Long-term effects of aromatase inhibitor withdrawal on bone mineral density in early breast cancer patients: 10-year follow-up results of the BREX study.

PURPOSE: We aimed to provide long-term bone mineral density (BMD) data on early breast cancer patients of the BREX (Breast Cancer and Exercise) study. The effects of exercise and adjuvant endocrine treatment 10 years after randomization were analyzed, with special emphasis on aromatase inhibitor (AI) therapy discontinuation at 5 years. METHODS: The BREX study randomized 573 pre- and postmenopausal breast cancer patients into a 1-year supervised exercise program or a control group. 372 patients were included into the current follow-up analysis. BMD (g/cm2) was measured by dual-energy X-ray absorptiometry at lumbar spine (LS), left femoral neck (FN), and the total hip. Separate groups were displayed according to baseline menopausal status, and whether the patient had discontinued AI therapy at 5 years or not. RESULTS: The BMD change from 5 to 10 years did not significantly differ between the two randomized arms. AI discontinuation at 5 years had statistically significant BMD effects. The FN BMD continued to decrease in patients who discontinued AI therapy during the first 5-year off-treatment, but the decrease was three-fold less than in patients without AI withdrawal (- 1.4% v. - 3.8%). The LS BMD increased (+ 2.6%) in patients with AI withdrawal during the first 5 years following treatment discontinuation, while a BMD decrease (-1.3%) was seen in patients without AI withdrawal. CONCLUSION: This study is to our knowledge the first to quantify the long-term impact of AI withdrawal on BMD. Bone loss associated with AI therapy seems partially reversible after stopping treatment. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov/ (Identifier Number NCT00639210).

The effect of palliative outpatient units on resource use for cancer patients in Finland.

BACKGROUND: As cancer incidences are increasing, the means to provide effective palliative care (PC) are called for. There is evidence, that PC may prevent futile treatment at the end of life (EOL) thus implicating that PC decreases resource use at the EOL, however, the effects of outpatient PC units remain largely unknown. We surveyed the national use of Finnish tertiary care PC units and their effects on resource use at the EOL in real-life environments. PATIENTS AND METHODS: Cancer patients treated in the departments of Oncology at all five Finnish university hospitals in 2013 and deceased by 31 December 2014 were identified; of the 6010 patients 2007 were randomly selected for the study cohort. The oncologic therapies received and the resource usage of emergency services and hospital wards were collected from the hospitals' medical records. RESULTS: A PC unit was visited by 37% of the patients a median 112 days before death. A decision to terminate all life-prolonging cancer treatments was more often made for patients visiting the PC unit (90% vs. 66%, respectively). A visit to a PC unit was associated with significantly fewer visits to emergency departments (ED) and hospitalization during the last 90 days of life; the mean difference in ED visits decreased by 0.48 (SD 0.33 - 0.62, p < 0.001), and the mean inpatient days by 7.1 (SD 5.93 - 8.25, p < 0.001). A PC visit unit was independently associated with decreased acute hospital resource use during the last 30 and 90 days before death in multivariable analyses. CONCLUSION: Cancer patients' contact with a PC unit was significantly associated with the reduced use of acute hospital services at the EOL, however; only one-third of the patients visited a PC unit. Thus, systematic PC unit referral practices for patients with advanced cancer are called for.

Effect of palliative care decisions making on hospital service use at end-of-life in patients with malignant brain tumors: a retrospective study.

