Advancing the integration of biosignal-based automated pain assessment methods into a comprehensive model for addressing cancer pain.

BACKGROUND: Tailoring effective strategies for cancer pain management requires a careful analysis of multiple factors that influence pain phenomena and, ultimately, guide the therapy. While there is a wealth of research on automatic pain assessment (APA), its integration with clinical data remains inadequately explored. This study aimed to address the potential correlations between subjective and APA-derived objectives variables in a cohort of cancer patients. METHODS: A multidimensional statistical approach was employed. Demographic, clinical, and pain-related variables were examined. Objective measures included electrodermal activity (EDA) and electrocardiogram (ECG) signals. Sensitivity analysis, multiple factorial analysis (MFA), hierarchical clustering on principal components (HCPC), and multivariable regression were used for data analysis. RESULTS: The study analyzed data from 64 cancer patients. MFA revealed correlations between pain intensity, type, Eastern Cooperative Oncology Group Performance status (ECOG), opioids, and metastases. Clustering identified three distinct patient groups based on pain characteristics, treatments, and ECOG. Multivariable regression analysis showed associations between pain intensity, ECOG, type of breakthrough cancer pain, and opioid dosages. The analyses failed to find a correlation between subjective and objective pain variables. CONCLUSIONS: The reported pain perception is unrelated to the objective variables of APA. An in-depth investigation of APA is required to understand the variables to be studied, the operational modalities, and above all, strategies for appropriate integration with data obtained from self-reporting. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number (NCT04726228), registered 27 January 2021, https://classic. CLINICALTRIALS: gov/ct2/show/NCT04726228?term=nct04726228&draw=2&rank=1.

Compliance with the breakthrough cancer pain European guidelines and impact on patients' quality of life: an observational prospective study.

Introduction: This study aimed to assess the percentage of patients treated according to the European Society for Medical Oncology (ESMO) 2018 guidelines for breakthrough cancer pain (BTcP) and the impact of guidelines adherence on patients' quality of life (QoL). Methods: Adult opioid-tolerant patients diagnosed with BTcP and locally advanced or recurrent metastatic cancer with a life expectancy of >3 months prospectively were included. Patients were followed up for 28 days. Results: Of 127 patients included, 37 were excluded due to the impossibility to establish adherence to the ESMO guidelines. Among the evaluable patients [51.1% female; with mean (SD) age of 66.4 (11.8) years], all were adherent. BTcP was diagnosed by the Association for Palliative Medicine algorithm in 47.8% of patients and by clinical experience in 52.2% of patients. The mean number of daily BTcP episodes ranged between 1 and 8, with a mean (95% CI) severity of 7.3 (7.0; 7.6) at week 0 and 6.2 (5.8; 6.6) at week 4. Time to maximum pain intensity was 3-15 min in 52.2% of patients, and BTcP lasted 30-60 min in 14.4% of patients at week 0 and 4.4% of patients at week 4. Mean (95% CI) treatment effectiveness was 6.6 (6.1; 7.1) at week 0 and 7.4 (7.0; 7.8) at week 4. Median (Q1-Q3) patients' global impression of clinical condition was 4.0 (4.0-4.0) at week 0 and 3.0 (2.0-3.0) at week 4. Conclusion: A clear BTcP assessment and strict follow-up could be crucial to guidelines adherence and for patient's QoL.

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

Current Status of Cognition and Clinical Practice of Refractory Cancer Pain in Shanghai: A Questionnaire Survey.

Purpose: This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai. Methods: From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China. Results: A total of 238 responses participated in the survey. This survey reports physicians' understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors' knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff's understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training. Conclusion: Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.

Breakthrough and Episodic Cancer Pain from a Palliative Care Perspective.

