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® : 6 9 ICD-11 , e 49 ; and (3) more specialist referrals for some 5 , Winfried Rief . This article describes the new classification of e The situation is made even more difficult by the fact are broad and do not relate treatment approaches to 6,22 10,40,46,53 Current treatment guidelines created by the World Health The term “ pain” is often poorly defined and is not Correctly identifying the nature and cause of pain in a cancer will experience pain and 55% ofmoderate all to patients will severe intensity. experience pain of therapy; (2) triggering support forself-management patients through to educational promote interventions, theirand resources, coping own strategies Organization (WHO) andies other national or international bod- synonymous with pain insurvivor. Causes of a cancer-related pain include cancer the tumour patient itselfits or metastases or inflaming or eroding pain , viscera or in ,related or pain a to tissue cancer or (surgery, damage induced , by cancer and treatments agnosed with radiation). cancer are Patients frequently older and whodiseases may unrelated have to comorbid are their cancer. di- Thepatients may aetiology therefore not of be pain cancer-related but in may insteadfrom some arise , diabeticdiseases. neuropathy, or a range of other patient or cancer survivorcontrol. is Accurate diagnosis important and tolead classification achieve to are optimal more 3 pain likely importantincorporating to benefits medicine, anticancer for therapies (including patients:modification of (1) the tailored cancer treatment treatment treatment regimen if pain a syndrome chronic cancer alreadyinterventions exists), such surgery, or as non–drug physiotherapy or cognitive behavioral that it is common forone patients of to these experience sources; pain one systematic from reviewa more found mean that than of there was 2 reported per patient with cancer. pain classification. Even with these guidelines and the availability patients, eg, multimodalblocks, or pain intraspinal analgesic treatment, procedures. interventional nerve is intended to help develop more individualized management plans , Beatrice Korwisi e De- f ICD-11 Department of , Cancer, Radiotherapy, Chemotherapy, Diagnosis c Every year, 8.5 20 ICD-11 By contrast, for those , Antonia Barke Institute of Clinical Medicine, . Chronic cancer-related pain is defined as caused by the primary cancer itself or 37,44 d b,c,d International Classification of Diseases (ICD-10) ed equally to this manuscript. R.-D. ICD-11 49-(0)621 383 71 401. E-mail address: 1 Division of Clinical Psychology and Psychotherapy, 160 (2019) 38–44 e · and rises in prevalence throughout and *, The IASP Taskforce for the Classification of Chronic Pain , Stein Kaasa f, a 7 Classification, Chronic pain, 2018 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited. M.I. Bennett et al.

49 (0)621 383 71 400; fax: Ó 1

2018 International Association for the Study of Pain how a new classification of chronic cancer-relatedfor pain in these patients and to stimulate research into these pain syndromes. metastases (chronic ) or itsby treatment comorbid (chronic postcancer disease. treatment pain). PainOrganization It and management should other be regimens international distinguished bodies. for from Anand pain terminally cancer important caused survivors, clinical ill where challenge chronic pain is cancer from the cancer, patients longer its term treatment, have and pain unrelated been management causes in may elaborated be cancer concurrent. by patients This article the describes World Health chronic cancer-related pain for Keywords: the pain caused by the cancer,is cancer treatment not may represented also lead in to the chronic pain. current Despite its importance, chronic cancer-related pain Abstract Worldwide, the prevalence of cancer isthe rising therapeutic and so successes too of is modern the . number One of of patients who the survive most their frequent cancer and for disabling many symptoms years of thanks to cancer is pain. In addition to Narrative Review European Research Centre (PRC), Oslo, Norway, Academic Unit of Palliative Care, University of Leeds, Leeds, United Kingdom, 38 Department of Psychology, Philipps-University Marburg, Marburg, Germany, survivors, that is personswas with completed, suffer from chronic cancer pain. whose curative treatment beyond cancer treatment. Between 33% and 40% of cancer M.I. Bennett, S. Kaasa, A.Treede, Barke W. contribut Rief also contributeda equally to this manuscript. b Sponsorships or competing interests that mayat be the relevant end to of content this are article. disclosed Worldwide, manyprevalence people is rising. are Estimates fornew affected 2020 cases, suggest 66% by that, will survive ofalive for 17 cancer, at more million least than and 5 10 years, and the years 40% after will be the diagnosis. 1. Background on cancer-related pain