BACKGROUND: Palliative care (PC) improves Quality of life and reduces the symptom burden. Aggressive treatments at end of life (EOL) postpone PC. The aim of this single-center retrospective study was to evaluate the timing of the PC decision i.e., termination of cancer-specific treatments and focusing on symptom-centered PC, and its impact on the use of tertiary hospital services at the EOL. METHODS: A retrospective cohort study on brain tumor patients, who were treated at the Comprehensive Cancer Center of the Helsinki University Hospital from November 1993 to December 2014 and died between January 2013 and December 2014, were retrospectively reviewed. The analysis comprised 121 patients (76 glioblastoma multiforme, 74 males; mean age 62 years; range 26-89). The decision for PC, emergency department (ED) visits and hospitalizations were collected from hospital records. RESULTS: The PC decision was made for 78% of the patients. The median survival after diagnosis was 16 months (13 months patients with glioblastoma), and after the PC decision, it was 44 days (range 1-293). 31% of the patients received anticancer treatments within 30 days and 17% within the last 14 day before death. 22% of the patients visited an ED, and 17% were hospitalized during the last 30 days of life. Of the patients who had a PC decision made more than 30 days prior to death, only 4% visited an ED or were hospitalized in a tertiary hospital in the last 30 days of life compared to patients with a late (< 30 days prior to death) or no PC decision (25 patients, 36%). CONCLUSIONS: Every third patient with malignant brain tumors had anticancer treatments during the last month of life with a significant number of ED visits and hospitalizations. Postponing the PC decision to the last month of life increases the risk of tertiary hospital resource use at EOL.

End-of-life care of patients with esophageal or gastric cancer: decision making and the goal of care.

BACKGROUND: Overall survival (OS) with advanced esophageal or gastric cancer is poor. To avoid overly aggressive treatments at the end-of-life and assure adequate end-of-life quality, the decision to focus on symptom-centered palliative care (PC) and terminate anticancer treatments, i.e., the PC decision, should be made in time. MATERIAL AND METHODS: We reviewed the charts of patients (N = 160) with esophageal or gastric cancer treated at the Department of Oncology at Helsinki University Central Hospital in 2013 and deceased by December 2014. The use of acute services (Emergency department (ED) visits and hospitalizations) and places of death were compared according to the timing of the PC decision. Reasons for ED visits and hospitalizations were collected. RESULTS: The median OS from diagnosis of advanced cancer was 6 months. Anti-cancer treatments were never started for 34% of the patients. The PC decision was made early (>30 days before death) for 54% of the patients and late (≤30 days before death) or not at all for 46%. Patients with late or no PC decision died more often in tertiary/secondary hospital (29 versus 7%, p = 0.001) and had more ED visits (49 versus 29%, p < 0.001) and hospitalizations (53 versus 28%, p = 0.001) in their last month, and visited the PC unit less often (18 versus 69%, p < 0.001), than the patients with early PC decision. The ED visits were most commonly related to cancer progression, and clinical deterioration (17%), fever (16%), and dysphagia (15%) were the most common symptoms. CONCLUSION: The decision to focus on PC and terminate anticancer treatments, i.e., the PC decision, was made late or not at all in every other patient, leading to increased tertiary/secondary hospital service use and deaths at tertiary/secondary hospital. Early decision-making increased end-of-life care at specialized PC services or at home, implying better end-of-life care.

Factors predicting long-term physical activity of breast cancer survivors. 5-year-follow-up of the BREX exercise intervention study.

BACKGROUND: The benefits of exercise training are well documented among breast cancer (BC) survivors. Patients decrease their physical activity during treatment, and many fail to regain their previous exercise levels. There is therefore a need to define factors supporting long-term physical activity behavior in this patient group, to target supporting interventions aimed at preventing the decline in physical activity (PA). AIM: The aim of this study was to determine physical and psychosocial factors explaining long-term physical activity after the adjuvant treatments in BC survivors. METHODS: Four-hundred forty-six BC survivors followed for 5-years within a randomized exercise trial participated. Factors explaining (1) physical activity after the adjuvant treatments and (2) changes in physical activity in long-term were analyzed using linear regression models and general estimating equation models. Pretreatment leisure-time physical activity (LTPA), demographic, and treatment factors, physical fitness, and quality of life (Qol) at baseline were independent factors. RESULTS: Exercise levels increased during the first year, and thereafter remained mostly stable. Higher LTPA, higher fitness level, better Qol and older age at baseline were associated with higher physical activity level after adjuvant treatments (p < .001) in multivariate analysis. Higher levels of fatigue (p < .008) and better emotional functioning (p = .017) at baseline were the main factors associated with increased physical activity during the follow-up. CONCLUSION: Previous exercise habits and Qol after adjuvant chemo-, and radiotherapy were the strongest determinants of long-term physical activity levels in breast cancer survivors. Patients with better emotional functioning increased their exercise activity most as did those patients with higher fatigue levels at baseline. Patients suffering from fatigue after adjuvant treatment managed to increase their exercise levels, in contrast to patients with low emotional functioning, and may benefit from physical exercise interventions. Emotionally deprived patients may benefit from psychosocial support to regain their previous exercise levels.

