A scoping review of breakthrough cancer pain: Multidimensional patient needs and influencing factors.

Introduction

Cancer pain is one of the most common and intolerable symptoms among cancer patients, with a prevalence ranging from 54.6% to 69% in patients with advanced, metastatic, and end-stage cancer. 1 , 2 Within this pain spectrum, breakthrough cancer pain (BTcP) represents a unique clinical entity characterized by brief yet intense pain episodes that occur even when background pain is effectively controlled. The Association for Palliative Medicine of Great Britain and Ireland (APM) defines BTcP as "a transient exacerbation of pain that occurs either spontaneously or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain". 3

Epidemiological data indicates that approximately 50–75% of cancer pain patients experience BTcP. 4 , 5 This pain is typically characterized by sudden onset, high intensity (usually 7–8/10 on the pain scale), 6 and transient duration (averaging 30–60 minutes), often manifesting as sharp, burning, or stabbing sensations. Patients experience an average of 2–3 episodes daily, reaching peak intensity within 5–10 minutes. BTcP can be classified into two categories: incident-induced and spontaneous, significantly disrupting patients' daily activities, work, sleep, and emotional states. 6 The impact of BTcP on patients' lives is comprehensive, leading to substantial functional impairment, mobility limitations, social isolation, and psychological distress, significantly reducing quality of life. 7 , 8 Unrelieved BTcP may also compel patients to discontinue potentially curative treatments, thereby jeopardizing survival, 9 while simultaneously increasing medical resource utilization and associated costs. 10 In China, research demonstrates that 53.41% of cancer patients experience more than three BTcP episodes within 24 hours, with over half of patients reporting low satisfaction with pain relief, 11 indicating significant deficiencies in BTcP management.

Despite the critical importance of BTcP management, clinical practice continues to face numerous challenges. BTcP characteristics demonstrate significant individual heterogeneity, influenced by multiple factors; 12 potential variations in etiology, comorbidities, and pathophysiological mechanisms; 13 cultural factors affecting pain expression and assessment difficulties in special populations further increase management complexity. 14 , 15 In China, patients harbor reservations about opioid medications, and healthcare professionals lack unified guidelines for assessment and management strategies. 15 Currently, BTcP management primarily focuses on pharmacological treatment, but a single pain control model fails to address patients' comprehensive needs. The International Association for the Study of Pain (IASP) proposed a multidimensional pain assessment framework that emphasizes the multidimensionality of pain experiences, necessitating an approach that extends beyond mere physiological dimensions to incorporate psychological, social, and environmental factors. 16 The Comfort Theory provides a more comprehensive theoretical framework, expanding patient needs across four dimensions: physical, psychological, sociocultural, and environmental. It advocates a strategic shift from simple pain control to holistic comfort enhancement. 17 , 18 The theory conceptualizes comfort as an immediate state, manifested through experiences of relief, ease, and transcendence across four contextual domains. 19 , 20 Through the lens of Comfort Theory, BTcP is no longer merely a symptom to be eliminated, but a multidimensional challenge affecting patients' overall comfort state.

Based on the aforementioned background, this study aims to systematically explore the multidimensional needs of BTcP patients and factors influencing their comfort by integrating the Comfort Theory framework with the IASP multidimensional pain assessment model. The research seeks to provide theoretical foundations for comprehensive clinical intervention strategies. By identifying comfort gaps across four dimensions—physical, psychological, sociocultural, and environmental—for BTcP patients, this study aims to transform BTcP management from a narrow symptom-control approach to a holistic, multidimensional comfort enhancement pathway. The ultimate goal is to improve patients' quality of life and disease experience.

This study aims to systematically explore the multidimensional needs and influencing factors of BTcP patients based on Kolcaba's Comfort Theory framework, providing theoretical foundations for developing holistic and multidimensional BTcP management strategies. Specific objectives include: (1) Identifying and categorizing the multidimensional needs characteristics of BTcP patients across the four dimensions of Comfort Theory (physical, psychological, sociocultural, and environmental); (2) Analyzing the key factors influencing BTcP patients' comfort experiences.

Methods

This study employs a scoping review methodology, strictly adhering to the guidelines of the Joanna Briggs Institute (JBI). 21 The selection of the JBI framework is based on its status as an advanced guideline building upon the collective work of Arksey and O'Malley 22 and Levac et al., 23 thus presenting the most methodologically robust framework for scoping reviews. 24 Consistent with the JBI framework, this study's reporting follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. 25

Search strategy and paper selection

Initial searches were conducted in MEDLINE (EBSCO) and CINAHL to preliminarily identify potential search terms by rapidly reviewing article titles and abstracts. After refining the search terms, a comprehensive second-stage search was performed. On January 4, 2025, a formal search was conducted across eight databases: PubMed, MEDLINE (EBSCO), CINAHL, Web of Science, Scopus, AMED, Embase, and Google Scholar. Following the comprehensive search, reference lists of included literature were quickly reviewed to ensure no potentially relevant studies were overlooked. Chinese databases were also searched to obtain evidence from the Chinese context. The search strategy is outlined in Appendix A . Retrieved literature was imported into Endnote X9 and deduplicated. Two independent reviewers screened titles and abstracts, excluding irrelevant literature. Subsequently, the review team independently examined the full texts of potentially relevant articles. Any discrepancies during the screening process were resolved through discussion with a third reviewer. The search results and literature screening process were documented in a PRISMA-ScR flow chart, with explicit reasons for exclusion noted. A narrative description consistent with the flow chart was prepared to illustrate the selection process.

Inclusion and exclusion criteria

Inclusion Criteria: (1) Population: Patients with confirmed cancer diagnosis; (2) Context: No geographical or environmental restrictions, includes all settings primarily focused on promoting, restoring, or maintaining health; (3) Content: Comprehensive review of BTcP in cancer patients; (4) No restrictions on research design. Both English- and Chinese-language literature were included. Rationale for language selection: The research team is proficient in both English and Chinese. (5) International mainstream databases predominantly feature English-language literature. English-language search maximizes comprehensive coverage of relevant research. Exclusion Criteria: conference abstracts, Duplicate publications, studies with incomplete or unavailable data.

Data extraction

The data extraction for this study was conducted by two nursing graduate students who had completed evidence-based research courses and possessed extensive research experience. The data extraction process followed a standardized methodology, systematically recording included literature information in an Excel spreadsheet. Extracted literature details encompassed key information including authors, publication year, country, study design, study participants, study location, research objectives, assessment tools, primary and secondary research indicators, and study results. To ensure the accuracy and comprehensiveness of data extraction, a second reviewer independently verified the extracted data. This dual-review approach aimed to minimize potential bias and enhance the reliability of data extraction. Through rigorous quality control procedures, the research team ensured the scientific and systematic nature of the literature data extraction process, laying a solid foundation for subsequent data analysis. The meticulous approach to data extraction reflects the study's commitment to methodological rigor and scientific precision. By implementing a comprehensive and structured data collection strategy, the researchers sought to capture the nuanced details of BTcP research across various contexts and methodological approaches.

Statistical analysis

This study employed a qualitative synthesis approach. After data extraction, the content was categorized and organized based on the four dimensions of Comfort Theory to ensure the accuracy of extracted information, with related concepts defined. 26 The physical comfort dimension refers to an individual's balanced state of physiological functioning and bodily perception, with its core focusing on the stability of the internal bodily environment and the degree of physiological needs satisfaction, including pain control, symptom management, and physical functional status. The psychological comfort dimension focuses on the individual's emotional state, cognitive function, and psychological adaptation mechanisms. The social comfort dimension indicates the individual's adaptation and integration within interpersonal relationships, social roles, and cultural backgrounds. The environmental comfort dimension concentrates on the impact of external environmental factors on an individual's comfort experience.