Michael I. Bennett The IASP classification of chronic pain for Rolf-Detlef Treede University of Oslo, Oslo, Norway, patients with advanced disease approaching death, at least 66% Oncology, Oslo University Hospital, Oslo, Norway, the journal’s Web site (www.painjournalonline.com). PAIN 160 (2019) 38–44 © http://dx.doi.org/10.1097/j.pain.0000000000001363 Tel.: [email protected] (R.-D. Treede). Supplemental digital content is available forin this the article. printed Direct text URL and citations are appear provided in the HTML and PDF versions of this article on University, Mannheim, Germany *Corresponding author. Address: Department ofBiomedicine Neurophysiology, and Centre Medical for Technology Mannheim,Heidelberg Medical University, Faculty Ludolf-Krehl-Str.13-17, Mannheim, 68167 Mannheim, Germany. partment of Neurophysiology, CBTM, Medical Faculty Mannheim of Heidelberg million people die from cancer. Pain is thecancer commonest symptom of at diagnosis chronic cancer-related pain Copyright

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of analgesia, barriers to management exist37 and undertreatment In the proposed classification, optional specifiers will allow for of cancer-related pain is common, in part related to lack of access recording the time course and severity of the pain as well as the or late access to .19,21,55 presence of psychosocial factors.48 Pain severity will take into account the pain intensity, pain-related distress, and functional impairment assessed with the help of standardized rating scales 2. The need for a classification system (numerical rating scales [NRS] or visual analogue scales [VAS]) The Edmonton Staging System for Cancer Pain has been (see general companion paper47 and supplementary material for developed as a consensus for assessment and classification details on coding the specifiers; available at http://links.lww.com/ tools for cancer-related pain.15,26,29 Important domains that PAIN/A658); functioning will in addition be specified according to should be included in an assessment system were identified.30 the International Classification of Functioning (ICF).36,54 As such, These were a standardized assessment of pain characteristics the specifiers tie in well with the recommendations regarding the (intensity, time course, and location), pathological processes and measurement of cancer-related pain.23,27,30 mechanisms, and patient-related factors (psychosocial factors and addictive behaviours). Classification and assessment are 4. The classification of chronic cancer-related pain related, but not identical, concepts. Assessment typically aims at quantifying certain parameters, whereas a classification strives to As in ICD-10, the codes for the cancer itself will be collected in their provide distinct categories that are mutually exclusive and jointly own chapter in the ICD-11 (foundation ID: 1630407678). The exhaustive; both endeavours can be seen as complementary. diagnosis of chronic cancer-related pain should be given in There is no widely recognized standardized taxonomy for the addition to these codes when appropriate (foundation ID: classification of cancer-related pain. The European Palliative Care 785363034). For a complete overview of all codes for chronic Research Collaborative recommendations emphasized the need cancer-related pain as implemented in the ICD-11 foundation for such a taxonomy and an agreed classification system.4,23 layer, please refer to the supplementary material (available at http:// Despite the ICD-10 containing a dedicated chapter with detailed links.lww.com/PAIN/A658). The foundation is the set of all entities codes C00-D48 for various types of cancer,52 there is only one represented in the ICD-11 and is continually updated and code (G89.3) that denotes -related pain, but this does expanded. Coherent subsets of the foundation, called “lineariza- not differentiate acute vs chronic pain. There are no detailed tions,” are prepared for actual diagnostic coding by the WHO. At codes in the ICD-10 that systematically distinguish between certain intervals, so-called “frozen versions” are prepared by the cancer patients with and without various types of chronic cancer- WHO. They are “snapshots” of the linearization at a particular point related pain. This shortcoming impedes the acquisition of to establish a common reference version during the developmental accurate epidemiological data for chronic cancer-related pain. process. The frozen version for implementation is from June 18, Because ICD codes are also used for the reporting of target 2018. Another novel feature in ICD-11 is the so-called “multiple diseases and patients’ comorbidities in clinical research, the lack parenting” that allows one and the same definition to be subsumed of such codes hinders the development and implementation of under (and be accessed from) more than one higher level category new therapies and may prevent adequate billing for health care (the so-called “parent”). As will become apparent below, it allows expenses related to pain treatment. Moreover, this also renders for (eg,) greater systematic clarity by listing neuropathic cancer pain chronic cancer-related pain statistically invisible and is detrimen- both as cancer pain and . tal to its recognition in public policy decisions. 