Objectives: Liquid biopsy (LBx) provides diagnostic, prognostic and predictive insights for malignant diseases and offers promising applications regarding tumor burden, tumor heterogeneity and clonal evolution. Methods: ALPS is a prospective trial for patients with metastatic cancer that comprises sequential collection of LBx samples, tumor tissue, radiological imaging data, clinical information and patient-reported outcomes. Peripheral blood plasma is collected based on the individual patient's staging intervals and LBx-derived ctDNA analyses are performed using CAncer Personalized Profiling sequencing (CAPP-seq). Results: From April 2021 to October 2023, 419 patients have been enrolled. A total of 1,293 LBx samples were collected, 419 samples (100 %) at the beginning of the study and an average of 3 (range 1-12) during the 30-month follow-up period of the current interim analysis. 380 tissue biopsy (TBx) samples (90.7 %) were available at baseline and 39.6 % had >= 1 TBx samples at follow-up. Lung cancer patients are most prevalent in ALPS (n=147), followed by colorectal (n=38), prostate (n=31) and gastroesophageal cancer (n=28). On average, 12.0 ng/mL plasma cell-free DNA (cfDNA) could be isolated. First CAPP-seq analyses in 60 patients comprised 110 samples and demonstrated a detection sensitivity of 0.1 %. Conclusions: The first interim analysis of ALPS confirms feasibility for comprehensive longitudinal evaluation of LBx and demonstrates suitability for ctDNA evaluation.

Hydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by coadministered proton pump inhibitors might reduce its solubility and absorption and thus its efficacy in patients. We addressed this question in a single-center, open-label, randomized, parallel drug-drug interaction trial in healthy adults (EudraCT No. 2020-001470-30). All participants received a single oral dose of 400-mg hydroxychloroquine, and one group additionally received 40 mg of pantoprazole once daily for 9 days dosed to steady state. Whole-blood samples were collected for 72 hours, and hydroxychloroquine was quantified by liquid chromatography–tandem mass spectrometry. Primary endpoints were whole-blood hydroxychloroquine areas under the concentration-time curve from 0 to 72 hours (AUC 0-72h ) and peak concentrations (C max ). Unpaired 2-sided t -tests of the log transformed pharmacokinetic parameters were performed to compare both groups. Twenty-four participants (12 per group) were included. Hydroxychloroquine AUC 0-72h and C max did not differ between groups without and with pantoprazole (arithmetic mean; AUC 0-72h , 7649 ng/ml • h, and 8429 ng/ml • h, P = .50; C max , 448 ng/mL and 451.5 ng/mL, P = .96, respectively). Pantoprazole did not alter hydroxychloroquine absorption, indicating that proton pump inhibitors do not affect its bioavailability.

