The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: A descriptive cohort study

The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: A descriptive cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: A descriptive cohort study Merlina Sulistio, Natalie Ling, Tara Finkelstein, Hoong jiun Tee, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1988014/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Apr, 2023 Read the published version in Supportive Care in Cancer → Version 1 posted 8 You are reading this latest preprint version Abstract Purpose : We describe the prevalence of the Edmonton Classification System for Cancer Pain (ECS-CP) features in patients with bone metastasis and cancer-induced bone pain (CIBP) and the relationship between ECS-CP features, pain intensity and opioid consumption. Methods : We assessed ECS-CP features and recoded pain mechanisms and opioid use in adult patients with bone metastasis. Validated measures were used to assess pain intensity, incident pain, psychological distress, addictive behavior and cognition. Results : Among 147 eligible patients, 95.2% completed assessment. Mean participant age was 73.2 years, the majority female (52.1%) with breast cancer occurring most commonly (25.7%). One or more ECS-CP features were present in 96.4% and CIBP in 75.7% of patients. The median average and worst pain scores were 3 and 6, respectively. Neuropathic pain was the most prevalent pain mechanism (45.0%) and associated with breakthrough pain frequency (p=0.014). Three-quarters had incident pain, which was strongly associated with a higher average and worst pain scores (3.5 and 7, p<0.001 for both), background oral morphine equivalent daily dose (26.7mg, p=0.005), and frequency of daily breakthrough analgesia (1.7 doses/day, p=0.007). Psychological distress (n=90, 64.3%) was associated with significantly higher average pain score (4, p=0.009) and slightly higher worst pain score (7, p=0.054). Addictive behaviour and cognitive dysfunction were relatively uncommon (18.6% and 12.9%, respectively). Conclusion : There is a need to promote standardized assessment and classification of pain syndromes such as CIBP. The ECS-CP may allow us to consider CIBP in a systematic manner and develop personalized pain interventions appropriate to the pain profile. Trial registration in ANZCTR ACTRN12622000853741 (16/06/2022) retrospectively registered. pain control bone pain symptom assessment opioid Figures Figure 1 Figure 2 Figure 3 Introduction Bone is a common site of metastasis and usually suggests non-curative cancer with a limited prognosis [ 1 ]. The majority (up to 80%) of bone metastasis arises from breast, prostate and lung cancer [ 2 , 3 ], and in most cases, presents across multiple sites and involves the axial skeleton [ 4 ]. Significant morbidity and mortality are associated with bone metastasis due to complications such as hypercalcemia, pathological skeletal fractures, severe pain, impaired mobility, spinal cord compression and bone marrow failure [ 1 – 3 ]. Bone metastasis results in particularly debilitating chronic pain [ 5 ], which traditionally presents with a continuous background pain, accompanied by episodes of predictable incident and spontaneous breakthrough pain, significantly affecting the patient's overall quality of life [ 6 ]. Cancer-induced bone pain (CIBP) is now recognized as a complex pain syndrome involving nociceptive, inflammatory and neuropathic mechanisms [ 7 ]. The pathophysiology of pain in the setting of bone metastasis is related to the stimulation of inflammatory mediators and acidosis caused by bone destructing osteoclasts via the increased expression of the receptor activator of nuclear factor k-B ligand (RANKL), resulting in mechanical destabilization and fractures [ 3 , 8 ]. This, in turn, results in the sensitization and activation of mechanosensitive nerve fibers, destruction of sensory nerve endings and the pathological sprouting of sensory and sympathetic nerve fibers. The above contributes to peripheral and central sensitization of pain and the patient's experience of chronic cancer pain [ 3 , 9 ]. The prevalence of CIBP varies widely in the literature, with recent research confirming a prevalence of up to 92% [ 10 ]. A third of those with CIBP report severe pain, but clinical documentation of pain severity and the appropriate prescribing of analgesia remains unsatisfactory [ 10 ]. Up to a quarter of patients with CIBP suffer from neuropathic pain [ 11 ], and 40–75% report incident pain [ 11 , 6 ], often of rapid onset (< 5 mins) and short duration (< 15 minutes) [ 6 ]. Incident pain, in particular, significantly affects daily life function [ 6 ] and causes psychological distress in up to 40% of patients [ 12 ]. The combined characteristics of CIBP, limited available appropriate therapies and lack of standardized and routine screening contribute to ongoing reports of inadequately managed CIBP [ 8 , 9 ]. Optimal pain management starts with systematic screening and identifying pain mechanisms [ 13 ]. The Edmonton Classification System for Cancer Pain (ECS-CP) is a standardized international classification system for cancer pain that integrates five features that predict pain management complexity: mechanism of pain, incident pain, psychological distress, addictive behaviour and cognitive function [ 14 , 15 ]. A multicenter international validation study of the ECS-CP investigated 1100 cancer patients and described a pain syndrome in 86% [ 14 ]. Younger patients (< 60), those with neuropathic and incident pain, psychological distress and higher pain intensity required a longer time to achieve stable pain control [ 14 ]. Additionally, independent of age, this cohort also required a higher mean oral morphine equivalent daily dose (OMEDD) and more co-analgesics to achieve stable pain control [ 14 ]. The median days to stable pain control increased as the number of prognostic factors (neuropathic pain, incident pain, psychological distress, age < 60, and initial pain intensity) increased [ 16 ]. Further evaluation studies of the ECS-CP have identified neuropathic pain [ 17 ] and incident pain [ 11 ] as independent poor prognostic factors in cancer patients. With the multidimensional nature of CIBP, a standardized application of the ECS-CP classification system may assist in identifying patients requiring more intensive pain management. This study aimed to evaluate the prevalence of the ECS-CP pain classification features in a cohort of patients with CIBP. The secondary aim was to examine the relationship between the ECS-CP features, pain intensity, daily opioid consumption and breakthrough analgesic use. Ultimately, such a study may reveal the utility of the routine use of the ECS-CP in patient care. Method Study design and sample This was a cross-sectional survey of consecutive cancer patients with bone metastasis conducted at an 850-bed metropolitan teaching hospital in Melbourne, Australia. Participants were recruited from the inpatient and ambulatory setting. Eligibility included: patients 18 years and older with a diagnosis of solid tumour or haematological malignancy and confirmation of bone metastasis on imaging. Patients who were unable to complete clinical assessment due to a language barrier, cognitive impairment or deemed too unwell to participate as determined by treating clinicians were excluded. Ethics approval was obtained from the local research governance committee (No: 04-04-02-21), and completion of the survey as a component of routine care implied consent. Data and measures A single patient assessment was conducted to collect all study data. The following demographic data were documented: age, sex, primary cancer diagnosis and site of bone metastasis (categorized into long bones, spine, ribs and/or pelvis). The following additional instruments were used: Edmonton Classification System for Cancer Pain (ECS-CP) [18] The ECS-CP (Appendix 1) is an international pain classification tool that evolved from the original instrument, the Edmonton Staging System, which was initially developed as a prognostic indicator for cancer pain management. It potentially identifies patients who may require complex pain management and provides a common language for pain classification to enable standardized reporting in research. The five discrete features of the ECS-CP allow for the assignment of a pain classification profile: mechanism of pain (N), incident pain (I), psychological distress (P), addictive behaviour (A) and cognitive function (C). The presence of each discrete feature of the ECS-CP was determined as below: 1. Mechanism of pain The presence of nociceptive and/or neuropathic pain was determined at assessment by certified palliative care physicians through history taking, clinical examination and correlation of findings with known sites of bone metastases. Neuropathic pain was deemed present if pain descriptors such as burning, electric shocks, shooting, pricking, tingling, pins and needles, or signs of hyper/hypoaesthesia were described by the patient or found on examination. 2. Incident pain: Breakthrough Pain Assessment Tool (BAT) [19] The BAT was developed and validated for the assessment of breakthrough cancer pain over the previous week and comprises 14 questions (9 relating to pain, 5 to pain treatment). Breakthrough cancer pain is defined as a transient pain exacerbation in patients with stable and controlled basal pain and may occur spontaneously or following predictable or unpredictable triggers [20]. We assessed the following components of the BAT: average daily frequency of incident pain, typical duration and intensity of incident pain, and if any precipitating/relieving factors were present. 3. Psychological distress: Distress Thermometer (DT) [21] The DT is a validated, self-reported tool measuring patient distress over the previous week on a 0-to-10 rating scale (0-no distress, 10-extreme distress). Psychological distress was determined with a score ≥4 [22]. 4. Addictive behaviour: Cut down, Annoyed, Guilty and Eye-opener questionnaire adapted to include drugs (CAGE-AID) [23] CAGE-AID is a validated screening tool used to detect drug and alcohol abuse, exploring four questions, with 1 point allocated for each positive response. We used a conservative cut-off point of ≥1 to suggest addictive behaviour. This has the sensitivity of detecting 91% of alcohol and 92% of drug abusers who are >50 years old [23]. 5. Cognitive impairment: Short Orientation Memory Concentration Test (SOMCT) [24] The SOMCT is a 6-item memory and concentration test validated against neuropathology. It covers the assessment of orientation, concentration on a short task, and learning and recall of simple information. The patient scores 1 point for each incorrect answer, which is subsequently weighted (Appendix 2). The total score of SOMCT can discriminate between normal to minimal (0-8), minimal-moderate (9-19) and severe cognitive (20-28) impairment. Patients with severe cognitive impairment were excluded from the study. One point was allocated for each negative feature of the ECS-CP (presence of neuropathic pain, incident pain, psychological distress, addictive behaviour and/or cognitive impairment) [25], which allowed for the calculation of the ECS-CP composite score ranging from 0-5 (total of all negative pain features) [26]. The following were also assessed: Pain intensity: 11-point numerical rating scale (NRS-11) [27] Pain intensity in the previous 24 hours was measured using the NRS-11 with 0 representing no pain, 1-3 mild pain, 3-4 moderate pain and 7-10 severe pain. Patients were asked to rate their average and worst pain and the severity of their typical episode of breakthrough pain. Opioid requirements The use of background and breakthrough opioid medications were determined from the inpatient electronic Medication Management chartsor via direct participant reports or pain diaries foroutpatients. The total dose of background analgesia (oral and parenteral) over the previous 24 hours was calculated and converted to an OMEDD using established opioid conversion ratios [28].The frequency of breakthrough opioid analgesia (BTA) use in 24 hours was calculated by averaging the number of breakthrough doses over 72 hours. Establishment of bone metastasis The presence of bone metastasis was established by a review of radiological imaging and reports (plain film radiography, computed tomography, Technetium 99m bone scan, magnetic resonance imaging, and/or positron emission tomography) [4]. As CIBP most commonly arises from bone metastasis in the spine, pelvis, long bones and ribs [2,4,29], only metastasis at these four sites was reported in this study. Statistical analysis Patient demographics and pain characteristics were summarised using proportions for categorical variables, means and standard deviations (SDs) for normally distributed or medians and inter-quartile ranges (IQRs) for continuous skewed data. Mann-Whitney U test was used to examine the association between pain intensity, breakthrough pain characteristics and opioid requirements and the various ECS-CP