A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity

MeV sterile neutrinos in low reheating temperature cosmological scenarios

It is commonly assumed that the cosmological and astrophysical bounds on the mixings of sterile with active neutrinos are much more stringent than those obtained from laboratory measurements. We point out that in scenarios with a very low reheating temperature T_RH << 100 MeV at the end of (the last episode of) inflation or entropy creation, the abundance of sterile neutrinos becomes largely suppressed with respect to that obtained within the standard framework. Thus, in this case cosmological bounds become much less stringent than usually assumed, allowing sterile neutrinos to be ``visible'' in future experiments. Here, we concentrate on massive (mostly sterile) neutrinos heavier than 1 MeV.Comment: 14 pp, 7 fig

Sterile neutrino dark matter in B−LB-L extension of the standard model and galactic 511 keV line

Sterile right-handed neutrinos can be naturally embedded in a low scale gauged $U(1)_{B-L}$ extension of the standard model. We show that, within a low reheating scenario, such a neutrino is an interesting candidate for dark matter. We emphasize that if the neutrino mass is of order of MeV, then it accounts for the measured dark matter relic density and also accommodates the observed flux of 511 keV photons from the galactic bulge.Comment: 10 pages, 1 figure, references added, final version appeared in JCA

Side effects of analgesia may significantly reduce quality of life in symptomatic multiple myeloma: a cross-sectional prevalence study

Background Pain is a common symptom in patients with multiple myeloma (MM). Many patients are dependent on analgesics and in particular opioids, but there is limited information on the impact of these drugs and their side effects on health-related quality of life (HRQoL). Method In a cross-sectional study, semi-structured interviews were performed in 21 patients attending the hospital with symptomatic MM on pain medications. HRQoL was measured using items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Results Patients were able to recall a median of two (range 0–4) analgesics. They spontaneously identified a median of two (range 1–5) side effects attributable to their analgesic medications. Patients’ assessment of HRQoL based on the EORTC QLQ-C30 questions 29/30 was mean 48.3 (95 % CI; 38.7–57.9) out of 100. Patients’ assessment of their HRQoL in the hypothetical situation, in which they would not experience any side effects from analgesics, was significantly higher: 62.6 (53.5–71.7) (t test, p=0.001). Conclusion This study provides, for the first time, evidence that side effects of analgesics are common in symptomatic MM and may result in a statistically and clinically significant reduction of self-reported HRQoL

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients

Background: We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. Materials and methods: World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. Results: Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. Conclusion: These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trial

The validation of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) in pre-operative patients with brain tumor in China

<p>Abstract</p> <p>Background</p> <p>Health related quality of life (HRQOL) has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0) in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery.</p> <p>Methods</p> <p>The questionnaire EORTC QLQ-C30 (version 3.0) was administered at three time points: T1, the first or the second day that patients were hospitalized after the brain tumor suspected or diagnosed by MRI or CT; T2, 1 to 2 days after T1, (T1 and T2 were both before surgery); T3, the day before discharge. Clinical variables included disease histologic types, cognitive function, and Karnofsky Performance Status.</p> <p>Results</p> <p>Cronbach's alpha coefficients for multi-item scales were greater than .70 and multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity, except for the cognitive functioning scale. All scales and items exhibited construct validity. Score changes over peri-operation were observed in physical and role functioning scales. Compared with mixed cancer patients assessed after surgery but before adjuvant treatment, brain tumor patients assessed pre-surgery presented better function and fewer symptoms.</p> <p>Conclusions</p> <p>The standard Chinese version of the EORTC QLQ-C30 was overall a valid instrument to assess HRQOL in brain tumor patients in China. The baseline HRQOL in brain tumor patients pre-surgery was better than that in mixed cancer patients post-surgery. Future study should modify cognitive functioning scale and examine test-retest reliability and response validity.</p

Amino-acid PET versus MRI guided re-irradiation in patients with recurrent glioblastoma multiforme (GLIAA) – protocol of a randomized phase II trial (NOA 10/ARO 2013-1)