BACKGROUND:Pirfenidone has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). However, there are few treatment options for progressive fibrotic interstitial lung diseases (ILDs)) other than IPF. In view of the pathomechanistic and clinical similarities between IPF and other progressive fibrotic ILDs, we aimed to assess the efficacy and safety of pirfenidone in patients with four non-IPF progressive fibrotic ILDs. METHODS:We did a multicentre, double-blind, randomised, placebo-controlled, parallel phase 2b trial (RELIEF) in 17 centres with expertise in ILD in Germany. Eligible participants were patients aged 18-80 years with progressive fibrotic ILD due to four diagnoses: collagen or vascular diseases (ie, connective tissue disease-associated ILDs), fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis. Other eligibility criteria included a forced vital capacity (FVC) of 40-90% predicted, a diffusing capacity of the lung for carbon monoxide of 10-90% predicted, and an annual decline of FVC of at least 5% predicted despite conventional therapy, based on at least three measurements within 6-24 months before enrolment. Patients who had received any previous antifibrotic therapy were excluded. We randomly assigned patients (1:1) to either oral pirfenidone (267 mg three times per day in week 1, 534 mg three times per day in week 2, and 801 mg three times per day thereafter) or matched placebo, added to their ongoing medication. Randomisation was done centrally using permuted block randomisation with varying block sizes stratified by the four diagnostic groups. Patients, investigators, statisticians, monitors, and the study coordinator were masked to treatment assignment until database closure. The placebo-controlled study period was 48 weeks (including up-titration). The primary endpoint was absolute change in percentage of predicted FVC (FVC % predicted) from baseline to week 48 in the intention-to-treat population, with imputation of missing data by the smallest sum of squared differences and attribution of deceased patients to the lowest rank in a rank ANCOVA model. Additionally, we did linear mixed-model repeated measures slope analyses of FVC % predicted longitudinal data over the course of the study as a prespecified sensitivity analysis and post-hoc sensitivity analyses of the primary endpoint in the intention-to-treat population using imputation methods of last observation carried forward [LOCF] and a regression-based multiple imputation procedure. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with EudraCT 2014-000861-32; DRKS00009822 and is no longer recruiting. FINDINGS:Between April 5, 2016, and Oct 4, 2018, we randomly assigned 127 patients to treatment: 64 to pirfenidone, 63 to placebo. After 127 patients had been randomised, the study was prematurely terminated on the basis of an interim analysis for futility triggered by slow recruitment. After 48 weeks and in the overall population of 127 patients, rank ANCOVA with diagnostic group included as a factor showed a significantly lower decline in FVC % predicted in the pirfenidone group compared with placebo (p=0·043); the result was similar when the model was stratified by diagnostic group (p=0·042). A significant treatment effect was also observed when applying the LOCF and multiple imputation methods to analyses of the primary endpoint. The median difference (Hodges-Lehmann estimate) between pirfenidone and placebo groups for the primary endpoint was 1·69 FVC % predicted (95% CI -0·65 to 4·03). In the linear mixed-model repeated measures slope analysis of FVC % predicted, the estimated difference between treatment and placebo groups from baseline to week 48 was 3·53 FVC % predicted (95% CI 0·21 to 6·86) with imputation of deaths as prespecified, or 2·79 FVC % predicted (95% CI 0·03 to 5·54) without imputation. One death (non-respiratory) occurred in the pirfenidone group (2%) and five deaths (three of which were respiratory) occurred in the placebo group (8%). The most frequent serious adverse events in both groups were infections and infestations (five [8%] in the pirfenidone group, ten [16%] in the placebo group); general disorders including disease worsening (two [3%] in the pirfenidone group, seven [11%] in the placebo group); and cardiac disorders (one ([2%] in the pirfenidone group, 5 [8%] in the placebo group). Adverse events (grade 3-4) of nausea (two patients on pirfenidone, two on placebo), dyspnoea (one patient on pirfenidone, one on placebo), and diarrhoea (one patient on pirfenidone) were also observed. INTERPRETATION:In view of the premature study termination, results should be interpreted with care. Nevertheless, our data suggest that in patients with fibrotic ILDs other than IPF who deteriorate despite conventional therapy, adding pirfenidone to existing treatment might attenuate disease progression as measured by decline in FVC. FUNDING:German Center for Lung Research, Roche Pharma.

Hydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by coadministered proton pump inhibitors might reduce its solubility and absorption and thus its efficacy in patients. We addressed this question in a single-center, open-label, randomized, parallel drug-drug interaction trial in healthy adults (EudraCT No. 2020-001470-30). All participants received a single oral dose of 400-mg hydroxychloroquine, and one group additionally received 40 mg of pantoprazole once daily for 9 days dosed to steady state. Whole-blood samples were collected for 72 hours, and hydroxychloroquine was quantified by liquid chromatography-tandem mass spectrometry. Primary endpoints were whole-blood hydroxychloroquine areas under the concentration-time curve from 0 to 72 hours (AUC0-72h ) and peak concentrations (Cmax ). Unpaired 2-sided t-tests of the log transformed pharmacokinetic parameters were performed to compare both groups. Twenty-four participants (12 per group) were included. Hydroxychloroquine AUC0-72h and Cmax did not differ between groups without and with pantoprazole (arithmetic mean; AUC0-72h , 7649 ng/ml • h, and 8429 ng/ml • h, P = .50; Cmax , 448 ng/mL and 451.5 ng/mL, P = .96, respectively). Pantoprazole did not alter hydroxychloroquine absorption, indicating that proton pump inhibitors do not affect its bioavailability.

