Intrathecal pain treatment for severe pain in patients with terminal cancer: A retrospective analysis of treatment-related complications and side effects.

OBJECTIVES: Two-thirds of patients with advanced cancer experience pain. Some of these patients have severe pain refractory to oral and parenteral medication, for whom intrathecal pain treatment could be an option. While intrathecal therapy is presently used with good results in clinical practice, the current evidence is limited. Hence, increased knowledge of intrathecal pain treatment is needed. This retrospective study aimed to assess complications and side effects related to intrathecal pain treatment in patients with terminal cancer. METHODS: A retrospective study on all patients who received intrathecal treatment with morphine and bupivacaine through externalized catheters for cancer-related pain at a single university hospital during a 5-year period. RESULTS: Treatment-related complications were reported in 24 out of 53 patients. The most common complications were catheter dislocation (13%), catheter occlusion (9%), falls due to bupivacaine-related numbness or weakness (9%), and reversible respiratory depression (8%). There were five serious complications, i.e., meningitis or neurological impairment, of which four were reversible. Side effects related to intrathecal drugs, or the implantation procedure were observed in 35 patients. The most common were bupivacaine-related numbness or weakness (57%) and reversible post-dural puncture headache (19%). Systemic opioid doses decreased during the first 3 weeks of intrathecal treatment, from a median daily dose of 681 to 319 oral morphine milligram equivalents. The median treatment duration time was 62 days. CONCLUSIONS: Complications related to intrathecal treatment are common, but mostly minor and reversible. Side effects are predominantly related to unwanted pharmacological effects from intrathecal drugs. Intrathecal treatment enables the reduction of systemic opioid doses, which indicates a good treatment effect on pain. Hence, intrathecal therapy can be considered a safe pain-relieving treatment in patients with severe refractory cancer-related pain. Future research is warranted on patient acceptability and satisfaction of intrathecal pain treatment.

The effects of opioid tapering on select endocrine measures in men and women with head and neck cancer-a longitudinal 12-month study.

Introduction: Opioid treatment may affect endocrine measures in humans either through centrally or peripherally mediated mechanisms. There is a general lack of longitudinal studies examining endocrine measures in opioid-treated patients. Objectives: To longitudinally follow the levels of select endocrine measures in men and women with head and neck cancer for 1 year, who after having completed radiotherapy began tapering opioids. Methods: This was a prospective, longitudinal, observational study. Testosterone and estradiol were measured in men and women, respectively. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), and prolactin were measured in both sexes. Women were grouped based on if premenopausal or postmenopausal. Samples were collected when opioid tapering started and at 1, 3, 6, and 12 months after tapering start. Daily opioid doses at the same time points were registered. Results: Twenty-five men and 12 women were followed for 12 months. In men, testosterone levels increased significantly during the first month after opioid tapering started (P < 0.001). Levels of testosterone, FSH, DHEAS, and prolactin changed significantly in men during the study period. A moderate correlation between opioid dose reduction and testosterone level increase in men aged ≤60 years was found (r s = -0.577, 95% CI -0.854 to -0.044, P = 0.039). In postmenopausal women (n = 10), levels of FSH and LH changed significantly during the study period. Conclusion: Previously known effects of opioids on endocrine measures in humans seem to be reversible as select endocrine measures changed significantly in men and postmenopausal women after opioid tapering was initiated.

Effects of Exercise in Adults With Cancer Pain: A Systematic Review and Network Meta-Analysis.

CONTEXT: Pain is one of the most common symptoms of cancer patients, affecting the patient's physical, psychological, behavioral, social relations and other aspects. Previous studies have demonstrated that exercise is effective for cancer pain, and the optimal exercise is still unknown. OBJECTIVES: This study aimed to compare the effects of different exercise interventions on cancer pain in adults. METHODS: Randomized control trials identified from medical literature databases that reported effects of exercise in adults with cancer pain were included in this study. Literature screening and data extraction were conducted independently by 2 researchers. Cochrane Bias Assessment 2.0 was used to assess the quality of the literature, and Stata 15.0 software was used for Network meta-analysis. RESULTS: Forty-one studies were included, involving 3537 patients with cancer pain. The types of exercise involved included aerobic exercise, medium intensity continuous training, high-intensity interval training, resistance exercise, mind-body exercise and comprehensive exercise program (CEP). The results suggested that CEP was more effective than the usual care in relieving pain intensity in cancer patients [SMD = -1.96,95% CI (-3.47, -0.44)] (SUCRA = 97.9%). Mind-body exercise outperformed usual care in reducing pain interference in cancer patients [SMD = -0.65, 95% CI (-1.21, -0.09)] (SUCRA = 83.8%). CONCLUSION: Current evidence shows that CEP is the best way to relieve the pain intensity of cancer patients, and mind-body exercise is the best way to reduce pain interference of cancer patients. Due to the limited number and quality of the included studies, the above conclusions need to be further verified by more high-quality studies.

