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Interventional Radiology Techniques for the Management of Painful Bone Metastases
Journal of Radiology Nursing xxx (2018) 1e8
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Interventional Radiology Techniques for the Management of Painful Bone Metastases Steven Yevich, MD, MPH *, Rahul Sheth, MD, Olalekan Ojeshina, RN, Alda Tam, MD, MBA Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
a b s t r a c t Keywords: Bone metastases Pain palliation Ablation Embolization Cement augmentation Fixation
Metastatic cancer to the osseous structures can result in significant pain that can often be difficult to control with narcotic medication. Multiple interventional radiology treatments can be applied for palliative relief and improvement in patient quality of life. The most commonly used interventional radiology techniques include embolization, thermal ablation, vertebral augmentation, cementoplasty, and percutaneous internal fixation. These procedures are associated with unique considerations for the radiology nurse. We review the most common palliative techniques performed by the radiology team for patients with musculoskeletal metastases and focus on the salient nursing implications for preprocedural, intraprocedural, and postprocedural care. Copyright © 2017 by the Association for Radiologic & Imaging Nursing.
Background Bone metastases are common in patients with advanced cancer, and the treatment of bone metastases is a known clinical challenge. As advances in oncological treatments continue to extend overall survival in patients with cancer, the incidence of metastatic musculoskeletal disease and skeletal-related events will become more frequent (Li et al., 2012; Oster et al., 2013). Cancers that often metastasize to bone include breast and prostate, followed by lung, colon, stomach, bladder, thyroid, and kidney (Roodman, 2004). The presence of bone metastases can be associated with significant morbidity, including pain, pathological fracture, hypercalcemia, or neurological deficits. The etiology of bone pain may be explained through a combination of the tumor pressure on the periosteum and adjacent nerves, tumor-induced osteolysis resulting in microfractures or complete fracture, and the effects of tumor growth factors and cytokines (Mundy, 1997). Interventional radiology options for the treatment of painful musculoskeletal metastases may vary based on treatment goals and location of disease but should always involve a multidisciplinary team approach that includes oncologists, radiation oncologists, and orthopedic surgeons. Nonradiological management options include surgical resection or amputation, local external beam radiotherapy, Conflict of interest: None to report. * Corresponding author: Steven Yevich, MD Anderson Cancer Center, 1400 Pressler Street, FCT14.6024, Houston, TX 77030. E-mail address: [email protected] (S. Yevich).
and bone-modifying agents (i.e., bisphosphonates). For patients, the goals of pain control and the maintenance of activities of daily living are paramount. For the clinical treatment team, meeting the patient's goals can translate to improvements in the patient's quality of life, decreased opioid dependence, decreased likelihood of immobility-associated morbidity, and lower overall health care costs (Lage, Barber, Harrison, & Jun, 2008; Oefelein et al., 2002; Saad et al., 2007; Sathiakumar et al., 2012; Weinfurt et al., 2002). The most common interventions performed by interventional radiologists for the palliation of metastatic bone tumors include embolization, thermal ablation, vertebral augmentation, cementoplasty, and percutaneous internal fixation. These minimally invasive treatments may be applied alone or in combination to achieve the desired palliative effect depending on treatment goals, tumor size and location, and surrounding anatomical structures.
Interventions Embolization Embolization describes the occlusion of the tumor arterial blood supply through the use of transcatheter endovascular techniques (Owen, 2010). This fluoroscopically guided technique works best for hypervascular bone tumors, of which the most common are renal and thyroid metastases. The goal of embolization is to devascularize and debulk the tumor, thereby providing pain relief by reduction of the compressive effects on the periosteum and adjacent nerves
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(Chuang et al., 1979; Koike et al., 2011). Typically, a 5-Fr catheter is introduced into the arterial system through a common femoral or radial artery access. Angiography is used to define the vascular distribution of the tumor and determine the branches to be targeted for embolization (Figure 1A and B). A microcatheter may be inserted coaxially to allow subselective catheterization of individual tumor-feeding vessels. Embolization from a subselective location allows for maximal delivery of the embolic agent to the tumor while minimizing the risk for nontarget embolization (Figure 1C). Embolization should be carried out until stasis of the vessel has been achieved (Figure 1D). The injected embolic material can vary from noncalibrated microparticles, calibrated microspheres, gelatin sponge, coils, or liquid agents such as glue or Onyx™ (ev3, Irvine, CA). The ultimate choice of embolic agent depends on operator experience, tumor vascularity, vessel accessibility, and collateralization with surrounding healthy tissue. For pain palliation purposes, microsphere or microparticulate embolization is typically performed; however, chemoembolization has been described for the treatment of sarcoma (Chu et al., 2017; Jiang et al., 2016). Embolization procedures are typically performed under monitored moderate sedation using a combination of fentanyl and midazolam. Adequate hydration is recommended before angiography as the use of significant amounts of contrast media may be required. The placement of a urinary catheter is often very helpful
for monitoring urine output during and after the procedure. For pelvic embolization procedures, a urinary catheter can also improve target visualization by voiding the bladder of radiopaque urine. Prophylactic antibiotics to cover skin flora may be administered, although there is no consensus in the literature on requirement for antibiotic prophylaxis (Abdelsalam, Kobayashi, Avritscher, Gupta, & Tam, 2014; Sutcliffe et al., 2015; Venkatesan et al., 2010). In addition to peripheral pulse and access site assessments, sensory-motor neurological examinations are critical. Specific questions related to symptoms of numbness or weakness may help with the early detection of procedural complications. Patients are expected to have postprocedure pain, which is typically greatest in the first few hours after injection of embolic material. Nontarget embolization, defined as reflux or undesired collateral administration of embolic material into nontumoral arteries, may result in pain, transient or permanent paresthesias, loss of sensation, or muscle and skin necrosis. Initial management includes conservative measures, such as warm compresses, oral anticoagulation medications, and physical therapy. If nontarget embolization results in vascular compromise of a distal extremity, a surgical consultation is warranted. Postembolization syndrome is an expected occurrence after tumor embolization irrespective of tumor location (Barton et al., 1996; Keller, Rosch, & Bird, 1983). Signs and symptoms include local pain at the tumor site, low-grade
Figure 1. (A) Embolization for a 64-year-old woman with hypervascular metastatic renal cell carcinoma to the right iliac anterior spine (large arrow). (B and C) Selective microcatheter angiography delineates vascular supply before selective embolization using 500 nm particles. (C) Note muscular branches (small white arrows), which if embolized by nontarget particles, could result in procedure-related musculoskeletal pain. (D) Final angiogram image demonstrates complete tumor embolization with preservation of muscular branches.
