Review and Meta-analysis
DOI: 10.31557/apjcc.2023.8.2.391-399
Submitted: 2023-01-11
Published: 2023-06-14

Role of Interventional Techniques in the Management of Cancer Pain

Department of Anaesthesia and Critical Care, Shri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
Department of Radiation Oncology, Shri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
Department of Anaesthesia and Critical Care, Shri Balaji Hospital, Kangra, H.P, India.
Department of Anaesthesia and Critical Care, Dr. Rajendra Prasad Government Medical College, Tanda, H.P, India.
Cancer pain, interventional techniques, sympathetic block, peripheral nerve block radiotherapy, radionuclides

Abstract

Pain is the major cause of morbidity in cancer patients. Interventional techniques should be considered for the management of pain that is refractory to traditional analgesics or when patients are unable to tolerate opioids. Interventional techniques are intended to stop pain signals through neural pathways from the periphery to the brain. This article deals with major interventional pain management techniques such as central neuraxial block, sympathetic block, peripheral nerve block, percutaneous cordotomy, percutaneous vertebroplasty and kyphoplasty, radiofrequency ablation, and cryoablation. Besides this, the role of radiotherapy and radionuclides in cancer pain have also been discussed. Central neuraxial block can effectively reduce pain while preventing opioid toxicity. It involves a percutaneous epidural or intrathecal catheter, an external syringe pump, or a fully implanted intrathecal drug delivery system to give medication. Sympathetic blocks such as celiac plexus and superior hypogastric block have role in patients with visceral abdominal pain. Peripheral nerve blocks may be employed when the distribution of somatic pain is restricted to a single nerve or plexus. Percutaneous cordotomy could be useful for any unilateral cancer pain below C4 dermatome. Percutaneous vertebroplasty (PV) treatment is used to alleviate axial back pain due to osteoporotic wedge fracture or malignant vertebral body disease. RFA and cryoablation techniques are now widely used for back pain due to osteoporotic and malignant vertebral collapse that are resistant to conservative treatment. External beam radiotherapy and radionuclides are useful in relieving cancer pain due to bone metastasis. This article aims at summarizing the indications, mechanisms, drug agents, contraindications, and complications of interventional pain management techniques that may offer benefits to patients coping with cancer and its terrible symptoms. Even though there is some risk involved with the techniques discussed in this article, the advantages of reduced pain and enhanced quality of life usually outweigh the risk.

Introduction

Pain is the major cause of morbidity for cancer patients [1-2]. Between 20% and 50% of cancer patients report experiencing pain in the early stages of the disease. Most of the cancer patients with advanced stage disease experience pain at multiple sites, with about 75 percent of them reporting moderate to severe pain [3-4]. Pain negatively affects the quality of life of cancer patients, and nearly 32% will have pain that is not adequately addressed [2, 5]. According to estimates, 66% of people with advanced cancer will feel pain as a result of their condition or its treatment.

The WHO Cancer Pain Ladder for Adults has been used as a model for the management of cancer-related pain since 1986. Their three-step approach suggests using non-opioids for early pain management, then mild opioids (such as codeine) for mild to moderate pain, and finally strong opioids (such as morphine) for moderate to severe pain. Most cancer patients who experience pain obtain effective results with drugs included in the WHO analgesic ladder [6].

Treating physicians believed that the WHO’s three- step pain management ladder had not kept up with the quickly developing breakthroughs in oncology and pain research. To make the 3-step WHO analgesic ladder effective after drugs fail, a fourth “interventional” step that included nerve blocks, intrathecal drug delivery systems, and palliative surgery was required to make the three-step WHO analgesic ladder effective [7].

In 80% to 90% of these patients, pain can be effectively managed with the help of oral, conventional analgesics. However, it has been estimated that in 10–20% of individuals with advanced disease, systemic analgesics and opiates are found to be ineffective in treating the pain [8]. Such a type of pain is known as refractory pain. Interventional techniques intended to stop pain signals through neural pathways from the periphery to the brain may be quite helpful for some patients. Additionally, opioid use is linked to side effects like cognitive impairment, nausea, and constipation; as a result, patients sometimes find it difficult to tolerate a dose increase, even when they need improved pain management [9].

Interventional pain management approaches can reduce opioid use and its negative effects. When conventional analgesics fail to provide sufficient pain relief or have severe side effects, interventional techniques should be taken into account, whether the disease process is early or late. This article aims at summarizing the indications, mechanisms, drug agents, contraindications, and complications of interventional pain management techniques that may offer benefit to patients coping with cancer and its terrible symptoms.

Central Neuraxial Blocks

The binding of an opioid to its spinal cord receptor inhibits or blocks the conduction of nociceptive signals, which is the basis for neuraxial analgesia. Opioids may also alter the pain pathway in the midbrain by disrupting the descending pathways. Although it can effectively reduce pain while preventing opioid toxicity, it should only be used on patients for whom simpler approaches have failed to adequately control their pain. Approximately 2% of patients will benefit from these techniques, depending on the population under consideration.