Results

A complete PRISMA-ScR flow chart is shown in Fig. 1 . At the end of screening, 30 literature sources were included, 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 published between 2011 and 2024 ( Table 1 ). The included studies contained a total of 17,686 patients, with sample sizes ranging from a minimum of 5 to a maximum of 4016. Fig. 1 Flow diagram illustrating the original process of screening and identification of studies. ∗Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). ∗∗If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools. Fig. 1 Table 1 General patient information. Table 1 Author Country Research Design Study Participants Research Location Research Objective Assessment Tools Outcome Indicators Research Results Homdee 2024 1 Thailand Cross-sectional Study 5 Advanced Cancer Patients Patient and Caregiver Homes in Central Virginia To explore the impact of environmental factors on the frequency and severity of breakthrough cancer pain (BTCP) in the home context from the perspective of patients with advanced cancer and their primary family caregiver -Numeric Rating Scale (NRS) - Ecological Momentary Assessments (EMAs) (brief surveys) - Frequency of breakthrough cancer pain (BTCP) events - Severity of breakthrough cancer pain events - Self-reported pain events and contextualenvironmental data (light, temperature, humidity, air pressure, environmental noise) - Environmental factors (especially light, noise, humidity, and air pressure) may significantly impact breakthrough cancer pain in home environments - Significant variability in sensitivity to environmental factors among patients and caregivers, supporting the necessity of personalized pain management strategies Bimonte 2024 2 Italy Multicenter Cross-sectional Survey Secondary Data Analysis 1871 Cancer Patients with Unpredictable Breakthrough Cancer Pain (NP-BTcP) Multiple Medical Institutions in Italy, Including Palliative Care Units (PCU), Oncology Centers (ONC), and Outpatient Pain Clinics (OPC) - To explore gender differences in the Unpredictable Breakthrough Cancer Pain (NP-BTcP) phenomenon - Analyze BTcP characteristicsand potential influencingfactors in differentenvironments - Collect information on BTcP diagnosis, management, andpatient treatment satisfaction - Numeric Rating Scale (NRS, 0–10) - Karnofsky Performance Status Scale - Differences in NP-BTcP across genders, including incidence, pain location, frequency, and treatment dosage - Assessment of patient quality of life and treatment satisfaction - Higher proportion of BTcP in male chest areas compared to females (15% vs 11%) - Higher BTcP incidence and treatment dosage in males - Lower Karnofsky scores in males, indicating poorer functional status - Among metastatic patients: Higher chest pain proportion in males, Higher abdominal pain proportion in females - Lower Karnofsky scores in metastatic male groups - Non-metastatic males more likely to belong to Phenomenology 2 (moderate severity BTcP subtype, characterized by rapid onset and high treatment demand) Mercadante 2023 3 Italy Multicenter Cross-sectional Survey Secondary Data Analysis 54 Multiple Myeloma (MM) Patients La Maddalena Cancer Center in Palermo, Italy - Describe breakthrough pain (BTcP) characteristics in Multiple Myeloma patients - Compare background pain and BTcP management between MM patients and other cancer patients - Assess patient satisfaction - Record patient background pain intensity and opioid medication usage - Assess breakthrough pain characteristics (frequency, intensity, onset, duration, predictability, impact on daily activities) - Document opioid medications for breakthrough pain, pain relief time, side effects, and patient satisfaction - Breakthrough pain characteristics (frequency, intensity, onset, duration, predictability) - Opioid medication usage patterns, side effects, and patient satisfaction - BTcP in Multiple Myeloma patients more predictable (44.4%), primarily triggered by movement (44.4%), significantly different from other cancer patients - Shorter pain relief time, averaging 13.5 minutes, significantly better than other cancer patients - Higher patient satisfaction: 58% satisfied, 18% very satisfied - No significant differences in background pain and BTcP medication usage patterns compared to other cancer patients Mercadante 2021 4 Italy Prospective, Multicenter, Observational Longitudinal Study 145 Adult Cancer Patients Diagnosed with Breakthrough Cancer Pain (BTcP) 32 Medical Centers in Italy - Longitudinal assessment of background pain and breakthrough cancer pain characteristics - Evaluate analgesic treatment effectiveness and patient treatment satisfaction - Numeric Rating Scale (NRS) - Pain Recording Tools - Satisfaction Score Scale - Medication Usage Records - Assessment Time: Follow-up 4 weeks after initial patient evaluation - Frequency and intensity of Breakthrough Cancer Pain (BTcP) - Background pain intensity - Treatment satisfaction scores - Predictability and triggers of breakthrough pain - Breakthrough period medication and its side effects - Treatment plan adjustment situation - After four weeks, significant reduction in BTcP frequency (from 2.5 to 2.1 times/day) - Slight reduction in breakthrough period pain intensity (from 7.37/10 to 7.02/10) - Significant decrease in background pain intensity (from 3.06/10 to 2.37/10,) - Slight, non-significant improvement in breakthrough period medication satisfaction - Primary medication category: Fentanyl-based drugs, with low side effect rates - No significant changes in breakthrough pain characteristics (duration, relief time) over four weeks - 9% of patients modified their breakthrough pain medication Cascella 2021 5 Italy Observational Study Secondary Data Analysis 2671 Cancer Patients with Unpredictable Breakthrough Cancer Pain (NP-BTcP) Multiple Medical Institutions in Italy Explore the characteristics of unpredictable breakthrough cancer pain and its manifestations across different patient populations Secondary Data Analysis Phenotypic characteristics of NP-BTcP (pain intensity, daily occurrence frequency, pain type), and treatment status for different phenotype patients - Identified four distinct phenotypes (P1–P4), ranging from mild to severe - P4 phenotype associated with lung cancer patients, treated with rapid-acting opioid medications - P1 phenotype patients primarily using morphine, characterized by gastrointestinal cancer Mercadante 2020 6 Italy Multicenter Cross-sectional Survey Secondary Data Analysis 1087 Lung Cancer Patients Multicenter study involving 32 centers in Italy, including oncology, palliative care, radiotherapy, and pain clinics - Characterize breakthrough cancer pain (BTcP) in lung cancer patients - Compare background pain and BTcP management in lung cancer patients vs. those with other cancers - Secondary Data Analysis - Numeric Rating Scale (0–10) for pain intensity assessment - Oral Morphine Equivalent (OME) for standardizing opioid dosage - Parameters for assessing BTcP characteristics: frequency, intensity, predictability, triggers, onset time, duration, and interference with daily life - Assess meaningful pain relief time after medication - Satisfaction assessment - Breakthrough pain characteristics (frequency, intensity, predictability, triggers, onset time, duration) - Interference with daily activities - Opioid medications for breakthrough pain - Meaningful pain relief time after medication - Satisfaction with breakthrough pain treatment - Adverse reactions Compared to other cancer patients, lung cancer patientsexhibited: Higher background pain intensity, Lower opioid medication dosage, Higher breakthrough cancer pain intensity - Movement (79.5%) and coughing (8.2%) as primary predictable BTcP triggers - Greater interference with daily activities - More frequent use of auxiliary medications - No significant differences found in other examined parameters Mercadante 2019 7 Italy Observational, Cross-sectional Study Secondary Data Analysis 205 Head and Neck Cancer (H&N) Patients 32 Medical Institutions Nationwide in Italy - Describe breakthrough pain (BTcP) characteristics and its impact on head and neck cancer patients - Analyze patient medication satisfaction, medication types for breakthrough pain, and related side effects - Medical history records - Medication usage records (including opioid dosage, converted to oral morphine equivalent) - Breakthrough pain questionnaire (recording frequency, intensity, predictability, triggers, duration, daily activity interference) - Oral mucositis severity assessment (WHO criteria) - Medication side effect evaluation - Breakthrough pain characteristics: frequency, intensity, predictability, triggers, onset speed, duration, daily activity interference - Medication usage: types and dosages for background and breakthrough pain - Medication side effects - Patient satisfaction - Average BTcP frequency: 2.8 times/day - High pain intensity (average 7.4/10) - More predictable breakthrough pain - Primary trigger: food intake (76.5%) - Rapid pain onset (72.2% reach peak within 10 minutes) - Significant daily activity interference (89.2% reported) - Medication treatment: transdermal drugs for background pain, nasal fentanyl for breakthrough pain -Pain relief within 15.3 minutes - 38.5% patients experienced varying degrees of oral mucositis, potentially affecting medication choice Mercadante 2019 8 Italy Multicenter, Observational Study Secondary Data Analysis 414 Advanced Abdominal Visceral Cancer Patients with Breakthrough Cancer Pain (BTcP) 32 Centers, Including Oncology, Pain Treatment, Palliative Care, and Radiotherapy Institutions Assess characteristics of abdominal visceral breakthrough cancer pain (BTcP), especially meal-related BTcP - Medical records and investigations - Digital Pain Intensity Scale (0–10) - Daily Activity Interference Scale (0–3) - Karnofsky Performance Status Score - BTcP occurrence frequency, intensity, predictability, triggers - Post-meal BTcP rate, intensity, duration, and triggers - BTcP interference with daily activities - Pain relief time and patient satisfaction BTcP Characteristics: Average daily BTcP: 2.2 times, intensity 7.3/10 - 70.5% unpredictable BTcP, 29.5% predictable BTcP, - Primary trigger: food intake (51.6%) - Average BTcP duration: 52.6 minutes - 65.5% patients reach maximum pain intensity within ≤ 10 minutes - Post-meal BTcP Characteristics: Lower intensity (6.9/10) ,Faster onset (77.8% reach maximum intensity within ≤ 10 minutes),Shorter duration (45.8 minutes) - More common in pancreatic cancer patients Associated with oseltamivir/naloxone use Treatment Results: 85.3% patients treated with strong opioids (e.g., fentanyl), High treatment satisfaction (64.3% satisfied or very satisfied) - Only 0.85% reported mild side effects (nausea and confusion) Gonella 2019 9 Italy Multicenter Longitudinal Observational Study Secondary Data Analysis 92 Advanced Cancer Patients Two Palliative Care Services in Northwestern Italy: 1 Palliative Care Service and 1 Hospice - Describe breakthrough pain (BTP) characteristics and its impact on quality of life - Compare similarities and differences between high and low predictability breakthrough pain - Italian Short Version of Alberta Breakthrough Pain Assessment Tool (ABPAT) - Palliative Outcome Scale (POS) - Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment - BTP frequency, duration, peak intensity, time to peak, relief time, relief intensity, and predictability - Patient descriptions of pain characteristics - Triggering and relieving factors - Median breakthrough pain duration: 30 minutes, peak intensity: 7/10 - Patients with high predictability: Shorter pain duration, Faster time to peak intensity - Significant negative impact on patient quality of life, No significant differences between predictability groups Mercadante 2018 10 Italy Multicenter, Retrospective, Observational Study 4016 Cancer Patients Diagnosed with Breakthrough Pain (BTP) 32 Medical Centers, Including Oncology, Pain Treatment, Palliative Care, and Radiotherapy Institutions Identify potential variables influencing breakthrough cancer pain (BTP) clinical presentation and explore BTP characteristics and associated patient background factors - Patient-reported data - Medical record review - BTP occurrence frequency, Intensity, Duration, Predictability, Daily activity interference, Triggering factors - Basic BTP Characteristics: Average daily BTP: 2.4 times, Intensity: 7.5/10, Average duration: 43.3 minutes, 68.9% patients: rapid onset (≤ 10 minutes) - Patient Satisfaction: 86.8% high satisfaction with BTP medication, 30.5% predictable pain 3. Factors Influencing BTP Occurrence: Age, Head and neck cancer, Karnofsky performance score, Background pain intensity Campagna 2018 11 Italy Multicenter, Longitudinal, Observational Study 101 Advanced Cancer Patients Two Palliative Care Service Institutions in Italy (One Palliative Care Service and One Hospice) Verify the circadian rhythm of breakthrough pain in Advanced Cancer Patients - Patient Personal Diaries: Recording breakthrough pain frequency, occurrence time, and rescue analgesia - Nurses and family members assist patients in recording to ensure accuracy - Alberta Breakthrough Pain Assessment Tool (Simplified Version) - Numeric Rating Scale (NRS) - Eastern Cooperative Oncology Group (ECOG) - Palliative Outcome Scale (POS) - Primary Indicators: Circadian rhythm of breakthrough pain - Secondary Indicators: Rescue analgesia medication usage - Breakthrough Pain (BTP) showed significant circadian rhythm, Peak frequency of pain occurrence at 12:30 PM - Average of 7.2 pain episodes per patient 80.6% of pain episodes occurred between 8:00 AM and 12:00 PM - Quality of life scores significantly decreased with increased pain episode frequency Tekie 2023 12 Ethiopia Multicenter Cross-sectional Study 424 Adult Cancer Patients (≥ 18 years) Three Comprehensive Specialized Hospitals in Northern Ethiopia Determine the prevalence and factors associated with breakthrough cancer pain (BTCP) among cancer patients in Northern Ethiopia - Numeric Rating Scale (NRS) Prevalence and associated factors of BTCP - BTCP Prevalence: 41.5% - Significantly Associated Factors: Colorectal cancer, Lung cancer, Cancer metastasis, Untreated background pain, Uncontrolled background pain Villarroel 2022 13 Spain Prospective, Multicenter Observational Study 104 Patients Over 64 Years Old with Advanced Cancer 13 Medical Oncology Departments Across Spain - Evaluate the impact of personalized treatment on quality of life in breakthrough cancer pain (BTcP) patients - Assessment timepoints: Baseline, 15 and 30 days after treatment Primary Tools: - Spanish version of Five-Level EQ-5D (EQ-5D-5L) - Visual Analog Scale (VAS) Secondary Tools: - Gijón Social-Familial Evaluation Scale - Medical Outcomes Study Sleep Scale (MOS-SS) - Goldberg Anxiety and Depression Scale - Caregiver Burden Index - Changes in EQ-5D-5L index - Improvement in pain intensity, BTcP frequency, sleep quality, Depression and anxiety state assessment Quality of Life: - Significant improvement in EQ-5D-5L index at 15 and 30 days,Significant improvement in pain/discomfort index Pain Characteristics :- Background pain intensity reduced from 4.1 to 2.7 - Breakthrough cancer pain intensity decreased from 8 to 6, Significant reduction in pain occurrence and duration Treatment Effects: Low-dose rapid-acting opioids (e.g., fentanyl) as primary treatment, good tolerability Secondary Outcomes: -Improved sleep quality, Correlated with life quality pain/discomfort and anxiety/depression indicators - Prevalent depression, but no significant improvement Villegas 2021 14 Spain Single-Arm Before-After Controlled Design 21 Late-Stage Cancer Pain Patients Cancer Unit at Castellon Provincial Hospital, Spain - Describe patient pain situation (baseline and breakthrough pain) and related factors using ecological momentary assessment method - Explore frequency and impact of clinical alerts in the application - Test feasibility of app-based monitoring system for cancer pain patients Mobile Application Data Collection: - Treatment adherence (single item) - Pain severity (0–10) - Fatigue level (0–10) - Emotional state (well-being, sadness, anxiety, 0–10) - Perceived pain treatment utility (0–100%) - Coping strategies - System Usability Scale (SUS) for app usability - Pain characteristics (baseline and breakthrough pain frequency, intensity, duration) - Types of clinical alerts and professional responses - Feasibility indicators (app usage adherence) - Patient and healthcare provider satisfaction Pain Characteristics: App-assessed breakthrough cancer pain similar to literature retrospective assessments - Lower breakthrough pain frequency in ecological assessment - Pain, fatigue, and emotions similar in morning and evening - Passive coping strategies most common Clinical Alerts: - Useful for detecting and addressing adverse events - Medical team can quickly respond to patient conditions Feasibility and Satisfaction: 61.9% participants used app daily for 30 days, - Average system usability score: 85.77 (SD ​= ​12.09), High medical team satisfaction - Perceived improvement in breakthrough cancer pain treatment safety and effectiveness Tuca Rodríguez 2021 15 Spain Prospective Multicenter Observational Study 93Advanced Cancer Patients Palliative Care Units at Acute Care Hospitals in Spain Evaluate the impact of personalized breakthrough cancer pain (BTcP) management on quality of life in late-stage cancer patients - EORTC QLQ-C30 scale - Pain Visual Analog Scale (VAS) - Eastern Cooperative Group Performance Status (ECOG-PS) - Edmonton Symptom Assessment System (ESAS) - Patient Global Impression of Improvement (PGI-I) - Clinical Global Impression of Improvement (CGI-I) Assessment timepoints: Baseline (V0), Day 15 (V15), Day 28 (V28) - Quality