Kirsten Papsdorf

Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial

BACKGROUND Radiotherapy is the standard care in elderly patients with malignant astrocytoma and the role of primary chemotherapy is poorly defined. We did a randomised trial to compare the efficacy and safety of dose-dense temozolomide alone versus radiotherapy alone in elderly patients with anaplastic astrocytoma or glioblastoma. METHODS Between May 15, 2005, and Nov 2, 2009, we enrolled patients with confirmed anaplastic astrocytoma or glioblastoma, age older than 65 years, and a Karnofsky performance score of 60 or higher. Patients were randomly assigned 100 mg/m(2) temozolomide, given on days 1-7 of 1 week on, 1 week off cycles, or radiotherapy of 60·0 Gy, administered over 6-7 weeks in 30 fractions of 1·8-2·0 Gy. The primary endpoint was overall survival. We assessed non-inferiority with a 25% margin, analysed for all patients who received at least one dose of assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01502241. FINDINGS Of 584 patients screened, we enrolled 412. 373 patients (195 randomly allocated to the temozolomide group and 178 to the radiotherapy group) received at least one dose of treatment and were included in efficacy analyses. Median overall survival was 8·6 months (95% CI 7·3-10·2) in the temozolomide group versus 9·6 months (8·2-10·8) in the radiotherapy group (hazard ratio [HR] 1·09, 95% CI 0·84-1·42, p(non-inferiority)=0·033). Median event-free survival (EFS) did not differ significantly between the temozolomide and radiotherapy groups (3·3 months [95% CI 3·2-4·1] vs 4·7 [4·2-5·2]; HR 1·15, 95% CI 0·92-1·43, p(non-inferiority)=0·043). Tumour MGMT promoter methylation was seen in 73 (35%) of 209 patients tested. MGMT promoter methylation was associated with longer overall survival than was unmethylated status (11·9 months [95% CI 9·0 to not reached] vs 8·2 months [7·0-10·0]; HR 0·62, 95% CI 0·42-0·91, p=0·014). EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy (8·4 months [95e% CI 5·5-11·7] vs 4·6 [4·2-5·0]), whereas the opposite was true for patients with no methylation of the MGMT promoter (3·3 months [3·0-3·5] vs 4·6 months [3·7-6·3]). The most frequent grade 3-4 intervention-related adverse events were neutropenia (16 patients in the temozolomide group vs two in the radiotherapy group), lymphocytopenia (46 vs one), thrombocytopenia (14 vs four), raised liver-enzyme concentrations (30 vs 16), infections (35 vs 23), and thromboembolic events (24 vs eight). INTERPRETATION Temozolomide alone is non-inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision-making. FUNDING Merck Sharp & Dohme.

Predictors of emotional distress in patients with head and neck cancer

Patients with head and neck cancer are known to be more commonly emotionally distressed than patients with other tumors. This study investigates reasons for this difference.

Malignant astrocytomas of elderly patients lack favorable molecular markers: an analysis of the NOA-08 study collective

BACKGROUND The number of patients age >65 years with malignant gliomas is increasing. Prognosis of these patients is worse compared with younger patients. To determine biological differences among malignant gliomas of different age groups and help to explain the survival heterogeneity seen in the NOA-08 trial, the prevalence and impact of recently established biomarkers for outcome in younger patients were characterized in elderly patients. METHODS Prevalences of mutations of isocitrate dehydrogenase 1 (IDH1) and histone H3.3 (H3F3A), the glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and methylation of alkylpurine DNA N-glycosylase (APNG) and peroxiredoxin 1 (PRDX1) promoters were determined in a representative biomarker subset (n = 126 patients with anaplastic astrocytoma or glioblastoma) from the NOA-08 trial. RESULTS IDH1 mutations (R132H) were detected in only 3/126 patients, precluding determination of an association between IDH mutation and outcome. These 3 patients also displayed the G-CIMP phenotype. None of the IDH1 wild-type tumors were G-CIMP positive. Mutations in H3F3A were absent in all 103 patients sequenced for H3F3A. MassARRAY analysis of the APNG promoter revealed generally low methylation levels and failed to confirm any predictive properties for benefit from alkylating chemotherapy. Neither did PRDX1 promoter methylation show differential methylation or association with outcome in this cohort. In a 170-patient cohort from The Cancer Genome Atlas database matched for relevant prognostic factors, age ≥65 years was strongly associated with shorter survival. CONCLUSIONS Despite an age-independent stable frequency of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation, tumors in this age group largely lack prognostically favorable markers established in younger glioblastoma patients, which likely contributes to the overall worse prognosis of elderly patients. However, the survival differences hint at fundamental further differences among malignant gliomas of different age groups.

Age- and sex-standardised prevalence rates of fatigue in a large hospital-based sample of cancer patients

Background:The aim of this longitudinal study was to determine age- and sex-standardised prevalence rates of cancer-related fatigue in different groups of patients.Methods:This was a prospective study in a cohort of N=1494 cancer patients investigating fatigue at three time points t1–t3 (t1: admission to hospital, t2: discharge, t3: half a year after t1). Fatigue was measured with the Multidimensional Fatigue Inventory. Age- and sex-adjusted norms were derived from a representative community sample of N=2037, using a cutoff at the 75th percentile.Results:At admission to the hospital, 32% of the patients were classified as fatigued. At discharge, the overall prevalence rate was 40%, and at half a year after t1, prevalence was 34%. Fatigue prevalence rates differed according to tumour stage, site, age, and sex of the patients.Conclusion:The prevalence rates provided by this study can be used for the planning of research and clinical routine.

