subtraction angiography was performed carefully to identify the anterior spinal artery. A chemotherapeutic agent (lobaplatin, 30 mg/m 2 ) was injected through a microcatheter. In cases with multiple feeders, the total dose of the chemotherapeutic agent was divided according to the degree of tumor staining in each artery 12 . The procedure involved the use of DC Bead™ particles (Boston Science, London, UK) with a size range of 300–500 µm to embolize the artery that supplies the tumor. These particles were loaded with 50 mg of epirubicin (Pfizer, NewYork) for targeted treatment. The embolization endpoint was stasis or near-stasis of the target vessel, or devascularization of the tumor. If one bolt of DC Bead™ particles could not reach the embolization endpoint, 300–500µm Embosphere microspheres were used for supplementation until complete embolization. D-BACE plus BAIC cycles were repeated on demand; when no vital tumor-feeding arteries were observed on contrast agent–enhanced CT at every 4–6 weeks, D-BACE plus BAIC was discontinued, and the patients underwent the next CT at 8-week intervals. Assessment of outcomes and safety The primary endpoint was to determine the rate of target tumor lesion response, which was assessed through the first follow-up contrast CT scan conducted 4–6 weeks after the initial D-BACE plus BAIC therapy. The evaluation of the response was carried out following the guidelines provided by the Response Evaluation Criteria in Solid Tumors (version 1.1) 13 . Secondary endpoints included progression-free survival (PFS), OS, and treatment-related complications. PFS was determined as the duration from the commencement of initial D-BACE plus BAIC therapy to either the occurrence of tumor progression or the occurrence of death. On the other hand, OS was determined as the time between the initiation of the D-BACE plus BAIC therapy and either death or the last follow-up. Complications were classified as minor or major according to the guidelines of the Society of Interventional Radiology. Statistical analysis Categorical variables were typically represented by frequencies and percentages, providing an understanding of the different categories and their proportions. On the other hand, continuous variables were described by the mean, which represents the average value, and the standard deviation (SD), which highlights the variability within the data. To investigate the correlation between previous immunotherapy and tumor response, Spearman’s rank test was used. Additionally, the OS and PFS were calculated using the Kaplan–Meier method. Any variables that had a P-value less than 0.1 in the univariate analyses were included as candidate variables in a stepwise Cox proportional hazards analysis. Through the multivariate analyses, independent predictors of PFS and OS were identified. The hazard ratios (HR) along with the corresponding 95% confidence intervals (95% CI) were compared. The data was analyzed using SPSS software (version 25.0; IBM, Armonk, New, USA). Statistical analysis was conducted using two-sided tests, and a significance level of P ≤ 0.05 was considered statistically significant. Results Patients’ demographics Demographic characteristics are summarized in Table 1 . Eight of the 19 patients with squamous carcinoma received D-BACE plus BAIC as secondary treatment after the first standard treatment progression. Of the 13 patients with non-squamous NSCLC, one patient with adenoid cystic carcinoma received D-BACE plus BAIC as a secondary line after chemotherapy immunotherapy progression, and one patient with pulmonary sarcomatoid cancer received D-BACE plus BAIC as a secondary line due to the development of immune-associated hepatitis after chemotherapy immunotherapy and refused to receive systemic therapy. Among the 11 remaining patients with adenocarcinoma, seven had no driver gene mutation, and five received D-BACE plus BAIC as second-line therapy due to the first standard treatment progression or intolerance to chemotherapy (Table 1 ). Table 1 Characteristics of Study Patients(N = 32) Variables Value (%) Age(y)* ≤65 years 19(59.4) >65years 13(40.6) Sex Male 26(81.3) Female 6(18.8) Performance status score 0 16(50.0) 1–2 16(50.0) Location of tumor Central type 16(50.0) Peripheral type 16(50.0) Histological type Squamous 19(59.4) Non-squamous 13(40.6) Adenocarcinoma 11(34.4) Other 2(6.2) Tumor size ≤5cm 15(46.9) >5 cm 17(53.1) TNM stage IIIA 7(21.9) IIIB 9(28.1) IIIC 1(3.1) IVA 11(34.4) IVB 4(12.5) Treatment Line 2 15(46.9) ≥ 3 17(53.1) *Data are means ± standard deviation; data in parentheses are ranges Treatment Details A total of 68 sessions (mean ± SD: 2.13 ± 1.77) of D-BACE plus BAIC were performed. Out of the 32 patients involved in the study, 22 of them were administered with 1–2 cycles of D-BACE in combination with BAIC. On the other hand, four patients underwent three cycles, two patients went through four cycles, one patient received five cycles, two patients completed six cycles, and finally, one patient completed a total of seven cycles. (Table 2 ). Table 2 D-BACE plus BAIC procedure details(N = 32) Variables Value (%) No. of cycles median (range) * 1( 1 – 7 ) 1 20(62.5) 2 2(6.3) More than 3 11(31.2) Targeted arteries Bronchial arteries 17(53.1) NBSA 7(21.9) Bronchial arteries + NBSA 8(25.0) *Data are medians; data in parentheses are ranges data in parentheses are ranges. Abbreviations: D-BACE, drug-eluting bead transbronchial artery chemoembolization; BAIC, bronchial artery infusion chemotherapy; NBSA, non-bronchial systemic artery. Of the 32 patients, 25 (78.1%) had lung tumors supplied by the bronchial arteries or intercostal bronchial arteries, with or without non-bronchial systemic arteries, while seven patients (21.9%) had lung tumors supplied solely by non-bronchial systemic arteries (Table 2 ). Six patients had systemic artery-to-pulmonary artery shunts, one patient had both bronchial arteriopulmonary artery shunts and bronchial arteriopulmonary venous shunts. Figure 2 and Fig. 3 demonstrate typical illustrations of bronchial and non- bronchial systemic angiograms. Tumor response The responses of the treated tumors at 4–6 weeks according to the RECIST were partial response (8 of 32 participants [25%]), stable disease (24 of 32 participants [75%]), and no complete response or progressive disease. The overall response rate (ORR) was 25% (CR + PR), and the disease control rate (DCR) was 100% (CR + PR + SD). Of the eight patients with PR, four had a history of immunotherapy before D-BACE plus BAIC. The association between previous immunotherapy and tumor response was analyzed using Spearman’s rank test, r s =0.462, P = 0.008. This indicates that previous immunotherapy was associated with tumor response to some extent. Complications No major procedure-related complications such as spinal cord infarction was observed. Minor complications included nausea, vomiting, transient chest pain, fever, and fatigue. Among the patients, eight (25.0%) had nausea and vomiting, 12 (37.5%) experienced pain, one (3.1%) had fever, seven (21.9%) had fatigue. All minor complications resolved after conservative symptomatic therapy. Survival analysis The median follow-up duration was 15 months (2.5–31 months). The percentage of patients who died during follow-up was 53.1% (17 of 32). The median PFS and OS were 6.0 months (95% CI: 4.1–7.9) and 14.0 months (95% CI: 4.8–23.2), respectively (Fig. 4 a and 4 b). The estimated PFS rates at 6-month, 1-year, and 2-year were 50.7%, 28.1%, and 0%, respectively, while the estimated OS rates at 6-month, 1-year, and 2-year were 81.3%, 57.4%, and 47.0%, respectively. In the univariate and multivariate analyses of PFS, only the number of D-BACE plus BAIC cycles (P = 0.022) was significantly associated with PFS and emerged as an independent predictor (Table 3 ). Similarly, in the univariate analyses of OS, performance status score (p = 0.029), number of D-BACE plus BAIC cycles (P = 0.017), and subsequent systemic therapies (P = 0.038) were significantly associated with OS (Table 4 ). In the multivariate analyses, only the number of D-BACE plus BAIC cycles (P = 0.017) was an independent predictor of OS (Table 4 ). Table 3 Univariate and Multivariate Analysis of Prognostic Factors for Progression-free Survival with Cox Proportional Hazards Model. Univariate Analysis Multivariate Analysis Variables HR (95%CI) P HR (95%CI) P Age (≤ 65 y vs > 65 y) 1.10(047,2.60) 0.820 Sex (male vs female) 0.94(0.31,2.79) 0.907 Performance status score (0 vs 1–2) 0.93(0.40,2.15) 0.857 Tumor size(≤ 5cm vs >5cm) 2.07(0.87,4.93) 0.100 Tumor location (center vs proximal) 1.50(0.64,3.51) 0.353 pathology (non-squamous vs squamous) 2.21(0.86,5.69) 0.100 No. of D-BACE plus BAIC cycles (≤ 2 vs >2) 0.27(0.09,0.83) 0.022 0.27(0.09,0.83) 0.022 Subsequent systemic therapies (No vs. Yes) 0.74(0.31,1.76) .500 Abbreviations: D-BACE, drug-eluting bead transbronchial artery chemoembolization; BAIC, bronchial artery infusion chemotherapy; HR, Hazard ratio. Table 4 Univariate and Multivariate Analysis of Prognostic Factors for Overall Survival with Cox Proportional Hazards Model. Univariate Analysis Multivariate Analysis Variables HR (95%CI) P HR (95%CI) P Age (≤ 65 y vs > 65 y) 1.69(0.62,4.57) 0.304 Sex (male vs female) 0.70(0.20,2.49) 0.586 Performance status score (0 vs 1–2) 3.56(1.14,11.13) 0.029 2.98(0.79,11.31) 0.108 Tumor size(≤ 5cm vs >5cm) 1.51(0.58,3.98) 0.401 Tumor location (center vs proximal) 0.71(0.25,1.99) 0.512 pathology (non-squamous vs squamous) 1.86(0.64,5.39) 0.255 No. of D-BACE plus BAIC cycles (≤ 2 vs >2) 0.20(0.05,0.75) 0.017 0.17(0.04,0.78) 0.022 Subsequent systemic therapies (No vs. Yes) 0.30(0.10,0.94) 0.038 0.53(0.15,1.86) 0.321 Abbreviations: D-BACE, drug-eluting bead transbronchial artery chemoembolization; BAIC, bronchial artery infusion chemotherapy; HR, Hazard ratio. Discussion For NSCLC that progresses after the first and secondary standard treatment, the current change in targeted drugs or chemotherapy regimens and multi-drug combination therapy are commonly used, but the results are still unsatisfactory. Patients with severe adverse reactions, such as severe immune-associated pneumonia, severe liver function injury, and severe bone marrow suppression, during systemic therapy in the first and second lines of treatment, may have poor compliance with systemic therapy in subsequent lines of treatment. The failure of first - and second-line treatments further reduces patient compliance with post-line treatment. This retrospective study of 32 patients suggests that D-BACE plus BAIC is a safe and effective treatment for refractory advanced NSCLC, with no major complications. Tumor control, defined as the achievement of CR, PR, or SD, was successfully achieved in all cases within this series. Furthermore, the median OS in this study was 14.0 months, which appears to be better than that achieved with gemcitabine plus carboplatin (10.0 months), pemetrexed (7.4months), or docetaxel (10.0months) 14, 15 . We also found that patients who had previously received immunotherapy had a better tumor response than those who had not. Our results add to the growing body of literature, suggesting that D-BACE plus BAIC is a promising treatment option and may provide a reasonable alternative for refractory advanced NSCLC. For the management of NSCLC, D-BACE plus BAIC offers two important advantages over systemic chemotherapy. First, the lesions in refractory advanced NSCLC are usually large, leading to blood circulation disorders in the tumor. As such, it is difficult to reach the tumor and its center through an intravenous drip, let alone the effective drug concentration, resulting in poor systemic efficacy and high toxicity 16 . The administration of transarterial chemoembolization and infusion chemotherapy leads to high concentrations of drugs within the tumor tissue, which can effectively overcome chemoresistance 3 . Second, drug-eluting beads have the capacity to embolize the arteries that supply nutrients to tumors, thereby depriving the tumor of its vital source. Additionally, these specialized beads gradually release the chemotherapy drugs, they are loaded with, over the course of a month, ensuring a sustained and controlled delivery of medication directly into the tumor tissue. As a result, the concentration of drugs in the peripheral blood remains minimal. Therefore, the incidence of adverse reactions caused by chemotherapeutic drugs in D-BACE plus BAIC is lower than that in systemic chemotherapy. The theoretical basis for selecting lobaplatin as an arterial infusion chemotherapy drug is as follows: 1) Although cisplatin, carboplatin, nedaplatin and other platinum-based chemotherapy drugs are commonly used in the clinic of non-small cell lung cancer, the patients in this study have been resistant to these drugs, so the efficacy of using these drugs after arterial infusion chemotherapy is expected to be poor, and lobaplatin does not have cross-resistance with the first-and second-generation platinum-based drugs mentioned above. 2) Lobaplatin, as a third-generation platinum, has lower toxic side effects than first-generation platinum, and has shown good anti-tumor effects on non-small cell lung cancer in previous animal experiments and clinical studies 17, 18 . 3) Compared with oxaliplatin, lobaplatin has better water solubility, and the pH value of its water soluble is 6–8, which is close to the normal physiological pH of human body, so it is more suitable for arterial perfusion chemotherapy, which will not cause arterial irritant spasm. Liu et al. conducted a study that revealed the superior outcomes of D-BACE in terms of PFS and OS when compared to chemotherapy for patients with refractory advanced NSCLC. This study indicates that D-BACE has the potential to serve as an additional treatment option due to its favorable therapeutic efficacy, ability to enhance quality of life, and its tolerable safety profile for these patients 1 . He et al. conducted a comprehensive analysis on the effectiveness and safety of D-BACE in comparison to that of BAIC, followed by polyvinyl alcohol (PVA) particle embolization, for treating advanced squamous cell lung cancer after the failure of systemic therapy. The study revealed that the D-BACE group demonstrated a median PFS of 4.3 months and OS of 12.6 months. In contrast, the BAIC plus PVA group exhibited a significantly shorter median PFS of 3.2 months and OS of 8.1 months. These results unequivocally indicate the superiority of D-BACE over BAIC plus PVA embolization in the treatment of advanced squamous cell lung cancer 19 . The median PFS and OS in the D-BACE group were shorter than those observed in our study. This may be because BAIC was not performed in the D-BACE group, and squamous cancer accounted for 59.4% (n = 19) of the patients in our study. According to a multicenter prospective study, the use of D-BACE resulted in a notable enhancement in the quality of life for patients with refractory NSCLC. Additionally, the study revealed a median OS of 11.5 months when utilizing this treatment approach 20 . However, it should be noted that squamous cancer accounted for 83.7% (36) of the patients in this prospective study, which might have influenced the observed OS. The study reported promising efficacy with a median PFS of 7.0–11.0 months and OS of 8.0–18.4 months, as well as tolerable toxicity in patients with refractory advanced NSCLC ( 6 , 19 – 21 ). The PFS and OS rates in these studies were better than those in our study. We suggest that the reason for this difference could be attributed to the fact that only 56.3% (18/32) of patients received systemic therapies in our study. However, patients who received subsequent systemic therapies had higher OS than those without, as shown in the univariate analysis, although subsequent systemic therapies were not identified as an independent influencing factor in the multivariate analysis. These findings suggest that combination therapy may benefit some patients. In this study, minor adverse events after D-BACE plus BAIC, such as transient chest pain, nausea, vomiting, fever, and fatigue, were usually self-limiting or resolved after conservative symptomatic therapies, which is consistent with previous studies 8, 20 . Major complications such as esophageal fistula, spinal cord infarction, posterior circulation cerebral infarction, and myocardial infarction due to non-target embolization were not observed in our study, and were also rare in a recent bronchial artery embolization series 5, 21 . However, these serious complications should be noted and avoided, with careful monitoring during the procedure. Based on our experience, the following points may help reduce the complications of the operation: iodized oil should be avoided for embolization of lung cancer because the small diameter of iodized oil droplets can easily cause ectopic embolization, which can further lead to serious complications, such as spinal cord injury and cerebral infarction 20 . Drug-eluting beads or microsphere embolization with an inner diameter ranging between 300 and 500 mm is strongly advised based on an in-depth anatomical study. This study proposes that the anastomotic diameter of both the bronchial and pulmonary arteries could potentially accommodate sizes of up to 325 mm 22 . An additional factor to consider is that when using an excessively large embolization material, it primarily leads to proximal embolization. This, in turn, significantly diminishes the effectiveness of the treatment due to the establishment of collateral circulation 20 . Drug-eluting beads or blank microspheres were utilized in all patients due to their superior size, uniformity, and improved penetration characteristics compared to those of PVA or gelatin sponge particles. Notably, these microspheres possess smooth hydrophilic-coated surfaces, which significantly reduce the risk of clumping within catheters 21 . These results indicate that regurgitation does not occur more easily with drug-eluting beads or blank microspheres than with PVA or gelatin sponge particles. As clumping increases the transient resistance to embolic injection, systemic pulmonary shunts should be identified, and a suitable particle embolic agent of particle size should be selected to seal the fistula before D-BACE. Vascular variation or abnormal anastomosis should also be recognized, especially if the tumor-feeding vessels originate from the subclavian artery branches or have anastomotic branches, because ectopic embolization may cause posterior circulation stroke. In addition, blood vessels that communicate with the coronary arteries should also be considered when embolizing, because ectopic embolization may cause myocardial infarction. The limitations of this study are predominantly associated with the limited sample size and the absence of a control group. In addition, there was heterogeneity in the standard systemic therapies given to patients included in this study; it is difficult to assess the potential effect. Additionally, it is still unknown which chemotherapeutic agents loaded with eluting beads are the most effective and safe in treating NSCLC. A multicenter prospective study had showed drug-eluting beads loaded with epirubicin for D-BACE was effective and safe in treating refractory NSCLC 20 . In this study, we also used epirubicin for loading DC Bead™ particles, while oxaliplatin, vinorelbine, and