Predictive Biomarkers of Dyspnea Response to Dexamethasone and Placebo in Cancer Patients.

CONTEXT: In the Alleviating Breathlessness in Cancer Patients with Dexamethasone (ABCD) trial, dexamethasone did not improve dyspnea more than placebo in unselected cancer patients. However, it is unclear if patients with greater inflammation would be more likely to derive a treatment response. OBJECTIVES: To examine the predictive utility of cytokines for dyspnea response. METHODS: We performed a secondary analysis of the ABCD double-blind, randomized clinical trial comparing high-dose dexamethasone to placebo (NCT03367156). The primary outcome was dyspnea intensity over 14 days. Blood cytokine levels (TNF, IL-6, IL-8, and IL-10) were measured at baseline, day seven, and day 14. We used a generalized additive model to examine the association between baseline cytokine level and change in dyspnea from baseline to day seven and baseline to day 14 in dexamethasone and placebo groups. RESULTS: Of the 128 enrolled patients, 45 provided blood samples. TNF, IL-6, and IL-8 decreased over 14 days in the dexamethasone group but not placebo (P<0.05). Lower baseline TNF was associated with a greater reduction in dyspnea intensity by day seven in the placebo group (P=0.0013); conversely, higher baseline TNF was associated with a greater reduction in dyspnea intensity by day 7 in the dexamethasone group (difference between groups P=0.0019). Similar patterns were observed for IL-6 (P=0.000051), IL-8 (P=0.00063), and IL-10 (P=0.01) on day seven, and all cytokines on day 14. CONCLUSION: Cytokines decreased with dexamethasone, but not placebo. Higher baseline cytokine levels may identify patients likely to respond to dexamethasone and less likely to respond to placebo.

Perceptions Toward Naloxone Among Patients With Cancer Receiving Opioids.

CONTEXT: Naloxone nasal spray is recommended for patients with risk factors for opioid overdose. However, cancer patients' perceptions and beliefs regarding naloxone prescriptions and their self-perceived risks for overdose are understudied. OBJECTIVE: To determine the proportion of cancer patients at risk for overdose who perceived naloxone as beneficial. METHODS: Between July 2020 and April 2022, we surveyed 150 adult patients from the supportive care ambulatory clinic at a tertiary cancer center in the United States who received a co-prescription of naloxone nasal spray. We measured patients' knowledge of overdose risk-factors, attitudes, beliefs, and education received on naloxone. Risk-factors between beneficial vs. nonbeneficial groups were analyzed. The survey was administered on paper or via a telephone interview. RESULTS: Of the 150 patients, 55% were male, 70% were white, and 81% had advanced cancer. The majority of patients believed naloxone was beneficial (100/150, 67%). When compared to the nonbeneficial group, more patients from the beneficial group agreed that the concurrent use of alcohol (100% vs. 90%; P = 0.004) or sedating drugs (96% vs. 85%; P = 0.04) with opioids could result in overdoses and felt safe having naloxone at home (95% vs. 60%; P <0.0001). More patients from the nonbeneficial group associated naloxone prescription with being suspected of misusing opioids (12/50 vs. 8/100; P = 0.01), and fewer had confidence in their caregivers' ability to administer naloxone (69% vs. 95%; P < 0.0001). CONCLUSION: Most patients understood the benefits of naloxone and felt safe having one at home. More research is needed to identify knowledge gaps and develop educational strategies for those who find it nonbeneficial.

Transdermal Fentanyl in Patients with Cachexia-A Scoping Review.

