Symptoms During Outpatient Cancer Treatment and Options for their Management
; ; ;
Background: Cancer patients account for a large segment of the German healthcare system, with a 5-year prevalence of around 1.7 million persons. Advances in oncological treatment, now frequently performed on an outpatient basis, are granting many of these individuals a longer life span. At the same time, cancer patients often suffer disease-related symptoms and adverse effects from their tumor treatment, which may strongly impair their quality of life despite the improved techniques for management of side effects.
Methods: This review is based on a selective literature search of the PubMed and Cochrane Library databases carried out in December 2019 and January 2020. Special attention was paid to guidelines, expert opinions, and recommendations from professional societies.
Results: Alongside decreased well-being, cancer patients often suffer from fatigue (70–100%), loss of appetite (6–53%), pain (30–80 %), and dyspnea (10–70%). The prevalence and severity of the symptoms varies depending on the tumor entity and the patient’s sex. A meta-analysis showed that besides causal treatment, physical activity achieves moderately strong effects in tumor-associated fatigue syndrome (Cohen’s d = 0.30 [0.25; 0.36]). The WHO recommends early use of opioids in tumor-associated pain. A meta-analysis of randomized trials described symptom relief by means of opioids also in dyspnea (standardized mean difference: −0.32 [−0.53; −0.10]). Increasingly, guidelines are recommending regular palliative medical symptom screening.
Conclusion: Regular documentation of symptoms in outpatients offers the opportunity for targeted management of symptoms during treatment with the involvement of various disciplines such as palliative medicine, exercise therapy, and psychotherapy.
With an incidence of around 492 000 and a 5-year prevalence of around 1.7 million people in 2016, patients with cancer represent a large treatment group in the Germany healthcare system (1). The oncological services network consists of hospitals and individual practices (1). Advances in oncological therapies have led to longer life span, even for patients with metastatic or locally advanced cancer; nonetheless, despite improved management of adverse effects, having advanced disease or metastastis can lead to increased rates of hospitalization and a poorer quality of life (e1, 2, e2, e3).
According to a survey of oncologists in the USA, the involvement of palliative (medical) care teams often takes place late in the course of disease (e4). The need for treatment due to certain symptoms is often not adequately met, for example for pain (25%), emotional needs (10–84%), and fatigue (18–74%) (3, e4, e5). A method of documentation of symptoms that is integrated into the clinical treatment context can help improve communication between doctor and patient (4, e6, e7) and align treatment more closely to needs, thereby increase patient wellbeing (4, 5, 6).
This article describes the symptoms of cancer patients who have received outpatient cancer therapy and the evidence-based treatment options for the four main symptoms.
This narrative review is based on a selective literature search in the PubMed and Cochrane Library databases using relevant keywords (such as “patient-reported outcome”, “outpatient”, “symptoms”, “cancer patients”, and “palliative care”) and supplemented with guidelines, expert opinions, and recommendations from specialist societies. The survey was carried out until October 2020.
Symptoms of cancer patients in an outpatient setting
Patients with cancer can experience various symptoms due to their disease and/or the therapy itself. In the literature, the prevalence of symptoms is presented differently in the order of precedence and in the percentages. In addition to a poor general condition, fatigue (70%–100%), loss of appetite (6%–53%), pain (30%–80%), and dyspnea (10%–70%) are described as the main symptoms of patients with cancer in an outpatient setting. Monocentric data are shown as an example in Figure 1 (e6, 7, 8, e7, e8). In particular, symptoms in the last six months of life include a decreased well-being, lack of appetite, and increased tiredness (9).
The severity of the symptoms depends on the cancer type and patient‘s sex (e7, e9, e10). While pain and fatigue are prevalent in patients with cancer of the central nervous system or head-and-neck area, loss of appetite and a poor general condition are more likely to occur in patients with cancer of the gastrointestinal tract, lungs, breasts, or genital area (e7, 10, e11). While these symptoms vary with the distinct types of cancer, fatigue, anxiety, and depression seem to occur regardless of the type of cancer. Differences between the sexes are also described. While dysphagia (22%–28% versus 14%–16%; male versus female) and insomnia (52%–61% versus 45%–56%) occur more frequently in male patients, nausea (34%–42% versus 22%–31%), vomiting (24%–28% versus 17%–22%), and anxiety (29%–60% versus 20%–51%) play a larger role for female patients (e7, e12, e13, e14).
The following sections describe the most common symptoms in cancer patients.
Cancer-related fatigue syndrome
The cancer-related fatigue syndrome is the most dominant symptom (70%–100%) in patients with cancer (e15). The symptoms of cancer-related fatigue syndrome range from excessive exhaustion that is not proportional to prior activities or the subsequent recovery phases, to impaired concentration and memory. This syndrome is often associated with numerous symptoms, including pain (effect size d = 0.6; U = 83.31; p = 0.00), dyspnea (d = 0.45; U = 25.91; p = 0.00), nausea/vomiting (d = 0.82; U = 119.76; p = 0.00), loss of appetite (d = 0.65; U = 63.47; p = 0.00), and psychological stress, especially depression (d = 1.49, U = 297.80, p = 0.00) and anxiety (d = 1.11; U = 227.79; p = 0.00) (11).