gemcitabine have been reported for loading CalliSpheres beads, which are commonly used for lung cancer in systemic chemotherapy 23–25 . However, these drugs are not available for being loaded onto DC Beads according to the manufacturer’s instructions. Moreover, we found a correlation between previous immunotherapy and tumor response after treatment. However, due to the retrospective nature of this study, conducting an in-depth analysis was difficult, and we could not provide a convincing explanation. Further studies on immune status and treatment response are expected to answer this question. Finally, only 31.2% of the patients underwent more than three sessions of D-TACE, which may be insufficient to achieve satisfactory efficacy. D-BACE combined with BAIC is a feasible, safe, and effective treatment option for patients with refractory advanced NSCLC. We present our experience using this technique for patient selection and demonstrate its feasibility with a satisfactory safety profile. Abbreviations NSCLC, non-small-cell lung cancer; D-BACE, drug-eluting bead transbronchial artery chemoembolization; BAIC, bronchial artery infusion chemotherapy; PFS, progression-free survival; OS, overall survival; CI, confidence interval; IRB, Institutional Review Board; CT, computed tomography; SD, standard deviation; HRs, Hazard ratios; ORR, overall response rate; DCR, disease control rate; PVA, polyvinyl alcohol Declarations Ethics approval and consent to participate This single-center retrospective study was approved by the Institutional Review Board (IRB) of our hospital（No. KY2024-050-02） Consent for publication Not applicable. Availability of data and material The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request. Competing interests The authors declare that there are no conflicts of interest regarding the publication of this paper. Funding Supported by grants from the National Natural Science Foundation of China (82102163) and the National Key Research and Development Program (Project No. 2023YFC2507104). Acknowledgements Not applicable. References Liu XF, Lin H, Wang Q, Mu M, Pan P, Tian FF, et al. Drug-eluting bead bronchial arterial chemoembolization vs. chemotherapy in treating advanced non-small cell lung cancer: comparison of treatment efficacy, safety and quality of life. Eur Rev Med Pharmacol Sci 2021; 25 (6): 2554-2566. doi: 10.26355/eurrev_202103_25419. Scartozzi M, Mazzanti P, Giampieri R, Berardi R, Galizia E, Gasparini S, et al. Clinical predictive factors for advanced non-small cell lung cancer (NSCLC) patients receiving third-line therapy: Selecting the unselectable? Lung Cancer 2010; 68 (3): 433-437. doi: 10.1016/j.lungcan.2009.07.008. Boas FE, Kemeny NE, Sofocleous CT, Yeh R, Thompson VR, Hsu M, et al. Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial. Radiology 2021; 301 (2): 474-484. doi: 10.1148/radiol.2021210213. Bi Y, Shi X, Yi M, Han X, Ren J. Pirarubicin-loaded CalliSpheres® drug-eluting beads for the treatment of patients with stage III–IV lung cancer. Acta Radiologica 2021; 63 (3): 311-318. doi: 10.1177/0284185121994298. Ren K, Wang J, Li Y, Li Z, Wu K, Zhou Z, et al. The Efficacy of Drug-eluting Bead Transarterial Chemoembolization Loaded With Oxaliplatin for the Treatment of Stage III-IV Non-small-cell Lung Cancer. Academic Radiology 2022; 29 (11): 1641-1646. doi: 10.1016/j.acra.2022.01.015. Liu J, Zhang W, Ren J, Li Z, Lu H, Sun Z, et al. Efficacy and Safety of Drug-Eluting Bead Bronchial Arterial Chemoembolization Plus Anlotinib in Patients With Advanced Non-small-Cell Lung Cancer. Front Cell Dev Biol 2021; 9 768943. doi: 10.3389/fcell.2021.768943. Bie Z, Li Y, Li B, Wang D, Li L, Li X. The efficacy of drug-eluting beads bronchial arterial chemoembolization loaded with gemcitabine for treatment of non-small cell lung cancer. Thoracic cancer 2019; 10 (9): 1770-1778. doi: 10.1111/1759-7714.13139. Liu X, Lin H, Wang Q, Mu M, Pan P, Tian F, et al. Drug-eluting beads bronchial arterial chemoembolization plus intercostals arterial infusion chemotherapy is effective and well-tolerated in treating non-small cell lung cancer patients with refractory malignant pleural effusion. J Thorac Dis 2021; 13 (4): 2339-2350. doi: 10.21037/jtd-20-1603. Kennoki N, Hori S, Yuki T, Hori A. Transcatheter Arterial Chemoembolization with Spherical Embolic Agent in Patients with Pulmonary or Mediastinal Metastases from Breast Cancer. J Vasc Interv Radiol 2017; 28 (10): 1386-1394. doi: 10.1016/j.jvir.2017.06.003. Hori A, Ohira R, Nakamura T, Kimura Y, Ueda S, Torii M, et al. Transarterial chemoembolization for pulmonary or mediastinal metastases from hepatocellular carcinoma. The British Journal of Radiology 2020; 93 (1110): 20190407. doi: 10.1259/bjr.20190407. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370 (9596): 1453-1457. doi: 10.1016/S0140-6736(07)61602-X. Hori S, Nakamura T, Kennoki N, Dejima I, Hori A. Transarterial management of advance lung cancer. Jpn J Clin Oncol 2021; 51 (6): 851-856. doi: 10.1093/jjco/hyab050. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). European Journal of Cancer 2009; 45 (2): 228-247. doi: 10.1016/j.ejca.2008.10.026. Du L, Morgensztern D. Chemotherapy for Advanced-Stage Non–Small Cell Lung Cancer. The Cancer Journal 2015; 21 (5): 366-370. doi: 10.1097/ppo.0000000000000141. Nishiyama A, Katakami N, Yoshioka H, Iwasaku M, Korogi Y, Hata A, et al. Retrospective efficacy and safety analyses of erlotinib, pemetrexed, and docetaxel in EGFR-mutation-negative patients with previously treated advanced non-squamous non-small-cell lung cancer. Lung Cancer 2015; 89 (3): 301-305. doi: 10.1016/j.lungcan.2015.06.017. Jin SQ, Zhao HY, Bai B, Ma CH, Cao HL. Transcatheter arterial chemoembolization improves clinical efficacy and life quality of patients with lung cancer and reduces adverse reactions. Am J Transl Res 2021; 13 (9): 10396-10403. Xie C, Xu Y, Jin W, Lou L. Antitumor activity of lobaplatin alone or in combination with antitubulin agents in non-small-cell lung cancer. Anti-cancer drugs 2012; 23 (7): 698-705. doi: 10.1097/CAD.0b013e328352cc10. Chen C, Wang W, Yu Z, Tian S, Li Y, Wang Y. Combination of computed tomography-guided iodine-125 brachytherapy and bronchial arterial chemoembolization for locally advanced stage III non-small cell lung cancer after failure of concurrent chemoradiotherapy. Lung Cancer 2020; 146 290-296. doi: 10.1016/j.lungcan.2020.06.010. He G, Yang K, Zhang X, Pan J, Han A, Gao Z, et al. Bronchial artery chemoembolization with drug-eluting beads versus bronchial artery infusion followed by polyvinyl alcohol particles embolization for advanced squamous cell lung cancer: A retrospective study. Eur J Radiol 2023; 161 110747. doi: 10.1016/j.ejrad.2023.110747. Zhao YW, Liu S, Qin H, Sun JB, Su M, Yu GJ, et al. Efficacy and safety of CalliSpheres drug-eluting beads for bronchial arterial chemoembolization for refractory non-small-cell lung cancer and its impact on quality of life: A multicenter prospective study. Front Oncol 2023; 13 1110917. doi: 10.3389/fonc.2023.1110917. Kettenbach J, Ittrich H, Gaubert JY, Gebauer B, Vos JA. CIRSE Standards of Practice on Bronchial Artery Embolisation. Cardiovasc Intervent Radiol 2022; 45 (6): 721-732. doi: 10.1007/s00270-022-03127-w. Pump K. Distribution of bronchial arteries in the human lung. Chest 1972; 62 (4): 447-451. doi: 10.1378/chest.62.4.447. Ma X, Zheng D, Zhang J, Dong Y, Li L, Jie B, et al. Clinical outcomes of vinorelbine loading CalliSpheres beads in the treatment of previously treated advanced lung cancer with progressive refractory obstructive atelectasis. Front Bioeng Biotechnol 2022; 10 1088274. doi: 10.3389/fbioe.2022.1088274. Li YM, Guo RQ, Bie ZX, Li B, Li XG. Sintilimab plus Bronchial Arterial Infusion Chemotherapy/Drug-Eluting Embolic Chemoembolization for Advanced Non-Small Cell Lung Cancer: A Preliminary Study of 10 Patients. J Vasc Interv Radiol 2021; 32 (12): 1679-1687. doi: 10.1016/j.jvir.2021.08.019. Bi Y, Li F, Ren J, Han X. The safety and efficacy of oxaliplatin-loaded drug-eluting beads transarterial chemoembolization for the treatment of unresectable or advanced lung cancer. Front Pharmacol 2022; 13 1079707. doi: 10.3389/fphar.2022.1079707. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4612874","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":330346521,"identity":"3ba20d87-1d29-4d11-a489-c76edebd9d80","order_by":0,"name":"Wei Cui","email":"","orcid":"","institution":"Department of Interventional Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Cui","suffix":""},{"id":330346524,"identity":"017aaaa9-12a1-4ee6-bea3-b01eb1fb7a78","order_by":1,"name":"Jing Li","email":"","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Li","suffix":""},{"id":330346525,"identity":"25376313-2fca-4cbe-afad-e6c11179ff15","order_by":2,"name":"Jie Tian","email":"","orcid":"","institution":"Department of Radiology, Yichang Central People’s Hospital, 183 Yiling Road, Yichang 443003, China; First College of Clinical Medical Science, China Three Gorges University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Tian","suffix":""},{"id":330346527,"identity":"f503eb70-d2e4-4391-8c94-8229f3201175","order_by":3,"name":"Yi Deng","email":"","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province. The Affiliated Hospital of Kunming University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Deng","suffix":""},{"id":330346528,"identity":"c23dcd53-dbe2-4040-8f9d-291b7e607ace","order_by":4,"name":"Jingjing Chen","email":"","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Chen","suffix":""},{"id":330346532,"identity":"074b5fd4-ab8a-4972-a22a-e6040f6f07ea","order_by":5,"name":"Jinghua