features. Multivariable gamma regression analysis was used to analyze the relationship between ECSS-CP composite score and pain intensity while controlling for patients' age and sex. A two-tailed p-value <0.05 indicated statistical significance. Results Study participants Of the 147 eligible patients, 140 (95.2%) completed the survey (Figure 1). Patient demographic and clinical characteristics are shown in Table 1. The mean (SD) age was 73.2 (11.2) years, with 47.9% male. The most common primary cancers were breast (25.7%), lung (24.3%) and prostate (20.0%). Bone metastasis was most commonly found in the spine (82.9%), with most patients (64.3%) having metastases across multiple sites. Thirty-two (22.9%) patients had bone metastases at all four sites, twenty-five (17.9%) at any three sites and thirty-three (23.6%) patients at any two sites (Figure 2). CIBP was present in 75.7% of patients, affecting approximately two-thirds of those with spinal or pelvic metastasis and approximately half of those with long bone and rib metastasis (Figure 2). Table 1 Patient Demographics Patient Characteristics (n=140) n (%) Age, mean in years (SD) 73.2 (11.2) Male 67 (47.9) Primary diagnosis Breast 36 (25.7) Lung 34 (24.3) Prostate 28 (20.0) Gastrointestinal 14 (10) Haematology 12 (8.6) Other a 16 (11.4) Site of bone metastases b Spine 116 (82.9) Pelvis 78 (55.7) Rib 66 (47.1) Long bone 59 (42.1) a Genitourinary, other than prostate cancer (n=8), melanoma (n=3), carcinoma of unknown primary and other cancers (n=5). b The overall percentage is greater than 100% as multiple variables apply to some participants Pain and analgesia Table 2 summarizes reported pain scores and analgesic use. The median reported average and worst pain intensity were 3 and 6, respectively. Moderate to severe (NRS average and worst pain was reported by 42.8% and 67.6% of patients, respectively. Up to three-quarters of patients had been prescribed a background opioid. The median background opioid OMEDD was 25.8mg, and the median frequency of breakthrough opioid use was 1.3 doses/ day. Oxycodone was the most commonly prescribed background (34.0%) and breakthrough (44.6%) opioid. Table 2 Pain features and Opioid Use Pain intensity n (%) Average pain (n=140), median (IQR) 3 (.75-5) No pain (0) 34 (24.3) Mild (1-3) 46 (32.9) Moderate (4-6) 44 (31.4) Severe (7+) 16 (11.4) Worst pain (n=139), median (IQR) 6 (2-8) No pain (0) 27 (19.4) Mild (1-3) 18 (13.0) Moderate (4-6) 27 (19.4) Severe (7+) 67 (48.2) Pain mechanism Nociceptive 51 (36.4) Neuropathic with/without nociceptive 63 (45.0) No pain syndrome 24 (17.1) Insufficient data to classify 2 (1.4) Incident pain 104 (74.3) Frequency Less than once a day 15 (14.4) 1-2 times a day 27 (26.0) 3-4 times a day 33 (31.7) >4 times a day 29 (27.9) Duration 60min 15 (14.4) Missing data 2 (1.9) Typical pan intensity (n=70), median (IQR) 6 (4.25-8) Psychological distress Distress thermometer (median, IQR) 90 (64.3) 5 (2-7) Addictive behaviour CAGE-AID score (median, IQR) 26 (18.6) 0 (0) Cognitive impairment SOMCT (median, IQR) 18 (12.9) 4 (0-6) Opioid Use Background opioid (n=103) Oxycodone 35/103 (34.0) Fentanyl 20/103 (19.4) Methadone 16/103 (15.5) Morphine 15/103 (14.6) Hydromorphone 9/103 (8.7) Others 8/103 (7.8) OMEDD, median in mg (IQR) 25.8 (6.7-47) Breakthrough opioid a (n=101) Oxycodone 45/101 (44.6) Fentanyl 33 /101 (32.7) Morphine 24/101 (23.8) Hydromorphone 18/101 (17.8) Others 2/101 (2.0) Daily frequency, median number of doses (IQR) 1.3 (0.3-2.7) CAGE-AID, Cut down, annoyed, guilty, and eye-opener-adapted to include drugs; ECS-CP, Edmonton classification system for cancer pain; IQR, Interquartile range; OMEDD, oral morphine equivalent daily dose; SOMCT, Short orientation memory concentration test a The overall percentage is greater than 100% as multiple variables apply to some participants Edmonton Classification System for Cancer Pain (ECS-CP) Features One or more ECS-CP features were present in 135 patients (Table 2). Neuropathic pain was reported in 45% of patients and was associated with a higher reported frequency of breakthroughs (p=0.014). Although it was the most prevalent mechanism of pain reported, it did not impact pain intensity or opioid requirements (Table 3). Three-quarters of patients reported having incident pain , with a reported median incident pain score of 6. Over half of patients reported a daily average of ≥ three episodes of incident pain; for 52.9% of patients, these episodes lasted ≤ 15 minutes. Of the ninety-one patients who identified triggers to their incident pain, the majority of patients had predictable pain with movement. The presence of incident pain was strongly associated with a higher average and worst pain scores (p<0.001 for both), higher background OMEDD (p=0.005) and a higher frequency of daily BTA use (p=0.007) (Table 2). Table 3 Association between the Edmonton Classification System for Cancer Pain features, pain intensity and Opioid requirement* ECSCP Features Average pain Worst pain Background OMEDD # , mg Breakthrough Opioid frequency # Pain mechanism Nociceptive Neuropathic 3 (2-5) 4 (2-5) P=0.510 6.5 (3-8) 7 (5-9) P=0.105 25 (6.7-47) 26.7 (4.8-60) P=0.539 1.5 (1-3) 1.3 (0.3-2.8) P=0.746 Incident pain Present Absent 3.5 (2-5) 0 (0-2) P<0.001 7 (5-8) 0 (0-4) P<0.001 26.7 (6.7-60.0) 11.7 (6.7-18.0) P=0.005 1.7 (0.7-3.0) 0.7 (0.3-1.3) P=0.007 Psychological distress Present Absent 4 (0.5-5) 2 (1-3) P=0.009 7 (2-8) 5 (2-7) P=0.054 26.7 (6.7-60.0) 23.5 (1.2-30.0) P=0.238 1.2 (0.3-2.8) 1.3 (0.7-2.8) P=0.988 Addictive behaviour Present Absent 4 (2-5) 2 (0-4) P=0.099 6.5 (5-8) 6 (2-8) P=0.497 33.8 (7.0-60) 21.8 (6.7-40.0) P=0.268 2.0 (0.3-3.3) 1.0 (0.3-2.3) P=0.217 Cognitive dysfunction Present Absent 4 (0-6) 3 (0.75-4) P=0.298 7 (0-8) 6 (2-8) P=0.825 30 (18-60) 24 (3.2-47) P=0.221 1.0 (0.7-1.7) 1.3 (0.3-3) P=0.409 OMEDD, Oral Morphine Equivalent Daily Dose *Mann-Whitney U-test; # values are based on those who had opioids Results reported as median (IQR) Two-thirds of patients reported psychological distress , associated with significantly higher average pain scores (p=0.009) and slightly higher worst pain scores (p=0.054). However, no correlation with opioid requirements was found (Tables 2 and 3). Addictive behaviour and cognitive dysfunction were relatively uncommon (18.6% and 12.9%, respectively) and were not associated with pain intensity or opioid requirements. The association between pain and ECS-CP composite score is depicted in Figure 3. Higher average and worst pain were associated with higher ECS-CP composite scores (p<0.001 for both). This association remained significant after adjustment for a patient’s age and gender, with a 1-point increase in the ECS-CP composite score leading to 43.6% (95% CI 22.6-68.2) and 46.9% (95% CI 28.5-67.9) increases in average and worst pain respectively. Discussion This is the first study to systematically explore the ECS-CP features in a cohort of adult cancer patients with bone metastasis and CIBP. We confirm the previously reported high prevalence of neuropathic pain, incident pain and psychological distress in cancer patients with bone metastases, with spinal metastasis being the most common site for CIBP. We detected a strong association between incident pain, psychological distress and pain intensity, with incident pain being the only factor associated with higher opioid requirements (background OMEDD and daily BTA frequency). Finally, we describe sites of metastasis, with the spine as the most common site and correlated reports of CIBP at these sites as previously reported [29]. Current treatment for CIBP can be classified into anticancer treatments (local radiotherapy, radioisotopes and systemic chemotherapeutics and immunotherapy), analgesic treatment using opioids, anti-inflammatory drugs and co-analgesics (antidepressants, anticonvulsants and gabapanetinoids), bone-targeted therapies (such as bisphosphonate and denosumab) and surgery [3,8]. Local radiotherapy, a commonly used modality has a reported pain response rate of 61% with a median response time of 4 weeks [30]. Whilst there has been increased interest in the study of bone pain [31], a translational paradigm has not successfully allowed the pathophysiology and mechanism of CIBP to inform the choice of pharmacotherapeutics [32]. Opioids remain the mainstay treatment with no evidence to guide the choice of the opioid molecule [3]. More recently, a multicenter randomized controlled study of 223 patients with CIBP receiving radiotherapy was allocated to receive pregabalin (targeting the neuropathic element of CIBP) or placebo. The study findings did not support the role of pregabalin in CIBP, with no significant difference in average pain or pain interference compared to placebo [33]. In recognition of the ongoing challenges of managing complex cancer pain, recommendations have been made for developing and implementing a widely recognized and standardized taxonomy and classification system for cancer pain [34]. More recently, the International Classification of Disease–11 was updated to reflect a new classification system for chronic cancer pain to aid the development of individualized management plans and stimulate research in pain syndromes [35]. Chronic cancer pain is now subdivided in this new classification system into four categories: visceral, bone, neuropathic and 'other', such as chronic bone cancer pain and chronic neuropathic pain. Thus far, the ECS-CP remains the most validated classification system for cancer pain [18]. The ECS-CP highlights the multidimensional nature of pain assessment and classification, delineating distinct and independent categories that can influence pain management outcomes. When compared to published data on ECS-CP features in cancer patients, our cohort with bone metastases reported a higher prevalence of neuropathic pain features (45% vs 16.9-35%) [11,14,36,26,17], experienced more incident pain (74.3% vs 28-61%) [11,37,14,36,26,17], psychological distress (64.3% vs 25-52.7%) [14,36,26,17] and addictive behaviour (18.6% vs 4-11%) [14,36,26,17], but reported a similar prevalence of cognitive dysfunction (12.9% vs 3-21%) [14,36,26,17]. We also reported a similar average (3 vs 4) and worst (6 vs 7) pain scores to that found in a regional European oncology cohort of fifty-five patients with bone metastasis [6]. Despite confirming the influence of incident pain on average and worst pain intensity, we did not observe a relationship between neuropathic pain, pain intensity and OMEDD use as reported in other studies [14,26,17]. Finally, we demonstrated a correlation between the ECS-CP composite scores and pain intensity. A retrospective study of 386 American cancer patients showed that those with neuropathic pain were less likely to achieve their pain goals [17]. This is unsurprising as neuropathic pain remains a significant unmet medical need, requiring a multimodal approach to care [38]. It is challenging to ascertain clearly in our study if the neuropathic element reported arose specifically from CIBP, commonly described mixed cancer pain or cancer treatments [39,40]. Nonetheless, its identification through routine screening is critical for considering appropriate pharmacotherapeutics [41] and other modalities due to the strong known association between poorly controlled neuropathic pain and overall quality of life [42]. Likewise, a multicenter international study of 606 patients with bone metastases confirmed the relationship between incident pain and worst pain intensity and its negative prognostic value at a month follow-up [11]. Incident pain is a subtype of breakthrough pain that occurs with normal voluntary (e.g. walking) or involuntary (e.g. cough) movement but is typically absent at rest [37]. Our findings with participants reporting an average of 3 breakthrough episodes a day, commonly lasting 5-15 minutes, mirror that of a European study of the characteristics of breakthrough cancer pain in 1000 oncology patients [37]. However, an ongoing challenge in clinical practice is the lack of congruence between the temporal pattern of the predictable incident pain that commonly occurs in CIBP (rapid onset and short duration) and the pharmacokinetics of the immediate release opioids currently prescribed. Commonly used immediate release formulations of oxycodone, morphine and hydromorphone (Table 2) provide a delayed onset of analgesia compared to the onset of incident pain. Thus, the onset of analgesia occurs after the episode of pain subsides, and the effects of analgesia last beyond the episode of pain. This, in turn, leads to patients commonly complaining of opioid-induced adverse effects. Thus, formulations of opioids with a rapid onset of analgesia and short duration of action, mimicking the temporal pattern of predictable incident pain in CIBP, may be the more appropriate opioid of choice [43]. This study has several limitations, being a single-site study of cancer patients with CIBP. We did not record data on non-opioid analgesics/ co-analgesics which may have affected overall pain scores and may explain the cohort of patients who report