A percutaneous epidural or intrathecal catheter, an external syringe pump, or a fully implanted intrathecal drug delivery system can all be utilized to give medication. Patients with shorter life expectancies (<3 months) may benefit from epidural therapy using implanted systems such as a catheter or port-a-catch connected to an external patient-controlled analgesia (PCA) pump, while patients with cancer-related pain and longer survival expectancies (>3 months) may benefit from neuraxial therapies using implantable systems as a permanent intrathecal catheter and subcutaneous pump [10]. The likelihood of survival, patient demands, and cost are typically taken into account while choosing a type of device. Other anaesthetics, such as bupivacaine, can be used instead of or in addition to opioids because of their long duration of action, low toxicity, and affordable price. Other agents such as clonidine, ketamine, and neostigmine may enhance analgesia and lower opioid dosages [10]. It is crucial to choose patients carefully and to educate the people who will be caring for patients who receive these infusions [11-12]. Complications of neuraxial therapy include damage to the spinal cord or fibers during catheter insertion, dural puncture headache, epidural hematoma, infection, and meningitis [13].

Kurita et al. in a systematic review, analyzed the analgesic efficacy and adverse effects of opioids with and without adjuvant analgesics when administered through the neuraxial route (epidural and subarachnoid) to adults with cancer pain. They demonstrated better pain control for all interventions analyzed [14]. However, the review concluded with a weak recommendation for the neuraxial administration of opioids in adult cancer patients, which might be attributed to the heterogeneous characteristics and many methodological flaws in the study.

Sympathetic nerve block

Despite the fact that abdominal pain frequently coexists with other pathophysiological symptoms, patients with visceral abdominal pain are advised to undergo neurolytic inhibition of sympathetic pathways at various levels [15]. The celiac plexus receives the sympathetic fibres from greater and lesser splanchnic nerves from T5 to T12 [16]. These nerve fibers extend inferiorly to the level of the superior and inferior mesenteric plexus and surround the celiac trunk.

Most of the abdominal viscera, including the stomach, liver, biliary tract, pancreas, spleen, kidneys, adrenals, omentum, small bowel, colon to the splenic flexure, are innervated by the celiac plexus. Celiac plexus block (CPB) is used to treat cancer-related pain arising from the upper abdominal viscera while the superior hypogastric plexus block (SHPB) is used to treat lower abdominal pain. In order to eliminate or lessen pain, these blocks interfere with neural conduction. The effectiveness of CPB is probably dependent on each patient’s anatomical distribution, which is probably going to change as the tumor grows locally. The block is probably going to be less effective when tumor spread involves other somatic regions like the peritoneum or diaphragm.

The general contraindications for neurolytic blocks of sympathetic pathways include tumor penetration into the insertion site, coagulopathy, systemic or localised infection, complicated anatomy, and bowel obstruction [17,18]. The main complications of sympathetic block are back pain, orthostatic hypotension, diarrhoea, retroperitoneal hematoma, bladder or ureteral injury, and unintentional somatic nerve damage [17,18]. CPB is believed to be safer than neurolytic somatic blocks because, when carried out under CT guidance, neurological complications are infrequent and mostly transient.

With total pain relief reported in up to 48% of patients in randomised controlled trials, celiac plexus neurolysis (CPN) has been demonstrated to be effective in reducing overall pain. Other randomised controlled trials have demonstrated that celiac plexus blocks and neurolysis lessen the overall need for opioids as well as their negative effects, such as nausea, vomiting, constipation, and hypotension [16]. Patients receiving CPN are advised to have post-procedure monitoring. The most frequent adverse effects are transitory diarrhoea and hypotension, with risk ratios of 5.88 and 7.43, respectively, according to a recent comprehensive review [18]. Compromised respiratory function (pneumothorax and pleural effusion), neurologic issues (transient dysesthesias or paraplegia), increased pain, alcohol intoxication, peritonitis, and hematuria are rare but potentially dangerous consequences of CPN [19].

In a systematic review by Mercadante et al, compared to standard analgesic care, celiac plexus blocks have been shown to increase analgesia, reduce opioid intake, and mitigate opioid-induced side effects [20]. Patients with painful, inoperable pancreatic adenocarcinoma may benefit from endoscopic ultrasonography guided celiac plexus neurolysis, as described by Wyse et al. in a randomised controlled trial [21]. Okumaya et al, have shown that that intraoperative celiac plexus block is an effective and safe, method for the management of pain caused by unresectable pancreatic cancer [22].

There is a lack of available data on superior hypogastric block. A study based on the use of anterior USG-guided superior hypogastric plexus neurolysis has reported that it is a useful technique in relieving pelvic pain in gynaecological malignancies. However, it requires expertise to perform the block [23]. The origin of pelvic cancer-related pain, is even more complex, because of different mechanisms involved due to the various overlapping structures, including muscles and nerves [24]. The study reported that patients with pelvic cancers with a neuropathic component showed worse pain relief. The evidence from the literature is weak in support of employing this intervention.

Other autonomic blocks

For pain with an autonomic component in the head or arm, a stellate ganglion block may be employed. As catheter procedures are challenging and neurolytic block poses major risks in light of the anatomical relations of the ganglion, single or repeated injections are carried out. For ischemic leg pain, pain mediated by the sympathetic nervous system, and bilaterally for tenesmus, a lumbar sympathetic block can be performed [25]. The superior hypogastric plexus neurolytic block [26] or the ganglion of impar can reduce pain from pelvic structures [27].

Peripheral nerve block

When the distribution of somatic pain is restricted to a single nerve or plexus, peripheral nerve blocks may be employed. The pain may be due to primary or secondary tumor deposits or as a result of treatment e.g. post-radiation pain, or due to secondary complications like pathological fracture or vascular blockage.