AB069. Type of personality and cancer-related pain in central nervous system (CNS) tumor patients: a cross-sectional study.

BACKGROUND: Pain is the most common complaint experienced by central nervous system (CNS) tumor patients. Pain, especially cancer pain, involves the whole aspect of a person, such as personality, cognition, and behavior. Personality characteristics play an important role in how a person perceives pain rate and deals with painful situation. This study aimed to describe types of personality and investigate relationship between types of personality and cancer-related pain in CNS patients. METHODS: This study was conducted at Cipto Mangunkusumo General Hospital from January to December 2023, that was determined by random sampling. The analysis included a total of 99 subjects from inpatient settings. In depth interview was used to assess type of personality and Numeric Rating Scale (NRS) was used to assess intensity of pain. Data analyses were carried out using the Chi-squared and Fisher's exact test to assess the relationship between types of personality and cancer-related pain in CNS patients. RESULTS: There were 99 subjects with mean age of 48.37±12.96 years, mostly women (60.6%). The results showed that in patients with CNS tumor, the most common neurological deficit was cancer pain (93.9%), consisting of no-mild pain (30.3%) and moderate-severe pain (69.7%). The prevalence of narcissistic personality was 73.7%, followed by histrionic personality 15.2%, and other personality (11.1%) such as borderline, obsessive-compulsive, and avoidant personality. Narcissistic personality traits were found in 48.5% of patients with moderate-severe pain. However, bivariate analysis showed that there was no significant relationship between types of personality and intensity of pain in CNS tumor patients (P=0.60). CONCLUSIONS: Although there was no significant relationship, cluster B personality (narcissistic, histrionic, and borderline) was found in a large percentage of CNS tumor patients. Research findings showed that intensity of pain was caused by biological components of pain and may be influenced by the patient's perception of pain itself, not solely due to personality. Therefore, it's important for health workers to pay attention and give optimal management to every patient's pain complaint, and not to ignore or minimize it. Psychiatrists can be involved by giving psychotherapy so that patients can deal with their pain in a more adaptive way.

Interventional Strategies for Alleviating Severe Abdominal Pain in Chronic Pancreatitis and Abdominal Cancer: A Case Report on the Use of Splanchnic Nerve Radiofrequency Ablation and Erector Spinae Plane Block.

A cancer diagnosis marks the beginning of a difficult path filled with a profound battle against the excruciating pain associated with the illness. Cancer-related pain, which is complex and emotionally distressing, presents unique challenges in terms of treatment. Abdominal cancers and metastases frequently result in severe and unmanageable pain that does not respond well to traditional medications. In such situations, interventions like neurolysis and radiofrequency ablation of the splanchnic nerves and celiac plexus have emerged as effective strategies, providing enhanced pain relief and reducing the need for narcotic painkillers. In this case report, we describe a case of a 38-year-old man with a longstanding history of chronic pancreatitis with a polypoid growth close to the ampulla in the duodenal bulb. The patient was given pain medications to alleviate the pain, but the severe stomach pain, vomiting, and fever persisted. Imaging tests supported the diagnosis and showed chronic pancreatitis, a continuing inflammatory process, and a periampullary adenocarcinoma. The patient had significant pain while being positioned prone for the diagnostic block, hence an erector spinae plane block was done before the radiofrequency ablation. The patient received radiofrequency ablation at the T11 and T12 levels after receiving a diagnostic splanchnic nerve block, significantly reducing pain. The effectiveness of these interventional procedures in enhancing the patient's quality of life and decreasing their dependence on narcotic drugs was highlighted by follow-up visits at two, four, and six months that revealed little to no discomfort. This instance emphasizes the importance of considering neurolysis and radiofrequency ablation as essential alternatives for treating severe abdominal pain brought on by chronic pancreatitis and abdominal cancer.

Outpatient Patient Controlled Analgesia (PCA) for the Palliative Care Patient.