In the case of pronounced fatigue or weakness during patient screening, specialist societies and expert working groups (12, 13, 14) recommend carrying out a fatigue assessment once other comorbidities (including anemia, infection, dehydration, and cachexia) have been excluded. In Germany, this assessment can use various validated German-language questionnaires (e.g., BFI, FACT-F, CFS, MFI-20, FSI) (e16). Indications of depression in the differential diagnosis include history of depression, pronounced listlessness, sustained feelings of worthlessness, thoughts of suicide, insomnia, and daily mood swings, while the main indication of cancer-related fatigue is exhaustion that is not proportional to recent activity (e17, e18, e19).
Discussing this syndrome in detail with patients can help them to better understand it. Treatment strategies can then be developed together. This process can be aided by The Blue Guide “Fatigue: Chronic Fatigue in Cancer” from the German Cancer Aid (Deutschen Krebshilfe) (15) or by special patient seminars.
In addition to cause-specific therapies, symptom-oriented therapies should also be used (Figure 2). According to meta-analyses, physical activity plays a major role in the treatment of cancer-related fatigue syndrome (weighted effect size, Cohen’s d: 0.30; 95% confidence interval [0.25; 0.36]), as does psychotherapeutic interventions (16, e20, e21, e22).
About 30% of patients undergoing curative therapy (e23), and 60% to 80% of patients with incurable cancer, experience pain (e24, 17). Therefore, these patients should be regularly recorded as part of a symptom screening; in Germany, this can be done for example using the Minimal Documentation System (MIDOS 2) (18) or the German Integrated Palliative Care Outcome Scale (IPOS) (19), in order to initiate adequate pain therapy at an early stage. Corresponding questionnaires are available for free download on the website of the German Society for Palliative Medicine (Deutschen Gesellschaft für Palliativmedizin) (20).
A distinction should be made between nociceptive (visceral or somatic) and neuropathic pain. In addition to the pain characteristics, the extent, dynamics, and intensity of pain at the beginning and during the treatment course should be recorded using a verbal rating scale (VRS; no pain, or mild, moderate, or severe pain) or a numeric rating scale (NRS; 0–10). The World Health Organization (WHO) recommends a 3-step ladder in which the use of opioids is recommended for moderate and severe cancer pain (21). If possible, medication should be administered orally and at a specified interval. The dose should be increased gradually until the patient is pain-free. At the beginning of pain control, an assessment should be carried out, for example with the help of the McGill Pain Questionnaire (e25) or the German Pain Questionnaire (DSF, Deutschen Schmerz-Fragebogens; ), in order to determine the type of pain, the cause of pain, and the appropriate pain management. Observation sheets in German, such as the “Observation Tool for Pain Assessment in Elderly People with Dementia” (BISAD, Beobachtungsinstrument für die Schmerzerfassung bei alten Menschen mit Demenz; [e26]) or the questionnaire “Assessment of Pain in Dementia” (BeSD, Beurteilung von Schmerzen bei Demenz), can help with assessment if a self-assessment is not possible (e27).
In 2018, the WHO made the following important updates to the recommendation for the treatment of cancer-related pain symptoms (21):
1. Patients with cancer pain should receive nonsteroidal anti-inflammatory drugs (NSAIDs, for example ibuprofen or paracetamol) and opioids. The pain intensity should decide whether this is initiated as a monotherapy or a combination therapy (high level of recommendation, low level of evidence). Thirteen studies were able to show evidence of pain reduction with the combination of NSAIDs and strong opioids (21).
2. For pain control, any opioid can be considered, with regular monitoring of the severity of the pain, alone or in combination with an NSAID (strong recommendation, low level of evidence; see also the German Guideline on Palliative Medicine ). Phase IV studies (e28), a meta-analysis (e29), and reviews (e30, e31) have shown comparable results in the efficacy of morphine, hydromorphone, oxycodone, fentanyl, and buprenorphine.
3. To achieve good pain control, opiates (slow- or immediate-release) should be taken orally, if possible. If oral or transdermal delivery is not an option, subcutaneous delivery is preferred (strong recommendation, moderate level of evidence). A total of seven studies have shown that subcutaneous administration is comparable to intravenous opioid administration in terms of effects and tolerance (24).
4. Supplementary steroids can be used for better pain control if indicated (high level of recommendation, moderate level of evidence). Steroids were found (in four trials for methylprednisolone, two trials for dexamethasone, and one trial for prednisolone) to reduce pain as compared to placebo (net difference of −9.9 [16.0; −3.8]) (21).
5. For bone metastases, bisphosphonates should be used to prevent and treat bone pain (strong recommendation, moderate level of evidence). Bisphosphonates showed a significant improvement in pain control as compared to placebo (net difference of −11.8 [−17.6; −6.1]) (21). Despite an equivalent reduction in pain, the WHO does not recommend RANK ligand antibodies (such as denosumab) for the management of pain related to bone metastases, due to the cost–benefit ratio (21). However, these drugs can prevent the occurrence of skeletal events and are recommended for preventive use by the German Clinical Practice Guideline for Supportive Therapy, as are bisphosphonates (25).