Peripheral nerve blocks are rarely used as the sole or even the primary form of treatment. Most people will have pain at multiple sites. However, when used in conjunction with other forms of therapy like systemic analgesics, radiotherapy, and chemotherapy, they may be able to effectively relieve one component of a patient’s overall pain while also facilitating other types of treatment like physiotherapy and lymphedema care.

Local anaesthetics are the medications used for nerve blocks, and due to their short duration of action, they must be used continuously or intermittently. Lidocaine, bupivacaine, and ropivacaine are a few examples of local anaesthetics in use. The analgesic effect is similar despite the potential toxicity in connection to cardiac events and other local anaesthetic toxic reactions. The risk of toxicity is negligible, nevertheless, provided the local anaesthetic is administered in accordance with the recommended doses. Each local anaesthetic has a distinct duration of action. as a different duration. Bupivacaine and ropivacaine are long-acting local anaesthetics (4-18 h), but lidocaine has an intermediate action and takes 1.5 to 3 hours to have effect [28]. The duration of action may vary depending on the location of the nerve block and may be affected by addition of other agents like epinephrine or clonidine [29]. Therefore, long-term treatment with local anaesthetics is best achieved by bupivacaine or ropivacaine; bupivacaine has been the most often reported drug for this purpose. According to some reports, peripheral nerve blocks were used with neurolytic agents such as glycerol, phenol, or alcohol. These substances irreversibly damage the neuron and need a single injection for a long-term block of the signalling of nerve impulse.

Most frequently, local anaesthetics are administered as single injections or catheter infusions to target the peripheral nervous system as part of a perioperative anaesthetic regimen [30]. Deep analgesia can be achieved by injecting local anaesthetics into the nerve supply of the affected extremities without the adverse side effects of parenteral medications like opioids [31]. The technique used for the management of acute postoperative pain might be applied for the treatment of cancer related pain. Although a single injection of local anaesthetic is sufficient for short-duration analgesia, such as during an imaging test, surgery, or rapid treatment of a pain crisis, continuous infusion via an indwelling catheter provides a longer period of analgesia.

The peripheral nerve blocks that have been reported in several studies include femoral nerve block, sciatic nerve block, paravertebral block, brachial plexus block, suprascapular, psoas compartment, distal lumbar plexus, and intrapleural blocks [32-39]. However, there are not many clinical studies on the usage of peripheral nerve blocks. Most of them are case reports or small case series containing a description of what has worked.

Contraindications to upper-extremity peripheral nerve block techniques include infection, deranged coagulation profile, past history of nerve injury, including exposure to certain chemotherapeutic medications that are neurotoxic [40]. Pneumothorax, spinal cord injury, nerve damage, respiratory depression secondary to phrenic nerve block, [41] and Horner’s syndrome are risks associated with interscalene blocks. Other methods of upper-extremity blocks carry similar risks. However, as one proceeds distally along the plexus, the risk of respiratory depression and Horner’s syndrome decreases.

A systematic review by Klepstad et al. which reported on the existing evidence of analgesic efficacy for peripheral nerve blocks in adult patients with cancer found that most cases experienced pain relief. The duration of efficacy lasted for several weeks even till death. However, peripheral blocks for cancer-related pain are currently only supported by anecdotal data [42].

Percutaneous Cordotomy

Percutaneous cordotomy is a technique in which a thermal lesion is created by radiofrequency electric current in the spinothalamic tract contralateral to the side of the pain. This interrupts conduction fibres and eliminates pain and temperature sensation from the affected half of the body. Its mechanism is unknown, however, alteration on descending impulse or dorsal horn modulation, C fiber damage, and immunomodulatory effects could all affect how pain is transmitted. Pulsed radiofrequency needle tips are maintained at 43 °C to minimize tissue injury, however typical radiofrequency needle tips are 80–90 °C [17].

Cordotomy can only alleviate pain below the C4 dermatome since certain second-order spinothalamic fibers decussate multiple spinal segments above or below their distal synaptic connections (i.e., below the clavicle). Radiofrequency current is typically used to achieve it percutaneously. However, open surgical techniques are an option. It is effective, as in 83% of patients undergoing the procedure opioid use is cut to half, and 38% of the patients can stop it altogether [43]. It is primarily utilised for refractory chest wall pain secondary to mesothelioma and infrequently for Pancoast tumours, although theoretically it could be useful for any unilateral cancer pain below C4. Percutaneous cordotomy by radiofrequency has emerged as a practical alternative because of developments in fluoroscopy that allow for treatment under sedation instead of general anaesthesia. These benefits are especially advantageous for frail patients with terminal cancer. Risks and outcomes should be carefully taken into consideration because this technique disrupts nerve conduction irreversibly. Cancer patients who are candidates for this procedure must have unilateral pain that is resistant to systemic analgesics and other non- destructive interventions, have a life expectancy of a few years or less taking into account the possibility of pain recurrence, and anatomic location of the intervention that permits a safe procedure [44].

Percutaneous cordotomy can be used for the treatment of brachial plexus pain associated to pancoast tumour, breast cancer, malignant pleural mesothelioma, unilateral leg pain, and pain related to breast cancer. Besides this, it can also be used for bilateral cancer-related pain, but bilateral treatments raise the risk of complications and mortality [45].

