National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

Factors influencing GPs' perception of specialised palliative homecare (SPHC) importance - results of a cross-sectional study.

BACKGROUND: General Practitioners (GPs) are the main providers of primary palliative care (PPC). At the same time they are the main initiators of specialised palliative homecare (SPHC). In Germany, little is known about factors which influence GPs in their involvement of SPHC. Aim of our study is to identify factors that drive GPs to give value to and involve SPHC. METHODS: A cross-sectional survey was performed. In 2018, questionnaires were mailed to 6000 randomly selected GPs from eight German federal states, focusing on the extent of GPs' palliative care activities and their involvement of SPHC. RESULTS: With a response rate of 19.4% and exclusion of GPs working in SPHC-teams, n = 1026 questionnaires were appropriate for analysis. GPs valued SPHC support as the most "important/very important" for both "technical/invasive treatment measures" (95%) and availability outside practice opening hours (92%). The most relevant factor influencing perceived SPHC-importance was GPs' self-reported extent of engagement in palliative care (ß = - 0.283; CI 95% = - 0.384;-0.182), followed by the perceived quality of utilised SPHC (ß = 0.119; CI 95% = 0.048;0.190), involvement in treatment of palliative patients after SPHC initiation (ß = 0.088; CI 95% = 0.042;0.134), and conviction that palliative care should be a central part of GPs' work (ß = - 0.062; CI 95% = - 0.116;-0.008). Perceived SPHC-importance is also associated with SPHC-referrals (ß =0.138; p < 0.001). The lower the engagement of GPs in palliative care, the more they involve SPHC and vice versa. CONCLUSIONS: GPs with low reported activity in palliative care are more likely to initialise SPHC for palliative care activities they do not deliver themselves for various reasons, which might mean that the involvement of SPHC is substitutive instead of complementary to primary palliative care. This finding and its interpretation should be given more attention in the future policy framework for (specialised) palliative homecare. TRIAL REGISTRATION: German Clinical Trials Register DRKS00014726 , 14.05.2018.

[Quality assurance in specialized palliative home care (QUAPS): a questionnaire's feasibility]. / Qualitätssicherung in der spezialisierten ambulanten Palliativversorgung (QUAPS) ­ Praktikabilität eines Fragebogens.

BACKGROUND: Structure and process parameters are not sufficient for adequate quality assurance in specialized palliative home care (SAPV). Asking the patients and their relatives for their assessment is crucial. A focus group in Jena, Germany, developed the quality assurance in specialized palliative home care (QUAPS) questionnaire for this assessment of outcome parameters, which was tested in two studies. OBJECTIVES: The aim of the study was to evaluate the feasibility of a questionnaire for patients, relatives and SAPV teams. MATERIAL AND METHODS: The questionnaire collects outcome parameters on a Likert scale as well as the distress of respondents using the numeric rating scale (NRS). In the pilot study, QUAPS I was tested in three SAPV teams. The survey was simplified in the follow-up study, QUAPS II, where 17 teams were included. Both studies were conducted with an ex-post-facto design. RESULTS: In QUAPS I, complete datasets could be obtained for 43 out of 308 surveyed cases. In QUAPS II, 169 complete datasets resulted from 371 surveyed cases. The SAPV staff assessed the QUAPS II survey as being organizationally feasible. The questionnaire shows good internal consistency and high approval for the surveyed aspects of SAPV care. Ceiling effects occurred. More than 70% of respondents reported a distress score >5. CONCLUSIONS: The simplified survey in QUAPS II resulted in a higher rate of complete datasets. The detected ceiling effects restrict the conclusions of the survey. Biases like social desirability cannot be ruled out. In the future, a combination of different questionnaires (e. g. integrated palliative outcome score [IPOS] and QUAPS) should be explored.

ESMO Consensus Conference on malignant lymphoma: general perspectives and recommendations for the clinical management of the elderly patient with malignant lymphoma.

The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommendations on critical subjects difficult to consider in detail in the ESMO Clinical Practice Guidelines. The following areas were identified: (1) the elderly patient, (2) prognostic factors suitable for clinical use, and (3) the 'ultra-high-risk' group. Before the conference, the expert panel was divided into three working groups; each group focused on one of these areas in order to address clinically-relevant questions relating to that topic. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, each working group developed recommendations to address each of the four questions assigned to their group. These recommendations were presented to the entire panel and a consensus was reached. This consensus, which was further developed in continuous post-meeting discussions, formed the basis of three manuscripts, each covering one of the three key areas identified. This manuscript presents the consensus recommendations regarding the clinical management of elderly patients diagnosed with malignant lymphoma. Four clinically-relevant topics identified by the panel were: 1) how to define patient fitness, 2) assessing quality of life, 3) diagnostic work-up and 4) clinical management of elderly patients with lymphoma. Each of these key topics is addressed in the context of five different lymphoma entities, namely: CLL, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma and diffuse large B-cell lymphoma. Results, including a summary of evidence supporting each recommendation, are detailed in this manuscript.

Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†.

BACKGROUND: Screening tools are proposed to identify those older cancer patients in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on the use of screening tools. MATERIALS AND METHODS: SIOG composed a task group to review, interpret and discuss evidence on the use of screening tools in older cancer patients. A systematic review was carried out and discussed by an expert panel, leading to a consensus statement on their use. RESULTS: Forty-four studies reporting on the use of 17 different screening tools in older cancer patients were identified. The tools most studied in older cancer patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons for detecting problems on a full GA, the G8 was more or equally sensitive than other instruments in all six comparisons, whereas results were mixed for the VES-13 in seven comparisons. In addition, different tools have demonstrated associations with outcome measures, including G8 and VES-13. CONCLUSIONS: Screening tools do not replace GA but are recommended in a busy practice in order to identify those patients in need of full GA. If abnormal, screening should be followed by GA and guided multidisciplinary interventions. Several tools are available with different performance for various parameters (including sensitivity for addressing the need for further GA). Further research should focus on the ability of screening tools to build clinical pathways and to predict different outcome parameters.

Management of elderly patients with NSCLC; updated expert's opinion paper: EORTC Elderly Task Force, Lung Cancer Group and International Society for Geriatric Oncology.

Non-small-cell lung cancer (NSCLC) is a very common disease in the elderly population and its incidence in this particular population is expected to increase further, because of the ageing of the Western population. Despite this, limited data are available for the treatment of these patients and, therefore, the development of evidence-based treatment recommendations is challenging. In 2010, European Organization for Research and Treatment of Cancer (EORTC) took an initiative in collaboration with International Society of Geriatric Oncology (SIOG) and created an experts panel that provided an experts' opinion consensus paper for the management of elderly NSCLC patients. Since this publication, important new data are available and EORTC and SIOG recommended to update the 2010 recommendations. Besides recommendations for surgery, adjuvant chemotherapy and radiotherapy, treatment of locally advanced and metastatic disease, recommendations were expanded, to include data on patient preferences and geriatric assessment.

Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper.

BACKGROUND: Comorbidities and risk factors likely to complicate treatment are common in elderly cancer patients. Anthracyclines remain the cornerstone of first-line therapy for non-Hodgkin's lymphoma (NHL) and metastatic and early breast cancer but can cause congestive heart failure. Elderly patients are at increased risk of this event and measures to reduce it should be considered. METHODS: A committee of experts in breast cancer and NHL met under the auspices of the International Society for Geriatric Oncology to review the literature and make recommendations, based on level of evidence, for the assessment, treatment and monitoring of elderly patients requiring anthracyclines. RESULTS AND RECOMMENDATIONS: Use of anthracycline-based chemotherapy illustrates many of the dilemmas facing elderly cancer patients. Age in itself should not prevent access to potentially curative treatment or treatment that prolongs life or improves its quality. The risk of cardiotoxicity with conventional anthracyclines is increased by the following factors: an existing or history of heart failure or cardiac dysfunction; hypertension, diabetes and coronary artery disease; older age (independent of comorbidities and performance status); prior treatment with anthracyclines; higher cumulative dose of anthracyclines and short infusion duration. The fact that cumulative and irreversible cardiotoxicity is likely to be greater in this population than among younger patients calls for effective pretreatment screening for risk factors, rigorous monitoring of cardiac function and early intervention. Use of liposomal anthracycline formulations, prolonging the infusion time for conventional anthracyclines and cardioprotective measures should be considered. However, when treatment is being given with curative intent, care should be taken to ensure reduced cardiotoxicity is not achieved at the expense of efficacy.

EORTC workshop on clinical trial methodology in older individuals with a diagnosis of solid tumors.

