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.

Evaluation of Gabapentin as a Treatment of Breakthrough Cancer Pain Caused by Metastatic Prostate Adenocarcinoma.

Introduction: Breakthrough Cancer Pain (BTcP) is defined as a temporary increase in pain that occurs spontaneously. The use of gabapentin is believed to be able to reduce pain complaints in patients with BTcP. However, research to support the efficacy of gabapentin in relieving pain in patients with BTcP is still limited. This study aims to determine the effectiveness of the use of gabapentin in patients with BTcP caused by metastatic prostate adenocarcinoma. Methods: The study was conducted by analytic study with a prospective approach. The subjects were all patients with metastatic prostate adenocarcinoma at Zainoel Abidin General Hospital during 2022-2023 which fulfilled inclusion and exclusion criteria (30 patients). Data analysis was performed in the form of reduction in pain scale in patients with BTcP caused by metastatic prostate adenocarcinoma using gabapentin and the combination of the opioid gabapentin with T-Test. Results: The results showed that there was no significant difference between the reduction in posttreatment pain in patients with BTcP caused by metastatic prostate adenocarcinoma taking gabapentin alone or taking the opioid gabapentin combination, either on days 3-4 or on days 5-6 (p > 0.05). However, based on the results of the evaluation on day 3-4, it was found that gabapentin was able to reduce pain by 2.2272, whereas the combination of opioid gabapentin was only able to reduce pain by 1.916. The evaluation on days 5-6 showed that gabapentin was able to reduce pain by 4.1363 and the combination of gabapentin opioids by 3.2083. Conclusion: The conclusion of this research is that gabapentin is effective in the treatment of BTcP caused by metastatic prostate adenocarcinoma.

A systematic review of qualitative research exploring patient and health professional perspectives of breakthrough cancer pain.

PURPOSE: Breakthrough cancer pain (BtCP) is a prevalent health issue which is difficult to manage. A plethora of quantitative research in this area exists. There is a paucity of research on the perspectives of health professionals and patients surrounding domains impacting effective treatment, including definitions of BtCP, treatment, and education opportunities. This review aims to identify and synthesize the extent of qualitative research exploring health professional and patient perspectives of BtCP. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach was undertaken. The approach was registered with Prospero. MEDLINE, EMBASE, and Web of Science were searched for peer-reviewed literature published any date prior to May 19, 2022. Eligible sources must have considered health professional and/or patient perspectives of BtCP. A narrative synthesis approach was utilized. RESULTS: Three sources met the review criteria. One source explored nurse perspectives, while two sources explored patient perspectives. Study quality was moderate to high. Overlapping themes across the three studies included communication, defining BtCP, impact of BtCP, management of BtCP, perceptions of BtCP, analgesia and pain relief, and training and professional development. CONCLUSION: Given limited research investigating clinician and patient perspectives of BtCP, a rich understanding informed by exploratory qualitative methods around identification, best management strategies, professional development, and factors promoting and inhibiting best practice remains unclear. Further qualitative inquiry is warranted, and it is expected such research will inform BtCP clinical guidelines.

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)

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.

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.

Increased quality of life in patients with breakthrough cancer pain after individualized therapy: the CAVIDIOM study.

Aim: To evaluate the quality of life (QoL) in patients with breakthrough cancer pain (BTcP) in Spanish medical oncology departments. Patients & methods: In a prospective, observational, multicenter study, we assessed QoL using the EQ-5D-5L instrument at baseline and after 15 and 30 days of individualized BTcP therapy, as well as BTcP characteristics and treatment. Results: Patients (n = 118) were mainly women, over 64 years old and with advanced cancer. QoL improved at 15 (p = 0.013) and 30 days (p = 0.011) versus baseline. Individualized BTcP therapy consisted mostly of rapid-onset opioids (transmucosal fentanyl at doses of 67-800 µg) according to the physician evaluation. BTcP improved, including statistically significant reductions in intensity, duration, number of episodes in the last 24 h and time to onset of BTcP relief. Conclusion: QoL increased after individualized pain therapy in patients with advanced cancer and BTcP in medical oncology departments.