Some people may experience numbness or dysesthesias below the level of the lesion as a result of this procedure. Contraindications are abnormal coagulation, infection, severe respiratory dysfunction, and advanced disease that prevents optimal positioning of the patient during the procedure [45]. The complications include hemiparesis, respiratory irregularities, bladder and bowel dysfunction (usually temporary), and ataxia [44]. Studies have shown it to be safe and effective in reducing cancer related pain [46-49].

Percutaneous vertebroplasty and kyphoplasty

Percutaneous vertebroplasty (PV) treatment is used to alleviate axial back pain due to osteoporotic wedge fracture or malignant vertebral body disease. In this procedure, bone cement is injected into the vertebral body under fluoroscopic supervision. It is believed to function by preventing painful aberrant macro- or micromovement of bony ends and stabilising fracture sites. The underlying mechanism of action is that the thermogenesis produced by the setting cement may have a neurolytic effect.

Despite the reported efficacy and low risk associated with these interventions, only a few patients have access to such minimally invasive procedures because of a shortage of skilled staff, imprecise indications, and higher costs [50]. Therefore, these treatments should only be used on a specific group of patients who have severe and incapacitating cancer-related back pain that is resistant to systemic analgesic therapy. In PV, a cement called polymethylmethacrylate is injected percutaneously into the vertebral bodies. This cement can mechanically stabilize the lesion or compression fracture, boost bone strength, and reduce pain.

In a related surgery called kyphoplasty, the height of the vertebral body is restored with the injection of cement into the cavity created by the repeated inflation of a balloon inserted into the vertebral body. Both PV and kyphoplasty have comparable indications and contraindications, and neither provides better pain relief than the other [51].

Several studies have suggested a potential therapeutic function for these treatments, but the available data are generally hampered by small sample sizes, retrospective designs, or a lack of comparability across study groups. A systematic review has reported that both vertebroplasty and kyphoplasty significantly and rapidly lowered pain severity in cancer patients with vertebral compression fractures. They also lowered the requirement for opioid pain medication, and functional limitations related to back and neck pain [52]. A systematic review involving five studies, recommended to perform kyphoplasty in patients with vertebral tumors or metastases [53]. However, a number of flaws and a poor study design compromise the validity of this recommendation, which is based on a single randomized controlled trial.

Radio frequency ablation and Cryoablation

Radio frequency ablation (RFA) ablates bone tumor or metastasis using the heat produced by medium frequency alternating current. Cryoablation (CA) is an alternative to radiofrequency ablation (RFA) for treating metastatic bone disease. It is performed with the use of cryoprobes that circulate cold, thermally conductive fluids. These techniques are now widely used for back pain due to osteoporotic and malignant vertebral collapse that is resistant to conservative treatment [50].

The use of these techniques, particularly in individuals with advanced cancer, is still debatable. Several studies have suggested a possible therapeutic role of these approaches, despite the fact that current data are limited to series with a small number of patients, retrospective designs, or mixed populations. Due to the small patient population and poor data quality, there is currently no evidence of efficacy of these techniques for cancer patients with spinal metastases or tumours.

Radiotherapy and Bisphosphonates

An external beam radiotherapy is a treatment option for metastatic bone pain [54-57]. According to a meta-analysis, external beam radiation provided partial pain relief in up to 60% to 90% of the patients with uncomplicated bone metastasis and about a quarter of these patients reported complete pain relief within 3-4 weeks [58]. According to various studies, single fraction radiation is just as efficient at relieving bone pain as fractionated radiation [59-60]. In other words, short course palliative radiation with a greater dose per fraction produce outcomes that are comparable to those of longer courses that with a small dose per fraction. Patients receiving unfractionated radiation appear to have a higher re-treatment rate and a higher incidence of pathological fractures. The minimal total dose of radiation required for pain relief is still unknown.

After radiation, patients who experience improvement in pain may also experience better emotional functioning, decreased insomnia, less constipation, and an overall increase in quality of life scores [61]. In order to alleviate pain and prevent additional symptoms, radiation therapy should be a crucial component of palliative care for bone metastases [62].

The absence of a dose-response relationship shows that the initial pain relief mechanism is more likely due to change in the local environment resulting in activation of bone resorption by osteoclasts rather than a decrease in tumour load [63]. This explains the seemingly paradoxical comparison of relief in pain between single-dose treatment and longer-course treatment.

The most appropriate treatment for patients with a poor performance status having difficulty in making multiple trips for treatment, extensive bony metastases, and/or a short life expectancy is a single fraction of 8 Gy. Patients with a limited expectancy (<3 months) also experience pain relief, and palliative radiotherapy should still be considered for such patients [64-65]. While patients with a good performance status, longer life expectancy and bone-only metastases, a longer course of treatment (30 Gy in 10 fractions) may be a better option to minimize the risk of retreatment. Treatment with a higher dose may be necessary for some patients with a single bone metastasis (referred to as a “oligometastasis”), although this must be balanced against the possibility of potential weakening of surrounding normal bone.

Reirradiation to the painful metastatic sites can be administered for some patients who do not respond to the initial course of treatment or for those who experience pain recurrence after an initial successful treatment [66]. Approximately 60% of retreated patients reported an improvement in their pain, with 16% to 28% of patients reporting a complete resolution of pain [67]. Patients also reported an improved overall quality of life and decrease in pain-related functional limitations with the retreatment of painful bone metastasis [68].

