Do Patient Demographics and Performance Status Influence Opioid Dose in Cancer Pain?

Context: There is limited evidence on the role of objective parameters in influencing analgesic use in cancer pain management.Objective: To investigate the significance of objective parameters (age, male/female and performance status) in influencing opioid dose. Methods: We conducted a retrospective cross-sectional audit of adult inpatients with metastatic cancer at a major cancer centre from 1 January 2016 to 31 December 2018, who were prescribed slow release opioids for cancer pain on discharge. Main outcome measures were demographics (age, male/female and performance status), oral morphine equivalent daily dose (oMEDD) and adjuvant analgesic use. Results: Of the 7,747 eligible records, 215 patient records fulfilled inclusion criteria. Older patients (≥75 years) received half of the median oMEDD dose (30 mg) compared to their youngest counterparts (60 mg oMEDD in age ≤50 years) (P = .003). No significant differences were observed between oMEDD and male/female and performance status. Conclusion: Older patients are prescribed half the opioid dose compared to their younger counterparts. This highlights the importance of vigilance in opioid prescribing in the elderly in order to balance side effects with under treatment. Although no other significant relationships were observed, future studies comparing objective patient parameters with opioid prescription may uncover other at risk populations.

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890.

DNA methylation-based profiling for paediatric CNS tumour diagnosis and treatment: a population-based study.

BACKGROUND: Marked variation exists in the use of genomic data in tumour diagnosis, and optimal integration with conventional diagnostic technology remains uncertain despite several studies reporting improved diagnostic accuracy, selection for targeted treatments, and stratification for trials. Our aim was to assess the added value of molecular profiling in routine clinical practice and the impact on conventional and experimental treatments. METHODS: This population-based study assessed the diagnostic and clinical use of DNA methylation-based profiling in childhood CNS tumours using two large national cohorts in the UK. In the diagnostic cohort-which included routinely diagnosed CNS tumours between Sept 1, 2016, and Sept 1, 2018-we assessed how the methylation profile altered or refined diagnosis in routine clinical practice and estimated how this would affect standard patient management. For the archival cohort of diagnostically difficult cases, we established how many cases could be solved using modern standard pathology, how many could only be solved using the methylation profile, and how many remained unsolvable. FINDINGS: Of 484 patients younger than 20 years with CNS tumours, 306 had DNA methylation arrays requested by the neuropathologist and were included in the diagnostic cohort. Molecular profiling added a unique contribution to clinical diagnosis in 107 (35%; 95% CI 30-40) of 306 cases in routine diagnostic practice-providing additional molecular subtyping data in 99 cases, amended the final diagnosis in five cases, and making potentially significant predictions in three cases. We estimated that it could change conventional management in 11 (4%; 95% CI 2-6) of 306 patients. Among 195 historically difficult-to-diagnose tumours in the archival cohort, 99 (51%) could be diagnosed using standard methods, with the addition of methylation profiling solving a further 34 (17%) cases. The remaining 62 (32%) cases were unresolved despite specialist pathology and methylation profiling. INTERPRETATION: Together, these data provide estimates of the impact that could be expected from routine implementation of genomic profiling into clinical practice, and indicate limitations where additional techniques will be required. We conclude that DNA methylation arrays are a useful diagnostic adjunct for childhood CNS tumours. FUNDING: The Brain Tumour Charity, Children with Cancer UK, Great Ormond Street Hospital Children's Charity, Olivia Hodson Cancer Fund, Cancer Research UK, and the National Institute of Health Research.

Health beliefs, attitudes, and health-related quality of life in persons with fibromyalgia: mediating role of treatment adherence.

Fibromyalgia is a chronic illness characterized by pain and fatigue. Persons with fibromyalgia experience increased the risk for poor mental and physical health-related quality of life, which may be dependent on multiple factors, including health beliefs, such as confidence in physicians and the health-care system, and health behaviors, such as treatment adherence. Respondents with fibromyalgia (n = 409) were recruited nationally, via support organizations, and completed self-report measures: Multidimensional Health Profile - Health Functioning Index (MHP-H), Short-Form-36 Health Survey (SF-36v2), and Medical Outcomes Study (MOS) Measure of Patient Adherence - General Adherence Items. In mediation models, belief in the healthcare system and health-care personnel, and health efficacy exerted an indirect effect through treatment adherence on mental and physical quality of life. Adaptive health beliefs and attitudes were related to greater treatment adherence and, in turn, to a better quality of life. Maladaptive health beliefs and mistrusting attitudes about physician-level and systemic-level healthcare provision are negatively related to both treatment adherence and consequent physical and mental health-related quality of life in persons with fibromyalgia. Future randomized controlled trials are needed to determine if therapeutic strategies to alter health values might improve adherence and self-rated health.

Efficacy of anti-PD-1 therapy in patients with melanoma brain metastases.

BACKGROUND: There is limited data on the efficacy of anti-programmed death 1 (PD-1) antibodies in patients (pts) with melanoma brain metastasis (BM), particularly those which are symptomatic. METHOD: We retrospectively assessed pts with melanoma BM treated with PD-1 antibodies, nivolumab and pembrolizumab. Clinicopathologic and treatment parameters were collected and outcomes determined for intracranial (IC) response rate (RR) using a modified RECIST criteria, with up to five IC target lesions used to determine IC response, disease control rate (DCR) and progression-free survival (PFS). RESULTS: A total of 66 pts were identified with a median follow up of 7.0 months (range 0.8-24.5 months). A total of 68% were male and 45% BRAF V600 mutation positive. At PD-1 antibody commencement, 50% had an elevated LDH; 64% had local therapy to BM prior to commencing anti-PD1, of which 5% had surgical resection, 14% stereotactic radiosurgery (SRS), 18% whole-brain radiotherapy (WBRT), 27% had surgery and radiotherapy. Twenty-one per cent started anti-PD-1 as first line systemic therapy. No pt had prior anti-PD-1 treatment. The IC overall RR was 21 and DCR 56%. Responses occurred in 21% of pts with symptomatic BM. The median OS was 9.9 months (95% CI 6.93-17.74). Pts with symptomatic BM had shorter PFS than those without symptoms (2.7 vs 7.4 months, P=0.035) and numerically shorter OS (5.7 vs 13.0 months, P=0.068). Pts requiring corticosteroids also had a numerically shorter PFS (3.2 vs 7.4 months, P=0.081) and OS (4.8 vs 13.1 months, P=0.039). CONCLUSIONS: IC responses to anti-PD-1 antibodies occur in pts with BM, including those with symptomatic BM requiring corticosteroids. Prospective trials evaluating anti-PD-1 therapy in pts with BM are underway.