Chronic Pain Management in Cancer Survivors

1104

Original Article

Natalie Moryl, MD; Nessa Coyle, NP, PhD; Samuel Essandoh, MD; and Paul Glare, MD; New York, New York

Key Words ican Pain Society (APS) have provided guidelines to Cancer survivor, pain, opioids, compliance manage pain in cancer patients and survivors. Although the guidelines do reflect variations, the goal should be Abstract not to discontinue opioids, but to thoroughly assess the The problem of pain in cancer survivors is attracting increased patient’s pain and arrive at an appropriate management attention. Although comprehensive information about the prevalence of persistent pain in the cancer survivor population is plan. Long-term opioid use may be necessary to treat currently lacking, it is known to depend on the type of cancer, cancer-related or non–cancer-related pain in cancer comorbid conditions, and the initial pain management. Epidemio- survivors. If opioids are to be initiated or continued, logic studies generally categorize pain in patients with cancer as then the approach is to optimize their risk–benefit ratio either pain directly caused by the neoplastic process or related through monitoring clinical effectiveness, addressing phenomena, pain occurring as a complication of anticancer treatment, or pain unrelated to the neoplastic process, caused by debil- side effects, and monitoring adherence. ity or concurrent disorders. This article focuses on pain syndromes in cancer survivors and the safe use of opioid therapy in this population when its ongoing use is part of the pain management plan. Who is a “Cancer Survivor”? The use of physical therapy, rehabilitation therapy, and cognitive The NCI, in conjunction with the National Coalition behavioral therapy, which are all extremely important aspects of pain management in the cancer survivor, are briefly mentioned. for Cancer Survivorship, uses the term cancer survivor (JNCCN 2010;8:1104–1110) to include anyone who has been diagnosed with cancer, from diagnosis throughout life.1 A more clinically meaningful definition is provided by Macmillian Can- cer Support, one of the largest British charities for pa- Unfortunately, some cancer survivors with chronic tients with cancer, which defines a cancer survivor as cancer-related pain meet significant barriers limiting someone who is “living with or beyond cancer,” namely their access to medications previously determined effec- someone who: tive and well-tolerated. An unintended consequence is • Has completed initial cancer treatment and has no pain that had been well controlled during active cancer apparent evidence of active disease; treatment becomes inadequately managed, resulting in • Is living with progressive disease and may be re- unnecessary suffering. The American Academy of Hos- ceiving cancer treatment but is not in the terminal phases of illness; or pice and Palliative Medicine (AAHPM) and the Amer- • Has had cancer in the past. The term long-term survivor is commonly used in re-

From Memorial Sloan-Kettering Cancer Center, New York, search literature. Most investigators use either 5-years New York. after diagnosis or 2-years after completion of therapy as Submitted May 5, 2010; accepted for publication August 9, 2010. their marker.2 The authors have disclosed that they have no financial interests, arrangements, or affiliations with the manufacturers of any Approximately 11 million Americans are either cur- products discussed in the article or their competitors. rently undergoing treatment for cancer or have done so in Correspondence: Natalie Moryl, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10045. the past. Long-term 10-year survival rates are approaching E-mail: [email protected] 59% in adults and 75% in children, making most cancer