of life score changes from baseline (V0) to 28 days after personalized BTcP treatment (V28) - Changes in BTcP characteristics (intensity, duration, frequency) - Overall improvement impression after personalized BTcP management - Frailty status and potential impact on quality of life Quality of Life Improvement: Significant increase in global health status score from 31.1 to 53.1 at V28 Pain Improvement: Significant decrease in pain scale score from 73.6 to 35.7 Symptom and Functional Improvement: Significant relief of fatigue, nausea, insomnia - Significant improvement in functional status (role, emotional, cognitive, social) Improvement Perception: 84.8% patients and 83.7% physicians reported some degree of improvement - Physician assessments more optimistic Negative Influences: Lower likelihood of quality of life improvement for patients > 65 years and hospitalized patients ( P ​< ​0.05) Hernanz de Lucas 2021 16 Spain Multicenter, Prospective, Observational Study 79 Stage IV Cancer Patients Top 10 Radiotherapy Departments in Spain - Evaluate quality of life for breakthrough cancer pain (BTcP) patients receiving palliative radiotherapy - Analyze pain management, sleep quality, caregiver burden, and patient perception of improvement - SF-12 Health Survey (assessing quality of life) - Visual Analog Scale (VAS) - Medical Outcomes Study–Sleep Scale (MOS-SS) - Short Version of Zarit Burden Interview - Patient Global Impression of Improvement (PGI-I) - Clinical Global Impression-Improvement (CGI-I) - Quality of life (SF-12 physical and mental components) - Sleep quality (MOS-Sleep Scale) - Caregiver burden (Zarit Scale) - Patient and physician improvement perception scores Pain Relief: - Significant reduction in BTcP Visual Analog Scale (VAS) scores ( P ​< ​0.001) - Shortened duration of severe pain episodes Quality of Life Improvement: - Significant improvement in SF-12 mental component ( P ​< ​0.001) - Enhanced social function, emotional role, vitality, and mental health Sleep Quality: - Significant reduction in sleep disturbance and insufficiency ( P ​< ​0.001) Caregiver Burden: - Significant decrease in Zarit Scale scores ( P ​< ​0.001) Improvement Perception: 43.6% patients felt "significantly improved", 81.9% physicians felt "significantly improved" González, Gemma Soler 2021 17 Spain Observational Cross-sectional Study 240 Frail Patients with Cancer and Breakthrough Pain Multiple Medical Institutions in Spain - Analyze clinical management and quality of life in frail cancer patients with chronic and breakthrough pain (BTP) - Assess whether pain control treatment is influenced by patient frailty status - Frailty Scale - Davies Criteria and Algorithm: BTP diagnosis - Karnofsky Performance Status: Patient performance evaluation - Gijón Scale- EuroQoL-5D-5L (including five-dimension questions and EQ-VAS) - BTP characteristics in frail patients Quality of life assessment, Pain treatment dosage and administration, Impact of socioeconomic status on quality of life BTP Characteristics: - Higher BTP frequency (3.8 times daily) - Shorter duration (34.6 minutes) - More progressive onset Treatment: - No significant differences - Similar chronic pain and BTP treatment dosages for frail and non-frail patients Quality of Life: Significantly lower quality of life for frail patients,Closely related to socioeconomic status and performance status, Poorer social and family conditions associated with worse quality of life - BTP significantly interferes with daily activities (93.7%) García-Foncillas 2020 18 Spain Multicenter Cross-sectional Survey Study 275 Cancer Patients Experiencing Breakthrough Pain 11 Autonomous Regions in Spain Evaluate pain management experiences and unmet needs of Spanish cancer patients, including: Understanding patient pain experiences, Assessing care quality, Determining pain management achievemen, Evaluating pain impact on quality of life, Discussing strategies to address identified needs Primary Tools: Specially designed patient questionnaire Assessment Content: Pain types (chronic and breakthrough), Pain intensity, location, and impact - Treatment satisfaction and adherence - Patient concerns about addiction and side effects - Healthcare professionals' pain assessment and communication - Pain characteristics (intensity, location, type, progression) - Pain impact on quality of life - Satisfaction with pain relief treatment - Treatment adherence - Physician pain assessment and management - Patient concerns about pain medications (addiction and adverse events) - Most patients experienced moderate to severe pain in the past 24 hours - Majority satisfied with pain management effectiveness Pain Locations: Most severe in abdomen, trunk, neck, spine, and hip - Varies across different cancer types Quality of Life Impact: Primarily affects life enjoyment and general activities Secondary impact on emotions Treatment Adherence: Low adherence - Mainly due to side effects and medication discomfort Pérez-Hernández 2019 19 Spain Multicenter, Observational, Cross-sectional, Multidisciplinary Study 3765 Cancer Patients Involved in BTP (Breakthrough Pain) Diagnosis and Management Outpatient Clinics in Multiple Spanish Hospitals (32 Sites) - Assess prevalence and characteristics of breakthrough cancer pain (BTP) - Evaluate 1-month cumulative incidence of newly diagnosed BTP - Describe clinical characteristics of untreated BTP patients - Assess BTP impact on daily activities and quality of life - Davies Algorithm: BTP diagnosis - Alberta Breakthrough Pain Assessment Tool (ABPAT) - Brief Pain Inventory (BPI) - SF-12 Questionnaire - Karnofsky Performance Status Scale - BTP prevalence - BTP clinical characteristics - BTP impact on daily activities and quality of life - 30% of patients with cancer-related pain, 48% (539 patients) diagnosed with BTP - Highest BTP prevalence in palliative care patients (61%), lowest in hematology patients (25%), Moderate to severe pain, significantly impacting daily activities and quality of life (BPI median score 5.3) - 37% of patients unable to predict pain onset - Pain often triggered by movement - 19% of BTP patients untreated - Significant BTP prevalence differences across tumor types and stages, Highest prevalence in pancreatic and colorectal cancer patients Pérez-Hernández 2018 20 Spain Prospective Observational Study 152 Advanced Cancer Patients Diagnosed with Breakthrough Pain (BTP) 17 Research Centers in Spain (8 Pain Units, 8 Palliative Care Units, 1 Oncology Unit) - Evaluate economic cost of breakthrough pain in cancer patients ,Direct medical costs, Non-medical direct costs, Indirect costs - Assess BTP impact on patient quality of life - Visual Analog Scale (VAS): - Edmonton Symptom Assessment Scale (ESAS) - Brief Pain Inventory (BPI): - EORTC QLQ-C30 v3 Questionnaire - Patient Satisfaction: 10-point VAS - Patient Diary: Medical visits, hospitalizations, non-medical resource consumption - Direct Costs: Medical costs (medications, consultations, procedures, hospitalization) Non-medical costs (transportation, assistive equipment) - Indirect Costs: Patient productivity loss,Caregiver impact (work productivity loss, time invested) - Quality of Life Indicators: Functional scale scores, Symptom scale scores - Breakthrough pain significantly increases medical costs, Estimated annual total cost: €35,299.20 - Direct medical costs account for 88% of total costs,Hospital admission fees are the primary component - Quality of life improvement correlates with cost reduction, Effective pain management improves patient quality of life and reduces overall medical costs Fan 2022 21 China Retrospective Cross-sectional Study 798 Advanced Cancer Patients Receiving Palliative Care Palliative Care Ward of a Specialized Oncology Hospital in Hunan Province, China Understand breakthrough pain (BTP) characteristics in late-stage cancer patients and identify related factors - Numeric Rating Scale (NRS): Pain intensity assessment (0–10) - ECOG Performance Status (PS) - Distress Thermometer (DT) - Barthel Index - Structured Electronic Extraction Form: Collect patient demographic and clinical characteristics BTP incidence, BTP intensity, BTP occurrence frequency, Hospital stay, Discharge pain scores, BTP-related factors - 53.6% of patients experienced breakthrough pain, Median BTP occurrence: 4 times, Median pain intensity: 6 (5–10) - BTP patients had higher pain scores at discharge - More symptoms and longer hospital stays Associated Factors: Younger age, Background pain, Anorexia, Constipation - BTP pain intensity independently associated with abdominal distension - Number of symptoms positively correlated with BTP occurrence frequency Liu 2018 22 China Qualitative Study 9 Advanced Cancer Patients Diagnosed with Breakthrough Pain, NRS Pain Score > 4 Northwest Region of China Explore Advanced Cancer Patients ' perception and experience of breakthrough pain Researchers - Patient pain perception, Suffering experience, Management approaches Theme 1: Pain Suffering, Impact on daily activities, Sleep disruption, Physiological and psychological distress Theme 2: Sense of Helplessness, Resignation about condition, Self-management attempts Theme 3: Perception of Pain and Painkillers, Misunderstandings, Fear of medication Theme 4: Influence of Chinese Traditional Culture, Tendency to endure pain, Reluctance to seek help Theme 5: Need for Medical System Support, Better communication, More pain management options Brant 2022 23 USA Prospective, Multicenter, Single-Arm, Longitudinal Study 51 Patients with Advanced Cancer Three Large US Cancer Centers - Assess feasibility of introducing Shared Decision-Making (SDM) in cancer pain management - Evaluate pain intensity, characteristics of breakthrough cancer pain, and patient satisfaction with pain care - Control Preferences Scale (CPS) - Expanded Pain Assessment (EPA) - Pain Care Quality Survey (PainCQ) - Quality Oncology Practice Initiative (QOPI) metrics - Changes in pain intensity and breakthrough cancer pain characteristics - QOPI quality indicator achievement rate, Patient satisfaction with pain care, SDM implementation in pain management - Average pain score maintained at 5 (moderate pain) throughout the study, 88% of patients experienced severe breakthrough cancer pain at baseline - Most patients satisfied with shared decision-making approach - Significant challenges in breakthrough cancer pain management, No significant changes in pain scores during the study period Katz 2017 24 USA Cross-sectional, Observational Survey 112 Community-Dwelling Cancer Patients US Community - Describe breakthrough cancer pain (BTcP) characteristics and burden - Explore BTcP impact on quality of life, psychological state, and work efficiency - Assess current BTcP management strategies and their effectiveness - Brief Pain Inventory–Short Form (BPI) - Short Form 12 Health Survey (SF-12v2) - Sheehan Disability Scale (SDS) - Work Performance Questionnaire (HPQ) - Generalized Anxiety Disorder-7 Screener (GAD-7) - Patient Health Questionnaire-2 (PHQ-2) - Structured Interview Questionnaire (BTcP characteristics and management strategies) - BTcP characteristics (frequency, intensity, duration, time to peak) - Pain control strategies and effectiveness - Health-related quality of life - Impact on daily activities, emotions, walking ability, work, social relationships, sleep, and life enjoyment - Work productivity and functional impairment - 83.3% experiencing ≥ 2 BTcP episodes/day during clinical remission - Median BTcP episode duration: 30 minutes, Most patients using oral immediate-release opioids, Only 24.1% satisfied with treatment effectiveness - High anxiety levels (GAD-7 score 7.9) - Significant quality of life decline, especially in activities, emotions, work capacity, and social relationships - Physical health score (PCS) far below normal, indicating severe functional limitations - 37.5% reported absence or reduced work performance due to pain - High level of functional disability Kang 2020 25 Republic of Korea Multicenter, Non-Interventional, Cross-sectional Nationwide Survey 438 Cancer Patients Experiencing Breakthrough Pain 33 Teaching Hospitals Affiliated with Korean Cancer Study Group (KCSG) Nationwide - Investigate the association between breakthrough cancer pain (BTCP) intensity and quality of life (QOL) - Examine the impact of BTCP on daily functioning - Numeric Rating Scale (NRS) - Korean Version of Brief Pain Inventory (BPI): Emotional domain (relationships, life enjoyment, sleep, emotions), Physical domain (walking ability, general activities, work) - Interference with Daily Function (IDF) score - Relationship between BTCP intensity, duration, frequency and IDF - Extent of impact on emotional and physical domains - Breakthrough cancer pain significantly affects patient daily functioning, most pronounced in moderate to severe pain groups - Positive correlation between pain intensity and daily function interference - Patients with pain duration ≤ 5 minutes had relatively better daily functioning, No significant differences in results for groups with pain duration > 5 minutes Tagami 2018 26 Japan Single-Center, Prospective, Observational Study Design 258 Cancer Patients Receiving Opioid Pain Treatment National Cancer Center East Hospital, Japan Investigate the influence of Breakthrough Pain (BTcP) on General activities - Pain management in patients with controlled background pain - Japanese Version of Brief Pain Inventory - Numeric Rating Scale (NRS): 0 (no symptoms/best) to 10 (most severe) - Personalized Pain Goal (PPG): Determined by asking patients "At what pain level would you feel comfortable?" - Interference of pain with general activities - Average background pain intensity in past 24 hours (24 h-PI) - PPG score - PPG achievement rate (24 h-PI ​≤ ​PPG) - BTcP characteristics (frequency, time to peak, duration) - BTcP Impact: Significant negative impact on patient daily activities and pain management - PPG Achievement Rate: Significantly lower in patients with BTcP compared to those without, Difference significant even in patients with mild background pain - BTcP Frequency and Intensity Characteristics: 49.4% of patients experience 2–3 BTcP episodes daily, 43.2% of patients reach peak BTcP intensity within 5 minutes, 32.1% of patients reach peak BTcP intensity within 6–10 minutes, Untreated BTcP episodes demonstrate diverse duration patterns Twomey 2015 27 Ireland Multicenter Observational 81 Cancer Patients Referred to Palliative Care 5 Specialized Palliative Care Services Assess BTcP Impact on Daily Life and Functional Status - Custom Questionnaire - Brief Pain Inventory - ECOG Performance Status BTcP Frequency and Duration Pain Intensity (0–10 Numeric Rating Scale) Impact of BTcP on:Daily activities, Emotions, Walking ability, Work, Interpersonal relationships, Sleep, Life enjoyment Actual and Emotional Impact of BTcP: Anxiety, Depression, Anger, Isolation - 70.4% experience 3–4 BTcP episodes/day - Pain usually ≤ 30 minutes - Significant impact on activities, emotions - Median life enjoyment: 7/10 - 88.9% feel understood by healthcare providers Pathmawathi 2015 28 Malaysia Descriptive Interpretive Qualitative Study 21 Advanced Cancer Patients Teaching Hospital in Malaysia Explore breakthrough pain experiences and perceptions of palliative care patients in Malaysia Researchers themselves Patients' subjective experience of breakthrough pain - Pain perceived as an unbearable experience causing enormous suffering - Patients have no hope for recovery, viewing pain as a sign of disease progression - Current pain management methods insufficient, patients dissatisfied with healthcare providers' management - Some healthcare providers insensitive to patient pain, inadequate communication - Patients employ multiple coping strategies, including religious and relaxation methods Bedard 2013 29 Canada Non-Interventional Survey Study 94 Cancer Patients Experiencing Breakthrough Pain Four Cancer Centers in Canada Explore Canadian cancer patients' understanding of breakthrough pain, experiences, and views on current management and new treatment methods - Modified Brief Pain Inventory Questionnaire on breakthrough pain characteristics, management, and attitudes toward alternative administration routes - Breakthrough pain frequency, duration, and intensity - Degree of pain impact on daily life - Current pain management methods and effectiveness - Patient expectations and acceptance of new treatments - Views and preferences on different administration routes - 96% reported cancer pain affecting daily life, 50% experienced breakthrough pain lasting over 60 minutes - Average pain score: 7.8/10 - Trigger Factors: Walking (44%), Standing (43%), Household activities (40%), Spontaneous pain (43%) - 35% very satisfied with current medication relief speed - Patients desire new treatments to quickly and completely relieve pain (47% and 43%) - 80% willing to try mucosal administration - 59% willing to try nasal administration - Impact on: Work (59%), Shopping (50%), Emotions (6.2/10), Life enjoyment (6.4/10) Webber 2011 30 UK Qualitative Study 10 Late-Stage Cancer Patients with Breakthrough Pain Large United Kingdom Cancer Centre Explore individual experiences of living with breakthrough cancer pain using qualitative methodology Researchers' direct interviews Exploring patients' experiences, feelings, and impacts of breakthrough pain, communication with healthcare professionals, and perspectives on pain management - Impact on Daily Life: Loss of control, Lifestyle changes, Pain as a constant reminder of cancer - Communication and Medication Management Challenges: Difficulty expressing subjective pain experiences - Challenges with pain language and scales - Impact of communication language - Need for comprehensive pain understanding Importance of Healthcare Professional Understanding