Cancer pain intensity (PI) fluctuates, but the relationship between pain flares and background pain with respect to pain management is not settled. We studied how flare and background PIs corresponded with treatment results for background cancer pain. Patients admitted to an acute palliative care unit with average and/or worst PI ≥ 1 on the 11-point numeric rating scale were included. Average and worst PI at admission and average PI at discharge were collected. We examined how the difference and ratio between worst and average PI and average PI at admission, were associated with average PI development during hospitalization. Positive differences between worst and average PI at admission were defined as pain flares. Ninety out of 131 patients had pain flares. The reduction in average PI for patients with flares was 0.9 and for those without, 1.9 (p = 0.02). Patients with large worst minus average PI differences reported the least improvement, as did those with large worst/average PI ratios. Patients with pain flares and average PI ≤ 4 at admission had unchanged average PI during hospitalization, while those with pain flares and average PI > 4 experienced pain reduction (2.1, p < 0.001). Large pain flares, in absolute values and compared to background PI, were associated with inferior pain relief.

Breakthrough pain among cancer patients at oncology units in Northern Ethiopia; a multi-center study.

Background: Breakthrough cancer pain (BTCP) is a transient exacerbation of pain that affects the length of hospitalization and quality of life of patients. The objective of this study was to determine the prevalence and factors associated with BTCP among cancer patients at oncology units in Northern Ethiopia in 2022. Methods: A multi-center cross-sectional study was conducted from April to June 2022. After obtaining ethical approval, data were collected prospectively from 424 adult cancer patients admitted to oncology units. Breakthrough cancer pain was assessed by the numeric rating scale. Descriptive and binary logistic regression analyses were performed to determine the factors associated with BTCP. The strength of association was described in adjusted odds ratio (AOR) with 95% confidence intervals and variables with a P-value < 0.05 were considered to have a statistically significant association with BTCP. Result: The prevalence of BTCP among cancer patients was 41.5%. The factors that were found to be associated with BTCP were colorectal cancer (AOR: 7.7, 95% CI: 1.8, 32.3), lung cancer (AOR: 6.9, 95% CI: 1.9, 26.0), metastasis (AOR: 9.3, 95% CI: 3.0, 29.1), mild background pain (AOR: 7.5, 95% CI: 2.5, 22.6), moderate background pain (AOR: 7.0, 95% CI: 2.2, 23.1), severe background pain (AOR: 7.1, 95% CI: 2.2, 22.8), no analgesics taken for background pain (AOR: 5.1, 95% CI: 2.8, 9.3) and uncontrolled background pain (AOR: 3.3, 95% CI: 1.8, 6.1). Conclusion: The prevalence of BTCP was high. Colorectal cancer, lung cancer, the presence of metastasis, the presence of background pain, not taking analgesics for background pain, and uncontrolled background pain were significantly associated with BTCP.

Estudio observacional, prospectivo y multicéntrico sobre el uso de citrato de fentanilo transmucosa en la práctica clínica habitual para el control de las crisis de dolor irruptivo en pacientes oncológicos / Observational, prospective and multicenter study on the use of transmucosal fentanyl citrate in regular clinical practice for the control of breakthrough pain crises in cancer patients

Objetivo: Evaluar el grado de satisfacción de los pacientes y/o cuidadores con el tratamiento de citrato de fentanilo transmucosa en la gestión de las crisis de dolor irruptivo oncológico en términos de facilidad de uso. Métodos: Se realizó un estudio observacional, prospectivo y multicéntrico con 48 pacientes sometidos a tratamiento de mantenimiento con opioides para el dolor crónico basal provocado por el cáncer y que, además, sufrían crisis de dolor irruptivo para las que estaban recibiendo tratamiento con citrato de fentanilo. La variable principal del estudio fue el grado de satisfacción de los pacientes y/o sus cuidadores con el citrato de fentanilo en el manejo de las crisis de dolor irruptivo oncológico, evaluadas mediante cuestionarios Escala Visual Analógica (EVA). Resultados: El 90,6 % de los pacientes/cuidadores muestran un elevado grado de satisfacción con el empleo de citrato de fentanilo en términos de facilidad de uso (valor medio EVA de 8,2). Por su parte, tanto la valoración general por parte de los pacientes/cuidadores como por parte de los sanitarios ha sido muy positiva (valor medio EVA 7,7). Conclusiones: El citrato de fentanilo es una terapia fácil de usar y eficaz para el tratamiento de las crisis de dolor irruptivo oncológico, con amplia aceptación tanto por parte de pacientes y cuidadores como de los profesionales sanitarios.(AU)