Pain in Cancer Survivors patients candidates for becoming cancer survivors. This When pain is from neither the disease or its population is different from people without a history treatment, it most often arises from muscles and con- of cancer in terms of their medical and psychosocial nective tissue.10,11 Although many cancer survivors needs, and general complexity. A treatment approach present with painful comorbidities, such as degen- specifically tailored to this population is required. erative disc disease or fibromyalgia, pain in cancer Survivors of cancer have significantly poorer survivors usually refers to chronic pain caused by suc- health outcomes across multiple burden-of-illness cessful treatment or related debility. measures for years after diagnosis than do people Prevalence of Pain in Survivors without a history of cancer.3,4 Psychosocial compli- Comprehensive information about the prevalence cations and concerns in cancer survivors are also im- of persistent pain in the cancer survivor population portant and can affect the pain experience. Depres- is currently lacking. To address this knowledge gap, sion, for example, is up to 4 times more prevalent research is being conducted to evaluate a random in cancer survivors than in the general population.5 sample of cancer survivors who completed treatment Medicare beneficiaries with prostate, breast, lung, or 1 to 10 years previously and were treated at Memo- colon cancers are at least twice as likely to use emer- rial Sloan-Kettering Cancer Center. These patients gency departments and receive inpatient medical are asked to complete a telephone-administered pain treatment if they have clinically significant depres- interview and assessment battery focusing on pain, sive symptoms than if they do not.6 The psychiatric quality of life, and psychological distress.12 and social needs of cancer survivors and their care- The prevalence of pain in cancer survivors de- givers have a direct effect on their pain experience pends on the type of cancer, comorbid conditions, and must be addressed long-term by clinicians moni- and initial pain management. For example, pain was toring these patients. reported 3 months after thoracotomy in 80% of cases in one series.13 Pain after amputation includes stump Pain Syndromes in Cancer Survivors pain and phantom limb pain and is reported in up to 70% patients.14 The prevalence of chronic pain in The problem of pain in cancer survivors is attracting breast cancer survivors is currently estimated to be increased attention.7 Epidemiologic studies generally at least 50%.15 Pain after treatment of head and neck categorize pain in patients with cancer as 1) directly cancer may also be as high as 50%, with more than caused by the neoplastic process or related phenom- 50% disabled by pain after 12 months. Predisposing ena (60% of cases); 2) occurring as a complication factors for pain in cancer survivors include preexist- of anticancer treatment (5%); or 3) unrelated to the ing pain, intensity of postoperative pain, treatment neoplastic process, caused by either debility (20%) modalities used, extent of treatment, and psycho- or concurrent disorders (15%).8 logical status. Posttreatment pain syndromes may result from surgery, radiation therapy (RT), or chemotherapy. Postmastectomy Pain The main postsurgical pain syndromes include those Although it is sometimes assumed that modern and related to mastectomy, amputation, and thoracoto- less-invasive surgical techniques should result in a my, and neuropathic pain secondary to treatment- decreased incidence of pain in this population, this related pathology in cranial nerves. Chronic radia- is not always the case. For example, lumpectomy and tion-induced damage may surface decades later but is axillary dissection may result in a higher incidence of less common than postsurgical pain. Postchemother- pain than a modified radical mastectomy. The extent apy painful neuropathy is well described, particularly of the axillary dissection increases the incidence of with the use of vincristine, platinum, taxanes, thalid- pain, and the need for combined treatment modali- omide, and bortezomib.9 Occurring in up to one third ties with RT or chemotherapy in breast-conserving of patients undergoing combination chemotherapy, surgery contributes to the pain. Breast reconstruc- painful neuropathy typically resolves within months tion surgery can also cause chronic pain. In a large after completion of therapy. Osteoporotic fractures Danish study of women who underwent breast sur- and avascular necrosis secondary to high-dose corti- gery, 47% reported pain, of whom 52% had moderate costeroids may also be included under this category. to severe pain.15 Factors associated with chronic pain

Moryl et al.

