Single-fraction stereotactic radiosurgery versus microsurgical resection for the treatment of vestibular schwannoma: a systematic review and meta-analysis.

BACKGROUND: Vestibular schwannomas are benign tumours for which various treatments are available. We performed a systematic review of prospective controlled trials comparing the patient-relevant benefits and harms of single-fraction stereotactic radiosurgery (sfSRS) with microsurgical resection (MR) in patients with vestibular schwannoma. METHODS: We searched for randomized controlled trials (RCTs) and non-randomized prospective controlled trials in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and study registries (last search: 09/2021) and also screened reference lists of relevant systematic reviews. Manufacturers were asked to provide unpublished data. Eligible studies investigated at least one patient-relevant outcome. We assessed the risk of bias (high or low) at the study and outcome level. If feasible, meta-analyses were performed. We graded the results into different categories (hint, indication, or proof of greater benefit or harm). RESULTS: We identified three non-randomized prospective controlled trials of generally low quality with evaluable data on 339 patients with unilateral vestibular schwannoma. There was an indication of greater benefit of sfSRS compared with MR for facial palsy (OR 0.06, 95% CI 0.02-0.21, p < 0.001, 2 studies), hearing function (no pooled estimate available, 2 studies), and length of hospital stay (no pooled estimate available, 2 studies). We found no clinically relevant differences for mortality, vertigo, headaches, tinnitus, balance function, work disability, adverse events, and health-related quality of life. CONCLUSIONS: Our systematic review indicates that sfSRS has greater benefits than MR in patients with unilateral vestibular schwannoma. However, it is unclear whether this conclusion still holds after 2 years, as long-term studies are lacking. It is also unclear whether the effects of sfSRS are similar in patients with bilateral vestibular schwannomas. Long-term prospective studies including patients with this condition would therefore be useful. SYSTEMATIC REVIEW REGISTRATION: The full (German language) protocol and report (Commission No. N20-03) are available on the institute's website: www.iqwig.de/en/projects/n20-03.html.

Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 1, 2010, on 'Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults'. Breathlessness is one of the most common symptoms experienced in the advanced stages of malignant and non-malignant disease. Benzodiazepines are widely used for the relief of breathlessness in advanced diseases and are regularly recommended in the literature. At the time of the previously published Cochrane review, there was no evidence for a beneficial effect of benzodiazepines for the relief of breathlessness in people with advanced cancer and chronic obstructive pulmonary disease (COPD). OBJECTIVES: The primary objective of this review was to determine the efficacy of benzodiazepines for the relief of breathlessness in people with advanced disease. Secondary objectives were to determine the efficacy of different benzodiazepines, different doses of benzodiazepines, different routes of application, adverse effects of benzodiazepines, and the efficacy in different disease groups. SEARCH METHODS: This is an update of a review published in 2010. We searched 14 electronic databases up to September 2009 for the original review. We checked the reference lists of all relevant studies, key textbooks, reviews, and websites. For the update, we searched CENTRAL, MEDLINE, and EMBASE and registers of clinical trials for further ongoing or unpublished studies, up to August 2016. We contacted study investigators and experts in the field of palliative care asking for further studies, unpublished data, or study details when necessary. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) assessing the effect of benzodiazepines compared with placebo or active control in relieving breathlessness in people with advanced stages of cancer, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), motor neurone disease (MND), and idiopathic pulmonary fibrosis (IPF). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed identified titles and abstracts. Three review authors independently performed assessment of all potentially relevant studies (full text), data extraction, and assessment of methodological quality. We carried out meta-analysis where appropriate. MAIN RESULTS: Overall, we identified eight studies for inclusion: seven in the previous review and an additional study for this update. We also identified two studies awaiting classification in this update. The studies were small (a maximum number of 101 participants) and comprised data from a total of 214 participants with advanced cancer or COPD, which we analysed. There was only one study of low risk of bias. Most of the studies had an unclear risk of bias due to lack of information on random sequence generation, concealment, and attrition. Analysis of all studies did not show a beneficial effect of benzodiazepines for the relief of breathlessness (the primary outcome) in people with advanced cancer and COPD (8 studies, 214 participants) compared to placebo, midazolam, morphine, or promethazine. Furthermore, we observed no statistically significant effect in the prevention of episodic breathlessness (breakthrough dyspnoea) in people with cancer (after 48 hours: risk ratio of 0.76 (95% CI 0.53 to 1.09; 2 studies, 108 participants)) compared to morphine. Sensitivity analyses demonstrated no statistically significant differences regarding type of benzodiazepine, dose, route and frequency of delivery, duration of treatment, or type of control. Benzodiazepines caused statistically significantly more adverse events, particularly drowsiness and somnolence, when compared to placebo (risk difference 0.74 (95% CI 0.37, 1.11); 3 studies, 38 participants). In contrast, two studies reported that morphine caused more adverse events than midazolam (RD -0.18 (95% CI -0.31, -0.04); 194 participants). AUTHORS' CONCLUSIONS: Since the last version of this review, we have identified one new study for inclusion, but the conclusions remain unchanged. There is no evidence for or against benzodiazepines for the relief of breathlessness in people with advanced cancer and COPD. Benzodiazepines caused more drowsiness as an adverse effect compared to placebo, but less compared to morphine. Benzodiazepines may be considered as a second- or third-line treatment, when opioids and non-pharmacological measures have failed to control breathlessness. There is a need for well-conducted and adequately powered studies.