6. In the case of pain related to bone metastases, a single-dose (SD) radiation therapy should be carried out (strong recommendation, high level of evidence). Irradiation with a low-fractionated dose or SD (8–15 Gy) as well as with a high-fractionated dose or multiple dose (MD; 20–30 Gy over several fractions) showed comparable results with a complete reduction in pain (SD 25%; MD 26%). Due to the significantly lower costs (SD, $998 versus MD, $2 316) and the more efficient use of resources (more patients in the same time with comparable pain reduction), the WHO recommends single-fraction radiotherapy for pain treatment (21).
For pain that is difficult or impossible to control, it is advisable to involve a pain therapist or palliative care specialist in pain management at an early stage.
Lack of appetite and cachexia
Cancer therapy–specific adverse effects, such as changes in taste, mucositis, nausea, or constipation, often lead to loss of appetite, malnutrition (cachexia), and muscle wasting (sarcopenia). These symptoms are often associated with a greater risk of hospitalization and higher costs, as well as a negative prognosis and increased mortality (e32, e33).
According to the definition, cancer cachexia is defined by an unintended weight loss of more than 5% over the past six months, weight loss of more than 2% with a body mass index <20, or a muscle mass index compatible with sarcopenia (26). According to this definition, weight loss over the past six months, the body mass index, or a measurement of muscle mass using a radiological density measurement (dual-energy X-ray absorptiometry, DXA) should therefore be monitored during the screening procedures (26). Useful German-language screening tools include the Nutritional Risk Screening (NRS 2002 ) or the Malnutrition Universal Screening Tool (MUST [e34]), which can be found on the website of the German Society for Nutritional Medicine e.V. (e35).
The therapy of cancer cachexia is based on the stage. A distinction is made between pre-cachexia, cachexia, and refractory cachexia (Table). For pre-cachexia (mild weight loss [≤ 5%] and metabolic changes, such as anorexia and reduced glucose tolerance), monitoring and preventive interventions (such as nutritional advice and appropriate exercise) should be continued in addition to cause-specific treatment (28). If cachexia is diagnosed, multimodal management should be followed, consisting of the following elements:
- Adequate nutrition (oral/parenteral, 25–30 kcal/kg body weight/day);
- Protein supplementation (1.0–1.5 g/kg body weight/day)
- Psychotherapeutic support;
- Targeted muscle and strength building (26, 29).
Currently, there is only a weak recommendation for a continual use of corticosteroids. For refractory cachexia (progressive cancer, poor state of well-being, and short life expectancy [<3 months]), exercise therapies are of less interest. In this phase, psycho-oncological support is particularly important, in order to avoid conflict situations between the patient, relatives, and caregivers (for example, eating-related distress) (e36, e37). Initial studies suggest that patients, relatives, and caregivers benefit from receiving, and agreeing on, family-centered nutritional advice (e38, e39).
Dyspnea is also a frequent symptom (10–70% [e40]) in patients with cancer treated in an outpatient setting, and it increases in frequency and severity at end of life (e41, 9). Treatment of dyspnea should not only be symptom-oriented but also should consider a cause-specific diagnosis (with appropriate therapy). Pulmonary (e.g., pneumonia, pneumonitis, pulmonary embolism, tumor-related obstruction, pleural effusion), cardiac (e.g., heart failure, arrhythmia, pericardial effusion) and hematological (e.g., anemia) causes are frequent causes of dyspnea in patients with a cancer (30, e42).
As shortness of breath has a pronounced affective component, general and non-drug interventions alone or in combination with medicines play a major role in the treatment of dyspnea (Box 1). In particular, patients can be helped by general measures, such as patient training with instructions of how to establish a body-friendly, adapted mobility, adjust the daily rhythm, keep the face area cool, and involve relatives; patients can then use emergency measures for an emergency respiratory attack. Despite only a moderate evidence level, using fans has proven itself in practice and is recommended in the guidelines for palliative medicine (23). Walking aids, such as rollators or walking sticks, also promote mobility. Due to the lack of evidence (31), continuous oxygen administration should only be prescribed in hypoxic patients for whom long-term oxygen therapy is indicated.
In symptom-oriented drug therapy of dyspnea, opioids are the only drug group to have sufficient evidence in the treatment of dyspnea based on advanced lung diseases (meta-analysis of randomized studies: standardized mean difference −0.32 [−0.53; −0.10], p = 0.004]) (32). The informative value of observational and pilot studies is not yet sufficient for transnasal and transmucosal delivery. For this reason, opiates should be used orally or parenterally for symptomatic relief of dyspnea (23). In opioid-naïve patients, symptom relief has been described as early as 10–30 mg orally (p.o.) (e43). Therefore, a morphine dose of 2.5–5 mg p.o. or 1–2.5 mg subcutaneously (s.c.) every four hours is recommended (off-label use). With previous opioid therapy, an effect can be achieved by increasing the dose by 25% (e44; Box 1).
There is no evidence for the use of benzodiazepines. Only one study showed an effect for midazolam (33). Despite the lack of evidence, the use of benzodiazepines is recommended in the German Clinical Practice Guideline on Palliative Medicine (23) based on the good clinical experience, especially if there is anxiety or panic.
Palliative care needs
An early integration of specialized palliative care into the oncological setting can help to improve the symptoms that accompany palliative cancer care (standardized mean difference [SMD] −0.23 [−0.35; −0.10]) and thus improve the quality of life of patients (SMD 0.27 [0.15; 0.38]) (e45, 34, –36).