included young age (18–39 years) and adjuvant RT, Postradiation Pain Syndromes but not chemotherapy. Axillary lymph node dissec- The most well-studied postradiation syndrome is tion was associated with increased likelihood of pain radiation-induced brachial plexopathy (RBP), al- compared with sentinel lymph node dissection. Pain though it is frequently painless. Typically occur- complaints originating from other parts of the body ring months to years after axillary or supraclavicular were associated with an increased risk of pain in the radiation, the incidence of severe RBP is less than surgical area.15 5% in women undergoing RT after mastectomy, but less-severe RBP may be present in another 10% of Postthoracotomy Pain patients. Severe RBP is more common with higher Postthoracotomy pain is primarily caused by damage doses of RT and after chemotherapy. An acute RBP to the intercostal nerve, but severe rib retraction may may develop either during radiation or within weeks also disarticulate the costochondral and costoverte- of treatment completion in patients undergoing ex- bral junctions, resulting in somatic pain and tender- ternal beam radiation when the treatment field in- ness. Ipsilateral arm disability is also common because cludes the brachial plexus. This pain usually resolves the latissimus dorsi and serratus anterior muscles are spontaneously within weeks or months. Radiation- frequently cut. Pain seems to be less common with induced lumbar plexopathy is rare. Like RBP, sen- video-assisted thoracic surgery than with an open tho- sory and motor symptoms commonly precede pain, racotomy. Pain is also less common with an anterolat- although pain does not develop in half of the pa- eral approach than with a posterolateral one. Chronic tients. Plexopathy follows radiation by an average of pain is present in more than 50% patients, with 60% 5 years, but this ranges considerably. Symptoms are still taking analgesics at 1 year.16,17 usually bilateral but asymmetric. Postamputation Pain Debility-Related Pain in Cancer Survivors Phantom limb pain is more common after leg am- Because inactivity and deconditioning predisposes to putation than arm. Older age, bilateral amputa- muscle pain, the debilitated cancer patient has good tions, and a more proximal amputation site are other reason to experience muscle pain. The fatigued pa- known risk factors. The time elapsed since amputa- tient is at a higher risk for muscle injury. Muscle pains tion is shorter among those with phantom pain. include trigger points and myofascial pain syndrome, Pain Status After Therapy for Head tension, weakness, stiffness, cramps, and spasms.20 and Neck Cancer Because treatment for head and neck cancer is usually a combination of surgery, RT, and/or chemotherapy, Standards for Cancer Pain Management, the incidence of chronic pain approaches 40% at 1 Including Nonpharmacologic year. The accessory nerve and nerves of the superficial As cancer evolves into a chronic illness, the land- cervical plexus are commonly injured, typically result- scape of cancer pain for many patients has shifted ing in neuropathic pain syndromes. In one study of pa- into a chronic pain situation lasting months, years, tients at 1 year after retroperitoneal lymph node dis- or a lifetime.21 section, 33% reported neck pain, 37% shoulder pain, When ongoing pain management is required for 46% myofascial pain, and 65% loss of sensation.18 a patient whose cancer is cured or in remission, and However, not all cancer surgeries are associated whose care has shifted from a tertiary cancer cen- with chronic pain. In a Norwegian study of long-term ter back into the community, the community phy- gynecologic cancer survivors with a median complete sician may be concerned if ongoing opioid therapy recurrence-free period of 12 years (range, 7–18), the is expected. These concerns generally focus on the prevalence of pain was 26%.19 The results showed no potential for harm associated with chronic opioid difference in the prevalence of pain between women use, including psychological dependence (addic- who survived gynecologic cancer and those with no tion), management of behavior classified as pseudo- history of gynecologic cancer. Women with musculo- addiction (drug-seeking and other behavior that is skeletal disorders or living in households with low in- consistent with addiction but actually results from come were more likely to experience pain, irrespective inadequate pain relief; once the pain is adequately of whether they were gynecologic cancer survivors.19 treated, the person no longer exhibits these behav-