"I Can Breathe Again!" Patients' Self-Management Strategies for Episodic Breathlessness in Advanced Disease, Derived From Qualitative Interviews.

CONTEXT: Episodic breathlessness causes additional distress to breathless patients with advanced disease, but management is still insufficient and there is a lack of knowledge on effective coping strategies. OBJECTIVES: The aim was to explore patients' self-management strategies for episodic breathlessness. METHODS: In-depth interviews with patients suffering from episodic breathlessness as a result of chronic heart failure, chronic obstructive pulmonary disease, lung cancer, or motor neuron disease were conducted. Interviews were transcribed verbatim and analyzed guided by the analytic hierarchy of Framework analysis. RESULTS: A total of 51 participants were interviewed (15 chronic heart failure, 14 chronic obstructive pulmonary disease, 13 lung cancer, and nine motor neuron disease; age, mean [SD], 68 [12], 41% women, median Karnofsky index 60%). They described six main strategies for coping with episodes of breathlessness: reduction of physical exertion, cognitive and psychological strategies, breathing techniques and positions, air and oxygen, drugs and medical devices, and environmental and other strategies. Some strategies were used in an opposing way, e.g., concentrating on the breathing vs. distraction from any thoughts of breathlessness or laying down flat vs. standing up and raising hands. CONCLUSION: Patients used a number of different strategies to cope with episodic breathlessness, adding more detailed understanding of existing strategies for breathlessness. The findings, therefore, may provide a valuable aid for health care providers, affected patients, and their relatives.

The Role of End-of-Life Issues in the Design and Reporting of Cancer Clinical Trials: A Structured Literature Review.

BACKGROUND: Randomized controlled trials (RCTs) are important sources of information on the benefits and harms patients may expect from treatment options. The aim of this structured literature review by the German Institute for Quality and Efficiency in Health Care was to explore whether and how the end-of-life (EoL) situation of patients with advanced cancer is considered in RCTs investigating anti-cancer treatments. METHODS: Our journal pool comprised 19 medical journals, namely five preselected key general medical journals as well as 14 specialist journals (mainly cancer) identified via a scoping search. We systematically searched these journals in MEDLINE to identify RCTs investigating anti-cancer treatments for the following four cancer types: glioblastoma, lung cancer (stage IIIb-IV), malignant melanoma (stage IV), and pancreatic cancer (search via OVID; November 2012). We selected a representative sample of 100 publications, that is, the 25 most recent publications for each cancer type. EoL was defined as a life expectancy of ≤ two years. We assessed the information provided on (1) the descriptions of the terminal stage of the disease, (2) the therapeutic goal (i.e. the intended therapeutic benefit of the intervention studied), (3) the study endpoints assessed, (4) the authors' concluding appraisal of the intervention's effects, and (5) the terminology referring to the patients' EoL situation. RESULTS: Median survival was ≤ one year for each of the four cancer types. Descriptions of the terminal stage of the disease were ambiguous or lacking in 29/100 publications. One or more therapeutic goals were mentioned in 51/100 publications; these goals were patient-relevant in 38 publications (survival alone: 30/38; health-related quality of life (HRQoL) or HRQoL and survival: 6/38; symptom control or symptom control and survival: 2/38). Primary endpoints included survival (50%), surrogates (44%), and safety (3%). Patient-reported outcomes (PROs) were assessed in 36/100 RCTs. The implications of treatment-related harms for the patients were discussed in 22/100 appraisals. Terminology referring to the patients' EoL situation (e.g. "terminal") was scarce, whereas terms suggesting control of the disease (e.g. "cancer control") were common. CONCLUSIONS: The EoL situation of patients with advanced cancer should be more carefully considered in clinical trials. Although the investigation and robust reporting of PROs is a prerequisite for informed decision-making in healthcare, they are rarely defined as endpoints and HRQoL is rarely mentioned as a therapeutic goal. Suggestions for improving standards for study design and reporting are presented.