This study explores the under-researched domain of patient-controlled analgesia (PCA) for cancer pain management in adult outpatients, focusing on the transition from patient-controlled analgesia pumps (PCA pump) to oral medications. While existing literature primarily addresses the use of PCA in inpatient settings, this descriptive study investigates the initiation of outpatient PCA in palliative care patients. The retrospective chart review includes data from all admissions between July 1, 2014, and December 31, 2020. Among the 49 identified patients, 41 were admitted for cancer-related pain, with an indication for PCA such as insufficient pain relief, highly fluctuating pain, or inadequate response to other routes. Of these patients, 13 were successfully transitioned from outpatient PCA to oral opioids. The study underscores the effective use of PCA as a transitional tool following a pain crisis that necessitates inpatient admission. Future research avenues could explore healthcare utilization, length of stay, and required outpatient resources, such as home visits or telehealth, for optimal PCA use in outpatient settings.

A Digital Therapeutic Application (ePAL) to Manage Pain in Patients With Advanced Cancer: A Randomized Controlled Trial.

BACKGROUND: Patients with advanced cancer often experience immense cancer pain that negatively impacts their quality of life. Interventions to address cancer-related pain are limited. METHODS: We conducted a randomized trial of a digital therapeutic app (ePAL) for patients with advanced cancer receiving care in a specialty palliative care clinic at a tertiary care hospital. Patients were randomized to ePAL or usual care. ePAL included 1) active pain monitoring; 2) artificial intelligence algorithm to triage patient symptoms; and 3) patient education to address barriers to pain management. Participants were instructed to use ePAL over eight weeks. Patient-reported pain symptoms were assessed at baseline, Week-4, and Week-8 (primary endpoint) using the Brief Pain Inventory. Secondary outcomes include pain-related hospitalizations by Week-8. RESULTS: We enrolled 112 patients who were randomly assigned to ePAL (N = 56) or usual care (N = 56). Patients utilized ePAL on average 2.1 times per week to report pain symptoms, and 47.6% reported their pain at least once per week over eight weeks. Patients randomized to ePAL reported lower pain scores at Week-4 (mean: 3.16 vs. 4.28, P = 0.010) and week-8 (mean:2.99 vs. 4.05, P = 0.017), compared to those receiving usual care. Participants randomized to ePAL were less likely to experience a pain-related hospitalization compared to those in the usual care group (7.1% vs. 23.2% P = 0.018) CONCLUSIONS: ePAL was associated with lower patient-reported pain and fewer pain-related hospitalizations compared to usual care in patients with advanced cancer. This study demonstrates the promise of digital therapeutics for improving patients' symptoms while reducing burdensome hospitalizations.

Incorporating Music Therapy With Acupuncture in Managing Cancer Pain at an Acupuncture Practice.

BACKGROUND: Complementary and alternative medicine encompasses various nonpharmacologic interventions for managing pain, such as acupuncture and music therapy. Few studies have combined these two interventions in the management of cancer-related pain. OBJECTIVES: The purpose of this evidence-based project was to compare acupuncture-only therapy versus dual therapy (acupuncture and music therapy) on pain intensity scores in patients with cancer. METHODS: This evidence-based project included 102 participants at a private acupuncture practice. One group had acupuncture only for six weeks, and another had six weeks of acupuncture and music therapy. The Numeric Pain Rating Scale was used to assess pain before and after the interventions. FINDINGS: Findings showed that both groups had clinically and statistically significant improvements in pain intensity scores. Although a significant difference was not noted between the two groups, acupuncture and music therapy were each found to be effective for managing cancer-related pain.

Prevalence of Reluctance to Prescribe Opioids Among Physicians in Oncology Departments: A Descriptive Cross-Sectional Study From Turkey.

Cancer-related pain (CrP) is a significant public health problem, and opioids are the mainstay of CrP treatment. Considering the persistent problem of inadequate treatment of cancer pain in Turkey, the study was conducted to determine the prevalence of reluctance to prescribe opioids among physicians in oncology departments. The descriptive cross-sectional study included oncology residents and residents without oncology specialization in oncology departments. One thousand physicians were invited by e-mail to the Google Forms survey platform. Two hundred and seventy-eight physicians completed the survey and were included, of which 50% (n: 139) were female. More than half (n: 166; 59.7%) of them were oncology subspecialists. The prevalence of reluctance to prescribe opioids was calculated to be 38.1% (n: 106). A significant positive association was found between the factor associated with reluctance to prescribe opioids and fear of opioid use disorder (ß = 0.964; 95% CI = 0.362-1.566; p = .002). Reluctance to prescribe opioids was inversely related to the oncology subspecialty (ß = -0.878; 95% CI = -1.54 to -0.213; p = 0.010) and education about CrP and opioid management (ß = -1.707; 95% CI = -2.404 to -1.009; p = 0.01). Reluctance to prescribe opioids appears to be associated with a lack of knowledge and fear of opioid use disorder.

