Leopold Hentschel

Mammalian-target of rapamycin inhibition with temsirolimus in myelodysplastic syndromes (MDS) patients is associated with considerable toxicity: results of the temsirolimus pilot trial by the German MDS Study Group (D-MDS).

The mammalian‐target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro‐proliferative and anti‐apoptotic stimuli and is involved in regulatory T‐cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion‐dependent/neutropenic or relapsed/refractory to 5‐azacitidine, respectively. All patients received TEM at a weekly dose of 25 mg. Of the 9 lower‐ and 11 higher‐risk patients included, only 4 (20%) reached the response assessment after 4 months of treatment and showed stable disease without haematological improvement. The remaining patients discontinued TEM prematurely due to adverse events. Median overall survival (OS) was not reached in the lower‐risk group and 296 days in the higher‐risk group. We observed a significant decline of bone marrow (BM) vascularisation (P = 0·006) but were unable to demonstrate a significant impact of TEM on the balance between TREG and pro‐inflammatory T‐helper‐cell subsets within the peripheral blood or BM. We conclude that mTOR‐modulation with TEM at a dose of 25 mg per week is accompanied by considerable toxicity and has no beneficial effects in elderly MDS patients.

A cluster-randomised, controlled proof-of-concept study to explore the feasibility and effect of a patient-directed intervention on quality of life in patients with advanced soft tissue sarcoma

Introduction Even with evolving and expanding therapeutical options for the treatment of advanced sarcomas over recent years, the balance between efficacy and toxicity still remains a major concern. Moreover, the symptom burden in patients with sarcoma remains high compared with other malignant diseases. It is, therefore, crucial to assess treatment effectiveness not only in terms of disease-related outcomes (eg, overall survival) but also from an individual and patient-centred perspective using the assessment of patient-reported outcomes (PROs). By focusing on PROs as a primary study endpoint, we aim to address key issues for patients with advanced soft tissue sarcoma (STS) undergoing palliative treatment. Methods and analysis The protocol of the YonLife study describes a multicentre, cluster-randomised, controlled, open-label proof-of-concept study conducted in patients with advanced or metastatic STS treated with trabectedin in seven German hospitals. The primary objective of the study is to exploratively compare overall quality of life between the patients receiving a multidimensional intervention based on individual PROs and those receiving usual supportive treatment. This complex intervention consists of the (1) electronic assessment of PRO, (2) creation of a case vignette based on PRO and clinical data and (3) treatment suggestions based on the discussion of these vignettes in a regularly meeting expert panel. Additionally, the YonLife trial assesses the applicability of a tablet-based assessment of PROs. Patients’ and physicians’ acceptance and challenges concerning the implementation process will be evaluated. Ethics and dissemination The YonLife trial has been approved by the Ethics Committee of the University Hospital Dresden as well as by the relevant institutions of each participating centre before patient enrolment. The findings will be reported via relevant peer-reviewed journals as well as through presentation at international conferences. Trial registration number NCT02204111, pre-results.

Effects of a home-based exercise program on physical capacity and fatigue in patients with low to intermediate risk myelodysplastic syndrome-a pilot study.

INTRODUCTION Fatigue is a frequent and disabling symptom in myelodysplastic syndromes (MDS). There is evidence for the benefit of exercise on fatigue in haematological malignancies, but clinical trials targeting patients with MDS do not exist. METHODS A prospective, non-randomized feasibility trial was conducted to assess the safety and efficacy of a home-based exercise intervention in patients with MDS. Exercise schedule contained endurance or strength training in daily turns over 12 weeks. Outcome measures included 6-min walking distance (6-MWD), an ergometer check, strength measurement of lower limb, abdomen and back, quality of life and fatigue. RESULTS Twenty-one patients (13 male, 8 female) were included. Median age was 66 years (range 29-87). Fifteen patients (71%) continued the program till week 12 (T1), of whom eleven patients met criteria for program completion. There were no adverse events reported due to the intervention. 6-MWD significantly improved from 580m at T0 to 645m at T1 (p<0.05). Fatigue scores did not significantly change over time (MFI: 12.8 vs. 12.3 vs. 11.9; QLQ-C30 fatigue scale: 48.2 vs. 46.7 vs. 47.4). CONCLUSION These data provide evidence that an unsupervised outpatient exercise program is feasible and can improve physical capacity. Randomized, controlled studies implementing these interventions are warranted.

Psychoonkologische Aspekte in der Versorgung von Prostatakarzinompatienten

ZusammenfassungHintergrundPsychosoziale und psychoonkologische Aspekte finden mittlerweile im Rahmen einer ganzheitlichen Behandlung von Tumorpatienten, welche körperliche, psychische und soziale Faktoren im Sinne des biopsychosozialen Verständnisses gleichgewichtig einbezieht, zunehmend Beachtung.ZielDie Autorin des Beitrags gibt einen Überblick über die psychische Belastung sowie die Verteilung von Störungsbildern bei Krebspatienten und vermittelt anhand von Fallvignetten exemplarisch Einblick in häufig thematisierte Probleme in den verschiedenen Behandlungsphasen des Prostatakarzinoms.MethodeEs erfolgte eine Auswertung der aktuellen Literatur sowie eigener Fallberichte.Ergebnisse und SchlussfolgerungAuch in der Urologie hat sich durch die Etablierung von zertifizierten onkologischen Zentren mit obligatorischen psychoonkologischen Angeboten die Versorgung der betroffenen Männer mit Prostatakarzinom auch im Hinblick auf deren psychosoziale Belastungsfaktoren verbessert. Dies ist ein bedeutsamer Entwicklungsschritt, wenngleich eine flächendeckende psychoonkologische Versorgung im ambulanten Sektor noch immer nicht gewährleistet ist.AbstractBackgroundIn recent years, psychosocial and psycho-oncological aspects have received increased attention within the framework of the biopsychosocial model of tumor patient treatment. ObjectiveThis article presents a short overview about psychological distress and disorders in patients treated for prostate cancer. Using exemplary patients, typical topics of the various illness and treatment phases will be illustrated.MethodResearch and analysis oft he current literature.Results and conclusionBy establishing certified oncological centers in urology and obligatory psycho-oncological contact, the psychosocial burden of patients has received more attention. Even though this is an important step, comprehensive nationwide psycho-oncological treatment in the outpatient sector cannot yet be provided.

Ongoing Clinical Trials

CAPP 2 Randomized controlled trial of colorectal polyp and cancer prevention using aspirin and resistant starch in carriers of hereditary nonpoly-posis colon cancer (HNPCC) Prof. John Burn University of Newcastle, UK Phase II, multicenter (33 centers), prospective, double-blind trial Factorial design Regimen: Aspirin 600 mg, resistant starch 30 g for 2-4 years Control: Placebo/active Endpoint: Colorectal neoplasm Patient population: Gene carriers of hereditary HNPCC n=1000 Ongoing (start January 1999; end December 2006) MRC, Cancer Research UK, Bayer AG, National Starch and Chemical Company Ms. Gail Barker Newcastle upon Tyne, UK