Cui","email":"","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jinghua","middleName":"","lastName":"Cui","suffix":""},{"id":330346534,"identity":"fc7ca4cc-0e40-4627-b90f-c14930f267ba","order_by":6,"name":"Qi Wang","email":"","orcid":"","institution":"Department of Interventional Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Wang","suffix":""},{"id":330346535,"identity":"0ae6d48c-e1b0-4498-ae96-adb72f3efcdb","order_by":7,"name":"Qicong Mai","email":"","orcid":"","institution":"Department of Interventional Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qicong","middleName":"","lastName":"Mai","suffix":""},{"id":330346536,"identity":"47b4f44f-93b4-4d74-92e9-f344964854f8","order_by":8,"name":"Xiaoming Chen","email":"","orcid":"","institution":"Department of Interventional Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoming","middleName":"","lastName":"Chen","suffix":""},{"id":330346537,"identity":"b433eb99-2bae-4245-b78b-ef02d85f9ad4","order_by":9,"name":"Jing Zhang","email":"","orcid":"","institution":"Department of Interventional Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Zhang","suffix":""},{"id":330346538,"identity":"75d39c53-00de-4518-916e-0cca0f4279cc","order_by":10,"name":"Rongde Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYPACZgZ+BgYDZtK0SDaQrMXgALFaDG7kPnxc8Mtazvj84m2PCxhs8uUdmJ89wKdFcka6sfHMvnRjsxvPyo1nMKRZbjzAZm6ATwu/RBqbNG/P4cRtN86YSfMwHDYwbOBhk8CnhQ2qpX7zDGK1gG3h+XE4wYC/B6JFnoGAFsmeZ8zGvA3phjNusJUb8xikGRgws5nh1WJwPI3xMc8fa3n+/sPbHvNU2BjItzc/w6sFDBjbgIREAhvQBCA6TFA9CPwB+eoAG5gt30CUllEwCkbBKBhBAADZCD5AU0zCJwAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Interventional Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","correspondingAuthor":true,"prefix":"","firstName":"Rongde","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2024-06-20 15:42:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4612874/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4612874/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60944718,"identity":"c9a3d0ca-55f7-477f-93e5-4b21de7ef1e7","added_by":"auto","created_at":"2024-07-23 22:14:33","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":28783,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flowchart\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4612874/v1/da204d3b33519e53645a9bd5.jpg"},{"id":60945298,"identity":"6a976fd0-54da-4ec2-9982-705e7f173b7a","added_by":"auto","created_at":"2024-07-23 22:22:33","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":84429,"visible":true,"origin":"","legend":"\u003cp\u003eA 59-year-old man with IIIC stage right lung squamous cell carcinoma received D-BACE plus BAIC, whose tumor progressed after chemotherapy and immunotherapy. Preoperative CT showing malignant tumor of the right lung (a and b); The right bronchial arteries(c) were the blood supply artery of the tumor. After 50 mg of epirubicin, drug-eluting beads transbronchial artery chemoembolization (D-BACE) were successfully embolized(d). 6 weeks after D-BACE plus BAIC the right lung tumor was significantly smaller than before (e and f).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4612874/v1/ae5cf6f727f7f80864e2fe46.jpg"},{"id":60944716,"identity":"2cc1b499-b36c-4d69-93a8-5aaef8eb7cb8","added_by":"auto","created_at":"2024-07-23 22:14:33","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":48592,"visible":true,"origin":"","legend":"\u003cp\u003eA 61-year-old man with right lung sarcomatoid carcinoma received D-BACE plus BAIC. Preoperative CT showing malignant tumor of the right lung (a and b); The intercostal arteries (c and e) and right bronchial arteries(d) were the blood supply artery of the tumor. Intercostal arteries (c and e) and right bronchial artery (d) angiogram shows a hypervascular staining lesion in the right lung as well as shunting with branches of the right pulmonary arteries (c and e, black arrows) or right pulmonary vein (d, white arrow). On three postembolization angiograms (h, i and j) obtained after drug-eluting beads transbronchial artery chemoembolization, neither the hypervascular lesion nor the pulmonary shunt is visualized. 6 weeks after D-BACE plus BAIC the right lung tumor was significantly smaller than before (f and g).\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4612874/v1/2acdffeca327455ca03453c3.jpg"},{"id":60944720,"identity":"98d9b742-ee4f-466a-a36e-7f2191a4f6d2","added_by":"auto","created_at":"2024-07-23 22:14:33","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":19006,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-free survival and Overall survival curves in patients with previously treated NSCLC after D-BACE plus BAIC treatment.\u003c/p\u003e\n\u003cp\u003ea. Progression-free survival curves \u0026nbsp;\u0026nbsp;b. Overall survival curves\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4612874/v1/0bdbd751c3f50a71b1208532.jpg"},{"id":63395708,"identity":"9a6c1b46-f53c-4255-95f1-005c9a5a0789","added_by":"auto","created_at":"2024-08-27 16:56:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":758365,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4612874/v1/2fc00ea2-12d7-4971-82de-a40d2d7fcc0a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Drug-eluting beads bronchial arterial chemoembolization in advanced and standard treatment-refractory/ineligible NSCLC","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNon-small cell lung cancer (NSCLC) is the predominant type of lung cancer, representing the majority of lung cancer cases. Due to the occult onset of NSCLC, approximately 70% of patients are diagnosed at an advanced stage, resulting in poor 5-year survival rates ranging from 10\u0026ndash;20% \u003csup\u003e1\u003c/sup\u003e. Systemic treatments, such as chemotherapy, molecular targeted therapy, and immunotherapy, are commonly used for patients with refractory advanced NSCLC. However, treatment options for NSCLC becomes limited when tumors stop responding to standard therapy. Additionally, patients with poor performance status as a result of cardiovascular and pulmonary ailments may not meet the criteria for receiving systemic therapy. The prognosis for refractory advanced NSCLC is extremely unfavorable, as indicated by a median time for disease progression of approximately 3.4 to 3.8 months. Furthermore, the median overall survival (OS) duration ranges from around 6.5 to 7 months \u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTranscatheter arterial chemoembolization of the bronchial arteries has emerged as a treatment option for large multifocal lung tumors \u003csup\u003e3\u003c/sup\u003e. Drug-eluting bead bronchial arterial chemoembolization (D-BACE) is an innovative drug delivery system that effectively blocks the arteries supplying nutrients to tumors, while also gradually releasing powerful chemotherapy drugs directly into the tumor tissue \u003csup\u003e4\u003c/sup\u003e. D-BACE is safe, feasible, and well tolerated in patients with advanced lung cancer \u003csup\u003e4\u0026ndash;7\u003c/sup\u003e. Bronchial arterial infusion chemotherapy (BAIC) is an effective intra-arterial intervention that efficiently administers concentrated doses of anticancer drugs directly to the tumor tissue. This treatment is commonly employed alongside other therapies, and it has showcased promising outcomes in terms of lung cancer treatment response. \u003csup\u003e8\u003c/sup\u003e. Both D-BACE and BAIC have the capability to effectively enhance drug concentrations in specific organs while simultaneously reducing drug levels in the peripheral areas of the body. \u003csup\u003e5\u003c/sup\u003e. Recently, a combination of embolization and arterial infusion was reported in patients with metastatic lung tumors \u003csup\u003e9, 10\u003c/sup\u003e. D-BACE plus intercostal arterial infusion chemotherapy has shown effectiveness and good tolerance in treating patients with NSCLC and previously treated malignant pleural effusion \u003csup\u003e8\u003c/sup\u003e. However, there have been limited studies investigating the efficacy and tolerability of D-BACE and BAIC in patients with refractory advanced NSCLC. Hence, this study introduces a novel approach termed salvage therapy, which combines D-BACE and BAIC, and aims to evaluate its effectiveness and safety in individuals who have undergone prior treatment for non-small cell lung cancer (NSCLC).\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and Patient selection\u003c/h2\u003e \u003cp\u003e This single-center retrospective study was approved by the Institutional Review Board (IRB) of our hospital(No. KY2024-050-02). The requirement for informed consent was waived by the IRB for retrospective analyses of patient records and imaging data. The study was conducted according to the STROBE guidelines\u003csup\u003e11\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBetween January 2018 and December 2022, 84 consecutive patients diagnosed with non-small cell lung cancer (NSCLC) through histological confirmation were included in this study. The inclusion criteria for patients were as follows: (a) age exceeding 18 years, (b) refractory advanced NSCLC with either local progression or intolerance to systemic therapies after standard treatment, and a (c) willingness to receive interventional therapy. The patient exclusion criteria were as follows: (a) Eastern Cooperative Oncology Group score\u0026thinsp;\u0026gt;\u0026thinsp;2; (b) incomplete data; (c) untreatable coagulation disorder; and (d) no measurable lung tumor lesions. Patients with refractory advanced NSCLC who underwent D-BACE plus BAIC as first-line therapy were also excluded from this study. A comprehensive flow diagram depicting the process of selecting patients is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Finally, this study including 32 patients with refractory advanced non-small cell lung cancer (NSCLC) who received treatment with D-BACE plus BAIC was analyzed. The mean age was 64\u0026thinsp;\u0026plusmn;\u0026thinsp;9.3 years (41\u0026ndash;78 years old).