Cachectic patients frequently require transdermal fentanyl (TDF) for pain management, but data on its efficacy and safety are scarce and inconsistent. This scoping review aims to analyze the evidence concerning TDF administration in patients with cachexia irrespective of the underlying pathology. The primary objective is to assess the analgesic efficacy and tolerability of TDF in cachectic patients. The secondary objective is to identify cachexia characteristics that may influence fentanyl pharmacokinetics (PK). A comprehensive search of PubMed, Embase, and Web of Science databases was conducted up to March 2024. The review included observational and clinical studies on cachectic patients with moderate to severe pain treated with TDF patches at any dosage or frequency. Phase 1 trials, animal studies, case reports, preclinical studies and conference abstracts were excluded. Nine studies were included: four studies reported that cachexia negatively impacted TDF efficacy, increasing required doses and lowering plasma concentrations; three studies found minimal or no impact of cachexia on TDF efficacy and PK; two studies suggested that cachexia might improve TDF outcomes. Study quality ranged from moderate to high, according to the National Institutes of Health (NIH) Quality Assessment Tool. The current evidence is insufficient to provide any definitive recommendations for TDF prescribing in cachectic patients.

Top Ten Tips Palliative Care Clinicians Should Know About Designing a Clinical Trial in Palliative Care.

The palliative care field is experiencing substantive growth in clinical trial-based research. Randomized controlled trials provide the necessary rigor and conditions for assessing a treatment's efficacy in a controlled population. It is therefore important that a trial is meticulously designed from the outset to ensure the integrity of the ultimate results. In this article, our team discusses ten tips on clinical trial design drawn from collective experiences in the field. These ten tips cover a range of topics that can prove challenging in trial design, from developing initial methodologies to planning sample size and powering the trial, as well as collaboratively navigating the ethical issues of trial initiation and implementation as a cohesive team. We aim to help new researchers design sound trials and continue to grow the evidence base for our specialty. The guidance provided here can be used independently or in addition to the ten tips provided by this team in a separate article focused on what palliative care clinicians should know about interpreting a clinical trial.

Conducting Physician Engagement Research in a Pandemic: Persevering when Burnout Mitigation Is Needed Most.

Background: We planned a pilot study on a physician engagement intervention, termed ECHO-MDA, using the Project ECHO framework. The study was approved and launched just as the COVID pandemic reached Texas. We pivoted to accommodate the realities of research in pandemic times. Objectives: The primary outcome was feasibility assessed by the proportion of participants attending at least 9 out of 13 ECHO-MDA sessions. Design: The study was envisioned as a randomized, wait-list pilot study exploring the impact ECHO-MDA with a planned enrollment of 50 physicians (25 per arm). Results: Due to pandemic-related challenges, 35 physicians were enrolled. Ten attended nine or more sessions. Participants indicated that the program was beneficial. Conclusion: Pandemic-related work and personal conditions likely had adverse impacts on enrollment and attendance. Launching professional wellness programs during a global crisis is challenging but can still yield benefits for participants. We offer suggestions for researchers launching professional engagement studies in unexpectedly challenging times.

Self and proxy symptom reporting in glioma patient-caregiver dyads: the role of psychosocial function in rating accuracy.

BACKGROUND: Illness-related communication and depressive symptoms within families may play an important role in caregivers' ability to accurately understand patients' symptom burden. We examined the associations between these psychosocial factors and symptom accuracy in patients with glioma and their family caregivers. METHODS: Patients and caregivers (n = 67 dyads) completed measures of depressive symptoms (CES-D), illness communication (CICS), and QOL (SF-36). Patients reported on their own cancer-related symptoms (MDASI-BT) while caregivers reported on their perception of the patients' symptoms (i.e., proxy reporting). Paired t-tests and difference scores were used to test for agreement (absolute value of difference scores between patients and caregiver proxy symptom and interference severity reports) and accuracy (caregiver underestimation, overestimation, or accurate estimation of patient symptom and interference severity). RESULTS: Clinically significant disagreement was found for all means scores of the MDASI-BT subscales except for gastrointestinal symptoms and general symptoms. Among caregivers, 22% overestimated overall symptom severity and 32% overestimated overall symptom interference. In addition, 13% of caregivers underestimated overall symptom severity and 21% of caregivers underestimated overall symptom interference. Patient illness communication was associated with agreement of overall symptom severity (r=-0.27, p = 0.03) and affective symptom subscale (r=-0.34, p < 0.01). Caregivers' reporting of illness communication (r=-0.33, p < 0.01) and depressive symptoms (r = 0.46, p < 0.0001) were associated with agreement of symptom interference. Caregiver underestimating symptom severity was associated with lower patient physical QOL (p < 0.01); caregiver underestimating symptom interference was associated with lower patient physical QOL (p < 0.0001) and overestimating symptom interference was associated with lower patient physical QOL (p < 0.05). Patient and caregiver mental QOL was associated with caregiver underestimating (p < 0.05) and overestimating (p < 0.05) symptom severity. CONCLUSION: The psychosocial context of the family plays an important role in the accuracy of symptom understanding. Inaccurately understanding patients experience is related to poor QOL for both patients and caregivers, pointing to important targets for symptom management interventions that involve family caregivers.