4.1. The general structure of the classification 3. The IASP Task Force ICD initiative The main sources for chronic pain in relation to cancer are the To remedy the lack of accurate classification of chronic pain in cancer itself and the treatments used to combat it. The general and chronic cancer-related pain in particular, the classification reflects this structure: The top-level entity chronic International Association for the Study of Pain (IASP) established cancer-related pain describes pain from both these sources. At a task force that worked in close co-operation with WHO the levels below, pain caused by the cancer itself and pain caused representatives in generating a systematic and improved by its treatment are distinguished (Fig. 1). classification of chronic pain.48 The classification is dedicated exclusively to chronic pain syndromes and excludes acute pain. Chronic pain was defined as persistent or recurrent pain lasting 4.2. The diagnostic codes in the classification of chronic cancer-related pain longer than 3 months. This definition was chosen because it provides a clear operationalization that is in line with widely used In the following, the codes that will be available in ICD-11 are criteria32 and includes most relevant conditions. described briefly. The IASP task force recognizes that while the 3-month definition is important for distinguishing chronic pain from acute 4.2.1. Chronic cancer-related pain pain, the criterion might be more challenging to apply in the context of pain from progressive cancer. First, in the face of Chronic cancer-related pain is chronic pain caused by the continuous and progressive tumour-related tissue destruction, primary cancer itself or metastases (chronic cancer pain) or its the distinction between acute and chronic pain is blurred. treatment (chronic postcancer treatment pain). It is distinct from Second, many patients with painful progressive tumour-related pain caused by comorbid disease. Pain in cancer survivors must pain may not survive more than 3 months from onset of be monitored carefully because a change in pain quality or continuous pain; median duration of strong treatment intensity can indicate recurrence of the initial malignancy. Careful before death in one cohort study was 9 weeks.55 Thus, the assessment is required to distinguish pain caused by cancer from proposed taxonomy could also be relevant in the context of pain caused by cancer treatment or comorbid conditions. It is continuous tumour-related pain before the 3-month mark, common for these pains to be concurrent, eg, thoracic surgery for particularly when no further anticancer treatments are indicated. a might cause postsurgical pain, which can be

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Figure 1. Organisation of cancer-related pain ICD-11 diagnoses. Levels 1 and 2 are part of the 2018 frozen version of the ICD-11; level 3 was entered into the foundation layer. According to the new concept of multiple parenting in ICD-11, an entity may belong to more than one group of diagnoses. aChronic postcancer surgery pain is coded with all other chronic postsurgical pain according to the type of surgery in the respective chapter.

exacerbated by cancer recurrence in the same area. In these additional unique features indicating that it should be regarded as situations, the clinician must decide the predominant cause of the a separate pain state.16 pain and prioritize the approach to pain treatment. The proposed The temporal characteristics of cancer pain will be described classification of chronic cancer-related pain provides specific as continuous (background pain) or intermittent (episodic pain). codes to cover these aspects (see below). The general diagnostic Intermittent pains can be predictable (incident pain), eg, an code “cancer-related pain” only demands that the pain arose in exacerbation of pain caused by weight bearing or activity relation to cancer; it does not require a decision on the exact (including swallowing, defaecation, coughing, or repeated aetiology (cancer itself or its treatment). This allows for coding the dressing changes), or unpredictable (spontaneous pain) un- cancer-related pain syndrome in situations in which the individual related to movement or activity, eg, colic, stabbing pain contributions of the various factors are not separable. The associated with nerve injury. Intermittent pains such as those