High prevalence of severe pain is associated with low opioid availability in patients with advanced cancer: Combined database study and nationwide questionnaire survey in Japan.

OBJECTIVES: Opioid availability for the palliative care of patients with advanced cancer is increasing globally. However, opioid availability remains extremely low in Japan. We investigated whether pain is appropriately controlled by low-dose opioid prescriptions in patients with advanced cancer in Japan. METHODS: A web-based nationwide survey for caregivers from 2000 community comprehensive support care centers was performed in Japan to assess details about pain in the 30 days before patients died of end-stage cancer. Separately, the data for opioid prescription doses and medical services in the 90 days before the death of patients with cancer were extracted from a health insurance claim database. RESULTS: Responses from 1034 responders were retrieved and 665 patients were included. In total, 254 patients (38.2%) complained of severe-to-intolerable cancer-related pain. The median cumulative prescription dose of opioids in the 90 days before patient death was 311.0 mg by oral morphine equivalent doses. Multiple regression analyses across prefectures revealed that the proportion of patients with severe-to-intolerable cancer-related pain was negatively associated with the cumulative opioid consumption expressed as morphine-equivalent doses within 90 days before death. CONCLUSIONS: The very low availability of opioids for patients with end-stage cancer could result in high rate of severe-to-intolerable cancer-related pain patients. There were several limitations in this study, and the interpretations of the findings should be carefully. However, the increase in the absolute dose of opioids could improve the palliative care framework to the pain control levels of the global standard.

Association between adverse childhood experiences and health related quality of life in adult cancer survivors in the United States.

PURPOSE: The impact of adverse childhood experiences (ACEs) on health-related quality of life (HRQOL) is increasingly recognized, however, this has not been studied in cancer survivors in the United States. This study investigates if ACEs are associated with HRQOL in cancer survivors. METHODS: We conducted a cross-sectional analysis of the 2020 Behavioral Risk Factor Surveillance System from states that administered ACEs and Cancer Survivorship modules. Eligibility criteria included being a cancer survivor and not currently receiving cancer treatment. Primary exposure was number of ACEs (categorized as 0, 1-2, 3, or ≥ 4). Primary outcomes were self-reported measures of HRQOL including worse overall health and ≥ 14 unhealthy days (mentally or physically) per month. Mantel-Haenszel stratified analyses were performed and prevalence ratios were adjusted for age. RESULTS: Of 5,780 participants, 62.0% were female and 67.8% were ≥ 65 years. Prevalence of worse overall health was 22.5% for individuals with no ACEs compared to 30.2% for 2-3 ACEs (aPR = 1.4, 95% CI 1.2, 1.5) and 38.5% for ≥ 4 ACEs (aPR = 1.7, 95% CI 1.5, 2.0). Prevalence of ≥ 14 unhealthy days was 18.1% with no ACEs compared to 21.0% for 1 ACE (aPR = 1.3, 95% CI 1, 1.3), 29.0% for 2-3 ACEs (aPR = 1.6, 95% CI 1.4, 1.8), and 44.8% for ≥ 4 ACEs (aPR = 2.2, 95% CI 2.0, 2.5). CONCLUSIONS: Our study provides novel evidence of the association of multiple ACEs with higher prevalence of poor HRQOL in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Screening for ACEs is warranted in all patients to guide targeted interventions to improve HRQOL and mitigate the impact of ACEs on HRQoL in cancer survivors.

Advancing Postoperative Pain Management in Oral Cancer Patients: A Systematic Review.