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fever, nausea, and vomiting, all of which can be managed with overthe-counter medications and are expected to resolve within 3 to 5 days after the procedure. Embolization treatments typically will require overnight observation for procedural pain control. A patient-controlled analgesic (PCA) device may be necessary for acute pain management. Postprocedure antibiotics are not routinely prescribed. The onset of pain relief can be seen as early as 12 hr after the procedure and may last up to 3 to 9 months in certain patients (EustatiaRutten et al., 2003; Forauer et al., 2007; Smit, Vielvoye, & Goslings, 2000). In describing their experience with 309 embolization procedures in 243 cancer patients with painful bone metastases, Rossi et al. (2011) reported achieving a clinical response in 97% of procedures, which was associated with a greater than 50% reduction in pain score and analgesic use. Percutaneous Ablation Percutaneous thermal ablation describes a variety of minimally invasive technologies that deliver energy in a controllable manner to achieve irreversible tumor cellular death within a defined ablation zone (Ahmed, Brace, Lee, & Goldberg, 2011). Thermal ablation refers to the direct application of either extreme heat (>50 C) or extreme cold (between 20 and 40 C) to the target tissue. Common modalities used in the United States include radiofrequency ablation (RFA), microwave (MW) ablation, and
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cryoablation. Although the mechanisms of cellular destruction differ, all thermal ablation modalities are thought to affect pain relief through similar multifactorial processes: destruction of sensory fibers supplying periosteum, decompression of tumor volume, eradication of cytokine-producing tumor cells, and inhibition of osteoclast activity (Callstrom et al., 2002). The selection of percutaneous ablation modality is often dictated by physician experience, patient comorbidities, tumor location and size, and anatomical considerations to minimize complications (Kurup et al., 2017). Treating the interface between the bone tumor and adjacent soft tissue is usually sufficient to engender symptomatic relief, which means ablation is a palliative treatment option for painful bone tumors irrespective of tumor size (Figure 2). Ablation procedures are typically performed with computed tomography (CT) guidance under monitored moderate sedation using a combination of fentanyl and midazolam or under deeper levels of sedation with the support of an anesthesiology team. As with all musculoskeletal interventions, the neurological examination that focused on a detailed sensory and motor assessment is critical in the preprocedural, intraprocedural, and postprocedural care phases. Prophylactic antibiotics to cover skin flora may be administered, although there is no consensus in the literature on the requirement for antibiotic prophylaxis (Sutcliffe et al., 2015; Venkatesan et al., 2010). If ablation is performed near the spine or peripheral nerves that are critical for extremity function, intraprocedural neurophysiological monitoring may be arranged with
Figure 2. (A and B) Computed tomography (CT)-guided cryoablation performed for a 61-year-old man with metastatic renal carcinoma to the left fifth rib (arrows identify tumor). (C) Protective measures undertaken during cryoablation to protect the adjacent lung by carbon dioxide gas dissection (small arrow) and overlying skin by sterile glove filled with warm saline (large arrow). (D) Cryoablation therapeutic ice ball monitored by CT (small arrows).
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somatosensory-evoked potentials, muscle motor-evoked potentials, and stimulated and spontaneous electromyography activity. During ablation, there are various measures that the operator may use in an attempt to displace critical healthy soft tissue structures from the ablation zone or provide a thermal temporizing measure for adjacent healthy tissue (Tsoumakidou, Buy, Garnon, Enescu, & Gangi, 2011). Common methods include the infusion of saline and D5W for hydrodissection or injection of carbon dioxide for gas dissection (Figure 2C). If the ablation zone is in close proximity to the skin, warm or cold saline compresses may be applied over the ablation zone to protect the skin during cryoablation or RFA/MW ablation, respectively. In the absence of a dedicated sterile heating or cooling pad, a makeshift alternative can be inexpensively and rapidly assembled by pouring warm (~40 C) or cool saline into a sterile glove that can subsequently be tied closed and applied to the overlying skin. Immediate postprocedural assessment should include evaluation for preserved baseline neurological status and the absence of thermal skin injury. Both RFA and MW ablation generate heat to induce tumor cell death. The ablation period is likely to cause the greatest pain during RFA or MW ablation, particularly if adjacent healthy muscles and nerves are damaged. Adequate pain control during the RFA and MW ablation cycles and immediately afterward will improve the patient experience. For patients undergoing RFA or MW ablation, appropriate precautions should be taken if the patient has a cardiac
defibrillator or pacer. Certain cardiac devices may need to be programmed to accommodate RFA or MW ablation. All RFA probes generate heat via the Joule heating mechanism by applying electrical current that oscillates between electrodes through the ion channels of the surrounding tissue. To close the generated electrical circuits during RFA, some manufacturers supply large grounding pads that can be applied to the skin in close proximity to the ablation zone. The pads should be adhered to dry skin free of excessive hair to ensure maximal grounding and prevention of electrical skin burns. To avoid unnecessary risk, care should be taken to ensure the pads are in a position that the electrical current traveling from the RFA probe to the pads does not pass through the heart or an implanted cardiac defibrillator or pacing device. During ablation, the cardiac rhythm should be carefully monitored for changes. External pacing and defibrillation equipment should be located in close proximity. MW ablation differs in mechanism of heat generation, which affects the specific risks and potential complications. MW ablation functions by generating electromagnetic energy that forces molecules, specifically water, to continuously realign with the magnetic field and produce thermal energy with greater efficacy than RFA. The absence of an electrical current obviates the need for grounding pads. The high energy carried by the MW coaxial cables, however, can cause skin burns if the cable is in direct contact with the skin. Care should be taken to ensure the cables are appropriately separated from the skin.
