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.