Developments in the management of bone metastases with interventional radiology.

Interventional radiology has known an exponential growth in the last years. Technological advances of the last decades, have made it possible to use new treatments on a larger scale, with safe and effective results. They could be considered as palliative treatments for painful lesions but also curative procedures, as single treatment or specially in combination with other techniques (surgery, radiation and oncology therapies, etc.).The main diffuse techniques are those of thermal ablation that destroy the target lesion through the heat; however there are also endovascular therapies that destroy the target tissue thanks to devascularization. Finally the is also the possibility to stabilize pathological fractures or impending fractures. In this paper all the most diffuse and effective techniques are reviewed and also a discussion of the main indications is done, with an analisys of the success and complications rates.

Introduction

Interventional Radiology (IR) is experiencing tremendous development and diffusion due to a variety of factors among which its minimal invasiveness. The interventional procedures, in fact, can be performed on clinically unstable patients, who hardly tolerate surgery, with the advantage of reducing hospitalization times (1-5). The technological advances of the last decades have made it possible to apply highly safe and efficient new treatment techniques on a larger scale, employing them as curative procedures and in combination with other techniques (surgery, radiation and oncology therapies, etc.). One limitation to the diffusion of these procedures, however, is represented by the educational effort needed to prepare the Interventional Radiologists, a specific multitasking category of professionals able to read and interpret images, while possessing the manual and cultural skills of a surgeon. In fact, if diagnostic imaging modalities are proved to be fundamental in the diagnosis of various diseases of the musculoskeletal system (6-15), spine (16-20) and tumors (21-26), on other hand, new technical and surgical skills have to be acquired. Also peculiar skills are required from the health care staff members who co-operate with them (nurses, technicians, etc.). In addition, the interventional radiologists are requested to be part of and interact with interdisciplinary teams, made up of oncologists, surgeons, radiotherapists, anaesthesiologists, etc. Despite all these factors, however, IR is gaining a more and more important role in the oncology field, and provides high quality results in terms of treatment efficacy and patient compliancy, accompanied by astonishingly low complication rates.

Interventional Radiology is currently applied as palliative treatment in patients with painful bone metastases (27-37). On this topic, there is plenty of scientific studies, but more randomized analyses are needed to validate the results obtained so far. Conversely, the curative application of IR is scarcely described in literature. Only in patients affected by oligometastatic diseases this approach was employed, even if limitally (32, 33, 38-41). Before going into details about the clinical indications, we present a brief description of the different techniques employed.

Interventional radiology techniques

Due to the wide choice of techniques available in the IR it is of paramount importance a deep study of the lesion that we are treating: localization, size and morphologic characteristics have to be deeply studied in order to plan also a consolidation (cementoplasty or vertoplasty) and not only the ablation, to spare the sensitive structures around the target lesion and also to choice and to use the more effective technique.

The main goal of the interventional radiologist is to obtain a tissutal damage that can be of double nature: ischemic (arterial embolization) and thermal-ablative. The latter is obtained through delivery of energy (radiofrequencies, microwaves, focused ultrasounds) and/or cold (cryoablation). Occluding the vessels that feed the target lesion, the intra-arterial embolization provokes the necrosis of the tissue (42-51). By selectively cauterizing all branches that feed the lesion, it is possible to obtain an optimal necrosis even of a lesion measuring several centimetres. The limits of this last technique, however, is represented by the impossibility to obtain a surgical sterilization of the lesion and by the fact that poor vascularity can impair the process of target tissue necrosis. The procedure is performed in the angiographic setting starting with an arterial peripheral access without general anesthesia of the patient, who is administered pain killer medicaments to avoid post-embolization syndromes that may occur when large lesions are treated.

Thermal and crio-ablation (28, 52-62) provoke necrosis of the target tissue through the employment of one or more needles delivering energy into the lesions. Under CT, MR and/or US guide (the latter is used in presence of soft tissue lesions) one or more needles are inserted into the lesion while energy is delivered. A necrotic area of varying size and morphology is obtained depending on number and technical features of the needles. Radiofrequencies (RFA) and microwaves (MWA) bring about necrosis through tissutal warming (60° and above), while cryoablation through a decrease in temperature (below 40°). All the procedures produce the same result, but have different characteristics as well as advantages and disadvantages.

