Interventional pain management in patients with cancer-related pain

3

ABSTRACT

Invasive interventional procedures for managing pain in cancer patients are often underutilized following the popularization of the WHO analgesic ladder. The procedures that were successfully used until then were relegated away from mainstream palliative care practice, with the advent of newer opioids and adjuvants. Even though nerve blocks, intrathecal pumps and spinal cord stimulation were reintroduced as the fourth step of the WHO ladder, often referrals for these procedures are too late to produce a meaningful effect on quality of life. At this point most patients have advanced disease and are requiring end of life care. Additionally, it is becoming evident that at least 10% of patients do not achieve good quality analgesia with oral opioids and are often troubled by unacceptable side effects. There is an increasing public awareness of the problems with long-term opioid therapy and some of these patients would certainly benefit from invasive procedures to alleviate their pain and improve their quality of life. Improving life quality and expectancy with better treatment options and increasing number of cancer survivors should be heralding a change and hence neurolytic procedures are to be used only in patients with limited life expectancy. ITDDs, neuromodulation and ever-increasing use of procedures routinely used in treating chronic nonmalignant pain would be the mainstay of interventional management until AI and nanotechnology would open doors for novel treatment options. Interventions should not be used as a last resort after multiple failed attempts at opioid therapy, but as an integral part of a management strategy including medical management, psychological and emotional welfare, and supportive care of the patient in a holistic manner. The curriculum of specialists should include appropriate training to safely perform and produce better quality evidence to validate the efficacy and safety of these challenging procedures.

KEYWORDS:

• Cancer pain
• percutaneous cordotomy
• neurosurgical procedures
• pain Management
• celiac block
• intrathecal

Pain is one of the most feared symptoms of cancer and poorly controlled pain is often debilitating and affects the quality of life at all stages of the disease. A meta-analysis of several studies concluded that 38.0% of all cancer patients reported moderate to severe pain (numerical rating scale score ≥5) with the prevalence rates of 55.0% during treatment, 39.3% after curative treatment, and up to 66.4% in the terminally ill patients [1]. The World Health Organization (WHO) analgesic ladder advocates the use of simple analgesia and opioids with adjuncts orally and this can effectively manage most of the pain in cancer patients [2]. However, 10% of patients do not achieve adequate analgesia with oral medications or suffer unacceptable side effects [3]; these patients could benefit from peripheral nerve and plexus blocks, central neuraxial blockade, sympathetic blocks, neurolytic blocks, intrathecal drug delivery systems, neuromodulation, and neurosurgical procedures and should have access to these services in a timely manner.

The Improving supportive and palliative care for adults with cancer document published by NICE in 2004 stipulated that each Cancer Network should have a named specialist for advanced pain management techniques and each Local Specialist MDT should have an anaesthetist with expertise in nerve blocks and neuromodulation techniques [4]. The results of a postal survey in 2007 from 107 pain clinics highlighted that more than half of them only received 5 or less referrals per annum and joint consultations with palliative care were rare, 75% of the pain consultants did not have cancer pain management as part of their job plan [5]. Another survey of palliative care services in 2007 indicated that though 96% had access to specialist pain services, less than a tenth of them had dedicated sessions for cancer pain management [6]. Unfortunately for cancer patients, this state of affairs has not changed much in 2020 and pain in cancer patients continues to be poorly managed.

The role of interventions to manage pain in cancer patients are poorly acknowledged and appreciated, resulting in late referrals – often with advanced stages of disease progression. It is often misunderstood that interventions for cancer related pain should be only done after exhausting other options due to the risk of serious complications. This misconception prevents patients being referred in a timely manner; earlier interventions can be highly effective in controlling intractable pain and bridges the gap between pain at rest and during movement. The vast majority of the procedures are exactly same as those performed for managing nonmalignant pain e.g. radiofrequency lesioning for axial back pain. Often diagnostic blocks with local anesthetics are used to confirm the efficacy and side-effect profile before proceeding to neurolytic blocks, which are used only when life expectancy is less than 12–18 months [7]. Barring complications, interventions have fewer side effects compared to systemic opioids and are more likely to provide better quality analgesia without side effects. Patient education on the importance of better pain management and the awareness of side effects of long-term opioid therapy is influencing patient care. This is reflected on the National Cancer Patient Experience Survey from 2019 where only 73% of patients reported that they felt that the hospital staff did everything possible to control their pain, as compared to 85% when the survey was first started in 2010 [8].