The goal of this review is to shed light on the management of orofacial discomfort after a cancer diagnosis in the head and neck region. A search was conducted on PubMed, Scopus, and Web of Science to identify studies on postoperative pain control in oral cancer. The review included open-access research, investigations into pain management, randomized clinical trials, retrospective studies, case-control studies, prospective studies, English-written studies, and full-text publications. Exclusion criteria included animal studies; in vitro studies; off-topic studies; reviews, case reports, letters, or comments; and non-English language. Three reviewers independently accessed databases and assigned a quality rating to the chosen articles. The review explores postoperative pain management in oral cancer patients; highlighting persistent opioid use; the efficacy of adjuvant drugs, such as gabapentin; and a multimodal approach. It emphasizes the need for personalized pain management, recognizing individual pain perception and tailoring interventions. Integrating pharmacological and non-pharmacological strategies is crucial for comprehensive pain management. The review also serves as a guide for future research, emphasizing the need for standardized methodologies and diverse participant populations.

The use of interventional procedures for cancer pain. A brief review.

CONTEXT: Pain is a common experience in people living with cancer. Concerns around opioid prescribing have seen a move toward a multi-modality management approach, which includes interventional pain procedures. PURPOSE: In this paper we discuss the interventional pain procedures used to treat cancer pain at two major tertiary centers in Australia. METHODS AND RESULTS: This expert review provides practical insights on cancer pain management from healthcare providers in different specialties. These insights can be used to guide the management of a wide range of cancer pain types. CONCLUSIONS: Furthermore, this review identifies the need for a systematic and comprehensive approach to the management of cancer pain that is broader than that of a single specialty. With recent advances in pain management procedures, an interdisciplinary approach is essential in order to provide an up to date, patient tailored approach to pain management. This review will help inform the development of a cancer pain intervention registry.

Cingulotomy for Intractable Pain: A Systematic Review of an Underutilized Procedure.

Pain management is a critical aspect of cancer treatment and palliative care, where pain can significantly impact quality of life. Chronic pain, which affects a significant number of people worldwide, remains a prevalent and challenging symptom for patients. While medications and psychosocial support systems play a role in pain management, surgical and radiological interventions, including cingulotomy, may be necessary for refractory cases. Cingulotomy, a neurosurgical procedure targeting the cingulate gyrus, aims to disrupt neural pathways associated with emotional processing and pain sensation, thereby reducing the affective component of pain. Although cingulotomy has shown promise in providing pain relief, particularly in patients refractory to traditional medical treatment, its use has declined in recent years due to advancements in non-destructive therapies and concerns about long-term efficacy and patient suitability. Modern stereotactic methods have enhanced the precision and safety of cingulotomy, reducing associated complications and mortality rates. Despite these advancements, questions remain regarding its long-term efficacy and suitability for patients with limited life expectancy, particularly those with cancer. A comprehensive systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, aimed at providing insights into the efficacy, potential benefits, and limitations of this neurosurgical procedure in managing intractable pain. An electronic search of PubMed, Embase, Scopus, and Web of Science was conducted with open database coverage dates. The review focused on outcomes such as pain intensity and quality of life. The inclusion criteria encompassed human studies of any age experiencing intractable cancer or non-cancer pain, with cingulotomy as the primary intervention. Various study designs were considered, including observational studies, clinical trials, and reviews focusing on pain and cingulotomy. Exclusion criteria included non-human studies, non-peer-reviewed articles, and studies unrelated to pain or cingulotomy. This review highlights the efficacy of stereotactic anterior cingulotomy in managing intractable pain, particularly when conventional treatments fail. Advanced MRI-guided techniques enhance precision, but challenges like cost and expertise persist. Studies included in this review showed significant pain relief with minimal adverse effects, although the optimal target remains debated. Neurocognitive risks exist, but outcomes are generally favorable. Expected adverse events include transient effects like urinary incontinence and confusion. Reoperation may be necessary for inadequate pain control, with a median pain relief duration of three months to a year. A double stereotactic cingulotomy appears to be safe and effective for refractory pain.

Access to psychological treatment for chronic cancer-related pain in Sweden.

