Indian Journal of Pain

REVIEW ARTICLE
Year
: 2021  |  Volume : 35  |  Issue : 1  |  Page : 11--15

Interventional management for cancer pain


Parmanand N Jain 
 Department of Anesthesiology, Critical Care and Pain, Division of Pain, Tata Memorial Centre, Mumbai, Maharashtra, India

Correspondence Address:
Prof. Parmanand N Jain
Department of Anesthesiology, Critical Care and Pain, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai - 400 012, Maharashtra
India

Abstract

The WHO analgesic ladder (1986) has recommended certain oral analgesics vis-a-vis intensity of cancer pain for optimum relief as a practical doctrine, easy to implement, and taught extensively to healthcare professionals globally. However, the WHO approach despite been implemented appropriately and aggressively in the last three decades, 10%–20% of patients may not achieve acceptable pain relief. There is a refractory group of patients which is considered for interventional pain management; however, reserving this modality as a last resort is questioned by interventional protagonists. It is anticipated that the general understanding of interventional approach on cancer pain relief may not only expedite pain relief but should also consider all potential therapeutic options. Interventional physicians, mainly anesthesiologists, have a well-defined and beneficial role in the treatment of cancer pain, if patients are appropriately selected with various cancer pain syndromes. Pain physicians should successfully optimize outcomes depends on timely referral with adequate assessment and patient selection. Pain physicians have a complex role. Managing expectations of referring physicians, of patients, and family members, assuring adequacy of interventional care is not an easy task. An experienced, skilled interventionist who is well versed in not only techniques of procedure but side effects management, if any, will assume full responsibility for pre- and postintervention evaluation and follow-up care as indicated by the circumstances of each patient to be managed.



How to cite this article:
Jain PN. Interventional management for cancer pain.Indian J Pain 2021;35:11-15


How to cite this URL:
Jain PN. Interventional management for cancer pain. Indian J Pain [serial online] 2021 [cited 2021 Jun 19 ];35:11-15
Available from: https://www.indianjpain.org/text.asp?2021/35/1/11/314694


Full Text



 Introduction



The WHO recommended oral analgesics as the main stay of cancer pain management.[1] Pain treatment using the WHO guidelines provides pain relief in majority of patients, though an effective pain relief may take a long time in one-third of the all patients. The National Cancer Care Network USA (2019) cancer pain guidelines recommend a flexible approach to control pain including employing multiple therapies simultaneously. Patients may suffer from pain due to various mechanisms caused by tissue damage. A pain physician should adopt a multidisciplinary approach and evaluate the “total pain” including physical, psychological, social, spiritual, and financial components. He dissects each element including the adequacy of ongoing or completed cancer therapy and response of previous prescribed analgesics before prescribing any new pain therapy. Approximately 12% of patients with inadequately managed pain on oral analgesics may have the option to proceed for interventional techniques for optimal pain relief.[2] The Indian Society for the Study of Pain (ISSP) has come out with ISSP interventional cancer pain guidelines in adults in 2019–2020.[3]

In true sense, any analgesic prescribed to the patient should also be considered an intervention but Dr. S Waldman conducted a meeting in Nice (France) in 1993 where 300 pain physicians participated and after a thorough discussion the term “intervention” was coined for all invasive procedure used for pain medicine.

A comprehensive patient assessment and counseling before any intervention is paramount. An informed consent shall be taken after full explanation about the cause of pain and the exact role of intervention with possible side effects. Interventional techniques have been shown, in some cases, to eliminate or significantly reduce the level of pain. Invasive procedures may allow a significant decrease in the dose of systemic analgesics. Various interventional therapies for relief of cancer pain include nerve blocks, vertebral augmentation, and regional infusion of analgesics, radiofrequency (RF) ablation, and many other interventional radiological techniques.

 Patient Selection



A detailed history and physical examination are required to decide upon the exact need of any intervention in cancer pain management.

Any possible cardiac and any pulmonary complications due to the procedure should be the essential part of evaluation. The thorough history of analgesics taken and their response including their allergy status should be ascertained. As many of our procedures are performed in prone position, airway, congenital, or physical deformities should be noted before any procedure.