Mindfulness is associated with improved psychological well-being but no change in stress biomarkers in breast cancer survivors with depression: a single group clinical pilot study.

BACKGROUND: The aim of this clinical single group pilot study was to assess mental well-being, psychological symptoms, and a set of stress biomarkers among breast cancer survivors with high depressive symptoms undergoing the Mindfulness-Based Stress Reduction (MBSR) program. METHODS: Participants included 23 curatively treated breast cancer survivors from the Helsinki University Central Hospital with clinically significant symptoms of depression (Beck Depression Inventory > 13, and assessed by a psychiatrist), at 1-year post-operative follow-up. Mental wellbeing and psychological symptoms were assessed with self-reported questionnaires (Resilience Scale, Self-Compassion Scale, Five Facet Mindfulness Questionnaire, World Health Organization Quality of Life-questionnaire, Perceived Stress Scale, Beck Depression Inventory, Beck Anxiety Inventory, Insomnia Severity Index); in addition, stress response was assessed with biomarkers (cortisol, adrenocorticotropine, and high-sensitivity-CRP from blood; 24 h-cortisol from urine). All measures were addressed at baseline, mid-program (4 weeks after baseline) and at the completion of the 8-week MBSR program. Engagement to the independent mindfulness home practice was collected with a diary. RESULTS: From baseline to the completion of the 8-week MBSR program, we observed significant increases in resilience (d = 0.60, p = 0.005), and quality of life (d = 0.92, p = 0.002), and significant reductions in symptoms of depression (d = - 1.17, p < 0.0001), anxiety (d = - 0.87, p < 0.0001), insomnia (d = - 0.58, p = 0.006), and marginally significant reduction in perceived stress (d = - 0.40, p = 0.09). We found no changes in self-compassion or mindfulness skills, nor in the stress biomarkers during or at the completion of the program. There was no association between the engagement time to the independent mindfulness practice and any of the outcomes. CONCLUSIONS: Attending the MBSR program was associated with increased wellbeing and reduced psychological symptoms in breast cancer survivors with clinically significant symptoms of depression. However, these favorably experienced changes did not transfer to the level of stress biomarkers during the 8-week program. Lack of association between the engagement in the mindfulness home practice and change in outcomes suggests that in the studied range of practice time, other qualities of MBSR despite the amount of independent practice may have a more important role for the improved wellbeing. Trial registration ISRCTN12326308 at 16/02/2021, retrospectively registered.

A Nordic survey of the management of palliative care in patients with head and neck cancer.

BACKGROUND: The five Nordic countries with a population of 27M people form a rather homogenous region in terms of health care. The management of Head and Neck Cancer (HNC) is centralized to the 21 university hospitals in these countries. Our aim was to survey the current status of organization of palliative care for patients with HNC in the Nordic countries as the field is rapidly developing. MATERIALS AND METHODS: A structured web-based questionnaire was sent to all the Departments of Otorhinolaryngology-Head and Neck Surgery and Oncology managing HNC in the Nordic countries. RESULTS: All 21 (100%) Nordic university hospitals responded to the survey. A majority (over 90%) of the patients are discussed at diagnosis in a multidisciplinary tumor board (MDT), but the presence of a palliative care specialist is lacking in 95% of these MDT's. The patients have access to specialized palliative care units (n = 14, 67%), teams (n = 10, 48%), and consultants (n = 4, 19%) in the majority of the hospitals. CONCLUSION: The present results show that specialized palliative care services are available at the Nordic university hospitals. A major finding was that the collaboration between head and neck surgeons, oncologists and palliative care specialists is not well structured and the palliative care pathway of patients with HNC is not systematically organized. We suggest that early integrated palliative care needs to be included as an addition to the already existing HNC care pathways in the Nordic countries.

