Feasibility and Safety of Cone-Beam Computed Tomography Advanced Navigation to Optimize Intra-arterial Chemotherapy Infusion of Skull Base Tumors

• Abstract
• Introduction
• Materials and Methods
• Patients
• Intra-arterial Chemotherapy Infusion Procedure
• Endpoints
• Statistical Analysis
• Results
• Patients
• Procedures and Adverse Events
• Outcomes
• Discussion
• Conclusion
• References

Abstract

Purpose To assess the feasibility and safety of cone-beam computed tomography (CBCT) advanced navigation for optimizing intra-arterial chemotherapy infusion (IACI) in patients with skull base tumors.

Materials and Methods Retrospective review on 10 consecutive IACI procedures performed in five patients (four women, 1 man) over a 1-year period. The median age of the patients was 71 years (interquartile range: 34–74). During the procedures, a CBCT-based navigation software was employed to evaluate tumor perfusion and guide the infusion methods. Catheterization of the primary tumor feeding vessel was performed in seven cases when it originated from the external carotid artery, whereas a temporary balloon-assisted occlusion technique was utilized in the remaining three cases where the tumor was primarily fed by the internal carotid artery. Carboplatin, topotecan, and melphalan were injected over a 10-minute period. Fluoroscopy time, reference dose, and Kerma area product, which estimates effective dose, were analyzed.

Results The technical success rate was 100%, with a median procedure length of 82 minutes (79–90). The median fluoroscopy time was 11.3 minutes (9.4–16.9), reference dose was 93.5 mGy (62–256.5), and Kerma area product was 11.6 Gy.cm² (9.5–25.4). The median effective dose was 3.8 mSv (1.5–5.1). The median follow-up duration was 233.5 days (186.3–432). One severe adverse event was reported, involving a right brachial hematoma and brachiocephalic artery dissection related to catheterization through a type III aortic arch. Three patients exhibited disease progression, but two patients showed stable disease.

Conclusion IACI for skull base tumors guided by CBCT navigation is both feasible and safe.

Introduction

Intra-arterial administration of chemotherapy has emerged as a minimally invasive procedure yielding successful outcomes for various malignancies, including retinoblastoma.[1] [2] Advancements in imaging technology have paved the way for the integration of cone-beam computed tomography (CBCT) allowing advanced navigation.[3] [4] [5] [6] This cutting edge technique offers high-resolution imaging capabilities, enabling precise catheter placement for targeted delivery of therapeutic agents while minimizing the potential for nontargeted treatment.[7] [8] [9] [10] Moreover, CBCT holds promise in mitigating radiation exposure for patients.[11]

Despite the increasing adoption of CBCT navigation, there remains a scarcity of systematic investigations evaluating its feasibility and safety during intra-arterial chemotherapy infusion (IACI).[12] Consequently, the objective of this study is to assess the feasibility and safety of CBCT advanced navigation to optimize IACI of skull base tumors.

Materials and Methods

Patients

This Institutional Review Board approved this retrospective study. The study was a retrospective analysis of 10 consecutive IACI performed in five patients at a single center over a 1-year period (April 2022–April 2023). The indications for IACI were skull base tumors nonamendable for any other local therapies, all of which were causing clinical symptoms, and radiographic progression after surgery and radiation therapy. The treatment protocol for each patient was to perform one IACI following by a second IACI 1 month after if the first procedure was tolerated clinically and/or biologically. Further IACI was be planned based on magnetic resonance (MR) imaging follow-up after two IACI with the goal to further improve local control. In case of tumor progression on MR imaging or poor tolerance, no further IACI was offered.

