Patient experiences of randomised placebo-controlled trial participation during end-of-life palliative cancer care.

BACKGROUND: Performing clinical trials in palliative cancer care is known to be challenging. OBJECTIVE: This study aimed to explore how patients with advanced cancer experienced their participation in a randomised, placebo-controlled trial while receiving palliative cancer care at end of life. METHOD: A descriptive design with a qualitative approach was used. 14 patients who had participated in the 'Palliative-D' study were interviewed. Data were analysed using content analysis. RESULTS: Three categories were identified understanding the study design, willingness to participate and collaboration with the research team alongside standard care. Being randomised, with the risk of receiving placebo, was perceived as non-problematic since it was understood as being important for the quality of the research. Patients showed a willingness to participate for the sake of others and also for their own sake, hoping for a cure or at least to live as long as possible. Patients felt proud of being useful and contributing to research. Consent to participate was made autonomously without discussing with others. Patients considered the study design uncomplicated and well-integrated into the standard care. CONCLUSION: Study participation in a randomised, placebo-controlled trial can be a positive and meaningful experience for patients despite advanced cancer in end of life. Participation may support patients' autonomy and give hope, and therefore, might have a positive effect on quality of life. A carefully planned and simple study design, well integrated into standard care, can facilitate the feasibility of clinical studies in specialised palliative home care.

Appetite in Palliative Cancer Patients and Its Association with Albumin, CRP and Quality of Life in Men and Women-Cross-Sectional Data from the Palliative D-Study.

Albumin is an important biochemical marker in palliative cancer care, used for assessment of nutritional status, disease severity and prognosis. Our primary aim was to investigate sex differences in the association between appetite and albumin levels in palliative cancer patients. We also aimed to study associations between appetite and C-reactive protein (CRP), Quality of Life (QoL), pain and fatigue. In the Palliative D-cohort, consisting of 266 men and 264 women, we found a correlation between appetite and albumin; low appetite, measured with the Edmonton Symptom Assessment System, correlated significantly with low albumin in men: (r = -0.33, p < 0.001), but not in women (r = -0.03, p = 0.65). In a regression analysis adjusted for confounding factors, results were similar. Lower appetite was correlated with higher CRP in men (r = 0.27, p < 0.001), but not in women (r = 0.12, p = 0.05). Appetite was correlated with QoL, fatigue and pain in both men and women; those with a low appetite had a low QoL and high fatigue- and pain-scores (p < 0.001). In conclusion, our results indicated possible sex differences in the associations between appetite and albumin, and between appetite and CRP, in palliative care patients. Understanding these associations could provide additional value for clinical practice.

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.

25-Hydroxyvitamin D in Cancer Patients Admitted to Palliative Care: A Post-Hoc Analysis of the Swedish Trial 'Palliative-D'.

The purpose of this study is to explore 25-hydroxyvitamin D (25-OHD) levels in patients with cancer in the palliative phase in relation to season, sex, age, tumor type, colectomy, and survival. To this end, we performed a post-hoc analysis of 'Palliative-D', a randomized placebo-controlled, double-blind trial investigating the effect of daily supplementation with 4000 IU of vitamin D for 12 weeks on pain in patients in palliative cancer care. In the screening cohort (n = 530), 10% of patients had 25-OHD levels < 25 nmol/L, 50% < 50, and 84% < 75 nmol/L. Baseline 25-OHD did not differ between seasons or tumor type and was not correlated with survival time. In vitamin D deficient patients supplemented with vitamin D (n = 67), 86% reached sufficient levels, i.e., >50 nmol/L, after 12 weeks. An increase in 25-OHD was larger in supplemented women than in men (53 vs. 37 nmol/L, p = 0.02) and was not affected by season. In the placebo-group (n = 83), decreased levels of 25-OHD levels were noted during the study period for patients recruited during the last quarter of the year. In conclusion, cancer patients in palliative phase have adequate increase in 25-OHD after vitamin D supplementation regardless of season, age, tumor type, or colectomy.