Background: Physical activity and quality of life (QoL) are significantly reduced in patients with fibrosing ILD (fILD). As until today improvements in these patient related outcomes could not have been achieved with drug treatments but with physical training, we aimed to assess effects of yoga. Methods: Patients with fILD were randomized between yoga (2x/week, 12 weeks, n=9) and surveillance (n=7) to our feasibility trial. Primary endpoint was change in QoL. Using a mixed method approach for QoL, qualitative data were collected in focus group interviews and quantitative data through established QoL questionnaires (K-BILD, HADS, LCQ, AVA) at baseline and at 12 weeks. Results: Baseline characteristics in the respective groups were yoga vs. surveillance: median age 65 vs. 71 years, female 44% vs. 14%, FVC 68% vs. 78%, DLCO 48% vs. 56%, 6MWT 412 m vs. 390 m. After 12 weeks there were no significant differences with regards to FVC, DLCO or 6 MWD. For QoL, the qualitative analyses showed discontent with own health status and QoL and expectation to improve health as main reasons for trial participation. At follow-up, health related improvements and transfer of yoga practices into daily life to overcome dyspnea sensation were perceived as main benefits. In the quantitative analyses there were significant differences for K-BILD total and dyspnea score (p<0.05) favoring Yoga, while HADS, LCQ and AVA showed no differences. Conclusion: Yoga for fILD might be associated with significant benefits in QoL. However, data interpretation is limited by imbalances in patient characteristics and small numbers. Yoga as a new therapy approach for fILD should be assessed in larger, controlled trials.

Primary objective: Evaluation of the effect of the proton pump inhibitor (PPI) pantoprazole on the absorption of hydroxychloroquine (HCQ). Secondary objectives: • Evaluation of the relationship between HCQ concentrations in whole blood, plasma and intracellular concentrations in target cells - peripheral blood mononuclear cells (PBMCs). • Evaluation of HCQ as a potential perpetrator in drug-drug interactions at the level of cytochrome P450 (CYP) 3A4 and CYP2D6 (major drug metabolizing enzymes).Single centre, open-label, parallel group, two-arm, phase I drug-drug interaction trial.Healthy volunteers (18-60 years old) are treated in the Clinical Pharmacological Trial Center of Heidelberg University Hospital, Germany.• Participants are randomized in a group to either receive a nine-day course of pantoprazole, or to a control group without pantoprazole. All participants receive a single dose of HCQ 400 mg. • Additionally, CYP3A4 and CYP2D6 phenotyping with microdosed probe drugs is performed using midazolam and yohimbine as enzyme activity markers, respectively.Primary endpoint: Area under the curve (AUC)0-72 h and maximum concentration (Cmax) of a single oral dose of 400 mg HCQ with and without pantoprazole (changes in these two values describe relevant aspects of exposure to HCQ with and without administration of pantoprazole). Secondary endpoints: • AUC2-4 h, AUC0-6 h and Cmax of midazolam and yohimbine. • Correlation of HCQ concentrations in whole blood with concentrations in plasma and peripheral blood mononuclear cells (PBMC).Participants are assigned to treatment groups by using a randomisation list (1:1, block size = 4) and consecutive enrolment.The trial is an open-label trial, participants and investigators are not blinded.A total number of 24 participants (12 per group) are planned to be randomised.Protocol version 2.1 dated 24/04/2020, first patient first visit. April 30th, 2020, recruitment ongoing, anticipated end of study June 30th, 2020.EudraCT Number: 2020-001470-30 , registered on 31 March 2020 German Clinical trials register number / International Clinical Trials Registry Platform: DRKS00021573, registered on 27 April 2020 FULL PROTOCOL: The full trial protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full trial protocol. The trial protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Objectives Primary objective: Evaluation of the effect of the proton pump inhibitor (PPI) pantoprazole on the absorption of hydroxychloroquine (HCQ). Secondary objectives: • Evaluation of the relationship between HCQ concentrations in whole blood, plasma and intracellular concentrations in target cells - peripheral blood mononuclear cells (PBMCs). • Evaluation of HCQ as a potential perpetrator in drug-drug interactions at the level of cytochrome P450 (CYP) 3A4 and CYP2D6 (major drug metabolizing enzymes). Trial design Single centre, open-label, parallel group, two-arm, phase I drug-drug interaction trial. Participants Healthy volunteers (18-60 years old) are treated in the Clinical Pharmacological Trial Center of Heidelberg University Hospital, Germany. Intervention and comparator • Participants are randomized in a group to either receive a nine-day course of pantoprazole, or to a control group without pantoprazole. All participants receive a single dose of HCQ 400 mg. • Additionally, CYP3A4 and CYP2D6 phenotyping with microdosed probe drugs is performed using midazolam and yohimbine as enzyme activity markers, respectively. Main outcomes Primary endpoint: Area under the curve (AUC) 0-72 h and maximum concentration (C max ) of a single oral dose of 400 mg HCQ with and without pantoprazole (changes in these two values describe relevant aspects of exposure to HCQ with and without administration of pantoprazole). Secondary endpoints: • AUC 2-4 h , AUC 0-6 h and C max of midazolam and yohimbine. • Correlation of HCQ concentrations in whole blood with concentrations in plasma and peripheral blood mononuclear cells (PBMC). Randomisation Participants are assigned to treatment groups by using a randomisation list (1:1, block size = 4) and consecutive enrolment. Blinding (masking) The trial is an open-label trial, participants and investigators are not blinded. Numbers to be randomised (sample size) A total number of 24 participants (12 per group) are planned to be randomised. Trial Status Protocol version 2.1 dated 24/04/2020, first patient first visit. April 30th, 2020, recruitment ongoing, anticipated end of study June 30th, 2020. Trial registration EudraCT Number: 2020-001470-30 , registered on 31 March 2020 German Clinical trials register number / International Clinical Trials Registry Platform: DRKS00021573, registered on 27 April 2020 Full protocol The full trial protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full trial protocol. The trial protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2 ).