Simulation-based caregiving skills training for family members of high-grade glioma patients.

Background: Because family caregivers of patients with a high-grade glioma experience high levels of distress and feel unprepared to perform the complex caregiving tasks associated with the disease and its treatment, we pilot-tested a caregiving skills intervention that integrates hands-on caregiving with coping skill training. Methods: In this single-arm trial, caregivers participated in a 4-session research nurse-led intervention involving simulation-based caregiving skills training at the hospital and psychoeducation delivered via videoconference. We collected measures of patients' and caregivers' psychological symptoms; caregivers' caregiving self-efficacy and role adjustment; and patients' cancer-related symptoms (MDASI) at baseline and again postintervention. We tracked feasibility data. Results: We approached 29 dyads of which 10 dyads (34%) consented. All patients (mean age: 60 years, 89% male) and caregivers (mean age: 58 years, 80% female, 80% spouses) completed the baseline and 7 dyads completed the follow-up assessments (attrition was related to patient's hospice transfer). Seven caregivers completed all 4 sessions and rated the program as beneficial. Paired t-tests revealed a significant improvement in caregiving self-efficacy at 6 weeks postintervention (t = -3.06, P = .02). Although improvements in caregiver role adjustment and patient and caregiver symptoms were not observed, no decreases in symptom burden or role adjustment were found during the follow-up period. Conclusions: This novel supportive care program appears to be safe, feasible, acceptable, and perceived as useful for caregivers of patients with high-grade glioma. Based on feasibility indicators and a signal of intervention efficacy, a randomized controlled trial is warranted.

Opioid analgesic dose and route conversion ratio studies: a scoping review to inform an eDelphi guideline.

BACKGROUND: Clinicians regularly prescribe opioids to manage acute and chronic cancer pain, frequently to address acute postoperative pain, and occasionally to manage chronic non-cancer pain. Clinical efficacy may be suboptimal in some patients due to side effects and/or poor response, and opioid rotation/switching (conversions) is frequently necessary. Despite the widespread practice, opioid conversion ratios are inconsistent between clinicians, practices, and countries. Therefore, we performed a scoping systematic review of opioid conversion studies to inform an international eDelphi guideline. METHODS: To ensure a comprehensive review, we conducted a systematic search across multiple databases (OVID Medline, PsycINFO, Embase, EBM-Cochrane Database of Systematic Reviews and Registered Trials, LILACS, IMEMR, AIM, WPRIM) using studies published up to June 2022. Additionally, we performed hand and Google Scholar searches to verify the completeness of our findings. Our inclusion criteria encompassed randomized and non-randomized studies with no age limit, with only a few pediatric studies identified. We included studies on cancer, non-cancer, acute, and chronic pain. The level and grade of evidence were determined based on the Multinational Supportive Care in Cancer (MASCC) criteria. RESULTS: Our search yielded 21,118 abstracts, including 140 randomized (RCT) and 68 non-randomized (NRCT) clinical trials. We compared these results with recently published conversion ratios. Modest correlations were noted between published reviews and the present scoping systematic review. CONCLUSION: The present scoping systematic review found low-quality evidence to support an opioid conversion guideline. We will use these data, including conversion ratios and type and route of administration, to inform an eDelphi guideline.

