Cementoplasty to cryoablation: review and current status.

Over the last few decades, various percutaneous image-guided ablation and stabilization techniques, including cryoablation and cementoplasty, have emerged in the management of musculoskeletal lesions. There is growing utility of these procedures especially in the context of malignancy, where bone pain is one of the most common types of pain, and the skeleton is the third most frequent site of metastases. 1 This is compounded by the prevalence of bone metastases, with the annual age-adjusted incidence rate of newly diagnosed bone metastasis approximately 18.8 per 100 000 in the United States. 2 Currently, radiotherapy is considered the preferred treatment option for palliation for uncomplicated metastatic bone pain. However, radiotherapy alone does not contribute to bone stability. 3 , 4 Other limitations of radiotherapy include radio-resistance of some tumours, risk of radiation-related fracture especially to weight-bearing bones, osteitis, osteonecrosis, as well as radiation dose limits for 1 body site. 5 , 6 Additionally, radiotherapy has a delayed pain relief onset, typically 4 weeks and occasionally up to 15 weeks. 7 Surgery is only indicated as first-line treatment for selected metastatic bone lesions, such as slow-growing tumours and patients with relatively good prognosis. 8 Surgical decompression and instrumentation have a primary role in the management of acute spinal instability and spinal cord compression with neurological deficits. 4 While opioids are recommended for management of cancer-related bone pain, they are associated with multiple common side effects and sometimes suboptimal pain relief. 9 , 10 Given the limitations of traditional strategies, this review article serves to provide an update on the increasing role of cementoplasty and cryoablation in the musculoskeletal system, with an emphasis on pain palliation and tumour control.

In the authors’ experience, cannula placement is usually performed under fluoroscopy, cone-beam CT, or conventional CT, sometimes with the assistance of advanced navigation software and real-time multiplanar reformats, depending on resource availability and operator preference. CT is preferred for cervical and upper thoracic spinal access due to the excellent spatial resolution of adjacent soft tissue structures. CT gantry angulation or needle guidance software are useful adjuncts in difficult-to-access lesions. Ultrasound is useful in certain situations such as visualizing critical neurovascular structures close to the cannula trajectory. Fluoroscopic guidance for cement injection is preferred to visualize real-time cement flow and distribution. As musculoskeletal interventional oncology procedures become increasingly complex, many procedures are performed under a combination of CT and fluoroscopic guidance. This allows the acquisition of excellent spatial resolution on the axial plane with CT and real-time visualization of cement injection or embolization under fluoroscopy. The newest cone-beam CT units have incorporated artificial intelligence capabilities including deep learning algorithms that allow guidance of bone access cannulas without requiring fluoroscopy, markedly reducing radiation dose. 31 MRI guidance has also emerged, allowing target identification in soft tissue lesions while avoiding ionizing radiation, 32 , 33 although its usage is limited by costs and availability.

In the authors’ experience, cementoplasty is usually tolerated well under conscious sedation with local anaesthesia; general anaesthesia can also be considered for certain patients. Patients are positioned according to the site of target lesion; in conventional vertebroplasty, this usually means a prone position with padding under the thorax and ankles. Local anaesthesia is administered along the puncture site and expected cannula trajectory, infiltrating the subcutaneous tissues, muscles, and pain-sensitive periosteum. For vertebroplasty of a lumbar segment, a transpedicular approach is preferred where the upper outer aspect of the pedicle is accessed. The cannula is directed medially through the pedicle and into the anterior third of the vertebral body to the midline inferiorly. This optimizes cement distribution to ideally include most of the vertebral body with cement crossing the midline ( Figure 1 ). 19 A costotransverse approach for the thoracic vertebra is also feasible due to smaller pedicle sizes. Bipedicular access may be considered in some scenarios including suboptimal positioning of a single cannula, or severe central vertebral height loss preventing cannula placement along the midline. Other novel access routes, including transoral access of C2 and a trans-discal approach, have been reported. 