 Selection Criteria of Interventional Techniques



The most important reason for offering an intervention is <50% pain relief on oral analgesics. When ongoing systemic drug therapy (oral, transdermal, subcutaneous, etc.,) fail to provide adequate pain relief or causes unacceptable side effectsAdequate counseling of the patient and caregivers is an integral part of selecting a patient suitable for a procedure. They should be apprised of the benefits, risks, expenses, complications, and also the potential of failure of nerve block or interventionWritten informed consent in the language best understood by the patient and family in a customized text made for the patient and not the common standard printed consent formRule out any other causes of pain apart from his primary cancerInterventionalist should be fully trained and having expertize in performing the procedureThere should no contraindications to the planned procedure due to his comorbid conditions or any ongoing thromboprophylaxis drugs. He should have a stable health status on prescribed drugs for his various coexisting diseasesScreening for any psychological disorder should also be done before any interventionAll neuroloytic block should precede a successful diagnostic block to demonstrate a temporary pain relief state and fully understand the etiology of pain better.

 Commonly used Interventional Procedures



Neuro-destructive procedures for localized cancer pain syndromes

Head-and-neck region: peripheral nerve blockUpper limb: brachial plexus block or intrathecal neurolysisChest wall: epidural/intrathecal/intercostal neurolysisUpper abdominal region (visceral): Celiac plexus neurolysis (CPN) or splanchnic neurolysisPelvic pain: superior hypogastric plexus (SHP) blockRectal or perineal pain: Intrathecal neurolytic saddle block, midline SHP block, Ganglion Impar blockUnilateral pain syndromes: cordotomy

Interventional radiological procedures for pain relief: Percutaneous vertebroplasty/kyphoplasty, radiofrequency (RF) ablation for bone lesionsNeuro-stimulation procedures for cancer pain (i.e., peripheral neuropathy)Regional analgesic infusions via catheter, pump and port (e.g., intrathecal drug delivery system) for infusions of opioids, local anesthetics, and clonidine.

 Neurolytic Procedures



Neurolytic procedures are slowly turning into a dying art and very sparingly used now for cancer pain control due to their potential of irreversible complications and lack of expertise and possible medico-legal implications. Many studies pertaining to neurolytic blocks were performed as observational studies, most of them from 1950s to 1970s during JJ Bonica's period, who was considered de facto the father of pain medicine. There are very few randomized controlled trials (RCT) on neurolytics and hence the evidence for various procedure is spread over a spectrum of credibility and firm conviction. Yet, nobody challenges the effectiveness of neurolytic procedures due to the lack of controlled trials. This treatment is firmly established because of the strong observational data. Neurolytic blockade is a therapeutic option when actual source of pain is untreatable.

The purpose is to relieve the pain by blocking the nerves that transmit pain from its noxious source. The primary indication for neurolytic blockade is complete relief of pain when the target is destroyed. Phenol, alcohol, and glycerol are locally neurotoxic substances used for blocking the nerves. These dehydrating agents cause a nonselective destruction of neuronal tissues followed by necrosis, nonsegmental demyelination, Wallerian degeneration, and complete conduction block, occurring within 10 min of application. Cryoneurotomy and thermal RF procedures are also done to break the link from noxious pain generator. Some common agents used for neurolysis are absolute alcohol or 50% alcohol, 6% aqueous phenol, and 6% phenol in glycerin. One retrospective study[4] comparing the effectiveness, duration of benefit, and complication profile of these two agents had shown no difference in pain outcomes, complications and duration of benefit. Thus, we recommend choice of neurolytic agent can be appropriately left to the good clinical judgment and availability of the expertize.