BACKGROUND: Due to the aging of the population, the number of older patients diagnosed with a malignant disease is increasing. A multidisciplinary approach to the senior adult cancer patient is mandatory, to assure optimal diagnosis and therapeutic management. DESIGN: European Organisation for Research and Treatment of Cancer (EORTC) has currently defined senior adult oncology as one of its priorities and has established an active Elderly Task Force (ETF). Under the auspices of the EORTC, the ETF organized a workshop on clinical trial methodology in older cancer patients and in this article, we present the conclusions of this workshop. RESULTS: Besides the 'classical' efficacy end points, quality of life, functional status and independence of the patient should be assessed in clinical trials in older patients. The participants of the workshop agreed on the use of a minimum dataset for the assessment of global health and functional status in older cancer patients. The panel also recommended that optimization of collaboration with pharmaceutical industry requires reporting of age-related data (subgroup analyses of clinical trials, age-related pooled analyses and obligatory post-marketing studies in vulnerable and frail older patients). CONCLUSION: The identification of proper clinical outcomes and the validation of geriatric screening tools are needed for conducting sound and comparable clinical trials.

EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology (SIOG) experts' opinion for the treatment of non-small-cell lung cancer in an elderly population.

Non-small-cell lung cancer (NSCLC) represents a common health issue in the elderly population. Nevertheless, the paucity of large, well-conducted prospective trials makes it difficult to provide evidence-based clinical recommendations for these patients. The present paper reviews the currently available evidence regarding treatment of all stages of NSCLC in elderly patients. Surgery remains the standard for early-stage disease, though pneumonectomy is associated with higher incidence of postoperative mortality in elderly patients. Given the lack of demonstrated benefit for the use of adjuvant radiotherapy, it is also not recommended in elderly patients. Elderly patients seem to derive the same benefit from adjuvant chemotherapy as younger patients do, with no significant increase in toxicity. For locally advanced NSCLC, concurrent chemoradiotherapy may be offered to selected elderly patients as there is a higher risk for toxicity reported in the elderly population. Third-generation single-agent treatment is considered the standard of care for patients with advanced/metastatic disease. Platinum-based combination chemotherapy needs to be evaluated in prospective trials. Unfortunately, with the exception of advanced/metastatic NSCLC, prospective elderly-specific NSCLC trials are lacking and the majority of recommendations made are based on retrospective data, which might suffer from selection bias. Prospective elderly-specific trials are needed.

[Chances and limitations of chemotherapy in elderly patients]. / Möglichkeiten und Grenzen der onkologischen Chemotherapie bei alten Patienten.

The chronological age of a patient should not be a barrier to apply chemotherapy. Elderly patients can benefit from chemotherapy. Chronological age should not be a reason for diagnostic or therapeutic nihilism, as the age of a patient poorly characterizes their health situation. Data with high level of evidence on treatment of elderly patients with cancer are limited. A comprehensive geriatric assessment (CGA) describes the individual deficits and resources of a patient much better. Limitations in CGA are risk factors for increased toxicity and decreased treatment benefit. The currently available data demonstrate under- and over-treatment in elderly patients with cancer.

The effect of adjuvant chemotherapy on symptom burden and quality of life over time; a preliminary prospective observational study using individual data of patients aged ≥70 with early stage invasive breast cancer.

OBJECTIVES: We aim to assess short and long term effects of chemotherapy on patient-reported quality of life (QOL) and patient versus clinician symptom reporting in older patients with breast cancer adjusted for tumour and aging parameters. MATERIAL AND METHODS: In this prospective, multicentre, non-interventional, observational study, women aged ≥70years were enrolled after surgery and assigned to a TC chemotherapy (docetaxel and cyclophosphamide) group or a control group depending on their planned adjuvant treatment. Longitudinal multivariate models were used to assess the statistical and minimal clinically important difference (MCID) in the impact of TC chemotherapy over time on QOL and symptom burden adjusted for baseline aging and tumour parameters. Statistical significance was set at 5% and MCID at 10 points. RESULTS: In total, 57 patients were enrolled in the chemotherapy and 52 patients in the control group. Within the chemotherapy group, clinical deterioration was reported at 3months for Fatigue (17.73), Dyspnoea (17.05), Diarrhoea (12.06) and Appetite Loss (17.05) scores (all p<0.001). However, the scores had returned to baseline (or even better for Role Functioning) at year 1. No clinical deterioration was reported in the control group. Symptom scores as reported by patients were significantly (p<0.05) higher than those reported by the clinicians, even more so for Fatigue, Dyspnoea, and Pain. CONCLUSION: Our results show that symptom burden and diminished QOL in an older breast cancer population receiving adjuvant TC chemotherapy are short-lived and disappear after a while with no long-term differences compared to a similar population not receiving chemotherapy.

Requestioning depression in patients with cancer: contribution of somatic and affective symptoms to Beck's Depression Inventory.