Patients benefit from a multidisciplinary assessment from oncology, pain medicine and palliative care specialists with support from radiology, surgery, orthopedics, neurosurgery, and gastroenterology. The role of family physicians, physiotherapists, clinical psychologists, pharmacists, occupational therapists, complimentary therapists, social workers, and specialist nurses in these assessments are invaluable. It enables practitioners to identify and manage debilitating symptoms such as malignant bowel obstruction, edema, breathlessness, fatigue as well as coexisting chronic pain unrelated to the cancer [7]. This multimodal approach enables to choose the best combination of treatments for the patient depending on their physical and emotional state. For example, pain due to a pathological hip fracture could be managed by a combination of surgical fixation and radiotherapy or by ultrasound-guided neurolytic block or radiofrequency of the articular branches. Prognosis, life expectancy, patient suitability, the pain problem, and the impact of interventions toward quality of life are factors to be considered before obtaining informed consent. The psychosocial and spiritual well-being of the patient should be considered and supported. Patients in remission or undergoing treatment with curative intent and cancer survivors should be treated similarly to those with nonmalignant pain. Even in terminally ill patients undergoing a neurolytic procedure, it should be ensured that there is no loss of motor or autonomic function [7].

Celiac plexus blocks have been widely acknowledged to treat pain in pancreatic cancer and could be used in managing pain in cancers involving lower esophagus, stomach, gall bladder, and bowel [9–11]. Unilateral blockade and lower injectate volume can minimize the side-effects of diarrhea and postural hypotension. Other serious complications like pneumothorax, vascular injury, retroperitoneal hematoma and hematuria, and serious neurological injury have been reduced with improved imaging guidance with fluoroscopy, CT and endoscopic ultrasound-guided approaches to inject lower volumes precisely. Radiofrequency ablation and retrocrural block of the splanchnic nerves are often effective in patients where celiac plexus blockade is not possible or ineffective due to tumor infiltration [7]. Hence, there is a compelling argument for early referral for neurolytic celiac plexus blocks for managing pain in patients diagnosed with pancreatic cancer, as it would become technically difficult to approach the plexus through the tumor mass. Additionally, there are significant cost benefits as most of these interventions are carried out as day case procedures and could prevent lengthy hospital or hospice stays to titrate opiates and other medications to effect. This could also help prevent the negative impact on quality of life due to the undesirable side effects of systemic medications. Superior and inferior hypogastric plexus blocks can be effective for pelvic cancer pain and ganglion impar block is often used to manage pain in localized anal cancers [12]. Ischemic and other sympathetically mediated pain in the lower limb could respond to lumbar sympathetic blockade, while stellate ganglion and T1-2 sympathetic block can be used to manage pain in head and neck cancers and upper limb pain.

Targeting the dorsal root ganglion/sensory root or having indwelling epidural/intrathecal catheters are superior to peripheral nerve or plexus catheters for long term management. The former is a specialist neurolytic procedure, though a ‘saddle-block’ via midline lower lumbar interlaminar approach targeting sacral roots intrathecally using phenol-in-glycerol is often used to alleviate perineal pain due to pelvic tumors. Neurolytic agents can be used to target sensory roots and DRG in the epidural space in the lumbosacral area. In the cervico-thoracic area, the presence of dendate ligament allows for selectively targeting the sensory roots by injecting absolute alcohol into the CSF with appropriate cephalo-caudal tilt of the operating table with the patient in a 45-degree semiprone position with affected side up for unilateral upper limb and chest wall pain [13]. Myofascial pain syndromes are common in cancer patients and could be managed successfully with acupuncture and trigger point injections under USG guidance [14]. Intra-articular injections and articular branch blocks are efficacious in managing musculoskeletal pain associated with prolonged poor mobility in patients with cancer.