Figure 3. (A and B) Combination of interventional radiology treatment with radiofrequency ablation (RFA) and vertebroplasty for a 47-year-old woman with metastatic renal cell carcinoma to the T5 vertebral body with compression fracture deformity causing mechanical pain (arrows identify tumor). Treatment with RFA for pain treatment and to prevent tumor extension into the (C) spinal canal, followed by vertebroplasty with polymethylmethacrylate cement for pain palliation and (D) prevention of further vertebral body collapse.
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Cryoablation functions by the application of extreme cold to the tissue. The placement of cryoablation probes is typically the aspect of the procedure that might induce the greatest pain. Unlike RFA or MW ablation, pain during the cryoablation cycles is typically minimal even if the therapeutic ice ball extends across adjacent muscles or nerves. The procedural imaging benefits of cryoablation include the ability to visualize the therapeutic ice ball on cross-sectional imaging (Figure 2D). The most commonly used technique relies on the forced compression of gases through needle probes to create freeze and thaw cycles under the Joule-Thomson effect. The compression of argon gas through the probes can create an intense freeze as low as 140 C, whereas the application of helium gas can induce heat to thaw the resultant therapeutic ice ball. As the cryoablation freeze cycle may lower body temperature, the application of warm blankets or a Bair hugger outside the sterile field is recommended during and after the procedure. All ablation treatments can typically be performed as outpatient procedures, with the option to retain the patient for overnight observation if necessary for procedural pain control. Postprocedure antibiotics are not routinely prescribed. In prospective studies, RFA and cryoablation have been shown to be effective for the palliation of bone pain that has proven refractory to standard therapy (Callstrom et al., 2006; Dupuy et al., 2010; Goetz et al., 2004). Patients can expect to have a lasting 2- to 3-point drop in worst visual analog scale (VAS) pain score within the first week after ablation.
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Vertebral Augmentation and Cementoplasty Vertebral augmentation and cementoplasty describe methods to reinforce structurally weakened or fractured bones by the injection of bone cement, most commonly the polymer polymethylmethacrylate. As opposed to ablation and embolization, vertebral augmentation and cementoplasty are consolidative treatments that provide pain palliation without causing tumor cellular death. The physical qualities of bone cement are thought to provide pain relief through durable resistance to axial compression forces, adhesion fixation of microfractures, and possibly exothermic destruction of nociceptive pain fibers during cement polymerization. Vertebral augmentation specifically refers to the treatment of fractured vertebral bodies by the methods of vertebroplasty or kyphoplasty (Gangi et al., 2003; Jensen & Kallmes, 2002). Both methods involve the passage of needles under imaging guidance into the vertebral body, typically via a posterior transpedicular approach. Vertebroplasty describes the injection of cement into the vertebral body under pressure for pain palliation and prevention of further loss of vertebral body height (Figure 3). Kyphoplasty attempts to undertake the additional step of restoring vertebral body height and reducing kyphosis before cement injection, with the most common technique using an inflatable balloon catheter passed through the needle to exert radial pressure on the vertebral body end plates and create a cavity to be subsequently filled with cement. No consensus exists in the literature as to whether
Figure 4. (A and B) Combination of interventional radiology treatment with cryoablation and cementoplasty in a 77-year-old man with metastatic thyroid cancer to the right acetabulum (A, computed tomography [CT] image [arrow]; B, positron emission tomography/CT) causing pain while walking. (C) Cryoablation for pain control and to debulk tumor volume followed by (D) consolidative cementoplasty. (D) Small amount of cement extrusion without significant sequela (arrows).
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vertebroplasty or kyphoplasty is universally optimal for pain relief. Selection of vertebroplasty versus kyphoplasty is at the preference and discretion of the physician operator depending on experience, degree of vertebral body compression, and the presence of tumor extension through the posterior vertebral body into the epidural space. Cementoplasty generally refers to bone cement injection under imaging guidance into any bone other than the vertebral body (Figure 4). The most common application for cementoplasty is in the load-bearing portions of the pelvis, specifically the superior acetabulum and sacral ala. Vertebral augmentation and cementoplasty procedures may be performed under fluoroscopy or CT guidance. Procedural pain control is often achievable with monitored moderate sedation using a combination of fentanyl and midazolam but may require additional sedation for patient comfort and positioning. A pain assessment should be carried out to determine the requisite level of sedation, given the patient's baseline pain, positioning requirements, and anticipated procedure duration. Prophylactic antibiotics to cover skin flora may be administered. Procedural pain is typically greatest during cement injection. Complications typically arise from needle trajectory that crosses a neurovascular structure or from cement leakage from the bone (Pitton et al., 2008; Trumm et al., 2012). Small foci of cement leakage typically are not symptomatic (Figure 4D), whereas large extrusions can have significant sequela in the event of nerve impingement. Postprocedure pain related to nerve impingement may be treated with oral or intravenous steroids, and if necessary, surgical decompression. Although rare, cement injection may also affect the cardiovascular system for multiple reasons. Cement extrusion from the bone into the periosteal venous plexi may embolize to the lungs and result in pulmonary hypertension with systemic hypotension. Similar cardiovascular effects may result from pulmonary fat embolism caused by cement displacement of intraosseous bone marrow into the periosteal venous plexi (Kosova, Bergmark, & Piazza, 2015). Finally, hypotension may result from biochemical interactions with the cement monomers and release of vasoactive mediators into the circulation (Peebles, Ellis, Stride, & Simpson, 1972).