26 , 27 Two-level vertebroplasty for osteoporotic lumbar compression fractures. Intra-procedural fluoroscopic images obtained in frontal (A) and lateral (B) planes to visualize cement deposition in the vertebral bodies. Postprocedural cone-beam CT images in coronal (C) and sagittal planes (D) demonstrated satisfactory cement fill with no leakage. Aside from vertebroplasty, other percutaneous vertebral augmentation procedures include balloon kyphoplasty and vertebral stenting. During kyphoplasty, a balloon-like device is inflated inside the vertebral body, and its expansion restores vertebral body height, creating a cavity into which cement is then injected. 24 Patient positioning and vertebral body access are similar to conventional vertebroplasty. A reamer is inserted over the access cannula, through which the stenting device or inflatable balloon is inserted. Once deployed, an intravertebral cavity is created with partial restoration of vertebral height. Cementoplasty has also been performed at extraspinal positions, notably the sacrum, acetabulum, and long bones. For percutaneous sacroplasty ( Figure 2 ), both a short-axis or long-axis cannula placement technique can be adopted depending on the size and extent of the fracture or lesions. The short-axis technique is better suited under CT guidance, with the cannula advanced perpendicular to the dorsal surface of the sacral ala. However, the volume of injected cement at each cannula may be limited, necessitating the placement of additional cannulas or adopting a more oblique approach. 28 Percutaneous sacroplasty. (A) MRI axial T 2 W with fat suppression image revealed marrow oedema in the sacral ala bilaterally (arrows) due to insufficiency fractures. (B) An oblique approach of cannula placement was planned on CT (arrow). Under CT guidance, bone cannulas were advanced into the sacral ala bilaterally (C and D), lateral to the sacral foramina. (E) Fluoroscopic control image in the sagittal plane was obtained prior to cement injection. Postprocedural images in the lateral (F) and frontal (G) projections demonstrated satisfactory cement fill with no cement leakage. For percutaneous acetabuloplasty ( Figure 3 ), either a posterior or anterior approach can be adopted. Cement is deposited along the acetabular roof and posterior column, as they form part of the load-transmission axis. Displaced fractures with acetabular protrusion are contraindications due to the risk of intra-articular cement leakage. Acetabular cementoplasty for a patient with metastatic lung cancer with persistent left hip pain. (A) Preprocedural CT coronal image revealed lytic lesions involving the left acetabular roof (arrows), while axial CT image (B) revealed sclerotic components in the iliac bone (arrowheads), suspicious for bony metastases. Under CT guidance with needle guidance software (XperGuide, Philips, Netherlands), acetabular cementoplasty was performed with 16 mL of cement deposited along the acetabular roof, preferentially at the posterior column as confirmed on axial (C), sagittal (D), and coronal (E) reformats. Other novel techniques described include the usage of curved or directional needles for cementoplasty of the acetabulum and vertebral bodies. 29 , 30

There have been substantial advancements and mounting evidence of safety and efficacy in percutaneous image-guided procedures for the musculoskeletal system, including cementoplasty and cryoablation techniques. These enable the interventional radiologist to offer a diverse repertoire of options in a multidisciplinary approach to patient management, especially cancer patients with bony metastases.

When considering cementoplasty for bone metastases, a multidisciplinary team including interventional radiologists, radiation oncologists, medical oncologists, and orthopaedic surgeons should be engaged. Cementoplasty is typically considered in the following clinical scenarios: persistent pain or imaging evidence of tumour progression despite maximized radiation therapy, contraindications to radiation therapy, lack of patient desire for radiation therapy, and/or inadequate treatment response to systemic therapies and analgesia, 13 as well as prophylactic stabilization for impending pathological fractures in the axial skeleton. 14 Preprocedural cross-sectional imaging is essential to determine the number and site of lesions, needle size, and approach, as well as measurements for ablation zone (if performed). MRI imaging features may also be useful to guide patient and vertebral level selection; levels with marrow oedema correlating with pain should be targeted for optimal pain relief. 15 Careful review of prior imaging, with a low threshold for repeating the patient’s cross-sectional imaging, is advised, especially if new or significantly worsening symptoms are reported since the latest imaging was performed. 