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTreatment procedures\u003c/h2\u003e \u003cp\u003eInterventional procedures were performed by one of two interventional radiologists with at least 20 years of experience. Potential tumor-feeding arteries were scrutinized on computed tomography (CT) angiography before endovascular treatment. After successful percutaneous right femoral artery puncture using the modified Seldinger technique under local anesthesia, a 5-Fr Cobra 2-shaped, MIK or RH catheter (Cook, USA) was successively inserted bilaterally in the bronchial and/or non-bronchial systemic arteries to localize the tumor-feeding arteries. Angiography was performed using a catheter to confirm that the tumor-feeding arteries were identified. Superselective angiography and intubation were performed using a 2.7-Fr microcatheter (Progreat, Terumo, Japan). Selective digital subtraction angiography was performed carefully to identify the anterior spinal artery. A chemotherapeutic agent (lobaplatin, 30 mg/m\u003csup\u003e2\u003c/sup\u003e) was injected through a microcatheter. In cases with multiple feeders, the total dose of the chemotherapeutic agent was divided according to the degree of tumor staining in each artery\u003csup\u003e12\u003c/sup\u003e. The procedure involved the use of DC Bead\u0026trade; particles (Boston Science, London, UK) with a size range of 300\u0026ndash;500 \u0026micro;m to embolize the artery that supplies the tumor. These particles were loaded with 50 mg of epirubicin (Pfizer, NewYork) for targeted treatment. The embolization endpoint was stasis or near-stasis of the target vessel, or devascularization of the tumor. If one bolt of DC Bead\u0026trade; particles could not reach the embolization endpoint, 300\u0026ndash;500\u0026micro;m Embosphere microspheres were used for supplementation until complete embolization. D-BACE plus BAIC cycles were repeated on demand; when no vital tumor-feeding arteries were observed on contrast agent\u0026ndash;enhanced CT at every 4\u0026ndash;6 weeks, D-BACE plus BAIC was discontinued, and the patients underwent the next CT at 8-week intervals.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of outcomes and safety\u003c/h2\u003e \u003cp\u003eThe primary endpoint was to determine the rate of target tumor lesion response, which was assessed through the first follow-up contrast CT scan conducted 4\u0026ndash;6 weeks after the initial D-BACE plus BAIC therapy. The evaluation of the response was carried out following the guidelines provided by the Response Evaluation Criteria in Solid Tumors (version 1.1) \u003csup\u003e13\u003c/sup\u003e. Secondary endpoints included progression-free survival (PFS), OS, and treatment-related complications. PFS was determined as the duration from the commencement of initial D-BACE plus BAIC therapy to either the occurrence of tumor progression or the occurrence of death. On the other hand, OS was determined as the time between the initiation of the D-BACE plus BAIC therapy and either death or the last follow-up. Complications were classified as minor or major according to the guidelines of the Society of Interventional Radiology.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were typically represented by frequencies and percentages, providing an understanding of the different categories and their proportions. On the other hand, continuous variables were described by the mean, which represents the average value, and the standard deviation (SD), which highlights the variability within the data. To investigate the correlation between previous immunotherapy and tumor response, Spearman\u0026rsquo;s rank test was used. Additionally, the OS and PFS were calculated using the Kaplan\u0026ndash;Meier method. Any variables that had a P-value less than 0.1 in the univariate analyses were included as candidate variables in a stepwise Cox proportional hazards analysis. Through the multivariate analyses, independent predictors of PFS and OS were identified. The hazard ratios (HR) along with the corresponding 95% confidence intervals (95% CI) were compared. The data was analyzed using SPSS software (version 25.0; IBM, Armonk, New, USA). Statistical analysis was conducted using two-sided tests, and a significance level of P\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u0026rsquo; demographics\u003c/h2\u003e \u003cp\u003eDemographic characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Eight of the 19 patients with squamous carcinoma received D-BACE plus BAIC as secondary treatment after the first standard treatment progression. Of the 13 patients with non-squamous NSCLC, one patient with adenoid cystic carcinoma received D-BACE plus BAIC as a secondary line after chemotherapy immunotherapy progression, and one patient with pulmonary sarcomatoid cancer received D-BACE plus BAIC as a secondary line due to the development of immune-associated hepatitis after chemotherapy immunotherapy and refused to receive systemic therapy. Among the 11 remaining patients with adenocarcinoma, seven had no driver gene mutation, and five received D-BACE plus BAIC as second-line therapy due to the first standard treatment progression or intolerance to chemotherapy (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of Study Patients(N\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(y)*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;65 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19(59.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;65years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13(40.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26(81.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6(18.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePerformance status score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16(50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16(50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocation of tumor\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16(50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16(50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistological type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSquamous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19(59.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-squamous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13(40.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11(34.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2(6.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor size\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;5cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15(46.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;5 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17(53.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTNM stage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7(21.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9(28.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIIC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1(3.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11(34.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4(12.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment Line\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15(46.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17(53.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e*Data are means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; data in parentheses are ranges\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Details\u003c/h2\u003e \u003cp\u003eA total of 68 sessions (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD: 2.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77) of D-BACE plus BAIC were performed. Out of the 32 patients involved in the study, 22 of them were administered with 1\u0026ndash;2 cycles of D-BACE in combination with BAIC. On the other hand, four patients underwent three cycles, two patients went through four cycles, one patient received five cycles, two patients completed six cycles, and finally, one patient completed a total of seven cycles. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eD-BACE plus BAIC procedure details(N\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. of cycles\u003c/b\u003e median (range) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(62.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(6.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(31.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTargeted arteries\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchial arteries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(53.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNBSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(21.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchial arteries\u0026thinsp;+\u0026thinsp;NBSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e*Data are medians; data in parentheses are ranges data in parentheses are ranges.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eAbbreviations: D-BACE, drug-eluting bead transbronchial artery chemoembolization; BAIC, bronchial artery infusion chemotherapy; NBSA, non-bronchial systemic artery.