Background Availability of tumor material at baseline and disease progression is increasingly important for patient management in non-small-cell lung cancer (NSCLC), especially for the application of targeted therapies like tyrosine kinase inhibitors and for immune checkpoint inhibitor treatment. Here we report the experience of prospective biomaterial acquisition in advanced NSCLC from a pilot project. Methods Main objective was the longitudinal collection of high-quality, cryoconserved biopsies in addition to formalin-fixed paraffin-embedded (FFPE) biopsies required for routine diagnostics, along with blood samples and detailed clinical annotation using standardized questionnaires. Results Over five years, 205 patients were enrolled for the project, yielding 387 cryoconserved biopsies and 1,098 serum, plasma and buffy-coat samples. The feasibility of obtaining the cryoconserved biopsies in addition to the FFPE biopsies was 89% for newly diagnosed cases, but dropped down to 56% and 47% at first and second disease progression, respectively. While forceps biopsy was the preferred procedure for tissue acquisition, the highest tissue amounts were received using the cryobiopsy method. Biopsies had a median tumor cellularity of 34% and yielded in median 13.6 µg DNA and 12 µg RNA (median RIN =8). During the five-year project, a maximum of 38 follow-up blood samples per patient were assembled in up to four therapy lines. Conclusions Despite the poor condition and limited prognosis of most NSCLC patients, this serial biomaterial acquisition including routine collection of cryoconserved biopsies is feasible to support individualized management. The standardized collection of high-quality material has enabled and enriched several translational research studies that can advance therapeutic options.

Pirfenidone is approved in the EU for the treatment of mild to moderate Idiopathic Pulmonary Fibrosis (IPF), but not for other forms of progressive fibrotic lung diseases, in which anti-inflammatory therapy is not sufficiently effective. RELIEF, a randomized, double-blind, placebo-controlled, parallel-group, multi-center, phase II study, aims to explore the efficacy and safety of oral pirfenidone for progressive, non-IPF lung fibrosis. The study population comprises patients with collagen/vascular disease-associated lung fibrosis (CVD-LF), fibrotic non-specific interstitial pneumonia (fNSIP), chronic hypersensitivity pneumonitis (cHP), and asbestos-induced lung fibrosis (ALF). Disease progression has to be proven by slope calculation of at least three Forced Vital Capacity (FVC) measurements obtained within 6-24 months prior to inclusion, documenting an annualized decline in percent predicted FVC of 5 % (absolute). The study medication (pirfenidone or placebo) is administered on top of existing anti-inflammatory medication, which has to be stable for at least three month. As primary endpoint the efficacy will be assessed by the absolute change in percent predicted FVC from baseline to week 48 in the Pirfenidone and placebo group. Data will be analyzed using a rank analysis of covariance (ANCOVA) model. A number of secondary endpoints will be analyzed, e.g. time to disease worsening, progression-free survival, categorical relative change of FVC from baseline to week 48. Patient recruitment started in April 2016, currently 15 study centers including all five DZL sites. 59 (16 CVD-LF, 19 fNSIP, 21 cHP, 3 ALF) of 374 planned patients have been randomized so far (February 1, 2017).