Top Ten Tips Palliative Care Clinicians Should Know About Interpreting a Clinical Trial.

Evidence-based practice is foundational to high-quality palliative care delivery. However, the clinical trials that compose the evidence base are often methodologically imperfect. Applying their conclusions without critical application to the clinical practice context can harm patients. The tips provided can help clinicians infer judiciously from clinical trial results and avoid credulously accepting findings without critique. We suggest that statistical and mathematical expertise is unnecessary, but rather a keen curiosity about investigators' rationale for certain design choices and how these choices can affect results is key. For a more comprehensive understanding of clinical trials, this article can be used with the authors' corresponding ten tips article that focuses on designing a clinical trial.

Cancer-related fatigue among patients with advanced cancer receiving immune-checkpoint inhibitors: a prospective study.

PURPOSE: The aim of this study was to determine the frequency and factors associated with severity of cancer related fatigue (CRF) as assessed by Functional Assessment of Cancer Illness Therapy-Fatigue (FACIT-F), prior to, and during 12 weeks of immune-checkpoint inhibitors (ICIs). We also explored the effects of ICIs on fatigue dimensions and interference with daily activities (Multidimensional Functional Symptom Inventory, MFSI-SF, Patient-Related Outcome Symptom Measurement Information System Short form Fatigue 7a, PROMIS F-SF), QOL (Functional Assessment of Cancer Therapy-General, FACT-G), and cancer symptoms (Edmonton Symptom Assessment Scale, ESAS). METHODS: In this prospective, longitudinal observational study, patients with a diagnosis of advanced cancer receiving ICIs were evaluated. Patient demographics, FACT-G, FACIT-F, MFSI-SF, PROMIS F-SF, and ESAS were collected prior to, and during 12 weeks of ICIs. RESULTS: A total of 160 of the 212 enrolled patients were analyzed. The median age was 61 years, 60% were female, most common cancer was melanoma (73%), and most common ICI was nivolumab 46%. The frequency of clinically significant fatigue (defined as ≤ 34/52 on FACIT-F score) was 25.6% at baseline, 25.7% at week 8, and 19.5% at week 12. There was significant improvement in FACIT-F (P = 0.016), FACT-G physical well-being (P = 0.041), FACT-G emotional well-being (P = 0.011), ESAS anxiety (P = 0.045), and ESAS psychological distress (P = 0.03) scores from baseline to week 12 of ICIs. Multivariate analysis found significant association between clinically significant CRF and PROMIS F-SF (P < 0.001) and MFSI-SF global scores (P < 0.001). CONCLUSIONS: CRF is frequent prior to the initiation of ICI treatment. Over 12 weeks of ICI treatment, CRF significantly improved. FACT-G physical well-being, FACT-G emotional well-being, ESAS anxiety, and ESAS psychological distress scores improved overtime. Further studies are needed to validate these findings.

Onabotulinum toxin injections for shoulder and chest wall muscle pain in breast cancer survivors: retrospective study - preliminary report.

