Jenny Bergqvist

Low Vitamin D Levels Are Associated with Higher Opioid Dose in Palliative Cancer Patients – Results from an Observational Study in Sweden

Background Vitamin D deficiency is common among palliative cancer patients and has been connected to an increased risk for pain, depressions and infections. Therefore we wanted to test the hypothesis that low 25-hydroxyvitamin D (25OHD) levels are associated with higher opioid dose, higher infectious burden and impaired quality of life in palliative cancer patients. The secondary aim was to investigate the association between 25OHD-levels and survival time. Method In this prospective, observational study in palliative cancer-patients (n = 100) we performed univariate and multiple linear regression analysis to assess the association of 25OHD levels with opioid dose, infectious burden (antibiotic consumption), quality of life (Edmonton Symptom Assessment Scale, ESAS) and survival time, controlling for potential confounding factors. Results The median 25OHD level was 40 nmol/L (range 8-154 nmol/L). There was a significant association between 25OHD levels and opioid dose, beta coefficient -0.67; p=0.02; i.e. a low 25OHD level was associated with a higher opioid dose. This association remained significant after adjustment for stage of the cancer disease in a multivariate analysis, beta coefficient -0.66; p = 0.04. There was no association between 25OHD levels and antibiotic use or quality of life. Univariate cox regression analysis showed a weak correlation between survival time and 25OHD levels (p<0.05). However, decreased albumin levels and increased CRP levels were superior markers to predict survival time; p<0.001 for both analyses. Conclusion Low 25OHD-levels are associated with increased opioid consumption in palliative cancer patients. Future interventional studies are needed to investigate if pain can be reduced by vitamin D supplementation in these patients. In addition, this study confirms previous findings that low albumin and increased CRP levels are useful markers for survival time in palliative cancer patients.

Antibiotic Treatment in End-of-Life Cancer Patients—A Retrospective Observational Study at a Palliative Care Center in Sweden

Background: The aim of this study was to elucidate whether palliative cancer patients benefit from antibiotic treatment in the last two weeks of life when an infection is suspected. Method: We reviewed medical records from 160 deceased palliative cancer patients that had been included in previous studies on vitamin D and infections. Patients treated with antibiotics during the last two weeks of life were identified and net effects of treatment (symptom relief) and possible adverse events were extracted from medical records. Results: Seventy-nine patients (49%) had been treated with antibiotics during the last two weeks in life. In 37% (n = 29), the treatment resulted in evident symptom relief and among these 50% had a positive bacterial culture, 43% had a negative culture and in 7% no culture was taken. Among the patients with no or unknown effect of antibiotics, 50% had a positive culture. When the indication for antibiotic treatment was to avoid or treat sepsis, symptom relief was achieved in 50% of the patients (n = 19). Only 4% (n = 3) of the patients experienced adverse events of the treatment (diarrhea, nausea). Conclusions: Treating infections with antibiotics in the last weeks of life may improve the quality of life for palliative cancer patients, especially if sepsis is suspected or confirmed. According to our results, the beneficial effects outweigh the potentially negative outcomes.

Vitamin D supplementation to palliative cancer patients shows positive effects on pain and infections—Results from a matched case-control study

Background We previously showed an association between low vitamin D levels and high opioid doses to alleviate pain in palliative cancer patients. The aim of this case-controlled study was to investigate if vitamin D supplementation could improve pain management, quality of life (QoL) and decrease infections in palliative cancer patients. Methods Thirty-nine palliative cancer patients with levels of 25-hydroxyvitamin D < 75 nmol/L were supplemented with vitamin D 4000 IE/day, and were compared to 39 untreated, matched “control”-patients from a previous study at the same ward. Opioid doses, antibiotic consumption and QoL-scores measured with the Edmonton Symptom Assessment Scale (ESAS) were monitored. The primary endpoint was the change from baseline after 1 and 3 months compared between the groups using linear regression with adjustment for a potential cofounding factor. Results After 1 month the vitamin D treated group had a significantly decreased fentanyl dose compared to the untreated group with a difference of 46 μg/h; 95% CI 24–78, which increased further at 3 months to 91 μg/h; 95% CI 56–140 μg/h. The ESAS QoL-score improved in the Vitamin D group the first month; -1.4; 95% CI -2.6 - (-0.21). The vitamin D-treated group had significantly lower consumption of antibiotics after 3 months compared to the untreated group, the difference was -26%; 95%CI -0.41%–(-0.12%). Vitamin D was well tolerated by all patients and no adverse events were reported. Conclusion Vitamin D supplementation to palliative cancer patients is safe and improvement in pain management is noted as early as 1 month after treatment. Decreased infections are noted 3 months after vitamin D treatment. The results from this pilot-study have been used for the power-calculation of a future randomized, placebo-controlled, double-blind study called “Palliative-D” that will start in Nov 2017 and will include 254 palliative cancer patients.