no CIBP. We only reported pain from the four most common sites of bone metastases. Using a standardized tool to screen for neuropathic pain, such as the Leeds Assessment of Neuropathic Symptom and Signs [44] or the Douleur Neuropathique 4 [45], may have improved our reporting and assessment of neuropathic pain. Finally, our ECS-CP composite score requires interpretation with caution as the number of patients with pain scores ≥4 remains small. Clinical Implications Considering the complexity of the pathophysiology of CIBP, the ECS-CP may allow us to consider CIBP more systematically and thus develop personalized pain management interventions according to the pain profile identified. It further allows for targeting more specialized input for patients with a high prevalence of neuropathic or incident pain and psychological distress. Targeted intervention studies may further demonstrate the utility of the ECS-CP in the clinical setting. Conclusion There is a need to promote a more standardized way to assess and classify pain syndromes such as CIBP. Our approach requires consideration of the multifactorial aetiology of CIBP that includes nociceptive, inflammatory and neuropathic components and warrants various modalities to manage symptoms in conjunction with disease-modifying therapies. Epidemiological, clinical and translational data may provide the avenues for us to consider how we further target and manage CIBP for each individual that experiences it. Declarations Ethics approval and consent to participate The study was approved by the Cabrini Research Governance Office (Approval Number 04-04-02-21). Completion of questionnaires as part of routine care implied consent. Consent for publication Not applicable Availability of data and materials Cabrini Research Institute retains primary control of the data presented in this manuscript. Data may be made available for external review if permission is obtained from the Cabrini Research Institute. Competing interests NM is an advisory board member of Menarini Australia Ltd. The remaining authors have no relevant financial or non-financial interests to disclose. Funding NL and TF were supported by the Cabrini Institute Medical Staff Research Scholarship. Authors’ Contributions MS and NM were involved in study conception and design. Data collection were performed by NL, TF, PT, NM and MS, with verification and quality control checked by MS. AG assisted with statistical analysis and DK, NM and MS were involved in data interpretation. All authors contributed and approved the final manuscript. Acknowledgements We thank all the staff and patients of Cabrini Supportive and Palliative care service for their input into this study. This study has been completed through funding support from the Cabrini Institute Medical Staff Research Scholarship. References Macedo F, Ladeira K, Pinho F, Saraiva N, Bonito N, Pinto L, Goncalves F (2017) Bone Metastases: An Overview. Oncol Rev 11 (1):321. doi: 10.4081/oncol.2017.321 Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12 (20 Pt 2):6243s-6249s. doi: 10.1158/1078-0432.CCR-06-0931 Zajaczkowska R, Kocot-Kepska M, Leppert W, Wordliczek J (2019) Bone Pain in Cancer Patients: Mechanisms and Current Treatment. Int J Mol Sci 20 (23). doi: 10.3390/ijms20236047 O'Sullivan GJ, Carty FL, Cronin CG (2015) Imaging of bone metastasis: An update. World J Radiol 7 (8):202–211. doi: 10.4329/wjr.v7.i8.202 Ahmad I, Ahmed MM, Ahsraf MF, Naeem A, Tasleem A, Ahmed M, Farooqi MS (2018) Pain Management in Metastatic Bone Disease: A Literature Review. Cureus 10 (9):e3286. doi: 10.7759/cureus.3286 Laird BJ, Walley J, Murray GD, Clausen E, Colvin LA, Fallon MT (2011) Characterization of cancer-induced bone pain: an exploratory study. Support Care Cancer 19 (9):1393–1401. doi: 10.1007/s00520-010-0961-3 Falk S, Dickenson AH (2014) Pain and nociception: mechanisms of cancer-induced bone pain. J Clin Oncol 32 (16):1647–1654. doi: 10.1200/JCO.2013.51.7219 Middlemiss T, Laird BJ, Fallon MT (2011) Mechanisms of cancer-induced bone pain. Clinical oncology (Royal College of Radiologists (Great Britain)) 23 (6):387–392. doi: 10.1016/j.clon.2011.03.003 Mantyh PW (2014) Bone cancer pain: from mechanism to therapy. Curr Opin Support Palliat Care 8 (2):83–90. doi: 10.1097/SPC.0000000000000048 Vieira C, Fragoso M, Pereira D, Medeiros R (2019) Pain prevalence and treatment in patients with metastatic bone disease. Oncol Lett 17 (3):3362–3370. doi: 10.3892/ol.2019.10013 Habberstad R, Hjermstad MJ, Brunelli C, Kaasa S, Bennett MI, Pardon K, Klepstad P (2019) Which factors can aid clinicians to identify a risk of pain during the following month in patients with bone metastases? A longitudinal analyses. Support Care Cancer 27 (4):1335–1343. doi: 10.1007/s00520-018-4405-9 Canal-Sotelo J, Trujillano-Cabello J, Larkin P, Arraras-Torrelles N, Gonzalez-Rubio R, Rocaspana-Garcia M, Barallat-Gimeno E (2018) Prevalence and characteristics of breakthrough cancer pain in an outpatient clinic in a Catalan teaching hospital: incorporation of the Edmonton Classification System for Cancer pain into the diagnostic algorithm. BMC Palliat Care 17 (1):81. doi: 10.1186/s12904-018-0336-y Caraceni A, Shkodra M (2019) Cancer Pain Assessment and Classification. Cancers (Basel) 11 (4). doi: 10.3390/cancers11040510 Fainsinger RL, Nekolaichuk C, Lawlor P, Hagen N, Bercovitch M, Fisch M, Galloway L, Kaye G, Landman W, Spruyt O, Zhukovsky D, Bruera E, Hanson J (2010) An international multicentre validation study of a pain classification system for cancer patients. Eur J Cancer 46 (16):2896–2904. doi: 10.1016/j.ejca.2010.04.017 Nekolaichuk CL, Fainsinger RL, Lawlor PG (2005) A validation study of a pain classification system for advanced cancer patients using content experts: the Edmonton Classification System for Cancer Pain. Palliat Med 19 (6):466–476. doi: 10.1191/0269216305pm1055oa Nekolaichuk CLF, R. L.; Lawlor, P.; Hagen, N.; Berkovitch, M.; Fisch, M.; Galloway, L.; Kaye, G.; Landman, W.; Spruyt, O.; Zhukovsky, D.; Bruera, E.; Hanson, J. (2010) A predictive model for identifying complex cancer pain syndromes in patients referred to specialist palliative care services using a pain classification system [abstract].. Palliat Med 24 (4) Arthur J, Tanco K, Haider A, Maligi C, Park M, Liu D, Bruera E (2017) Assessing the prognostic features of a pain classification system in advanced cancer patients. Support Care Cancer 25 (9):2863–2869. doi: 10.1007/s00520-017-3702-z Lawlor PG, Lawlor NA, Reis-Pina P (2018) The Edmonton Classification System for Cancer Pain: a tool with potential for an evolving role in cancer pain assessment and management. Expert Review of Quality of Life in Cancer Care 3 (2–3):47–64. doi: 10.1080/23809000.2018.1467211 Webber K, Davies AN, Zeppetella G, Cowie MR (2014) Development and validation of the breakthrough pain assessment tool (BAT) in cancer patients. J Pain Symptom Manage 48 (4):619–631. doi: 10.1016/j.jpainsymman.2013.10.026 Davies AN, Dickman A, Reid C, Stevens AM, Zeppetella G, Science Committee of the Association for Palliative Medicine of Great B, Ireland (2009) The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. Eur J Pain 13 (4):331–338. doi: 10.1016/j.ejpain.2008.06.014 Ownby KK (2019) Use of the Distress Thermometer in Clinical Practice. J Adv Pract Oncol 10 (2):175–179 Donovan KA, Grassi L, McGinty HL, Jacobsen PB (2014) Validation of the distress thermometer worldwide: state of the science. Psychooncology 23 (3):241–250. doi: 10.1002/pon.3430 Hinkin CH, Castellon SA, Dickson-Fuhrman E, Daum G, Jaffe J, Jarvik L (2001) Screening for drug and alcohol abuse among older adults using a modified version of the CAGE. Am J Addict 10 (4):319–326 Wade DT, Vergis E (1999) The Short Orientation-Memory-Concentration Test: a study of its reliability and validity. Clin Rehabil 13 (2):164–170. doi: 10.1191/026921599673848768 Bruera E, Schoeller T, Wenk R, MacEachern T, Marcelino S, Hanson J, Suarez-Almazor M (1995) A prospective multicenter assessment of the Edmonton staging system for cancer pain. J Pain Symptom Manage 10 (5):348–355. doi: 10.1016/0885-3924(95)00052-z Arthur J, Yennurajalingam S, Nguyen L, Tanco K, Chisholm G, Hui D, Bruera E (2015) The routine use of the Edmonton Classification System for Cancer Pain in an outpatient supportive care center. Palliat Support Care 13 (5):1185–1192. doi: 10.1017/S1478951514001205 Atisook R, Euasobhon P, Saengsanon A, Jensen MP (2021) Validity and Utility of Four Pain Intensity Measures for Use in International Research. J Pain Res 14:1129–1139. doi: 10.2147/JPR.S303305 Caraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, Dale O, De Conno F, Fallon M, Hanna M, Haugen DF, Juhl G, King S, Klepstad P, Laugsand EA, Maltoni M, Mercadante S, Nabal M, Pigni A, Radbruch L, Reid C, Sjogren P, Stone PC, Tassinari D, Zeppetella G, European Palliative Care Research C, European Association for Palliative C (2012) Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. The Lancet Oncology 13 (2):e58-68. doi: 10.1016/S1470-2045(12)70040-2 Kakhki VR, Anvari K, Sadeghi R, Mahmoudian AS, Torabian-Kakhki M (2013) Pattern and distribution of bone metastases in common malignant tumors. Nucl Med Rev Cent East Eur 16 (2):66–69. doi: 10.5603/NMR.2013.0037 van der Velden JM, van der Linden YM, Versteeg AL, Verlaan JJ, Sophie Gerlich A, Pielkenrood BJ, Kasperts N, Verkooijen HM (2018) Evaluation of effectiveness of palliative radiotherapy for bone metastases: a prospective cohort study. J Radiat Oncol 7 (4):325–333. doi: 10.1007/s13566-018-0363-6 Zhen G, Fu Y, Zhang C, Ford NC, Wu X, Wu Q, Yan D, Chen X, Cao X, Guan Y (2022) Mechanisms of bone pain: Progress in research from bench to bedside. Bone Res 10 (1):44. doi: 10.1038/s41413-022-00217-w Park SH, Eber MR, Widner DB, Shiozawa Y (2018) Role of the Bone Microenvironment in the Development of Painful Complications of Skeletal Metastases. Cancers (Basel) 10 (5):141. doi: 10.3390/cancers10050141 Fallon M, Hoskin PJ, Colvin LA, Fleetwood-Walker SM, Adamson D, Byrne A, Murray GD, Laird BJ (2016) Randomized Double-Blind Trial of Pregabalin Versus Placebo in Conjunction With Palliative Radiotherapy for Cancer-Induced Bone Pain. J Clin Oncol 34 (6):550–556. doi: 10.1200/JCO.2015.63.8221 Bennett MI (2010) Cancer pain terminology: time to develop a taxonomy that promotes good clinical practice and allows research to progress. Pain 149 (3):426–427. doi: 10.1016/j.pain.2010.01.013 Bennett MI, Kaasa S, Barke A, Korwisi B, Rief W, Treede RD, Pain ITftCoC (2019) The IASP classification of chronic pain for ICD-11: chronic cancer-related pain. Pain 160 (1):38–44. doi: 10.1097/j.pain.0000000000001363 Nekolaichuk CL, Fainsinger RL, Aass N, Hjermstad MJ, Knudsen AK, Klepstad P, Currow DC, Kaasa S, European Palliative Care Research C (2013) The Edmonton Classification System for Cancer Pain: comparison of pain classification features and pain intensity across diverse palliative care settings in eight countries. J Palliat Med 16 (5):516–523. doi: 10.1089/jpm.2012.0390 Davies A, Buchanan A, Zeppetella G, Porta-Sales J, Likar R, Weismayr W, Slama O, Korhonen T, Filbet M, Poulain P, Mystakidou K, Ardavanis A, O'Brien T, Wilkinson P, Caraceni A, Zucco F, Zuurmond W, Andersen S, Damkier A, Vejlgaard T, Nauck F, Radbruch L, Sjolund KF, Stenberg M (2013) Breakthrough cancer pain: an observational study of 1000 European oncology patients. J Pain Symptom Manage 46 (5):619–628. doi: 10.1016/j.jpainsymman.2012.12.009 Davis MP (2018) Cancer-Related Neuropathic Pain: Review and Selective Topics. Hematology/oncology clinics of North America 32 (3):417–431. doi: 10.1016/j.hoc.2018.01.005 Lee DY, Lee JJ, Richeimer SH (2021) Cancer Pain Syndromes. Cancer Treat Res 182:17–25. doi: 10.1007/978-3-030-81526-4_2 Fallon MT (2013) Neuropathic pain in cancer. Br J Anaesth 111 (1):105–111. doi: 10.1093/bja/aet208 Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M (2015) Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14 (2):162–173. doi: 10.1016/S1474-4422(14)70251-0 Ulas S, Eyigor S, Caramat I (2018) Quality of Life and Neuropathic Pain in Hospitalized Cancer Patients: A Comparative Analysis of Patients in Palliative Care Wards Versus Those in General Wards. Indian J Palliat Care 24 (3):325–333. doi: 10.4103/IJPC.IJPC_12_18 Brzakala J, Leppert W (2019) The role of rapid onset fentanyl products in the management of breakthrough pain in cancer patients. Pharmacol Rep 71 (3):438–442. doi: 10.1016/j.pharep.2019.01.010 Bennett M (2001) The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain 92 (1–2):147–157. doi: 10.1016/s0304-3959(00)00482-6 Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lanteri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E (2005) Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114 (1–2):29–36. doi: 10.1016/j.pain.2004.12.010 Additional Declarations Competing interest reported. NM is an advisory board member of Menarini Australia Ltd. The remaining authors have no relevant financial or non-financial interests to disclose. Supplementary Files Appendix1.docx Appendix2.docx Cite Share Download PDF Status: Published