16 In the authors’ experience, preprocedural imaging is usually current, preferably within a few days of procedure, and at most within a month from procedure. Severity of the spinal instability is an important consideration and can be evaluated via various scoring systems, including the Spinal Instability Neoplastic Score (SINS). 17 Surgical consultation for potential tumour resection or debulking with stabilization is suggested for patients with a SINS of 7 or higher. Spinal metastases resulting in central canal stenosis are typically managed with surgical intervention. 18 As regards the spine, suitable patients for vertebroplasty include those with chronic pathological fractures refractory to radiotherapy or other conservative measures, acute vertebral fractures with less than 6 weeks of symptoms, and painful pathological vertebral fractures without spinal cord compression or significant neurological deficit. 19 The most appropriate timeframe for substantial pain relief may be 2-4 weeks from onset of injury, as suggested by a meta-analysis. 20 However, treatment in the initial 4 weeks of vertebral fractures may lead to a higher risk of complications, including cement leakage. 21 , 22 In the authors’ experience, vertebroplasty can be performed before or after radiotherapy and readily coordinated during multidisciplinary discussions. Cementoplasty is contraindicated in patients with coagulopathy, unstable spinal lesions, presence of local or systemic infections, allergy to bone cement, and asymptomatic vertebral compression. 23 , 24 Vertebral plana with 90% or greater height loss and extensive osteolytic destruction especially at the posterior cortex of the target vertebral body are relative contraindications. 25

Percutaneous cementoplasty is a minimally invasive technique comprising of cannula placement within a bone lesion with subsequent cement injection. 11 The cement, usually polymethylmethacrylate, hardens in consistency after about 10-20 min. Cement polymerization and hardening involve an exothermic reaction, with temperature peaks of up to 75°C, and play an accessory analgesic role through the destruction of adjacent nociceptors. 12

There is mounting evidence of cryoablation for bone metastases both for palliation purposes ( Figure 7 ), as well as curative aim in oligometastatic disease, 97 , 111–113 which is defined as 1-5 metastases, where all metastatic sites are considered safely treatable. 114 Most recently, the MOTION trial reported rapid and durable pain relief for patients with metastatic bone disease, as well as improved quality of life and maintained functional status over 6 months. 112 Percutaneous cryoablation as an alternative or adjunct therapy for selected patients with plasmacytomas has also been reported. 115 CT-guided percutaneous cryoablation of a T10 vertebral metastatic lesion. (A) MRI T 1 W sagittal image revealed a hypointense lesion involving the T10 vertebral body and posterior elements (arrow). It demonstrated hyperintense signal on (B) sagittal STIR image (arrow in B) with avid enhancement on (C) axial postcontrast T 1 W with fat saturation (arrow in C), encroaching into the spinal canal (arrowhead in C). (D) Under CT guidance, 2 IceRod cryoablation probes (Boston Scientific, USA) were placed within the T10 vertebral lesion (arrow in D) via a posterior approach, with the more cranial probe inserted coaxially through a 13G Arrow needle (arrowheads in D). (E) Two freeze-active thaw cycles were performed, with the first freeze cycle of 3.5-min duration and the second freeze cycle of 2-min duration, with iceball visualization on CT soft tissue window (arrow in E). Soft tissue sarcomas are rare tumours with multiple subtypes, the most common of which are liposarcomas and leiomyosarcomas. 116 There is emerging evidence of cryoablation as a feasible and safe treatment option for these tumours, especially in recurrent or metastatic disease. 117 , 118 Other tumour subtypes treated by cryoablation include abdominal wall endometriosis, 119 neurofibromas, 120 and gastrointestinal stromal tumours. 121 This is especially so for extra-abdominal desmoid fibromatosis ( Figure 8 ). 111 Previously, treatment consists of a combination of surgery and radiotherapy. 