The timely involvement of specialized palliative care is recommended by the specialist societies, as the effects are classified as clinically relevant (despite the statistically low effect size) (23, e46, e47). The early involvement of an in-hospital palliative care service promotes patient orientation and effectively supports the treating oncologist in controlling symptoms (e48).
An international committee of experts recommended several criteria for referral, including two time-based and nine needs-based criteria (37), which record the following information: one or more severe physical symptoms, severe emotional distress, request for hastened death, spiritual crisis, the need for advance planning, patient request for referral, delirium, brain or leptomeningeal metastases, and spinal canal compression (Box 2).
- Visiting hours for specialized palliative medicine in oncological centers;
- General care by general practitioners and specialists, as well as outpatient nursing services with basic palliative care qualifications;
- Specialized care (general outpatient palliative care [AAPV, allgemeine ambulante Palliativversorgung] and specialized outpatient palliative care [SAPV, spezialisierte ambulante Palliativversorgung]).
Psycho-oncological and palliative care screening
Regular self-assessment of the symptoms and needs of patients with cancer (Patient Reported Outcome Measurement, PROM) enables a patient’s experiences to be recorded in a structured manner (38, e51). Early and repeated monitoring of symptoms in routine outpatient care correlates with an improved quality of life for patients (34% versus 18%), with a extended phase in which chemotherapy can be carried out (8.2 versus 6.3 months, p = 0.002) as well as reduced emergency room visits (34% versus 41%, p = 0.02), lower hospitalization rates (45% versus 49%, p = 0.08), and longer survival times (31.5 months versus 26.0 months, p = 0.03; hazard ratio [HR] 0.83, p = 0.04) (6, 39).
Psycho-oncological and palliative care screening is increasingly required by specialist societies and is firmly anchored in the oncological guidelines (e52). In German-language countries, symptom screening for palliative care is predominantly carried out using MIDOS_2 (18) or IPOS (19). Psychosocial stress can be assessed with the Hornheider Screening Instrument (HSI) (e53), while the questionnaires PHQ9 (e54) and GAD7 (e55) can document depression and anxiety in patients. This makes it possible for the oncological treatment team to monitor the symptoms of patients with cancer in an interdisciplinary manner based on oncological guidelines in an outpatient setting, and to treat them in an evidence-based and targeted manner.
Already the frequency of the most common symptoms, such as fatigue, pain, lack of appetite, and dyspnea, make it clear that psycho-oncological, supportive therapy, and palliative care expertise should be included within the outpatient cancer therapy, based on symptoms and needs. This can be achieved with psycho-oncological–palliative care screening.
Conflict of interest statement
PD Dr. Baumann has received meeting participation fees, travel expenses, and lecture fees from Roche, MSD, Pfizer, Novartis, Lilly, AstraZeneca, Takeda, Nutricia, and BMS, and has received unrestricted research support (third-party funding) from Milon and Technogyn.
Prof. Teufel has received unrestricted study support (third-party funding) from the DKH and the Hiermaier Stiftung.
Prof. Ostgathe has received unrestricted research support (third-party funding) from the DKH, the BMBF, and bidt.
PD Dr. Tewes has received unrestricted research support from the Stiftung Universitätsmedizin Essen and the Förderverein Innere Klinik–Tumorforschung–Essen e. V.
Manuscript received on 22 June 2020, revised version accepted on 4 December 2020
Translated from the original German by Veronica A. Raker, PhD
PD Dr. med. Mitra Tewes
Innere Klinik (Tumorforschung)
Westdeutsches Tumorzentrum Essen, Uniklinikum Essen
Hufelandstraße 55, 45122 Essen, Germany
Cite this as:
Tewes M, Baumann F, Teufel M, Ostgathe C: Symptoms during outpatient cancer treatment and options for their management. Dtsch Arztebl Int 2021; 118: 291–7. DOI: 10.3238/arztebl.m2021.0028
For eReferences please refer to:
Department 1 of Internal Medicine, Center for Integrated Oncology Aachen, Bonn, Cologne, Düsseldorf, University Hospital of Cologne, Cologne, Germany: PD Dr. sportwiss. Freerk Baumann
University of Duisburg-Essen, Clinic for Psychosomatic Medicine and Psychotherapy, LVR University Hospital Essen, Essen, Germany: Prof. Dr. med. Martin Teufel