OBJECTIVES: The primary objective of this retrospective review is to describe patient-reported improvement in muscular pain after initial treatment with onabotulinum toxin. A secondary objective was to determine other physiatry (physical medicine & rehabilitation (PM&R)) interventions ordered. METHODS: Preliminary retrospective review of physiatry interventions for 47 patients referred by breast radiation oncology to PM&R at a tertiary referral-based academic cancer centre clinic from 1 January 2018 to 31 December 2021 for muscular shoulder/chest wall pain. RESULTS: Patients were most commonly diagnosed with muscle spasm 27/47 (58%), lymphedema 21/47 (45%), myalgia/myofascial pain 16/47 (34%), radiation fibrosis 14/47 (30%), fatigue/deconditioning 13/47 (28%), neurological impairment 11/47 (23%) and joint pathology 3/47 (6%). The top three physiatric interventions were home exercise programme education (17/47, 36%), botulinum toxin injection (17/47, 36%) and physical or occupational therapy referral (15/47, 32%). Patients who had muscle spasms documented were more likely to have botulinum toxin recommended by physiatry (24/24) compared with those with questionable spasms (4/7) and those without spasms(0/16) (p=0.0005). 17/28 (60.7%) received botulinum toxin injection, and a total of 35 injections were performed during the study period. 94% (16/17) of patients who received botulinum toxin injection voiced improvement in pain after injection. CONCLUSION: Botulinum toxin injections may play a role in the treatment of muscle spasm-related pain in breast cancer survivors. Additional blinded controlled research on the effectiveness of botulinum toxin injection after breast cancer treatment with spastic muscular shoulder/chest wall pain is needed.

Palliative Surgery for Patients with Gastroesophageal Junction or Gastric Cancer: A Report on Clinical Observational Outcomes.

BACKGROUND: Few studies have focused on palliative surgery in patients with advanced gastroesophageal junction (GEJ) or gastric cancer. We sought to evaluate clinical observational outcomes following palliative surgery in this population. PATIENTS AND METHODS: Patients with GEJ or gastric cancer who underwent palliative surgery (1/2010-11/2022) were identified. The primary outcomes were symptom improvement, ability to tolerate an oral diet, discharge to home, 30 "good days" without hospitalization, and receipt of systemic treatment. Postoperative outcomes and survival were secondarily evaluated. RESULTS: Among 93 patients, the median age was 59 (IQR 47-68) years, and the median Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was 1 (range 0-3). The most frequent indication for palliative surgery was primary tumor obstruction [75 (81%) patients]. The most common procedures were feeding tube placement in 60 (65%) and intestinal bypass in 15 (16%) patients. A total of 75 (81%) patients experienced symptom improvement. Of these, 19 (25%) developed recurrent and 49 (65%) developed new symptoms. ECOG-PS was significantly associated with symptom-free time. Among those who underwent a bypass, resection, or ostomy creation for malignant obstruction, 16 (80%) tolerated an oral diet. Postoperatively, 87 (94%) were discharged home, 72 (77%) had 30 good days, and 64 (69%) received systemic treatment. Postoperative complications occurred in 35 (38%) patients, and 7 (8%) died within 30 days. The median survival time was 7.7 (95% CI 6.4-10.40) months. CONCLUSIONS: Patients with incurable GEJ or gastric cancer can benefit from palliative surgery. Prognosis and performance status should inform goals-of-care discussions and patient selection for surgical palliation.

Early palliative care perceptions by patients with cancer and primary caregivers: metaphorical language.

OBJECTIVE: This article reports on the results of an analysis of metaphorical language used by patients diagnosed with advanced cancer and their caregivers receiving early palliative care (EPC). METHODS: Data were collected through a pen-and-paper questionnaire on respondents' perceptions of the disease, its treatment and their idea of death, before and after receiving EPC. The data were analysed by identifying all metaphorical uses of language, following the 'metaphor identification procedure' proposed by the Praggjelaz Group. RESULTS: Metaphors were used from a variety of semantic fields. EPC was described using spiritual terms, to indicate that this approach was instrumental in 'restoring life', 'producing hope' and making patients feel 'accompanied'. The most recurrent metaphors were those referring to light and salvation; spatial metaphors were used to describe the treatment and the hospital as a 'safe haven' and 'an oasis of peace'. Patients and caregivers were overall consistent in the aforementioned ways of referring to illness and treatment; caregivers were more likely than patients to use war metaphors, although their use overall was rare. CONCLUSIONS: Our results suggest that EPC is perceived positively by patients and their caregivers and provide insights regarding the manner in which EPC could be presented to patients, caregivers and the public.