Healthcare resource use, comorbidity, treatment and clinical outcomes for patients with primary intracranial tumors : a Swedish population-based register study

Abstract Background: Primary intracranial tumors are relatively uncommon and heterogeneous, which make them challenging to study. We coupled data from unique Swedish population-based registries in order to deeper analyze the most common intracranical tumor types. Patient characteristics (e.g. comorbidities), care process measures like adherence to national guidelines, healthcare resource use and clinical outcome was evaluated. Materials and methods: A register-based study including several population-based registries for all patients living in Stockholm-Gotland, diagnosed with primary intracranial tumor between 2001 and 2013 was performed. Patient characteristics were captured and investigated in relation to survival, healthcare resource use (inpatient-, outpatient- and primary care) and treatment process. Results: High-grade glioma and meningioma were the most common tumor types and most patients (76%) were above the age of 40 in the patient population (n = 3664). Older age, comorbidity (Elixhauser comorbidity index) and type of tumor (high-grade glioma) were associated with lower survival rate and increased use of healthcare resources, analyzed for patients living in Stockholm (n = 3031). The analyses of healthcare use and survival showed no differences between males and females, when stratifying by tumor types. Healthcare processes were not always consistent with existing national treatment recommendations for patients with high-grade gliomas (n = 474) with regard to specified lead times, analyzed in the Swedish Brain Tumor Registry, as also observed at the national level. Conclusions: Age, comorbidity and high-grade gliomas, but not sex, were associated with decreased survival and increased use of healthcare resources. Fewer patients than aimed for in national guidelines received care according to specified lead times. The analysis of comprehensive population-based register data can be used to improve future care processes and outcomes.

The will to live – breast cancer patients perceptions’ of palliative chemotherapy

Abstract Background: For women with metastatic breast cancer, late lines of chemotherapy might be beneficial but also harmful. Ongoing chemotherapy late in life increase the risk of late or absent discussions of palliative care and access to symptom relief by other options than chemotherapy. Our aim was, therefore, to investigate breast cancer patients’ motives, perceptions, and experiences of late lines of palliative oncologic treatment. Material and methods: A qualitative study with semi-guided face-to-face interviews with 20 women on at least their second line of palliative chemotherapy (second–eighth line). All women had breast cancer and were 40–80 years old. The interviews were analyzed by a phenomenographical approach according to seven steps, which uses a second-order perspective, i.e., how the informants experience the world. Results: The categories that surrounded the decision to continue with palliative chemotherapy were: The decision, Personal motives and goals and The treatment. All women acknowledged that they knew they had incurable breast cancer and that the treatment goal was to slow down cancer growth. Fear of death was a strong motive for all women in addition to experience of new values of life, still they preferred the doctor to make the decision. Cancer symptoms, especially pain triggered death anxiety, whereas the patients patiently accepted similar side effects from the treatment. There were also external motives for treatment like wishes from family, friends, but also health care staff. Conclusions: All women knew they had disseminated breast cancer, still they expressed hopes for cure, therefore, death was more of a threat than a reality of an imminent death. None of the women had perceived there was an option to stop treatment. They felt both their families and doctors expected them to continue. Death threat was their main motive for accepting treatment.