122 The current first-line treatment for symptomatic desmoid tumours is based on medical therapies, including tyrosine kinase inhibitors and chemotherapy (including methotrexate), 123 with respective systemic side effects. Percutaneous cryoablation for desmoid fibromatosis in a 32-year-old patient. (A) MRI axial postcontrast T 1 W with fat saturation image revealed a heterogeneously enhancing infiltrative predominantly intramuscular mass in the left glutaeal region (arrow), representing desmoid fibromatosis. Under CT guidance, multiple cryoablation probes were deployed to customize a large ablation zone as visualized by ice formation (arrowheads). Posttreatment MRI axial postcontrast T 1 W with fat saturation image performed at 1 month (C) and 6 months (D) showed reduced enhancing tissue at ablation site with residual enhancement (arrow in D). The patient proceeded to undergo further cryoablation sessions at residual and recurrent sites. Recent studies have demonstrated cryotherapy as a safe and effective treatment modality for extra-abdominal desmoid tumours, with efficacy similar to those managed via conventional approaches in the short to medium term. 124 , 125 Percutaneous image-guided neurolysis ( Figures 9 - 12 ) is a safe, efficient, and relatively cost-effective means of managing refractory pain, which may arise from direct tumour invasion or iatrogenic to surgical and radiation therapy. 101 Unlike heat-mediated ablation, cryoablation does not disrupt the acellular epineurium or perineurium, reducing risk of neuroma formation and potentially allowing nerve regeneration. 126 Cryoneurolysis is also not associated with systemic toxicity occasionally encountered with chemical nerve ablation. 127 Cryoablation for Morton metatarsalgia. (A) MRI long-axis T 2 W fat-suppressed image of the forefoot and (B) MRI short-axis T 1 W sagittal image at the level of the metatarsal heads revealed a T2w-hypointense (arrowheads in A) and T1w hypointense lesions in the second and third web spaces (arrows in B), in keeping with Morton neuromas. The third web space lesion was treated with cryoablation. (C) Preprocedural CT revealed soft tissue density (arrow) corresponding with MRI images. (D) An IceSeed cryoablation probe (Boston Scientific, USA) was advanced into the lesion (arrow) with adjacent iceball formation (arrowheads). Intercostal nerve cryoneurolysis. (A) CT axial bone window image revealed extensive lytic bony metastases from lung cancer, involving the left seventh rib (arrow), eighth rib (not shown), and vertebral bodies (arrowheads). (B) An IceRod cryoablation probe (Boston Scientific, USA) was advanced into the intercostal groove of the seventh rib close to the costotransverse junction. (C) CT sagittal reformats confirmed appropriate position of cryoablation probes at the intercostal grooves (arrows), with soft tissue window (D) demonstrating iceball formation (arrows). Images courtesy of Dr Alfred Tan and Dr Too Chow Wei (Singapore General Hospital). L5 cryorhizotomy for metastatic colorectal cancer in a 65-year-old male. Preprocedural CT images in (A) axial bone window, (B) axial soft tissue window, and (C) sagittal bone window revealed an expansile aggressive sclerotic lesion in the L5 vertebral body and right posterior elements (arrowheads in A) in keeping with bony metastases, invading the L5-S1 neural foramen (arrows in B and C). (D) Under CT guidance, an IceForce cryoablation probe (Boston Scientific, USA) was advanced into the lesion (arrow) and commenced with CT soft tissue window demonstrating iceball formation (arrowheads). Cryoablation of neurogenic tumour (40-year-old male). (A) MRI axial T 2 W fat-suppressed image and (B) axial T 1 W image revealed a small well-circumscribed T 2 W hyperintense (arrow in A), T 1 W hypointense (arrow in B) lesion closely related to the posterior left iliac bone, probably a neurogenic tumour with no overt aggressive features. (A) Under CT guidance, an IceSeed cryoablation probe (Boston Scientific, USA) was advanced into the lesion (arrow), with cryoablation performed and iceball visualized (arrowheads). Cryotherapy has also been evaluated as a treatment option for vascular malformations, in particular venous malformations ( Figure 13 ) and fibroadipose vascular anomalies, either as a first-line treatment 128 or second-line treatment after sclerotherapy. 129 A systematic review of cryoablation in the treatment of venous malformations (55 lesions) reported promising results in terms of lesion size decrease and symptom improvement, with weighted mean postprocedural decrease in lesion size of 92.0%, weighted mean reduction in pain score of 77%, and complete resolution of symptoms (35/55) (63.6%). 130 Cryoablation for a vascular lesion (52-year-old female). Pretreatment MRI elbow with (A) axial T 1 W, (B) axial T 2 W, (C) coronal STIR, and (D) axial postcontrast T 1 W with fat saturation images. There was a lobulated T 1 W-mildly hyperintense mass-like lesion at the supracondylar region of the humerus (arrow in A), T 2 W-hyperintense with thin internal septation (arrows in B and C) and mild enhancement postgadolinium administration (arrow in D). (E) Under CT guidance, an IceRod cryoablation probe (Boston Scientific, USA) was advanced into the lesion (arrow); with cryoablation performed and iceball visualized in soft tissue window (arrowheads). Bone tumour cryoablation is safe, with a reported 2.5% rate of major complications, most commonly secondary fracture (1.2%). Major complications are associated with age greater than 70 years and use of more than 3 cryoprobes. 