Journal Publication published 28 Apr, 2023 Read the published version in Supportive Care in Cancer → Version 1 posted Editorial decision: Major revision 24 Oct, 2022 Reviews received at journal 18 Oct, 2022 Reviewers agreed at journal 07 Oct, 2022 Reviewers agreed at journal 08 Sep, 2022 Reviewers invited by journal 08 Sep, 2022 Editor assigned by journal 08 Sep, 2022 Submission checks completed at journal 07 Sep, 2022 First submitted to journal 22 Aug, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1988014","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":134837316,"identity":"23f379ca-dc73-45f0-a1be-1a83de8b7b33","order_by":0,"name":"Merlina Sulistio","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYDAC/saGAwk//snxszeAuMxAnEBAi8Thxgcfew4YS/YcIFYLQ3qz4Qy2A4kbbiQQqUW+4WCbNA/PncQNN1+nSTDusGbgZ88xYPjZhluLweFGoBaLZ8Yzb+duk2A8k84g2fPGgLEXnxYGsC3Msn1gLW2HGQxuAG3hxaNFviERqIWNmbHh5lmIFnugFsa/eLQwHEgEef+w4oQbvFBbJHIMmPHZYnDjICiQ04CBnLvZIrEtnUfizLOCwzLn8Disv/0BMCptgFF5duONj23WcvztyRsfvinD4zAkwCKRwMDAA3YtcRqA0fiBWJWjYBSMglEwsgAA+05ZUFsja6IAAAAASUVORK5CYII=","orcid":"","institution":"University of Notre Dame Australia","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Merlina","middleName":"","lastName":"Sulistio","suffix":""},{"id":134837317,"identity":"22081d44-5bb0-45e1-a8ef-cd4d456015b0","order_by":1,"name":"Natalie Ling","email":"","orcid":"","institution":"Monash University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Natalie","middleName":"","lastName":"Ling","suffix":""},{"id":134837318,"identity":"4f5103d7-da62-4e3f-9444-7733c68a6c42","order_by":2,"name":"Tara Finkelstein","email":"","orcid":"","institution":"Monash University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tara","middleName":"","lastName":"Finkelstein","suffix":""},{"id":134837319,"identity":"7f20299f-b9fd-427e-b82c-56bc900d1cbe","order_by":3,"name":"Hoong jiun Tee","email":"","orcid":"","institution":"Cabrini Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hoong","middleName":"jiun","lastName":"Tee","suffix":""},{"id":134837320,"identity":"c4f53309-8e67-43a2-b065-aa3c606adfd4","order_by":4,"name":"Alexandra Gorelik","email":"","orcid":"","institution":"Cabrini Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alexandra","middleName":"","lastName":"Gorelik","suffix":""},{"id":134837321,"identity":"f98e5280-3d4a-43d6-be3d-98798a5ff4f2","order_by":5,"name":"David Kissane","email":"","orcid":"","institution":"University of Notre Dame Australia","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Kissane","suffix":""},{"id":134837322,"identity":"9740f988-bf40-4d12-8819-a86e95a97711","order_by":6,"name":"Natasha Michael","email":"","orcid":"","institution":"Cabrini Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Natasha","middleName":"","lastName":"Michael","suffix":""}],"badges":[],"createdAt":"2022-08-23 01:44:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1988014/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1988014/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00520-023-07711-9","type":"published","date":"2023-04-28T20:37:57+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":26360247,"identity":"972a9662-9cd2-4011-a6ba-234a394f1da7","added_by":"auto","created_at":"2022-09-12 18:54:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":38343,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubject selection\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1988014/v1/74200e65107058ffd83f2688.png"},{"id":26360248,"identity":"7ee73a69-2ce7-4312-8563-590ec28e0a31","added_by":"auto","created_at":"2022-09-12 18:54:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":121255,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea Distribution of bone metastases in patients(n=140)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb Distribution of \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003epainful\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e bone metastases in patients (n=106)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1988014/v1/87b6473ee543ccc2df2ffe21.png"},{"id":26360527,"identity":"609f2bb0-5ad2-49b6-900c-8351809c7ead","added_by":"auto","created_at":"2022-09-12 18:59:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":23540,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssociation of ECS-CP composite score and pain intensity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eECS-CP, Edmonton classification system for cancer pain\u003c/p\u003e\n\u003cp\u003eECS-CP composite score 0 to 5; n (%), respectively: 5 (3.6), 37 (26.4), 44 (31.4), 38 (27.1), 15 (10.7), 1 (0.7).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1988014/v1/070c58b16b1903d31e2bc567.png"},{"id":44729405,"identity":"8fc302a0-1acb-41f1-be47-2f06cea7fb63","added_by":"auto","created_at":"2023-10-16 21:15:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":807995,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1988014/v1/32ed4d3f-a63b-42ac-9e8c-fb022c6a1bc1.pdf"},{"id":26360251,"identity":"ad400ef8-6ab1-4e67-8e8f-6bb093060ede","added_by":"auto","created_at":"2022-09-12 18:54:22","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":625823,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix1.docx","url":"https://assets-eu.researchsquare.com/files/rs-1988014/v1/c7c1e2aee2a2fc386c2037fc.docx"},{"id":26360250,"identity":"d67f2b04-e90d-405f-b358-df5fda8c4d1f","added_by":"auto","created_at":"2022-09-12 18:54:22","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":96096,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix2.docx","url":"https://assets-eu.researchsquare.com/files/rs-1988014/v1/8dcc8ca4a51e558c9507535f.docx"}],"financialInterests":"Competing interest reported. NM is an advisory board member of Menarini Australia Ltd. The remaining authors have no relevant financial or non-financial interests to disclose.","formattedTitle":"The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: A descriptive cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBone is a common site of metastasis and usually suggests non-curative cancer with a limited prognosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The majority (up to 80%) of bone metastasis arises from breast, prostate and lung cancer [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and in most cases, presents across multiple sites and involves the axial skeleton [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Significant morbidity and mortality are associated with bone metastasis due to complications such as hypercalcemia, pathological skeletal fractures, severe pain, impaired mobility, spinal cord compression and bone marrow failure [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Bone metastasis results in particularly debilitating chronic pain [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], which traditionally presents with a continuous background pain, accompanied by episodes of predictable incident and spontaneous breakthrough pain, significantly affecting the patient's overall quality of life [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCancer-induced bone pain (CIBP) is now recognized as a complex pain syndrome involving nociceptive, inflammatory and neuropathic mechanisms [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The pathophysiology of pain in the setting of bone metastasis is related to the stimulation of inflammatory mediators and acidosis caused by bone destructing osteoclasts via the increased expression of the receptor activator of nuclear factor k-B ligand (RANKL), resulting in mechanical destabilization and fractures [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This, in turn, results in the sensitization and activation of mechanosensitive nerve fibers, destruction of sensory nerve endings and the pathological sprouting of sensory and sympathetic nerve fibers. The above contributes to peripheral and central sensitization of pain and the patient's experience of chronic cancer pain [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe prevalence of CIBP varies widely in the literature, with recent research confirming a prevalence of up to 92% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A third of those with CIBP report severe pain, but clinical documentation of pain severity and the appropriate prescribing of analgesia remains unsatisfactory [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Up to a quarter of patients with CIBP suffer from neuropathic pain [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and 40\u0026ndash;75% report incident pain [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], often of rapid onset (\u0026lt;\u0026thinsp;5 mins) and short duration (\u0026lt;\u0026thinsp;15 minutes) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Incident pain, in particular, significantly affects daily life function [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and causes psychological distress in up to 40% of patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The combined characteristics of CIBP, limited available appropriate therapies and lack of standardized and routine screening contribute to ongoing reports of inadequately managed CIBP [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOptimal pain management starts with systematic screening and identifying pain mechanisms [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The Edmonton Classification System for Cancer Pain (ECS-CP) is a standardized international classification system for cancer pain that integrates five features that predict pain management complexity: mechanism of pain, incident pain, psychological distress, addictive behaviour and cognitive function [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A multicenter international validation study of the ECS-CP investigated 1100 cancer patients and described a pain syndrome in 86% [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Younger patients (\u0026lt;\u0026thinsp;60), those with neuropathic and incident pain, psychological distress and higher pain intensity required a longer time to achieve stable pain control [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Additionally, independent of age, this cohort also required a higher mean oral morphine equivalent daily dose (OMEDD) and more co-analgesics to achieve stable pain control [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The median days to stable pain control increased as the number of prognostic factors (neuropathic pain, incident pain, psychological distress, age\u0026thinsp;\u0026lt;\u0026thinsp;60, and initial pain intensity) increased [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Further evaluation studies of the ECS-CP have identified neuropathic pain [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and incident pain [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] as independent poor prognostic factors in cancer patients.\u003c/p\u003e \u003cp\u003eWith the multidimensional nature of CIBP, a standardized application of the ECS-CP classification system may assist in identifying patients requiring more intensive pain management. This study aimed to evaluate the prevalence of the ECS-CP pain classification features in a cohort of patients with CIBP. The secondary aim was to examine the relationship between the ECS-CP features, pain intensity, daily opioid consumption and breakthrough analgesic use. Ultimately, such a study may reveal the utility of the routine use of the ECS-CP in patient care.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003e\u003cstrong\u003eStudy design and sample\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a cross-sectional survey of consecutive cancer patients with bone metastasis conducted at an 850-bed metropolitan teaching hospital in Melbourne, Australia. Participants were recruited from the inpatient and ambulatory setting. Eligibility included: patients 18 years and older with a diagnosis of solid tumour or haematological malignancy and confirmation of bone metastasis on imaging. Patients who were unable to complete clinical assessment due to a language barrier, cognitive impairment or deemed too unwell to participate as determined by treating clinicians were excluded. Ethics approval was obtained from the local research governance committee (No:\u0026nbsp;04-04-02-21), and completion of the survey as a component of routine care implied consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData and measures\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA single patient assessment was conducted to collect all study data. The following demographic data were documented: age, sex, primary cancer diagnosis and site of bone metastasis (categorized into long bones, spine, ribs and/or pelvis). The following additional instruments were used:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEdmonton Classification System for Cancer Pain\u003c/em\u003e\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003e(ECS-CP)\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e[18]\u003c/p\u003e\n\u003cp\u003eThe ECS-CP (Appendix 1) is an international pain classification tool that evolved from the original instrument, the Edmonton Staging System, which was initially developed as a prognostic indicator for cancer pain management. It potentially identifies patients who may require complex pain management and provides a common language for pain classification to enable standardized reporting in research. The five discrete features of the ECS-CP allow for the assignment of a pain classification profile: mechanism of pain (N), incident pain (I), psychological distress (P), addictive behaviour (A) and cognitive function (C).