Objective: To assess the degree of satisfaction of patients and/or caregivers with transmucosal fentanyl citrate treatment in the management of breakthrough cancer pain crises in terms of ease of use. Methods: An observational, prospective and multicenter study was carried out with 48 patients undergoing maintenance treatment with opioids for baseline chronic cancer pain and who, in addition, suffered breakthrough pain crises for those who were receiving treatment with fentanyl citrate. The main variable of the study was the degree of satisfaction of the patients and/or their caregivers with fentanyl citrate in the management of breakthrough cancer pain crises, evaluatedby means of Visual Analogue Scale (VAS) questionnaires. Results: 90.6 % of patients/caregivers show a high degree of satisfaction with the use of fentanyl citrate in terms of ease of use (mean VAS value of 8.2). For its part, both the general assessment by the patients/caregivers and by the healthcare professionals has been very positive (mean VAS value 7.7). Conclusions: Fentanyl citrate is an easy-to-use and effective therapy for the treatment of breakthrough cancer pain crises, widely accepted by both patients and caregivers as well as health professionals.(AU)

Analysis of influencing factors for breakthrough cancer pain in patients with advanced pancreatic cancer / 中华胰腺病杂志

Objective:To investigate the influencing factors of breakthrough cancer pain (BTcP) in patients with advanced pancreatic cancer.Methods:According to the inclusion and exclusion criteria, patients with advanced pancreatic cancer who were diagnosed and followed up by outpatient service in the 909th Hospital of the Joint Logistic Support Force from January 2019 to December 2020 were prospectively selected as the study subjects. According to whether breakthrough cancer pain occurred, all patients were divided into observation group (breakthrough cancer pain) and control group (no breakthrough cancer pain). The relevant clinical data of the included patients including age, gender, presence or absence of vomit, constipation, sleep disruption, frequency of basic pain every week, with or without regular medication, heavy physical labor, with or without vascular invasion, bone metastasis, abdominal metastasis and lung metastasis, as well as whether surgery, radiotherapy or chemotherapy were collected and the data of evaluation indicators during follow-up were recorded. Digital pain score (NRS) and visual analog score (VAS) were used as pain evaluation score. Univariate and logistic regression were used to analyze the related influencing factors of breakthrough cancer pain. Receiver operating characteristic curve (ROC) was drawn, and area under curve (AUC), sensitivity and specificity were calculated to analyze the predictive value for breakthrough cancer pain.Results:A total of 173 patients were included in the study, with 49 cases in the observation group and 124 cases in the control group. Univariate analysis showed that aged ≥50 years old, constipation, sleep disruption, frequency of basic pain ≥3 times, irregular medication, heavy physical labor, bone metastasis, lung metastasis, radiochemotherapy, high NRS score and high VAS score were the influencing factors for breakthrough cancer pain (all P value <0.05). Multivariate analysis showed that irregular medication ( OR=1.879, 95% CI 2.473-4.757, P=0.002), basal pain ≥3 times ( OR=2.067, 95% CI 1.364-6.825, P=0.004), bone metastasis ( OR=2.756, 95% CI 1.153-5.846, P<0.001), NRS score ( OR=3.787, 95% CI 2.647-5.958, P<0.001), VAS score ( OR=2.684, 95% CI 1.545-7.878, P<0.001), were the risk factors for breakthrough cancer pain. The AUC of NRS score for predicting the occurrence of breakthrough cancer pain was 0.665 (95% CI0.573-0.757, P=0.001), and the cut-off value was 2.5 score with a sensitivity of 61.2% and a specificity of 77.1%. The AUC for predicting breakthrough cancer pain by VAS score was 0.608 (95% CI0.515-0.701, P=0.028), and the cut-off value was 2.5 score with a sensitivity of 67.9% and a specificity of 63.7%. The AUC of NRS+ VAS score for predicting breakthrough cancer pain was 0.692 (95% CI0.604-0.780), and the cut-off value was 4.5 score with a sensitivity of 81.6% and a specificity of 79.8%. Conclusions:Patients with advanced pancreatic cancer have a high incidence of breakthrough cancer pain, which was related to a variety of factors. NRS combined with VAS score can effectively predict the occurrence of breakthrough cancer pain.

