Recognizing Radiation Therapy as Both Cause and Treatment for Cancer Pain

A comprehensive analysis of advanced kidney cancer tumors from the IMmotion151 trial provided new insights on the tumor features that underpin responses to therapy.
Estimates vary, but research has suggested that roughly 60% of patients undergoing cancer therapy experience pain.
Identification of cancer pain syndromes involves differential diagnosis of possible syndromes based on tumor biology and treatment.

Cancer pain syndromes are a complex, debilitating collection of complications caused by tumors or their treatment. Their intensity can vary dramatically depending on type and cause, tumor location, and even patient genetics.1,2 In severe forms, pain compounds patients’ suffering and existential dread, and disrupts treatment.

Radiotherapy is both a cause and a potential treatment for cancer pain. Each cancer pain syndrome is associated with the biology and location of tumors, or their treatment, and defined by suspected or inferred underlying physiological pain pathways.2-6 There appear to be gene variants associated with individual patients’ experienced pain and responses to opioid analgesics.7 Inflammatory cytokine gene variants are associated with pain severity in patients with lung, pancreatic, and breast cancer, for example.

Someday, research into genetic associations might open the door to biomarker tests and individually tailored treatments for cancer pain syndromes. But for now, it falls to the cancer care team to recognize the symptoms and signs of these syndromes, to educate patients about their options, and to help alleviate patients’ suffering.

Estimates vary, but research has suggested that approximately 60% of patients who are undergoing cancer therapy experience pain, and nearly 25% of patients have more than 1 form of cancer-related pain.2,3

The intensity of cancer pain can vary markedly over time and between patients, from mild or moderate discomfort to excruciating and debilitating — even incapacitating — pain that profoundly impacts patients’ quality of life and ability to cope.2-6 Cancer pain can be intermittent or constant. Frequently recurring or persistent pain can disrupt patients’ appetite and sleep, leading to malnutrition, exhaustion, cognitive impairment, social isolation, fear, anxiety, depression, and hopelessness.2,4

Because pain is common in patients with cancer, caregivers can, at times, become desensitized to it, coming to see it as the nearly inevitable “noise” of malignancy. But pain must never be ignored and should be mitigated as much as possible to improve patients’ lives. It is also a signal that can convey important clinical information. For example, acute-onset tumor-centered pain can be caused by intratumoral hemorrhage, which must be urgently confirmed with medical imaging because it can be immediately life-threatening.6

Types of Pain

Pain is frequently categorized as somatic, visceral, or neuropathic.

  • Somatic pain is the most common form of cancer pain. It is localized and often intermittent. It is usually described as an ache, cramping, or throbbing, and it can be associated with bone metastasis. Patients can usually point to the source of the pain.
  • Visceral pain is internal and sometimes vaguely described as pain in the chest, abdomen, or pelvic organs. Patients frequently use a hand motion over an area of anatomy to convey the painful region rather than pointing to a specific spot.
  • Neuropathic pain affects approximately 1 in 3 patients reporting pain during cancer treatment and is caused by damaged or dysfunctional nerves in the peripheral nervous system. It can be caused by chemotherapy and, in rare cases, is a late-emerging complication of radiotherapy. Peripheral neuropathy commonly initially involves painful pinpricks or tingling sensations, which can evolve to a loss of sensation, a dulled sense of touch or numbness in the hands or feet. Such sensations or numbness sometimes progresses up the limbs over time. Cancer patients with neuropathic pain often describe the pain as sharp, shooting, burning, or electrical shocks. Symptoms are typically asymmetric or worse on one limb than the other.

Another form of cancer pain syndrome is nociceptive pain. This type of pain is caused by the activation of pain receptors by tumors. Patients with nociceptive pain often describe it as aching, throbbing, or cramping.

Acute and Chronic Pain Syndromes

The duration of pain can last from several days to months or even years after a patient’s treatment has been completed.2,6 A common rule of thumb is that acute cancer pain syndromes are more frequently caused by cancer surgery, chemotherapy, or radiotherapy, whereas chronic pain is more typically caused by tumors themselves.2 However, tumors and their treatments can cause both acute and chronic pain. Up to one-quarter of patients’ chronic cancer pain syndromes are associated with cancer treatment, including radiotherapy, chemotherapy, and surgery.2

Acute-onset tumor-centered pain can be caused by displacement or compression of organs or nerves by the growing tumor, or as noted above, by intratumoral hemorrhage, which can be immediately life-threatening.6

The single most common form of chronic somatic pain is bone metastasis, which can involve any bony structure but most frequently occurs in spinal vertebrae.2 Bone pain can be focal, meaning it affects 1 location, or multifocal, which is frequently associated with multiple metastatic tumors in the bone. (Less frequently, generalized regional bone pain, particularly in patients with hematologic malignancies, affects large portions of long bones without identifiable specific foci of pain.2)

Chronic visceral pain syndromes frequently involve tumor obstruction of the intestines (abdominal pain, particularly among patients with gastrointestinal or pelvic cancers), urinary tract, or biliary tract. Hepatic distention syndrome results from liver metastases causing biliary obstruction and can cause pain beneath the patient’s ribs, the right mid-back, or right side.2 Liver pain can also be experienced as referred or displaced pain in the right neck or shoulder.2

This article originally appeared on Cancer Therapy Advisor

References:

1. Yang GS, Barnes NN, Lyon DE, Dorsey SG. Genetic variants associated with cancer pain and response to opioid analgesics: implications for precision pain management. Semin Oncol Nursing. 2019;35(3):291-299. doi:10.1016/j.soncn.2019.04.011

2. Cherny N, Carver A, Newton HB. Chronic cancer pain syndromes and their treatment. In: Newton HB, Malkin MG, eds. Neurological Complications of Systemic Cancer and Antineoplastic Therapy, 2nd ed. Elsevier/Academic Press; London, UK; 2022:587-610.

3. Brant JM. The assessment and management of acute and chronic cancer pain syndromes. Semin Oncol Nursing. 2022;38(1):151248. doi:10.1016/j.soncn.2022.151248

4. Strang P. Existential consequences of unrelieved cancer pain. Palliat Med. 1997;11(4):299-305. doi:10.1177/026921639701100406

5. Arnstein P. Adult cancer pain: an evidence-based update. J Radiol Nursing. 2018;37(1):15-20. doi:10.1016/j.jradnu.201.10.009

6. Portenoy RK, Ahmed E. Cancer pain syndromes. Hematol Oncol Clin North Am. 2018;32(3):371-386. doi:10.1016/j.hoc.2018.01.002

7. Webb JA, LeBlanc TW. Evidence-based management of cancer pain. Semin Oncol Nursing. 2018;34(3):215-226. doi:10.1016/j.soncn.2018.06.003

8. Karri J, Lachman L, Hanania A, et al. Radiotherapy-specific chronic pain syndromes in the cancer population: an evidence-based narrative review. Adv Ther. 2021;38(3):1425-1446. doi:10.1007/s12325-021-01640-x

9. Radiation Myelopathy. Accessed November 22, 2022. https://www.sciencedirect.com/topics/medicine-and-dentistry/radiation-myelopathy