availability of this diagnosis helps to distinguish these patients related to single clinical procedures (injections or biopsies) are from cancer patients without chronic pain. regarded as acute pains and not included within the chronic pain classification. Chronic cancer pain is subdivided into 4 catego- 4.2.1.1. Chronic cancer pain ries: 3 with distinct aetiologies: visceral, bone and neuro- 11,22,45 Chronic cancer pain is defined as chronic pain caused by the pathic, and the final category as “other.” primary cancer or metastases. Chronic cancer pain consists of 4.2.1.1.1. Chronic visceral cancer pain inflammatory and neuropathic mechanisms as a direct effect of tissue response to the primary tumour or metastases. These are Chronic visceral cancer pain is chronic pain caused by the primary caused by tumour expansion, which induces tissue damage and tumour or metastases damaging or injuring visceral organs in the release of various inflammatory mediators. In addition, the cancer head and neck region or within thoracic, abdominal, or pelvic can also compress and destroy a sensory nerve, which cavities. Examples include painful liver metastases, coeliac plexus denervates the target tissue resulting in neuropathic changes. by a pancreatic tumour,17 and retrosternal pain from Cancer pain can be considered a type of mixed nociceptive and locally progressive oesophageal or lung tumours. Chronic visceral neuropathic pain, but increasing amounts of evidence suggest cancer pain is often poorly localized and indeed may present as

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(eg, shoulder tip pain from liver metastases is to be therapies. The most common form of anticancer medicine is coded as chronic visceral cancer pain); pain mechanisms include systemic chemotherapy given orally or intravenously. How- compression, distension, inflammation, and ischaemia. The pain ever, hormonal treatments such as anti-oestrogens (tamoxi- can be continuous or may be episodic, particularly if associated fen), anti-androgens (bicalutamide and abiraterone), with organ distension (for an illustration of this type of pain see case aromatase inhibitors (arimidex and letrozole), and luteinizing vignette 1). Chronic secondary is a secondary parent hormone inhibitors (goserelin) are commonly used and are for this diagnosis.1 associated with different chronic pain syndromes. Newer biological therapies such as monoclonal antibodies and 4.2.1.1.2. Chronic bone cancer pain protein kinase inhibitors are increasingly used as targeted Chronic bone cancer pain is chronic pain caused by the primary therapies. Other examples include used to tumour or metastases damaging or injuring boney skeleton, and it manage bone metastases, which may cause painful osteo- is the most common type of chronic cancer pain.33 Metastases necrosis of the jaw, and corticosteroids leading to painful from other cancer sites are the most common form of chronic of the femoral head. bone cancer pain as primary bone tumours are rare. Examples Painful chemotherapy-induced polyneuropathy (CIPN) is de- include an isolated to femoral shaft from colon cancer, scribed as a specific ICD-11 diagnosis (below). Chronic or multiple metastases from breast or , or multiple presenting as symmetrical joint pains, most commonly affecting myeloma. The most common sites of metastases are vertebrae, the wrists, hands, and knees, is reported in 45% of women pelvis, long , and ribs.28 A can weaken receiving hormonal treatment for .3 This bone sufficiently such that an innocuous movement, bump, or fall is the most common reason for treatment discontinuation.31 may result in a pathological fracture. Anecdotal case reports have suggested associations between some newer biological therapies and chronic pain syndromes 4.2.1.1.3. Chronic neuropathic cancer pain such as chronic abdominal and musculoskeletal pain, but clinical Chronic neuropathic cancer pain is chronic pain caused by a primary experience is not yet sufficiently established to determine tumour or metastases damaging or injuring the peripheral or central causality. nervous system.42 Examples of chronic peripheral neuropathic 4.2.2.1.1. Chronic painful chemotherapy-induced cancer pain include thoracic tumour or metastases damaging the polyneuropathy brachial plexus or abdominal or pelvic damaging the lumbosacral plexus. compression (from collapsed Chronic painful CIPN is chronic peripheral neuropathic pain vertebral boney metastases) can result in chronic central neuro- caused by oral or intravenous chemotherapy given to treat the pathic cancer pain. Chronic neuropathic cancer pain may be primary tumour or metastases. Common chemotherapy agents associated with distinct symptom descriptors,34 and the pain is that cause include taxanes (paclitaxel and typically perceived in the distribution of affected nerves. Neuropathic docetaxel), platinum-based drugs (cisplatin and oxaliplatin), vinca mechanisms are associated with poorer outcomes in cancer pain.39 alkaloids (vincristine), thalidomide, and proteasome inhibitors It is important to identify correctly the neuropathic mechanisms to (bortezomib). Painful CIPN can begin after the first dose of guide the use of additional analgesic treatment.35 chemotherapy and is often related to cumulative dose. Chemotherapy-induced polyneuropathy affects 60% of patients 4.2.1.1.4. Other chronic cancer pain 3 months after treatment with chemotherapy and some protein 44 This code applies to chronic pain caused by the primary cancer or kinase inhibitors, and 30% at 6 months or more. Pre-existing 24 metastases that is not visceral, neuropathic, or bone in origin, and neuropathy is a risk factor for developing CIPN. Painful CIPN where the aetiology is known. For example, this code may be manifests in hands, feet, and sometimes face and can extend in assigned to painful soft-tissue invasion by tumour, skin pain in T-cell a glove and stocking distribution to affect lower arms and lower or painful lymph node metastases. If the aetiology is not legs. The pain is typically of pricking or burning character and may known,orifthepainisamixofknownaetiologiescausedbyprimary be described as an “electric sensation” (For an illustration of this cancer or metastases, then the parent code “chronic cancer pain” type of pain see case vignette 2). Chronic painful polyneuropathy will apply. is a secondary parent for this diagnosis.42

4.2.2.2. Chronic postradiotherapy pain 4.2.2. Chronic postcancer treatment pain Chronic postradiotherapy pain is chronic pain caused by delayed In addition to the cancer itself, the treatments for cancer also may local damage to the nervous system, bones, or other soft tissues cause pain. Typical treatments for cancer are surgery, chemother- in the field of radiotherapy given to treat the primary tumour or 38 apy, and radiotherapy, all of which may result in chronic pain. In metastases. Chronic postradiotherapy pain is rare, but its patients who have received extensive anticancer treatment, eg, occurrence is better recognized with improved long-term cancer pelvic surgery, systemic chemotherapy, and radical pelvic radio- survival.12,25 Onset can be within a few months of the end of therapy, it can be difficult to isolate the exact aetiology of the chronic radiotherapy or up to several years later. Risk factors include large postcancer treatment pain. For these instances, the general overall treatment dose, large dose per radiotherapy treatment, diagnosis of chronic postcancer treatment pain will be appropriate. and combined treatment with surgery or chemotherapy. If the cause of the pain is known, or only one treatment was given, Although overall the incidence is falling, nevertheless, about 2% specific subdiagnoses as detailed below can be used. of breast cancer survivors and up to 15% of survivors can experience this type of pain.12 Pain from 4.2.2.1. Chronic postcancer medicine pain cancer recurrence should be excluded before making this Chronic postcancer medicine pain is chronic pain caused by diagnosis. The most recognized form of postradiotherapy pain any disease-modifying anticancer medicine, including sys- is chronic radiation-induced neuropathy, which is described in temic chemotherapy, hormonal treatment, and biological a separate ICD-11 diagnosis (below).12 Other forms include

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chronic and chronic head and .41 Chronic 4.2.2.4. Other chronic postcancer treatment pain pelvic and low are likely to be caused by insufficiency This code will apply to chronic pain caused by cancer treatment fractures of bone.25 that is not related to cancer medicine, radiotherapy, or surgery, 4.2.2.2.1. Chronic painful radiation-induced neuropathy and where the aetiology is known. Currently, there are very few cancer treatments that would fulfill these criteria but they might Chronic painful radiation-induced neuropathy is chronic pain include, eg, pain after insertion of oesophageal or rectal stent. If caused by delayed local damage to the nervous system in the the aetiology is not known, or the pain is a mix of known cancer field of radiotherapy given to treat the primary tumour or treatment aetiologies, then the parent code “chronic postcancer metastases. It is probably caused by nerve compression as treatment pain” should be allocated. a consequence of radiation-induced fibrosis, but direct injury to nerves and blood vessels is also likely after microvascular ischaemia.12,13 It usually occurs several years after radiother- 5. Discussion apy and is often progressive and irreversible. The most frequent As codes for chronic secondary pain syndromes, the and best-known form of radiation-induced neuropathy is cancer-related chronic pain codes are intended to be given brachial ,18 which may follow