Background: The higher specificity of amino-acid positron emission tomography (AA-PET) in the diagnosis of gliomas, as well as in the differentiation between recurrence and treatment-related alterations, in comparison to contrast enhancement in T1-weighted MRI was demonstrated in many studies and is the rationale for their implementation into radiation oncology treatment planning. Several clinical trials have demonstrated the significant differences between AA-PET and standard MRI concerning the definition of the gross tumor volume (GTV). A small single-center non-randomized prospective study in patients with recurrent high grade gliomas treated with stereotactic fractionated radiotherapy (SFRT) showed a significant improvement in survival when AA-PET was integrated in target volume delineation, in comparison to patients treated based on CT/MRI alone. Methods: This protocol describes a prospective, open label, randomized, multi-center phase II trial designed to test if radiotherapy target volume delineation based on FET-PET leads to improvement in progression free survival (PFS) in patients with recurrent glioblastoma (GBM) treated with re-irradiation, compared to target volume delineation based on T1Gd-MRI. The target sample size is 200 randomized patients with a 1:1 allocation ratio to both arms. The primary endpoint (PFS) is determined by serial MRI scans, supplemented by AA-PET-scans and/or biopsy/surgery if suspicious of progression. Secondary endpoints include overall survival (OS), locally controlled survival (time to local progression or death), volumetric assessment of GTV delineated by either method, topography of progression in relation to MRIor PET-derived target volumes, rate of long term survivors (> 1 year), localization of necrosis after re-irradiation, quality of life (QoL) assessed by the EORTC QLQ-C15 PAL questionnaire, evaluation of safety of FET-application in AA-PET imaging and toxicity of re-irradiation. Discussion: This is a protocol of a randomized phase II trial designed to test a new strategy of radiotherapy target volume delineation for improving the outcome of patients with recurrent GBM. Moreover, the trial will help to develop a standardized methodology for the integration of AA-PET and other imaging biomarkers in radiation treatment planning. Trial registration: The GLIAA trial is registered with ClinicalTrials.gov (NCT01252459, registration date 02.12.2010), German Clinical Trials Registry (DRKS00000634, registration date 10.10.2014), and European Clinical Trials Database (EudraCT-No. 2012-001121-27, registration date 27.02.2012)

The effects of exercise on pain, fatigue, insomnia, and health perceptions in patients with operable advanced stage rectal cancer prior to surgery: a pilot trial

Background: Promoting quality of life (QoL) is a key priority in cancer care. We investigated the hypothesis that, in comparison to usual care, exercise post-neoadjuvant chemoradiation therapy/prior to surgical resection will reduce pain, fatigue, and insomnia, and will improve physical and mental health perceptions in patients with locally advanced stage rectal cancer. Methods: In this non-randomized controlled pilot trial, patients in the supervised exercise group (EG; Mage = 64 years; 64% male) and in the control group (CG; Mage = 72 years; 69% male) completed the European Organization for Research and Treatment of Cancer core Quality of Life questionnaire and the RAND 36-Item Health Survey three times: pre-neoadjuvant chemoradiation therapy (Time 1; nEC = 24; nCG = 11), post-neoadjuvant chemoradiation therapy/pre-exercise intervention (Time 2; nEC = 23; nCG = 10), and post-exercise intervention (Time 3; nEC = 22; nCG = 10). The 6-week exercise intervention was delivered in hospital and comprised of interval aerobic training. Patients trained in pairs three times per week for 30 to 40 minutes. Data were analyzed by Mann-Whitney tests and by Wilcoxon matched-pairs signed rank tests. Results: No significant between-group differences in change were found for any of the outcomes. In both groups, fatigue levels decreased and physical health perceptions increased from pre- to post-exercise intervention. Pain levels also decreased from pre- to post-exercise intervention, albeit not significantly. Conclusions: The findings from this study can be used to guide a more definitive trial as they provide preliminary evidence regarding the potential effects of pre-operative exercise on self-reported pain, fatigue, insomnia, and health perceptions in patients with locally advanced rectal cancer. Trial registration: This study has been registered with clinicaltrials.gov (NCT01325909; March 29, 2011)