Progress in breakthrough cancer pain management / 中华全科医师杂志

Pain is one of the most frightening and unbearable symptoms in cancer patients, approximately 80% of patients with advanced cancer have pain, and a systematic review shows that the prevalence of breakthrough cancer pain (BTcP) was 59.2%. Breakthrough pain often has a significant negative effect on quality of life of patients, which is related to a direct effect (suffering) and an indirect effect (interference with activities of daily living). Clinical management of BTcP is still not satisfactory despite the availability of various effective pain relief agents. The purpose of this review is to summarize the current situation of the management of BTcP at home and abroad, and to discuss the factors that hinder the management of BTcP.

Management and perception of therapeutic adherence of breakthrough cancer pain by oncologists in Spain / Manejo y percepción de la adherencia al tratamiento del dolor irruptivo oncológico por oncólogos españoles

Objectives:The objective of this study was to evaluate the perception of oncologists on adherence to opioid treatment for breakthrough cancer pain (BTcP) in current clinical practice. Our study also included an assessment of other aspects of the management of BTcP, such as the reasons for non-adherence, the adequacy of the treatment, or the possible interventions required to improve adherence.Methods:This observational, multicentric study was carried out in 84 hospitals throughout Spain. Oncologists were surveyed by means of an online questionnaire on their management of background cancer pain and BTcP, and their perception of adherence to the treatments.Results:Oncologists (N = 97) reported that their first choice for BTcP was fentanyl (various formulations), with high perceived tolerance (> 76 % of patients). Most oncologists (96.8 %) evaluated adherence in their patients but only 69. 1% always prescribed medication to prevent adverse effects of opioids and only 74.2 % always titrated the minimum dose. Most oncologists (51.0 %) perceived that 25-50 % of the patients did not adhere to the treatment for BTcP. Adherence to background pain treatments was high, although many oncologists considered that patients usually stopped taking the medication when feeling better. The main reported reasons for non-adherence were the self-perceived feeling that treatment was unnecessary, perceived inefficacy of the treatment, concerns about potential adverse effects, and lack of family support.Conclusions:Oncologists perceived that adherenceto BTcP treatment can be improved and recommended treatment of adverse effects, better education about pain management to patients and relatives, written prescription instructions, and simplification of drug regimens.(AU)

Introducción:El objetivo de este estudio fue evaluar la percepción de los oncólogos sobre la adherencia al tratamiento con opioides para el dolor irruptivo oncológico (DIO) en la práctica clínica real. El estudio también incluyó una evaluación de otros aspectos del manejo del DIO, como las razones de la no adherencia, la adecuación del tratamiento, o las posibles intervenciones necesarias para mejorar la adherencia.Métodos:Este estudio observacional multicéntrico se realizó en 84 hospitales de toda España. Los oncólogos fueron encuestados por medio de un cuestionario online sobre su manejo del dolor oncológico basal y del DIO, y su percepción de la adherencia a los tratamientos.Resultados:Los oncólogos (n = 97) indicaron que su primera opción para el DIO fue el fentanilo (varias formulaciones), con alta tolerancia (> 76 % de los pacientes). La mayoría de los oncólogos (96,8 %) evaluaron la adherencia en sus pacientes, pero solo el 69,1 % siempre prescribió medicamentos para prevenir los efectos adversos de los opioides, y solo el 74,2 % siempre tituló la dosis mínima. La mayoría de los oncólogos (51 %) percibieron que el 25-50 % de los pacientes no mostraban buena adherencia al tratamiento para DIO. La adherencia a los tratamientos de dolor basal fue alta, aunque muchos oncólogos consideraron que los pacientes generalmente dejaban de tomar el medicamento cuando se sentían mejor. Las principales razones para la no adherencia fueron la sensación de que el tratamiento era innecesario, la ineficacia percibida del tratamiento, la preocupación por los posibles efectos adversos y la falta de apoyo familiar.Conclusiones:Los oncólogos percibieron que la adherencia al tratamiento para el DIO puede mejorarse y recomendaron el tratamiento de los efectos adversos de la medicación, una mejor educación sobre el manejo del dolor a los pacientes y familiares, instrucciones escritas de prescripción y simplificación de los regímenes de medicamentos.(AU)