131 The most important potential complication of thermal ablation of skeletal metastases remains nontarget thermal injury to the spinal cord or adjacent neural structures. These are usually transient and typically managed with local injection of steroids and long-acting anaesthetic agents. 13 Knowledge of neuroanatomy is crucial and can prevent inadvertent thermal injury. 132 Thermal injury to the vital organs and skin should be minimized by implementing thermal protection strategies such as hydrodissection or pneumo-dissection. Other complications vary depending on the site of ablation. When treating lesions near the skin, skin necrosis is a consideration. Caution should be taken when treating lesions near joint to avoid joint effusion, synovitis, and osteonecrosis. Other potential side effects of cryoneurolysis include bleeding, bruising, and rarely infection. 103 If the target nerve is superficial, skin and hair in the adjacent region may be affected, including hyperpigmentation, depigmentation, and alopecia, particularly near the eyebrow when treating the supraorbital nerve. 133 Percutaneous cementoplasty and thermal ablation have synergistic properties. Given a potential complication of pathological fracture due to cryoablation-induced necrosis, adjunct cementoplasty has successfully been performed and demonstrated durable pain relief and stabilization ( Figure 14 ). 134–136 Cementoplasty has little to no antitumoural effect and has been reported to transiently increase the level of circulating cancer cells in the minutes following injection. 137 Therefore, ablation prior to cement injection may be indicated in cases requiring local tumour control or tumour debulking to prevent complications, such as a growing lesion near a nerve, improve the quality of consolidation and decrease tumour seeding. Combined cryoablation and cementoplasty for hepatocellular carcinoma metastases to the left iliac bone. (A) MRI axial T 2 W with fat suppression image revealed an expansile hyperintense lesion in the left iliac crest (arrow) with extraosseous component at the glutaeal muscles (arrowheads) suspicious for metastases, and (B) MRI coronal T 1 W image demonstrated craniocaudal extent of the lesion adjacent to the acetabular roof (arrow). (B) Under CT guidance, 2 bone access cannulas were advanced into the lesion, with position confirmed on oblique sagittal reformats (arrows). (D) Cryoablation probes were advanced into the lesion coaxially (arrow). (E) Cryoablation was performed with iceball formation visualized on CT axial soft tissue window (arrow). (F) Cementoplasty was subsequently performed under fluoroscopic guidance (arrow). (G) Postprocedural CT revealed satisfactory cement fill (arrow) with no leakage or immediate complication. Other ablation techniques such as radiofrequency ablation and microwave ablation with concurrent stabilization have also yielded effective results. 138–142 In the authors’ experience, temperature-controlled radiofrequency ablation (“coablation”) of vertebral metastases provided satisfactory results in selected patients who have limited pain relief despite prior radiotherapy and opioid titration ( Figure 15 ); similar results have been reported for pelvic and acetabular metastases. 143 Combined ablation and vertebroplasty for L3 vertebral body breast cancer metastases in a 62-year-old female. (A) Preprocedural CT images revealed lucent lesions in the vertebral body anteriorly (arrow in A), as well as a sizeable paravertebral extraosseous component (arrowheads in A). (B) Under CT guidance, a bilateral transpedicular approach was performed, with bone access cannulas in place. (C) Fluoroscopy lateral image confirmed satisfactory placement of the Osteocool (Medtronic, Ireland) radiofrequency ablation probes within the vertebral body, with posterior margins of the ablation zones indicated by the radio-opaque markers (arrows in C). (D) Postprocedural images revealed satisfactory cement fill of the metastatic lesions (arrows in D), with no cement leak. To date, there are limited data comparing the effectiveness of combined cryoablation and cementoplasty procedures versus other combined ablation-stabilization techniques, partly due to the complexity of conducting randomized trials regarding individualized therapy for palliative procedures. 144 It is also difficult to evaluate the exact benefit of combined ablation and cementoplasty versus cementoplasty alone, especially for bony lesions without extraosseous component. 140 , 145 In a retrospective study of 35 patients, Wang et al 146 reported a better analgesic effect, increased cement injected, and lower cement leakage rates from combined RFA and vertebroplasty, compared to vertebroplasty alone.