Country of origin

The main countries included were Italy (10), 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 Spain (8), 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 Thailand (1), 27 Ethiopia (1), 38 China (2), 47 , 48 United States (2), 49 , 50 South Korea (1), 51 Japan (1), 52 Ireland (1), 54 Malaysia (1), 55 Canada (1), 56 and the United Kingdom (1). 57

Participants

Cancer types: Multiple myeloma patients: 54 patients (1 study), Lung cancer patients: 1087 patients (1 study), Head and neck cancer patients: 205 patients (1 study), Abdominal visceral cancer patients: 414 patients (1 study). Disease progression stage: Late-stage/terminal/Stage IV cancer patients: 1536 patients, distributed across 13 studies.

Study design

The 30 studies included in this research had diverse research design types. By research center classification: multi-center studies: 17 (56.7%). 28 , 29 , 31 , 32 , 33 , 34 , 35 , 37 , 38 , 39 , 41 , 42 , 44 , 45 , 49 , 51 , 54 By research timeline classification: longitudinal studies: 4 (13.3%), 29 , 31 , 33 , 49 prospective studies: 7 (23.3%), 33 , 41 , 43 , 44 , 45 , 49 , 52 retrospective studies: 2 (6.7%). 35 , 47 By research method classification: cross-sectional studies: 12 (40.0%), 27 , 28 , 34 , 36 , 37 , 38 , 39 , 40 , 42 , 47 , 50 , 51 secondary data analysis: 7 (23.3%), 28 , 30 , 31 , 32 , 34 , 36 , 37 qualitative studies: 3 (10.0%), 48 , 55 , 57 intervention studies: 2 (6.7%). 44 , 46 See Table 1 for details.

Multidimensional needs of BTcP patients based on the comfort theory framework

This study systematically analyzed the needs characteristics of BTcP patients from four dimensions—physical, psychological, sociocultural, and environmental—based on the Comfort Theory framework. 26 , 58 , 59 The results revealed that BTcP patients' needs demonstrated multidimensionality, with interactions between dimensions forming a complex network of needs ( Table 2 ). Table 2 Comfort needs of cancer breakthrough pain patients based on comfort theory. Table 2 Comfort theory dimension Need category Need assessment Physical Dimension Functional Status and Daily Activities - Patient functional status impaired, with lower Karnofsky scores for males 2 , 8 , 17 , 19 - Breakthrough Pain (BTcP) severely interferes with daily activities 7 , 17 , 29 - Daily function limited, affecting basic activity capacity 19 , 22 , 25 , 26 , 30 Sleep Quality - Decreased sleep quality, with sleep disruption and insufficient sleep 13 , 16 -Pain directly impacts sleep, causing sleep interruptions 22 , 27 Pain Characteristics - Pain intensity typically moderate to severe 19 - Pain duration usually within 30 minutes 27 - Pain described as an unbearable experience 28 Treatment and Medication Management - Need for additional auxiliary medications to control pain 6 - Pain management challenging, existing treatment methods limited in effectiveness 26 Psychological Dimension Emotional and Psychological Symptoms - Depression universally present, anxiety symptoms significant 13 , 14 , 24 - Obvious psychological distress, emotional role function impaired 16 , 22 - Emotions significantly affected 18 , 27 , 29 Quality of Life and Life Enjoyment - Quality of life significantly decreased, especially in life enjoyment 9 , 18 - Severe impairment of life pleasure 24 , 29 Psychological Adaptation and Hope - Lack of hope for recovery, viewing pain as a sign of disease progression 28 - Low psychological vitality and mental health levels 16 Social Dimension Socioeconomic Factors - Quality of life significantly correlated with socioeconomic status 17 - Patients with poorer social and family conditions have lower quality of life 17 - Pain management related to medical economic burden, improvement can reduce total costs 20 Work and Daily Social Activities - Work capacity impaired, work affected 24 , 27 , 29 - Daily social activities limited, including basic activities like shopping 29 Interpersonal Relationships - Decline in social relationships and interpersonal communication quality 24 , 27 Caregiver Burden - Caregiver burden significantly increased 16 Environmental dimension Treatment System Support - Low treatment adherence, mainly due to side effects and medication discomfort 7 , 18 - Existing pain management methods insufficient, unable to meet patient needs 28 Medical-Patient Communication and Relationship - Healthcare providers lacking pain sensitivity, insufficient communication 28 - Patients dissatisfied with healthcare providers' management effectiveness 28 Coping Resources and Environmental Support - Patients need diverse coping strategies, including religious and relaxation methods 28

