Methylphenidate for treating fatigue in palliative cancer care - effect and side effects in real-world data from a palliative care unit.

BACKGROUND: Methylphenidate can be used for the treatment of cancer-related fatigue (CRF), although randomized controlled trials have shown conflicting results. The aim of this study was to use 'real-world' data to evaluate the effect and side effects of using methylphenidate in palliative cancer care with a focus on the late palliative phase and dose-response. METHOD: A retrospective review of medical records from a palliative care unit in Sweden was performed to evaluate the effect and adverse events (AEs) of using methylphenidate to treat CRF. Univariable and multivariable regression was performed and odds ratio (OR) calculated. Adjustments were made for sex, age, cancer type, dose and starting treatment <4 weeks before death. RESULTS: Of the 2,419 screened patients, 112 had been treated with methylphenidate for CRF. The treatment was assessed as being effective in 51 patients (46%). Twenty-six patients (23%) experienced AEs that were generally mild, including anxiety, palpitations, and insomnia. Patients starting the treatment <4 weeks before death (n = 54) were less likely to have an effect from treatment compared to those starting earlier; adjusted OR 0.24 (95% CI 0.10-0.55). Doses of 20 mg and above were well-tolerated and had a higher frequency of effect in the crude data but not after adjustment for confounding factors. CONCLUSION: Methylphenidate is generally effective and well-tolerated for the treatment of CRF in palliative care. However, patients with a short life expectancy (<4 weeks) seem to benefit less from the treatment regardless of age, cancer type and dose.

Deprescribing in Palliative Cancer Care.

The aim of palliative care is to maintain as high a quality of life (QoL) as possible despite a life-threatening illness. Thus, the prescribed medications need to be evaluated and the benefit of each treatment must be weighed against potential side effects. Medications that contribute to symptom relief and maintained QoL should be prioritized. However, studies have shown that treatment with preventive drugs that may not benefit the patient in end-of-life is generally deprescribed very late in the disease trajectory of cancer patients. Yet, knowing how and when to deprescribe drugs can be difficult. In addition, some drugs, such as beta-blockers, proton pump inhibitors, anti-depressants and cortisone need to be scaled down slowly to avoid troublesome withdrawal symptoms. In contrast, other medicines, such as statins, antihypertensives and vitamins, can be discontinued directly. The aim of this review is to give some advice according to when and how to deprescribe medications in palliative cancer care according to current evidence and clinical praxis. The review includes antihypertensive drugs, statins, anti-coagulants, aspirin, anti-diabetics, proton pump inhibitors, histamin-2-blockers, bisphosphonates denosumab, urologicals, anti-depressants, cortisone, thyroxin and vitamins.

Evaluation of Whole Brain Radiotherapy among Lung Cancer Patients with Brain Metastases in Relation to Health Care Level and Survival.

Whole-brain radiotherapy (WBRT) as a treatment for brain metastases has been questioned over the last years. This study aimed to evaluate health care levels and survival after WBRT in a cohort of lung cancer patients with brain metastases receiving WBRT in Stockholm, Sweden, from 2008 to 2019 (n = 384). If the patients were able to come home again was estimated using logistic regression and odds ratios (OR) and survival by using Cox regression. The median age in the cohort was 65.6 years, the median survival following WBRT was 2.4 months (interquartile range (IQR) 1.2-6.2 months), and 84 (22%) patients were not able to come home after treatment. Significantly more males could come home again after WBRT compared to women (OR = 0.37, 95%CI 0.20-0.68). Patients with performance status scores WHO 3-4 had a median survival of 1.0 months, hazard ratio (HR) = 4.69 (95%CI 3.31-6.64) versus WHO score 0-1. Patients admitted to a palliative ward before WBRT had a median survival of 0.85 months, HR = 2.26 (95%CI 1.53-3.34) versus being at home. In conclusion, patients treated with WBRT had a short median survival and 20% could not be discharged from the hospital following treatment. Significantly more women did not come home again.

Sex-Differences in Discontinuation of Statin Treatment in Cancer Patients the Year before Death.

Statin treatment is often terminated in patients with advanced cancer but guidelines for statin discontinuation are still lacking. The aim of this study was to investigate sex-differences in time-points of statin discontinuation in patients with advanced cancer. Medical records from 1535 deceased patients enrolled at a Palliative Home Care Unit were reviewed. A total of 149 patients (42 women and 107 men) who were diagnosed with cancer, and were treated with statins one year before death, were identified. Statin treatment was terminated earlier in women than in men, 3.0 months prior to death (IQR 0.88-7.25) as compared to 1.5 months (IQR 0.5-4.0) (p < 0.05), respectively. In a longitudinal analysis there was a significant difference between men and women still on statin treatment at all studied time-points, 9, 6, and 3 months before death (p < 0.05), where women terminated statin treatment earlier in the disease trajectory. Baseline demographics were similar between the sexes except that more men than women had a history of previous cardiovascular events (p < 0.01). However, neither the indication for statin treatment, i.e., primary prevention versus secondary prevention, nor age could explain the sex-difference in statin discontinuation. There was no difference in cardiovascular events or mortality between men and women after statin discontinuation.