OBJECTIVES: Cancer-related pain (CRP) is among the most frequent collateral effects of cancer, with chronic CRP, lasting at least 3 months, affecting >40% of cancer survivors. Evidence-based treatments, including pain-focused cognitive behavioral therapy (CBT), are available, but it appears that cancer patients/survivors are often poorly informed about CRP or the potential benefits of CBT for such pain. This study examined current experience of Swedish cancer patients/survivors in relation to CRP. METHODS: Participants (N = 276; 83% female; mean age = 55.5 years, SD = 11.9) were recruited to an online survey via cancer websites in Sweden, and they provided information about their history of chronic CRP and whether they received information about or treatment for CRP from a healthcare professional. RESULTS: Participants had a history of breast (36%), gynecological (12%), lung (10%), colon (8%), and other forms of cancer (36%). A majority (74%) reported a history of chronic CRP and being prescribed analgesic medications (70%). Less than half (47%) received information from their healthcare provider about the risk of CRP and only 13% with chronic CRP received psychological treatment, and of these, only 33% received CBT. Among those receiving psychological treatment for chronic CRP, satisfaction rates were moderate, reported as an average of 6 on a 0-10 scale (standard deviation 2.6). CONCLUSIONS: Greater efforts are needed to raise awareness among cancer patients/survivors and healthcare providers about the risk of CRP and evidence-based interventions, including CBT, the first-line intervention for chronic pain. These efforts will need to be matched with increases in treatment capacity, particularly pain-focused CBT.

Dysregulation of sphingolipid metabolism in pain.

Pain is a clinical condition that is currently of great concern and is often caused by tissue or nerve damage or occurs as a concomitant symptom of a variety of diseases such as cancer. Severe pain seriously affects the functional status of the body. However, existing pain management programs are not fully satisfactory. Therefore, there is a need to delve deeper into the pathological mechanisms underlying pain generation and to find new targets for drug therapy. Sphingolipids (SLs), as a major component of the bilayer structure of eukaryotic cell membranes, also have powerful signal transduction functions. Sphingolipids are abundant, and their intracellular metabolism constitutes a huge network. Sphingolipids and their various metabolites play significant roles in cell proliferation, differentiation, apoptosis, etc., and have powerful biological activities. The molecules related to sphingolipid metabolism, mainly the core molecule ceramide and the downstream metabolism molecule sphingosine-1-phosphate (S1P), are involved in the specific mechanisms of neurological disorders as well as the onset and progression of various types of pain, and are closely related to a variety of pain-related diseases. Therefore, sphingolipid metabolism can be the focus of research on pain regulation and provide new drug targets and ideas for pain.

Benefits, Harms, and Stakeholder Perspectives Regarding Opioid Therapy for Pain in Individuals With Metastatic Cancer: Protocol for a Descriptive Cohort Study.

BACKGROUND: Opioids are a key component of pain management among patients with metastatic cancer pain. However, the evidence base available to guide opioid-related decision-making in individuals with advanced cancer is limited. Patients with advanced cancer or cancer that is unlikely to be cured frequently experience pain. Opioids are a key component of pain management among patients with metastatic cancer pain. Many individuals with advanced cancer are now living long enough to experience opioid-related harm. Emerging evidence from chronic noncancer pain literature suggests that longer-term opioid therapy may have limited benefits for pain and function, and opioid-related harms are also a major concern. However, whether these benefits and harms of opioids apply to patients with cancer-related pain is unknown. OBJECTIVE: This manuscript outlines the protocol for the "Opioid Therapy for Pain in Individuals With Metastatic Cancer: The Benefits, Harms, and Stakeholder Perspectives (BEST) Study." The study aims to better understand opioid decision-making in patients with advanced cancer, along with opioid benefits and harms, through prospective examination of patients' pain experiences and opioid side effects and understanding the decision-making by patients, care partners, and clinicians. METHODS: This is a multicenter, prospective cohort study that aims to enroll 630 patients with advanced cancer, 20 care partners, and 20 clinicians (670 total participants). Patient participants must have an advanced solid cancer diagnosis, defined by the American Cancer Society as cancer that is unlikely to be cured. We will recruit patient participants within 12 weeks after diagnosis so that we can understand opioid benefits, harms, and perspectives on opioid decision-making throughout the course of their advanced cancer (up to 2 years). We will also specifically elicit information regarding long-term opioid use (ie, opioids for ≥90 consecutive days) and exclude patients on long-term opioid therapy before an advanced cancer diagnosis. Lived-experience perspectives related to opioid use in those with advanced cancer will be captured by qualitative interviews with a subset of patients, clinicians, and care partners. Our data collection will be grounded in a behavioral decision research approach that will allow us to develop future interventions to inform opioid-related decision-making for patients with metastatic cancer. RESULTS: Data collection began in October 2022 and is anticipated to end by November 2024. CONCLUSIONS: Upon successful execution of our study protocol, we anticipate the development of a comprehensive evidence base on opioid therapy in individuals with advanced cancer guided by the behavioral decision research framework. The information gained from this study will be used to guide interventions to facilitate opioid decisions among patients, clinicians, and care partners. Given the limited evidence base about opioid therapy in people with cancer, we envision this study will have significant real-world implications for cancer-related pain management and opioid-related clinical decision-making. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54953.