irradiation for breast as codiagnoses of the underlying oncological conditions. cancer or apical lung cancer. However, painful lumbosacral The case vignettes provide contains examples of how such plexopathy after pelvic radiotherapy and axial neuropathy of the chronic pain may be coded including use of the optional spinal cord after cervical radiotherapy have also been de- specifiers for temporal course and for severity (pain in- scribed.14 Chronic painful polyneuropathy is a secondary tensity, distress, and disability). This will flag the need for medical care in its own right for this type of pain, despite the parent for this diagnosis.42 pain being considered a symptom. For patients with more advanced disease nearing the end of life, pain treatment 4.2.2.3. Chronic postcancer surgery pain pathways directed by palliative care specialists will apply. A first line treatment for many cancers is surgery to remove the For patients living with and beyond cancer (cancer survi- cancer or the metastases. Because surgery-related chronic pain vors), chronic pain treatment pathways directed by pain will be the same regardless whether the surgery is related to cancer specialists will apply. This treatment may outlast the initial or to some other condition, chronic postcancer surgery pain will be oncological treatment, and hence,thecodeforchronic postcancer treatment pain may become the leading code for coded alongside other chronic postsurgical pain according to the these patients over time (as in case vignette 2). In the pilot type of surgery in the section on postsurgical pain. This will also field testing of the classification, the inclusion of chronic include chronic pain after biopsy or from a chest or abdominal drain cancer-related pain codes was welcomed very strongly.2 insertion for pleural effusion or peritoneal ascites.43 Chronic postcancer surgery pain is particularly common after treatment for breast (postmastectomy pain) or lung 6. Summary and conclusions cancer (post-thoracotomy pain) but can follow any cancer surgery or surgical procedure (eg, a tissue biopsy or insertion Including a distinct cancer-related pain classification within the ICD-11 will lead to multiple benefits, stimulate research into these of a thoracic drain). At 9 months after mastectomy, 63% of pain syndromes, their treatment and prevention, including women reported persistent pain that was moderate to severe 8 multimodal and behavioral interventions, and further promote in 25% of the whole sample. After thoracotomy for lung a standardized assessment for cancer-related pain. For the cancer, 33% reported pain at 3 years after surgery, which was individual patient, it may contribute to improved access to 51 moderate to severe in 11% to 18% of the whole sample. The treatments. Further refinements to this classification can be made predominant mechanism of postsurgical pain is likely to be in the light of new data from epidemiological, translational, and neuropathic but not exclusively so.50 clinical studies.

Case vignette 1: Chronic visceral cancer pain; continuous; overall severity code 3.3.3 A 78-year-old woman with experiences upper abdominal pain with occasional radiation into her upper back between the scapulae. The patient underwent surgery followed by 3 cycles of chemotherapy, but the tumour has progressed despite treatment. The pain is always present (extension code for the temporal course: “continuous” applies) and is described as dull, aching, gnawing, and nauseating. The pain intensity is rated 8/10 by the patient (extension code 3 5 severe) and prevents her from doing much activity (interference of pain with daily activity 9/10, extension code 3 5 severe). She reports pain-related emotional distress of 7/10 (extension code 3 5 severe). The pain can sometimes be worse after meals or lying supine. On examination, there is tenderness in the epigastrium but no tenderness over the back. She has been treated with oral sustained release 80 mg twice daily with some improvement.

Case vignette 2: Chronic painful chemotherapy-induced polyneuropathy; continuous; overall severity code 2.1.1 A 56-year-old man with colon cancer complains of painful feet 3 months after completing 6 cycles of platinum-based chemotherapy. The pain is constant but worse at night and on standing. It is described as numb, tingling, and pricking and sometimes radiates into the lower leg. The pain intensity is rated as 4/10 by the patient (extension code 2 5 moderate), and he is able to carry on most of his usual activities (interference rating 1 5 mild). He reports pain-related emotional distress of 3/10 (extension code 1 5 mild). On examination, there is loss of sensation to soft touch and pin prick over both feet to just above the ankles, and reduced discrimination between hold and cold sensations. He has been treated with pregabalin 75 mg twice daily but with no benefit.