 Sympathetic Block Procedures



Celiac plexus neurolysis

There are many case series and uncontrolled, RCTs and meta-analysis been reported on its beneficial effects. CPN is used for the pain relief of upper abdominal structures, for example, pancreas, liver and biliary tract, kidney, ureter, spleen, bowel up to proximal third of transverse colon. Procedures were done using the landmark guided or fluoroscopy-guided technique since the last three decades, however, newer modalities such as endoscopic ultrasound, trans-abdominal ultra-sound or sometimes computed tomography (CT) guidance is employed to delineate the precise delivery of the neurolytic solution causing the block. CPN may provide good pain relief and lower the opioid requirement, reducing their side effects and improving the quality of life (QOL). There are four randomized controlled trials (RCT) comparing fluoroscopic-guided CPN with standard analgesics. One comparing CT-guided CPN with analgesics showed good and prolonged pain relief with reduced opioids and better QOL.[5],[6],[7],[8],[9] No RCT has compared endoscopic or trans-abdominal ultrasound-guided neurolysis as compared with standard analgesics. There are observational studies on the USG-guided CPN showing positive results.[10],[11],[12] Interestingly, one recently published trial showed endoscopic ultra sound (EUS) guided RF neurolysis resulted in good pain relief and QOL versus endoscopic neurolysis.[13] Two recent meta-analysis has shown EUS guided CPN is effective for pain relief in 80% and 72% of cancer patients, respectively.[14],[15] Furthermore, the Cochrane review had demonstrated that CPN may cause fewer adverse effects and should be considered for pain relief.[16]

Splanchnic nerve neurolysis

Splanchnic nerve neurolysis (SNN) was first described by Kappis in 1919 and thereafter multiple studies had shown its benefit. SNN may have gone out of vogue due to its higher complications owing to its proximity to the lower dorsal dermatomes with possible pulmonary, vascular and neurological complications. Although upper abdominal tumors cause little anatomical disturbance in the posteriorly located territory of retrocrural splanchnic nerves, hence, SNN may be employed in advanced disease too, however SNN has limited evidence having only one observational and three retrospective studies.[17],[18],[19]

The evidence on the RF CPN is limited with only one retrospective study.[20] Some clinicians may combine RF lesioning with CNN for better long-term effect.

Superior hypogastric plexus block

One RCT and three observational studies have shown good pain relief consequent to SHP block.[21],[22],[23],[24] The neurolysis can be done under fluoroscopy, CT or USG guidance; with the CT and USG approach may be attempted in supine position with lesser potential of a vascular injury.

Ganglion impar block

There are case series on the use of ganglion impar block[25],[26] for pain relief from perianal structures. The block can be performed with the aid of ultrasound, fluoroscopy, or CT guidance. It may be combined with SHP block for combined pelvic and perianal pain.

 Peripheral Nerve Blocks



Intercostal neurolysis

Although the intercostal neurolysis or radiofrequency ablation has been used for chest wall pain from cancer, the evidence is limited with observational studies and case series.[27],[28],[29],[30]

Brachial plexus neurolysis

The brachial plexus neurolysis has been useful for relieving intractable pain arising from tumor compressing upon it. It may lead to loss of motor function of the limb and should be best avoided due to better available modalities of pain management.[31],[32],[33] Use of continuous brachial plexus block with a catheter may be a good alternative and has been described in a few descriptive studies.[34],[35] Intrathecal selective sensory neurolysis should be attempted by positioning the patient in such a way that it does not compromise motor function.

 Neuraxial Blocks



Epidural neurolysis

Evidences on interlaminar or transforaminal epidural neurolysis have been tried in cancer cervix and colorectal disease.[36],[37],[38] However, these are not attempted nowadays due to the lack of expertize and also due to available safer options such as intrathecal delivery of opioids.

Intrathecal neurolysis

The literature on the intrathecal neurolysis is also scarce with a few old studies or some case reports.[39],[40],[41] Most commonly chemical agents such as alcohol with concentrations of 50%–100% and phenol 6%–12% are used for neurolysis. Alcohol is hypobaric and the affected side is positioned up at 45°. Phenol solution is hyperbaric and the affected side is positioned down at 45°. Their limitations include poor pain control due to disease progression, or shorter duration of effect due to imprecision, rarely motor weakness of leg, and bowel or bladder dysfunction.[42]

The procedure may be useful in patients with <1 year life expectancy with well localized intractable somatic pain rather than visceral pain.[43]

Epidural, intrathecal or intra-ventricular opioid infusions

This technique provides good benefit to select group of patients. There are only two randomized trials[44],[45] showing both improved analgesia and prolonged survival in patients receiving neuraxial opioids versus conventional medical management. Another high-quality review[46] has found similar efficacy of opioids.