BACKGROUND: Depressive symptoms are a major complaint reported by cancer patients. Somatic and affective symptoms can contribute to depression. PATIENTS AND METHODS: We investigated the prevalence of somatic and affective depressive symptoms with the Beck Depression Inventory (BDI) in 213 hospitalized cancer patients prior to the start of chemotherapy. RESULTS: Seventeen of 213 patients (8%) were screened positive for major depression; 40 (19%) had mild to moderate depressive symptoms. The corresponding figures for somatic and affective symptoms were 33.3% and 2.8% in the patients with major depression and 23.0% and 8.0% in those with mild to moderate depressive symptoms. Female patients, patients with solid tumour and those with functional limitations had significantly higher mean scores. All differences were related to higher scores in somatic and not in affective items. CONCLUSIONS: Most alterations in the BDI in cancer patients are related to somatic and not to affective symptoms and may be attributed not to depression but to severity of the underlying disease.

Multicolor-FISH applied to resolve complex chromosomal changes in a case of T-ALL (FAB L2).

We report on a patient with a clinically diagnosed acute lymphoblastic leukemia (ALL) with partial unrecorded complex translocation events especially involving chromosomes 5, 9 and 18. At the GTG-band level the karyotype was abnormal in 20% of the analyzed cells. The complex karyotype was studied in more detail by spectral karyotyping (SKY) and multicolor banding (MCB) to characterize it in more detail. Thus, the karyotype could be described very accurately and in summary three different clones were detected, reflecting a high rate of karyotypic evolution in this patient.

Chronomodulated chemotherapy with oxaliplatin, 5-FU and sodium folinate in metastatic gastrointestinal cancer patients: original analysis of non-hematological toxicity and patient characteristics in a pilot investigation.

OBJECTIVE: Several clinical trials have demonstrated that oxaliplatin is a useful agent in combination with 5-fluorouracil (5-FU) and folinic acid (FA) for the treatment of patients with colorectal carcinoma. The aims of this pilot study were to evaluate non-hematological toxicity and patient characteristics in gastrointestinal cancer patients treated with chronomodulated chemotherapy consisting of oxaliplatin, 5-FU and sodium folinate. METHODS: Patients with metastatic gastrointestinal cancer received a chronomodulated regimen with oxaliplatin (25 mg/m2), 5-FU (750 mg/m2) and sodium folinate (150 mg/m2). Non-hematological toxicities were evaluated and analyzed in relation to patient characteristics, i.e. age, sex, body weight, body mass index (BMI), body surface area and smoking status. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria. RESULTS: The severity of non-hematological toxicity was generally moderate. Grade 4 toxicity was only found in 2 patients with diarrhea (12.5%). The most frequent common adverse events were nausea, Grades 1 - 2 in 13 patients (81.3%), followed by motor neuropathy, Grades 1 - 3 in 11 patients (68.9%). The analyses showed that patient characteristics such as BMI and smoking status were associated with mucositis/stomatitis, vomiting or mood alteration. Furthermore, there was a relationship between smoking status and the overall non-hematological toxicity. Smokers had significantly higher overall toxicity than non-smokers and body mass index correlated significant with overall toxicity. CONCLUSION: The results of this pilot investigation suggest that a chronomodulated regimen with oxaliplatin, 5-FU and sodium folinate has a manageable non-hematological toxicity profile and that toxicity of the chronomodulated schedule studied depends on the patient characteristics. In further investigations, risk factors determining chemotherapeutic toxicity should be considered. Because of the small number of patients in this pilot investigation, the findings need to be confirmed in a larger clinical study.

Pharmacokinetics of oxaliplatin and non-hematological toxicity in metastatic gastrointestinal cancer patients treated with chronomodulated oxaliplatin, 5-FU and sodium folinate in a pilot investigation.

OBJECTIVE: To analyze in a pilot study the association between the pharmacokinetics of chronomodulated administered oxaliplatin and non-hematological toxicity in patients with metastatic gastrointestinal cancer. METHODS: 16 patients received a 4-day chemotherapeutic regimen consisting of a 12-h chronomodulated infusion of oxaliplatin (25 mg/m2) followed by a 12-h chronomodulated infusion of 5-fluorouracil (750 mg/m2) and sodium folinate (150 mg/m2) daily. Plasma pharmacokinetics of oxaliplatin, measured as ultrafiltrable platinum, were determined. RESULTS: Pharmacokinetics and non-hematological adverse events could be assessed in all patients included in the study. Pharmacokinetic parameters showed moderate interpatient variability. The occurrence of nausea and vomiting, but not diarrhea, was significantly associated with the pharmacokinetics of ultrafiltrable platinum. Thus, increased AUC values were observed in patients who experienced nausea or vomiting. No differences in pharmacokinetic parameters were found between patients with and without oxaliplatin-induced neurotoxicity or the other selected non-hematological toxicities. CONCLUSION: The preliminary results in this pilot study suggest an association between pharmacokinetics of ultrafiltrable platinum and non-hematological toxicity such as nausea and vomiting. Furthermore, although the sample size is limited, systemic exposure to ultrafiltrable platinum appears to predict the risk of non-hematological toxicity in patients treated with chronomodulated oxaliplatin combined with 5-FU and FS.