Physical Dimension

In terms of physical comfort, patients primarily demonstrated needs focused on maintaining functional status and daily activities, hoping to preserve basic self-care abilities and daily functionality. 42 , 48 , 51 , 52 , 57 They expressed needs related to sleep quality, expecting to obtain sufficient and high-quality rest. 41 , 45 , 48 , 54 Patients showed significant attention to pain characteristics, yearning for effective pain assessment and relief. 42 , 54 , 55 Additionally, they had expectations regarding treatment and medication management, seeking to reduce treatment burden and medication side effects. 37 , 52

Psychological Dimension

Psychological comfort needs were primarily manifested in the desire for emotional and psychological symptom management. Patients hoped to alleviate negative emotional experiences such as anxiety and depression. 39 , 41 , 45 , 46 , 48 , 50 , 54 , 56 They pursued quality of life and life enjoyment, expecting to maintain life satisfaction despite their disease state. 31 , 39 , 50 , 56 Additionally, patients demonstrated needs for psychological adaptation and hope, yearning to accept their current reality while maintaining a positive outlook for the future. 41 , 55

Sociocultural dimension

In terms of social comfort, patients focused on the impacts of socioeconomic factors, requiring economic and resource support to alleviate disease burden. 40 , 43 They demonstrated needs for participation in work and daily social activities, hoping to maintain social roles and social functioning. 50 , 54 , 56 Patients expressed needs for maintaining interpersonal relationships, expecting to preserve family and social connections. 41 , 50 , 54 Additionally, they showed concern for reducing caregiver burden, hoping that family caregivers would also receive support. 39 , 55

Environmental dimension

Environmental comfort needs were reflected in expectations of support from the treatment system, with patients requiring high-quality and accessible medical services. They emphasized medical communication and relationships, yearning for effective communication and respect from healthcare personnel. Additionally, patients expressed needs for coping resources and environmental support, hoping to obtain a comfortable treatment environment and comprehensive resource support. 36 , 39 , 55

Multidimensional factor analysis of BTcP's impact on patient comfort

This study systematically analyzed various influencing factors of BTcP. The results demonstrated that these factors also exhibit multidimensionality, corresponding to the four dimensions of the Comfort Theory, and collectively influence patients' BTcP experience and comfort state ( Table 3 ). Table 3 Comfort influencing factors for breakthrough cancer pain patients based on comfort theory. Table 3 I. Physical comfort dimension Involving physiological sensations, bodily symptoms, and bodily function comfort Comfort Theory Classification Characteristic classification Summary analysis Pain Characteristics Onset Features - Breakthrough cancer pain (BTcP) basic characteristics: multiple daily high-intensity short-duration attacks, predominantly rapid-onset type 8 , 10 , 27 Temporal Characteristics - BTcP demonstrates clear temporal patterns, typically lasting around 30 minutes, with attacks concentrated in the morning 8 , 9 , 27 Circadian Rhythm - BTcP shows significant circadian rhythm, with peak incidence in the morning, reaching maximum at noon 11 Physiological Triggers Activity-Related Triggers - Movement, walking, standing, coughing, food intake are potential BTcP triggers, especially in specific cancer types 3 , 6 , 8 , 19 Disease-Specific Triggers - Different cancer types have characteristic BTcP triggers, such as head and neck cancer related to diet 3 , 7 Diet-Related BTcP - Post-meal BTcP has unique characteristics, with faster onset but shorter duration 8 Disease-Related Factors Cancer Type-Associated Risk - High BTcP risk associated with specific cancers, highest in colorectal, lung, and pancreatic cancers 12 , 19 Disease Stage Impact - BTcP risk highest in palliative period, lower in hematological tumor patients 19 Disease Progression Correlation - Frequent BTcP attacks during recovery period, with higher baseline pain severity 23 , 24 Treatment Physiological Response Treatment Response - Rapid-acting fentanyl-type preparations are BTcP first choice, low side effects but low satisfaction with traditional oral formulations 4 , 13 , 24 Intervention Effects - Interventions can significantly improve BTcP indicators, but pain management still faces bottlenecks 4 , 13 , 23 Duration Threshold Effect - 5 minutes is the critical point for functional impact 25 II. Psychospiritual Comfort Dimension Involving emotional state, sense of meaning, self-esteem, and spiritual health comfort Comfort Theory Classification Characteristic Classification Summary Analysis Emotional Impact Psychological Influence - BTcP leads to high levels of anxiety, helplessness, and loss of control, perceived as a signal of disease progression 22 , 24 , 28 Quality of Life Impact - BTcP's impact on quality of life stratified, primarily affecting life enjoyment and general activities 11 , 17 , 28 Cognitive Impact Treatment Barriers - Side effects, misconceptions, and cultural factors are primary treatment obstacles 18 , 22 Communication Challenges - BTcP patients face expression difficulties, with subjective experiences hard to fully articulate 28 , 30 Sense of Control Predictability Distribution - Most BTcP is unpredictable, with differences in temporal characteristics between predictive and non-predictive BTcP 9 , 19 Treatment Experience - BTcP treatment satisfaction: patients expect new treatments with rapid onset and complete relief 28 , 29 Mental Adaptation Gender Differences - Significant variations in BTcP location, incidence, and treatment needs between male and female patients 2 Frailty Impact - Unique BTcP characteristics in frail patients: high frequency but short duration, primarily progressive 17 Belief Systems - Religious coping strategies 28 III. Sociocultural Comfort Dimension Involving interpersonal relationships, family support, social roles, and cultural background comfort Comfort Theory Classification Characteristic Classification Summary Analysis Social Role Impact Work and Social Activity Influence - BTcP significantly affects work attendance and social activities, with work and shopping most notably limited 24 , 29 Functional Impact - BTcP's impact on daily function is widespread and severe, with moderate to severe BTcP having the most significant effect 17 , 24 Family Impact Caregiver Burden - BTcP increases family caregiving burden, effective interventions can alleviate this burden 5 , 16 Social Support Needs - Social support is a critical factor influencing quality of life for BTcP patients 17 Cultural Factors Treatment Barriers - Pain tolerance attitudes across different cultural backgrounds influence treatment behaviors 18 , 22 Communication Patterns - Cultural factors affect patients' pain expression and help-seeking behaviors 28 , 30 Economic Impact Economic Consequences - BTcP significantly increases medical costs, primarily direct medical expenses and hospitalization fees 17 , 20 , 22 Resource Allocation - BTcP management requires rational medical resource allocation, effective interventions can reduce overall costs 22 , 30 IV. Environmental Comfort Dimension Involving external environment, treatment environment, and overall care system comfort Comfort Theory Classification Characteristic Classification Summary Analysis Physical Environment Environmental Factors - Physical environmental factors are important BTcP triggers, with significant individual sensitivity differences 1 Comorbidity-Related Factors - Age, comorbidity symptoms, and gastrointestinal function status are critical BTcP predictors 21 Sleep Environment Sleep Impact - Decreased sleep quality is a significant BTcP effect, improving sleep is key to enhancing quality of life 13 , 16 Medical System Environment System Support Needs - BTcP patients require improved medical system support, including professional knowledge and communication 22 , 23 , 30 Digital Management - Digital tools like mobile applications can effectively improve BTcP scoring and characteristics 14 , 16 Treatment Choice Environment Classification System - BTcP can be classified into four different phenotypes, ranging from mild to severe, associated with different cancer types 5 , 17 Treatment Intervention Selection - Different BTcP types require differentiated treatment strategies, increasing patient treatment choices 15 System Support Needs - BTcP patients need better medical system support, including professional knowledge and communication 22 , 30 Treatment Barriers (Environmental Aspects) - Side effects, misconceptions, and cultural factors are primary treatment obstacles 18 , 22

Physical comfort dimension

Involving physiological sensations, bodily symptoms, and physical function comfort, the research findings integrated the discovery that the degree of physical comfort is related to patients' pain nature, physiological triggers, disease-related factors, and treatment physiological responses. Pain characteristics include the nature, timing, and circadian rhythm of pain episodes; trigger factors encompass activities, disease, and diet; disease-related aspects involve cancer type, disease stage, and disease progression; treatment physiological responses include patient treatment reactions, intervention effectiveness, and duration of response.

Pain characteristics influencing factors

The characteristics of BTcP significantly impact patients' physical comfort. Its episodic features (such as sudden onset and intensity variations) often prevent patients from predicting pain, increasing psychological burden. Time-related characteristics (including duration and frequency of episodes) determine the cumulative pain burden, with different impact patterns between frequent short episodes and continuous pain on quality of life. 31 , 32 , 35 , 54 Circadian rhythm characteristics manifest as some patients experiencing BTcP more easily during specific time periods (such as early morning or night), with this rhythmic pattern disrupting patients' normal daily routines and sleep cycles, further reducing physical comfort. 29

Physiological trigger influencing factors

Different physiological trigger factors affect patient comfort through various mechanisms. Activity-related triggers cause breakthrough pain during daily activities (such as walking, coughing, defecation), restricting patients' activity capabilities and self-care levels. 32 , 34 , 37 , 42 Disease-specific triggers are associated with particular cancer types or pathological processes, such as bone metastasis patients potentially experiencing breakthrough pain due to skeletal loading. 34 , 36 Diet-related BTcP manifests as pain triggered by eating behaviors (like swallowing, digestion), directly impacting patients' nutritional intake and appetite, exacerbating physical discomfort and malnutrition risk. 32

Disease-related influencing factors

The characteristics of the disease significantly impact the manifestation and management difficulty of breakthrough pain. Cancer type-related risks indicate that different cancer types (such as pancreatic cancer, bone metastasis) have varying breakthrough pain incidence and characteristic patterns. 38 , 42 Disease stage impact is reflected in the changes of breakthrough pain nature and management complexity as the disease progresses. 42 Disease progression-related findings show that late-stage patients typically face more frequent and harder-to-control breakthrough pain, which is closely associated with increased disease burden and declining physiological function. 49 , 50

Treatment physiological response influencing factors

Treatment factors also significantly impact patients' pain experience and comfort level. Treatment response manifests as individual variations in pain medication, including drug efficacy onset speed and duration. 33 , 45 , 50 Intervention effectiveness is reflected in the differences of various treatment schemes' efficacy, which directly relates to breakthrough pain control level and patient comfort. 33 , 45 , 49 The duration threshold effect indicates that specific treatments must be maintained for a certain period to reach the pain control threshold, and this time window is crucial for determining optimal medication timing and maintaining patient comfort. 51

Psychological comfort dimension

Psychological comfort involves comfort related to emotional states, sense of meaning, self-esteem, and mental health. The integrated research findings reveal that BTcP influencing patients' psychological comfort encompasses emotional responses, cognitive processes, sense of control, and patients' ability to mentally adapt.