Sex Differences in the Effect of Vitamin D on Fatigue in Palliative Cancer Care-A Post Hoc Analysis of the Randomized, Controlled Trial 'Palliative-D'.

In the randomized, placebo-controlled, double-blind trial 'Palliative-D', vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; -1.50 ESAS points (95%CI -2.57 to -0.43; p = 0.007) but not in women; -0.75 (95%CI -1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (-0.33 (95%CI -0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.

Successful Strategies and Areas of Improvement-Lessons Learned from Design and Conduction of a Randomized Placebo-Controlled Trial in Palliative Care, 'Palliative-D'.

Clinical trials in palliative care are challenging to design and conduct. Burden on patients should be minimized, while gatekeeping by professionals and next-of kin needs to be avoided. Clinical deterioration due to disease progression affects attrition unrelated to intervention, and different care settings complicate comparisons and reduce the generalizability of the results. The aim of this review is to provide advice for colleagues planning to perform clinical trials in palliative care based on our own experiences from performing the Palliative-D study and by a thorough literature review on this topic. The Palliative-D study was a double-blind trial with 244 randomized patients comparing the effect of vitamin D3 to placebo in patients with advanced or metastatic cancer in the palliative phase of their disease trajectory who were enrolled in specialized palliative home care teams. Endpoints were opioid and antibiotic use, fatigue, and QoL. Recruitment was successful, but attrition rates were higher than expected, and we did not reach targeted power. For the 150 patients who completed the study, the completeness of the data was exceptionally high. Rather than patient reported pain, we choose the difference in the mean change in opioid dose between groups after twelve weeks compared to baseline as the primary endpoint. In this paper we discuss challenges in palliative care research based on lessons learned from the "Palliative-D" trial regarding successful strategies as well as areas for improvement.

CYP3A Activity in End-of-Life Cancer Patients Measured by 4ß-Hydroxycholesterol/cholesterol Ratio, in Men and Women.

More than 50% of all drugs are metabolized by the cytochrome P450 3A enzyme (CYP3A). The aim of this study was to investigate if the CYP3A activity, measured by the endogenous marker 4ß-hydroxycholesterol/cholesterol ratio (4ß-OHC/C), is changed during the last weeks and days of life in men and women. To this end, serum samples from 137 deceased patients (median age 70 years) collected at a single time point 1-60 days before death, were analyzed and compared to 280 young (median 27 years), and 30 elderly (median age 70 years) non-cancer controls. There were no significant differences in the 4ß-OHC/C ratio between men and women in end-of-life patients (p < 0.25). The median 4ß-OHC/C was significantly higher in end-of-life male patients compared to both young (p < 0.0001) and elderly (p < 0.05) male controls. In a similar manner, 4ß-OHC/C in end-of-life female patients was significantly higher compared to young and elderly female controls, p < 0.0001 and p < 0.001, respectively. There was no significant correlation between 4ß-OHC/C and survival time. The results from this study suggest maintained CYP3A activity to the very last days of life and even a capacity of induction of the enzyme in end-of-life cancer patients.

'Palliative-D'-Vitamin D Supplementation to Palliative Cancer Patients: A Double Blind, Randomized Placebo-Controlled Multicenter Trial.

The aim of the 'Palliative-D' study was to test the hypothesis that correction of vitamin D deficiency reduces opioid use in cancer patients admitted to palliative care. A multicenter randomized, placebo-controlled, double-blind trial in three home-based palliative care facilities in Sweden was performed. Patients with advanced cancer and 25-hydroxyvitamin D < 50 nmol/L were randomized to vitamin D3 4000 IU/day or placebo for 12 weeks. The primary endpoint was the difference of long-acting opioid use (fentanyl ug/h) between the groups during 12 weeks, based on four time points. Secondary outcomes included changes in antibiotic use, fatigue and Quality of Life (QoL). A total of 244 patients were randomized, and 150 patients completed the 12 weeks. The major reason for drop-out was death due to cancer. The vitamin D-group had a significantly smaller increase of opioid doses compared to the placebo-group; beta coefficient -0.56 (p = 0.03), i.e., 0.56 µg less fentanyl/h per week with vitamin D treatment. Vitamin D-reduced fatigue assessed with ESAS was -1.1 points after 12 weeks (p < 0.01). Antibiotic use or QoL did not differ significantly between the groups. The treatment was safe and well-tolerated. In conclusion, correction of vitamin D deficiency may have positive effects on opioid use and fatigue in palliative cancer patients, but only in those with a survival time more than 12 weeks.