Characteristics of episodic breathlessness as reported by patients with advanced chronic obstructive pulmonary disease and lung cancer: Results of a descriptive cohort study.

BACKGROUND: Episodic breathlessness is one form of refractory breathlessness. Better understanding of the symptom is necessary for effective management. AIM: The aim was to describe the characteristics of episodic breathlessness in patients with advanced chronic obstructive pulmonary disease or lung cancer. DESIGN: This is a longitudinal cohort study. Outcomes were assessed monthly by up to 13 telephone interviews: peak severity (modified Borg scale: 0-10), duration, frequency, and timing of breathlessness episodes. Data from each episode were pooled and analyzed using descriptive statistics. Associations between outcomes were explored by correlation coefficients. SETTING/PARTICIPANTS: Patients with chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease classification stage III or IV) or primary lung cancer (any stage) were recruited in two inpatient units (internal medicine) and two outpatient clinics in Oldenburg, Germany. RESULTS: A total of 82 patients (50 chronic obstructive pulmonary disease, 32 lung cancer), mean age (standard deviation) 67 years (8 years) and 36% female, were included reporting on 592 breathlessness episodes (chronic obstructive pulmonary disease: 403, lung cancer: 189). Peak severity was perceived significantly higher in chronic obstructive pulmonary disease patients than in lung cancer patients (mean (standard deviation) Borg scale: 6.2 (2.1) vs 4.2 (1.9); p < 0.001). Episodes described by chronic obstructive pulmonary disease patients were longer than those described by lung cancer patients (median (range): 7 min (0-600) vs 5 min (0.3-120), p = 0.002)). Frequency was similar and most often daily in both groups. Severity and frequency of episodes were correlated in lung cancer patients (r = 0.324, p = 0.009). CONCLUSION: Most breathlessness episodes are short (minutes) and severe with significant differences between chronic obstructive pulmonary disease and lung cancer patients. Effective management strategies are warranted to improve symptom relief and coping.

Is breathlessness what the professional says it is? Analysis of patient and professionals' assessments from a German nationwide register.

PURPOSE: Breathlessness is a common and distressing symptom in patients with advanced disease. Patients' self-report is deemed to be the most valid method of symptom assessment. When patients are not capable of self-assessment, professionals' assessment is often used as alternative but evidence on the validity is conflicting. The aim of this study was to compare self- and professionals' assessment of breathlessness regarding presence and severity in patients with advanced disease. METHODS: Secondary analysis of a cross-sectional, multi-centre and nationwide register (HOspice and Palliative Care Evaluation (HOPE)). Documented inpatients from hospices and palliative care units from 2006 to 2008 who completed the self-assessed MInimal DOcumentation System (MIDOS) were included. Professionals' assessment were based on the integrated symptom and problem checklist (symptom scores, 0-3). Cohen's kappa (κ) was used to estimate the 'level of agreement' (LoA). RESULTS: Two thousand six hundred twenty-three patients (mean age, 66.9 (SD, 12.8); 54.4% female; median Eastern Cooperative Oncology Group score, 3; 95.9% with malignant disease) were analysed. Prevalence of breathlessness was 53.4% (1,398 patients) by professionals' and 53.1% (1,410 patients) by self-assessment. Presence was correctly evaluated by professionals in 80.9% of cases (sensitivity, 81.8%; specificity, 79.8%). Severity of breathlessness was correctly estimated in 65.7% of cases. LoA was good (κ=0.62) for the evaluation of presence of breathlessness and moderate (κ=0.5) for the estimation of severity. The proportion of over- or underestimated scores was similar. CONCLUSIONS: If patient's self-rating, the gold standard of symptom assessment, is not possible, professionals' assessment might be a valid alternative, at least for assessing the presence of breathlessness.

Definition, categorization, and terminology of episodic breathlessness: consensus by an international Delphi survey.