Pain in Cancer Survivors iors), tolerance necessitating escalating opioid doses community physicians have access to state-of-the- to manage the pain, and opioid side effects that are science education on the management of cancer-re- difficult to manage. lated pain and chronic pain in cancer survivors. This The management of pain in patients with can- includes knowledge of the appropriate use and titra- cer is well studied, and various clinical guidelines, in- tion of opioid drugs in response to pain, management cluding those from the APS and NCCN, have been of opioid-related side effects, and use of coanalgesics, developed to help clinicians manage the pain. How- such as antidepressants and anticonvulsants. Rapidly ever, few data have been collected on the long-term escalating pain in cancer survivors or a sudden onset use of opioids in cancer survivors.22,23 Unfortunately, of new opioid-related side effects usually indicates some cancer survivors with chronic cancer-related that something else is occurring in the patient medi- pain encounter significant barriers that limit their cally. Ethical issues surrounding undertreatment of access to the previously effective and well-tolerated pain in cancer survivors also warrant attention. medications. Patient, family, professional, and sys- In most cancer survivors who require opioid therapy to adequately manage pain, these drugs can tem-related barriers that may be seen during active be used responsibly and safely. Optimizing pain con- treatment can become even more problematic dur- trol and preserving or improving function is the goal. ing survivorship (Table 1).23–28 It is important that Any patient with a history of cancer who presents Table 1 Factors Affecting Optimal Pain Relief with acute or chronic pain requires a careful evalua- in Cancer Survivorship tion not only to establish a pain diagnosis clarifying the causes of the pain, but also to guide the treat- Patient Factors ment approach. The patient may have several sites Comorbidities and sources of pain, and each site requires a care- Aging ful assessment. New pain or escalation of previously Reluctance to report symptoms (symptom as a reminder of cancer and fear of recurrence) well-controlled pain should be promptly evaluated to Fear of addiction (reinforced by the community) rule out cancer recurrence or progression. The basic Negative experiences with pain medication in the past components of a pain history are 1) sites and qual- (adverse side effects) ity of the pain, 2) exacerbating and relieving factors, Cost of medications 3) temporal pattern of the pain, 4) associated signs Professional Factors and symptoms, and 5) degree of interference with Lack of knowledge about: function. These should be placed within the context • Prevalence of chronic pain in cancer survivors of the patient’s cancer history and treatment. • Assessment and management of chronic pain in cancer If pain subsides or a patient prefers to stop taking survivors opioids, a slow taper to prevent opioid withdrawal • Basic pain assessment and management skills symptoms can be implemented. The lowest effective System-Related Factors dose should be continued when appropriate. Usually, Reimbursement policies 25% of the daily opioid dose is sufficient to prevent Cost withdrawal symptoms. In some patients it may take Community pharmacies reluctance to carry opioids several months to taper and discontinue even small (reinforces fears of addiction) opioid doses, such as 5 mg of oxycodone taken twice Scientific Factors daily. In rare instances, a clonidine patch and acet- Limited research in chronic pain syndromes aminophen may be used to treat withdrawal symp- Lack of well-validated research instruments for chronic toms. Both clonidine and acetaminophen are associ- pain ated with a ceiling effect (increasing the dose will not Limited research in the quality of cancer survivorship increase the desired effect but will increase adverse Lack of comprehensive and clear guidelines for follow-up side effects). As with any medications, side effects care, including the management of chronic pain in cancer survivors should be anticipated and managed as appropriate. Examples of treatment-related pain that require Adapted from Levy MH, Chwistek M, Mehta RS. Management of chronic pain in cancer survivors. Cancer J chronic pain management include chronic postmas- 2008;14:401–409. tectomy pain syndrome, severe hip pain from arthritis

Moryl et al.