Availability of tumour material at baseline and disease progression is increasingly important for patient management in non-small-cell lung cancer (NSCLC), especially in tyrosine kinase and immune checkpoint inhibitor treatment. Here, we report the experience with prospective biobanking for advanced NSCLC from a pilot project in the academic setting. Main objective was the longitudinal collection of snap-frozen in addition to formalin-fixed paraffin-embedded (FFPE) biopsies required for routine diagnostics, along with blood samples and detailed clinical annotation using standardized questionnaires. Over five years, 205 patients were enrolled yielding 387 cryoconserved biopsies and 1098 serum, plasma and buffy-coat samples. The feasibility of obtaining cryoconserved in addition to FFPE biopsies was 89 % for newly diagnosed cases but dropped down to 56 % and 47 % at first and second disease progression, respectively. Main obstacle was increased procedural risk due to patient deterioration, but no complications occurred. Biopsies had a tumour cellularity of 34 % and yielded 13.6 μg DNA and 12 μg RNA in median. Despite the poor condition and limited prognosis of most NSCLC patients, systematic, serial biomaterial acquisition including routine collection of cryoconserved biopsies is feasible in order to facilitate individualized management and support research that will advance therapeutic options.

Background: Exercise is beneficial for various cancer populations. However, there is limited evidence regarding inoperable lung cancer patients with advanced or metastatic disease. Thus, we assessed in this population the impact of an extended care intervention with or without an exercise program, on fatigue, quality of life and physical fitness. Methods: We randomly assigned 227 patients with advanced or metastatic lung cancer within 3 months after primary diagnosis to an experimental group (EX+) and a control group (CON). EX+ received a 24-week partly-supervised combined resistance and aerobic training 3x/week and weekly care management phone calls (CMPC). CON received CMPC alone. Primary endpoints were physical well-being and general fatigue at week 12 assessed by the Functional Assessment for Cancer Therapy - Lung (FACT-L) questionnaire and the Multidimensional Fatigue Inventory. Secondary endpoints comprised quality of life outcomes, psychological distress and physical performance. Analysis of covariance models were conducted regarding changes from baseline to week 12. Results: No significant effects on the primary endpoints were observed. Intent-to-treat analyses showed significant between group differences for knee extensor muscle strength favoring EX + (p=.04). Subgroup analyses revealed that EX+ patients with good training adherence, i.e. regularly participating in supervised exercise sessions with adherence rates >70% (n = 46), achieved significant benefits with respect to general fatigue (p=.01), functional well-being (p=.03) and the Trial Outcome Index of the FACT-L (p=.04). Conclusions: Inoperable lung cancer patients might not benefit from additional exercise programs beyond an extended care intervention during palliative treatment. However, among patients with good adherence, training may have favorable effects. Clinical trial identification: NCT02055508. Legal entity responsible for the study: Michael Thomas, Simone Hummler, Joachim Wiskemann. Funding: German Cancer Aid/Deutsche Krebshilfe. Disclosure: All authors have declared no conflicts of interest.

The aim of this work was to evaluate exercise behavior and physical fitness of advanced lung cancer patients shortly after primary diagnosis.

Authors: Thomas Bahmer (t.bahmer@lungenclinic.de;bahmer.thomas@googlemail.com) Anne-Marie Kirsten (a.kirsten@pulmoresearch.de) Benjamin Waschki (b.waschki@lungenclinic.de) Klaus Rabe (k.f.rabe@lungenclinic.de) Helgo Magnussen (magnussen@pulmoresearch.de) Detlef Kirsten (DetlefKirsten@online.de) Marco Gramm (mail.mgramm@gmail.com) Simone Hummler (Simone.Hummler@med.uni-heidelberg.de) Eva Brunnemer (eva.baroke@web.de) Michael Kreuter (michael.kreuter@med.uni-heidelberg.de) Henrik Watz (h.watz@pulmoresearch.de)

Cachexia and sarcopenia are associated with poor outcome and increased chemotherapy-induced toxicity in lung cancer patients. However, the complex interplay of obesity, sarcopenia and cachexia, and its impact on survival in the context of first-line-chemotherapy is not yet understood.In 200 consecutively recruited lung cancer patients (70 female, mean age 62y; mean BMI 25 kg/m2; median follow-up 15.97 months) with routine staging-CT before and after chemotherapy (CTX, mean interval: 4.3 months), densitometric quantification of total (TFA), visceral (VFA), and subcutaneous-fat-area (SFA), inter-muscular-fat-area (IMFA), muscle-density (MD), muscle-area (MA) and skeletal-muscle-index (SMI) was performed retrospectively to evaluate changes under chemotherapy and the impact on survival.We observed increases in TFA, VFA, SFA, VFA/SFA, and IMFA (p<0.05-0.001), while there were decreases in MA, MD and BMI (p<0.05-0.001) after chemotherapy. High pre-therapeutic VFA/SFA was a predictive factor for poor survival (HR = 1.272; p = 0.008), high pre-therapeutic MD for improved survival (HR = 0.93; p<0.05). Decrease in BMI (HR = 1.303; p<0.001), weight (HR = 1.067; p<0.001) and SMI (HR = 1.063; p<0.001) after chemotherapy were associated with poor survival. Patients with ≥4 CTX-cycles showed increased survival (17.6 vs. 9.1months), less muscle depletion (SMIdifference: p<0.05) and no BMI loss (BMIdifference: p<0.001).After chemotherapy, patients exhibited sarcopenia with decreased muscle and increased adipose tissue compartments, which was not adequately mirrored by BMI and weight loss but by imaging. Particularly sarcopenic patients received less CTX-cycles and had poorer survival. As loss of BMI, weight and muscle were associated with poor survival, early detection (via imaging) and prevention (via physical exercise and nutrition) of sarcopenia may potentially improve outcome and reduce chemotherapy-induced toxicity.