Emotional influencing factors

BTcP significantly impacts patients' emotional states and subjective experiences. Psychological impacts manifest as fear, anxiety, and a sense of helplessness experienced by patients after repeated, unpredictable pain episodes, with these negative emotions potentially further lowering pain thresholds, creating a vicious cycle. 48 , 50 , 55 Life quality impacts are reflected in activity limitations, social isolation, and sleep disorders caused by breakthrough pain. Patients report significantly reduced life satisfaction and sense of well-being, often unable to enjoy normal life even during pain-free periods due to the fear of impending pain episodes. 29 , 40 , 55

Cognitive influencing factors

Cognitive function and communication abilities are significantly impacted by breakthrough pain. Treatment barriers manifest as patients developing incorrect perceptions about pain treatment, such as excessive concerns about opioid addiction and misguided expectations regarding pain relief medication efficacy, with these cognitive obstacles affecting treatment adherence and outcomes. 39 , 48 Communication challenges are reflected in patients' difficulty accurately describing the complex and variable characteristics of breakthrough pain, resulting in low communication efficiency between patients and healthcare providers. This leads to inaccurate symptom assessment and mismatched treatment plans, increasing patients' feelings of frustration and helplessness. 55 , 57

Sense of control influencing factors

Patients' sense of control over pain and life is a critical determinant of psychological comfort. Predictability distribution refers to the varying degrees of patients' ability to anticipate breakthrough pain episodes, with patients who can predict pain onset demonstrating higher psychological adaptability and sense of control. 31 , 42 Treatment experience involves patients' level of participation and proactivity in pain management plans. When patients can engage in decision-making and understand treatment options, their sense of disease mastery is enhanced, anxiety levels significantly decrease, and subjective comfort improves notably, even when objective pain parameters remain similar. 55 , 56

Spiritual adaptation influencing factors

Individual differences and spiritual adaptation strategies significantly influence the psychological experience of breakthrough pain. Gender differences manifest in distinct patterns of pain responses and coping mechanisms between males and females, with research indicating that women may be more willing to express pain experiences but potentially bear a greater psychological burden. 28 Debilitating impacts refer to the influence of previous mental health status and coping abilities on pain adaptation, with patients demonstrating lower psychological resilience facing greater adaptation challenges. 40 Belief factors are reflected in spiritual or religious beliefs providing a meaning framework and spiritual support for some patients, helping them more effectively cope with the uncertainty and fear induced by breakthrough pain, thus enhancing psychological resilience. 55

Socio-cultural comfort dimension

Socio-cultural comfort involves comfort related to interpersonal relationships, family support, social roles, and cultural backgrounds. The integrated research findings reveal that BTcP impacts encompass social roles, family dynamics, cultural contexts, and economic aspects.

Social role influencing factors

BTcP severely disrupts patients' social functioning and role performance. Work and social activity impacts are manifested by patients reducing work participation and productivity due to unpredictable pain episodes, and in some cases, being forced to abandon work entirely. Simultaneously, social and recreational activities significantly decrease, leading to an increased sense of social isolation. 50 , 56 Functional impacts are reflected in breakthrough pain limiting patients' ability to fulfill family and social roles, such as being unable to continue as the family's primary breadwinner, care for children, or participate in community activities. This role transformation not only affects patients' social identity but also alters their interaction patterns with family and society. 40 , 50

Family influencing factors

Breakthrough pain exerts profound impacts on family systems. Caregiver burden is manifested through family members' need to constantly respond to patients' pain crises and undertake additional caregiving responsibilities. This unpredictability increases caregivers' physical and mental stress and sense of exhaustion, with family caregivers frequently reporting sleep deprivation, anxiety, and professional interruptions. 30 , 41 Social support needs are reflected in patients' and their families' increased dependence on professional support and community resources. However, social support systems often struggle to meet the unique, rapidly changing demands brought about by breakthrough pain, resulting in patients and families experiencing resource insufficiency and systemic support inadequacies. 40

Cultural factors influence

Cultural backgrounds significantly impact the expression and management of breakthrough pain. Treatment barriers manifest in patients' varying cognitive and acceptance levels regarding pain medications (especially opioids) across different cultural contexts. Patients from certain cultural backgrounds may refuse adequate analgesic medications due to fears of addiction or cultural expectations of pain endurance. 39 , 48 Communication patterns are reflected in the diverse ways patients express pain across different cultural backgrounds. Some cultures encourage restrained pain expression, while others allow more open communication. These differences affect medical-patient communication efficiency and pain assessment accuracy, thereby influencing treatment outcomes and patient trust in medical systems. 55 , 57

Economic influencing factors

Breakthrough pain brings significant economic burdens and resource allocation challenges. Economic impacts are characterized by the dual pressure of increased treatment costs (including medication expenses, emergency medical visits, and hospitalization fees) and reduced income (due to diminished work capacity), with many patients reporting severe economic difficulties resulting from pain management. 40 , 43 , 48 Resource allocation involves how families balance breakthrough pain management with other needs under limited resources, including prioritizing time, caregiving resources, and economic resources. This resource allocation stress may lead to internal family conflicts and relationship tensions, further reducing patients' social comfort. 48 , 57

Environmental comfort dimension

The environmental comfort dimension encompasses comfort related to external environments, treatment settings, and the overall care system. The integrated research findings reveal that the environmental dimension of comfort includes physical environments, sleep environments, medical systems, and treatment choice environments.

Physical environment influencing factors

Physical environmental factors directly impact the triggering and management of breakthrough pain. Environmental factors manifest through temperature, humidity, noise, and other physical conditions that can serve as triggers or exacerbating factors. For instance, some patients experience increased breakthrough pain frequency during environmental temperature changes or weather transitions, and pain perception may intensify in noisy environments. 27 Comorbidity symptom correlation is reflected in the interaction between breakthrough pain and other symptoms (such as nausea, breathing difficulties, fatigue), where the coexistence of these symptoms creates cumulative environmental demand effects. This requires specific indoor arrangements, assistive devices, or environmental adjustments to simultaneously manage multiple symptoms, thereby increasing the complexity of environmental adaptation. 47

Sleep environment influencing factors

A bidirectional relationship exists between sleep and breakthrough pain. Sleep impacts are manifested through nighttime breakthrough pain-induced sleep interruptions, difficulty falling asleep, and decreased sleep quality, which subsequently trigger daytime fatigue and increased pain sensitivity. Simultaneously, sleep environment factors (such as mattress firmness, pillow height, room temperature, and lighting) can potentially serve as triggers for nocturnal breakthrough pain. Many patients require specially adjusted sleep environments to reduce nighttime pain episodes, and these specific needs are particularly challenging to meet in hospital or travel settings, further exacerbating patients' environmental adaptability issues. 41 , 45

Medical system environment influencing factors

Medical system characteristics significantly impact breakthrough pain management effectiveness. System support needs are reflected in patients' dependence on medical resource accessibility, continuity of care, and rapid response mechanisms. Due to the sudden and urgent nature of breakthrough pain, patients require medical support systems that can provide swift assistance. Uneven medical resource distribution and response time delays become critical factors affecting patient comfort. 48 , 49 , 57 Digital management involves the application of remote monitoring systems, electronic pain diaries, and mobile health applications in breakthrough pain management. These technological tools create new medical environments that enable patients to access support beyond physical space limitations, while simultaneously confronting challenges of digital literacy and unequal technological accessibility. 41 , 46

Treatment choice environment influencing factors

The characteristics of treatment plans constitute the patient's therapeutic environment. The classification system focuses on the impact of breakthrough pain categorization and individualized assessment on the treatment environment. Different types of breakthrough pain (such as spontaneous and triggered) require distinct prevention and management strategies, with accurate classification helping to create a more patient-tailored treatment environment. 30 , 40 Treatment intervention selection is reflected in the impact of available analgesic medications, administration routes, and auxiliary treatment methods on patient environmental comfort. This includes factors such as the accessibility of fast-acting opioid medications, availability of non-pharmacological intervention methods, and the portability and privacy of treatment plans, which ultimately determine patients' ability to maintain comfort across various environments. 44

Discussion

Main findings

This study innovatively applies Kolcaba's Comfort Theory to BTcP management, transforming it from a single pain control paradigm to a holistic, multi-dimensional comfort enhancement approach. Through this theoretical framework, we identified the comfort needs of BTcP patients across four dimensions - physical, psychological, social, and environmental - and explored potential influencing factors affecting comfort due to BTcP. This approach provides a theoretical foundation for developing individualized intervention strategies, particularly suitable for managing pain symptoms that cannot be completely eliminated.

Currently, BTcP research is primarily concentrated in Italy and Spain, followed by China and the United States. Italian studies predominantly employ secondary analysis methods, exploring BTcP characteristics from different cancer type perspectives, thereby establishing foundations for cancer-specific BTcP management. Overall, existing research primarily consists of cross-sectional surveys, with a relative scarcity of intervention studies, indicating that the field remains in an exploratory stage. Moreover, this study similarly finds diverse assessment tools for BTcP, with most utilizing numerical rating scales (NRS, 0–10 points), suggesting a continued need for developing specific assessment tools. Among the included studies, only two were intervention-based research, 44 , 46 necessitating further in-depth investigation to more comprehensively address patient needs. Bossi et al.'s research 60 demonstrated that adhering to European Society for Medical Oncology (ESMO) guidelines for standardized BTcP diagnosis and treatment could effectively improve patient pain conditions and quality of life, with significant reductions in pain intensity and duration during treatment progression. Lee et al. 61 discovered significant correlations between cancer patients' fatigue symptoms and various quality of life aspects, with pain, fatigue, emotional issues, and sleep quality being closely interrelated. BTcP management strategies should comprehensively consider attack frequency, suffering levels, and patient preferences, adopting personalized approaches. 62 Research by Zhang 63 and Yu et al. 64 revealed significant gaps in healthcare professionals' knowledge and practices of BTcP management, particularly regarding comprehensive assessment and personalized treatment. García-Foncillas et al.'s study 39 showed that while most patients were satisfied with pain management, some remained concerned about medication dependence and adverse reactions. Future research can build upon this study to further develop comprehensive nursing interventions and promote patient comfort.

Comfort, as a universal cross-disciplinary cultural concept, is particularly core in healthcare and represents the primary clinical practice goal and ideal health outcome. 58 Multiple nursing theorists, such as Nightingale and Mores, have explored the concept of comfort in their theories. In 1991, 26 American nursing scholar Dr. Kolcaba established a comprehensive comfort theory through systematic concept analysis, providing a theoretical framework and practical guidance for this concept. Kolcaba defined comfort as an immediate enhanced experience generated by meeting relief, ease, or transcendence needs across four contextual dimensions: physical, psychospiritual, environmental, and sociocultural. 59 The comfort theory provides a systematic framework for comprehensively understanding BTcP patients' needs. Within this framework, we discovered that BTcP impacts patients' comfort experiences across multiple dimensions: Physical Dimension, Functional impacts, Sleep experiences, Treatment experiences. Psychological Dimension: Emotional influences, Psychological barriers; Social Dimension: Activity limitations, Economic burden, Caregiver stress; Environmental Dimension: System support needs, Treatment accessibility issues. This multi-dimensional analysis helps develop more comprehensive BTcP management strategies.