Cancer patients can experience flares of pain, called breakthrough pain (BTcP), despite treatment with painkillers. Although BTcP can be excruciating, its intensity and other characteristics depend on several factors, including its treatment. However, even if treated, BTcP can impair quality of life for cancer patients. We assessed quality of life in 118 patients with advanced cancer and BTcP treated in 13 medical oncology departments across Spain. We treated BTcP with individualized therapy, taking into account both pain-related and patient-related factors. We also measured quality of life using a specific, widely-used questionnaire at the study visits: at onset of individualized pain therapy and after 3, 15 and 30 days' treatment. At each visit, flare-up pain therapy was adjusted or maintained as necessary. Throughout the study, quality of life and sleep quality improved for all participants. Furthermore, there was a greater reduction in intensity, duration and frequency of BTcP. The most common treatments for flare-ups were low doses of rapid-onset opioids (fentanyl given by sublingual, buccal or nasal administration), which were much better tolerated than high-dose opioids. Overall, the study showed that quality of life in patients with advanced cancer and BTcP increased after individualized pain therapy, mainly with low doses of rapid-onset opioids.

Bayesian Network Analysis for Prediction of Unplanned Hospital Readmissions of Cancer Patients with Breakthrough Cancer Pain and Complex Care Needs.

BACKGROUND: Unplanned hospital readmissions (HRAs) are very common in cancer patients. These events can potentially impair the patients' health-related quality of life and increase cancer care costs. In this study, data-driven prediction models were developed for identifying patients at a higher risk for HRA. METHODS: A large dataset on cancer pain and additional data from clinical registries were used for conducting a Bayesian network analysis. A cohort of gastrointestinal cancer patients was selected. Logical and clinical relationships were a priori established to define and associate the considered variables including cancer type, body mass index (BMI), bone metastasis, serum albumin, nutritional support, breakthrough cancer pain (BTcP), and radiotherapy. RESULTS: The best model (Bayesian Information Criterion) demonstrated that, in the investigated setting, unplanned HRAs are directly related to nutritional support (p = 0.05) and radiotherapy. On the contrary, BTcP did not significantly affect HRAs. Nevertheless, the correlation between variables showed that when BMI ≥ 25 kg/m2, the spontaneous BTcP is more predictive for HRAs. CONCLUSIONS: Whilst not without limitations, a Bayesian model, combined with a careful selection of clinical variables, can represent a valid strategy for predicting unexpected HRA events in cancer patients. These findings could be useful for calibrating care interventions and implementing processes of resource allocation.

Breakthrough Cancer Pain: What Outpatient Oncology Nurses Need to Know.

Breakthrough cancer pain (BCP) is a devastating symptom that can occur in individuals with cancer throughout the disease trajectory, particularly in those with advanced cancer. Oncology nurses have a critical role in treating.

Patient Preferences for Rescue Medications in the Treatment of Breakthrough Cancer Pain.

OBJECTIVE: The discrete choice experiment (DCE) is conducted in this study to discuss Chinese cancer patients' risk-benefit preferences for rescue medications (RD) and their willingness to pay (WTP) in the treatment of breakthrough cancer pain (BTcP). METHOD: Through literature reviews, specialist consultation, and patient surveys, this work finally included five attributes in the DCE questionnaire, i.e., the remission time of breakthrough pain, adverse reactions of the digestive system, adverse reactions of the neuropsychiatric system, administration routes, and drug costs (estimating patients' WTP). The alternative-specific conditional logit model is used to analyze patients' preferences and WTP for each attribute and its level and to assess the sociodemographic impact and clinical characteristics. RESULTS: A total of 134 effective questionnaires were collected from January, 1 to April, 5 in 2022. Results show that the five attributes all have a significant impact on cancer patients' choice of "rescue medications" (P<0.05). Among these attributes, the remission time after drug administration (10.0; 95%CI 8.5-11.5) is the most important concern for patients, followed by adverse reactions of the digestive system (8.5; 95%CI 7.0-10.0), adverse reactions of the neuropsychiatric system (2.9; 95%CI 1.4-4.3), and administration routes (0.9; 95%CI 0-1.8). The respondents are willing to spend 1182 yuan (95%CI 605-1720 yuan) per month for "rescue medications" to take effect within 15 minutes and spend 1002 yuan (95%CI 605-1760 yuan) per month on reducing the incidence of drug-induced adverse reactions in the digestive system to 5%. CONCLUSION: For Chinese cancer patients, especially those with moderate/severe cancer pain, the priority is to relieve the BTcP more rapidly and reduce adverse drug reactions more effectively. This study indicates these patients' expectations for the quick control of breakthrough pain and their emphasis on the reduction of adverse reactions. These findings are useful for doctors, who are encouraged to communicate with cancer patients about how to better alleviate the BTcP.

Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain.

Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment of BTcP. Light-activated drugs offer a novel potential strategy for the rapid control of pain without the typical adverse effects of systemic analgesic drugs. mGlu5 metabotropic glutamate receptor antagonists display potent analgesic activity, and light-induced activation of one of these compounds (JF-NP-26) in the thalamus was found to induce analgesia in models of inflammatory and neuropathic pain. We used an established mouse model of BTcP based on the injection of cancer cells into the femur, followed, 16 days later, by systemic administration of morphine. BTcP was induced by injection of endothelin-1 (ET-1) into the tumor, 20 min after morphine administration. Mice were implanted with optic fibers delivering light in the visible spectrum (405 nm) in the thalamus or prelimbic cortex to locally activate systemically injected JF-NP-26. Light delivery in the thalamus caused rapid and substantial analgesia, and this effect was specific because light delivery in the prelimbic cortex did not relieve BTcP. This finding lays the groundwork for the use of optopharmacology in the treatment of BTcP.

Rapid-Onset Opioids for Management of Breakthrough Cancer Pain: Considerations for Daily Practice.

Background and Objective: Rapid-onset opioids (ROOs) are effective treatments for breakthrough cancer pain (BTcP) given their rapid onset of action and relatively short duration of analgesia. The aim of this article is to describe specific considerations for the use of ROOs in daily practice, focusing on dose titration and treatment of specific populations. Type of Review: We conducted a narrative review on the use of ROOs for BTcP. We selected papers according to the following search terms: "breakthrough cancer pain" and "rapid onset opioids". Results: ROOs may be considered as the most suitable drugs to treat BTcP and can be used "on-demand". Several fentanyl formulations are available and have been associated with control of BTcP and with improvement in quality of life. Various titration schemes have been used to optimize ROO dosing; however, a dose-proportional scheme could be considered safe and effective in most patients. Specific formulations may be more suitable for specific patient subgroups; for example, patients with oral mucositis may prefer intranasal to oral formulations. Moreover, elderly patients or those without caregivers should be clearly educated on the use of these formulations. A key element in achieving successful treatment of BTcP is awareness of the barriers to pain management, including poor overall assessment, patient reluctance to take opioids or report pain, and physician reluctance to prescribe opioids. Conclusion: A personalized approach is fundamental when prescribing a medication for BTcP, and careful attention should be given to drug choice and route of administration, and to the need for alternative therapeutic options.

Management of Metastatic Disease in Campania (MAMETIC): An Observational Multicenter Retrospective and Prospective Trial on Palliative Radiotherapy in an Italian Region. Study Protocol.