CONTEXT: Episodic breathlessness is a common and distressing symptom in patients with advanced disease. Still, it is not yet clearly defined. OBJECTIVES: The aim of this work was to develop an international definition, categorization, and terminology of episodic breathlessness. METHODS: An online Delphi survey was conducted with international breathlessness experts. We used a structured questionnaire to identify specific aspects and reach agreement on a definition, categorization, and terminology (five-point Likert scale). Consensus was defined in advance as ≥70% agreement. RESULTS: Thirty-one of 68 (45.6%), 29 of 67 (43.3%), and 33 of 67 (49.3%) experts responded in the first, second, and third rounds, respectively. Participants were 20-79 years old, about 60% male, and more than 75% rated their own breathlessness expertise as moderate to high. After three rounds, consensus was reached on a definition, categorization, and terminology (84.4%, 96.3%, and 92.9% agreement). The final definition includes general and qualitative aspects of the symptom, for example, time-limited severe worsening of intensity or unpleasantness of breathlessness in the patient's perception. Categories are predictable or unpredictable, depending on whether any triggers can be identified. CONCLUSION: There is high agreement on clinical and operational aspects of episodic breathlessness in advanced disease among international experts. The consented definition and categorization may serve as a catalyst for clinical and basic research to improve symptom control and patients' quality of life.

[Transferability of patient safety indicators to the German hospital setting: results of a Delphi survey]. / Übertragbarkeit krankenhausbezogener Patientensicherheitsindikatoren für Deutschland: Ergebnis einer Delphi-Befragung.

AIM: To assess the transferability of 14 evidence-based patient safety indicators (PSI) to the German hospital system. METHODS: A two-staged modified multidisciplinary Delphi process was used, applying the scientific criteria of the QUALIFY instrument. RESULTS: Eleven of the 14 PSI were judged to be transferable to and feasible in the German hospital setting. CONCLUSIONS: The consented PSI are potentially suitable for German quality assurance measurement. Prior to implementation, further operationalisation and empirical validation is recommended.

Characterizing episodic breathlessness in patients with advanced disease.

BACKGROUND: Episodic breathlessness is a common and distressing symptom in advanced cancer and nonmalignant diseases but there is a lack of evidence on the characteristics of the symptom. OBJECTIVE: The aim of this study was to determine the duration, severity, frequency and timing of breathlessness episodes in patients with advanced diseases. METHODS: Explorative analysis of pooled cross-sectional data on episodic breathlessness collected in personal interviews with patients suffering from chronic obstructive pulmonary disease, lung cancer, chronic heart failure, or motor neuron disease. Interviews were conducted as part of two studies in the UK and in Germany that included the same questions on duration, frequency, timing, and peak severity of breathlessness episodes. Severity was measured on the modified Borg scale (0-10). RESULTS: One hundred and twenty-nine patients, 61% male, mean age of 67 years (SD 9.8), were included. The episodes described were mainly short (75%≤10 min), severe (mean 6.5 (SD 2.4), and occurred mostly daily. Frequency of episodes triggered by exertion could hardly be determined as these varied depending on patients' activity. CONCLUSION: Our study reveals clinically important information on the characteristics of episodic breathlessness in patients with advanced diseases. Findings have implications for the treatment of episodic breathlessness since most short-acting drugs in use have a longer onset of action compared to the duration of episodes. We need to determine patient-relevant therapeutic targets for future evaluation of adequate pharmacological and nonpharmacological management options that are urgently warranted.

Early palliative care for patients with advanced cancer: how to make it work?

PURPOSE OF REVIEW: As the benefit of early palliative care for the quality of life of patients with advanced cancer is currently receiving widespread recognition, cancer specialists increasingly inquire about the practical implications of this concept. This publication presents the available information about how to provide early palliative care for patients with advanced cancer. RECENT FINDINGS: Oncologists and other cancer specialists provide general palliative care from the time of diagnosis of incurable cancer together with the patients' family doctors. This includes basic assessment of symptoms and distress, their initial management as well as sensitive communication with the patient, including advance care planning and end-of-life issues and hope. The additional integration of a specialized palliative care team early in the care trajectory has been found to be beneficial for quality of life and survival. This concept is known as 'early palliative care' or 'early integration' and has become recommended by institutions such as the American Society of Clinical Oncology. SUMMARY: Palliative care is warranted from the time of diagnosis of incurable cancer. From this early stage, palliative care consists of general palliative care provided by cancer specialists and family doctors and additional support of a specialized palliative care program. Guidance from different guidelines is presented alongside practical recommendations derived from our experience with an early palliative care program for comprehensive cancer care over the last 7 years.