Different types of pumps, connected to percutaneous catheters to fully implantable programmable pumps ones available. Furthermore, after 3 months, the cost of therapy of implantable pumps is less than nonimplantable ones.

If patient's life expectancy <3 months, an epidural route and if >3 months, intra-thecal route is preferred. The epidural catheter is usually placed percutaneously and fixed by tunneling and connected via a programmable pump or syringe driver. The programmable pumps need refilling after few weeks or months, and these patients needs to in close follow-up with the managing specialists.

Most commonly, opioids such as morphine is used for patients who respond partially to systemic morphine and/or are limited by side effects. For patients, who fail to respond to opioids, other medications such as local anesthetics, clonidine, and ziconitidine can also be used and have shown good results [Table 1].[47],[48],[49]{Table 1}

 Other Interventional Procedures



Cementoplasty

Cementoplasty types are: vertebroplasty, kyphoplasty, sacroplasty, acetabuloplasty, and osteoplasty. In cementoplasty, the injection of acrylic bone cement into the malignant bone cavities is done to either relieve the pain or stabiles the bone, or both. Vertebroplasty means injection of bone cement into the vertebral body. Cement into the sacrum, acetabulum and other weight bearing bones termed as sacroplasty, acetabuloplasty, and osteoplasty, respectively. Kyphoplasty restores of the original height of the vertebrae by inflating a balloon in the cavity of vertebra and then the space filled with bone cement. Cementoplasty may be considered after tumor ablation using RF.

A recent review of the studies has showed that cementoplasty has significantly reduced the pain, opioids needs, and functional disabilities.[50]