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.

Fatigue in Cancer Patients in Palliative Care-A Review on Pharmacological Interventions.

Fatigue is one of the most distressing symptoms experienced by cancer patients. The suggested biological mechanism for cancer related fatigue (CRF) includes immune activation triggered by tumor tissue or by anticancer treatment but other mechanisms have also been proposed. Previous large meta-analysis of interventions on fatigue focuses mostly on patients early in the disease trajectory, with only one tenth of included studies performed in palliative cohorts. The aim of this narrative review is therefore to present a background on CRF with focus on the palliative setting. A summary of recent randomized, controlled trials on pharmacological interventions on CRF in palliative care is presented, including studies on psychostimulants, corticosteroids, testosterone and melatonin. Interestingly, in several of these studies there was a positive and similar effect on fatigue in both the intervention and the placebo arm-indicating an important placebo effect for any pharmacological treatment. In addition, studies on dietary supplements and on pharmacological complementary medicines are discussed. To conclude, the evidence is still weak for using pharmacological treatments on CRF in palliative care patients-although methylphenidate and corticosteroids might be considered.

Vitamin D and Fatigue in Palliative Cancer: A Cross-Sectional Study of Sex Difference in Baseline Data from the Palliative D Cohort.

Background: Fatigue is one of the most distressing symptoms in patients with advanced cancer. Previous studies have shown an association between low vitamin D levels and fatigue. Objectives: The aim of this study was to investigate the association between vitamin D levels and self-assessed fatigue in cancer patients admitted to palliative care, with focus on possible sex differences. Design: This is a cross-sectional study. Subjects: Baseline data from 530 screened patients, 265 women and 265 men, from the randomized placebo-controlled trial "Palliative-D" were analyzed. Measurements: Vitamin D status was measured as 25-hydroxyvitamin D (25-OHD) and fatigue was assessed with EORTC-QLQ-PAL15 and with Edmonton Symptom Assessment System (ESAS). Results: In men, there was a significant correlation between 25-OHD and fatigue measured with the "Tiredness question" (Q11) in EORTC-QLQ-PAL15 (p < 0.05), where higher 25-OHD levels were associated with less fatigue. No correlation between 25-OHD and fatigue was seen for women. Fatigue measured with ESAS did not show any significant association with 25-OHD levels neither in men nor in women. Conclusion: Low vitamin D levels were associated with more fatigue in men but not in women. The study underscores the importance of subgroup analysis of men and women when evaluating the effect of vitamin D in clinical trials since the effect may differ between the sexes. The ongoing "Palliative-D study" will reveal whether vitamin D supplementation may counteract fatigue in both men and women. ClinicalTrial.gov: NCT03038516.

Are Vitamin D3 Tablets and Oil Drops Equally Effective in Raising S-25-Hydroxyvitamin D Concentrations? A Post-Hoc Analysis of an Observational Study on Immunodeficient Patients.