Department of Palliative Medicine, Universitätsklinikum Erlangen, Comprehensive Cancer Center CCC Erlangen – EMN, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany: Prof. Dr. med. Christoph Ostgathe
|1.||Robert Koch-Institut, Zentrum für Krebsregisterdaten: Krebs in Deutschland. 17. 12 2019. www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebs_in_Deutschland/kid_2019/kid_2019_c00_97_krebs_gesamt.pdf?__blob=publicationFile. (last accessed on 28 September 2020).|
|2.||Howlader N, Noone AM, Krapcho M, et al. (eds).: SEER Cancer Statistics Review, 1975–2016, National Cancer Institute. Bethesda, MD. www.seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site, April 2019. (last accessed on 22 January 2020).|
|3.||Greco MT, Roberto A, Corli O, et al.: Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer. J Clin Oncol 2014; 32: 4149–54 CrossRef MEDLINE|
|4.||Detmar SB, Muller MJ, Schornagel JH, et al.: Health-related quality-of-life assessments and patient-physician communication: a randomized controlled trial. JAMA 2002; 288: 3027–34. Erratum in: JAMA 2003; 289: 987 CrossRef MEDLINE|
|5.||Kaasa S, Loge JH, Aapro M, et al.: Integration of oncology and palliative care: a Lancet Oncology Commission. Lancet Oncol 2018; 19: e588–e653 CrossRef|
|6.||Basch E, Deal AM, Kris MG, et al.: Symptom monitoring with patient-reported outcomes during routine cancer treatment: a randomized controlled trial. J Clin Oncol 2016; 34: 557–65 CrossRef MEDLINE PubMed Central|
|7.||Tewes M, Rettler TM, Beckmann M, et al.: Patient-Reported-Outcome-Messung (PROM) psychosozialer Belastung und Symptome für ambulante Patienten unter kurativer oder palliativer Tumortherapie. Onkologe 2018: 24: 69–75 CrossRef|
|8.||Henson LA, Maddocks M, Evans C, Davidson M, Hicks S, Higginson IJ: Palliative care and the management of common distressing symptoms in advanced cancer: pain, breathlessness, nausea and vomiting, and fatigue. J Clin Oncol 2020; 38: 905–14 CrossRef MEDLINE PubMed Central|
|9.||Seow H, Barbera L, Sutradhar R, et al.: Trajectory of performance status and symptom scores for patients with cancer during the last six months of life. J Clin Oncol 2011; 29: 1151–8 CrossRef MEDLINE|
|10.||Dong ST, Butow PN, Costa DS, Lovell MR, Agar M: Symptom clusters in patients with advanced cancer: a systematic review of observational studies. J Pain Symptom Manage 2014; 48: 411–50 CrossRef MEDLINE|
|11.||Oh HS, Seo WS: Systematic review and meta-analysis of the correlates of cancer-related fatigue. Worldviews Evid Based Nurs 2011; 8: 191–201 CrossRef MEDLINE|
|12.||Cuhls H, Mochamat, Mücke M, et al.: SOP – Fatigue. Onkologe 2017; 23: 462–8.|
|13.||Berger AM, Mooney K, Banerjee C, et al.: NCCN clinical practice guidelines in oncology. Cancer related fatigue, version 2.2018. 20. Feb 2018. www.oncolife.com.ua/doc/nccn/fatigue.pdf. (last accessed on 22 January 2021).|
|14.||Radbruch L, Strasser F, Elsner F, et al.: Fatigue in palliative care patients—an EAPC approach. Palliat Med 2008; 22: 13–32 CrossRef MEDLINE|
|15.||Stiftung Deutsche Krebshilfe (ed.): Fatigue – Chronische Müdigkeit bei Krebs. Antworten. Hilfen. Perspektiven. Dec 2017. www.krebshilfe.de/infomaterial/Blaue_Ratgeber/Fatigue-Chronische-Muedigkeit-bei-Krebs_BlaueRatgeber_DeutscheKrebshilfe.pdf. (last accessed on 13 January 2020).|
|16.||Mustian KM, Alfano CM, Heckler C, et al.: Comparison of pharmaceutical, psychological, and exercise treatments for cancer-related fatigue: a meta-analysis. JAMA Oncol 2017; 3: 961–8 CrossRef MEDLINE PubMed Central|
|17.||van den Beuken-van Everdingen MHJ, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J: Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol 2007; 18: 1437–49 CrossRef MEDLINE|
|18.||Stiel S, Matthes M, Bertram L, et al.: Validierung der neuen Fassung des Minimalen Dokumentationssystems (MIDOS2) für Patienten in der Palliativmedizin. Schmerz 2010; 24, 596–604 CrossRef MEDLINE|
|19.||Bausewein C, Fegg M, Radbruch L, et al.: Validation and clinical application of the German version of the palliative care outcome scale. J Pain Symptom Manage 2005; 30: 51–62 CrossRef MEDLINE|
|20.||Deutsche Gesellschaft für Palliativmedizin: Dokumentationshilfen – Palliativmedizinisches Basisassessment (PBA). Jan 2016. www.dgpalliativmedizin.de/category/3-pba-dokumentationshilfen.html. (last accessed on 11 October 2020).|
|21.||World Health Organization. WHO guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents. Geneva: World Health Organization 2018.|
|22.||Deutsche Schmerzgesellschaft e. V.: Schmerzfragebogen. 2019. www.schmerzgesellschaft.de/schmerzfragebogen. (last accessed on 7 October 2020).|