All vertebral augmentation and cementoplasty treatments can typically be performed as outpatient procedures, with the option to retain the patient for overnight observation if necessary for pain control. Postprocedure antibiotics are not routinely prescribed. Patients may expect relief from mechanical pain in 6 to 48 hr after the procedure; however, the full effects may be masked because of procedure-related soreness that may last up to 2 weeks. For vertebroplasty, Gangi et al. (2003) reported that satisfactory outcome in 83% of patients with vertebral tumors decreased opiate analgesic dose requirements. For cementoplasty outside the spine, Anselmetti (2010) reported a significant pain reduction in 91% of 105 patients treated for 140 painful bone lesions, with mean VAS pain score improvement from 8.7 to 1.9 for a median follow-up of 9 months. Percutaneous Internal Fixation Percutaneous internal fixation describes a palliative treatment to stabilize a fracture or prevent an impending fracture by the placement of metallic screws through a minimally invasive technique under imaging guidance (Cazzato et al., 2016; Deschamps et al., 2012, 2016). The principles of internal fixation have been developed in surgical subspecialities, whereas the radiology team's advanced imaging capabilities and imaging guidance expertise provide the potential to extend this valuable palliative treatment option for nonsurgical candidates or for patients with bone tumors in locations difficult to access by the conventional surgical approaches. Cannulated titanium or stainless steel screws are advanced through small skin incisions to span across a pathological fracture, tumor-related insufficiency fracture, or large lytic tumor to provide therapeutic or prophylactic fixation (Figure 5). The number of screws placed typically varies depending on the treatment location and size. Once the screws are in location, bone cement is injected to anchor the screw in place, further stabilize the pathological bone, and adhesively fixate any associated microfractures. Screw placement is typically performed under general anesthesia for patient comfort. Prophylactic antibiotics to cover skin
Figure 5. (A) Percutaneous internal fixation performed for an 88-year-old woman with sacral chordoma (arrow) status post resection complicated by progressive extensive sacral fractures (B, magnetic resonance imaging; C, computed tomography) resulting in debilitating pain with weight bearing that limits mobility. (D) Percutaneous internal fixation with stainless steel screw and polymethylmethacrylate cement consolidation.
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flora should be administered. Either CT or fluoroscopy may be used for imaging guidance depending on operator experience and location of tumor. Patient positioning will vary depending on the required screw approach. Appropriate patient cushioning is encouraged to prevent position-related musculoskeletal discomfort as these procedures may be lengthy in duration. For the same reason, a bladder catheter is recommended. The neurological examination including detailed sensory and motor assessment is again critical in the preprocedural, intraprocedural, and postprocedural care phases. Procedural pain is typically greatest when advancing the screw through the muscles and across cortical bone, and the anesthesiology team should be forewarned to adjust medication appropriately during these portions of the procedure. During and immediately after cement injection, the cardiovascular system should be carefully monitored for the rare sequelae of pulmonary emboli and biochemical interactions discussed in the preceding section. Percutaneous internal fixation will require extended recovery in the hospital for one to three nights for postprocedure pain control, as well as reassessment and reinvigoration of physical activity goals. After the procedure, prophylactic antibiotics are typically administered for 7 to 14 days to cover skin flora. A PCA device will be necessary for acute pain management, followed by oral analgesic regimen for approximately 2 weeks. Although procedure-related pain may be significant for several days, the pain caused by the pathological fracture or lytic tumor should significantly decrease shortly after the procedure. Cazzato et al. (2016) reported an 87.8% clinical improvement in 1-month follow-up of 29 patients. Prolonged postprocedure pain or new neurosensory pain should prompt evaluation for neurovascular injury because of screw trajectory or cement leakage outside the bone. Patients are expected to be able to bear weight on the region the day after the procedure and should be encouraged to immediately begin physical rehabilitation. As patients typically present with disuse muscle atrophy from the pathological fracture or large lytic bone tumor, outpatient physical therapy should be regularly scheduled for 3 to 6 months to improve muscle strength and coordination.
Clinical Practices Tips Patient selection is critical to the success of pain palliation procedures. All patients should be seen in clinic to ensure that their symptoms can be relieved by an intervention. In addition to a history and physical examination, quantification of the patient's pain using a validated pain scale and inventory of the narcotic usage should be performed. A focused neurological examination, including sensory and motor assessment, of the area to be treated is essential before the procedure and during the postprocedure recovery period. Non-narcotic medications such as intravenous acetaminophen and ketorolac can be given intraprocedurally to mitigate postprocedure pain. Regional pain blockade may be considered in cases of severe postprocedure pain. Signs of nontarget embolization affecting the extremities can present as symptoms of paresthesia or signs of motor weakness and skin mottling. If the postprocedure neurological examination indicates preservation of sensation but weakness in the motor examination, this indicates neurapraxia and may be the result of compression of the neurovascular bundle because of inflammatory changes from the treatment. Typically, neurapraxia resolves, but its resolution can be hastened with the administration of intravenous or oral corticosteroids (Philip, Gupta, Ahrar, & Tam, 2013). The use of corticosteroids should be carefully considered in diabetic patients.
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Summary Pain from bone metastases is a prevalent and difficult clinical problem that requires a multidisciplinary team approach. A multitude of radiology treatments have been developed for the palliation of musculoskeletal pain in patients with cancer, which may be used alone or in combination. It is important for providers to understand the goals of treatment for pain palliation and recognize the importance and role of the neurological examination in the management of these patients undergoing radiology interventions.