and avascular necrosis resulting from high-dose ste- roids given during bone marrow transplantation, or If total daily oral morphine dose < 100 mg over 24 hours, change to methadone, 2.5–5.0 mg every 8 to 12 hours chronic pelvic pain after extensive radiation for uter- and discontinue opioid ine carcinoma. Opioids should not be automatically stopped in a cancer survivor who is compliant with If oral morphine > 100 mg over 24 hours, use the following the medications and has stable and well-controlled morphine to methadone conversion ratios: pain. Bothersome opioid-related side effects should be • Morphine 100–300 mg over 24 hours, use 8:1 ratio assessed and managed whenever possible. Difficult to • Morphine > 300 mg over 24 hours, use 12:1 ratio control or neglected constipation is a major concern and may be the reason patients ask to have an opioid Example: Extended-release morphine, 40 mg, every 8 hours by mouth (or 120 mg over 24 hours) will be rotated to tapered or discontinued despite significant pain. methadone, 15 mg by mouth over 24 hours (i.e., 5 mg A multidisciplinary approach tailored to the in- every 8 hours) dividual patient needs using a combination of opioids, coanalgesics, physical therapy, psychosocial Figure 1 Guide for rotation from morphine to methadone. interventions, and complementary and alternative modalities is usually the most effective approach to release opioid formulations when a patient has a strong managing pain in cancer survivors. Some patients history of substance abuse. Risk of relapse in this group need only one of these interventions, whereas others of patients may be higher with the use of short-acting benefit from a combination. In some instances, inva- opioids. Whenever a patient is on chronic opioid thera- sive interventional procedures can be helpful. py to manage pain, ongoing monitoring and follow-up is The pharmacologic management of pain in can- mandatory, including assessment of analgesic effective- cer survivors usually consists of opioids in combina- ness, activities of daily living, and adverse drug effects tion with coanalgesics, such as antidepressants and such as constipation, nausea, or sedation, and screening anticonvulsants, for controlling neuropathic pain, or for aberrant drug-taking behaviors. Almost all patients with nonsteroidal anti-inflammatory drugs for con- undergoing chronic opioid therapy require a consistent trolling nociceptive pain. bowel regimen involving a combination of a large bowel For chronic pain, opioids should be prescribed stimulant, a stool softener, and other laxatives as need- on an-around-the clock basis, and long-acting opioid ed, including osmotic agents. preparations are preferred. Commonly used opioids include controlled-release morphine, controlled-release oxycodone, transdermal patches of fentanyl, and Individualizing Goals for methadone. Rotation among different opioids requires Pain Management consideration of their different relative potency ratios. Although the pain management guidelines proposed In the case of methadone, rotation is complicated by by the AAHPM and APS contain variations, the the fact that the ratio is dose-related, as seen in Fig- common goal is not to deny cancer survivors opioids ure 1. Methadone is also known to have a long and if their use is indicated.23–28 unpredictable half-life. Careful titration with close The cancer survivor with chronic pain who is monitoring of pain intensity and side effects, espe- no longer followed up at a tertiary cancer center and cially sedation, is required during the first 5 to 7 days now presents to the primary care clinician for care of treatment. Because of these factors, methadone is needs the risk–benefit ratio of long-term opioid treat- usually considered a third-line opioid, and best used ment assessed and documented. The goal is not to in experienced hands. taper down opioids, but to optimize the risk–benefit In most situations, immediate-release preparations ratio; in other words, to achieve analgesia or improve should also be made available to patients for episodes of functional status with minimal side effects and with- breakthrough pain. The dose for the breakthrough pain out aberrant drug-taking behavior. is proportional to the 24-hour around-the-clock dosage, The treatment plan should include an open dis- is usually 10% to 20% of the patient’s 24-hour dose, and cussion about goals and expectations of chronic opioid should be made available every 3 to 4 hours as needed. treatment. Consent for initiating opioid therapy and a Long-acting opioids may be used without immediate- contract outlining the physician and patient responsi-