Patients with osseous metastases typically have multiple lesions. Radiation therapy can relieve pain in a few specific sites, but it cannot treat widespread disease. Wide-field radiation treatment, also known as hemibody irradiation, is a method of treating a sizable area of the body with an external beam of radiation. Although the term hemibody irradiation is used, the field normally treats around one-third of the body, rather than the entire body. The treatment has been used as an adjuvant to stop the development of new bone metastases as well as to relieve symptoms. Patients with diffuse, extensive bone metastases benefit the most from the treatment for pain relief.

Trials evaluating multifraction courses of HBI were conducted by both the RTOG and the International Atomic Energy Agency [69-70]. The total dosage ranged from 8 to 20 Gy, with doses per fraction varying from 2.5 to 4 Gy. On the RTOG 88-08 study, 17.5 Gy in seven fractions was the highest tolerated dose. According to the study by the International Atomic Energy Agency, 3 Gy twice day for 2 days (12 Gy total) or 3 Gy every day for 5 days (15 Gy total) were more efficient than 4 Gy every day for 2 days. The use of bisphosphonates is recommended as they have a role in reducing skeletal morbidity in bony metastatis [64-65,71]. Although a thorough study found little evidence of an analgesic effect, bisphosphonates may delay the onset of pain [72]. In a study by Vassiliou et al., bone density in the area of the metastases increased by 73% by 10 months after treatment [73].

Radionuclides

Radionuclide therapy is as effective as external radiation therapy in relieving cancer pain due to bone metastasis. The concept of radiopharmaceutical treatment is compelling [74]. Calcium (and to a lesser extent phosphorous) analogs will preferentially accumulate in bone in areas of active bone turnover. A targeted treatment in the regions where the radiopharmaceutical accumulates will be possible using a radioactive isotope that is beta emitter or low-energy gamma emitter. This reduces side effects and provides an excellent therapeutic ratio. A single injection is used to administer the radiopharmaceuticals, making it simple to administer. It is possible to combine the therapy with other approaches, such as chemotherapy or external radiation therapy.

Phosphorus-32 was the first radiopharmaceutical used to treat bone metastases (P-32). Subjective pain alleviation with P-32 treatment for diffuse bone metastases was achieved, albeit at the expense of significant bone marrow damage. With a better therapeutic ratio than P-32, several radioisotopes have been applied to the palliation of diffuse osseous metastases.

Chemically comparable to calcium, strontium-89 (Sr-89) is deposited in the bone matrix, preferentially in areas where osteogenesis is actively taking place. Sr-89 is a pure beta emitter with a half-life of 50.6 days and an energy of 1.4 MeV [75]. Although samarium-153 (Sm-153) is largely beta emitter, it also possesses a gamma emission component that is useful for imaging purposes.

Multiple prospective trials have been conducted to assess these two isotopes. Other, more recent isotopes like tin-117m, rhenium-186, and rhenium-188 are being studied. Radium-223 may also increase overall survival in individuals with castrate-resistant metastatic prostate cancer in addition to pain relief. All of these isotopes accumulate in areas of osteoblastic activity, especially in areas of increased uptake on bone scintigraphy. This is the reason why most of the patients entered on prospective trials have metastatic prostate cancer.

In a study by Porter and McEwan, after receiving involved-field radiation treatment, the patients were assigned to receive 400 MBq of Sr-89 or a placebo. Even while there was no statistically significant difference in the primary objective of pain alleviation, the Sr-89 had superior results in a number of secondary end points. In the patients who got Sr-89, more patients (17% vs. 2%) were able to stop using their analgesics, and there were fewer sites of new pain requiring radiotherapy [76]. Studies have reported significant improvement in pain relief, decrease in the average opioid dose in the patients receiving Sm-153 [77-78].

In conclusion, the treatment of a patient with refractory pain due to cancer may be incredibly challenging. Those patients who do not respond well to the systemic opioids and adjuvant analgesics should be actively examined for more advanced pain treatment alternatives. It is crucial to pay close attention to the selection of the technique, skill to perform the procedure, logistics, appropriate indication, type of pain if well-defined/localized, benefits and risks involved. Besides this, patient’s health status, estimated survival time, and requirements should be taken into account when treating cancer-related pain in order to prevent complications and ensure that the right intervention is chosen. Even though there is some risk involved with the advanced interventional techniques discussed in this article, the advantages of reduced pain and enhanced quality of life usually outweigh the risk.