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Interventional Radiology Techniques for the Management of Painful Bone Metastases Steven Yevich, MD, MPH *, Rahul Sheth, MD, Olalekan Ojeshina, RN, Alda Tam, MD, MBA Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
a b s t r a c t Keywords: Bone metastases Pain palliation Ablation Embolization Cement augmentation Fixation
Metastatic cancer to the osseous structures can result in significant pain that can often be difficult to control with narcotic medication. Multiple interventional radiology treatments can be applied for palliative relief and improvement in patient quality of life. The most commonly used interventional radiology techniques include embolization, thermal ablation, vertebral augmentation, cementoplasty, and percutaneous internal fixation. These procedures are associated with unique considerations for the radiology nurse. We review the most common palliative techniques performed by the radiology team for patients with musculoskeletal metastases and focus on the salient nursing implications for preprocedural, intraprocedural, and postprocedural care. Copyright © 2017 by the Association for Radiologic & Imaging Nursing.
Background Bone metastases are common in patients with advanced cancer, and the treatment of bone metastases is a known clinical challenge. As advances in oncological treatments continue to extend overall survival in patients with cancer, the incidence of metastatic musculoskeletal disease and skeletal-related events will become more frequent (Li et al., 2012; Oster et al., 2013). Cancers that often metastasize to bone include breast and prostate, followed by lung, colon, stomach, bladder, thyroid, and kidney (Roodman, 2004). The presence of bone metastases can be associated with significant morbidity, including pain, pathological fracture, hypercalcemia, or neurological deficits. The etiology of bone pain may be explained through a combination of the tumor pressure on the periosteum and adjacent nerves, tumor-induced osteolysis resulting in microfractures or complete fracture, and the effects of tumor growth factors and cytokines (Mundy, 1997). Interventional radiology options for the treatment of painful musculoskeletal metastases may vary based on treatment goals and location of disease but should always involve a multidisciplinary team approach that includes oncologists, radiation oncologists, and orthopedic surgeons. Nonradiological management options include surgical resection or amputation, local external beam radiotherapy, Conflict of interest: None to report. * Corresponding author: Steven Yevich, MD Anderson Cancer Center, 1400 Pressler Street, FCT14.6024, Houston, TX 77030. E-mail address: [email protected] (S. Yevich).
and bone-modifying agents (i.e., bisphosphonates). For patients, the goals of pain control and the maintenance of activities of daily living are paramount. For the clinical treatment team, meeting the patient's goals can translate to improvements in the patient's quality of life, decreased opioid dependence, decreased likelihood of immobility-associated morbidity, and lower overall health care costs (Lage, Barber, Harrison, & Jun, 2008; Oefelein et al., 2002; Saad et al., 2007; Sathiakumar et al., 2012; Weinfurt et al., 2002). The most common interventions performed by interventional radiologists for the palliation of metastatic bone tumors include embolization, thermal ablation, vertebral augmentation, cementoplasty, and percutaneous internal fixation. These minimally invasive treatments may be applied alone or in combination to achieve the desired palliative effect depending on treatment goals, tumor size and location, and surrounding anatomical structures.
Interventions Embolization Embolization describes the occlusion of the tumor arterial blood supply through the use of transcatheter endovascular techniques (Owen, 2010). This fluoroscopically guided technique works best for hypervascular bone tumors, of which the most common are renal and thyroid metastases. The goal of embolization is to devascularize and debulk the tumor, thereby providing pain relief by reduction of the compressive effects on the periosteum and adjacent nerves
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(Chuang et al., 1979; Koike et al., 2011). Typically, a 5-Fr catheter is introduced into the arterial system through a common femoral or radial artery access. Angiography is used to define the vascular distribution of the tumor and determine the branches to be targeted for embolization (Figure 1A and B). A microcatheter may be inserted coaxially to allow subselective catheterization of individual tumor-feeding vessels. Embolization from a subselective location allows for maximal delivery of the embolic agent to the tumor while minimizing the risk for nontarget embolization (Figure 1C). Embolization should be carried out until stasis of the vessel has been achieved (Figure 1D). The injected embolic material can vary from noncalibrated microparticles, calibrated microspheres, gelatin sponge, coils, or liquid agents such as glue or Onyx™ (ev3, Irvine, CA). The ultimate choice of embolic agent depends on operator experience, tumor vascularity, vessel accessibility, and collateralization with surrounding healthy tissue. For pain palliation purposes, microsphere or microparticulate embolization is typically performed; however, chemoembolization has been described for the treatment of sarcoma (Chu et al., 2017; Jiang et al., 2016). Embolization procedures are typically performed under monitored moderate sedation using a combination of fentanyl and midazolam. Adequate hydration is recommended before angiography as the use of significant amounts of contrast media may be required. The placement of a urinary catheter is often very helpful
for monitoring urine output during and after the procedure. For pelvic embolization procedures, a urinary catheter can also improve target visualization by voiding the bladder of radiopaque urine. Prophylactic antibiotics to cover skin flora may be administered, although there is no consensus in the literature on requirement for antibiotic prophylaxis (Abdelsalam, Kobayashi, Avritscher, Gupta, & Tam, 2014; Sutcliffe et al., 2015; Venkatesan et al., 2010). In addition to peripheral pulse and access site assessments, sensory-motor neurological examinations are critical. Specific questions related to symptoms of numbness or weakness may help with the early detection of procedural complications. Patients are expected to have postprocedure pain, which is typically greatest in the first few hours after injection of embolic material. Nontarget embolization, defined as reflux or undesired collateral administration of embolic material into nontumoral arteries, may result in pain, transient or permanent paresthesias, loss of sensation, or muscle and skin necrosis. Initial management includes conservative measures, such as warm compresses, oral anticoagulation medications, and physical therapy. If nontarget embolization results in vascular compromise of a distal extremity, a surgical consultation is warranted. Postembolization syndrome is an expected occurrence after tumor embolization irrespective of tumor location (Barton et al., 1996; Keller, Rosch, & Bird, 1983). Signs and symptoms include local pain at the tumor site, low-grade
Figure 1. (A) Embolization for a 64-year-old woman with hypervascular metastatic renal cell carcinoma to the right iliac anterior spine (large arrow). (B and C) Selective microcatheter angiography delineates vascular supply before selective embolization using 500 nm particles. (C) Note muscular branches (small white arrows), which if embolized by nontarget particles, could result in procedure-related musculoskeletal pain. (D) Final angiogram image demonstrates complete tumor embolization with preservation of muscular branches.