Pain in Cancer Survivors bilities may be introduced. A similar approach may be opioid diversion and abuse in cancer survivors. In this useful if established opioid therapy is to be continued. population, with the higher comorbidities, mortality, Patients as unique individuals will vary not only and psychosocial sequela associated with cancer treat- in their reports of pain intensity and pain relief, but ment, adequate treatment of pain and risk assessment in their functional status related to opioid use. For ex- of patients undergoing chronic opioid therapy is para- ample, a 43-year-old man with a history of recurrent mount. Survivor populations at especially high-risk lymphoma and recently diagnosed leukemia presents for the undertreatment of pain include children, mi- to the clinic complaining of severe back pain and re- norities, and persons who are elderly, have develop- quests a prescription for Percocet. Radiologic studies mental disabilities, or have serious chronic diseases. confirm severe lumbar stenosis as the likely source of Patients at risk for the undertreatment of pain are his pain. After reviewing his medical records, the phy- those who are active drug abusers or have a history of sician notes that the patient has run out of Percocet drug abuse, however distant. Patients who are actively and OxyContin on several occasions over the past 4 abusing drugs or have a recent history of drug abuse years. The reason was identified as unilateral and the benefit from the expertise of pain and addiction spe- increases in his opioid dosage determined to be unsanc- cialists working together; care of these patients can be tioned despite clear instructions not to do so. It was complex and time-consuming. also revealed that the patient had obtained opioid pre- Some physicians are reluctant to prescribe opi- scriptions from multiple prescribers. The patient had oids to patients with chronic pain because of the mild renal insufficiency and was unable to receive non- concerns about legal or regulatory scrutiny, licen- steroid anti-inflammatory medications. Despite the sure issues, and fear of iatrogenic addiction and drug patient’s painful condition, the decision was made not overdose. Most prescription drug overdose, however, to prescribe further opioids. His aberrant drug behavior occurs outside of the patient–physician relation- was deemed to be more detrimental to his health and ship.28 A recent study showed that 66% of overdoses functional status than the pain itself. The patient was occurred in persons who had never received a pre- referred for physical therapy and to a neurosurgeon to scription for an opioid, and another 21% occurred be evaluated for decompression surgery to alleviate the in those who had received opioid prescriptions from pain. A different patient with a similar chronic pain multiple prescribers (≥ 5 physicians).29 syndrome but no evidence of aberrant drug behavior With appropriate patient selection, screening, would probably have been managed with a combina- and monitoring, chronic opioid use can be safe for tion of low-dose opioid therapy and physical therapy. most cancer survivors and result in good pain relief, In another case, a 50-year-old breast cancer sur- with maintenance or improvement of functional vivor with severe chronic peripheral neuropathy se- status.26 Patients who are identified as high risk for vere enough to interfere with her ability to work was opioid abuse require adjustment of the clinic routine prescribed oral methadone, 20 mg, every 8 hours, for to provide closer monitoring, especially in cases of pain. This regimen has been continued for several active or past history of substance abuse, psychiat- years with what the patient describes as incomplete ric illness, or serious drug aberrant behavior.30,31 Risk but “acceptable and sufficient” analgesia. Side effects factors for opioid abuse include personal history of were limited to mild fatigue. In this case, the pa- substance abuse, family history of substance abuse, tient’s functional status and pain control improved, age (young), history of preadolescent sexual abuse, and this improvement was maintained with a stable mental disease, psychological stress, polysubstance opioid dose. She is seen every 3 months for reevalu- abuse, poor social support, cigarette dependency, and ation and an opioid prescription refill. history of repeated drug/alcohol rehabilitation. Adherence monitoring includes measures taken by health care providers to ensure adherence to opi- Issues of Addiction/Diversion oid therapy, and to recognize and prevent aberrant Of the approximately 11 million cancer survivors liv- behavior, abuse, and addiction.32 Clinical literature ing in the United States today, up to 30% have chron- suggests a 50% or more reduction in opioid abuse oc- ic pain. This statistic creates a large public health curs in the presence of opioid adherence and moni- concern about adequate analgesia and prevention of toring programs.32