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Conflict of interest statement [9] Bruel BM, Burton AW. Intrathecal therapy for cancer-related pain. Pain Med 2016;17:2404–21. The authors have no conflict of interest to declare. [10] Caraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, Dale O, S. Kaasa reports that he is Eir solution—stockholder. A. Barke De Conno F, Fallon M, Hanna M, Haugen DF, Juhl G, King S, Klepstad P, reports personal fees from IASP, during the conduct of the study. Laugsand EA, Maltoni M, Mercadante S, Nabal M, Pigni A, Radbruch L, W. Rief reports grants from IASP, during the conduct of the study; Reid C, Sjogren P, Stone PC, Tassinari D, Zeppetella G. Use of opioid in the pain: evidence-based personal fees from Heel, personal fees from Berlin Chemie, recommendations from the EAPC. Lancet Oncol 2012;13:e58–e68. outside the submitted work. R.-D. Treede reports grants from [11] Caraceni A, Portenoy RK; Working Group of the IASP Task Force on Boehringer Ingelheim, Astellas, AbbVie, Bayer, personal fees Cancer Pain. An international survey of cancer pain characteristics and from Astellas, Grunenthal, ¨ Bauerfeind, Hydra, Bayer, grants from syndromes. PAIN 1999;82:263–74. [12] Delanian S, Lefaix JL, Pradat PF. Radiation-induced neuropathy in cancer EU, DFG, BMBF, outside the submitted work. The remaining survivors. Radiother Oncol 2012;19:1985–91. authors have no conflicts of interest to declare. [13] Denham JW, Hauer-Jensen M. The radiotherapeutic injury—a complex “wound”. Radiother Oncol 2002;63:129–45. [14] Ducray F, Guillevin R, Psimaras D, Sanson M, Mokhtari K, Delanian S, Acknowledgements Navarro S, Maisonobe T, Cornu P, Hoang-Xuan K, Delattre JY, Pradat PF. Post-radiation lumbosacral radiculopathy with spinal root The authors gratefully acknowledge the financial support by the cavernomas mimicking carcinomatous meningitis. Neuro Oncol 2008; International Association for the Study of Pain and the excellent 10:1035–1039. discussions with Dr Robert Jakob of WHO. [15] Fainsinger RL, Nekolaichuk C, Lawlor P, Hagen N, Bercovitch M, Fisch M, Members of the Taskforce: Rolf-Detlef Treede (Chair), Winfried Galloway L, Kaye G, Landman W, Spruyt O, Zhukovsky D, Bruera E, Hanson J. An international multicentre validation study of a pain Rief (Co-chair), Antonia Barke, Qasim Aziz, Michael I. Bennett, classification system for cancer patients. Eur J Cancer 2010;46: Rafael Benoliel, Milton Cohen, Stefan Evers, Nanna B. Finnerup, 2896–904. Michael First, Maria Adele Giamberardino, Stein Kaasa, Beatrice [16] Falk S, Dickenson AH. Pain and : mechanisms of cancer- Korwisi, Eva Kosek, Patricia Lavand’homme, Michael Nicholas, induced . J Clin Oncol 2014;32:1647–54. Serge Perrot, Joachim Scholz, Stephan Schug, Blair H. Smith, [17] Fasanella KE, Davis B, Lyons J, Chen Z, Lee KK, Slivka A, Whitcomb DC, Guillevin R, Psimaras D, Sanson M, Mokhtari K, Delanian S, Navarro S, Peter Svensson, Johannes Vlaeyen, Shuu-Jiun Wang. Maisonobe T, Cornu P, Hoang-Xuan K, Delattre JY, Pradat PF. Pain in chronic pancreatitis and pancreatic cancer. Gastroenterol Clin North Am 2007;36:335–64. Appendix A. Supplemental digital content [18] Fathers E, Thrush D, Huson SM, Norman A. Radiation-induced brachial plexopathy in women treated for carcinoma of the breast. Clin Rehabil Supplemental digital content associated with this article can be 2002;16:160–5. found online at http://links.lww.com/PAIN/A658. SDC includes [19] Gagnon B, Scott S, Nadeau L, Lawlor P, Johnell K. Patterns of a complete reference list of the diagnoses entered into the community-based opioid prescriptions in people dying of cancer. foundation with the foundation IDs as well as the extension codes J Pain Symptom Manage 2015;49:36–44. (specifier). 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