Co-morbid mental health conditions in cancer patients at working age - prevalence, risk profiles, and care uptake

This study examined the prevalence of mental health conditions in cancer patients, the role of socioeconomic position in relation to that, and the use of professional mental health care.

Identifying tumor patients' depression.

PurposeThe aim of this study was to compare the precision of two different methods in detecting clinical depression in tumor patients: the use of a screening questionnaire versus the assessment by health care providers (nurses and doctors).MethodsDuring their first days of inpatient cancer treatment, tumor patients were interviewed using the Structured Clinical Interview for DSM (SCID). Their physicians and nurses were asked to assess the mental health of the patients and their need for professional psychosocial support. Additionally, every patient completed the Hospital Anxiety and Depression Scale (HADS).ResultsOut of 329 patients, 28 were diagnosed with either a major or a minor depression according to the SCID. Physicians assessed 15 of the depressed patients as being depressed (sensitivity, 0.54; specificity, 0.38). Nurses identified 19 (sensitivity, 0.68; specificity, 0.45) and the HADS 27 (sensitivity, 0.96; specificity, 0.50) of the depressed patients.ConclusionThe HADS performed well in detecting depressed cancer patients in acute oncological care, whereas physicians and nurses often were unable to recognize depressed patients.

Is it useful to calculate sum scores of the quality of life questionnaire EORTC QLQ-C30?

The aim of this paper is to test the psychometric properties of sum scores of the quality of life questionnaire EORTC QLQ-C30. A sample of cancer patients (n= 1529) and a sample of the general population (n= 1185) were tested with the EORTC QLQ-C30, the Hospital Anxiety and Depression Scale and the Multidimensional Fatigue Inventory. Three sum scores of the EORTC QLQ-C30 are defined: a score concerning functioning, a score concerning symptoms and a total score. Compared with the two-item quality of life scale of the EORTC QLQ-C30, the psychometric quality of the total score and the functioning score is superior with respect to reliability, convergent validity and discriminant validity. Cronbachs alpha of the total score is 0.94 (cancer patients) and 0.95 (general population). The effect size discriminating between patients and controls is d= 0.83 for the total score, compared to only 0.50 obtained with the two-item quality of life scale. The results prove that the calculation of sum scores provides useful information for clinicians who are interested in one generalising score of quality of life.

Early retirement in cancer patients with or without comorbid mental health conditions: A prospective cohort study

The authors investigated whether cancer patients who have comorbid mental health disorders (MD) are at greater risk of early retirement compared with those who do not have MD.

Effect of a structured psycho-oncological screening and treatment model on mental health in cancer patients (STEPPED CARE): study protocol for a cluster randomized controlled trial.

BackgroundHigh levels of emotional distress in cancer patients often goes unnoticed in daily clinical routine, resulting in severe undertreatment of mental health problems in this patient group. Screening tools can be used to increase case identification, however, screening alone does not necessarily translate into better mental health for the patient. Doctors play a key role in providing basic emotional support and transferring the patients in need of such specific support to mental health professionals. This study investigates whether a stepped care model, combining screening, doctor consultation and professional psycho-oncological service in a structured way, improves the emotional wellbeing of cancer patients.Methods/DesignThis study is a cluster randomized trial with two parallel groups (intervention vs. care as usual), set in an academic hospital. Participants are cancer patients, a total of 1,000 at baseline. The intervention consists of stepped psychosocial care. Step one: screening for distress, step two: feedback of screening results to the doctor in charge of the patient and consultation with the patient, and step three: based on a shared patient-doctor decision, either transferal to the consultation liaison (CL) service or not. The outcome will be emotional well-being half a year after baseline, ascertained with the Hospital Anxiety and Depression Scale. Randomization will be done by the cluster randomization of wards.DiscussionMental health problems not only cause emotional suffering but also direct and indirect costs. This calls for timely and adequate psychosocial support, especially as we know that such support is effective. However, not every cancer patient can and must be treated by a mental health professional. Allocating limited resources most sensibly and economically is of crucial importance for our healthcare system to ensure the best quality of care to as many patients as possible. It is the hope of the STEPPED CARE trial that this model is both effective and efficient, and that it can be implemented in other hospitals as well, if proven to be effective.Trial registrationClinical Trials Register (Clinicaltrials.gov) identifier: NCT01859429 registration date 17 May 2013.

Impact of socio‐economic position on cancer stage at presentation: Findings from a large hospital‐based study in Germany

We explored the relationship between socio‐economic characteristics and cancer stage at presentation. Patients admitted to a university hospital for diagnosis and treatment of cancer provided data on their education, vocational training, income, employment, job, health insurance and postcode. Tumor stage was classified according to the Union International Contre le Cancer (UICC). To analyze disparities in the likelihood of late‐stage (UICC III/IV vs. I/II) diagnoses, logistic regression models adjusting for age and gender were used. Out of 1,012 patients, 572 (59%) had late‐stage cancer. Separately tested, increased odds of advanced disease were associated with post‐compulsory education compared to college degrees, with apprenticeship and no vocational training, with unemployment, disability pension, jobs with a low hierarchy level, blue collar jobs and with low income. Health insurance and community size were not related with late‐stage cancer. Jointly modelled, there was evidence for an independent effect of unemployment (odds ratio (OR) 1.7, CI 1.0–2.8), disability pension (OR 1.8, CI 1.0–3.2) and very low income (OR 2.6, CI 1.1–6.1) on the likelihood of advanced disease stage. It is of great concern that these socio‐economic gradients occur even in systems with equal access to health care.