References

References

  1. Beuken-van Everdingen MHJ, Rijke JM, Kessels AG, Schouten HC, Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Annals of Oncology: Official Journal of the European Society for Medical Oncology. 2007; 18(9)DOI
  2. Beuken-van Everdingen MHJ, Hochstenbach LMJ, Joosten EAJ, Tjan-Heijnen VCG, Janssen DJA. Update on Prevalence of Pain in Patients With Cancer: Systematic Review and Meta-Analysis. Journal of Pain and Symptom Management. 2016; 51(6)DOI
  3. Grond S, Zech D, Diefenbach C, Radbruch L, Lehmann KA. Assessment of cancer pain: a prospective evaluation in 2266 cancer patients referred to a pain service. Pain. 1996; 64(1)DOI
  4. Twycross R. Cancer pain classification. Acta Anaesthesiologica Scandinavica. 1997; 41(1 Pt 2)DOI
  5. Greco MT, Roberto A, Corli O, Deandrea S, Bandieri E, Cavuto S, Apolone G. Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2014; 32(36)DOI
  6. World Health Organization. Cancer Pain Relief ; World Health Organization: Geneva, Switzerland. 1996.
  7. Miguel R. Interventional treatment of cancer pain: the fourth step in the World Health Organization analgesic ladder?. Cancer Control: Journal of the Moffitt Cancer Center. 2000; 7(2)DOI
  8. Sloan PA. Neuraxial pain relief for intractable cancer pain. Current Pain and Headache Reports. 2007; 11(4)DOI
  9. Koyyalagunta D, Bruera E, Solanki DR, Nouri KH, Burton AW, Toro MP, Bruel BM, Manchikanti L. A systematic review of randomized trials on the effectiveness of opioids for cancer pain. Pain Physician. 2012; 15(3 Suppl)
  10. Sharma V, de Leon-Casasola O. Cancer pain. In Practical Management of Pain, 5th ed.; Benzon, H.T., Rathmell, J.P., Wu, C.L., Turk, D.C., Argoff, C.E., Hurley, R.W., Eds.; Mosby (Elsevier): Philadelphia, PA, USA, 2014; pp. 335–345 e.3. ISBN 9780323170802..
  11. Staats P. Neuraxial infusion for pain control. Oncology. 1999; 13
  12. Buchheit T, Rauck R. Subarachnoid Techniques for Cancer Pain Therapy: When, Why, and How?. Current Review of Pain. 1999; 3(3)DOI
  13. Moeschler SM, Rosenberg C, Trainor D, Rho RH, Mauck WD. Interventional modalities to treat cancer-related pain. Hospital Practice (1995). 2014; 42(5)DOI
  14. Kurita GP, Benthien KS, Nordly M, Mercadante S, Klepstad P, Sjøgren P. The evidence of neuraxial administration of analgesics for cancer-related pain: a systematic review. Acta Anaesthesiologica Scandinavica. 2015; 59(9)DOI
  15. Caraceni A, Portenoy RK. An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. International Association for the Study of Pain. Pain. 1999; 82(3)DOI
  16. Bahn BM, Erdek MA. Celiac plexus block and neurolysis for pancreatic cancer. Current Pain and Headache Reports. 2013; 17(2)DOI
  17. Scott-Warren J, Bhaskar A. Cancer pain management: Part II: Interventional techniques. Continuing Education in Anaesthesia Critical Care & Pain. 2015; 15(2)DOI
  18. Kambadakone A, Thabet A, Gervais DA, Mueller PR, Arellano RS. CT-guided celiac plexus neurolysis: a review of anatomy, indications, technique, and tips for successful treatment. Radiographics: A Review Publication of the Radiological Society of North America, Inc. 2011; 31(6)DOI
  19. Nagels W, Pease N, Bekkering G, Cools F, Dobbels P. Celiac plexus neurolysis for abdominal cancer pain: a systematic review. Pain Medicine (Malden, Mass.). 2013; 14(8)DOI
  20. Mercadante S, Klepstad P, Kurita GP, Sjøgren P, Giarratano A. Sympathetic blocks for visceral cancer pain management: A systematic review and EAPC recommendations. Critical Reviews in Oncology/Hematology. 2015; 96(3)DOI
  21. Wyse JM, Carone M, Paquin SC, Usatii M, Sahai AV. Randomized, double-blind, controlled trial of early endoscopic ultrasound-guided celiac plexus neurolysis to prevent pain progression in patients with newly diagnosed, painful, inoperable pancreatic cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2011; 29(26)DOI
  22. Okuyama M, Shibata T, Morita T, Kitada M, Tukahara Y, Fukushima Y, Ikeda K, Fuzita J, Shimano T. A comparison of intraoperative celiac plexus block with pharmacological therapy as a treatment for pain of unresectable pancreatic cancer. Journal of Hepato-Biliary-Pancreatic Surgery. 2002; 9(3)DOI
  23. Mishra S, Bhatnagar S, Rana SPS, Khurana D, Thulkar S. Efficacy of the anterior ultrasound-guided superior hypogastric plexus neurolysis in pelvic cancer pain in advanced gynecological cancer patients. Pain Medicine (Malden, Mass.). 2013; 14(6)DOI
  24. Mercadante S, Fulfaro F, Casuccio A. Pain mechanisms involved and outcome in advanced cancer patients with possible indications for celiac plexus block and superior hypogastric plexus block. Tumori. 2002; 88(3)DOI
  25. Leon-Casasola OA. Critical evaluation of chemical neurolysis of the sympathetic axis for cancer pain. Cancer Control: Journal of the Moffitt Cancer Center. 2000; 7(2)DOI
  26. Leon-Casasola OA, Kent E, Lema MJ. Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer. Pain. 1993; 54(2)DOI
  27. Wilsey C, Ashford NS, Dolin SJ. Presacral neurolytic block for relief of pain from pelvic cancer: description and use of a CT-guided lateral approach. Palliative Medicine. 2002; 16(5)DOI