Implanted drug delivery systems are used when systemic analgesic doses are not giving benefit despite dose escalation and the side effects are becoming undesirable and unacceptable. Epidural systems and peripheral nerve catheters do not have a role except as a short-term measure and has been superseded by intrathecal analgesia in terms of safety and efficacy [15]. Frequent episodes of catheter displacement, the need for stringent monitoring and infection risks have been noted against external systems including tunneled systems attached to a Portacath. The implanted ITDD systems addresses these problems as well as encourages domiciliary management and becomes cost effective if the life expectancy is more than 3 months [16]. Modern ITDD systems have the provision of delivering a predetermined dose as a bolus on top of a background infusion which enables the patient to manage their pain better by addressing their analgesic requirements. Opioids (Morphine, Hydromorphone), Clonidine (an α₂-receptor agonist) and a local anesthetic (Bupivacaine) is the commonly used drug combination for effective analgesia [17]. The catheter tip should be at or slightly cephalad to the painful dermatomal level as the spread of the drug is limited to only one or two levels. It has been observed in studies that an external infusion at a similar rate is more reliable than a single bolus of the injectate to determine long term efficacy of ITDD. Ziconotide (Ca [2]+ channel blocker) is a potent analgesic which does not require precise catheter placement but is rarely used in the management of cancer pain due to time limitations as it requires monitored slow titration due to the risk of developing neuropsychiatric complications. There should be a plan to taper down the systemic opioids over 72–96 hours and clinicians should be vigilant against opioid-toxicity and opioid withdrawal [7]. Any complications including infection or neurological symptoms should be addressed immediately and expert input is to be sought if required.

Surgical neuroablative procedures were the mainstay of cancer pain management prior to the WHO ladder and opioids being the analgesic of choice. Various neurosurgical procedures were used to disrupt neural pathways in the brain and spinal cord in patients with terminal cancer to provide relief from intractable pain. Most of the procedures have been discontinued because the quality of evidence is poor consisting of a plethora of case reports/case series, few retrospective studies, fewer prospective blinded comparative studies and very few prospective, blinded randomized placebo-controlled studies [18]. Midline myelotomy is still used, albeit rarely, in cases of intractable visceral pain. Median tractotomy and thalamotomy are rarely carried out, though there is some renewed interest in cingulotomy. DREZ lesions are carried in a few centers for pain due to traumatic brachial plexus avulsion rather than for cancer pain and pituitary alcohol injections are no longer practised. Percutaneous cordotomy were the most commonly performed procedure and is still being practised regularly in a few centers[19]. The lateral spinothalamic tract on the contralateral side is disrupted by a radiofrequency lesion at C1-2 level for managing unilateral pain below C4 and beyond six inches from the midline. The commonest indications are pain from brachial plexus or chest wall invasion, malignant pleural mesothelioma, and tumor infiltration of ilium and lumbosacral plexus. When effective, it provides good analgesia and about 30% of patients would discontinue their opioids. Percutaneous cordotomy was traditionally performed using fluoroscopy and lately under CT guidance; more recently an endoscopic-guided technique under direct vision is claiming better safety profile [7]. Complications include cord edema resulting in ipsilateral motor weakness, pain on the side of cordotomy, and failure of the procedure. Severe and refractory deafferentation pain has been reported in patients who have survived for more than two years. Open cordotomies are rare and considered only when bilateral cordotomies are required; the second or sometimes both lesions are done at C6 level to protect diaphragmatic function.

Due to advances in oncological treatment, 50% of patients diagnosed with cancer now survive longer than ten years and development of immunotherapy and biologics could further improve survivorship in many cancers. Neuroablative procedures would be limited and could be replaced by implantable neuromodulation systems for spinal cord stimulation, DRG stimulation, and peripheral nerve stimulation for managing intractable pain [20]. Compatibility and conditional use of implanted systems in MRI scanners had previously limited its use in managing pain in cancer patients. Spinal cord stimulation has been successful in treating pain in chemotherapy-induced neuropathy and along with other modalities can also be used for managing localized cancer pain [21]. Long-term use of intrathecal opioids could result in immune and hormonal suppression, hence there is a need for a novel compound, that would give good analgesia without any major side-effect profile. Noninvasive modalities like transcranial magnetic stimulation may have a future role in managing cancer pain [22]. Artificial Intelligence (AI) is showing an increasing presence in diagnostics and treatment algorithms in many cancers and it is not far before it would play a significant role in patient-orientated treatment of cancer-related pain and other chronic pain conditions. Nanotechnology and AI could revolutionize the way pain management could be implemented in helping cancer patients. Till such time, it is important to support referral for interventional options without delay in patients who have failed medical management or those who have specific conditions that would benefit from early delivery of suitable interventions. There should also be provision to impart appropriate training to medical personnel to safely and effectively carry out these procedures for managing pain in cancer patients.

Declaration of interest

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.