\u003c/p\u003e\n\u003cp\u003eThe presence of each discrete feature of the ECS-CP was determined as below:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e1. Mechanism of pain\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe presence of nociceptive and/or neuropathic pain was determined at assessment by certified palliative care physicians through history taking, clinical examination and correlation of findings with known sites of bone metastases. Neuropathic pain was deemed present if pain descriptors such as burning, electric shocks, shooting, pricking, tingling, pins and needles, or signs of hyper/hypoaesthesia were described by the patient or found on examination.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2. Incident pain: Breakthrough Pain Assessment Tool (BAT)\u003c/em\u003e\u003c/strong\u003e [19]\u003c/p\u003e\n\u003cp\u003eThe BAT was developed and validated for the assessment of breakthrough cancer pain over the previous week and comprises 14 questions (9 relating to pain, 5 to pain treatment).\u0026nbsp;Breakthrough cancer pain is defined as a transient pain exacerbation in patients with stable and controlled basal pain and may occur\u0026nbsp;spontaneously or following predictable or unpredictable triggers [20]. We assessed the following components of the BAT: average daily frequency of incident pain, typical duration and intensity of incident pain, and if any precipitating/relieving factors were present.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3. Psychological distress:\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003cem\u003eDistress Thermometer (DT)\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e[21]\u003c/p\u003e\n\u003cp\u003eThe DT is a validated, self-reported tool measuring patient distress over the previous week on a 0-to-10 rating scale (0-no distress, 10-extreme distress). Psychological distress was determined with a score \u0026ge;4 [22].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e4. Addictive behaviour: Cut down, Annoyed, Guilty and Eye-opener questionnaire adapted to include drugs (CAGE-AID)\u003c/em\u003e\u003c/strong\u003e [23]\u003c/p\u003e\n\u003cp\u003eCAGE-AID is a validated screening tool used to detect drug and alcohol abuse, exploring four questions, with 1 point allocated for each positive response. We used a conservative cut-off point of \u0026ge;1 to suggest addictive behaviour. This has the sensitivity of detecting 91% of alcohol and 92% of drug abusers who are \u0026gt;50 years old [23].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e5. Cognitive impairment: Short Orientation Memory Concentration Test (SOMCT)\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e[24]\u003c/p\u003e\n\u003cp\u003eThe SOMCT is a 6-item memory and concentration test validated against neuropathology. It covers the assessment of orientation, concentration on a short task, and learning and recall of simple information. The patient scores 1 point for each incorrect answer, which is subsequently weighted (Appendix 2). The total score of SOMCT can discriminate between normal to minimal (0-8), minimal-moderate (9-19) and severe cognitive (20-28) impairment. Patients with severe cognitive impairment were excluded from the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;One point was allocated for each negative feature of the ECS-CP (presence of neuropathic pain, incident pain, psychological distress, addictive behaviour and/or cognitive impairment) [25], which allowed for the calculation of the ECS-CP composite score ranging from 0-5 (total of all negative pain features) [26].\u003c/p\u003e\n\u003cp\u003eThe following were also assessed:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePain intensity: 11-point numerical rating scale (NRS-11)\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e[27]\u003c/p\u003e\n\u003cp\u003ePain intensity in the previous 24 hours was measured using the NRS-11 with 0 representing no pain, 1-3 mild pain, 3-4 moderate pain and 7-10 severe pain. Patients were asked to rate their average and worst pain and the severity of their typical episode of breakthrough pain.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eOpioid requirements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe use of background and breakthrough opioid medications were determined from the\u0026nbsp;inpatient electronic Medication Management chartsor via direct participant reports or pain diaries foroutpatients. The total dose of background analgesia (oral and parenteral) over the previous 24 hours\u0026nbsp;was calculated and converted to an OMEDD using established opioid conversion ratios [28].The frequency of breakthrough opioid analgesia (BTA) use in 24 hours was calculated by averaging the number of breakthrough doses over 72 hours.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEstablishment of bone metastasis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe presence of bone metastasis was established by a review of radiological imaging and reports (plain film radiography, computed tomography, Technetium 99m bone scan, magnetic resonance imaging, and/or positron emission tomography) [4]. As CIBP most commonly arises from bone metastasis in the spine, pelvis, long bones and ribs [2,4,29], only metastasis at these four sites was reported in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient demographics and pain characteristics were summarised using proportions for categorical variables, means and standard deviations (SDs) for normally distributed or medians and inter-quartile ranges (IQRs) for continuous skewed data. Mann-Whitney U test was used to examine the association between pain intensity, breakthrough pain characteristics and opioid requirements and the various ECS-CP features. Multivariable gamma regression analysis was used to analyze the relationship between ECSS-CP composite score and pain intensity while controlling for patients\u0026apos; age and sex. A two-tailed p-value \u0026lt;0.05 indicated statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 147 eligible patients, 140 (95.2%) completed the survey (Figure 1). Patient demographic and clinical characteristics are shown in Table 1. The mean (SD) age was 73.2 (11.2) years, with 47.9% male. The most common primary cancers were breast (25.7%), lung (24.3%) and prostate (20.0%). Bone metastasis was most commonly found in the spine (82.9%), with most patients (64.3%) having metastases across multiple sites. Thirty-two (22.9%) patients had bone metastases at all four sites, twenty-five (17.9%) at any three sites and thirty-three (23.6%) patients at any two sites (Figure 2). CIBP was present in 75.7% of patients, affecting approximately two-thirds of those with spinal or pelvic metastasis and approximately half of those with long bone and rib metastasis (Figure 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePatient Demographics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient Characteristics (n=140)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003eAge,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003emean in years (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e73.2 (11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e67 (47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003ePrimary diagnosis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Breast\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e36 (25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Lung\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e34 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003eProstate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e28 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003eGastrointestinal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e14 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Haematology\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e12 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003eOther\u003csup\u003ea\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e16 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003eSite of bone metastases\u003csup\u003eb\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Spine\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e116 (82.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Pelvis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e78 (55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003eRib\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e66 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.47935368043088%\"\u003e\n \u003cp\u003eLong bone\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.52064631956912%\"\u003e\n \u003cp\u003e59 (42.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eGenitourinary, other than prostate cancer (n=8), melanoma (n=3), carcinoma of unknown primary\u0026nbsp;and other cancers (n=5).\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u0026nbsp;\u003c/sup\u003eThe overall percentage is greater than 100% as multiple variables apply to some participants\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePain and analgesia\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 summarizes reported pain scores and analgesic use. The median reported average and worst pain intensity were 3 and 6, respectively. Moderate to severe (NRS \u0026nbsp;average and worst pain was reported by 42.8% and 67.6% of patients, respectively. Up to three-quarters of patients had been prescribed a background opioid. The median background opioid OMEDD was 25.8mg, and the median frequency of breakthrough opioid use was 1.3 doses/ day. Oxycodone was the most commonly prescribed background (34.0%) and breakthrough (44.6%) opioid.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Pain features and Opioid Use\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePain intensity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eAverage pain (n=140), median (IQR)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e3 (.75-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eNo pain (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e34 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eMild (1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e46 (32.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eModerate (4-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e44 (31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eSevere (7+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e16 (11.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eWorst pain (n=139), median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e6 (2-8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eNo pain (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e27 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eMild (1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e18 (13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eModerate (4-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e27 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eSevere (7+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e67 (48.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePain mechanism\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eNociceptive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e51 (36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eNeuropathic with/without nociceptive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e63 (45.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eNo pain syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e24 (17.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eInsufficient data to classify\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e2 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncident pain\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u003cstrong\u003e104 (74.3)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Frequency\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Less than once a day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e15 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1-2 times a day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e27 (26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 3-4 times a day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e33 (31.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026gt;4 times a day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e29 (27.