 Summary



Interventional pain management has brought out a revolution in the armamentarium of cancer pain helping patients, pain physicians, palliative care physicians, and others who are involved in cancer pain care for better pain control with a minimum side effects ensuring maintained QOL.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1World Health Organization. Cancer pain relief : with a guide to opioid availability. World Health Organization 1996;2. Available from: https://apps.who.int/iris/handle/10665/37896. [Last accessed on 2021 Mar 13].
2Forbes K. Pain in patients with cancer: The World Health Organization analgesic ladder and beyond. Clin Oncol (R Coll Radiol) 2011;23:379-80.
3Ahmed A, Thota RS, Chatterjee A, Jain P, Ramanjulu R, Bhatnagar S, et al. Indian society for study of pain, cancer pain special interest group guidelines on interventional management for cancer pain. Indian J Palliat Care 2020;26:203-9.
4Koyyalagunta D, Engle MP, Yu J, Feng L, Novy DM. The effectiveness of alcohol versus phenol based splanchnic nerve neurolysis for the treatment of intra-abdominal cancer pain. Pain Physician 2016;19:281-92.
5Kawamata M, Ishitani K, Ishikawa K, Sasaki H, Ota K, Omote K, et al. Comparison between celiac plexus block and morphine treatment on quality of life in patients with pancreatic cancer pain. Pain 1996;64:597-602.
6Mercadante S. Celiac plexus block versus analgesics in pancreatic cancer pain. Pain 1993;52:187-92.
7Polati E, Finco G, Gottin L, Bassi C, Pederzoli P, Ischia S. Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 1998;85:199-201.
8Wong GY, Schroeder DR, Carns PE, Wilson JL, Martin DP, Kinney MO, et al. Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: A randomized controlled trial. JAMA 2004;291:1092-9.
9Zhang CL, Zhang TJ, Guo YN, Yang LQ, He MW, Shi JZ, et al. Effect of neurolytic celiac plexus block guided by computerized tomography on pancreatic cancer pain. Dig Dis Sci 2008;53:856-60.
10Tadros MY, Elia RZ. Percutaneous ultrasound-guided celiac plexus neurolysis in advanced upper abdominal cancer pain. Egypt J Radiol Nucl Med 2015;46:993-8.
11Bhatnagar S, Gupta D, Mishra S, Thulkar S, Chauhan H. Bedside ultrasound-guided celiac plexus neurolysis with bilateral paramedian needle entry technique can be an effective pain control technique in advanced upper abdominal cancer pain. J Palliat Med 2008;11:1195-9.
12Bhatnagar S, Joshi S, Rana SP, Mishra S, Garg R, Ahmed SM. Bedside ultrasound-guided celiac plexus neurolysis in upper abdominal cancer patients: A randomized, prospective study for comparison of percutaneous bilateral paramedian vs. unilateral paramedian needle-insertion technique. Pain Pract 2014;14:E63-8.
13Bang JY, Sutton B, Hawes RH, Varadarajulu S. EUS-guided celiac ganglion radiofrequency ablation versus celiac plexus neurolysis for palliation of pain in pancreatic cancer: A randomized controlled trial (with videos). Gastrointest Endosc 2019;89:58-66.
14Kaufman M, Singh G, Das S, Concha-Parra R, Erber J, Micames C, et al. Efficacy of endoscopic ultrasound-guided celiac plexus block and celiac plexus neurolysis for managing abdominal pain associated with chronic pancreatitis and pancreatic cancer. J Clin Gastroenterol 2010;44:127-34.
15Puli SR, Reddy JB, Bechtold ML, Antillon MR, Brugge WR. EUS-guided celiac plexus neurolysis for pain due to chronic pancreatitis or pancreatic cancer pain: A meta-analysis and systematic review. Dig Dis Sci 2009;54:2330-7.
16Arcidiacono PG, Calori G, Carrara S, McNicol ED, Testoni PA. Celiac plexus block for pancreatic cancer pain in adults. Cochrane Database of Systematic Reviews 2011(3): CD007519.
17Ahmed A, Arora D. Fluoroscopy-guided neurolytic splanchnic nerve block for intractable pain from upper abdominal malignancies in patients with distorted celiac axis anatomy: An effective alternative to celiac plexus neurolysis – A retrospective study. Indian J Palliat Care 2017;23:274-81.
18Marra V, Debernardi F, Frigerio A, Menna S, Musso L, Di Virgilio MR. Neurolytic block of the celiac plexus and splanchnic nerves with computed tomography. The experience in 150 cases and an optimization of the technic. Radiol Med 1999;98:183-8.
19Shwita AH, Amr YM, Okab MI. Comparative study of the effects of the retrocrural celiac plexus block versus splanchnic nerve block, c-arm guided, for upper gastrointestinal tract tumors on pain relief and the quality of life at a six-month follow up. Korean J Pain 2015;28:22-31.
20Papadopoulos D, Kostopanagiotou G, Batistaki C. Bilateral thoracic splanchnic nerve radiofrequency thermocoagulation for the management of end-stage pancreatic abdominal cancer pain. Pain Physician 2013;16:125-33.
21Mishra S, Bhatnagar S, Rana SP, Khurana D, Thulkar S. Efficacy of the anterior ultrasound-guided superior hypogastric plexus neurolysis in pelvic cancer pain in advanced gynecological cancer patients. Pain Med 2013;14:837-42.
