Alternate modalities for palliation

Introduction

More than 16.9 million people are living with cancer in the United States, and approximately 1.8 million new cancer cases are expected to be diagnosed in 2020. The population of cancer survivors in the United States is predicted to reach 26 million by 2040. Cancer survivors—defined here as individuals with cancer from the time of diagnosis and for the balance of life, including post-treatment survivorship and end-of-life —are a growing population with significant unmet needs, ^, in particular pain management. About 53% of patients suffer from pain at all stages of cancer. This number increases to as high as 69% in patients with advanced cancer. The use of analgesic medications such as opioids and radiotherapy may only provide partial relief in cancer populations. Indeed, 10% to 15% of cancer patients may continue to have intractable pain despite the use of systemic analgesics, surgery, or radiotherapy. ^, Furthermore, given the rise in the prevalence and recognition of opioid misuse (for example, diversion, nonmedical opioid use, and opioid use disorders ) in cancer populations, as well as a lack of adequate palliative care services to treat the growing number of cancer patients in America, ^, the need for alternative modalities for palliation of cancer pain becomes especially pressing.

Interventional pain in cancer populations, also known as Interventional Oncology, offers strategies to palliate pain in cancer patients at any stage of illness from post-treatment survivorship to patients approaching the end-of-life. The goals of interventional pain treatments are to reduce the burden of pain on a patient’s quality of life (QoL), allow for reduction of systemic analgesics that may carry an unfavorable risk/benefit ratio, to reduce the intensity of pain, and to improve the functional status of the patient. Interventional therapies are myriad and can target pain derived from the nervous system and from bony lesions using neuromodulation, ablations, and surgery. Interventional strategies are particularly attractive given that most are brief, outpatient procedures and generally carry minimal morbidity. For the radiation oncologist, knowledge of the practice and scope of interventional pain is critical to providing optimal care for patients who are in greatest need. In this chapter, we will address nonradiation-based approaches to treat severe, intractable cancer pain using interventional pain strategies, including percutaneous techniques (i.e., sympathetic blocks, neurolysis, and ablation), epidural and intrathecal opioid infusions and pumps, surgical augmentation of the skeleton using vertebroplasty, kyphoplasty, and other orthopedic surgical techniques. This chapter places particular emphasis on when to consider interventions for which population of cancer patients. Optimal utilization of a multidisciplinary team of pain specialists, including the use of palliative care, is essential to the care of cancer populations in pain. ^,

Types of cancer pain

Cancer pain can generally be classified as nociceptive or neuropathic pain. Nociceptive pain is characterized by tissue damage causing either visceral or somatic pain. Visceral nociceptive pain is caused by infiltration, extension, stretching, or compression or the thoracic, abdominal, or pelvic viscera. Patients often describe this pain as a deep, squeezing, pressure pain that is not localized to a specific anatomic site. Somatic nociceptive pain, in contrast, is characterized by tissue damage in the cutaneous or deep somatic structures. Patients describe somatic pain as sharp, stabbing and more localized compared to visceral pain.

Neuropathic pain is associated with damage or dysfunction in the nervous system. It can be caused by tumor invasion to nerve structures or iatrogenically from surgery or chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN) is a common cause of pain in cancer patients and is most commonly associated with platinum analogs, antitubulins, proteasome inhibitors, and immunomodulatory agents. Common symptoms of CIPN include paresthesias, dysesthesias, sensory loss, and motor weakness. Patients will often report feeling num, tingling, and/or burning sensations in their hands and feet, often with weakness as well leading to dropping items or falls. Patients can also present with mixed pain syndromes with both nociceptive and neuropathic dimensions.

Etiology of cancer pain

Cancer pain can be caused by (1) tumor destruction of tissue; (2) cancer-directed therapy, including chemotherapy (e.g., CIPN); surgery (e.g., postmastectomy pain, phantom pain); and radiation (e.g., brachial plexopathy); or (3) co-incidental pain, such as headache (e.g., headache in the setting of glioblastoma), back pain, or myofascial pain. Tumor destruction can lead to bony pain, soft tissue pain, or nerve pain. Furthermore, pain can also be mediated by psychological factors such as rumination, demoralization, or catastrophizing. Given that cancer pain is a complex, multimorphic phenomenon encompassing multiple etiologies, both physical and psychological, at present, there is no widely accepted taxonomy of cancer pain. Identifying the cause of cancer pain and its mediating factors is essential to tailoring a patient-centered treatment approach to improve pain and QoL in cancer patients.