  28. Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesthesia Progress. 2012; 59(2)DOI
  29. Butterwhorth JF, Lahaye L. Clinical use of local anesthetics in anesthesia. UpToDate. Available online: https://www.uptodate.com/contents/clinical-use-of-local-anesthetics-in-anesthesia.
  30. Hebl JR, Dilger JA, Byer DE, Kopp SL, Stevens SR, Pagnano MW, Hanssen AD, Horlocker TT. A pre-emptive multimodal pathway featuring peripheral nerve block improves perioperative outcomes after major orthopedic surgery. Regional Anesthesia and Pain Medicine. 2008; 33(6)
  31. Buchanan D, Brown E, Millar F, Mosgrove F, Bhat R, Levack P. Outpatient continuous interscalene brachial plexus block in cancer-related pain. Journal of Pain and Symptom Management. 2009; 38(4)DOI
  32. Khor KE, Ditton JN. Femoral nerve blockade in the multidisciplinary management of intractable localized pain due to metastatic tumor: a case report. Journal of Pain and Symptom Management. 1996; 11(1)DOI
  33. Smith BE, Fischer HB, Scott PV. Continuous sciatic nerve block. Anaesthesia. 1984; 39(2)DOI
  34. Eason MJ, Wyatt R. Paravertebral thoracic block-a reappraisal. Anaesthesia. 1979; 34(7)DOI
  35. Vranken JH, Zuurmond WW, Lange JJ. Continuous brachial plexus block as treatment for the Pancoast syndrome. The Clinical Journal of Pain. 2000; 16(4)DOI
  36. Mercadante S, Sapio M, Villari P. Suprascapular nerve block by catheter for breakthrough shoulder cancer pain. Regional Anesthesia. 1995; 20(4)
  37. Calava JM, Patt RB, Reddy S, Varma DG, Chiang J. Psoas sheath chemical neurolysis for management of intractable leg pain from metastatic liposarcoma. The Clinical Journal of Pain. 1996; 12(1)DOI
  38. Kaki AM, Lewis GW. Inguinal paravascular (lumbar plexus) neurolytic block--description of a catheter technique: case report. Regional Anesthesia and Pain Medicine. 1998; 23(2)DOI
  39. Myers DP, Lema MJ, Leon-Casasola OA, Bacon DR. Interpleural analgesia for the treatment of severe cancer pain in terminally ill patients. Journal of Pain and Symptom Management. 1993; 8(7)DOI
  40. Montoro E, Ferré F, Yonis H, Gris C, Minville V. Pneumothorax as a complication of ultrasound-guided interscalene block for shoulder surgery. European Journal of Anaesthesiology. 2013; 30(2)DOI
  41. Verelst P, Zundert A. Respiratory impact of analgesic strategies for shoulder surgery. Regional Anesthesia and Pain Medicine. 2013; 38(1)DOI
  42. Klepstad P, Kurita GP, Mercadante S, Sjøgren P. Evidence of peripheral nerve blocks for cancer-related pain: a systematic review. Minerva Anestesiologica. 2015; 81(7)
  43. Jackson MB, Pounder D, Price C, Matthews AW, Neville E. Percutaneous cervical cordotomy for the control of pain in patients with pleural mesothelioma. Thorax. 1999; 54(3)DOI
  44. Lake WB, Konrad PE. Cordotomy procedures for cancer pain: A discussion of surgical procedures and a review of the literature. World Journal of Surgical Procedures. 2015; 5(1)DOI
  45. Feizerfan A, Antrobus JHL. Role of percutaneous cervical cordotomy in cancer pain management. Contin. Educ. Anaesth. Crit. Care Pain. 2014; 14:23-26.
  46. Viswanathan A, Bruera E. Cordotomy for treatment of cancer-related pain: patient selection and intervention timing. Neurosurgical Focus. 2013; 35(3)DOI
  47. Bain E, Hugel H, Sharma M. Percutaneous cervical cordotomy for the management of pain from cancer: a prospective review of 45 cases. Journal of Palliative Medicine. 2013; 16(8)DOI
  48. Bentley JN, Viswanathan A, Rosenberg WS, Patil PG. Treatment of medically refractory cancer pain with a combination of intrathecal neuromodulation and neurosurgical ablation: case series and literature review. Pain Medicine (Malden, Mass.). 2014; 15(9)DOI
  49. France BD, Lewis RA, Sharma ML, Poolman M. Cordotomy in mesothelioma-related pain: a systematic review. BMJ supportive & palliative care. 2014; 4(1)DOI
  50. Papanastassiou ID, Filis AK, Gerochristou MA, Vrionis FD. Controversial issues in kyphoplasty and vertebroplasty in malignant vertebral fractures. Cancer Control: Journal of the Moffitt Cancer Center. 2014; 21(2)DOI
  51. Lieberman IH, Dudeney S, Reinhardt MK, Bell G. Initial outcome and efficacy of &quot;kyphoplasty&quot; in the treatment of painful osteoporotic vertebral compression fractures. Spine. 2001; 26(14)DOI
  52. Health Quality Ontario. Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: A Systematic Review. Ontario Health Technology Assessment Series. 2016; 16(11)
  53. Mercadante S, Klepstad P, Kurita GP, Sjøgren P, Pigni A, Caraceni A. Minimally invasive procedures for the management of vertebral bone pain due to cancer: The EAPC recommendations. Acta Oncologica (Stockholm, Sweden). 2016; 55(2)DOI
  54. Fallon M, Giusti R, Aielli F, Hoskin P, Rolke R, Sharma M, Ripamonti CI. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Annals of Oncology: Official Journal of the European Society for Medical Oncology. 2018; 29(Suppl 4)DOI
  55. Wordliczek J, Kotlińska-Lemieszek A, Leppert W, Woroń J, Dobrogowski J, Krajnik M, Przeklasa-Muszyńska A, et al. Pharmacotherapy of pain in cancer patients - recommendations of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons. Polski Przeglad Chirurgiczny. 2018; 90(4)DOI