|23.||Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF: Leitlinienprogramm Onkologie: Erweiterte S3-Leitlinie Palliativmedizin für Patienten mit einer nicht-heilbaren Krebserkrankung. Langversion 2.0, 2019. www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/Downloads/Leitlinien/Palliativmedizin/Version_2/LL_Palliativmedizin_2.1_Langversion.pdf. (last accessed on 20 January 2020).|
|24.||Radbruch L, Trottenberg P, Elsner F, Kaasa S, Caraceni A: Systematic review of the role of alternative application routes for opioid treatment for moderate to severe cancer pain: an EPCRC opioid guidelines project. Palliat Med 2011; 25: 578–96 CrossRef MEDLINE|
|25.||Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF: Leitlinienprogramm Onkologie: S3-Leitlinie Supportive Therapie bei onkologischen PatientInnen. Langversion 1.3, 20. Mar 2020. www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/Downloads/Leitlinien/Supportivtherapie/LL_Supportiv_Langversion_1.3.pdf. (last accessed on 12 October 2020).|
|26.||Fearon K, Strasser F, Anker SD, et al.: Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12: 489–95 CrossRef|
|27.||Kondrup J, Rasmussen HH, Hamberg O, Stanga Z, Ad Hoc ESPEN Working Group: Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr 2003; 22: 321–36 CrossRef|
|28.||Eschbach C, Stachura P, Villalobos M, Wolf C, Thomas M: SOP – Inappetenz und Kachexie. Onkologe 2017; 23: 651–5 CrossRef|
|29.||Arends J, Bachmann P, Baracos V, et al.: ESPEN guidelines on nutrition in cancer patients. Clin Nutr 2017; 36: 11–48 CrossRef MEDLINE|
|30.||Rosenbruch J, Eschbach C, Viehrig M, Ostgathe C, Bausewein C: SOP – Atemnot bei erwachsenen Palliativpatienten. Onkologe 2018; 24: 18–21 CrossRef|
|31.||Abernethy AP, McDonald CF, Frith PA, et al.: Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial. Lancet 2010; 376: 784–93 CrossRef|
|32.||Barnes H, McDonald J, Smallwood N, Manser R: Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database Syst Rev 2016; 3: CD011008 CrossRef MEDLINE PubMed Central|
|33.||Simon ST, Higginson IJ, Booth S, Harding R, Weingärtner V, Bausewein C: Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev 2016; 10: CD007354 CrossRef MEDLINE PubMed Central|
|34.||DansM, Smith T, Back A, et al.: Palliative care, version 2.2017 featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2017; 15: 989–97.|
|35.||Smith TJ, Temin S, Alesi ER, et al.: American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. J Clin Oncol 2012; 30: 880–7 CrossRef MEDLINE|
|36.||Haun MW, Estel S, Rücker G, et al.: Early palliative care for adults with advanced cancer. Cochrane Database Syst Rev 2017; 6: CD011129 CrossRef MEDLINE PubMed Central|
|37.||Hui D, Masanori M, Watanabe S, et al.: Referral criteria for outpatient specialty palliative cancer care: an international consensus. Lancet Oncol 2016; 17: e552–e9 CrossRef|
|38.||Schäffeler N, Sedelmaier J, Möhrer H, et al.: Patientenautonomie und -informiertheit in der Psychoonkologie: Computerbasiertes Belastungs-screening zur interaktiven Behandlungsplanung (ePOS-react). Psychother Psychosom Med Psychol 2017; 67: 296–303 CrossRef MEDLINE|
|39.||Basch E, Deal AM, Dueck AC, et al.: Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. JAMA 2017; 318: 197–8 CrossRef MEDLINE PubMed Central|
|e1.||Barnes B, Bertz J, Buttmann-Schweiger N, et al.: Folgen von Krebserkrankungen. In: Robert Koch-Institut, Zentrum für Krebsregisterdaten (ed.): Bericht zum Krebsgeschehen in Deutschland 2016. Berlin; 2016: 137–71.|
|e2.||Paessens BJ, von Schilling C, Berger K, et al.: Health resource consumption and costs attributable to chemotherapy-induced toxicity in German routine hospital care in lymphoproliferative disorder and NSCLC patients. Ann Oncol 2011; 22: 2310–9 CrossRef MEDLINE|
|e3.||McKenzie H, Hayes L, White K, et al.: Chemotherapy outpatients’ unplanned presentations to hospital: a retrospective study. Support Care Cancer 2011; 19: 963–9 CrossRef MEDLINE|
|e4.||Schenker Y, Crowley-Matoka M, Dohan D, et al.: Oncologist factors that influence referrals to subspecialty palliative care clinics. J Oncol Pract 2014; 10: e37–44 CrossRef MEDLINE PubMed Central|
|e5.||Wang T, Molassiotis A, Chung BPM, Tan JY: Unmet care needs of advanced cancer patients and their informal caregivers: a systematic review. BMC Palliat Care 2018; 17: 96 CrossRef MEDLINE PubMed Central|
|e6.||Barbera L, Seow H, Howell D, et al.: Symptom burden and performance status in a population-based cohort of ambulatory cancer patients. Cancer 2010; 116: 5767–76 CrossRef MEDLINE|
|e7.||Teunissen SC, Wesker W, Kruitwagen C, de Haes HC, Voest EE, de Graeff A: Symptom prevalence in patients with incurable cancer: a systematic review. J Pain Symptom Manage 2007; 34: 94–104 CrossRef MEDLINE|