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fever, nausea, and vomiting, all of which can be managed with overthe-counter medications and are expected to resolve within 3 to 5 days after the procedure. Embolization treatments typically will require overnight observation for procedural pain control. A patient-controlled analgesic (PCA) device may be necessary for acute pain management. Postprocedure antibiotics are not routinely prescribed. The onset of pain relief can be seen as early as 12 hr after the procedure and may last up to 3 to 9 months in certain patients (EustatiaRutten et al., 2003; Forauer et al., 2007; Smit, Vielvoye, & Goslings, 2000). In describing their experience with 309 embolization procedures in 243 cancer patients with painful bone metastases, Rossi et al. (2011) reported achieving a clinical response in 97% of procedures, which was associated with a greater than 50% reduction in pain score and analgesic use. Percutaneous Ablation Percutaneous thermal ablation describes a variety of minimally invasive technologies that deliver energy in a controllable manner to achieve irreversible tumor cellular death within a defined ablation zone (Ahmed, Brace, Lee, & Goldberg, 2011). Thermal ablation refers to the direct application of either extreme heat (>50 C) or extreme cold (between 20 and 40 C) to the target tissue. Common modalities used in the United States include radiofrequency ablation (RFA), microwave (MW) ablation, and
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cryoablation. Although the mechanisms of cellular destruction differ, all thermal ablation modalities are thought to affect pain relief through similar multifactorial processes: destruction of sensory fibers supplying periosteum, decompression of tumor volume, eradication of cytokine-producing tumor cells, and inhibition of osteoclast activity (Callstrom et al., 2002). The selection of percutaneous ablation modality is often dictated by physician experience, patient comorbidities, tumor location and size, and anatomical considerations to minimize complications (Kurup et al., 2017). Treating the interface between the bone tumor and adjacent soft tissue is usually sufficient to engender symptomatic relief, which means ablation is a palliative treatment option for painful bone tumors irrespective of tumor size (Figure 2). Ablation procedures are typically performed with computed tomography (CT) guidance under monitored moderate sedation using a combination of fentanyl and midazolam or under deeper levels of sedation with the support of an anesthesiology team. As with all musculoskeletal interventions, the neurological examination that focused on a detailed sensory and motor assessment is critical in the preprocedural, intraprocedural, and postprocedural care phases. Prophylactic antibiotics to cover skin flora may be administered, although there is no consensus in the literature on the requirement for antibiotic prophylaxis (Sutcliffe et al., 2015; Venkatesan et al., 2010). If ablation is performed near the spine or peripheral nerves that are critical for extremity function, intraprocedural neurophysiological monitoring may be arranged with
Figure 2. (A and B) Computed tomography (CT)-guided cryoablation performed for a 61-year-old man with metastatic renal carcinoma to the left fifth rib (arrows identify tumor). (C) Protective measures undertaken during cryoablation to protect the adjacent lung by carbon dioxide gas dissection (small arrow) and overlying skin by sterile glove filled with warm saline (large arrow). (D) Cryoablation therapeutic ice ball monitored by CT (small arrows).
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somatosensory-evoked potentials, muscle motor-evoked potentials, and stimulated and spontaneous electromyography activity. During ablation, there are various measures that the operator may use in an attempt to displace critical healthy soft tissue structures from the ablation zone or provide a thermal temporizing measure for adjacent healthy tissue (Tsoumakidou, Buy, Garnon, Enescu, & Gangi, 2011). Common methods include the infusion of saline and D5W for hydrodissection or injection of carbon dioxide for gas dissection (Figure 2C). If the ablation zone is in close proximity to the skin, warm or cold saline compresses may be applied over the ablation zone to protect the skin during cryoablation or RFA/MW ablation, respectively. In the absence of a dedicated sterile heating or cooling pad, a makeshift alternative can be inexpensively and rapidly assembled by pouring warm (~40 C) or cool saline into a sterile glove that can subsequently be tied closed and applied to the overlying skin. Immediate postprocedural assessment should include evaluation for preserved baseline neurological status and the absence of thermal skin injury. Both RFA and MW ablation generate heat to induce tumor cell death. The ablation period is likely to cause the greatest pain during RFA or MW ablation, particularly if adjacent healthy muscles and nerves are damaged. Adequate pain control during the RFA and MW ablation cycles and immediately afterward will improve the patient experience. For patients undergoing RFA or MW ablation, appropriate precautions should be taken if the patient has a cardiac
defibrillator or pacer. Certain cardiac devices may need to be programmed to accommodate RFA or MW ablation. All RFA probes generate heat via the Joule heating mechanism by applying electrical current that oscillates between electrodes through the ion channels of the surrounding tissue. To close the generated electrical circuits during RFA, some manufacturers supply large grounding pads that can be applied to the skin in close proximity to the ablation zone. The pads should be adhered to dry skin free of excessive hair to ensure maximal grounding and prevention of electrical skin burns. To avoid unnecessary risk, care should be taken to ensure the pads are in a position that the electrical current traveling from the RFA probe to the pads does not pass through the heart or an implanted cardiac defibrillator or pacing device. During ablation, the cardiac rhythm should be carefully monitored for changes. External pacing and defibrillation equipment should be located in close proximity. MW ablation differs in mechanism of heat generation, which affects the specific risks and potential complications. MW ablation functions by generating electromagnetic energy that forces molecules, specifically water, to continuously realign with the magnetic field and produce thermal energy with greater efficacy than RFA. The absence of an electrical current obviates the need for grounding pads. The high energy carried by the MW coaxial cables, however, can cause skin burns if the cable is in direct contact with the skin. Care should be taken to ensure the cables are appropriately separated from the skin.