BACKGROUND: Vitamin D3 supplements are available as tablets or oil drops, but there is no consensus as to whether either of these preparations is more effective than the other. METHODS: We compared the effectiveness of tablets versus oil in raising S-25-hydroxyvitamin D (S-25-OHD) in plasma by re-analyzing data from a previously performed observational study in which immunodeficient patients with S-25-OHD concentrations <75 nmol/L were randomly prescribed vitamin D3 tablets (1600 IU/day) or vitamin D3 oil-drops (1500 IU/day) for twelve months. Tablets and oil were compared for the effect on S-25-OHD concentrations after 3-5 months and antibiotic use. RESULTS: Data on S-25-OHD after ≥ 3 months was available for 137 patients treated with tablets and 69 with oil drops. Both groups exhibited a significant increase in S-25-OHD-oil-drops from 55 to 86 nmol/L and tablets from 52 to 87 nmol/L-with no difference between groups (p = 0.77). In a subgroup of patients without immunoglobulin replacement, vitamin D3 supplementation with oil drops (n = 34) but not with tablets (n = 60) resulted in significantly lower antibiotic administration (p < 0.001 and p = 0.58). CONCLUSION: Vitamin D3 supplementation with tablets and oil drops were equally efficient in raising S-25-OHD concentrations. Only oil drops caused a reduction in antibiotic consumption in immuno-deficient patients who did not receive immunoglobulin replacement.

Death at home: predictive factors in a medical home care unit.

OBJECTIVES: The aim of this study was to investigate factors predictive for 'death at home' for patients admitted to an advanced medical home care unit in Stockholm, Sweden, with a focus on possible gender differences. In addition, place of death in relation to the patient's wishes was studied. METHOD: A retrospective review of medical records of all 456 deceased patients, 233 men and 223 women, admitted to the unit during 2017 was performed. Data on age, diagnosis, living conditions, Swedish language skills, desired place of death (if stated) and place of death were retrieved from the patients' charts. RESULTS: A total of 114 of 456 patients died at home (25%). The probability of 'death at home' was independent of gender, age, diagnosis, living conditions and Swedish language skills. In a binary logistic regression model, the only factor significantly associated with death at home was 'the wish to die at home' (p<0.001). In the study population, 154 patients (34%) had expressed a preferred place of death, 116 (75%) wanted to die at home and 38 (25%) wanted to die in hospice. Of all patients who expressed a preferred place of death, 80% (n=123) had their wishes fulfilled and there were no differences between the sexes. CONCLUSION: This study indicates equal opportunities regarding the possibility to die at home for patients admitted to advanced medical home care. It emphasises the importance of asking patients where they want to be at the end of life, as it was the foremost prognostic factor for place of death.

Differences in discontinuation of statin treatment in women and men with advanced cancer disease.

BACKGROUND: Statins are often discontinued in patients with advanced cancer since the net effect of treatment is considered negative. However, guidelines concerning discontinuation of statin treatment are lacking. The aim of this study was to investigate any differences in time of discontinuation of statin treatment between men and women with advanced cancer disease. METHODS: Medical records from 195 deceased palliative cancer patients from a previous study cohort were reviewed. Patients treated with statins 2 years before death were identified as "statin users." The time of discontinuation of statin therapy was identified and correlated to time of death. Only patients that had incurable cancer disease at time of statin discontinuation were included in the analysis. RESULTS: Fifty-four patients were identified as statin users, 29 women and 25 men. The average time span between discontinuation of statin treatment and time of death was significantly longer in women than in men, 10 months compared to 4 months (p < 0.01), with a range of 1-24 months among women and 1-12 months for men. All patients died due to their cancer disease. More men than women had a history of stroke or cardiac infarction (p = 0.02). There were no differences in age, socioeconomic factors, or survival time from study inclusion between men and women. There was no difference in self-assessed quality of life (QoL) between statin users who had discontinued statin treatment and those who are still on treatment. Men generally assessed their QoL lower than women in this study (p = 0.03). CONCLUSION: Statin treatment was discontinued earlier in women than in men in patients with advanced cancer. The data suggest that statins may be discontinued earlier in men as well, since earlier discontinuation did not affect cardiovascular mortality.

Vitamin D in Pain Management.