Vitamin D supplementation to palliative cancer patients: protocol of a double-blind, randomised controlled trial ‘Palliative-D’

Background According to a small pilot study on palliative cancer patients at our ward, vitamin D supplementation had beneficial effects on pain (measured as opioid consumption), infections and quality of life (QoL) without having any significant side effects. Objective The primary objective of the ‘Palliative-D’ study is to test the hypothesis that vitamin D supplementation for 12 weeks reduces opioid consumption. The secondary objectives are to study if reduction of antibiotic consumption and fatigue as well as improvement in QoL assessments can be observed. Effect on the 25-hydroxy vitamin D (25-OHD) levels in serum after 12 weeks of treatment will be studied, as well as the change in opioid dose in relation to genetic polymorphism in genes involved in the effect and metabolism of vitamin D. Method A randomised, double-blind placebo-controlled multicentre trial has been designed. The trial will include 254 adult palliative cancer patients with 25-OHD levels <50 nmol/L and a life expectancy of more than 3 months recruited from two advanced palliative home care centres in Stockholm. Included patients will be randomly assigned to 12 weeks of treatment with cholecalciferol (vitamin D3) 4000 IU/day or placebo. The study will start in November 2017 and will finish in December 2019. The study is approved by the Regional Ethical Committee, Dnr2017/405-31/1, by the Swedish Medical Products Agency, EudraCT: 2017-000268-14, and is registered at Clinicaltrial.gov: NCT03038516. The study is financed with research grants from the Swedish Cancer Society and the Stockholm County Council.

The effects of clinical and sociodemographic factors on survival, resource use and lead times in patients with high-grade gliomas: a population-based register study

BackgroundPrevious studies indicate an effect of sociodemographic factors on risk for being diagnosed with, as well as on survival of cancer in general. Our primary aim was to analyse sociodemographic factors, resource use and lead times in health care after diagnosis with high grade malignant glioma (HGG) in a large population based cohort.MethodsA register-based study using several unique high-coverage registries. All patients over the age of 18 diagnosed with HGG in the Swedish Stockholm–Gotland region between 2001 and 2013 (n = 1149) were included.ResultsIn multivariable cox proportional hazard model of survival, older age, male sex and high tumour grade were associated with worse survival. No significant differences could be seen related to country of birth. A high disposable income was associated with better survival and fewer occasions of pre-diagnostic inpatient care. Older age and comorbidities were correlated with a significantly increased number of outpatient visits the year before HGG diagnosis. In addition, male sex, being born outside Sweden was associated to a higher number of outpatient visits the year after diagnosis in multivariable analysis. Leadtime from diagnosis (first suspicion on brain scan) to surgery showed that the oldest patients, patients with comorbidity and patients born outside Europe had to wait longer for surgery.ConclusionsSociodemographic factors like education, income and country of birth have impact on care processes both before and after the diagnosis HGG. This needs to be acknowledged in addition to important clinical factors like age, comorbidity and tumour grade, in order to accomplish more equal cancer care.

Does palliative chemotherapy provide a palliative effect on symptoms in late palliative stages? An interview study with oncologists

Abstract Background: The possible chemotherapy effects on symptoms in late stages of palliative chemotherapy are seldom registered in clinical practice or investigated as primary outcomes. The aim was therefore to study physicians’ opinions and experiences about chemotherapy effects on symptoms. Material and methods: Thirty-five physicians (mainly oncologists) with variation as regards age, gender and experience were included in a qualitative study with semi-structured interviews. A qualitative content analysis was used for the 30–60 min long interviews. Results: According to all the informants, symptoms were possible to control in successful cases but the chances reduce rapidly with the number of chemotherapy lines. Symptoms possible to control included various types of pain (bone pain, neuropathic cranial as well as meningeal nerve pain, colic pain, “liver” pain, headache and pain from cutaneous metastases); nausea and vomiting caused by obstruction; dyspnoea due to pleural effusions or bronchial obstructions. Also fatigue and B-symptoms were possible targets, as were diagnosis-specific symptom clusters (e.g., liver metastasis causing pain, nausea, tumour fever and night sweats; or head–neck cancers resulting in nerve pain, ulcerations, odour, dysphagia and impaired breathing). Some of the oncologists discussed whether the effects were related to chemotherapy treatment only or partly to premedication with steroids. Despite the claimed effects, the physicians did not keep record on symptoms, they did not evaluate them with validated instruments. Conclusions: Palliative chemotherapy has a substantial potential to reduce agonizing symptoms especially in first line treatments, but the effect is limited in late stages. The actual awareness of and knowledge about situations where the treatment has a reasonable potential, should be improved and symptoms should be monitored during treatment.