Figure 3. (A and B) Combination of interventional radiology treatment with radiofrequency ablation (RFA) and vertebroplasty for a 47-year-old woman with metastatic renal cell carcinoma to the T5 vertebral body with compression fracture deformity causing mechanical pain (arrows identify tumor). Treatment with RFA for pain treatment and to prevent tumor extension into the (C) spinal canal, followed by vertebroplasty with polymethylmethacrylate cement for pain palliation and (D) prevention of further vertebral body collapse.
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Cryoablation functions by the application of extreme cold to the tissue. The placement of cryoablation probes is typically the aspect of the procedure that might induce the greatest pain. Unlike RFA or MW ablation, pain during the cryoablation cycles is typically minimal even if the therapeutic ice ball extends across adjacent muscles or nerves. The procedural imaging benefits of cryoablation include the ability to visualize the therapeutic ice ball on cross-sectional imaging (Figure 2D). The most commonly used technique relies on the forced compression of gases through needle probes to create freeze and thaw cycles under the Joule-Thomson effect. The compression of argon gas through the probes can create an intense freeze as low as 140 C, whereas the application of helium gas can induce heat to thaw the resultant therapeutic ice ball. As the cryoablation freeze cycle may lower body temperature, the application of warm blankets or a Bair hugger outside the sterile field is recommended during and after the procedure. All ablation treatments can typically be performed as outpatient procedures, with the option to retain the patient for overnight observation if necessary for procedural pain control. Postprocedure antibiotics are not routinely prescribed. In prospective studies, RFA and cryoablation have been shown to be effective for the palliation of bone pain that has proven refractory to standard therapy (Callstrom et al., 2006; Dupuy et al., 2010; Goetz et al., 2004). Patients can expect to have a lasting 2- to 3-point drop in worst visual analog scale (VAS) pain score within the first week after ablation.
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Vertebral Augmentation and Cementoplasty Vertebral augmentation and cementoplasty describe methods to reinforce structurally weakened or fractured bones by the injection of bone cement, most commonly the polymer polymethylmethacrylate. As opposed to ablation and embolization, vertebral augmentation and cementoplasty are consolidative treatments that provide pain palliation without causing tumor cellular death. The physical qualities of bone cement are thought to provide pain relief through durable resistance to axial compression forces, adhesion fixation of microfractures, and possibly exothermic destruction of nociceptive pain fibers during cement polymerization. Vertebral augmentation specifically refers to the treatment of fractured vertebral bodies by the methods of vertebroplasty or kyphoplasty (Gangi et al., 2003; Jensen & Kallmes, 2002). Both methods involve the passage of needles under imaging guidance into the vertebral body, typically via a posterior transpedicular approach. Vertebroplasty describes the injection of cement into the vertebral body under pressure for pain palliation and prevention of further loss of vertebral body height (Figure 3). Kyphoplasty attempts to undertake the additional step of restoring vertebral body height and reducing kyphosis before cement injection, with the most common technique using an inflatable balloon catheter passed through the needle to exert radial pressure on the vertebral body end plates and create a cavity to be subsequently filled with cement. No consensus exists in the literature as to whether
Figure 4. (A and B) Combination of interventional radiology treatment with cryoablation and cementoplasty in a 77-year-old man with metastatic thyroid cancer to the right acetabulum (A, computed tomography [CT] image [arrow]; B, positron emission tomography/CT) causing pain while walking. (C) Cryoablation for pain control and to debulk tumor volume followed by (D) consolidative cementoplasty. (D) Small amount of cement extrusion without significant sequela (arrows).
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vertebroplasty or kyphoplasty is universally optimal for pain relief. Selection of vertebroplasty versus kyphoplasty is at the preference and discretion of the physician operator depending on experience, degree of vertebral body compression, and the presence of tumor extension through the posterior vertebral body into the epidural space. Cementoplasty generally refers to bone cement injection under imaging guidance into any bone other than the vertebral body (Figure 4). The most common application for cementoplasty is in the load-bearing portions of the pelvis, specifically the superior acetabulum and sacral ala. Vertebral augmentation and cementoplasty procedures may be performed under fluoroscopy or CT guidance. Procedural pain control is often achievable with monitored moderate sedation using a combination of fentanyl and midazolam but may require additional sedation for patient comfort and positioning. A pain assessment should be carried out to determine the requisite level of sedation, given the patient's baseline pain, positioning requirements, and anticipated procedure duration. Prophylactic antibiotics to cover skin flora may be administered. Procedural pain is typically greatest during cement injection. Complications typically arise from needle trajectory that crosses a neurovascular structure or from cement leakage from the bone (Pitton et al., 2008; Trumm et al., 2012). Small foci of cement leakage typically are not symptomatic (Figure 4D), whereas large extrusions can have significant sequela in the event of nerve impingement. Postprocedure pain related to nerve impingement may be treated with oral or intravenous steroids, and if necessary, surgical decompression. Although rare, cement injection may also affect the cardiovascular system for multiple reasons. Cement extrusion from the bone into the periosteal venous plexi may embolize to the lungs and result in pulmonary hypertension with systemic hypotension. Similar cardiovascular effects may result from pulmonary fat embolism caused by cement displacement of intraosseous bone marrow into the periosteal venous plexi (Kosova, Bergmark, & Piazza, 2015). Finally, hypotension may result from biochemical interactions with the cement monomers and release of vasoactive mediators into the circulation (Peebles, Ellis, Stride, & Simpson, 1972).
