Pain and quality of life in palliative care

This issue of Annals of Palliative Medicine features several articles addressing pain, from defining pain severity cut points, to quantifying and reducing pain acquired after bone marrow biopsy, to treating neuropathic pain, to using reirradiation for recurrent pain from bone metastases.

Several pain-rating scales have been validated and are in widespread clinical use (1,2). Currently, several studies have employed a numeric rating scale to assess pain severity or to group patients into pain categories within a single patient population (3,4). However, recent review articles across patient populations and current recommendations for the optimal pain cut points for mild, moderate, and severe pain are lacking. In this issue of Annals of Palliative Medicine, Woo et al. provide a thorough and thought-provoking review of cut points for mild, moderate, and severe pain for both cancer and non-cancer patients (5). This is a high-impact publication that can help clinicians assess for changes in the functional status of their patients and better develop and evaluate treatment options to improve the pain of their patients. Given the broad scope of the review, this report has clear implications for patients suffering from pain from a plethora of causes, from osteoarthritis to lower back pain to diabetic neuropathy to cancer-related pain.

Pain is one of the most common symptoms experienced by patients with cancer and a common cause for depression, sense of hopelessness and fear, and decline in quality of life (6-8). Neuropathic bone pain is just one of a number of types of pain that can result from bone metastasis, which is reviewed in detail along with optimal treatment approaches in this issue of Annals of Palliative Medicine by Roos (9). Despite improvements in the understanding of the different causes and types of pain experiences by patients with cancer, implementation of clinical guidelines recommending systemic pain assessments, and high pain response rates that are achievable with analgesics and other medical interventions, many patients with cancer continue to receive inadequate medical management of their pain (10-12). This is particularly true in the approximately half of all advanced cancer patients who develop bone metastases (13).

Palliative radiation therapy is a commonly utilized modality for treating pain from cancer, and particularly from bone metastasis, and it is effective in achieving a pain response in the majority of patients (14). However, not all patients have a pain response to radiation therapy, and a significant portion that do have a pain response that is not durable, allowing for pain to recur. This is a byproduct of the improvements in systemic therapy and supportive care, which have allowed patients with metastatic disease to live longer, and often to outlive the duration of benefit from an initial short-course course of palliative radiotherapy (15).

The utilization of and need for palliative reirradiation has received increasing attention and is highlighted in the current issue’s Palliative Radiotherapy Column. Chiu and colleagues address optimal management of painful bone metastasis previously treated with palliative radiotherapy in an evidence-based review (16). Reirradiation can be considered after lack of pain relief following an initial course of radiotherapy, after a partial but unsatisfying pain response to an initial course of radiotherapy, or after pain recurrence following a complete or partial pain response to an initial course of radiotherapy. Reirradiation has been shown to be effective at controlling cancer-related pain, and it may be most optimally used in patients who achieve an initial pain response to a first course of palliative radiotherapy (17,18). In this setting, the majority of patients can achieve a pain response to reirradiation based on a recent systemic review report (19).

Despite the potential benefits of reirradiation in improving pain and quality of life for patients with advanced malignancies, the optimal dose and fractionation for reirradiation remains undefined. The first randomized controlled trial comparing different schedules of reirradiation to palliative painful bone metastases, which was undertaken by the National Cancer Institute of Canada (NCIC) Clinical Trials Group (CTG) Symptom Control (SC20), was published in 2014 (20). This 850-patient international study compared 8 Gy in a single fraction to 20 Gy in multiple fractions for patients with bone metastases requiring analgesics for pain following a prior course of palliative radiotherapy. The study found no significant difference in overall pain response to treatment for intention-to-treat (28% for single fraction vs. 32% for multiple fractions, P=0.21) or per-protocol analysis (45% vs. 51%, P=0.17), whereas acute toxicities of lack of appetite (56% vs. 66%, P=0.011) and diarrhea (23% vs. 31%, P=0.018) were less common with the single-fraction regimen. While tradeoffs in efficacy and toxicity need to be considered, this study established 8 Gy in a single fraction to be non-inferior than multiple fraction reirradiation regimens for patients with painful bone metastases requiring a repeat course of radiation therapy.

The review by Chiu et al. fills a current knowledge gap following the recent publications of NCIC CTG SC20 and other primary reports on reirradiation, and it outlines the optimal reirradiation dose fractionation in the treatment of painful bone metastases (16). The authors also discuss novel bone biomarkers as a potential means for predicting patients who will and will not response to reirradiation.