The required competencies of physicians within palliative care from the perspectives of multi-professional expert groups: a qualitative study.

BACKGROUND: Although statements on the competencies required from physicians working within palliative care exist, these requirements have not been described within different levels of palliative care provision by multi-professional workshops, comprising representatives from working life. Therefore, the aim of this study was to describe the competencies required from physicians working within palliative care from the perspectives of multi-professional groups of representatives from working life. METHODS: A qualitative approach, using a workshop method, was conducted, wherein the participating professionals and representatives of patient organizations discussed the competencies that are required in palliative care, before reaching and documenting a consensus. The data (n = 222) was collected at workshops held in different parts of Finland and it was analyzed using a qualitative content analysis method. RESULTS: The description of the competencies required of every physician working within palliative care at the general level included 13 main categories and 50 subcategories in total. 'Competence in advanced care planning and decision-making' was the main category which was obtained from the highest number of reduced expressions from the original data (f = 125). Competence in social interactions was another strong main category (f = 107). In specialist level data, six main categories with 22 subcategories in total were found. 'Competence in complex symptom management' was the main category which was obtained from the biggest number of reduced expressions (f = 46). A notable association between general level and specialist level data was related to networking, since one of the general level categories was 'Competence in consultations and networking' (f = 34) and one of the specialist level categories was 'Competence to offer consultative and educational support to other professionals' (f = 30). Moreover, part of the specialist level results were subcategories which belonged to the main categories produced from the general level data. CONCLUSIONS: The competencies described in this study emphasize decision-making, social interactions and networking. It is important to listen to the voices of the working-life representatives when planning curricula. Moreover, the views of the working-life representatives inform how the competencies gained during their education meet the challenges of the ordinary work.

The impact of the duration of the palliative care period on cancer patients with regard to the use of hospital services and the place of death: a retrospective cohort study.

BACKGROUND: In order to avoid unnecessary use of hospital services at the end-of-life, palliative care should be initiated early enough in order to have sufficient time to initiate and carry out good quality advance care planning (ACP). This single center study assesses the impact of the PC decision and its timing on the use of hospital services at EOL and the place of death. METHODS: A randomly chosen cohort of 992 cancer patients treated in a tertiary hospital between Jan 2013 -Dec 2014, who were deceased by the end of 2014, were selected from the total number of 2737 identified from the hospital database. The PC decision (the decision to terminate life-prolonging anticancer treatments and focus on symptom centered palliative care) and use of PC unit services were studied in relation to emergency department (ED) visits, hospital inpatient days and place of death. RESULTS: A PC decision was defined for 82% of the patients and 37% visited a PC unit. The earlier the PC decision was made, the more often patients had an appointment at the PC unit (> 180 days prior to death 72% and < 14 days 10%). The number of ED visits and inpatient days were highest for patients with no PC decision and lowest for patients with both a PC decision and an PC unit appointment (60 days before death ED visits 1.3 vs 0.8 and inpatient days 9.9 vs 2.9 respectively, p < 0.01). Patients with no PC decision died more often in secondary/tertiary hospitals (28% vs. 19% with a PC decision, and 6% with a decision and an appointment to a PC unit). CONCLUSIONS: The PC decision to initiate a palliative goal for the treatment had a distinct impact on the use of hospital services at the EOL. Contact with a PC unit further increased the likelihood of EOL care at primary care.

The association of financial difficulties and out-of-pocket payments with health-related quality of life among breast, prostate and colorectal cancer patients.