A Korean Nationwide Survey for Breakthrough Cancer Pain in an Inpatient Setting / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the prevalence and characteristics of breakthrough cancer pain (BTcP) in Korean patients admitted with cancer pain. MATERIALS AND METHODS: In-hospital patients with cancer pain completed a questionnaire concerning severity of background cancer pain (BCP), prevalence and treatment for BTcP, sleep disorders, and satisfaction with cancer pain treatment. Medical records showing medications for BCP and BTcP were also evaluated. RESULTS: Total 609 patients with controlled BCP enrolled. Mean age of the patients was 59.5 years old, and 59% were male. Of all patients, 177 (29%) complained of BTcP. No clinical characteristic predicted BTcP. Of the 177 patients with BTcP, 56% did not receive treatment for BTcP. Patients with BTcP showed significant association with a sleep disorder and dissatisfaction with pain control, compared to those without BTcP (p < 0.0001 and p=0.0498, respectively). Oxycodone-immediate release was the most commonly used short-acting analgesic, followed by intravenous morphine. CONCLUSION: The prevalence of BTcP was 29% in patients admitted with controlled BCP. Although the patients had well-controlled BCP, BTcP showed association with a lower quality of life in patients with cancer. More medical attention is needed for detection and management of BTcP.

The research of the combination of Oxycodone and intravenous injection of morphine in treatment of cancer pain and breakthrough cancer pain / 实用肿瘤学杂志

Objective To investigate the combination of Oxycodone and Morphine Hydrochloride Injec-tion in cancer pain and breakthrough cancer pain (BtCP).Methods This study included 78 patients with moder-ate or severe cancer pain ,which was titration with Oxycodone and Morphine Hydrochloride Injection .All data were obtained from diagnosed malignant tumors and followed up in the people ′s hospital of Jiangmen city between Jan 2011 and Dec 2015.Results The first 5 days of the titration with a total Morphine Equivalent Dose (MED)be-tween 156~1 491 mg(426.46 ±286.00 mg),and a total dose of IV morphine hydrochloride injection between 2~57 mg(20.96 ±13.25 mg).The mean dose used in the treatment of BtCP was 2.23 ±2.50 mg in Phase B(8 pm~8 am)and 1.96 ±2.14 mg in Phase A(P<0.05).When the treatment begun Numerical Rating Scale (NRS)showed a significant decrease .All the patients were less likely to experience any severe side -effects. Conclusion The titration by Oxycodone and Morphine Hydrochloride Injection is a simple , safe and efficient method,with less side-effect,significantly improve the living quality .It′s a good choice in the titration of moder-ate or severe cancer pain .

An audit of transmucosal immediate-release fentanyl prescribing at a university hospital

Transmucosal Immediate-Release Fentanyl（TIRF）can be a key-drug for breakthrough cancer pain. Prescription audit is needed because there are concerns about tolerance or serious adverse events including respiratory suppression and addiction due to inappropriate use of these drugs. The aim of this audit study is to evaluate appropriateness of TIRF prescriptions, reasons of violation, and adverse events in the real-world setting. A retrospective chart review was conducted in 31 patients who had breakthrough cancer pain and were treated with TIRF. A 2-step algorithm was generated：baseline pain and administration situation of other opioid rescues. TIRF was prescribed appropriately in six patients（19.4％）. Reasons of violation were as follows：prescriptions only for using same drug with around-the-clock opioids（fentanyl transdermal patches, <i>n</i>＝19）, and patients could take oral medicines and use of morphine or oxycodone rescues would be preferable（<i>n</i>＝12）. TIRF was initiated with a minimum dose in all patients and no serious adverse events were observed. Although TIRF was used widely for breakthrough cancer pain, prescription was not necessarily done appropriately. Detailed assessment of breakthrough cancer pain and consideration of the use the other rescue medication would be required.