In the second article on this important topic in the current issue of Annals of Palliative Medicine, Tsang et al. author an interesting debate on the current best practices for the retreatment of uncomplicated bone metastases (21). Single-fraction reirradiation offers optimal patient convenience and a more mild acute toxicity profile, whereas multi-fraction reirradiation, most commonly delivered in 5 to 10 fractions, is commonly believed to provide superior and/or more durable pain control. The debate format is quite lively and interesting, and the article is complete with commentary to summarize the relevant issues, pros, and cons of single- and multi-fraction reirradiation. Ultimately, as in the setting of an initial course of palliative radiotherapy (22), the choice of dose and fractionation for reirradiation should be individualized to provide personalized care to patients that offers the greatest chance of pain response and durable pain control while maximizing quality of life and convenience of treatment with as few side effects as possible.

Bone marrow biopsy and aspiration are commonly employed diagnostic tools for a variety of benign and malignant hematologic disorders. Although the procedure has exceptionally low rates of major complications, the majority of patients do experience pain of variable duration, and up to half of all patients report severe or unbearable pain following bone marrow biopsy (23). Currently, the most common pain mitigation strategy used clinically is local anesthetics, which has only modest effects at reducing sensations and minimizing pain at the biopsy site (24). In this issue of Annals of Palliative Medicine, Zahid discusses other methods in use that can reduce pain during bone marrow biopsy and focuses on other pharmacological agents, including sedatives, opioids, and inhalation anesthetics, as well as non-pharmacologic methods, including cognitive behavioral therapy, hypnosis, and music therapy (25).

In the Surgical Palliative Care Column, Rodriguez et al. report on a novel assessment of the utilization of palliative care consultation service by surgical services (26). Despite the significant increase in hospital-based palliative care services over the past decade, there currently are little data on how palliative care consultation services are utilized by surgical services. In a single tertiary care center in the United States, the authors found that 15% of all palliative care consultations were requested by surgical services and 85% by medical services, and important differences in patients and reasons for consultation were identified between medical-based and surgical-based palliative care consultations. Despite the work of the American College of Surgeons Committee on Surgical Palliative Care to improve the knowledge and integration of palliative care among surgeons (27), this study reinforces other recent findings that referrals to palliative care by surgeons remain underutilized (28). The Surgical Palliative Care Column also features a novel original report assessing the ability of using the American College of Surgeon’s National Surgical Quality Improvement Program (ACS-NSQIP) as a surgical quality-measurement tool for advanced cancer patients (29).

This issue of Annals of Palliative Medicine also features innovative reports on symptomatic control for brain metastasis and voice-related quality of life after total laryngectomy. Following the recently reported interim analysis of the Medical Research Council’s Quality of Life after Treatment for Brain Metastases (QUARTZ) trial (30) and the 2015 randomized phase III report of combining stereotactic radiosurgery with whole brain radiation therapy (31), Tsao reports on a systematic review summarizing management options for patients with brain metastases. She discusses medical management with steroids and anti-epileptics, systemic therapy and molecular targeted therapy, whole brain radiation therapy, stereotactic radiosurgery, and surgical resection for patients with both single and multiple brain metastases, and she focuses on symptom management, quality of life, and neurological function in addition to detailing survival and brain control outcomes (32). Agarwal and colleagues assess voice-related quality of life after total laryngectomy using patient-reported outcomes for a large patient population in India (33). Their findings that patients with lower socioeconomic status had better voice preservation and quality of life may offer interesting insights into the important of social support on yet another aspect of quality of life for patients with advanced diseases.

Acknowledgements

None.

Footnote

Conflicts of Interest: The author has no conflicts of interest to declare.