Background: Physical activity (PA) is associated with disease severity in idiopathic pulmonary fibrosis (IPF), but longitudinal studies evaluating its prognostic value and changes over time are lacking.Methods: We measured PA (steps per day, SPD) in a cohort of 46 IPF-patients (mean age, 67 years; mean FVC, 76. 1% pred.) by accelerometry at baseline, recorded survival status during 3 years follow-up and repeated measurements in survivors. We compared the prognostic value of PA to established mortality predictors including lung function (FVC, DLCO) and 6-min walking-distance (6MWD).Results: During follow-up (median 34 months) 20 patients (43%) died. SPD and FVC best identified non-survivors (AUROC-curve 0.79, p < 0.01). After adjustment for confounders (sex, age, therapy), a standardized increase (i.e. one SD) in SPD, FVC% pred. or DLCO% pred. was associated with a more than halved risk of death (HR < 0.50; p < 0.01). Compared to baseline, SPD, FVC, and 6MWD annually declined in survivors by 973 SPD, 130 ml and 9 m, resulting in relative declines of 48.3% (p < 0.001), 13.3% (p < 0.001) and 7.8% (p = 0.055), respectively.Conclusion: While PA predicts mortality of IPF patients similar to established functional measures, longitudinal decline of PA seems to be disproportionally large. Our data suggest that the clinical impact of disease progression could be underestimated by established functional measures.

Die Erkrankung fortgeschrittener Lungenkrebs ist nicht nur für Patienten, sondern auch für Angehörige und behandelnde Ärzte eine Herausforderung. Ein vielversprechender Ansatz zum Erhalt oder sogar Verbesserung der Lebensqualität und körperlichen Leistungsfähigkeit ist die Durchführung von individuell angepasstem Kraft- und Ausdauertraining (Kuehr/Wiskemann et al., 2014). Seit November 2013 (ClinicalTrials.gov: NCT02055508) werden in der Thoraxklinik Heidelberg in einer der aktuell größten Studien zu körperlicher Aktivität Patienten mit fortgeschrittenem Lungenkrebs rekrutiert. Hier berichten wir über vorläufige Rekrutierungs- sowie Adhärenzraten. Die Patienten erhalten entweder ein 24-wöchiges individuelles Kraft- und Ausdauertraining (3 Mal/Woche; nach Einweisung sowohl unter Supervision wohnortnah in einem kooperierenden Trainingszentrum als auch "home based") mit zusätzlicher wöchentlicher telefonischer Erfassung von Symptomen und Nebenwirkungen (CMPC = Care Management Phone Calls) oder das telefonische Symptommanagement allein. Die primären Studienendpunkte sind körperliches Wohlbefinden (FACT-L Fragebogen) und Fatigue (MFI Fragebogen) nach 12 Wochen, sekundäre Endpunkte umfassen u.a. die körperliche Leistungsfähigkeit.

Introduction: Physical exercise intervention programs show beneficial effects in early stage cancer patients during and after treatment. There is also growing evidence that physical exercise is safe and feasible for advanced cancer patients but knowledge is limited.Areas covered: This review provides an overview of randomized controlled exercise trials implemented in palliative care settings with advanced cancer patients. A comprehensive literature search was carried out in PubMed (MEDLINE), CINAHL, and the Cochrane Library. Six articles providing data of 590 patients met the predefined inclusion criteria. Mainly resistance exercise was applied and duration of interventions was between 8 and 16 weeks.Expert commentary: Beneficial effects for exercise patients were reported for both physical and psychological outcomes. However, general exercise recommendation for patients undergoing palliative treatment cannot be derived from the six analyzed studies. This is due to large heterogeneity of the applied exercise programs, included patient groups and performed assessment methods.