Study protocol: fish oil supplement in prevention of oxaliplatin-induced peripheral neuropathy in adjuvant colorectal cancer patients - a randomized controlled trial. (OxaNeuro).

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN. METHODS: The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy. DISCUSSION: If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25th. 2023.

Physical activity, return to work self-efficacy, and work status among employees undergoing chemotherapy for cancer - a prospective study with 12 months follow-up.

BACKGROUND: Numerous studies emphasize the positive effects of physical activity on health and well-being in cancer patients. The effects of physical activity on the working lives of cancer patients have received less attention. The aim of the present study was to examine the association between physical activity and work status in employees with cancer, and the mediating role of return to work self-efficacy (RTWSE) in this association. METHODS: Data from questionnaires (physical activity, RTWSE, performance status, sociodemographic), patient records, and Danish national registries (work status, education) were collected for 217 employees initiating chemotherapy for cancer. The associations of physical activity at baseline with work status at baseline and at twelve months follow-up, respectively, were estimated with logistic regression. The mediating role of RTWSE was investigated using the Sobel Goodmann test. RESULTS: Employees with moderate (> 30 min/day) or high (> 150 min/day) levels of current daily activity at baseline had significantly increased odds for working at baseline (OR = 2.83, 95%CI = 0.73-10.96 and OR = 6.13, 95%CI = 1.68-22.40, respectively) and at twelve months (OR = 3.90, 95%CI = 1.19-12.77 and OR = 3.43, 95%CI = 1.12-10.51, respectively), compared to sedentary employees. Likewise, employees, physically active in their leisure time (light or vigorous psychical activity) for 2-4 h/week or > 4 h/week of light activity at baseline, had increased odds for working at twelve months (OR range = 1.20 (95%CI = 0.40-3.61)-5.39(95%CI = 0.78-37.32)), compared to sedentary employees. RTWSE was not found to mediate the observed associations. CONCLUSIONS: Physical activity appears positively associated with work status in employees undergoing treatment for cancer in the twelve months period after initiating chemotherapy.

A systematic review and meta-analysis of randomized controlled head-to-head trials of recommended drugs for neuropathic pain.

Neuropathic pain is a challenging chronic pain condition. Limited knowledge exists regarding the relative effectiveness of pharmacological treatments, and differences in trial design and impact of the placebo response preclude indirect comparisons of efficacy between drug classes. The purpose of this systematic review and meta-analysis of head-to-head trials was to compare the efficacy and tolerability of drugs recommended for neuropathic pain. We conducted a systematic review and meta-analysis of direct-comparison double-blind randomized trials. Primary outcomes were mean change in pain intensity and number of responders with a 50% reduction in pain intensity. Secondary outcomes encompassed quality of life, sleep, emotional functioning, and number of dropouts because of adverse events. We included 30 trials (4087 patients), comprising 16 crossover and 14 parallel-group design studies. All studies were conducted in adults, and the majority were investigator-initiated trials. We found moderate-quality evidence for equivalence (no clinically relevant difference) between tricyclic antidepressants (TCA) and gabapentin/pregabalin with a combined mean difference in pain score of 0.10 (95% CI -0.13 to 0.32). We could not document differences between TCA and serotonin-noradrenaline reuptake inhibitors (SNRI), between SNRI and gabapentin/pregabalin, or between opioids and TCA (low quality of evidence). We found more dropouts because of adverse events with SNRI and opioids compared with TCA (low quality of evidence). We did not identify any studies that included topical treatments. This systematic review of direct-comparison studies found evidence for equivalence between TCA and gabapentin/pregabalin and fewer dropouts with TCA than SNRI and opioids.

Assessing pain after cancer treatment.

OBJECTIVES: Chronic pain is common following cancer treatment. This is a brief discussion of pain assessment after cancer treatment. METHODS: Summary of a lecure for the SASP (Scandinavian Journal of Pain) annual meeting 2022. RESULTS: Assessment of pain involves identifying the presence of pain, its underlying cause, its impact as well as underlying mechanisms. CONCLUSIONS: Detailed pain assessment is important for the clinic and for epidemiological and mechanistic studies as well as pain treatment studies.