Intra-arterial Chemotherapy Infusion Procedure

The procedure was performed under general anesthesia by an experienced interventional radiologist with 15 years of experience using image guidance (Allia, GE Healthcare, Milwaukee, Wisconsin, United States). A 6-F access to the right common femoral artery was obtained using local anesthesia and ultrasound guidance. A Berenstein 5-F catheter and a 6-F distal access catheter (Benchmark, Penumbra, Alameda, California, United States) were used to perform diagnostic angiography of the common carotid artery. Rotational angiography of the carotid arteries was acquired using a total of 30 mL of iohexol 350 mg (Omnipaque 350, GE Healthcare, Milwaukee, Wisconsin, United States), injected at 2 mL/s (450 psi) with an X-ray delay of 3 seconds in 10 seconds, with the C-arm rotating 200 degrees around the patient at 20 degree/s, acquiring a series of 300 projections at 30 frames/s. The reconstructed 3D field of view was a cylinder of about 16 cm diameter and height. The matrix size was 512 × 512 × 512. A planning software (Embo ASSIST, GE Healthcare) was used to analyze the vasculature in 3D, identify the origin of the main tumor feeder if any, and used for navigation augmented guidance in the external carotid artery overlaying the 3D vasculature on fluoroscopy.

In external carotid artery and branches, the targeted vessel was catheterized after the introduction of a microcatheter (Headway 1.6F, Microvention, Terumo, Tokyo, Japan) over a 0.010 guide wire (Transend, Boston Scientific, Boston, Massachusetts, United States) ([Fig. 1]). If a stable microcatheter position without risk of reflux was achieved, for all IACI, successively 40 mg of carboplatin in 10 mL; 2mg of topotecan in 3 mL; and 5 mg of melphalan in 10 mL were delivered over 10 minutes to avoid reflux. To deliver the chemotherapy in the terminal (C7) internal carotid artery, a 4 × 7mm hyperglide balloon (Hyperform, Medtronic, Minneapolis, Minnesota, United States) was further advanced into the internal carotid artery distal the origin of the ophthalmic artery and slowly inflated as detailed in.[13] The same chemotherapy regimen was delivered through the 6-F catheter.

Repeat angiography was immediately performed to assess patency of carotid and cerebral arteries and subsequently the catheters were removed. An occlusion device (Angioseal, Terumo, Tokyo, Japan) was systematically used when removing the catheter sheath.

Endpoints

The primary outcome measure was the procedure-related complications using the Society of Interventional Radiology Adverse Event Classification System,[14] and secondary outcome measure was treatment failure. The outcomes were assessed through clinical and radiographic follow-up after the procedure when participants return for visit to conduct physical examinations, interviews, laboratory tests, or imaging studies. The dose was evaluated by measuring the fluoroscopy time (FT), reference dose (RD), and Kerma area product (KAP). The effective dose was calculated as follow: effective dose = FT × (dose rate × KAP / Area) × W. The weighting factor (W) was based on the organs and tissues that are most sensitive to radiation exposure are the thyroid gland, the salivary glands, and the lens of the eye. The weighting factors for these organs and tissues are: thyroid gland: 0.04; salivary glands: 0.01; lens of the eye: 0.01. The estimated area of irradiation was of 200 cm². According to RECIST version 1.1 criteria, a complete response was defined as the disappearance of all target lesions on follow-up MR imaging; a partial response (PR) was defined as at least a 30% decrease in the sum of the longest diameter of the target lesions; progressive disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of the target lesions; and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor a sufficient increase to qualify for PD.

Statistical Analysis

All statistical analyses were performed using the Statistical Package for the Social Sciences version 21.0 (SPSS Inc., Chicago, Illinois, United States).

Results

Patients

Among the five patients who underwent IACI, four were female (83.3%), one was male (16.7%), and the median (interquartile range) age was 71 (34–74) years ([Table 1]). The median body mass index was 30.2 (22.6–31.1). The most common primary indication for the procedure was radiographic progression, which occurred in 100% of the patients (10/10), followed by headache 50% (3/6), neurological deficit manifested as focal weakness in 50% of patients (3/6).