When to consider alternative modalities of palliation

Often, palliative radiation—in conjunction with pharmacological therapies such as opioids, nonopioid analgesics (i.e., acetaminophen and nonsteroidal antiinflammatory drugs [NSAIDs]), and adjuvant analgesics (i.e., anticonvulsants, antidepressants, cannabinoids, or drugs with mixed properties)—may not provide enough relief for the patient, or the side effect profile outweighs any analgesic benefit. Intractable pain may be the result of many mechanisms, including but not limited to opioid-induced hyperalgesia, central sensitization, and “total pain” phenotypes common in palliative care populations in which biopsychosocial factors such as social, emotional, and spiritual distress exacerbate sensory pain. Identifying the underlying etiology(ies) driving a cancer patient’s pain requires detailed history-taking by the radiation oncologist, and may also necessitate involvement of psychologists, palliative care specialists, and interventional pain specialists to tailor a treatment plan targeting multidimensional causes of pain and suffering in cancer populations.

The World Health Organization (WHO) developed guidelines for the management of cancer pain in the mid-1990s to guide the adequate provision of pain medications to cancer patients. This three-step pain ladder is a cornerstone in managing both malignant and nonmalignant pain, and provides a stepwise approach to treating gradations of pain, starting from treating mild pain to severe pain in the following order: (1) mild pain is treated with nonopioid medications (e.g., acetaminophen, nonsteroidal antiinflammatory drugs, or NSAIDs); (2) for moderate pain that persists or worsens, the recommendation is to treat with “weak opioids” (e.g., codeine); and (3) for persistent or worsening pain, treat with a “strong opioid” such as morphine or oxycodone.

Notably, up to 20% of patients do not achieve adequate pain relief with this three-step ladder approach. ^, A central criticism of the WHO ladder is that it focuses primarily on nociceptive pain without considering the complex nociceptive, neuropathic, and mixed mechanisms underlying cancer pain. ^, To address this complexity, more contemporary iterations of this pain ladder recommend adding a fourth-step to the ladder to include interventional procedures for refractory cancer pain. More recent calls to include interventional approaches to cancer pain management are the result of technological advances in pain medicine, as well as the recognition of the risks associated with opioid use. Interventionalists have called for a “paradigm shift” to consider alternative modalities of palliation earlier for patients with pain and not as a “fourth step” on the latter when other approaches fail. While currently there is a paucity of research to support the comparative effectiveness of interventional approaches compared to medical management in cancer populations, using a shared decision-making approach, patients should be informed of interventional options to manage cancer pain throughout their illness course. Radiation oncologists should also consult with interventional pain specialists to identify opportunities to provide various interventions that could improve a cancer patient’s QoL throughout the patient’s course of illness.

Furthermore, certain cancer patients may not respond to opioid-based therapies or other oral or parenteral analgesics; nor are certain patients ideal candidates for opioid-based therapies. Patients with neuropathic and bony metastatic pain are generally more resistant to opioid therapy than those with nociceptive pain. Patients with opioid use disorders, demonstrated misuse of their opioids (for example, diversion, repeated requests for early refills, urine drug screening inconsistent with prescribed medications), drug allergies, and who are at high risk of developing use disorders as demonstrated by risk tools (i.e., Opioid Risk Tool ) may be ideal candidates for interventions directed prior to exhausting other pain management options. In the modern age of cancer therapeutics, patients are living longer into post-treatment survivorship, yet many continue to live with chronic pain syndromes. Indeed, certain populations with advanced, incurable cancers on palliative care treatments are now living for years into a stage called metastatic cancer survivorship. In these populations in particular, long-term opioid use may carry an unfavorable risk/benefit ratio. Long-term opioid use can cause progressive central sensitization, hyperalgesia, immune suppression, hypogonadism, and even increased risk of cancer progression. Opioid-related morbidity may hinder return to a functional capacity that cancer patients may find acceptable. ^, Interventional procedures in this setting can be strategies to improve function across the spectrum of cancer survivorship. ^, In summary, while no strong evidence-base exists to introduce interventional strategies when cancer patients have mild to moderate cancer pain, we recommend interventional procedures as the “fourth step” in the WHO pain ladder when systemic analgesics are inadequate to control cancer pain. Furthermore, certain clinical situations where the risk/benefit ratio favors interventions, such as opioid addiction or patient preference, may make interventions an attractive option for pain management for many patients. Shared decision-making approaches elevating the patient’s voice and preference, as well as incorporating members of the interdisciplinary team, including radiation oncologists, are critical to providing patient-centered pain management.