Integrative Medicine for Cancer-Related Pain: A Narrative Review.

Cancer-related pain (C-RP) is a prevalent and debilitating concern among patients with cancer, with conventional treatments limited in their ability to provide adequate relief, and by the adverse effects associated with their use. Complementary and integrative medicine (CIM) modalities have been shown to be potentially effective and safe for the treatment of pain and related symptoms, when used in conjunction with conventional medications and under medical supervision. An increasing number of oncology centers provide CIM within their conventional supportive and palliative care service, in an "Integrative Oncology" (IO) setting. A large body of clinical research, including systematic reviews and guidelines such as those published in 2022 by the Society for Integrative Oncology (SIO), in collaboration with the American Society for Clinical Oncology (ASCO), support the use of some CIM modalities for C-RP and related concerns. These include acupuncture for general and peri-operative/procedural pain, as well as aromatase inhibitor-associated arthralgia (AIA); reflexology or acupressure for pain during systemic therapy for cancer; hypnosis for procedural pain or pain due to diagnostic workup; and massage for pain experienced by patients during palliative and hospice care. Further research is needed, within both randomized control trials and pragmatic non-controlled studies which are more reflective of the real-life IO setting. This review summarizes the evidence supporting the use of CIM for C-RP; the analgesic mechanism of the modalities presented; and the challenges facing IO researchers, as well as the implementation of the 2022 SIO-ASCO guideline recommendations.

Cytokine Expression in Cancer Survivors Suffering From Chronic Pain: A Systematic Review.

BACKGROUND: Chronic cancer-related pain remains underdiagnosed and undertreated, although it affects 40% of cancer survivors. Recent insights suggest that cytokine signaling between immune, neuro, and glial cells contributes to chronic pain. OBJECTIVES: This study systematically reviewed cytokine levels and their relation to chronic cancer-related pain and, additionally, investigated differences in cytokine levels between cancer survivors with and without chronic pain. STUDY DESIGN: Systematic review. METHODS: This systematic review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). The study conducted a systematic literature search in the databases PubMed, Web of Science, and Embase for articles examining cytokine levels and pain experience at a time point of a minimum of 3 months post-cancer diagnosis. Pain experience was categorized into a total pain score, pain intensity, and pain interference. The risk of bias was assessed using the Newcastle Ottawa Scale. RESULTS: Eight articles were included, investigating 6 cancer types and 30 cytokines. Moderate evidence was found for pro-inflammatory cytokine IL-6 to be correlated with pain intensity, of which higher levels are observed in cancer survivors experiencing chronic pain compared to pain-free survivors. Moderate evidence was found for TNF-alpha to be not correlated with any pain experience, which is similar for anti-inflammatory cytokines IL-8 and IL-10 with pain intensity. For the remaining 26 cytokines and pain outcomes, only limited evidence was found for an association or alteration. LIMITATIONS: The number of included studies was small. Overall, studies showed a moderate risk of bias, except one indicated a high risk of bias. CONCLUSION: More standardized post-cancer treatment studies are warranted to confirm these results and explore associations and alterations of other cytokines. Nonetheless, moderate evidence suggests that elevated levels of IL-6, in contrast with TNF-alpha levels, are correlated with pain intensity in cancer survivors experiencing chronic pain compared to pain-free survivors.

Cannabinoids for Cancer-related Pain Management: An Update on Therapeutic Applications and Future Perspectives.

Pain is a debilitating phenomenon that dramatically impairs the quality of life of patients. Many chronic conditions, including cancer, are associated with chronic pain. Despite pharmacological efforts that have been conducted, many patients suffering from cancer pain remain without treatment. To date, opioids are considered the preferred therapeutic choice for cancer-related pain management. Unfortunately, opioid treatment causes side effects and inefficiently relieves patients from pain, therefore alternative therapies have been considered, including Cannabis Sativa and cannabinoids. Accumulating evidence has highlighted that an increasing number of patients are choosing to use cannabis and cannabinoids for the management of their soothing and non-palliative cancer pain and other cancer-related symptoms. However, their clinical application must be supported by convincing and reproducible clinical trials. In this review, we provide an update on cannabinoid use for cancer pain management. Moreover, we tried to turn a light on the potential use of cannabis as a possible therapeutic option for cancer-related pain relief.