Procedures and Adverse Events

The technical success rate was 100%. Median length of procedure was 82 minutes (79–90). The median FT was 11.3 minutes (9.4–16.9); the median RD was 93.5 mGy (62–256.5); and the median KAP was 11.6 Gy.cm² (9.5–25.4) ([Table 2]). The median effective dose was 3.8 mSv (1.5–5.1).

In the 7 days after IACI, the labs remained within normal for all patients: white blood cells count of 8.4 K/µL in median (6.4–11), neutrophils 82.5% (80.4–86.8), platelets 211.5 K/µL (155.3–223.8), hemoglobin 10.5 g/dL (9–11.7), aspartate aminotransferase 20.5 U/L (14.8–28.3), alanine aminotransferase 24 U/L (12–36.8), total bilirubin 0.6 mg/dL (0.5–0.7), and creatinine 0.7 mg/dL (0.7–0.8).

One patient developed a right brachial hematoma and a dissection of the brachiocephalic trunk due to a through and through access to the common carotid artery in a patient presenting with a type III aortic arch ([Fig. 2]). The patient was treated conservatively after the procedure and did not require reintervention.

Outcomes

The median follow-up was 233.5 days (186.3–432) after IACI. SD was reported in two patients according to RECIST. Progression disease was observed in three patients: two patients died 186 and 140 days after the last procedures, respectively, but the third patient was alive 466 days after the last procedure.

Discussion

The purpose of this retrospective study was to evaluate the feasibility and safety of CBCT advanced navigation to optimize IACI in a specific population of patients diagnosed with skull base tumors. The study showed a high rate of successful technical outcomes. Additionally, the incidence of adverse events was low, indicating that the procedure is safe.

The utilization of CBCT in neurovascular interventions provides several benefits. It improves the quality of imaging, facilitating accurate identification of anatomical structures and aiding in procedural planning.[10] Real-time guidance during the intervention also helps minimize radiation exposure for both patients and health care providers. Compared with conventional computed tomography or digital subtraction angiography, CBCT utilizes lower radiation doses, reducing the risk of radiation-related complications for patients and health care providers. In this study, the median dose metrics, including KAP, RD, and FT, were calculated and found to be consistent with the suggested reference levels for cerebral angiography in interventional radiology (KAP = 90 Gy.cm², reference dose = 630 mGy, and FT = 15 minutes).[15] [16] This approach is comparable to a previous report on chemoinfusion of retinoblastoma performed in children (mean FT: 10.2 ± 8.4 minutes, KAP: 21.9 ± 24.1 Gy.cm², and total radiation dose: 42.3 ± 41.4 mGy)[17]

IACI is an effective treatment option for certain conditions, and the incidence of associated complications is generally low.[1] [2] [18] Potential complications may arise from arterial access, such as the development of a pseudoaneurysm or a dissection, or due to unintentional infusion into an artery supplying cranial nerves. Developments of new operative techniques may help, such as through and through innominate access,[19] but advanced imaging guidance such as CBCT and navigation software may further improve the outcomes.

The limitations of this study include its retrospective and nonrandomized design as well as the relatively small number of patients included, which may introduce biases in patient selection and data collection. The absence of a control group makes it challenging to compare the treatment outcomes with other interventions or the absence of treatment. Follow-up is short to evaluate the potential adverse events but comparable with previous publications.[12] Furthermore, the study was conducted at a single center, which restricts the generalizability of the findings to other health care settings. Future studies with larger sample sizes and randomized controlled designs are needed to further evaluate the effectiveness of this approach.

Conclusion

This retrospective study assessing the feasibility and safety of IACI infusion using CBCT in patients with skull base tumors revealed a high technical success rate and a low incidence of adverse events. The use of CBCT in neurovascular interventions offers advantages such as improved image quality and real-time guidance, leading to reduced radiation exposure. However, the study's limitations, including its retrospective design and small patient cohort, warrant further investigation with larger randomized controlled trials to validate these findings and provide more robust evidence.

Conflict of Interest

None declared.