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Duration\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026lt;5 min\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e24 (23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 5-15min\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e31 (29.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 15-30min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e20 (19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 30-60min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e12 (11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026gt;60min\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e15 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Missing data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e2 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Typical pan intensity (n=70), median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e6 (4.25-8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePsychological distress\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Distress thermometer (median, IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u003cstrong\u003e90 (64.3)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e5 (2-7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAddictive behaviour\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; CAGE-AID score (median, IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u003cstrong\u003e26 (18.6)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCognitive impairment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; SOMCT (median, IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u003cstrong\u003e18 (12.9)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e4 (0-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOpioid Use\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u003cem\u003eBackground opioid (n=103)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Oxycodone\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e35/103 (34.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Fentanyl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e20/103 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Methadone\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e16/103 (15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Morphine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e15/103 (14.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Hydromorphone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e9/103 (8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Others\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e8/103 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eOMEDD,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003emedian in mg (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e25.8 (6.7-47)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Breakthrough opioid\u003csup\u003ea\u003c/sup\u003e (n=101)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Oxycodone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e45/101 (44.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Fentanyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e33 /101 (32.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Morphine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e24/101 (23.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Hydromorphone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e18/101 (17.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Others\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e2/101 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"70.48611111111111%\"\u003e\n \u003cp\u003eDaily frequency, median number of doses (IQR)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.51388888888889%\"\u003e\n \u003cp\u003e1.3 (0.3-2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCAGE-AID, Cut down, annoyed, guilty, and eye-opener-adapted to include drugs; ECS-CP, Edmonton classification system for cancer pain; IQR, Interquartile range; OMEDD, oral morphine equivalent daily dose; SOMCT, Short orientation memory concentration test\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eThe overall percentage is greater than 100% as multiple variables apply to some participants\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEdmonton Classification System for Cancer Pain\u003c/strong\u003e \u003cstrong\u003e(ECS-CP)\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003eFeatures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne or more ECS-CP features were present in 135 patients (Table 2). \u003cem\u003eNeuropathic pain\u003c/em\u003e was reported in 45% of patients and was associated with a higher reported frequency of breakthroughs (p=0.014). Although it was the most prevalent mechanism of pain reported, it did not impact pain intensity or opioid requirements (Table 3). Three-quarters of patients reported having \u003cem\u003eincident pain\u003c/em\u003e, with a reported median incident pain score of 6. Over half of patients reported a daily average of \u0026ge; three episodes of incident pain; for 52.9% of patients, these episodes lasted \u0026le; 15 minutes. Of the ninety-one patients who identified triggers to their incident pain, the majority of patients had predictable pain with movement. The presence of incident pain was strongly associated with a higher average and worst pain scores (p\u0026lt;0.001 for both), higher background OMEDD (p=0.005) and a higher frequency of daily BTA use (p=0.007) (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Association between the Edmonton Classification System for Cancer Pain features, pain intensity and Opioid requirement*\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"34.437086092715234%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eECSCP Features\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAverage pain\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWorst pain\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBackground OMEDD\u003csup\u003e#\u003c/sup\u003e, mg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBreakthrough Opioid frequency\u003csup\u003e#\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePain mechanism\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.728476821192054%\"\u003e\n \u003cp\u003eNociceptive\u003c/p\u003e\n \u003cp\u003eNeuropathic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e3 (2-5)\u003c/p\u003e\n \u003cp\u003e4 (2-5)\u003c/p\u003e\n \u003cp\u003eP=0.510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e6.5 (3-8)\u003c/p\u003e\n \u003cp\u003e7 (5-9)\u003c/p\u003e\n \u003cp\u003eP=0.105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e25 (6.7-47)\u003c/p\u003e\n \u003cp\u003e26.7 (4.8-60)\u003c/p\u003e\n \u003cp\u003eP=0.539\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e1.5 (1-3)\u003c/p\u003e\n \u003cp\u003e1.3 (0.3-2.8)\u003c/p\u003e\n \u003cp\u003eP=0.746\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncident pain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.728476821192054%\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e3.5 (2-5)\u003c/p\u003e\n \u003cp\u003e0 (0-2)\u003c/p\u003e\n \u003cp\u003eP\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e7 (5-8)\u003c/p\u003e\n \u003cp\u003e0 (0-4)\u003c/p\u003e\n \u003cp\u003eP\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e26.7 (6.7-60.0)\u003c/p\u003e\n \u003cp\u003e11.7 (6.7-18.0)\u003c/p\u003e\n \u003cp\u003eP=0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e1.7 (0.7-3.0)\u003c/p\u003e\n \u003cp\u003e0.7 (0.3-1.3)\u003c/p\u003e\n \u003cp\u003eP=0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePsychological distress\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.728476821192054%\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e4 (0.5-5)\u003c/p\u003e\n \u003cp\u003e2 (1-3)\u003c/p\u003e\n \u003cp\u003eP=0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e7 (2-8)\u003c/p\u003e\n \u003cp\u003e5 (2-7)\u003c/p\u003e\n \u003cp\u003eP=0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e26.7 (6.7-60.0)\u003c/p\u003e\n \u003cp\u003e23.5 (1.2-30.0)\u003c/p\u003e\n \u003cp\u003eP=0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e1.2 (0.3-2.8)\u003c/p\u003e\n \u003cp\u003e1.3 (0.7-2.8)\u003c/p\u003e\n \u003cp\u003eP=0.988\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAddictive behaviour\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.728476821192054%\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e4 (2-5)\u003c/p\u003e\n \u003cp\u003e2 (0-4)\u003c/p\u003e\n \u003cp\u003eP=0.099\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e6.5 (5-8)\u003c/p\u003e\n \u003cp\u003e6 (2-8)\u003c/p\u003e\n \u003cp\u003eP=0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e33.8 (7.0-60)\u003c/p\u003e\n \u003cp\u003e21.8 (6.7-40.0)\u003c/p\u003e\n \u003cp\u003eP=0.268\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e2.0 (0.3-3.3)\u003c/p\u003e\n \u003cp\u003e1.0 (0.3-2.3)\u003c/p\u003e\n \u003cp\u003eP=0.217\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCognitive dysfunction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.728476821192054%\"\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e4 (0-6)\u003c/p\u003e\n \u003cp\u003e3 (0.75-4)\u003c/p\u003e\n \u003cp\u003eP=0.298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.072847682119205%\"\u003e\n \u003cp\u003e7 (0-8)\u003c/p\u003e\n \u003cp\u003e6 (2-8)\u003c/p\u003e\n \u003cp\u003eP=0.825\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e30 (18-60)\u003c/p\u003e\n \u003cp\u003e24 (3.2-47)\u003c/p\u003e\n \u003cp\u003eP=0.221\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.70860927152318%\"\u003e\n \u003cp\u003e1.0 (0.7-1.7)\u003c/p\u003e\n \u003cp\u003e1.3 (0.3-3)\u003c/p\u003e\n \u003cp\u003eP=0.409\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eOMEDD, Oral Morphine Equivalent Daily Dose\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e*Mann-Whitney U-test; \u003csup\u003e#\u003c/sup\u003evalues are based on those who had opioids\u003c/p\u003e\n\u003cp\u003eResults reported as median (IQR)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTwo-thirds of patients reported \u003cem\u003epsychological distress\u003c/em\u003e, associated with significantly higher average pain scores (p=0.009) and slightly higher worst pain scores (p=0.054). However, no correlation with opioid requirements was found (Tables 2 and 3). \u003cem\u003eAddictive behaviour\u003c/em\u003e and \u003cem\u003ecognitive dysfunction\u003c/em\u003e were relatively uncommon (18.6% and 12.9%, respectively) and were not associated with pain intensity or opioid requirements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe association between pain and \u003cem\u003eECS-CP composite score\u003c/em\u003e is depicted in Figure 3. Higher average and worst pain were associated with higher ECS-CP composite scores (p\u0026lt;0.001 for both). This association remained significant after adjustment for a patient\u0026rsquo;s age and gender, with a 1-point increase in the ECS-CP composite score leading to 43.6% (95% CI 22.6-68.2) and 46.9% (95% CI 28.5-67.9) increases in average and worst pain respectively.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the first study to systematically explore the ECS-CP features in a cohort of adult cancer patients with bone metastasis and CIBP. We confirm the previously reported high prevalence of neuropathic pain, incident pain and psychological distress in cancer patients with bone metastases, with spinal metastasis being the most common site for CIBP. We detected a strong association between incident pain, psychological distress and pain intensity, with incident pain being the only factor associated with higher opioid requirements (background OMEDD and daily BTA frequency). Finally, we describe sites of metastasis, with the spine as the most common site and correlated reports of CIBP at these sites as previously reported [29].\u003c/p\u003e\n\u003cp\u003eCurrent treatment for CIBP can be classified into anticancer treatments (local radiotherapy, radioisotopes and systemic chemotherapeutics and immunotherapy), analgesic treatment using opioids, anti-inflammatory drugs and co-analgesics (antidepressants, anticonvulsants and gabapanetinoids), bone-targeted therapies (such as bisphosphonate and denosumab) and surgery [3,8]. Local radiotherapy, a commonly used modality has a reported pain response rate of 61% with a median response time of 4 weeks [30]. Whilst there has been increased interest in the study of bone pain [31], a translational paradigm has not successfully allowed the pathophysiology and mechanism of CIBP to inform the choice of pharmacotherapeutics [32]. Opioids remain the mainstay treatment with no evidence to guide the choice of the opioid molecule [3]. More recently, a multicenter randomized controlled study of 223 patients with CIBP receiving radiotherapy was allocated to receive pregabalin (targeting the neuropathic element of CIBP) or placebo. The study findings did not support the role of pregabalin in CIBP, with no significant difference in average pain or pain interference compared to placebo [33].