  56. WHO. Guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents. Geneva: World Health Organization, 2018. https://www.ncbi.nlm.nih.gov/books/NBK537492/..
  57. Jara C, Del Barco S, Grávalos C, Hoyos S, Hernández B, Muñoz M, Quintanar T, et al. SEOM clinical guideline for treatment of cancer pain (2017). Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2018; 20(1)DOI
  58. Chow E, Zeng L, Salvo N, Dennis K, Tsao M, Lutz S. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clinical Oncology (Royal College of Radiologists (Great Britain)). 2012; 24(2)DOI
  59. Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M, Suh JH, et al. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. Journal of the National Cancer Institute. 2005; 97(11)DOI
  60. Steenland E, Leer JW, Houwelingen H, Post WJ, Hout WB, Kievit J, Haes H, et al. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology. 1999; 52(2)DOI
  61. Caissie A, Zeng L, Nguyen J, Zhang L, Jon F, Dennis K, Holden L, et al. Assessment of health-related quality of life with the European Organization for Research and Treatment of Cancer QLQ-C15-PAL after palliative radiotherapy of bone metastases. Clinical Oncology (Royal College of Radiologists (Great Britain)). 2012; 24(2)DOI
  62. Lutz S, Berk L, Chang E, Chow E, Hahn C, Hoskin P, Howell D, et al. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. International Journal of Radiation Oncology, Biology, Physics. 2011; 79(4)DOI
  63. Smith HS. Painful osseous metastases. Pain Physician. 2011; 14(4)
  64. Dennis K, Wong K, Zhang L, Culleton S, Nguyen J, Holden L, Jon F, et al. Palliative radiotherapy for bone metastases in the last 3 months of life: worthwhile or futile?. Clinical Oncology (Royal College of Radiologists (Great Britain)). 2011; 23(10)DOI
  65. Meeuse JJ, Linden YM, Tienhoven G, Gans ROB, Leer JWH, Reyners AKL. Efficacy of radiotherapy for painful bone metastases during the last 12 weeks of life: results from the Dutch Bone Metastasis Study. Cancer. 2010; 116(11)DOI
  66. Chow E, Linden YM, Roos D, Hartsell WF, Hoskin P, Wu JSY, Brundage MD. Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. The Lancet. Oncology. 2014; 15(2)DOI
  67. Huisman M, Bosch MAAJ, Wijlemans JW, Vulpen M, Linden YM, Verkooijen HM. Effectiveness of reirradiation for painful bone metastases: a systematic review and meta-analysis. International Journal of Radiation Oncology, Biology, Physics. 2012; 84(1)DOI
  68. Chow E, Meyer RM, Chen BE, Linden YM, Roos D, Hartsell WF, Hoskin P, et al. Impact of reirradiation of painful osseous metastases on quality of life and function: a secondary analysis of the NCIC CTG SC.20 randomized trial. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2014; 32(34)DOI
  69. Salazar OM, Sandhu T, Motta NW, Escutia MA, Lanzós-Gonzales E, Mouelle-Sone A., Moscol A, et al. Fractionated half-body irradiation (HBI) for the rapid palliation of widespread, symptomatic, metastatic bone disease: a randomized Phase III trial of the International Atomic Energy Agency (IAEA). International Journal of Radiation Oncology, Biology, Physics. 2001; 50(3)DOI
  70. Scarantino CW, Caplan R, Rotman M, Coughlin C, Demas W, Delrowe J. A phase I/II study to evaluate the effect of fractionated hemibody irradiation in the treatment of osseous metastases--RTOG 88-22. International Journal of Radiation Oncology, Biology, Physics. 1996; 36(1)DOI
  71. O'Carrigan B, Wong MH, Willson ML, Stockler MR, Pavlakis N, Goodwin A. Bisphosphonates and other bone agents for breast cancer. The Cochrane Database of Systematic Reviews. 2017; 10(10)DOI
  72. Porta-Sales J, Garzón-Rodríguez C, Llorens-Torromé S, Brunelli C, Pigni A, Caraceni A. Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A systematic review within the European Association for Palliative Care guidelines project. Palliative Medicine. 2017; 31(1)DOI
  73. Vassiliou V, Kalogeropoulou C, Christopoulos C, Solomou E, Leotsinides M, Kardamakis D. Combination ibandronate and radiotherapy for the treatment of bone metastases: clinical evaluation and radiologic assessment. International Journal of Radiation Oncology, Biology, Physics. 2007; 67(1)DOI
  74. Bauman G, Charette M, Reid R, Sathya J. Radiopharmaceuticals for the palliation of painful bone metastasis-a systemic review. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology. 2005; 75(3)DOI
  75. Siegel HJ, Luck JV, Siegel ME. Advances in radionuclide therapeutics in orthopaedics. The Journal of the American Academy of Orthopaedic Surgeons. 2004; 12(1)DOI
  76. Porter AT, McEwan AJ. Strontium-89 as an adjuvant to external beam radiation improves pain relief and delays disease progression in advanced prostate cancer: results of a randomized controlled trial. Seminars in Oncology. 1993; 20(3 Suppl 2)
  77. Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, Bertrand A, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 1998; 16(4)DOI
  78. Sartor O, Quick D, Reid R, et al. A double blind placebo controlled study of 153 samarium-EDTMP for palliation of bone pain in patients with hormonerefractory prostate cancer [Abstract]. J Urol. 1997; 157:321.