• References

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• 12 Ishikura R, Ando K, Nagami Y. et al. Evaluation of vascular supply with cone-beam computed tomography during intraarterial chemotherapy for a skull base tumor. Radiat Med 2006; 24 (05) 384-387
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• 13 Klufas MA, Gobin YP, Marr B, Brodie SE, Dunkel IJ, Abramson DH. Intra-arterial chemotherapy as a treatment for intraocular retinoblastoma: alternatives to direct ophthalmic artery catheterization. AJNR Am J Neuroradiol 2012; 33 (08) 1608-1614
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• 14 Khalilzadeh O, Baerlocher MO, Shyn PB. et al. Proposal of a new adverse event classification by the Society of Interventional Radiology Standards of Practice Committee. J Vasc Interv Radiol 2017; 28 (10) 1432-1437.e3
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• 15 Miller DL, Kwon D, Bonavia GH. Reference levels for patient radiation doses in interventional radiology: proposed initial values for U.S. practice. Radiology 2009; 253 (03) 753-764
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• 16 Etard C, Bigand E, Salvat C. et al. Patient dose in interventional radiology: a multicentre study of the most frequent procedures in France. Eur Radiol 2017; 27 (10) 4281-4290
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• 17 Boddu SR, Abramson DH, Marr BP, Francis JH, Gobin YP. Selective ophthalmic artery chemosurgery (SOAC) for retinoblastoma: fluoroscopic time and radiation dose parameters. A baseline study. J Neurointerv Surg 2017; 9 (11) 1107-1112
  CrossrefPubMedSearch in Google Scholar
• 18 Francis JH, Levin AM, Zabor EC, Gobin YP, Abramson DH. Ten-year experience with ophthalmic artery chemosurgery: ocular and recurrence-free survival. PLoS One 2018; 13 (05) e0197081
  CrossrefPubMedSearch in Google Scholar
• 19 Kuo M-J, Chen P-L, Shih C-C, Chen I-M. Establishing stable innominate access by inserting a body floss wire from the brachial artery to the femoral artery facilitates right carotid artery stenting in Type III arch anatomy. Interact Cardiovasc Thorac Surg 2018; 26 (01) 8-10
  CrossrefPubMedSearch in Google Scholar