\u003c/p\u003e\n\u003cp\u003eIn recognition of the ongoing challenges of managing complex cancer pain, recommendations have been made for developing and implementing a widely recognized and standardized taxonomy and classification system for cancer pain [34]. More recently, the International Classification of Disease–11 was updated to reflect a new classification system for chronic cancer pain to aid the development of individualized management plans and stimulate research in pain syndromes [35]. Chronic cancer pain is now subdivided in this new classification system into four categories: visceral, bone, neuropathic and 'other', such as chronic bone cancer pain and chronic neuropathic pain.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThus far, the ECS-CP remains the most validated classification system for cancer pain [18]. The ECS-CP highlights the multidimensional nature of pain assessment and classification, delineating distinct and independent categories that can influence pain management outcomes. When compared to published data on ECS-CP features in cancer patients, our cohort with bone metastases reported a higher prevalence of neuropathic pain features (45% vs 16.9-35%) [11,14,36,26,17], experienced more incident pain (74.3% vs 28-61%) [11,37,14,36,26,17], psychological distress (64.3% vs 25-52.7%) [14,36,26,17] and addictive behaviour (18.6% vs 4-11%) [14,36,26,17], but reported a similar prevalence of cognitive dysfunction (12.9% vs 3-21%) [14,36,26,17]. We also reported a similar average (3 vs 4) and worst (6 vs 7) pain scores to that found in a regional European oncology cohort of fifty-five patients with bone metastasis [6]. Despite confirming the influence of incident pain on average and worst pain intensity, we did not observe a relationship between neuropathic pain, pain intensity and OMEDD use as reported in other studies [14,26,17]. Finally, we demonstrated a correlation between the ECS-CP composite scores and pain intensity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA retrospective study of 386 American cancer patients showed that those with neuropathic pain were less likely to achieve their pain goals [17]. This is unsurprising as neuropathic pain remains a significant unmet medical need, requiring a multimodal approach to care [38]. \u0026nbsp;It is challenging to ascertain clearly in our study if the neuropathic element reported arose specifically from CIBP, commonly described mixed cancer pain or cancer treatments [39,40]. Nonetheless, its identification through routine screening is critical for considering appropriate pharmacotherapeutics [41] and other modalities due to the strong known association between poorly controlled neuropathic pain and overall quality of life [42].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLikewise, a multicenter international study of 606 patients with bone metastases confirmed the relationship between incident pain and worst pain intensity and its negative prognostic value at a month follow-up [11]. Incident pain is a subtype of breakthrough pain that occurs with normal voluntary (e.g. walking) or involuntary (e.g. cough) movement but is typically absent at rest [37]. Our findings with participants reporting an average of 3 breakthrough episodes a day, commonly lasting 5-15 minutes, mirror that of a European study of the characteristics of breakthrough cancer pain in 1000 oncology patients [37]. However, an ongoing challenge in clinical practice is the lack of congruence between the temporal pattern of the predictable incident pain that commonly occurs in CIBP (rapid onset and short duration) and the pharmacokinetics of the immediate release opioids currently prescribed. Commonly used immediate release formulations of oxycodone, morphine and hydromorphone\u0026nbsp;(Table 2) provide a delayed onset of analgesia compared to the onset of incident pain. Thus, the onset of analgesia occurs after the episode of pain subsides, and the effects of analgesia last beyond the episode of pain. This, in turn, leads to patients commonly complaining of opioid-induced adverse effects. Thus, formulations of opioids with a rapid onset of analgesia and short duration of action, mimicking the temporal pattern of predictable incident pain in CIBP, may be the more appropriate opioid of choice [43].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study has several limitations, being a single-site study of cancer patients with CIBP. We did not record data on non-opioid analgesics/ co-analgesics which may have affected overall pain scores and may explain the cohort of patients who report no CIBP. \u0026nbsp;We only reported pain from the four most common sites of bone metastases. Using a standardized tool to screen for neuropathic pain, such as the Leeds Assessment of Neuropathic Symptom and Signs [44] or the Douleur Neuropathique\u0026nbsp;4 [45],\u0026nbsp;may have improved our reporting and assessment of neuropathic pain. Finally, our ECS-CP composite score requires interpretation with caution as the number of patients with pain scores ≥4 remains small. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Implications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsidering the complexity of the pathophysiology of CIBP, the ECS-CP may allow us to consider CIBP more systematically and thus develop personalized pain management interventions according to the pain profile identified. It further allows for targeting more specialized input for patients with a high prevalence of neuropathic or incident pain and psychological distress. Targeted intervention studies may further demonstrate the utility of the ECS-CP in the clinical setting.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThere is a need to promote a more standardized way to assess and classify pain syndromes such as CIBP. Our approach requires consideration of the multifactorial aetiology of CIBP that includes nociceptive, inflammatory and neuropathic components and warrants various modalities to manage symptoms in conjunction with disease-modifying therapies. Epidemiological, clinical and translational data may provide the avenues for us to consider how we further target and manage CIBP for each individual that experiences it.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e The study was approved by the Cabrini Research Governance Office (Approval Number\u0026nbsp;04-04-02-21).\u0026nbsp;Completion of questionnaires as part of routine care implied consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003eCabrini Research Institute retains primary control of the data presented in this manuscript. Data may be made available for external review if permission is obtained from the Cabrini Research Institute.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e NM is an advisory board member of Menarini Australia Ltd. The remaining\u003cem\u003e\u0026nbsp;\u003c/em\u003eauthors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e NL and TF were supported by the Cabrini Institute Medical Staff Research Scholarship.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u0026nbsp;\u003c/strong\u003eMS and NM\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewere involved in study conception and design.\u0026nbsp;Data collection were performed by NL, TF, PT, NM and MS, with verification and quality control checked by MS. AG assisted with statistical analysis and DK, NM and MS were involved in data interpretation. All authors contributed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eWe thank all the staff and patients of Cabrini Supportive and Palliative care service for their input into this study. This study has been completed through funding support from the Cabrini Institute Medical Staff Research Scholarship.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eMacedo F, Ladeira K, Pinho F, Saraiva N, Bonito N, Pinto L, Goncalves F (2017) Bone Metastases: An Overview. Oncol Rev 11 (1):321. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4081/oncol.2017.321\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eColeman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12 (20 Pt 2):6243s-6249s. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1158/1078-0432.CCR-06-0931\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eZajaczkowska R, Kocot-Kepska M, Leppert W, Wordliczek J (2019) Bone Pain in Cancer Patients: Mechanisms and Current Treatment. Int J Mol Sci 20 (23). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijms20236047\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eO\u0026apos;Sullivan GJ, Carty FL, Cronin CG (2015) Imaging of bone metastasis: An update. World J Radiol 7 (8):202\u0026ndash;211. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4329/wjr.v7.i8.202\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAhmad I, Ahmed MM, Ahsraf MF, Naeem A, Tasleem A, Ahmed M, Farooqi MS (2018) Pain Management in Metastatic Bone Disease: A Literature Review. Cureus 10 (9):e3286. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.3286\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLaird BJ, Walley J, Murray GD, Clausen E, Colvin LA, Fallon MT (2011) Characterization of cancer-induced bone pain: an exploratory study. Support Care Cancer 19 (9):1393\u0026ndash;1401. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00520-010-0961-3\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eFalk S, Dickenson AH (2014) Pain and nociception: mechanisms of cancer-induced bone pain. J Clin Oncol 32 (16):1647\u0026ndash;1654. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/JCO.2013.51.7219\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMiddlemiss T, Laird BJ, Fallon MT (2011) Mechanisms of cancer-induced bone pain. Clinical oncology (Royal College of Radiologists (Great Britain)) 23 (6):387\u0026ndash;392. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clon.2011.03.003\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMantyh PW (2014) Bone cancer pain: from mechanism to therapy. Curr Opin Support Palliat Care 8 (2):83\u0026ndash;90. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/SPC.0000000000000048\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eVieira C, Fragoso M, Pereira D, Medeiros R (2019) Pain prevalence and treatment in patients with metastatic bone disease. Oncol Lett 17 (3):3362\u0026ndash;3370. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3892/ol.2019.10013\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHabberstad R, Hjermstad MJ, Brunelli C, Kaasa S, Bennett MI, Pardon K, Klepstad P (2019) Which factors can aid clinicians to identify a risk of pain during the following month in patients with bone metastases? A longitudinal analyses. Support Care Cancer 27 (4):1335\u0026ndash;1343. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00520-018-4405-9\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCanal-Sotelo J, Trujillano-Cabello J, Larkin P, Arraras-Torrelles N, Gonzalez-Rubio R, Rocaspana-Garcia M, Barallat-Gimeno E (2018) Prevalence and characteristics of breakthrough cancer pain in an outpatient clinic in a Catalan teaching hospital: incorporation of the Edmonton Classification System for Cancer pain into the diagnostic algorithm. BMC Palliat Care 17 (1):81. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12904-018-0336-y\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCaraceni A, Shkodra M (2019) Cancer Pain Assessment and Classification. Cancers (Basel) 11 (4). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cancers11040510\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eFainsinger RL, Nekolaichuk C, Lawlor P, Hagen N, Bercovitch M, Fisch M, Galloway L, Kaye G, Landman W, Spruyt O, Zhukovsky D, Bruera E, Hanson J (2010) An international multicentre validation study of a pain classification system for cancer patients. Eur J Cancer 46 (16):2896\u0026ndash;2904. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ejca.2010.04.017\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eNekolaichuk CL, Fainsinger RL, Lawlor PG (2005) A validation study of a pain classification system for advanced cancer patients using content experts: the Edmonton Classification System for Cancer Pain. Palliat Med 19 (6):466\u0026ndash;476. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1191/0269216305pm1055oa\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eNekolaichuk CLF, R. L.; Lawlor, P.; Hagen, N.; Berkovitch, M.; Fisch, M.; Galloway, L.; Kaye, G.; Landman, W.; Spruyt, O.; Zhukovsky, D.; Bruera, E.; Hanson, J. (2010) A predictive model for identifying complex cancer pain syndromes in patients referred to specialist palliative care services using a pain classification system [abstract].. Palliat Med 24 (4)\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eArthur J, Tanco K, Haider A, Maligi C, Park M, Liu D, Bruera E (2017) Assessing the prognostic features of a pain classification system in advanced cancer patients. Support Care Cancer 25 (9):2863\u0026ndash;2869. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00520-017-3702-z\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLawlor PG, Lawlor NA, Reis-Pina P (2018) The Edmonton Classification System for Cancer Pain: a tool with potential for an evolving role in cancer pain assessment and management. Expert Review of Quality of Life in Cancer Care 3 (2\u0026ndash;3):47\u0026ndash;64. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/23809000.2018.1467211\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eWebber K, Davies AN, Zeppetella G, Cowie MR (2014) Development and validation of the breakthrough pain assessment tool (BAT) in cancer patients. J Pain Symptom Manage 48 (4):619\u0026ndash;631. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpainsymman.2013.10.026\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDavies AN, Dickman A, Reid C, Stevens AM, Zeppetella G, Science Committee of the Association for Palliative Medicine of Great B, Ireland (2009) The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. Eur J Pain 13 (4):331\u0026ndash;338. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ejpain.2008.06.014\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eOwnby KK (2019) Use of the Distress Thermometer in Clinical Practice. J Adv Pract Oncol 10 (2):175\u0026ndash;179\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDonovan KA, Grassi L, McGinty HL, Jacobsen PB (2014) Validation of the distress thermometer worldwide: state of the science. Psychooncology 23 (3):241\u0026ndash;250. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/pon.3430\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHinkin CH, Castellon SA, Dickson-Fuhrman E, Daum G, Jaffe J, Jarvik L (2001) Screening for drug and alcohol abuse among older adults using a modified version of the CAGE. Am J Addict 10 (4):319\u0026ndash;326\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eWade DT, Vergis E (1999) The Short Orientation-Memory-Concentration Test: a study of its reliability and validity. Clin Rehabil 13 (2):164\u0026ndash;170. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1191/026921599673848768\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBruera E, Schoeller T, Wenk R, MacEachern T, Marcelino S, Hanson J, Suarez-Almazor M (1995) A prospective multicenter assessment of the Edmonton staging system for cancer pain. J Pain Symptom Manage 10 (5):348\u0026ndash;355. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0885-3924(95)00052-z\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eArthur J, Yennurajalingam S, Nguyen L, Tanco K, Chisholm G, Hui D, Bruera E (2015) The routine use of the Edmonton Classification System for Cancer Pain in an outpatient supportive care center. Palliat Support Care 13 (5):1185\u0026ndash;1192. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1017/S1478951514001205\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAtisook R, Euasobhon P, Saengsanon A, Jensen MP (2021) Validity and Utility of Four Pain Intensity Measures for Use in International Research. J Pain Res 14:1129\u0026ndash;1139. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2147/JPR.S303305\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCaraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, Dale O, De Conno F, Fallon M, Hanna M, Haugen DF, Juhl G, King S, Klepstad P, Laugsand EA, Maltoni M, Mercadante S, Nabal M, Pigni A, Radbruch L, Reid C, Sjogren P, Stone PC, Tassinari D, Zeppetella G, European Palliative Care Research C, European Association for Palliative C (2012) Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. The Lancet Oncology 13 (2):e58-68. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1470-2045(12)70040-2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKakhki VR, Anvari K, Sadeghi R, Mahmoudian AS, Torabian-Kakhki M (2013) Pattern and distribution of bone metastases in common malignant tumors. Nucl Med Rev Cent East Eur 16 (2):66\u0026ndash;69. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5603/NMR.2013.0037\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003evan der Velden JM, van der Linden YM, Versteeg AL, Verlaan JJ, Sophie Gerlich A, Pielkenrood BJ, Kasperts N, Verkooijen HM (2018) Evaluation of effectiveness of palliative radiotherapy for bone metastases: a prospective cohort study. J Radiat Oncol 7 (4):325\u0026ndash;333. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s13566-018-0363-6\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eZhen G, Fu Y, Zhang C, Ford NC, Wu X, Wu Q, Yan D, Chen X, Cao X, Guan Y (2022) Mechanisms of bone pain: Progress in research from bench to bedside. Bone Res 10 (1):44. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41413-022-00217-w\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePark SH, Eber MR, Widner DB, Shiozawa Y (2018) Role of the Bone Microenvironment in the Development of Painful Complications of Skeletal Metastases. Cancers (Basel) 10 (5):141. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cancers10050141\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eFallon M, Hoskin PJ, Colvin LA, Fleetwood-Walker SM, Adamson D, Byrne A, Murray GD, Laird BJ (2016) Randomized Double-Blind Trial of Pregabalin Versus Placebo in Conjunction With Palliative Radiotherapy for Cancer-Induced Bone Pain. J Clin Oncol 34 (6):550\u0026ndash;556. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/JCO.2015.63.8221\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBennett MI (2010) Cancer pain terminology: time to develop a taxonomy that promotes good clinical practice and allows research to progress. Pain 149 (3):426\u0026ndash;427. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pain.2010.01.013\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBennett MI, Kaasa S, Barke A, Korwisi B, Rief W, Treede RD, Pain ITftCoC (2019) The IASP classification of chronic pain for ICD-11: chronic cancer-related pain. Pain 160 (1):38\u0026ndash;44. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/j.pain.0000000000001363\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eNekolaichuk CL, Fainsinger RL, Aass N, Hjermstad MJ, Knudsen AK, Klepstad P, Currow DC, Kaasa S, European Palliative Care Research C (2013) The Edmonton Classification System for Cancer Pain: comparison of pain classification features and pain intensity across diverse palliative care settings in eight countries. J Palliat Med 16 (5):516\u0026ndash;523. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/jpm.2012.0390\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDavies A, Buchanan A, Zeppetella G, Porta-Sales J, Likar R, Weismayr W, Slama O, Korhonen T, Filbet M, Poulain P, Mystakidou K, Ardavanis A, O\u0026apos;Brien T, Wilkinson P, Caraceni A, Zucco F, Zuurmond W, Andersen S, Damkier A, Vejlgaard T, Nauck F, Radbruch L, Sjolund KF, Stenberg M (2013) Breakthrough cancer pain: an observational study of 1000 European oncology patients. J Pain Symptom Manage 46 (5):619\u0026ndash;628. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpainsymman.2012.12.009\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDavis MP (2018) Cancer-Related Neuropathic Pain: Review and Selective Topics. Hematology/oncology clinics of North America 32 (3):417\u0026ndash;431. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.hoc.2018.01.005\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLee DY, Lee JJ, Richeimer SH (2021) Cancer Pain Syndromes. Cancer Treat Res 182:17\u0026ndash;25. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-3-030-81526-4_2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eFallon MT (2013) Neuropathic pain in cancer. Br J Anaesth 111 (1):105\u0026ndash;111. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/bja/aet208\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eFinnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M (2015) Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14 (2):162\u0026ndash;173. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1474-4422(14)70251-0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eUlas S, Eyigor S, Caramat I (2018) Quality of Life and Neuropathic Pain in Hospitalized Cancer Patients: A Comparative Analysis of Patients in Palliative Care Wards Versus Those in General Wards. Indian J Palliat Care 24 (3):325\u0026ndash;333. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/IJPC.IJPC_12_18\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBrzakala J, Leppert W (2019) The role of rapid onset fentanyl products in the management of breakthrough pain in cancer patients. Pharmacol Rep 71 (3):438\u0026ndash;442. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pharep.2019.01.010\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBennett M (2001) The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain 92 (1\u0026ndash;2):147\u0026ndash;157. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0304-3959(00)00482-6\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lanteri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E (2005) Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114 (1\u0026ndash;2):29\u0026ndash;36. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pain.2004.12.010\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"pain control, bone pain, symptom assessment, opioid","lastPublishedDoi":"10.21203/rs.3.rs-1988014/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1988014/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: We describe the prevalence of the Edmonton Classification System for Cancer Pain (ECS-CP) features in patients with bone metastasis and cancer-induced bone pain (CIBP) and the relationship between ECS-CP features, pain intensity and opioid consumption.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We assessed ECS-CP features and recoded pain mechanisms and opioid use in adult patients with bone metastasis. Validated measures were used to assess pain intensity, incident pain, psychological distress, addictive behavior and cognition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Among 147 eligible patients, 95.2% completed assessment. Mean participant age was 73.2 years, the majority female (52.1%) with breast cancer occurring most commonly (25.7%). One or more ECS-CP features were present in 96.4% and CIBP in 75.7% of patients. The median average and worst pain scores were 3 and 6, respectively. Neuropathic pain was the most prevalent pain mechanism (45.0%) and associated with breakthrough pain frequency (p=0.014). Three-quarters had incident pain, which was strongly associated with a higher average and worst pain scores (3.5 and 7, p\u0026lt;0.001 for both), background oral morphine equivalent daily dose (26.7mg, p=0.005), and frequency of daily breakthrough analgesia (1.7 doses/day, p=0.007). Psychological distress (n=90, 64.3%) was associated with significantly higher average pain score (4, p=0.009) and slightly higher worst pain score (7, p=0.054). Addictive behaviour and cognitive dysfunction were relatively uncommon (18.6% and 12.9%, respectively).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: There is a need to promote standardized assessment and classification of pain syndromes such as CIBP. The ECS-CP may allow us to consider CIBP in a systematic manner and develop personalized pain interventions appropriate to the pain profile.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration in ANZCTR\u003c/strong\u003e ACTRN12622000853741 (16/06/2022) retrospectively registered.\u003c/p\u003e","manuscriptTitle":"The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: A descriptive cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-12 18:54:20","doi":"10.21203/rs.3.rs-1988014/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-10-24T14:16:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-10-18T09:49:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"91519bd7-4877-433e-a69d-49b6e28833ab","date":"2022-10-07T07:34:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2bf053f3-b0e6-4d1c-96ce-39ba06518b12","date":"2022-09-08T18:07:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-09-08T14:36:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-09-08T14:33:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-09-07T10:44:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2022-08-23T01:36:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"e3b19b82-ffc8-40ee-9fc4-f955720b1958","owner":[],"postedDate":"September 12th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T21:01:28+00:00","versionOfRecord":{"articleIdentity":"rs-1988014","link":"https://doi.org/10.1007/s00520-023-07711-9","journal":{"identity":"supportive-care-in-cancer","isVorOnly":false,"title":"Supportive Care in Cancer"},"publishedOn":"2023-04-28 20:37:57","publishedOnDateReadable":"April 28th, 2023"},"versionCreatedAt":"2022-09-12 18:54:20","video":"","vorDoi":"10.1007/s00520-023-07711-9","vorDoiUrl":"https://doi.org/10.1007/s00520-023-07711-9","workflowStages":[]},"version":"v1","identity":"rs-1988014","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1988014","identity":"rs-1988014","version":["v1"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}