|e8.||Yamagishi A, Morita T, Miyashita M, Kimura F: Symptom prevalence and longitudinal follow-up in cancer outpatients receiving chemotherapy. J Pain Symptom Manage 2009; 37: 823–30 CrossRef MEDLINE|
|e9.||Cheung WY, Le LW, Zimmermann C: Symptom clusters in patients with advanced cancers. Support Care Cancer 2009; 17: 1223–30 CrossRef MEDLINE|
|e10.||Bubis LD, Davis L, Mahar A, et al.: Symptom burden in the first year after cancer diagnosis: an analysis of patient-reported outcomes. J Clin Oncol 2018; 36: 1103–11 CrossRef MEDLINE|
|e11.||Kwekkeboom KL: Cancer symptom cluster management. Semin Oncol Nurs 2016; 32: 373–82 CrossRef MEDLINE PubMed Central|
|e12.||Grond S, Zech D, Diefenbach C, Bischoff A: Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation of 1635 cancer patients referred to a pain clinic. J Pain Symptom Manage 1994; 9: 372–82 CrossRef|
|e13.||Lidstone V, Butters E, Seed PT, Sinnott C, Beynon T, Richards M: Symptoms and concerns amongst cancer outpatients: identifying the need for specialist palliative care. Palliat Med 2003; 17: 588–95 CrossRef MEDLINE|
|e14.||Walsh D, Donnelly S, Rybicki L: The symptoms of advanced cancer: relationship to age, gender, and performance status in 1,000 patients. Support Care Cancer 2000; 8: 175–9 CrossRef MEDLINE|
|e15.||Alberg K, Ekman T, Gaston-Johansson F, Mock V: Assessment and management of cancer-related fatigue in adults. Lancet 2003; 362: 640–50 CrossRef|
|e16.||Schwartz AH: Validity of cancer-related fatigue instruments. Pharmacotherapy 2002; 22: 1433–41 CrossRef|
|e17.||Jacobsen PB, Donovan KA, Weitzner MA: Distinguishing fatigue and depression in patients with cancer. Semin Clin Neuropsychiatry 2003; 8: 229–40.|
|e18.||Thompson LMA, Bobonis Babilonia M: Distinguishing depressive symptoms from similar cancer-related somatic symptoms: implications for assessment and management of major depression after breast cancer. South Med J 2017; 110: 667–72 CrossRef MEDLINE|
|e19.||von Blanckenburg P, Leppin N: Psychological interventions in palliative care. Curr Opin Psychiatry 2018; 31: 389–95 CrossRef MEDLINE|
|e20.||van Vulpen JK, Peeters PH, Velthuis MJ, van der Wall E, May AM: Effects of physical exercise during adjuvant breast cancer treatment on physical and psychosocial dimensions of cancer-related fatigue: a meta-analysis. Maturitas 2016; 85: 104–11 CrossRef MEDLINE|
|e21.||Hilfiker R, Meichtry A, Eicher M, et al.: Exercise and other non-pharmaceutical interventions for cancer-related fatigue in patients during or after cancer treatment: a systematic review incorporating an indirect-comparisons meta-analysis. Br J Sports Med 2018; 52: 651–8 CrossRef MEDLINE PubMed Central|
|e22.||Schmitz KH, Campbell AM, Stuiver MM, et al.: Exercise is medicine in oncology: engaging clinicians to help patients move through cancer. CA Cancer J Clin 2019; 69: 468–84 CrossRef MEDLINE PubMed Central|
|e23.||Brown MR, Ramirez JD, Farquhar-Smith P: Pain in cancer survivors. Br J Pain 2014; 8: 139–53 CrossRef MEDLINE PubMed Central|
|e24.||Bradley N, Davis L, Chow E: Symptom distress in patients attending an outpatient palliative radiotherapy clinic. J Pain Symptom Manage. 2005; 30: 123–31 CrossRef MEDLINE|
|e25.||Stein C, Mendl G: The German counterpart to McGill Pain Questionnaire. Pain 1988; 32: 251–5 CrossRef|
|e26.||Fischer T: Schmerzeinschätzung bei Menschen mit schwerer Demenz – Das Beobachtungsinstrument für das Schmerzassessment bei alten Menschen mit schwerer Demenz (BISAD). München: Hans Huber; 2012.|
|e27.||Arbeitskreis Schmerz und Alter der Deutschen Schmerzgesellschaft e. V.: Hinweise zur Verwendung von BESD (Beurteilung von Schmerzen bei Demenz), 2013. www.schmerzgesellschaft.de/fileadmin/pdf/BESD_Kurzanleitung_130626.pdf. (last accessed on 8 November 2020).|
|e28.||Corli O, Floriani I, Roberto A, et al.: Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV ‚real life‘ trial on the variability of response to opioids. Ann Oncol 2016; 27: 1107–15 CrossRef MEDLINE|
|e29.||Reid CM, Martin RM, Sterne JA , Davies AN, Hanks GW: Oxycodone for cancer-related pain: meta-analysis of randomized controlled trials. Arch Intern Med 2006; 166: 837–43 CrossRef MEDLINE|
|e30.||Wiffen PJ, Wee B, Moore RA: Oral morphine for cancer pain. Cochrane Database Syst Rev 2016; 4: CD003868 CrossRef MEDLINE PubMed Central|
|e31.||Caraceni A, Pigni A, Brunelli C: Is oral morphine still the first choice opioid for moderate to severe cancer pain? A systematic review within the European Palliative Care Research Collaborative guidelines project. Palliat Med 2011; 25: 402–9 CrossRef MEDLINE|
|e32.||Bozzetti F: Forcing the vicious circle: sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy. Ann Oncol 2017; 28: 2107–18 CrossRef MEDLINE|