Address for correspondence

Publication History

Received: 21 November 2023

Accepted: 28 January 2024

Accepted Manuscript online:
30 January 2024

Article published online:
01 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1 Abramson DH, Gobin YP, Francis JH. Orbital retinoblastoma treated with intra-arterial chemotherapy. Ophthalmology 2021; 128 (10) 1437
  CrossrefPubMedSearch in Google Scholar
• 2 Francis JH, Roosipu N, Levin AM. et al. Current treatment of bilateral retinoblastoma: the impact of intraarterial and intravitreous chemotherapy. Neoplasia 2018; 20 (08) 757-763
  CrossrefPubMedSearch in Google Scholar
• 3 Blanc R, Seiler A, Robert T. et al. Multimodal angiographic assessment of cerebral arteriovenous malformations: a pilot study. J Neurointerv Surg 2015; 7 (11) 841-847
  CrossrefPubMedSearch in Google Scholar
• 4 Perhac J, Spaltenstein J, Pereira VM. et al. Improving workflows of neuro-interventional procedures with autostereoscopic 3D visualization of multi-modality imaging in hybrid interventional suites. Int J CARS 2016; 11 (02) 189-196
  CrossrefPubMedSearch in Google Scholar
• 5 Traynor L, Levy E, Choi JJ, Cleary K, Zeng J, Lindisch D. Software development for registration of digital subtraction angiography (DSA) images in uterine fibroid embolization. Stud Health Technol Inform 2000; 70: 350-355
  PubMedSearch in Google Scholar
• 6 Cooke DL, Levitt M, Kim LJ, Hallam DK, Ghodke B. Intraorbital access using fluoroscopic flat panel detector CT navigation and three-dimensional MRI overlay. J Neurointerv Surg 2010; 2 (03) 249-251
  CrossrefPubMedSearch in Google Scholar
• 7 Wang MQ, Duan F, Yuan K, Zhang GD, Yan J, Wang Y. Benign prostatic hyperplasia: cone-beam CT in conjunction with DSA for identifying prostatic arterial anatomy. Radiology 2017; 282 (01) 271-280
  CrossrefPubMedSearch in Google Scholar
• 8 Schott P, Katoh M, Fischer N, Freyhardt P. Radiation dose in prostatic artery embolization using cone-beam CT and 3D roadmap software. J Vasc Interv Radiol 2019; 30 (09) 1452-1458
  CrossrefPubMedSearch in Google Scholar
• 9 Bagla S, Rholl KS, Sterling KM. et al. Utility of cone-beam CT imaging in prostatic artery embolization. J Vasc Interv Radiol 2013; 24 (11) 1603-1607
  CrossrefPubMedSearch in Google Scholar
• 10 Dzaye O, Brahmbhatt A, Abajian A. et al. Middle meningeal artery embolization using cone-beam computed tomography augmented guidance in patients with cancer. Diagn Interv Imaging 2023; 104 (7-8): 368-372
  CrossrefPubMedSearch in Google Scholar
• 11 Nakagawa I, Park HS, Kotsugi M. et al. Enhanced hematoma membrane on DynaCT images during middle meningeal artery embolization for persistently recurrent chronic subdural hematoma. World Neurosurg 2019; 126: e473-e479
  CrossrefPubMedSearch in Google Scholar
• 12 Ishikura R, Ando K, Nagami Y. et al. Evaluation of vascular supply with cone-beam computed tomography during intraarterial chemotherapy for a skull base tumor. Radiat Med 2006; 24 (05) 384-387
  CrossrefPubMedSearch in Google Scholar
• 13 Klufas MA, Gobin YP, Marr B, Brodie SE, Dunkel IJ, Abramson DH. Intra-arterial chemotherapy as a treatment for intraocular retinoblastoma: alternatives to direct ophthalmic artery catheterization. AJNR Am J Neuroradiol 2012; 33 (08) 1608-1614
  CrossrefPubMedSearch in Google Scholar
• 14 Khalilzadeh O, Baerlocher MO, Shyn PB. et al. Proposal of a new adverse event classification by the Society of Interventional Radiology Standards of Practice Committee. J Vasc Interv Radiol 2017; 28 (10) 1432-1437.e3
  CrossrefPubMedSearch in Google Scholar
• 15 Miller DL, Kwon D, Bonavia GH. Reference levels for patient radiation doses in interventional radiology: proposed initial values for U.S. practice. Radiology 2009; 253 (03) 753-764
  CrossrefPubMedSearch in Google Scholar
• 16 Etard C, Bigand E, Salvat C. et al. Patient dose in interventional radiology: a multicentre study of the most frequent procedures in France. Eur Radiol 2017; 27 (10) 4281-4290
  CrossrefPubMedSearch in Google Scholar
• 17 Boddu SR, Abramson DH, Marr BP, Francis JH, Gobin YP. Selective ophthalmic artery chemosurgery (SOAC) for retinoblastoma: fluoroscopic time and radiation dose parameters. A baseline study. J Neurointerv Surg 2017; 9 (11) 1107-1112
  CrossrefPubMedSearch in Google Scholar
• 18 Francis JH, Levin AM, Zabor EC, Gobin YP, Abramson DH. Ten-year experience with ophthalmic artery chemosurgery: ocular and recurrence-free survival. PLoS One 2018; 13 (05) e0197081
  CrossrefPubMedSearch in Google Scholar
• 19 Kuo M-J, Chen P-L, Shih C-C, Chen I-M. Establishing stable innominate access by inserting a body floss wire from the brachial artery to the femoral artery facilitates right carotid artery stenting in Type III arch anatomy. Interact Cardiovasc Thorac Surg 2018; 26 (01) 8-10
  CrossrefPubMedSearch in Google Scholar