22Serra G, Giacomello S, Terziotti L, Romano L, Pasetto I, Kourtesiss D. Superior hypogastric plexus block (SHPB) for pelvic pain secondary to cancer: Anterior approach with computed tomographic (CT) guidance: 262. Reg Anesth Pain Med 2005;30:91.
23de Leon-Casasola OA, Kent E, Lema MJ. Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer. Pain 1993;54:145-51.
24Plancarte R, de Leon-Casasola OA, El-Helaly M, Allende S, Lema MJ. Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer. Reg Anesth 1997;22:562-8.
25Ho KY, Nagi PA, Gray L, Huh BK. An alternative approach to ganglion impar neurolysis under computed tomography guidance for recurrent vulva cancer. Anesthesiology 2006;105:861-2.
26Ahmed DG, Mohamed MF, Mohamed SA. Superior hypogastric plexus combined with ganglion impar neurolytic blocks for pelvic and/or perineal cancer pain relief. Pain Physician 2015;18:E49-56.
27Wong FC, Lee TW, Yuen KK, Lo SH, Sze WK, Tung SY. Intercostal nerve blockade for cancer pain: Effectiveness and selection of patients. Hong Kong Med J 2007;13:266-70.
28Matchett G. Intercostal nerve block and neurolysis for intractable cancer pain. J Pain Palliat Care Pharmacother 2016;30:114-7.
29Gulati A, Shah R, Puttanniah V, Hung JC, Malhotra V. A retrospective review and treatment paradigm of interventional therapies for patients suffering from intractable thoracic chest wall pain in the oncologic population. Pain Med 2015;16:802-10.
30Ahmed A, Bhatnagar S, Khurana D, Joshi S, Thulkar S. Ultrasound-guided radiofrequency treatment of intercostal nerves for the prevention of incidental pain arising due to rib metastasis. Am J Hosp Palliat Care 2017;34:115-24.
31Nader A, Kendall MC. Selective infraclavicular brachial plexus phenol injection for the relief of cancer pain. Anesthesiology 2015;122:1153.
32Ronald K, Zenaida A, Werner P. Phenol brachial plexus block for upper extremity cancer pain. Reg Anesth Pain Med 1998;13:58-61.
33Loh TH, Patel S, Mirchandani A, Eckmann M. Brachial plexus chemical neurolysis with ethanol for cancer pain. Case Rep Med 2018:1-3: 8628645.
34Buchanan D, Brown E, Millar F, Mosgrove F, Bhat R, Levack P. Outpatient continuous interscalene brachial plexus block in cancer-related pain. J Pain Symptom Manage 2009;38:629-34.
35Vranken JH, van der Vegt MH, Zuurmond WW, Pijl AJ, Dzoljic M. Continuous brachial plexus block at the cervical level using a posterior approach in the management of neuropathic cancer pain. Reg Anesth Pain Med 2001;26:572-5.
36Candido KD, Philip CN, Ghaly RF, Knezevic NN. Transforaminal 5% phenol neurolysis for the treatment of intractable cancer pain. Anesth Analg 2010;110:216-9.
37Korevaar WC. Transcatheter thoracic epidural neurolysis using ethyl alcohol. Anesthesiology 1988;69:989-93.
38Bhade MA, Sanghvi PR, Shahand BC, Patel BM. Transcatheter thoracic epidural neurolysis using ethyl alcohol. Pain Clin 2005;4:55-60.
39Candido K, Stevens RA. Intrathecal neurolytic blocks for the relief of cancer pain. Best Pract Res Clin Anaesthesiol 2003;17:407-28.
40Watanabe A, Yamakage M. Intrathecal neurolytic block in a patient with refractory cancer pain. J Anesth 2011;25:603-5.
41Lynch J, Zech D, Grond S. The role of intrathecal neurolysis in the treatment of cancer-related perianal and perineal pain. Pal Med 1992;6:140-5.
42Hay RC. Subarachnoid alcohol block in the control of intractable pain: Report of results in 252 patients. Anesth Analg 1962;41:12-6.
43Gerbershagen HU. Neurolysis. Subarachnoid neurolytic blockade. Acta Anaesthesiol Belg 1981;32:45-57.
44Smith TJ, Staats PS, Deer T, Stearns LJ, Rauck RL, Boortz-Marx RL, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol 2002;20:4040-9.
45Smith TJ, Coyne PJ, Staats PS, Deer T, Stearns LJ, Rauck RL, et al. An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug-related toxicity, and possibly better survival compared with comprehensive medical management (CMM). Ann Oncol 2005;16:825-33.
46Ballantyne JC, Carwood C, Gupta A, Bennett MI, Simpson KH, Dhandapani K, et al. Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer. Cochrane Database of Systematic Reviews 2005(2): CD005178.
47Eisenach, JC, De Kock M, Klimscha W. Alpha sub 2-andrenergic agonists for regional anesthesia: A clinical review of clonidine (1984-1995). Anesthesiology 1996;85:655-74.
48van Dongen RT, Crul BJ, van Egmond J. Intrathecal coadministration of bupivacaine diminishes morphine dose progression during long-term intrathecal infusion in cancer patients. Clin J Pain 1999;15:166-72.
49Staats PS, Yearwood T, Charapata SG, Presley RW, Wallace MS, Byas-Smith M, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: A randomized controlled trial. JAMA 2004;291:63-70.
50Health Quality Ontario. Vertebral augmentation involving vertebroplasty or kyphoplasty for cancer-related vertebral compression fractures: A systematic review. Ont Health Technol Assess Ser 2016;16:1-202.