References

1. Serlin RC, Mendoza TR, Nakamura Y, et al. When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain 1995;61:277-84. [PubMed]
2. Jensen MP, Smith DG, Ehde DM, et al. Pain site and the effects of amputation pain: further clarification of the meaning of mild, moderate, and severe pain. Pain 2001;91:317-22. [PubMed]
3. Zelman DC, Dukes E, Brandenburg N, et al. Identification of cut-points for mild, moderate and severe pain due to diabetic peripheral neuropathy. Pain 2005;115:29-36. [PubMed]
4. Kapstad H, Hanestad BR, Langeland N, et al. Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery. BMC Musculoskelet Disord 2008;9:55. [PubMed]
5. Woo A, Lechner B, Fu T, et al. Cut points for mild, moderate, and severe pain among cancer and non-cancer patients: a literature review. Ann Palliat Med 2015;4:176-83.
6. Spiegel D, Sands S, Koopman C. Pain and depression in patients with cancer. Cancer 1994;74:2570-8. [PubMed]
7. Simone CB 2nd, Vapiwala N, Hampshire MK, et al. Palliative care in the management of lung cancer: analgesic utilization and barriers to optimal pain management. J Opioid Manag 2012;8:9-16. [PubMed]
8. Reddick BK, Nanda JP, Campbell L, et al. Examining the influence of coping with pain on depression, anxiety, and fatigue among women with breast cancer. J Psychosoc Oncol 2005;23:137-57. [PubMed]
9. Roos DE. Radiotherapy for neuropathic pain due to bone metastases. Ann Palliat Med 2015;4:220-4.
10. Cleeland CS, Gonin R, Hatfield AK, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994;330:592-6. [PubMed]
11. Simone CB 2nd, Vapiwala N, Hampshire MK, et al. Cancer patient attitudes toward analgesic usage and pain intervention. Clin J Pain 2012;28:157-62. [PubMed]
12. Schultz J. U.S. falls short of top-notch health care, report says. J Natl Cancer Inst 2003;95:258-9. [PubMed]
13. Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1-18. [PubMed]
14. Chow E, Zeng L, Salvo N, et al. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol) 2012;24:112-24. [PubMed]
15. Chow E, Hoskin PJ, Wu J, et al. A phase III international randomised trial comparing single with multiple fractions for re-irradiation of painful bone metastases: National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) SC 20. Clin Oncol (R Coll Radiol) 2006;18:125-8. [PubMed]
16. Chiu N, Chiu L, Popovic M, et al. Re-irradiation for painful bone metastases: evidence-based approach. Ann Palliat Med 2015;4:214-9.
17. Jeremic B, Shibamoto Y, Igrutinovic I. Single 4 Gy re-irradiation for painful bone metastasis following single fraction radiotherapy. Radiother Oncol 1999;52:123-7. [PubMed]
18. Mithal NP, Needham PR, Hoskin PJ. Retreatment with radiotherapy for painful bone metastases. Int J Radiat Oncol Biol Phys 1994;29:1011-4. [PubMed]
19. Wong E, Hoskin P, Bedard G, et al. Re-irradiation for painful bone metastases - a systematic review. Radiother Oncol 2014;110:61-70. [PubMed]
20. Chow E, van der Linden YM, Roos D, et al. Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol 2014;15:164-71. [PubMed]
21. Tsang DS, Yau V, Raziee H, et al. Debate: Single-fraction treatment should be standard in the retreatment of uncomplicated bone metastases. Ann Palliat Med 2015;4:207-13.
22. Jones JA, Simone CB 2nd. Palliative radiotherapy for advanced malignancies in a changing oncologic landscape: guiding principles and practice implementation. Ann Palliat Med 2014;3:192-202. [PubMed]
23. Hjortholm N, Jaddini E, Hałaburda K, et al. Strategies of pain reduction during the bone marrow biopsy. Ann Hematol 2013;92:145-9. [PubMed]
24. Riley RS, Hogan TF, Pavot DR, et al. A pathologist's perspective on bone marrow aspiration and biopsy: I. Performing a bone marrow examination. J Clin Lab Anal 2004;18:70-90. [PubMed]
25. Zahid MF. Methods of reducing pain during bone marrow biopsy: a narrative review. Ann Palliat Med 2015;4:184-93.
26. Rodriguez R, Marr L, Rajput A, et al. Utilization of palliative care consultation service by surgical services. Ann Palliat Med 2015;4:194-9.
27. Dunn GP. Surgery, palliative care, and the American College of Surgeons. Ann Palliat Med 2015;4:5-9. [PubMed]
28. Karlekar M, Collier B, Parish A, et al. Utilization and determinants of palliative care in the trauma intensive care unit: results of a national survey. Palliat Med 2014;28:1062-8. [PubMed]
29. Vidri RJ, Blakely AM, Kulkarni SS, et al. American College of Surgeons National Surgical Quality Improvement Program as a quality-measurement tool for advanced cancer patients. Ann Palliat Med 2015;4:200-6.
30. Jones JA, Simone CB 2nd. Whole brain radiotherapy for patients with poor prognosis: possibilities for the impact of the QUARTZ trial. Ann Palliat Med 2015;4:58-60. [PubMed]
31. Brown PD, Asher AL, Ballman KV, et al. NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases. J Clin Oncol 2015;33:abstr LBA4.
32. Tsao MN. Brain metastases: advances over the decades. Ann Palliat Med 2015;4:225-32.
33. Agarwal SK, Gogia S, Agarwal A, et al. Assessment of voice related quality of life and its correlation with socioeconomic status after total laryngectomy. Ann Palliat Med 2015;4:169-75.