However, the core challenge of effectively assessing and managing the multidimensional comfort of BTcP patients in busy clinical environments lies in constructing an assessment and intervention framework that is both scientific and efficient. Future research can further achieve the comprehensive assessment of patients' physical, psychological, social, and environmental comfort in 5–10 minutes through the development of a standardized and rapid multidimensional screening tool; 65 and at the same time, establish an urgency-based tiered management strategy, supplemented by an intelligent e-assessment system and an interdisciplinary collaboration mechanism, so that clinicians can accurately identify the most urgent comfort needs of patients within the limited outpatient time, and thus formulate corresponding individualized intervention plans, thus enhancing the overall comfort experience of BTcP patients under the realistic conditions of resource constraints. 66

Implications for nursing practice and research

In nursing practice, nurses should prioritize the comprehensive assessment of physical comfort. The results of this study indicate that physical comfort is closely related to the nature of patients' pain, physiological triggers, the stage of the disease, and treatment responses. Nurses need to develop patient-centered care plans, paying special attention to pain characteristics, such as the nature and timing of pain episodes, as well as physiological triggers, including activities and dietary habits. Additionally, nurses should meticulously monitor patients' physiological responses following treatment. This process requires nurses not only to evaluate the effectiveness of pain management but also to design individualized interventions that enhance patients' physical function and overall comfort. Regarding psychological comfort, nurses must proactively identify and assess patients' emotional states and mental health. Breakthrough cancer pain can significantly impact patients' emotions, cognition, and sense of control, underscoring the importance of psychological support. Therefore, nurses should establish trusting relationships with patients, employ effective communication techniques to support their psychological adaptation, and collaborate with mental health professionals to provide the necessary emotional support and psychological treatment, thereby improving patients' quality of life. The social and cultural dimensions highlight the crucial role of patients' social roles, family support, and cultural background in the management of BTcP. In nursing practice, it is imperative for nurses to assess patients' social support systems and the status of caregivers to ensure that patients receive essential support while being able to engage in social and family activities. Furthermore, considering the economic factors affecting patients and their treatment can help provide necessary resources and educational support to both patients and their families, thereby alleviating caregiver burdens and improving the overall care experience for patients. Lastly, the enhancement of environmental comfort should not be overlooked. When developing care plans, nurses should comprehensively consider external environments, treatment settings, and the overall care system to ensure that patients have access to quality medical support. Research indicates that the physical environment of hospitals, sleep settings, and treatment options can significantly affect patients' comfort levels. Therefore, nurses need to focus on these environmental factors and actively advocate for improvements within the healthcare system to provide a higher quality of nursing experience and facilitate access to resources, ultimately optimizing patient treatment outcomes and overall comfort. Given that BTcP research remains in its preliminary exploratory stage, future investigations should deepen and expand across multiple critical dimensions. The primary task is to conduct more high-quality intervention studies, with a specific focus on systematically assessing nursing intervention strategies to provide robust support for clinical practice. Simultaneously, an in-depth analysis of the complex mechanisms by which BTcP influences patients' multidimensional comfort needs becomes a crucial research direction, aiming to construct a more comprehensive and precise assessment system. Considering the geographical limitations of existing research, studies on BTcP characteristics and management across cultural backgrounds urgently need to be advanced. This approach not only helps validate the universality of existing research findings but also broadens the overall understanding of the disease. Furthermore, future research should comprehensively examine the multifaceted influencing factors of BTcP, encompassing physiological, psychological, and social dimensions. Through comprehensive and personalized management strategies, the ultimate goal is to enhance patients' overall quality of life.

Limitations

This scoping review presents several noteworthy limitations. First, we did not conduct a strict methodological quality assessment of the included studies, which, while facilitating a comprehensive analysis of a broader literature range, may potentially compromise the reliability and generalizability of the results. The absence of rigorous quality evaluation standards implies that the academic quality of the included literature may vary, potentially leading to biased and uncertain research conclusions. Secondly, the geographical distribution of the included studies exhibits a significant bias, primarily concentrated in specific regions such as Spain, which limits the applicability of research findings across different cultural contexts. This geographical concentration suggests that the research results may fail to adequately reflect the diversity and complexity of BTcP across different cultural and medical system backgrounds, thereby reducing the universality of the research findings. Moreover, this study only extracted and integrated existing quantitative and qualitative results, with significant heterogeneity among quantitative research findings, potentially affecting the accuracy of comprehensive analysis. Differences in measurement methods, sample selection, and research backgrounds across various studies increase the difficulty of result integration and may lead to uncertain comprehensive conclusions. The currently included studies are predominantly cross-sectional surveys, with a relative scarcity of intervention studies, especially those focusing on nursing interventions, which restricts the exploration of causal relationships. Cross-sectional studies primarily reflect the status quo at a specific time point and struggle to reveal dynamic changes and causal mechanisms between variables. Particularly in the complex field of BTcP management, the lack of intervention studies impedes a deeper understanding of effective intervention strategies. Despite these limitations, this study still provides an important comprehensive perspective and foundation for BTcP research. These limitations not only reveal the current research deficiencies but also point the direction for future research, encouraging researchers to conduct more in-depth and comprehensive investigations in methodological design, geographical coverage, research types, and causal relationship exploration.

Conclusions

The comfort theory provides an innovative paradigm shift in BTcP management, evolving from traditional single-dimensional pain control to a comprehensive, multi-dimensional comfort enhancement approach. This theory systematically identifies and assesses patients' complex comfort needs across physical, psychological, social, and environmental dimensions, conducting an in-depth analysis of the multifaceted factors influencing patient comfort in BTcP, thus offering a more precise and comprehensive theoretical foundation for clinical practice. This theoretical framework extends beyond mere symptom relief, emphasizing patients' holistic experience and quality of life. By integrating multi-dimensional assessment strategies, the comfort theory promotes the development of personalized intervention plans, enabling medical teams to transcend conventional symptomatic treatment and transition towards a more holistic and humanistic care model. Particularly in contexts where BTcP cannot be completely eliminated, this comprehensive comfort management approach provides patients with a more humane and empathetic nursing framework.

CRediT authorship contribution statement

Qingyi Li: Conceptualization, Methodology, Formal Analysis; Yanlei Sheng: Data Curation, Investigation, Writing – Original Draft; Luhong Hu (corresponding author): Supervision, Project Administration, Writing – Review & Editing; Xinyu Liu: Visualization, Software, Validation; Jie Li: Resources, Investigation, Data Curation; Lisi Zhu: Writing – Original Draft, Methodology; Yang Yang: Writing – Review & Editing, Formal Analysis. All authors have read and approved the final manuscript.

Ethics statement

Not required.

Data availability statement

Data supporting the findings of this study are available from the corresponding author upon request.

Declaration of generative AI and AI-assisted technologies in the writing process

No AI tools/services were used during the preparation of this work.

Funding

This work was supported by the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Research Fund [grant numbers 2024C09].

Declaration of competing interest

The authors declare no conflict of interest.

References

1 Snijders R.A.H. Brom L. Theunissen M. Update on prevalence of pain in patients with cancer 2022: a systematic literature review and meta-analysis Cancers (Basel) 15 3 2023 10.3390/cancers15030591 PMC9913127 36765547

2 Van Den Beuken-Van Everdingen M.H.J. Van Kuijk S.M.J. Janssen D.J.A. Treatment of pain in cancer: towards personalised medicine Cancers (Basel) 10 12 2018 10.3390/cancers10120502 PMC6316711 30544683

3 Bernardes S.F. Matos M. Mourão S. Cultural adaptation and psychometric validation of the Portuguese breakthrough pain assessment tool with cancer patients Scand J Pain 21 4 2021 688 695 33930265 10.1515/sjpain-2021-0002

4 Makhlouf S.M. Pini S. Ahmed S. Managing pain in people with Cancer-a systematic review of the attitudes and knowledge of professionals, patients, caregivers and public J Cancer Educ 35 2 2020 214 240 31119708 10.1007/s13187-019-01548-9 PMC7076060

5 Camps Herrero C. Batista N. Díaz Fernández N. Breakthrough cancer pain: review and calls to action to improve its management Clin Transl Oncol 22 8 2020 1216 1226 32002739 10.1007/s12094-019-02268-8

6 Greenfield K. Schoth D.E. Hain R. A rapid systematic review of breakthrough pain definitions and descriptions Br J Pain 18 3 2024 215 226 38751563 10.1177/20494637231208093 PMC11092936

7 Davies A.N. Elsner F. Filbet M.J. Breakthrough cancer pain (BTcP) management: a review of international and national guidelines BMJ Support Palliat Care 8 3 2018 241 249 10.1136/bmjspcare-2017-001467 29875184

8 Yeo J. Breakthrough pain and rapid-onset opioids in patients with cancer pain: a narrative review J Yeungnam Med Sci 41 1 2024 22 29 37424088 10.12701/jyms.2023.00367 PMC10834265

9 International Association for the Study of Pain [Z] 2024 January 6

10 Lakkad M. Martin B. Li C. Healthcare costs and utilization associated with pain among breast cancer survivors: a propensity score matched cohort study using SEER-medicare data J Cancer Survivorship: Res Pract 17 4 2023 917 950 10.1007/s11764-022-01282-0 36369622

11 Yang H. Zhang S.Y. Ma X.X. Pain intensity and satisfaction of pain relief in discharged cancer patients: a large sample study in China Pain Manag Nurs 25 4 2024 e295 e301 38609804 10.1016/j.pmn.2024.03.013

12 Scarborough B.M. Smith C.B. Optimal pain management for patients with cancer in the modern era CA Cancer J Clin 68 3 2018 182 196 29603142 10.3322/caac.21453 PMC5980731

13 Liossi C. Greenfield K. Schoth D.E. A systematic review of measures of breakthrough pain and their psychometric properties J Pain Symptom Manag 62 5 2021 1041 1064 10.1016/j.jpainsymman.2021.04.018 33933619

14 Mustajoki M. Forsén T. Kauppila T. Pain assessment in native and non-native language: difficulties in reporting the affective dimensions of pain Scand J Pain 18 4 2018 575 580 29990307 10.1515/sjpain-2018-0043

15 Crawford G.B. Lakhani A. Palmer L. A systematic review of qualitative research exploring patient and health professional perspectives of breakthrough cancer pain Support Care Cancer 31 12 2023 619 37812248 10.1007/s00520-023-08076-9 PMC10562491

16 Raja S.N. Carr D.B. Cohen M. The revised international association for the study of pain definition of pain: concepts, challenges, and compromises Pain 161 9 2020 1976 1982 32694387 10.1097/j.pain.0000000000001939 PMC7680716

17 Pinto S. Fumincelli L. Mazzo A. Comfort, well-being and quality of life: discussion of the differences and similarities among the concepts Porto Biomed J 2 1 2017 6 12 32258577 10.1016/j.pbj.2016.11.003 PMC6806988

18 Kolcaba K.Y. A theory of holistic comfort for nursing J Adv Nurs 19 6 1994 1178 1184 7930099 10.1111/j.1365-2648.1994.tb01202.x

19 Lin Y. Zhou Y. Chen C. Application of Kolcaba's comfort theory in healthcare promoting adults' comfort: a scoping review BMJ Open 14 10 2024 e077810 10.1136/bmjopen-2023-077810 PMC11474854 39389601

20 Cohen S.P. Vase L. Hooten W.M. Chronic pain: an update on burden, best practices, and new advances Lancet 397 10289 2021 2082 2097 34062143 10.1016/S0140-6736(21)00393-7