Vitamin D is a hormone synthesized in the skin in the presence of sunlight. Like other hormones, vitamin D plays a role in a wide range of processes in the body. Here we review the possible role of vitamin D in nociceptive and inflammatory pain. In observational studies, low vitamin D levels have been associated with increased pain and higher opioid doses. Recent interventional studies have shown promising effects of vitamin D supplementation on cancer pain and muscular pain-but only in patients with insufficient levels of vitamin D when starting intervention. Possible mechanisms for vitamin D in pain management are the anti-inflammatory effects mediated by reduced cytokine and prostaglandin release and effects on T-cell responses. The recent finding of vitamin D-mediated inhibition of Prostaglandin E2 (PGE2) is especially interesting and exhibits a credible mechanistic explanation. Having reviewed current literature, we suggest that patients with deficient levels defined as 25-hydroxyvitamin D (25-OHD) levels <30 nmol/L are most likely to benefit from supplementation, while individuals with 25-OHD >50 nmol/L probably have little benefit from supplementation. Our conclusion is that vitamin D may constitute a safe, simple and potentially beneficial way to reduce pain among patients with vitamin D deficiency, but that more randomized and placebo-controlled studies are needed before any firm conclusions can be drawn.

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.

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.

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.

Unfavorable cancers of unknown primaries: presentation and prognostic factors. A population-based 8-year experience.

Cancer of unknown primary is a mostly disseminated malignancy where detailed investigations cannot reveal a probable origin. A few subsets may respond to specific therapy, but the large majority of cases have a median survival of 3-4 months in the few population-based reports, which, however, did not use current investigations and therapy. It is not known if survival can be prolonged by chemotherapy or if supportive care is preferable, especially in the most unfavorable cases in whom chemotherapy may impair the quality of life without prolonging it. We therefore studied prognosis of 134 recent population-based consecutive unfavorable patients. Multiple involvements of the liver, nodes, lungs and skeleton, polysymptomatology, and biochemical abnormalities were common. The median survival time was 103 days, and the 1-year survival was 19%. Hypoalbuminemia, weight loss, and anemia in this order were the strongest negative prognostic factors in multivariate analysis, but univariate analysis added involvement of multiple sites or of the liver, high age, male gender, adenocarcinoma histology, and tobacco use as unfavorable factors. About 10% of patients became long-term survivors, sometimes in the presence of one or more of negative prognostic factors but in particular those with limited nodal spread. A previously unreported finding was that nodal involvement of squamous cell carcinoma limited to the iliacoinguinal region could seemingly be cured by surgery ± radiotherapy. In the absence of efficient treatment and controlled therapeutic trials, supportive care alone seems justified for patients with the worst prognostic factors.

Treatment decisions and discontinuation of palliative chemotherapy near the end-of-life, in relation to socioeconomic variables.

UNLABELLED: During the last decades, the possibilities to prolong survival with chemotherapy even in metastatic disease have increased. Our aim was to study treatment decisions and treatment discontinuation decisions in the proximity of death. METHODS: The medical records of 346 patients with disseminated cancer and a recorded death during 2009 were assessed in relation to demographic and clinical variables and documented treatment decisions were recorded. RESULTS: Palliative chemotherapy was offered in 54% or these cases and generally one or two regimens were administered, before ending treatment. During the last month of life, 32% received treatment and much more often as an oral (instead of intravenous) treatment than in earlier stages (p < 0.001). Younger patients (p = 0.02) and those with young children (p < 0.001) were treated to a higher degree and also closer to death (p = 0.03). Other variables associated with a higher probability of treatment were high education level (p = 0.001), living with a partner (p = 0.001), female gender (p = 0.023) and ethnicity of non-European origin (p = 0.031). In a multivariate analysis, young age and high education remained as independent factors. In 57% of the cases there was no formal documentation of treatment discontinuation or end-of-life discussions with the patient. CONCLUSION: Socioeconomic status (SES) is of importance for the treatment decisions. About half of the patients with disseminated disease receive palliative chemotherapy and of these, about one third are treated even during the last month of life. In a majority of cases, there is no formal documentation of treatment discontinuation or end-of-life discussions.