Background: In the Italian Campania Region, 30.517 new cases of solid cancer have been diagnosed, in 2019. Of those, patients with metastatic disease are up to 20%. This class of patients is extremely diversified and copious, and the offer of radiotherapy may vary in different geographical areas within the same region. The aim of this observational multicenter retrospective and prospective trial is to evaluate the occurrence of metastatic metastatic cancer patients candidates for palliative radiotherapy in several areas of a great Italian region, the management of the disease through RT approaches, and its impact on cancer-related pain and overall HRQoL. Methods: This is a multicenter, retrospective and prospective observational investigation. The retrospective part of the study concerns all patients enrolled with a diagnosis of metastatic disease and treated in RT centers within the Campania Region between January 2019 and July 2020. The prospective phase is going to involve all the metastatic patients with an indication of palliative RT. Considering regional epidemiological data, we expect an enrollment of 12.500-21.000 patients in 5 years. Conclusion: The MAMETIC Trial in an observational study designed for investigating on the use of radiotherapy in patients with advanced disease within a regional area, and for evaluating the local response to the patient's request. It can be a unique opportunity, not only to highlight possible geographic differences but also to regularly collect and share data to standardize the therapeutic offer within the regional area. ClinicalTrials.gov ID NCT04595032, retrospectively registered.

Strengths and Weaknesses of Cancer Pain Management in Italy: Findings from a Nationwide SIAARTI Survey.

OBJECTIVES: Despite guidelines, a large percentage of cancer patients continue to suffer from ineffectively treated pain. The authors undertook this survey to assess the strengths and weaknesses of cancer pain management in Italy. DESIGN: This was a prospectively administered survey. PARTICIPANTS: The participants were anesthesiologists of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). INTERVENTION: A 58-item questionnaire covered the demographics and features of cancer pain management in the Italian context. RESULTS: The authors received responses from 611 pain therapists of 279 centers. Only 22% of physicians are exclusively pain therapists. Seventy-five percent are specialists in anesthesiology, intensive care, and pain medicine. Most pain centers are hospital or university facilities (78%). The strengths of cancer pain management in Italy are the careful opioid prescriptions, the use of strategies for the treatment of neuropathic pain, patient/healthcare provider partnerships, and breakthrough cancer pain management. Weaknesses to be addressed include poor adherence to guidelines, inadequate attention toward the patient's quality of life, insufficient use of minimally invasive techniques, lack of teamwork approaches, inappropriate timing of pain specialist engagement, and poor telemedicine use. CONCLUSIONS: Despite several strengths, further efforts are needed to improve the care of patients suffering from cancer pain in Italy.

Patients' Satisfaction with Breakthrough Cancer Pain Therapy: A Secondary Analysis of IOPS-MS Study.

Background: Cancer pain is one of the most important symptoms for patients. Pharmacological control is central for clinical management and to ensure well-being. In cancer patients, the management of breakthrough cancer pain (BTcP) is also crucial. This study aims to identify factors that can predict patients' satisfaction with pain relief for BTcP. Methods: This was a secondary analysis of the IOPS-MS study, a large, observational, multicenter, national study where thirty-two Italian centers were involved to explore BTcP management. Clinical and pathologic features were recorded, as well as the patients' degree of satisfaction with BTcP medications classified as dissatisfied (not or indifferent satisfied) versus satisfied (or very satisfied). Frequency distributions and the chi-squared test of independence were performed. A multivariate model was carried out by selecting significant variables upon univariate analysis using logistic regression. Results: From the original 4016 patients enrolled, 3840 were available for the study purpose. Seventy-one per cent of patients declared satisfaction with BTcP medications. Young age [odds ratio (OR) 1.29 (95% confidence interval, CI: 1.12-1.50)], non-metastatic cancer stage [OR 1.53 (95% CI: 1.22-1.91)], high Karnofsky performance status [OR 1.63 (95% CI:1.33-1.99)], the absence of anticancer treatment [OR 1.42 (95% CI: 1.19-1.69)], the NSAIDs/paracetamol use for background pain [OR 1.56 (95% CI: 1.34-1.82)] and a high BTcP interference in activities of daily living [OR 2.34 (95% CI: 1.81-3.01)] resulted positively correlated with dissatisfaction in the multivariate analyses. Also, the setting of care was related to difference in BTcP therapy satisfaction. Conclusion: This study proposes several key points to be considered in the pharmacological management of BTcP, useful to ensure patients' satisfaction and optimal quality of life.