Objectives: Financial difficulties experienced by cancer patients may affect their health-related quality of life (HRQoL). This study assessed the direct economic burden that out-of-pocket (OOP) payments cause and explored how they and financial difficulties are associated with HRQoL. Methods: This is a cross-sectional registry and survey study of 1978 cancer patients having either prostate (630), breast (840) or colorectal cancer (508) treated in Finland. The patients were divided into five groups according to the stage of their disease: primary treatment, rehabilitation, remission, metastatic disease and palliative care. The cost data and OOP payments were retrieved from primary and secondary healthcare registries, the Social Insurance Institution of Finland, and a patient questionnaire. HRQoL was measured by 15D, EQ-5D-3L and by EORTC-QLQ-C30. Financial difficulties were evaluated based on patients' self-assessment in the EORTC-QLQ-C30 four-level question about financial difficulties. A path analysis was used to explore the relationship between clinical and demographic factors, HRQoL, OOP payments and financial difficulties. Results: The highest OOP payments were caused by outpatient medication. Total costs and OOP payments were highest in the palliative care group in which the OOP payments consisted mostly of outpatient medication and public sector specialist care. Private sector health care was an important item of OOP payments in the early stages of cancer. Financial difficulties increased together with OOP payments. HRQoL deteriorated the more a person had financial difficulties. In the path analysis, financial difficulties had a major negative direct and total effect on the HRQoL. Factors that attenuated financial difficulties were age, cohabiting and higher education and factors that increased them were OOP payments, total costs of healthcare use, and unemployment. Conclusions: High OOP payments are related to financial difficulties, which have a negative effect on HRQoL. Outpatient medication was a major driver of OOP payments. Among palliative patients, the economic burden was highest and associated with impaired HRQoL.

Assessing the utilization of the decision to implement a palliative goal for the treatment of cancer patients during the last year of life at Helsinki University Hospital: a historic cohort study.

Background: To avoid aggressive treatments at the end-of-life and to provide palliative care (PC), physicians need to terminate futile anti-cancer treatments and define the palliative goal of the treatment in time. This single center study assesses the practices used to make the decision that leads to treatment with a palliative goal, i.e., the PC decision and its effect on anti-cancer treatments at the end of life.Material and methods: Patients with a cancer diagnosis treated in tertiary hospital during 1st January 2013 - 31st December 2014 and deceased by the end of 2014 were identified in the hospital database (N = 2737). Of these patients, 992 were randomly selected for this study. The PC decision was screened from patient records, i.e., termination of cancer-specific treatments and a focus on symptom-centered PC.Results: The PC decision was defined in 82% of the patients during the last year of life (49% >30 days and 33% ≤30 days before death, 18% with no decision). The median time from the decision to death was 46 days. Systemic cancer therapy was given during the last month of life in 1%, 36% and 38% (p < .001) and radiotherapy 22%, 40% and 31% (p = .03) cases, respectively; referral to a PC unit was made in 62%, 22% and 11%, respectively (p < .001). In logistic regression analyses younger age, shorter duration of the disease trajectory and type of cancer (e.g., breast cancer) were associated with a lack or late timing of the PC decision.Conclusion: The decision to initiate a palliative goal for the treatment was frequently made for cancer patients but occurred late for every third patient. Younger age and certain cancer types were associated with late PC decisions, thus leading to anti-cancer treatments continuing until close to the death with low access to a PC unit.

Health-related quality of life in different states of breast cancer - comparing different instruments.

BACKGROUND: The prognosis of breast cancer has improved significantly during the last few decades increasing the interest in health-related quality of life (HRQoL). The aim of this study was to compare the HRQoL scores produced by different instruments and to shed light on their validity in various states of breast cancer by studying the association of cancer-related symptoms with HRQoL. MATERIAL AND METHODS: An observational, cross-sectional study of breast cancer patients treated in the Helsinki and Uusimaa Hospital District from September 2009 to April 2011. A total of 840 patients completed three HRQoL questionnaires: the EQ-5D-3L (including VAS), 15D and EORTC QLQ-30 and a questionnaire concerning sociodemographic factors. Patients were divided into five mutually exclusive groups: primary treatment (n = 118), recovery (6-18 months from diagnosis) (n = 150), remission (>18 months) (n = 382), metastatic disease (n = 176) and palliative care (n = 14). The association of HRQoL with sociodemographic and clinical factors and cancer-related symptoms, screened by the EORTC QLQ-30, was studied by multivariate modeling using stepwise linear regression analysis. RESULTS: HRQoL scores were the best at the time closest to diagnosis and deteriorated with disease progression. The EQ-5D had a pronounced ceiling effect with 40.8% of the respondents scoring 1 (perfect health) compared to 6% for the 15D and 5.6% for VAS. In regression analyses, pain, fatigue and financial difficulties were the most important predictors of lower HRQoL. The 15D showed better discriminatory power and content validity. The EORTC QLQ-C30 functioning deteriorated in advanced states of the disease with physical, social and role functioning being the most affected. Insomnia, fatigue and pain were the most commonly reported symptoms in all groups. CONCLUSIONS: Different HRQoL instruments produce notably different HRQoL scores. The EQ-5D has a pronounced ceiling effect. Pain and fatigue are the most common symptoms associated with poor HRQoL in all disease states.