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOf the 32 patients, 25 (78.1%) had lung tumors supplied by the bronchial arteries or intercostal bronchial arteries, with or without non-bronchial systemic arteries, while seven patients (21.9%) had lung tumors supplied solely by non-bronchial systemic arteries (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Six patients had systemic artery-to-pulmonary artery shunts, one patient had both bronchial arteriopulmonary artery shunts and bronchial arteriopulmonary venous shunts. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e demonstrate typical illustrations of bronchial and non- bronchial systemic angiograms.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eTumor response\u003c/h2\u003e \u003cp\u003eThe responses of the treated tumors at 4\u0026ndash;6 weeks according to the RECIST were partial response (8 of 32 participants [25%]), stable disease (24 of 32 participants [75%]), and no complete response or progressive disease. The overall response rate (ORR) was 25% (CR\u0026thinsp;+\u0026thinsp;PR), and the disease control rate (DCR) was 100% (CR\u0026thinsp;+\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;SD). Of the eight patients with PR, four had a history of immunotherapy before D-BACE plus BAIC. The association between previous immunotherapy and tumor response was analyzed using Spearman\u0026rsquo;s rank test, r\u003csub\u003es\u003c/sub\u003e=0.462, P\u0026thinsp;=\u0026thinsp;0.008. This indicates that previous immunotherapy was associated with tumor response to some extent.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eComplications\u003c/h2\u003e \u003cp\u003eNo major procedure-related complications such as spinal cord infarction was observed. Minor complications included nausea, vomiting, transient chest pain, fever, and fatigue. Among the patients, eight (25.0%) had nausea and vomiting, 12 (37.5%) experienced pain, one (3.1%) had fever, seven (21.9%) had fatigue. All minor complications resolved after conservative symptomatic therapy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSurvival analysis\u003c/h2\u003e \u003cp\u003eThe median follow-up duration was 15 months (2.5\u0026ndash;31 months). The percentage of patients who died during follow-up was 53.1% (17 of 32). The median PFS and OS were 6.0 months (95% CI: 4.1\u0026ndash;7.9) and 14.0 months (95% CI: 4.8\u0026ndash;23.2), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003ea and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003eb). The estimated PFS rates at 6-month, 1-year, and 2-year were 50.7%, 28.1%, and 0%, respectively, while the estimated OS rates at 6-month, 1-year, and 2-year were 81.3%, 57.4%, and 47.0%, respectively. In the univariate and multivariate analyses of PFS, only the number of D-BACE plus BAIC cycles (P\u0026thinsp;=\u0026thinsp;0.022) was significantly associated with PFS and emerged as an independent predictor (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Similarly, in the univariate analyses of OS, performance status score (p\u0026thinsp;=\u0026thinsp;0.029), number of D-BACE plus BAIC cycles (P\u0026thinsp;=\u0026thinsp;0.017), and subsequent systemic therapies (P\u0026thinsp;=\u0026thinsp;0.038) were significantly associated with OS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In the multivariate analyses, only the number of D-BACE plus BAIC cycles (P\u0026thinsp;=\u0026thinsp;0.017) was an independent predictor of OS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and Multivariate Analysis of Prognostic Factors for Progression-free Survival with Cox Proportional Hazards Model.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026le;\u0026thinsp;65 y vs \u0026gt; 65 y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.10(047,2.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.820\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male vs female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.94(0.31,2.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.907\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerformance status score (0 vs 1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93(0.40,2.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.857\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size(\u0026le;\u0026thinsp;5cm vs \u0026gt;5cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.07(0.87,4.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location (center vs proximal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.50(0.64,3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.353\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epathology (non-squamous vs squamous)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.21(0.86,5.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of D-BACE plus BAIC cycles (\u0026le;\u0026thinsp;2 vs \u0026gt;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.27(0.09,0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.27(0.09,0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubsequent systemic therapies (No vs. Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.74(0.31,1.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: D-BACE, drug-eluting bead transbronchial artery chemoembolization; BAIC, bronchial artery infusion chemotherapy; HR, Hazard ratio.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and Multivariate Analysis of Prognostic Factors for Overall Survival with Cox Proportional Hazards Model.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026le;\u0026thinsp;65 y vs \u0026gt; 65 y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.69(0.62,4.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male vs female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.70(0.20,2.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.586\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerformance status score (0 vs 1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.56(1.14,11.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.98(0.79,11.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size(\u0026le;\u0026thinsp;5cm vs \u0026gt;5cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.51(0.58,3.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.401\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location (center vs proximal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.71(0.25,1.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.512\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epathology (non-squamous vs squamous)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.86(0.64,5.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of D-BACE plus BAIC cycles (\u0026le;\u0026thinsp;2 vs \u0026gt;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.20(0.05,0.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17(0.04,0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubsequent systemic therapies (No vs. Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.30(0.10,0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53(0.15,1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: D-BACE, drug-eluting bead transbronchial artery chemoembolization; BAIC, bronchial artery infusion chemotherapy; HR, Hazard ratio.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eFor NSCLC that progresses after the first and secondary standard treatment, the current change in targeted drugs or chemotherapy regimens and multi-drug combination therapy are commonly used, but the results are still unsatisfactory. Patients with severe adverse reactions, such as severe immune-associated pneumonia, severe liver function injury, and severe bone marrow suppression, during systemic therapy in the first and second lines of treatment, may have poor compliance with systemic therapy in subsequent lines of treatment. The failure of first - and second-line treatments further reduces patient compliance with post-line treatment. This retrospective study of 32 patients suggests that D-BACE plus BAIC is a safe and effective treatment for refractory advanced NSCLC, with no major complications. Tumor control, defined as the achievement of CR, PR, or SD, was successfully achieved in all cases within this series. Furthermore, the median OS in this study was 14.0 months, which appears to be better than that achieved with gemcitabine plus carboplatin (10.0 months), pemetrexed (7.4months), or docetaxel (10.0months) \u003csup\u003e14, 15\u003c/sup\u003e. We also found that patients who had previously received immunotherapy had a better tumor response than those who had not. Our results add to the growing body of literature, suggesting that D-BACE plus BAIC is a promising treatment option and may provide a reasonable alternative for refractory advanced NSCLC.\u003c/p\u003e \u003cp\u003eFor the management of NSCLC, D-BACE plus BAIC offers two important advantages over systemic chemotherapy. First, the lesions in refractory advanced NSCLC are usually large, leading to blood circulation disorders in the tumor. As such, it is difficult to reach the tumor and its center through an intravenous drip, let alone the effective drug concentration, resulting in poor systemic efficacy and high toxicity\u003csup\u003e16\u003c/sup\u003e. The administration of transarterial chemoembolization and infusion chemotherapy leads to high concentrations of drugs within the tumor tissue, which can effectively overcome chemoresistance \u003csup\u003e3\u003c/sup\u003e. Second, drug-eluting beads have the capacity to embolize the arteries that supply nutrients to tumors, thereby depriving the tumor of its vital source. Additionally, these specialized beads gradually release the chemotherapy drugs, they are loaded with, over the course of a month, ensuring a sustained and controlled delivery of medication directly into the tumor tissue. As a result, the concentration of drugs in the peripheral blood remains minimal. Therefore, the incidence of adverse reactions caused by chemotherapeutic drugs in D-BACE plus BAIC is lower than that in systemic chemotherapy. The theoretical basis for selecting lobaplatin as an arterial infusion chemotherapy drug is as follows: 1) Although cisplatin, carboplatin, nedaplatin and other platinum-based chemotherapy drugs are commonly used in the clinic of non-small cell lung cancer, the patients in this study have been resistant to these drugs, so the efficacy of using these drugs after arterial infusion chemotherapy is expected to be poor, and lobaplatin does not have cross-resistance with the first-and second-generation platinum-based drugs mentioned above. 