RFA (Fig. 1) is the most widely diffuse procedure being the most cost-effective and the first to find application in several fields (56, 63-68). The needles employed deliver radiofrequencies that induce a temperature increase around the needle tip. The needle size varies from 0.5 to 4 max 5 centimetres, which guarantee spherical ablation areas. The needles cannot be used simultaneously to cover large volumes, but only sequentially. Additionally, the effects of RFA are impaired by the heat sink effect, occurring near the blood vessels. Finally, RFA does not propagate energy as homogeneously and deeply as MWA.

Figure 1.

Osteosclerotic lesion of the sacrum. a. and b. Scintigraphy and CT that detected the lesion (arrows); c. image during the treatment: RFA needle inside the lesion (arrow)

It is widely accepted that MWA (28, 52, 69-74) (Fig. 2) is more powerful than RFA for its ability in delivering immediate and optimal diffusion of energy around the needle (antenna). The heat sink effect is minimal and does not depend on the characteristics of non-conductivity of the tissues. On the other hand, some authors describe MWA energy delivery as less manageable than that delivered by RFA. In addition, MWA produces an oval ablation area considered as a limitation that the researchers are currently directing their efforts to overcome.

Figure 2.

a. Osteolytic lesion of the sacrum treated with two MW antennas (b); c. After treatment it is possible to appreciate air inside the treated lesion: this is an effect of the thermoablation (lung windowing, black arrows)

Crioablation (54, 55, 75-80) (Fig. 3) is extremely more expensive, but also more promising than the techniques described above. First, the ablation area can reach several centimetres (10 cm or even more) and presents an irregular morphology due to the possibility to employ more needles at the same time. The ablated area is imaged with CT where it appears hypodense to the surrounding tissue, not involved in the cooling process. This represents a great advantage to the radiologist who can rely on the possibility to assess in real time both the target area and the procedure. Finally yet importantly, pain is relieved by the antalgic effect of ice both in and around the lesion.

Figure 3.

Cryoablation of a sacral osteolytic lesion: two cryoprobes surrounded by the iceballs that appears hypodense compared with the safe tissues

A separate description deserves thermal ablation with MR-guided Focused Ultrasounds (MRgFUS) (29, 40, 63, 81-85) (Fig. 4). With this technique, energy is delivered without the employment of any other device (needles, antennas, etc.), than focused ultrasound beams that pass through the tissues without damaging them. The main advantage is minimal invasiveness. The main disadvantage lies in the impossibility to treat lesions that cannot be reached by the ultrasound beam. For this reason, it is possible to treat only superficial bone lesions that are not hidden by bone cortex and/or other structures, impairing the propagation of the beams (gut or metallic devices). MR guidance allows control of both the lesion and the healthy surrounding structures. Real time control of the temperature in the target lesion is possible by means of specific sequences, which allow evaluation of the efficiency while carrying out the treatment.

Figure 4.

a. Met of femur (dashed line) treated with MRgFUS: * transducer that generates the Ultrasound beam (represented by the triangle, in b)

Another field of application of IR is the use for consolidation and stabilization of pathologic fractures as well as prevention of the latter when the bone segment is replaced by pathologic tissue (impending fractures) (86-90). Due to the intrinsic properties of the material employed in cementoplasty (PMMA), which is quite resistant to compressive forces and less to torsional ones, the stabilization and prevention techniques are more broadly used for treatment of spinal and acetabular lesions than for peripheral extra spinal ones. Suggested indications for percutaneous stabilization of lytic lesions are painful and/or fractured lesions or those at higher risk of fracture according to Mireles’s classification (91-96), in patients unlikely to tolerate a surgical intervention, which remains the therapeutical gold standard. A typical case is represented by vertebroplasty during which cement is injected under fluoroscopic control into the pathologic bone segment. The fractures can also be fixed through percutaneous positioning of screws under CT and fluoroscopy monitoring. Other devices provide a major resistance to torsional forces in combination to cement (metallic nets created by percutaneous injection of thin metallic needles through bioptic needles). The screws are successfully employed for the stabilization of pathologic fractures of the ileo- and ischiopubic tracts, the iliac crest and acetabular region (97-102).