Automatic referral to standardize palliative care access: an international Delphi survey.

PURPOSE: Palliative care referral is primarily based on clinician judgment, contributing to highly variable access. Standardized criteria to trigger automatic referral have been proposed, but it remains unclear how best to apply them in practice. We conducted a Delphi study of international experts to identify a consensus for the use of standardized criteria to trigger automatic referral. METHODS: Sixty international experts stated their level of agreement for 14 statements regarding the use of clinician-based referral and automatic referral over two Delphi rounds. A consensus was defined as an agreement of ≥70% a priori. RESULTS: The response rate was 59/60 (98%) for the first round and 56/60 (93%) for the second round. Twenty-six (43%), 19 (32%), and 11 (18%) respondents were from North America, Asia/Australia, and Europe, respectively. The panel reached consensus that outpatient palliative care referral should be based on both automatic referral and clinician-based referral (agreement = 86%). Only 18% felt that referral should be clinician-based alone, and only 7% agreed that referral should be based on automatic referral only. There was consensus that automatic referral criteria may increase the number of referrals (agreement = 98%), facilitate earlier palliative care access, and help administrators to set benchmarks for quality improvement (agreement = 86%). CONCLUSIONS: Our panelists favored the combination of automatic referral to augment clinician-based referral. This integrated referral framework may inform policy and program development.

The indirect costs of palliative care in end-stage cancer: A real-life longitudinal register- and questionnaire-based study.

BACKGROUND: Palliative care needs are increasing as more people are dying from incurable diseases. Healthcare costs have been reported to be highest during the last year of life, but studies on the actual costs of palliative care are scarce. AIM: To explore the resource use and costs of palliative care among end-stage breast, colorectal and prostate cancer patients after termination of life-prolonging oncological treatments, that is, during the palliative care period. DESIGN: A real-life longitudinal register- and questionnaire-based study of cancer patients' resource use and costs. PARTICIPANTS: In total, 70 patients in palliative care with no ongoing oncological treatments were recruited from the Helsinki University Hospital or from the local hospice. Healthcare costs, productivity costs and informal care costs were included. RESULTS: The mean duration of the palliative care period was 179 days. The healthcare cost accounted for 55%, informal care for 27% and productivity costs for 18% of the total costs. The last 2 weeks of life contributed to 37% of the healthcare cost. The costs of the palliative care period were higher in patients living alone, which was mostly caused by inpatient care ( p = 0.018). CONCLUSION: The 45% share of indirect costs is substantial in end-of-life care. The healthcare costs increase towards death, which is especially true of patients living alone. This highlights the significant role of caregivers. More attention should be paid to home care and caregiver support to reduce inpatient care needs and control the costs of end-of-life care.

Undergraduate curriculum in palliative medicine at Tampere University increases students' knowledge.