No association between low-dose aspirin use and breast cancer outcomes overall: a Swedish population-based study.

BACKGROUND: Results from previous studies indicate that use of low-dose aspirin may improve breast cancer prognosis. We evaluated aspirin use and breast cancer outcomes in relation to clinical characteristics as well as dose and duration of aspirin use. METHODS: We used information from the Regional Breast Cancer Quality-of-Care Registries in three Swedish regions to identify 21,414 women diagnosed with a first stage I-III breast cancer between 1 April 2006 and 31 December 2012. The cohort was further linked to nationwide registers to retrieve information about dispensing low-dose aspirin before and after breast cancer diagnosis, comorbidity and causes of death. In a separate analysis, we investigated time to breast cancer death among 621 women with stage IV disease at diagnosis. Associations were evaluated using a multivariable Cox proportional hazards model. RESULTS: Among women with stage I-III breast cancer, 2660 (12.4%) used low-dose aspirin shortly before breast cancer diagnosis and 4091 (19.1%) were users during follow-up. Women were followed for a median of 3.8 years after diagnosis. There was no association between aspirin use and breast cancer-specific death in multivariable analyses (use before diagnosis: hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.77-1.12; use after diagnosis: HR 1.00, 95% CI 0.74-1.37). Similarly, aspirin use was not associated with risk of first recurrence/metastases in a subgroup of stage I-III breast cancer patients (HR 0.97, 95% CI 0.86-1.10). However, in analyses stratified by stage, an inverse association between low-dose aspirin use after diagnosis and breast cancer death was found for women with stage I tumors (HR 0.53, 95% CI 0.29-0.96). Among women with stage IV disease at diagnosis, aspirin use was not associated with time to breast cancer death (HR 0.91, 95% CI 0.67-1.23). CONCLUSION: In this large population-based cohort study there was no evidence that low-dose aspirin use before or after breast cancer diagnosis is associated with a reduced risk of adverse outcomes overall in breast cancer. However, a potential benefit was noted among women with stage I tumors, warranting further investigation.

Survival and level of care among breast cancer patients with brain metastases treated with whole brain radiotherapy.

PURPOSE: The benefit of whole brain radiotherapy (WBRT) for late stage breast cancer patients with brain metastases has been questioned. In this study we evaluated survival and level of care (hospital or home) following WBRT in a population-based cohort by personal and tumor characteristics. METHODS: We identified 241 consecutive patients with breast cancer and brain metastases receiving WBRT in Stockholm, Sweden, 1999-2012. Through review of medical records, we collected data on prognostic determinants including level of care before and after WBRT. Survival was estimated using Cox regression, and odds ratios (OR) of not coming home using logistic regression. RESULTS: Median age at WBRT was 58 years (range 30---88 years). Most patients (n = 212, 88%) were treated with 4 Gray × 5. Median survival following WBRT was 2.9 months (interquartile range 1.1-6.6 months), and 57 patients (24%) were never discharged from hospital. Poor performance status and triple-negative tumors were associated with short survival (WHO 3-4 median survival 0.9 months, HR = 5.96 (3.88-9.17) versus WHO 0-1; triple-negative tumors median survival 2.0 months, HR = 1.87 (1.23-2.84) versus Luminal A). Poor performance status and being hospitalized before WBRT were associated with increased ORs of not coming home whereas cohabitation with children at home was protective. CONCLUSION: Survival was short following WBRT, and one in four breast cancer patients with brain metastases could never be discharged from hospital. When deciding about WBRT, WHO score, level of care before WBRT, and the patient's choice of level of care in the end-of-life period should be considered.

High prevalence of human cytomegalovirus in brain metastases of patients with primary breast and colorectal cancers.

BACKGROUND: Brain metastases (BMs) develop by largely unknown mechanisms and cause major morbidity and mortality in patients with solid tumors. Human cytomegalovirus (HCMV) is frequently detected in tumor tissue from patients with different cancers. Here, we aimed to determine the prevalence and potential prognostic role of HCMV in BMs. METHODS: We obtained archived samples of BMs from 41 patients with breast cancer and 37 with colorectal cancer and paired primary tumor tissues from 13 and 12 patients in each respective group. In addition, primary breast cancer tissues from 15 patients were included. HCMV proteins were detected with an immunohistochemical technique and Western blot. HCMV nucleic acids were detected with TaqMan polymerase chain reaction (PCR) assay. RESULTS: HCMV proteins were abundantly expressed in 99% of BM specimens, and in 12 of 13 (92%) paired primary breast cancer specimens. All 12 paired colon cancer samples were positive for HCMV proteins. Protein staining was mainly confined to neoplastic cells. Western blot analysis detected an HCMV-IE reactive protein in 53% of breast cancer specimens, and PCR detected the presence of HCMV DNA and transcripts in 92% and 80% of samples, respectively. Patients with high-level expression of HCMV-IE proteins in their tumors had a shorter time to tumor progression and shorter overall survival. CONCLUSIONS: The prevalence of HCMV proteins and nucleic acids is very high in primary and metastatic tumors and may drive the development of metastatic brain tumors; therefore, this virus may represent a potential therapeutic target in metastatic cancer.