Clinical indications, validation of results and discussion

The main indication for IR treatments in the field of malignant bone lesions is the palliation of painful metastases through direct destruction of neoplastic cells (tumoural mass effect and inflammatory cytokines) and adjacent nervous ends. Despite the presence of several multicentre studies, it is still not possible to intervene radiologically as first choice on painful secondary bone lesions for the lack of randomized studies validating the safety and efficacy of these techniques. Although its limited rate of success (treatment response in 80% of patients; complete response in scarce 30% of treated patients; latency time between treatment and pain relief about 3 weeks; risk of pain recurrence 50%), the gold standard in this field remains radiation therapy (103-107). IR is quite promising in terms of both palliation and stabilization of the bone segment (53, 108-113). There is plenty of scientific literature describing each ablation technique in terms of safety and efficacy. About cryoablation of painful bone metastases, Callstrom et al. (54) describe a 75% response rate in 61 patients with a 24-week follow up and a mean pain reduction by 90%. Pusceddu et al. (28) describe the role of MWA highlighting a 91% rate of improvement in the BPI scale at 12-week follow-up and 72% of patients free from symptomatology. Dupuy et al. (27) strongly suggest the use of RFA for the treatment of painful bone metastases. In their patient series studied over a 3-month period, the authors observed remarkable improvement of symptomatology. The complication rate of these techniques is low, ranging between 0% (Pusceddu) and 5% (Dupuy). Focused ultrasounds present a 1.8% rate of complications and efficacy comparable to radiation therapy, and shorter latency times (pain disappears after only 3 days from the treatment). The use of transarterial embolization for treatment of bone metastases is scarcely described in literature. This technique, in fact, is mainly employed as adjuvant to others. Its main role is to provide devascularization of the target area in order to guarantee safety and efficacy to the procedures carried out subsequently (surgery or percutaneous thermal ablation). The combination of this technique with radiation therapy is described as highly efficient in terms of pain relief in one case of bone metastases secondary to liver cancer (Uemura et al.) (42). The main advantages of Interventional Radiology in the treatment of secondary bone lesions lie in the fact that the procedures allow direct damage of the tumoural tissue; this explains the shorter latency times between treatment and effects compared to radiation therapy and the higher percentage of success in the treated patients. The procedures are repeatable and, apart from complications, can be exclusively focused on the target area, without possibility to damage the surrounding structures. The periprocedural sedation and one night hospitalization after the treatment are considered as major limitations of these techniques.

Another feather in the interventional radiologist’s cap, however, is the possibility to stabilize pathologic fractures or prevent those secondary to metastases. The stabilization by means of cement and/or screws of pathologic fractures provoking pain produces pain relief owing to the antalgic effect of cement. It deserves recognition that preventing fractures and improving quality of life through mini-invasive treatments is better than operating to stabilize pathologic fractures, not to mention the related complications (recovery times, infectious complications, and latency times before starting chemo- and/or radiation therapy).

The technological advances associated to experience of the operators is making these procedures more and more radical and similar to surgery. There is a trend to treat the entire lesion to obtain the most satisfying results in terms of response, pain relief and symptom-free patients. All these factors will certainly pave the way to future, more challenging applications. In the peculiar field of the oligometastatic diseases, for example, the interventional radiologist could operate radically on the low number of metastases, by ablating all the pathologic foci percutaneously. While operating on the lesion, large margins should be maintained in order to ablate also the neighbouring microscopic foci.

Additionally, it has been largely described that radiofrequency and cryoablation prove useful when used in combination with radiation therapy (15, 31, 64, 87, 110, 114, 115). The reason for this favourable synergy is that radiation therapy has low effect on scarcely vascularized tissue, while radiofrequency and cryoablation do not depend on these characteristics of the tissue.