BACKGROUND: Education in palliative medicine (PM) at medical schools reveals wide variation despite the increasing importance of palliative care. Many universities present poor description of the benefits and detailed content of the total curriculum in PM. Using the recommendations of European Association for Palliative Care (EAPC) as a reference, we evaluated the content and outcomes of the curriculum in PM at the University of Tampere, Finland. METHODS: We searched for a PM curriculum by examining the teaching offered by every specialty and compared it to EAPC recommendations. Students' knowledge was evaluated using a progress test over three consecutive years. RESULTS: We found 53.5 teaching hours addressing PM issues, which exceeds the recommendation of the EAPC. Basics, symptom management, ethics, and communication skills were well established, while education in psychosocial/spiritual aspects, teamwork and self-reflection failed to reach the recommendations. Out of the maximum of 4.0, the progress test mean scores in PM among the third, fourth, fifth and sixth year students were 0.1 (SD 0.71), 0.69 (SD 1.28), 1.38 (SD 1.46) and 2.53 (SD 1.26), respectively (p < 0.001). This growing knowledge was associated with the timely increase in teaching provided through the PM discipline. In addition, the students who completed the optional PM course achieved better mean scores (2.66; SD 1.27) than the others (1.33; SD 1.43) (p < 0.001). CONCLUSIONS: The curriculum in PM at the University of Tampere is integrated into the teaching of many disciplines and complied well with the EAPC recommendations. This education led to increasing knowledge in PM among medical students.

Referral criteria for outpatient specialty palliative cancer care: an international consensus.

Although outpatient specialty palliative-care clinics improve outcomes, there is no consensus on who should be referred or the optimal timing for referral. In response to this issue, we did a Delphi study to develop consensus on a list of criteria for referral of patients with advanced cancer at secondary or tertiary care hospitals to outpatient palliative care. 60 international experts (26 from North America, 19 from Asia and Australia, and 11 from Europe) on palliative cancer care rated 39 needs-based criteria and 22 time-based criteria in three iterative rounds. Nearly all experts responded in each round. Consensus was defined by an a-priori agreement of 70% or more. Panellists reached consensus on 11 major criteria for referral: severe physical symptoms, severe emotional symptoms, request for hastened death, spiritual or existential crisis, assistance with decision making or care planning, patient request for referral, delirium, spinal cord compression, brain or leptomeningeal metastases, within 3 months of advanced cancer diagnosis for patients with median survival of 1 year or less, and progressive disease despite second-line therapy. Consensus was also reached on 36 minor criteria for specialist palliative-care referral. These criteria, if validated, could provide guidance for identification of patients suitable for outpatient specialty palliative care.

Costs in different states of prostate cancer.

OBJECTIVES: This cross-sectional study assesses resource use and costs in different states of prostate cancer (PCa) in a real-life setting. Costs were estimated as incremental costs due to cancer for a six-month period and they included direct medical costs, productivity costs and costs of informal care. METHODS: Resource use and cost data, irrespective of who the payer was, were retrieved from the registries for 611 PCa patients in the Helsinki area in Finland. In addition, patients answered background questions concerning informal care, work capacity and educational status. Patients were divided into four mutually exclusive groups based on disease state and time from diagnosis: primary (local disease, first six months after diagnosis; n = 47), rehabilitation (local disease, 0.5-1.5 years after diagnosis or recurrence; n = 158), remission (local disease, more than 1.5 years after diagnosis; n = 317) and metastatic (after detection of metastases; n = 89). RESULTS: Costs differed markedly between the states of disease. Mean direct health care costs for the six-month periods were: primary treatment state € 2750, rehabilitation state € 1143, remission state € 760 and metastatic state € 7423. Productivity costs were also highest (€ 4277) in the metastatic state. Overall, the average share of indirect costs was around one third of the total costs. However, when including informal care, their combined share of the total costs increased to around half or more. CONCLUSIONS: The results provided state-specific estimates of the direct health care and indirect costs of PCa in Finland. The treatment of metastatic disease is significantly more costly than treatment of early stage PCa. Although direct medical costs were higher compared to productivity costs, they should be taken into consideration when evaluating the costs of PCa.

Costs of colorectal cancer in different states of the disease.