21 Peters M.D.J. Godfrey C. Mcinerney P. Best practice guidance and reporting items for the development of scoping review protocols JBI Evid Synth 20 4 2022 953 968 35102103 10.11124/JBIES-21-00242

22 Arksey H. O'Malley L. Scoping studies: towards a methodological framework Int J Soc Res Methodol 8 1 2005 19 32

23 Levac D. Colquhoun H. O'Brien K.K. Scoping studies: advancing the methodology Implement Sci 5 2010 69 20854677 10.1186/1748-5908-5-69 PMC2954944

24 Peters M.D. In no uncertain terms: the importance of a defined objective in scoping reviews JBI Database System Rev Implement Rep 14 2 2016 1 4 10.11124/jbisrir-2016-2838 27536788

25 Tricco A.C. Lillie E. Zarin W. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation Ann Intern Med 169 7 2018 467 473 30178033 10.7326/M18-0850

26 Kolcaba K.Y. Kolcaba R.J. An analysis of the concept of comfort J Adv Nurs 16 11 1991 1301 1310 1753026 10.1111/j.1365-2648.1991.tb01558.x

27 Homdee N. Lach J. Blackhall L. The influence of ambient environmental factors on breakthrough cancer pain: insights from remote health home monitoring and a proposed data analytic approach BMC Palliat Care 23 1 2024 10.1186/s12904-024-01392-9 PMC10908209 38429698

28 Bimonte S. DI Gennaro P. Crispo A. Assessing gender differences for non-predictable breakthrough cancer pain phenomenon: a secondary analysis from IOPS-MS study J Pain Res 17 2024 2861 2871 39253738 10.2147/JPR.S445222 PMC11382666

29 Campagna S. Sperlinga R. Milo A. The circadian rhythm of breakthrough pain episodes in terminally-ill cancer patients Cancers (Basel) 11 1 2018 10.3390/cancers11010018 PMC6356835 30586878

30 Cascella M. Crispo A. Esposito G. Multidimensional statistical technique for interpreting the spontaneous breakthrough cancer pain phenomenon. A secondary analysis from the IOPS-MS study Cancers (Basel) 13 16 2021 10.3390/cancers13164018 PMC8391336 34439173

31 Gonella S. Sperlinga R. Sciannameo V. Characteristics of breakthrough pain and its impact on quality of life in terminally ill cancer patients Integr Cancer Ther 18 2019 1534735419859095 10.1177/1534735419859095 PMC6589949 31220961

32 Mercadante S. Adile C. Masedu F. Breakthrough cancer pain in patients with abdominal visceral cancer pain J Pain Symptom Manag 57 5 2019 966 970 10.1016/j.jpainsymman.2019.02.014 30822530

33 Mercadante S. Caraceni A. Cuomo A. A longitudinal study of breakthrough cancer pain: an extension of IOPS-MS study J Clin Med 10 11 2021 10.3390/jcm10112273 PMC8197313 34073907

34 Mercadante S. Caraceni A. Cuomo A. Breakthrough pain in patients with multiple myeloma: a secondary analysis of IOPS MS study Eur Rev Med Pharmacol Sci 27 3 2023 1134 1139 36808361 10.26355/eurrev_202302_31219

35 Mercadante S. Marchetti P. Cuomo A. Factors influencing the clinical presentation of breakthrough pain in cancer patients Cancers (Basel) 10 6 2018 10.3390/cancers10060175 PMC6025469 29865170

36 Mercadante S. Masedu F. Valenti M. Breakthrough pain in patients with head & neck cancer. A secondary analysis of IOPS MS study Oral Oncol 95 2019 87 90 31345399 10.1016/j.oraloncology.2019.06.006

37 Mercadante S. Masedu F. Valenti M. Breakthrough pain in patients with lung cancer. A secondary analysis of IOPS MS study J Clin Med 9 5 2020 10.3390/jcm9051337 PMC7290905 32375331

38 Tekie Y. Nigatu Y.A. Mekonnen W. Breakthrough pain among cancer patients at oncology units in northern Ethiopia; a multi-center study Front Oncol 13 2023 1248921 10.3389/fonc.2023.1248921 PMC10805268 38264754

39 García-Foncillas J. Antón-Torres A. Caballero-Martínez F. Patient perspective on the management of cancer pain in Spain J Patient Exp 7 6 2020 1417 1424 33457596 10.1177/2374373520978872 PMC7786723

40 González G.S. Cajaraville J.P. Sanjuan S.F. Analysis of the Clinical Management and Quality of Life of Frail Patients with Cancer and Breakthrough Pain in Clinical Practice 2021

41 Hernanz de Lucas R Nuñez Fernández M. Gómez-Caamaño A. Quality of life in patients with breakthrough cancer pain in radiation oncology departments in Spain: the CAVIDIOR study Future Oncol 17 8 2021 943 954 33289432 10.2217/fon-2020-1063

42 Pérez-Hernández C. Blasco A. Gándara Á. Prevalence and characterization of breakthrough pain in patients with cancer in Spain: the CARPE-DIO study Sci Rep 9 1 2019 17701 10.1038/s41598-019-54195-x PMC6881364 31776408

43 Pérez-Hernández C. Jiménez-López A.J. Sanz-Yagüe A. Observational study evaluating the economic impact of breakthrough pain in cancer patients in clinical practice in Spain: the IMDI study Pain Ther 7 2 2018 227 240 29974351 10.1007/s40122-018-0102-0 PMC6251832

44 Tuca Rodríguez A. Núñez Viejo M. Maradey P. Impact of individualized management of breakthrough cancer pain on quality of life in advanced cancer patients: CAVIDIOPAL study Support Care Cancer 29 8 2021 4799 4807 33533986 10.1007/s00520-021-06006-1 PMC8236456

45 Villarroel P.G. Padró J.G. Marquina G. Increased quality of life in patients with breakthrough cancer pain after individualized therapy: the CAVIDIOM study Future Oncol 18 35 2022 3913 3927 36537885 10.2217/fon-2022-0758

46 Villegas F. Martínez-Borba V. Suso-Ribera C. Characterizing breakthrough cancer pain using ecological momentary assessment with a smartphone app: feasibility and clinical findings Int J Environ Res Publ Health 18 11 2021 10.3390/ijerph18115991 PMC8199778 34204871

47 Fan R. Li X. Yang S. Retrospective observational study on the characteristics of pain and associated factors of breakthrough pain in advanced cancer patients Pain Res Manag 2022 2022 8943292 10.1155/2022/8943292 PMC9023204 35463627

48 Liu Q. Gao L.L. Dai Y.L. Breakthrough pain: a qualitative study of patients with advanced cancer in northwest China Pain Manag Nurs 19 5 2018 506 515 29506898 10.1016/j.pmn.2017.11.006

49 Brant J.M. Wujcik D. Dudley W.N. Shared decision-making in managing breakthrough cancer pain in patients with advanced cancer J Adv Pract Oncol 13 1 2022 19 29 35173986 10.6004/jadpro.2022.13.1.2 PMC8805806

50 Katz N.P. Gajria K.L. Shillington A.C. Impact of breakthrough pain on community-dwelling cancer patients: results from the national breakthrough pain study Postgrad Med J 129 1 2017 32 39 10.1080/00325481.2017.1261606 27846789

51 Kang J.H. Koh S.J. Oh S.Y. Interference with daily functioning by breakthrough pain in patients with cancer Support Care Cancer 28 11 2020 5177 5183 32056013 10.1007/s00520-020-05329-9

52 Tagami K. Okizaki A. Miura T. Breakthrough cancer pain influences general activities and pain management: a comparison of patients with and without breakthrough cancer pain J Palliat Med 21 11 2018 1636 1640 29975582 10.1089/jpm.2017.0675

53 Barbato M. Barclay G. Potter J. Breakthrough medication in unresponsive palliative care patients: indications, practice, and efficacy J Pain Symptom Manag 56 6 2018 944 950 10.1016/j.jpainsymman.2018.08.020 30201486

54 Twomey F. O'Brien T. O'Reilly M. An observational research study to evaluate the impact of breakthrough cancer pain on the daily lives and functional status of patients Ir Med J 108 6 2015 174 176 26182800

55 Pathmawathi S. Beng T.S. Li L.M. Satisfaction with and perception of pain management among palliative patients with breakthrough pain: a qualitative study Pain Manag Nurs 16 4 2015 552 560 26256219 10.1016/j.pmn.2014.10.002

56 Bedard G. Hawley P. Zhang L. A survey of Canadian cancer patients' perspectives on the characteristics and treatment of breakthrough pain Support Care Cancer 21 9 2013 2557 2563 23636647 10.1007/s00520-013-1817-4

57 Webber K. Davies A.N. Cowie M.R. Breakthrough pain: a qualitative study involving patients with advanced cancer Support Care Cancer 19 12 2011 2041 2046 21181210 10.1007/s00520-010-1062-z

58 Coelho A. Parola V. Cardoso D. Use of non-pharmacological interventions for comforting patients in palliative care: a scoping review JBI Database System Rev Implement Rep 15 7 2017 1867 1904 10.11124/JBISRIR-2016-003204 28708751

59 Wensley C. Botti M. Mckillop A. A framework of comfort for practice: an integrative review identifying the multiple influences on patients' experience of comfort in healthcare settings Int J Qual Health Care 29 2 2017 151 162 28096279 10.1093/intqhc/mzw158

60 Bossi P. Pietrzyńska T. Margarit Ferri C Compliance with the breakthrough cancer pain European guidelines and impact on patients’ quality of life: an observational prospective study Front Pain Res (Lausanne) 5 2024 1388837 39006759 10.3389/fpain.2024.1388837 PMC11239570

61 Lee N. Kim B. The Most important factor influencing quality of life among cancer-related psychological symptoms J Res Health 14 6 2024 527 536

62 Mercadante S. Portenoy R.K. Understanding the chameleonic breakthrough cancer pain Drugs 81 4 2021 411 418 33515376 10.1007/s40265-021-01466-5

63 Zhang J. Ma K. Yan J. Current status of cognition and clinical practice of refractory cancer pain in shanghai: a questionnaire survey J Pain Res 17 2024 1413 1422 38618294 10.2147/JPR.S452605 PMC11015849

64 Yu Y. Zhang P. Chen D. Knowledge and practice of the management of breakthrough cancer pain among general practitioners providing palliative care in shanghai, China: a cross-sectional survey BMJ Open 13 9 2023 e073670 10.1136/bmjopen-2023-073670 PMC10546098 37770268

65 Adrien-Lara M. Pereira A. Vitale S.G. HYSPAIN CLINICAL TRIAL testing the efficacy of paracervical anesthesia for pain control during office hysteroscopy: a randomized, single-center, double-blind, placebo-controlled clinical trial J Clin Med 13 24 2024 7856 39768779 10.3390/jcm13247856 PMC11728129

66 De Groef A. Evenepoel M. Van Dijck S. Feasibility and pilot testing of a personalized eHealth intervention for pain science education and self-management for breast cancer survivors with persistent pain: a mixed-method study Support Care Cancer: Official J Multinatl Assoc Support Care Cancer 31 2 2023 119 10.1007/s00520-022-07557-7 36645526

Supplementary data

The following is the Supplementary data to this article: Multimedia component 1 Multimedia component 1

Supplementary data to this article can be found online at https://doi.org/10.1016/j.apjon.2025.100780 .