The impact of comorbidity on the survival of postmenopausal women with breast cancer.

PURPOSE: The aim was to assess the impact of comorbidity on survival of postmenopausal women with breast cancer diagnosis in the period 1995-1997. METHODS: The level of comorbidity was described by the methods suggested by Satariano and Charlson. Cox's proportional hazard models were used to explore the impact of comorbidity on all-cause mortality. RESULTS: After a median follow-up time of 52 months, an increasing level of comorbidity was associated with a higher all-cause mortality. Compared to patients with-out comorbid conditions, the hazard ration of death (HR) was 1.2 (95% CI: 0.8-1.7) for Satariano index 1 and HR 2.3 (95% CI: 1.5-3.5) for Satariano index >or=2, and HR 1.6 and 2.1 for the Charlson comorbidity index, respectively. Independent of comorbidity, the treatment pattern had a strong impact on survival. The level of comorbidity has an influence on the 3-year survival of postmenopausal women with breast cancer. CONCLUSIONS: Long-term follow-up is required to appraise these findings in relation to treatment strategies.

A population-based study on variations in the use of adjuvant systemic therapy on postmenopausal patients with early stage breast cancer.

PURPOSE: To assess adherence to treatment recommendations regarding adjuvant systemic therapy of postmenopausal patients with early stage breast cancer. METHODS: A population-based cohort of women from Eastern Thuringia/Germany with first diagnosis of breast cancer in 1995-2000 was studied. The use of adjuvant therapy was assessed separately for patients with positive and negative nodal status fitting polytomous logistic regression models. RESULTS: Among 396 women with positive lymph nodes and 832 with negative lymph nodes, 92.9% and 87.3% received an adjuvant systemic treatment, respectively. Age, comorbidity, hormone receptor status, histological grading, and additionally, in nodal positives, the number of involved lymph nodes, were associated with treatment patterns. Age had the strongest impact on treatment decision. Older women more often received hormone- or no adjuvant therapy. However, 26.3% of the women with lymph node involvement and positive hormone receptor status received no hormone therapy, whereas 35.7% of women with negative hormone receptor status received hormone therapy. CONCLUSION: The number of patients with adjuvant systemic therapy is high in women with positive and those with negative lymph nodes, reflecting adherence to the recommendations. Better outcome could be expected if hormone therapy was used adequately in receptor positives. Further follow-up is required to monitor the outcome and changes in adherence to treatment recommendations.

[Geriatric oncology]. / Geriatrische Onkologie.

The demographic development will result in a major increase in the number of elderly cancer patients. Age is the main risk factor for the development of a malignant disease. The incidence of the main cancer diagnosis increases with advancing age. Treatment of elderly cancer patients is an exquisite task. On the one hand, an increased morbidity and mortality may be the result of an unreflected transfer into the geriatric setting of treatment schedules developed for younger patients. On the other hand, reduction of dose intensity can result in decreased survival, life prolongation or insufficient palliation. Elderly people are a very heterogeneous group. Some are in a very good health status. Others are impaired, dependent, suffer from a number of comorbidities and have to take a variety of drugs. Those conditions and not the chronological age influence tolerance against tumour therapy. For elderly patients maintenance of independence and quality of life is more important than disease free survival and prolongation of life.

[Geriatric assessment prior to oncological therapy]. / Geriatrisches Assessment vor onkologischer Therapie.

Ageing is the single most important risk factor for cancer. This is also true for most cancer diseases of the genitourinary tract. In combination with the demographic changes in Germany and most other countries, the consequence is a substantial increase in the number of elderly patients with cancer. Most therapies in oncology have a high risk for toxic side effects. Ageing is a very heterogeneous process. The chronological age of a patient insufficiently reflects the individual resources, deficits and risk factors but this can be assessed by a structured geriatric assessment. Integration of geriatric assessment into oncological treatment decisions is still low and is one of the major tasks in cancer care in the future.