OBJECTIVES: This cross-sectional study estimates the resource use and costs among prevalent colorectal cancer (CRC) patients in different states of the disease. METHODS: Altogether 508 Finnish CRC patients (aged 26-96; colon cancer 56%; female 47%) answered a questionnaire enquiring about informal care, work capacity, and demographic factors. Furthermore, data on direct medical resource use and productivity costs were obtained from registries. Patients were divided into five mutually exclusive groups based on the disease state and the time from diagnosis: primary treatments (the first six months after the diagnosis), rehabilitation, remission, metastatic disease, and palliative care. The costs were calculated for a six-month period. Multivariate modeling was performed to find the cost drivers. RESULTS: The costs were highest during the primary treatment state and the advanced disease states. The total costs for the cross-sectional six-month period were €22 200 in the primary treatment state, €2106 in the rehabilitation state, €2812 in the remission state, €20 540 in the metastatic state, and €21 146 in the palliative state. Most of the costs were direct medical costs. The informal care cost was highest per patient in the palliative care state, amounting to 33% of the total costs. The productivity costs varied between disease states, constituting 19-40% of the total costs, and were highest in the primary treatment state. CONCLUSIONS: The first six months after the diagnosis of CRC are resource intensive, but compared with the metastatic disease state, which lasts on average for 2-3 years, the costs are rather modest. Informal care constitutes a remarkable share of the total costs, especially in the palliative state. These results form a basis for the evaluation of the cost effectiveness of new treatments when allocating resources in CRC treatment.

The effect of ovarian dysfunction on bone mineral density in breast cancer patients 10 years after adjuvant chemotherapy.

BACKGROUND: Premenopausal patients treated with adjuvant chemotherapy often develop early menopause and thus, may encounter significant bone loss. We studied the long-term effects of chemotherapy-induced ovarian dysfunction on bone mineral density in breast cancer patients. MATERIAL AND METHODS: The effect of menstrual status after adjuvant chemotherapy on bone mineral density (BMD) was examined in 29 premenopausal breast cancer patients. RESULTS: During 10 years of follow-up, nearly 90% of women developed menstrual irregularities or amenorrhea. The total bone loss at the lumbar spine was -5.4% in women with preserved menstruation, -15.3% in those with irregular menses and -13.2% in amenorrheic women 10 years after adjuvant chemotherapy. The changes in lumbar spine BMD correlated significantly with menstrual function. Both amenorrhea and menstrual irregularities shortly after chemotherapy increased the risk of osteoporosis later on: one third of women with ovarian dysfunction developed osteoporosis of the lumbar spine during the follow-up. Osteopenia before adjuvant therapy predicted an increased risk for osteoporosis. CONCLUSION: The present study with a unique follow-up period of 10 years shows that ovarian dysfunction leads to long-term deleterious BMD changes and predisposes breast cancer survivors to osteoporosis.

Health-related quality of life among breast, prostate, and colorectal cancer patients with end-stage disease.

PURPOSE: To explore end-stage breast, prostate, and colorectal cancer patients' health-related quality of life (HRQoL); to compare results obtained by different HRQoL instruments; and to explore factors related to impaired HRQoL. METHODS: A cross-sectional observational study utilized two generic HRQoL instruments, the 15D and the EQ-5D, and a cancer-specific instrument, the EORTC QLQ-C30. Patients were recruited from the Helsinki University Hospital's Department of Oncology and from a local hospice. RESULTS: Of the 114 palliative care patients included in the analysis, 27 had breast cancer, 30 had prostate cancer, and 57 had colorectal cancer. Of these, 28 % died within 3 months after their response, while 32 % died within three to 6 months, and 39 % died more than 6 months after. Utility values varied widely by instrument: the 15D gave the highest utility values and VAS the lowest (15D: 0.74, EQ-5D: 0.59 and VAS: 55). Patients close to death had lower HRQoL scores independently from the instrument used. The EQ-5D showed a pronounced ceiling effect, with 13 % of patients reporting full health, whereas the corresponding figures for the 15D and VAS were 1 and 0 %, respectively. Fatigue was the most common symptom and also predicted impaired HRQoL most significantly. CONCLUSIONS: All instruments were applicable for the evaluation of HRQoL among end-stage cancer patients. Fatigue seemed to be the most significant deteriorating factor, whereas clinical and demographic factors had less of an effect on HRQoL.