|e33.||Wesseltoft-Rao N, Hjermstad MJ, Ikdahl T, et al.: Comparing two classifications of cancer cachexia and their association with survival in patients with unresected pancreatic cancer. Nutr Cancer 2015; 67: 472–80 CrossRef MEDLINE|
|e34.||Bapen: ‚MUST‘ – Deutsch. www.bapen.org.uk/screening-and-must/must/must-toolkit/the-must-itself/must-deutsch (last accessed 10 February 2021).|
|e35.||Deutsche Gesellschaft für Ernährungsmedizin e. V.. Screening auf Mangelernährung – den Ernährungszustand richtig einschätzen. www.dgem.de/screening. (last accessed on 7 October 2020).|
|e36.||Amano K, Baracos VE, Hopkinson JB: Integration of palliative, supportive, and nutritional care to alleviate eating-related distress among advanced cancer patients with cachexia and their family members. Crit Rev Oncol Hematol 2019; 143: 117–23 CrossRef MEDLINE|
|e37.||Strasser F, Binswanger J, Cerny T, Kesselring A: Fighting a losing battle: eating-related distress of men with advanced cancer and their female partners. A mixed-methods study. Pall Med 2007; 21: 129–37 CrossRef MEDLINE|
|e38.||Molassiotis A, Roberts S, Cheng HL, et al: Partnering with families to promote nutrition in cancer care: feasibility and acceptability of the PIcNIC intervention. BMC Palliat Care 2018; 17: 50 CrossRef MEDLINE PubMed Central|
|e39.||Hopkinson JB, Fenlon DR, Foster CL: Outcomes of a nurse-delivered psychosocial intervention for weight- and eating-related distress in family carers of patients with advanced cancer. Int J Palliat Nurs 2013; 19: 116, 118–23 CrossRef MEDLINE|
|e40.||Solano JP, Gomes B, Higginson IJ: A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease. J Pain Symptom Manage 2006; 31: 58–69 CrossRef MEDLINE|
|e41.||Currow DC, Smith JM, Chansriwong P, et al.: Missed opportunity? Worsening breathlessness as a harbinger of death: a cohort study. Eur Respir J 2018; 52: 1800684 CrossRef MEDLINE|
|e42.||Bausewein C, Simon ST: Shortness of breath and cough in patients in palliative care. Dtsch Arztebl Int 2013; 110: 563–72 VOLLTEXT|
|e43.||Currow DC, McDonald C, Oaten S, et al.: Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study. J Pain Symptom Manage 2011; 42: 388–99 CrossRef MEDLINE|
|e44.||Allard P, Lamontagne C, Bernard P, Tremblay C: How effective are supplementary doses of opioids for dyspnea in terminally ill cancer patients? A randomized continuous sequential clinical trial. J Pain Symptom Manage 1999; 17: 256–65 CrossRef|
|e45.||Ferrell BR, Temel JS, Temin S, et al.: Integration of palliative care into standard oncology care: American society of clinical Oncology clinical practice guideline update. J Clin Oncol 2017; 35: 96–112 CrossRef MEDLINE|
|e46.||World Health Organization: Palliative care; 2020. www.who.int/cancer/palliative/definition/en/. (last accessed on 9 October 2020).|
|e47.||May P, Normand C, Cassel JB, et al.: Economics of palliative care for hospitalized adults with serious illness: a meta-analysis. Intern Med 2018; 178: 820–9 CrossRef MEDLINE PubMed Central|
|e48.||Bakitas M, Lyons KD, Hegel MT, Ahles T: Oncologists‘ perspectives on concurrent palliative care in a National Cancer Institute-designated comprehensive cancer center. Palliat Support Care 2013; 11: 415–23 CrossRefMEDLINE PubMed Central|
|e49.||Berendt J, Thomas M, Neukirchen M, Schwartz J, Hense J, Tewes M: Integration von Palliativmedizin in onkologische Spitzenzentren Deutschlands – ambulante Sprechstunden und Rotationsprogramme der spezialisierten Palliativmedizin. Dtsch Med Wochenschr 2018; 143: e139–e45 CrossRef MEDLINE|
|e50.||Deutsche Gesellschaft für Palliativmedizin: Allgemeine Ambulante Palliativversorgung (AAPV). Definition; 2009. www.dgpalliativmedizin.de/allgemein/allgemeine-ambulante-palliativversorgung-aapv.html. (last accessed on 12 October 2020).|
|e51.||Schaeffeler N, Pfeiffer K, Ringwald J, et al.: Assessing the need for psychooncological support: screening instruments in combination with patients‘ subjective evaluation may define psychooncological pathways. Psychooncology 2015; 24: 1784–91 CrossRef MEDLINE|
|e52.||Deutsche Krebsgesellschaft e. V., Office des Leitlinienprogrammes Onkologie: Onkologische Leitlinien; 2019. www.leitlinienprogramm-onkologie.de/leitlinien/. (last accessed on 7 October 2020).|
|e53.||Rumpold G, Augustin M, Zschocke I, Strittmatter G, Söllner W: Die Validität des Hornheider Fragebogens zur psychosozialen Unterstützung bei Tumorpatienten. Psychother Psychosom Med Psychol 2001; 51: 25–33 CrossRef MEDLINE|
|e54.||Kroenke K, Spitzer RL, Williams JB: The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16: 606–13 CrossRef MEDLINE PubMed Central|
|e55.||Spitzer RL, Kroenke K, Williams JB, Löwe B: A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 2006; 166: 1092–7 CrossRef MEDLINE|