All vertebral augmentation and cementoplasty treatments can typically be performed as outpatient procedures, with the option to retain the patient for overnight observation if necessary for pain control. Postprocedure antibiotics are not routinely prescribed. Patients may expect relief from mechanical pain in 6 to 48 hr after the procedure; however, the full effects may be masked because of procedure-related soreness that may last up to 2 weeks. For vertebroplasty, Gangi et al. (2003) reported that satisfactory outcome in 83% of patients with vertebral tumors decreased opiate analgesic dose requirements. For cementoplasty outside the spine, Anselmetti (2010) reported a significant pain reduction in 91% of 105 patients treated for 140 painful bone lesions, with mean VAS pain score improvement from 8.7 to 1.9 for a median follow-up of 9 months. Percutaneous Internal Fixation Percutaneous internal fixation describes a palliative treatment to stabilize a fracture or prevent an impending fracture by the placement of metallic screws through a minimally invasive technique under imaging guidance (Cazzato et al., 2016; Deschamps et al., 2012, 2016). The principles of internal fixation have been developed in surgical subspecialities, whereas the radiology team's advanced imaging capabilities and imaging guidance expertise provide the potential to extend this valuable palliative treatment option for nonsurgical candidates or for patients with bone tumors in locations difficult to access by the conventional surgical approaches. Cannulated titanium or stainless steel screws are advanced through small skin incisions to span across a pathological fracture, tumor-related insufficiency fracture, or large lytic tumor to provide therapeutic or prophylactic fixation (Figure 5). The number of screws placed typically varies depending on the treatment location and size. Once the screws are in location, bone cement is injected to anchor the screw in place, further stabilize the pathological bone, and adhesively fixate any associated microfractures. Screw placement is typically performed under general anesthesia for patient comfort. Prophylactic antibiotics to cover skin
Figure 5. (A) Percutaneous internal fixation performed for an 88-year-old woman with sacral chordoma (arrow) status post resection complicated by progressive extensive sacral fractures (B, magnetic resonance imaging; C, computed tomography) resulting in debilitating pain with weight bearing that limits mobility. (D) Percutaneous internal fixation with stainless steel screw and polymethylmethacrylate cement consolidation.
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flora should be administered. Either CT or fluoroscopy may be used for imaging guidance depending on operator experience and location of tumor. Patient positioning will vary depending on the required screw approach. Appropriate patient cushioning is encouraged to prevent position-related musculoskeletal discomfort as these procedures may be lengthy in duration. For the same reason, a bladder catheter is recommended. The neurological examination including detailed sensory and motor assessment is again critical in the preprocedural, intraprocedural, and postprocedural care phases. Procedural pain is typically greatest when advancing the screw through the muscles and across cortical bone, and the anesthesiology team should be forewarned to adjust medication appropriately during these portions of the procedure. During and immediately after cement injection, the cardiovascular system should be carefully monitored for the rare sequelae of pulmonary emboli and biochemical interactions discussed in the preceding section. Percutaneous internal fixation will require extended recovery in the hospital for one to three nights for postprocedure pain control, as well as reassessment and reinvigoration of physical activity goals. After the procedure, prophylactic antibiotics are typically administered for 7 to 14 days to cover skin flora. A PCA device will be necessary for acute pain management, followed by oral analgesic regimen for approximately 2 weeks. Although procedure-related pain may be significant for several days, the pain caused by the pathological fracture or lytic tumor should significantly decrease shortly after the procedure. Cazzato et al. (2016) reported an 87.8% clinical improvement in 1-month follow-up of 29 patients. Prolonged postprocedure pain or new neurosensory pain should prompt evaluation for neurovascular injury because of screw trajectory or cement leakage outside the bone. Patients are expected to be able to bear weight on the region the day after the procedure and should be encouraged to immediately begin physical rehabilitation. As patients typically present with disuse muscle atrophy from the pathological fracture or large lytic bone tumor, outpatient physical therapy should be regularly scheduled for 3 to 6 months to improve muscle strength and coordination.
Clinical Practices Tips Patient selection is critical to the success of pain palliation procedures. All patients should be seen in clinic to ensure that their symptoms can be relieved by an intervention. In addition to a history and physical examination, quantification of the patient's pain using a validated pain scale and inventory of the narcotic usage should be performed. A focused neurological examination, including sensory and motor assessment, of the area to be treated is essential before the procedure and during the postprocedure recovery period. Non-narcotic medications such as intravenous acetaminophen and ketorolac can be given intraprocedurally to mitigate postprocedure pain. Regional pain blockade may be considered in cases of severe postprocedure pain. Signs of nontarget embolization affecting the extremities can present as symptoms of paresthesia or signs of motor weakness and skin mottling. If the postprocedure neurological examination indicates preservation of sensation but weakness in the motor examination, this indicates neurapraxia and may be the result of compression of the neurovascular bundle because of inflammatory changes from the treatment. Typically, neurapraxia resolves, but its resolution can be hastened with the administration of intravenous or oral corticosteroids (Philip, Gupta, Ahrar, & Tam, 2013). The use of corticosteroids should be carefully considered in diabetic patients.
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Summary Pain from bone metastases is a prevalent and difficult clinical problem that requires a multidisciplinary team approach. A multitude of radiology treatments have been developed for the palliation of musculoskeletal pain in patients with cancer, which may be used alone or in combination. It is important for providers to understand the goals of treatment for pain palliation and recognize the importance and role of the neurological examination in the management of these patients undergoing radiology interventions.
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