2) Lobaplatin, as a third-generation platinum, has lower toxic side effects than first-generation platinum, and has shown good anti-tumor effects on non-small cell lung cancer in previous animal experiments and clinical studies\u003csup\u003e17, 18\u003c/sup\u003e. 3) Compared with oxaliplatin, lobaplatin has better water solubility, and the pH value of its water soluble is 6\u0026ndash;8, which is close to the normal physiological pH of human body, so it is more suitable for arterial perfusion chemotherapy, which will not cause arterial irritant spasm. Liu et al. conducted a study that revealed the superior outcomes of D-BACE in terms of PFS and OS when compared to chemotherapy for patients with refractory advanced NSCLC. This study indicates that D-BACE has the potential to serve as an additional treatment option due to its favorable therapeutic efficacy, ability to enhance quality of life, and its tolerable safety profile for these patients \u003csup\u003e1\u003c/sup\u003e. He et al. conducted a comprehensive analysis on the effectiveness and safety of D-BACE in comparison to that of BAIC, followed by polyvinyl alcohol (PVA) particle embolization, for treating advanced squamous cell lung cancer after the failure of systemic therapy. The study revealed that the D-BACE group demonstrated a median PFS of 4.3 months and OS of 12.6 months. In contrast, the BAIC plus PVA group exhibited a significantly shorter median PFS of 3.2 months and OS of 8.1 months. These results unequivocally indicate the superiority of D-BACE over BAIC plus PVA embolization in the treatment of advanced squamous cell lung cancer \u003csup\u003e19\u003c/sup\u003e. The median PFS and OS in the D-BACE group were shorter than those observed in our study. This may be because BAIC was not performed in the D-BACE group, and squamous cancer accounted for 59.4% (n\u0026thinsp;=\u0026thinsp;19) of the patients in our study. According to a multicenter prospective study, the use of D-BACE resulted in a notable enhancement in the quality of life for patients with refractory NSCLC. Additionally, the study revealed a median OS of 11.5 months when utilizing this treatment approach \u003csup\u003e20\u003c/sup\u003e. However, it should be noted that squamous cancer accounted for 83.7% (36) of the patients in this prospective study, which might have influenced the observed OS. The study reported promising efficacy with a median PFS of 7.0\u0026ndash;11.0 months and OS of 8.0\u0026ndash;18.4 months, as well as tolerable toxicity in patients with refractory advanced NSCLC (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The PFS and OS rates in these studies were better than those in our study. We suggest that the reason for this difference could be attributed to the fact that only 56.3% (18/32) of patients received systemic therapies in our study. However, patients who received subsequent systemic therapies had higher OS than those without, as shown in the univariate analysis, although subsequent systemic therapies were not identified as an independent influencing factor in the multivariate analysis. These findings suggest that combination therapy may benefit some patients.\u003c/p\u003e \u003cp\u003eIn this study, minor adverse events after D-BACE plus BAIC, such as transient chest pain, nausea, vomiting, fever, and fatigue, were usually self-limiting or resolved after conservative symptomatic therapies, which is consistent with previous studies \u003csup\u003e8, 20\u003c/sup\u003e. Major complications such as esophageal fistula, spinal cord infarction, posterior circulation cerebral infarction, and myocardial infarction due to non-target embolization were not observed in our study, and were also rare in a recent bronchial artery embolization series \u003csup\u003e5, 21\u003c/sup\u003e. However, these serious complications should be noted and avoided, with careful monitoring during the procedure. Based on our experience, the following points may help reduce the complications of the operation: iodized oil should be avoided for embolization of lung cancer because the small diameter of iodized oil droplets can easily cause ectopic embolization, which can further lead to serious complications, such as spinal cord injury and cerebral infarction \u003csup\u003e20\u003c/sup\u003e. Drug-eluting beads or microsphere embolization with an inner diameter ranging between 300 and 500 mm is strongly advised based on an in-depth anatomical study. This study proposes that the anastomotic diameter of both the bronchial and pulmonary arteries could potentially accommodate sizes of up to 325 mm \u003csup\u003e22\u003c/sup\u003e. An additional factor to consider is that when using an excessively large embolization material, it primarily leads to proximal embolization. This, in turn, significantly diminishes the effectiveness of the treatment due to the establishment of collateral circulation \u003csup\u003e20\u003c/sup\u003e. Drug-eluting beads or blank microspheres were utilized in all patients due to their superior size, uniformity, and improved penetration characteristics compared to those of PVA or gelatin sponge particles. Notably, these microspheres possess smooth hydrophilic-coated surfaces, which significantly reduce the risk of clumping within catheters \u003csup\u003e21\u003c/sup\u003e. These results indicate that regurgitation does not occur more easily with drug-eluting beads or blank microspheres than with PVA or gelatin sponge particles. As clumping increases the transient resistance to embolic injection, systemic pulmonary shunts should be identified, and a suitable particle embolic agent of particle size should be selected to seal the fistula before D-BACE. Vascular variation or abnormal anastomosis should also be recognized, especially if the tumor-feeding vessels originate from the subclavian artery branches or have anastomotic branches, because ectopic embolization may cause posterior circulation stroke. In addition, blood vessels that communicate with the coronary arteries should also be considered when embolizing, because ectopic embolization may cause myocardial infarction.\u003c/p\u003e \u003cp\u003eThe limitations of this study are predominantly associated with the limited sample size and the absence of a control group. In addition, there was heterogeneity in the standard systemic therapies given to patients included in this study; it is difficult to assess the potential effect. Additionally, it is still unknown which chemotherapeutic agents loaded with eluting beads are the most effective and safe in treating NSCLC. A multicenter prospective study had showed drug-eluting beads loaded with epirubicin for D-BACE was effective and safe in treating refractory NSCLC\u003csup\u003e20\u003c/sup\u003e. In this study, we also used epirubicin for loading DC Bead\u0026trade; particles, while oxaliplatin, vinorelbine, and gemcitabine have been reported for loading CalliSpheres beads, which are commonly used for lung cancer in systemic chemotherapy \u003csup\u003e23\u0026ndash;25\u003c/sup\u003e. However, these drugs are not available for being loaded onto DC Beads according to the manufacturer\u0026rsquo;s instructions. Moreover, we found a correlation between previous immunotherapy and tumor response after treatment. However, due to the retrospective nature of this study, conducting an in-depth analysis was difficult, and we could not provide a convincing explanation. Further studies on immune status and treatment response are expected to answer this question. Finally, only 31.2% of the patients underwent more than three sessions of D-TACE, which may be insufficient to achieve satisfactory efficacy.\u003c/p\u003e \u003cp\u003eD-BACE combined with BAIC is a feasible, safe, and effective treatment option for patients with refractory advanced NSCLC. We present our experience using this technique for patient selection and demonstrate its feasibility with a satisfactory safety profile.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNSCLC, non-small-cell lung cancer; D-BACE, drug-eluting bead transbronchial artery chemoembolization; BAIC, bronchial artery infusion chemotherapy; PFS, progression-free survival; OS, overall survival; CI, confidence interval; IRB, Institutional Review Board; CT, computed tomography; SD, standard deviation; HRs, Hazard ratios; ORR, overall response rate; DCR, disease control rate; PVA, polyvinyl alcohol\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis single-center retrospective study was approved by the Institutional Review Board (IRB) of our hospital（No. KY2024-050-02）\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflicts of interest regarding the publication of this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupported by grants from the National Natural Science Foundation of China (82102163) and the National Key Research and Development Program (Project No. 2023YFC2507104).