Moryl et al.

In these high-risk situations, clinicians may con- treatment. Cancer Invest 2005;23:84–93. sider a consultation with a mental health profession- 12. Clinicaltrials.gov. Available at: http://clinicaltrials.gov/ct2/show/ NCT00581724. Accessed August 10, 2010. al or an addiction specialist.32 13. Burton AW, Fancuilllo GJ, Beasley RD. Pain in the cured cancer patient. In: Fisch MJ, Burton AW, eds. Cancer Pain Management. New York: McGraw Hill; 2007:155–163. Conclusions 14. van der Schans CP, Geertzen JH, Schoppen T, Dijkstra PU. Phantom pain and health-related quality of life in lower limb Cancer survivors with residual pain continue to amputees. J Pain Symptom Manage 2002;24:429–436. need safe and effective analgesia. Chronic pain 15. Gartner R, Jensen MB, Nielsen J, et al. Prevalence of and factors management in this group requires clinical skills associated with persistent pain following breast cancer surgery. and knowledge regarding the principles of opioid JAMA 2009;302:1985–1992. and adjuvant analgesics prescribing, and the assess- 16. Landreneau RJ, Mack MJ, Hazelrigg SR, et al. Prevalence of chronic pain after pulmonary resection by thoracotomy or video-assisted ment and management of risks associated with opi- thoracic surgery. J Thorac Cardiovasc Surg 1994;107:1079–1085; oid abuse and addiction. The goal should not be to discussion 1085–1086. arbitrarily taper down opioids, but to optimize the 17. Dajczman E, Gordon A, Kreisman H, Wolkove N. Long-term risk–benefit ratio; in other words, to achieve anal- postthoracotomy pain. Chest 1991;99:270–274. gesia or improve functional status with minimal side 18. Van Wilgen CP, Dikjstra PU. Morbidity of the neck after head and neck cancer therapy. Head Neck 2004; 26:785–791. effects and without aberrant drug-taking behavior. 19. Rannestad T, Skjeldestad FE. Pain and quality of life among long- Some patients may want to discontinue their opi- term gynecological cancer survivors: a population-based case- oids, and this can be done safely through a moni- control study. Acta Obstet Gynecol Scand 2007;86:1510–1516. tored taper. The use of physical therapy, rehabilita- 20. Marcus NJ. Pain in cancer patients unrelated to the cancer or tion therapy, and cognitive–behavioral therapy are treatment. Cancer invest 2005;23:84–93. 21. Levy MH, Chwistek M, Mehta RS. Management of chronic pain in all extremely important aspects of pain management cancer survivors. Cancer J 2008;14:401–409. in the cancer survivor. 22. Sun V, Borneman T, Piper B, et al. Barriers to pain assessment and management in cancer survivorship. J Cancer Surviv 2008;2:65–71. 23. Swarm R, Abernethy AP, Anghelescu DL, et al. NCCN clinical References practice guidelines in oncology: adult cancer pain. Version 1, 2010. Available at: http://www.nccn.org/professionals/physician_gls/ 1. National Cancer Institute. Facing Forward: Life After Cancer PDF/pain.pdf. Accessed August 11, 2010. Treatment. Available at: http://www.cancer.gov/cancertopics/life- 24. American Pain Society. Guidelines for the Management of Cancer after-treatment. Accessed August 11, 2010. Pain in Adults and Children. Available at: www.ampainsoc.org. 2. National Cancer Institute. Long Term Cancer Survivors: Research Accessed August 10, 2010. Initiatives. RFA: CA-04-003. Available at: http://grants.nih.gov/grants/ 25. American Pain Society. Principles of Analgesic Use in the guide/rfa-files/RFA-CA-04-003.html. Accessed August 11, 2010. Treatment of Acute Pain and Cancer Pain – sixth edition. 3. Earle CC, Neville BA. Underuse of necessary care among cancer Available at: www.ampainsoc.org. Accessed August 10, 2010. survivors. Cancer 2004;101:1712–1719. 26. Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the 4. National Cancer Institute. Surveillance Epidemiology and End use of chronic opioid therapy in chronic noncancer pain. J Pain Results. SEER Cancer Statistics Review 1975–2007. Available at: 2009;10:113–130. http://seer.cancer.gov/csr/1975_2007/index.html. Accessed August 27. Chou R, Ballantyne JC, Fanciullo GJ, et al. Research gaps on use of 11, 2010. opioids for chronic non-cancer pain: findings from a review of the 5. Polsky D, Doshi JA, Marcus S. Long-term risk for depressive evidence for an American Pain Society and American Academy of symptoms after a medical diagnosis. Arch Intern Med Pain Medicine clinical practice guidelines. J Pain 2009;10:147–159. 2005;165:1260–1266. 28. Burton AW, Fanciullo GJ, Beasley RD, Fisch MJ. Chronic pain in 6. Himelhoch S, Weller WE, Wu AW, et al. Chronic medical illness, the cancer survivor: a new frontier. Pain Med 2007;8:189–198. depression, and use of acute medical services among Medicare 29. Hall AJ, Logan JE, Toblin RL, et al. Patterns of abuse among beneficiaries. Med Care 2004;42:512–521. unintentional pharmaceutical overdose fatalities. JAMA 7. Foley KM. The treatment of pain in the patient with cancer. CA 2008;300:2613–2620. Cancer J Clin 1986;36:194–215. 30. Edlund MJ, Steffick ,D Hudson T, et al. Risk factors for clinically 8. Portenoy RK. Cancer pain: epidemiology and syndromes. Cancer recognized opioid abuse and dependence among veterans using 1989;63:2298–2307. opioids for chronic non-cancer pain. Pain 2007;129:355–362. 9. Cavaletti G, Zanna C. Current status and future prospects for the 31. Kahan M, Srivastava A, Wilson L, et al. Misuse of and dependence treatment of chemotherapy-induced peripheral neurotoxicity. Eur J on opioids: study of chronic pain patients. Can Fam Physician Cancer 2002;38:1832–1837. 2006;52:1081–1087. 10. Twycross, R. Pain Relief in Advanced Cancer. Churchill 32. Manchikanti L, Manchukonda R, Damron KS, et al. Does Livingstone: New York; 1994:5–61. adherence monitoring reduce controlled substance abuse in 11. Marcus NJ. Pain in cancer patients unrelated to the cancer or chronic pain patients? Pain Physician 2006;9:57–60.