General considerations when considering interventions in cancer populations

When considering interventional procedures in cancer a patient, it is recommended that patient has a trial of systemic analgesics, as per the WHO pain ladder, and that the patient’s pain is refractory to treatments or the patient is intolerant of side effects from treatment. However, as noted above, certain patients who may be at high risk for controlled medications secondary to dependence, abuse, or use disorder, or who may prefer to have a procedure to avoid potential side effects from systemic analgesics, can also be considered for interventional therapy. A proper pain history should be obtained. This includes the location of the pain, its intensity, frequency, exacerbating and alleviating factors, and medications that have been used to potentially mitigate the pain. A history of drug allergy should also be obtained. Co-morbidities that may either preclude or complicate outcomes of the intervention—such as decompensated congestive heart failure, cirrhosis of the liver, or chronic obstructive pulmonary disease—should be assessed. In particular, patients should be able to lie in a prone position for certain pain procedures, and certain cardiopulmonary conditions may prevent the patient from lying prone for the duration needed to perform the procedure. Providers should inspect the site of the intended puncture site to rule out infections, sores, or other findings that may complicate carrying out the procedure.

Imaging to identify the site for intervention is up to the discretion of the interventionalist. Generally, a diagnostic or prognostic block will be performed with a local anesthetic to identify whether a more definitive procedure, such as a neurolysis, will be effective for pain relief. A diagnostic block is also performed to identify sensory or motor deficits that could be exacerbated by a neurolytic or similar definitive therapeutic procedure.

Absolute contraindications to an intervention include local or systemic infection, uncorrected coagulopathy (INR >1.5, platelet count <50,000), or allergy to the intended drug for the intervention. Relative contraindications include neutropenia or other immune-suppression, poor performance status, and the practitioner’s comfort with identifying a safe path to the target location for the intervention.

Types of interventional pain specialists

Interventional pain specialists, sometimes known as interventional oncologists, comprise a diverse array of healthcare disciplines including anesthesia, physical medicine and rehabilitation (also known as physiatry or PM&R), orthopedics, and interventional radiology. Typically, pain specialist physicians complete a fellowship program in pain management following their residency. Most pain specialists have board-certifications in anesthesiology or PM&R, and less commonly, psychiatry and neurology. These physicians are generally well-trained to use invasive techniques such as joint injections nerve blocks, epidural and intrathecal infusions, neuromodulation, cement augmentation, and radiofrequency ablation (RFA) to provide treatment options for pain syndromes that are unresponsive to conventional management. However, they can also manage systemic analgesics, both orally and parenterally, in inpatient and outpatient settings. Interventional radiologists, in contrast, generally do not manage systemic analgesics and, instead, have expertise in techniques such as cryoablation, thermal ablation, as well as nerve blocks, epidural, and intrathecal infusions. It is important to identify the scope and skills of practice of pain specialists who care for cancer patients in order to properly refer patients to the appropriate service.

Commonly used interventional procedures

The National Comprehensive Cancer Network (NCCN), which produces guidelines for oncology and adult cancer pain, updated their guidelines in 2020. This chapter is divided into four sections based on the general approaches, including regional and neuroaxial infusions, neurodestructive procedures, neurostimulation, percutaneous vertebral augmentation and ablation for bony lesions, and orthopedic surgery.