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLiu XF, Lin H, Wang Q, Mu M, Pan P, Tian FF, et al. Drug-eluting bead bronchial arterial chemoembolization vs. chemotherapy in treating advanced non-small cell lung cancer: comparison of treatment efficacy, safety and quality of life. Eur Rev Med Pharmacol Sci 2021; 25 (6): 2554-2566. doi: 10.26355/eurrev_202103_25419.\u003c/li\u003e\n\u003cli\u003eScartozzi M, Mazzanti P, Giampieri R, Berardi R, Galizia E, Gasparini S, et al. Clinical predictive factors for advanced non-small cell lung cancer (NSCLC) patients receiving third-line therapy: Selecting the unselectable? Lung Cancer 2010; 68 (3): 433-437. doi: 10.1016/j.lungcan.2009.07.008.\u003c/li\u003e\n\u003cli\u003eBoas FE, Kemeny NE, Sofocleous CT, Yeh R, Thompson VR, Hsu M, et al. Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial. Radiology 2021; 301 (2): 474-484. doi: 10.1148/radiol.2021210213.\u003c/li\u003e\n\u003cli\u003eBi Y, Shi X, Yi M, Han X, Ren J. Pirarubicin-loaded CalliSpheres\u0026reg; drug-eluting beads for the treatment of patients with stage III\u0026ndash;IV lung cancer. Acta Radiologica 2021; 63 (3): 311-318. doi: 10.1177/0284185121994298.\u003c/li\u003e\n\u003cli\u003eRen K, Wang J, Li Y, Li Z, Wu K, Zhou Z, et al. The Efficacy of Drug-eluting Bead Transarterial Chemoembolization Loaded With Oxaliplatin for the Treatment of Stage III-IV Non-small-cell Lung Cancer. Academic Radiology 2022; 29 (11): 1641-1646. doi: 10.1016/j.acra.2022.01.015.\u003c/li\u003e\n\u003cli\u003eLiu J, Zhang W, Ren J, Li Z, Lu H, Sun Z, et al. Efficacy and Safety of Drug-Eluting Bead Bronchial Arterial Chemoembolization Plus Anlotinib in Patients With Advanced Non-small-Cell Lung Cancer. Front Cell Dev Biol 2021; 9 768943. doi: 10.3389/fcell.2021.768943.\u003c/li\u003e\n\u003cli\u003eBie Z, Li Y, Li B, Wang D, Li L, Li X. The efficacy of drug-eluting beads bronchial arterial chemoembolization loaded with gemcitabine for treatment of non-small cell lung cancer. Thoracic cancer 2019; 10 (9): 1770-1778. doi: 10.1111/1759-7714.13139.\u003c/li\u003e\n\u003cli\u003eLiu X, Lin H, Wang Q, Mu M, Pan P, Tian F, et al. Drug-eluting beads bronchial arterial chemoembolization plus intercostals arterial infusion chemotherapy is effective and well-tolerated in treating non-small cell lung cancer patients with refractory malignant pleural effusion. J Thorac Dis 2021; 13 (4): 2339-2350. doi: 10.21037/jtd-20-1603.\u003c/li\u003e\n\u003cli\u003eKennoki N, Hori S, Yuki T, Hori A. Transcatheter Arterial Chemoembolization with Spherical Embolic Agent in Patients with Pulmonary or Mediastinal Metastases from Breast Cancer. J Vasc Interv Radiol 2017; 28 (10): 1386-1394. doi: 10.1016/j.jvir.2017.06.003.\u003c/li\u003e\n\u003cli\u003eHori A, Ohira R, Nakamura T, Kimura Y, Ueda S, Torii M, et al. Transarterial chemoembolization for pulmonary or mediastinal metastases from hepatocellular carcinoma. The British Journal of Radiology 2020; 93 (1110): 20190407. doi: 10.1259/bjr.20190407.\u003c/li\u003e\n\u003cli\u003evon Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370 (9596): 1453-1457. doi: 10.1016/S0140-6736(07)61602-X.\u003c/li\u003e\n\u003cli\u003eHori S, Nakamura T, Kennoki N, Dejima I, Hori A. Transarterial management of advance lung cancer. Jpn J Clin Oncol 2021; 51 (6): 851-856. doi: 10.1093/jjco/hyab050.\u003c/li\u003e\n\u003cli\u003eEisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). European Journal of Cancer 2009; 45 (2): 228-247. doi: 10.1016/j.ejca.2008.10.026.\u003c/li\u003e\n\u003cli\u003eDu L, Morgensztern D. Chemotherapy for Advanced-Stage Non\u0026ndash;Small Cell Lung Cancer. The Cancer Journal 2015; 21 (5): 366-370. doi: 10.1097/ppo.0000000000000141.\u003c/li\u003e\n\u003cli\u003eNishiyama A, Katakami N, Yoshioka H, Iwasaku M, Korogi Y, Hata A, et al. Retrospective efficacy and safety analyses of erlotinib, pemetrexed, and docetaxel in EGFR-mutation-negative patients with previously treated advanced non-squamous non-small-cell lung cancer. Lung Cancer 2015; 89 (3): 301-305. doi: 10.1016/j.lungcan.2015.06.017.\u003c/li\u003e\n\u003cli\u003eJin SQ, Zhao HY, Bai B, Ma CH, Cao HL. Transcatheter arterial chemoembolization improves clinical efficacy and life quality of patients with lung cancer and reduces adverse reactions. Am J Transl Res 2021; 13 (9): 10396-10403.\u003c/li\u003e\n\u003cli\u003eXie C, Xu Y, Jin W, Lou L. Antitumor activity of lobaplatin alone or in combination with antitubulin agents in non-small-cell lung cancer. Anti-cancer drugs 2012; 23 (7): 698-705. doi: 10.1097/CAD.0b013e328352cc10.\u003c/li\u003e\n\u003cli\u003eChen C, Wang W, Yu Z, Tian S, Li Y, Wang Y. Combination of computed tomography-guided iodine-125 brachytherapy and bronchial arterial chemoembolization for locally advanced stage III non-small cell lung cancer after failure of concurrent chemoradiotherapy. Lung Cancer 2020; 146 290-296. doi: 10.1016/j.lungcan.2020.06.010.\u003c/li\u003e\n\u003cli\u003eHe G, Yang K, Zhang X, Pan J, Han A, Gao Z, et al. Bronchial artery chemoembolization with drug-eluting beads versus bronchial artery infusion followed by polyvinyl alcohol particles embolization for advanced squamous cell lung cancer: A retrospective study. Eur J Radiol 2023; 161 110747. doi: 10.1016/j.ejrad.2023.110747.\u003c/li\u003e\n\u003cli\u003eZhao YW, Liu S, Qin H, Sun JB, Su M, Yu GJ, et al. Efficacy and safety of CalliSpheres drug-eluting beads for bronchial arterial chemoembolization for refractory non-small-cell lung cancer and its impact on quality of life: A multicenter prospective study. Front Oncol 2023; 13 1110917. doi: 10.3389/fonc.2023.1110917.\u003c/li\u003e\n\u003cli\u003eKettenbach J, Ittrich H, Gaubert JY, Gebauer B, Vos JA. CIRSE Standards of Practice on Bronchial Artery Embolisation. Cardiovasc Intervent Radiol 2022; 45 (6): 721-732. doi: 10.1007/s00270-022-03127-w.\u003c/li\u003e\n\u003cli\u003ePump K. Distribution of bronchial arteries in the human lung. Chest 1972; 62 (4): 447-451. doi: 10.1378/chest.62.4.447.\u003c/li\u003e\n\u003cli\u003eMa X, Zheng D, Zhang J, Dong Y, Li L, Jie B, et al. Clinical outcomes of vinorelbine loading CalliSpheres beads in the treatment of previously treated advanced lung cancer with progressive refractory obstructive atelectasis. Front Bioeng Biotechnol 2022; 10 1088274. doi: 10.3389/fbioe.2022.1088274.\u003c/li\u003e\n\u003cli\u003eLi YM, Guo RQ, Bie ZX, Li B, Li XG. Sintilimab plus Bronchial Arterial Infusion Chemotherapy/Drug-Eluting Embolic Chemoembolization for Advanced Non-Small Cell Lung Cancer: A Preliminary Study of 10 Patients. J Vasc Interv Radiol 2021; 32 (12): 1679-1687. doi: 10.1016/j.jvir.2021.08.019.\u003c/li\u003e\n\u003cli\u003eBi Y, Li F, Ren J, Han X. The safety and efficacy of oxaliplatin-loaded drug-eluting beads transarterial chemoembolization for the treatment of unresectable or advanced lung cancer. Front Pharmacol 2022; 13 1079707. doi: 10.3389/fphar.2022.1079707.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Interventional Radiology, Chemoembolization, Non-Small-Cell Lung Cancer, Catheterization, Bronchial Artery","lastPublishedDoi":"10.21203/rs.3.rs-4612874/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4612874/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eOBJECTIVES: \u003c/strong\u003eThe treatment strategy for previously standard treated non-small-cell lung cancer (NSCLC) still remained challenge. This study was to evaluate the effectiveness and safety of epirubicin-loaded drug-eluting bead transbronchial artery chemoembolization (D-BACE) plus bronchial artery infusion chemotherapy (BAIC) in patients with refractory advanced NSCLC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMETHODS:\u003c/strong\u003e Between January 2018 and December 2022, 32 patients with refractory advanced NSCLC (26 males; mean age of 64±9.3years [range 41-78]; 19 squamous carcinomas [59.4%]) who had received one or more previous standard treatments and received D-BACE (epirubicin 50mg) plus BAIC (lobaplatin 30 mg/m2) were included in our study. The study evaluated several parameters including local tumor response based on RECIST 1.1 criteria, progression-free survival (PFS), overall survival (OS), and complication rates. To examine the impact of different factors on PFS and OS, Kaplan–Meier and Cox regression analyses were performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRESULTS:\u003c/strong\u003e A total of 68 D-BACE plus BAIC sessions (median, 1, range 1-7) were performed. Overall response and disease control rates were 25% and 100%, respectively. The median PFS and median overall survival were 6.0 months (95% confidence interval (CI): 4.1–7.9) and 14.0 months (95% CI: 4.8–23.2), respectively. The number of cycles in the D-BACE plus BAIC treatment was found to be an independent predictor of PFS and OS. There were no instances of severe procedure-related complications or deaths during the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONCLUSIONS: \u003c/strong\u003eThe combination of D-BACE and BAIC shows great potential as a treatment choice for patients with refractory advanced NSCLC.\u003c/p\u003e","manuscriptTitle":"Drug-eluting beads bronchial arterial chemoembolization in advanced and standard treatment-refractory/ineligible NSCLC","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-23 22:14:28","doi":"10.21203/rs.3.rs-4612874/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3a01bde7-bdba-40cd-980e-61b0a8551a56","owner":[],"postedDate":"July 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-27T16:48:08+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-23 22:14:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4612874","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4612874","identity":"rs-4612874","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}