A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced non-small cell lung cancer

Purpose: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m2on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of

Training medical specialists to communicate better with patients with medically unexplained physical symptoms (MUPS). A randomized, controlled trial

Background Patients with medically unexplained physical symptoms (MUPS) are prevalent 25-50% in general and specialist care. Medical specialists and residents often find patients without underlying pathology difficult to deal with, whereas patients sometimes don't feel understood. We developed an evidence-based communication training, aimed to improve specialists' interviewing, information-giving and planning skills in MUPS consultations, and tested its effectiveness. Methods The intervention group in this multi-center randomized controlled trial received a 14-hour training program to which experiential learning and feedback were essential. Using techniques from Cognitive Behavioral Therapy, they were stimulated to seek interrelating factors (symptoms, cognitions, emotions, behavior, and social environment) that reinforced a patient's symptoms. They were taught to

Training specialists to write appropriate reply letters to general practitioners about patients with medically unexplained physical symptoms; A cluster-randomized trial.

Objective: To evaluate effects of a communication training for specialists on the quality of their reply letters to general practitioners (GPs) about patients with medically unexplained physical symptoms (MUPS). Methods: Before randomization, specialists included ≤3 MUPS patients in a multi-center cluster-randomized trial. In 14 h of MUPS-specific communication training, 2.5 h focused on reply letters. Letters were discussed with regard to reporting and answering GPs' referral questions and patients' questions, and to reporting findings, explaining MUPS with perpetuating factors and giving advice. After the training, all doctors again included ≤3 MUPS patients. Reply letters to GPs were assessed for quality and blindly rated on a digital scale. Results: We recruited 478 MUPS patients and 123 specialists; 80% of the doctors wrote ≥1 reply letters, 285 letters were assessed. Trained doctors reported (61% versus 37%, OR=2.55, F(1281)=6.60, pgroup*time=.01) and answered (63% versus 33%, OR=3.31, F(1281)=5.36, pgroup*time=.02) patients' questions more frequently than untrained doctors. Conclusion: Training improves reply letters with regard to patients' questions, but not with regard to the following: GPs' referral questions, somatic findings, additional testing, explaining, and advice. Practice implications: Training specialists to write appropriate reply letters needs more focus on explanation and advice

Peptides from the variable region of specific antibodies are shared among lung cancer patients

Late diagnosis of lung cancer is still the main reason for high mortality rates in lung cancer. Lung cancer is a heterogeneous disease which induces an immune response to different tumor antigens. Several methods for searching autoantibodies have been described that are based on known purified antigen panels. The aim of our study is to find evidence that parts of the antigen-binding-domain of antibodies are shared among lung cancer patients. This was investigated by a novel approach based on sequencing antigen-binding- fragments (Fab) of immunoglobulins using proteomic techniques without the need of previously known antigen panels. From serum of 93 participants of the NELSON trial IgG was isolated and subsequently digested into Fab and Fc. Fab was purified from the digested mixture by SDS-PAGE. The Fab containing gel-bands were excised, tryptic digested and measured on a nano-LC-Orbitrap-Mass- spectrometry system. Multivariate analysis of the mass spectrometry data by linear canonical discriminant analysis combined with stepwise logistic regression resulted in a 12-antibody-peptide model which was able to distinguish lung cancer patients from controls in a high risk population with a sensitivity of 84% and specificity of 90%. With our Fab-purification combined Orbitrap-mass-spectrometry approach, we found peptides from the variable-parts of antibodies which are shared among lung cancer patients

Comparison of 2D (RANO) and volumetric methods for assessment of recurrent glioblastoma treated with bevacizumab-a report from the BELOB trial

textabstractBackground. The current method for assessing progressive disease (PD) in glioblastoma is according to the Response Assessment in Neuro-Oncology (RANO) criteria. Bevacizumab-treated patients may show pseudoresponse on postcontrast T1-weighted (T1w) MRI, and a more infltrative non-enhancing growth pattern on T2w/?uid attenuated inversion recovery (FLAIR) images. We investigated whether the RANO criteria remain the method of choice for assessing bevacizumab-treated recurrent glioblastoma when compared with various volumetric methods. Methods. Patients with assessable MRI data from the BELOB trial (n = 148) were included. Patients were treated with bevacizumab, lomustine, or both. At frst and second radiological follow-up (6 and 12 wk), PD was determined using the 2D RANO criteria and various volumetric methods based on enhancing tumor only and enhancing plus non-enhancing tumor. Differences in overall survival (OS) between PD and non-PD patients were assessed with the log-rank test and a Cox model. Hazard ratios (HRs) and their 95% CIs were determined. Results. For all patients together, all methods (except subtraction of non-enhancing from enhancing volume at frst follow-up) showed signifcant differences in OS between PD and non-PD patients (P <.001). The largest risk increase for death in case of PD at both frst and second follow-up was found with the RANO criteria: HR = 2.81 (95% CI, 1.92-4.10) and HR = 2.80 (95% CI, 1.75-4.49), respectively. In the bevacizumab-treated patients, all methods assessed showed signifcant differences in OS between PD and non-PD patients. There were no signifcant differences between methods. Conclusions. In the frst 12 weeks, volumetric methods did not provide signifcant improvement over the RANO criteria as a posttreatment prognostic marker

Comparison of 2D (RANO) and volumetric methods for assessment of recurrent glioblastoma treated with bevacizumab-a report from the BELOB trial

Background. The current method for assessing progressive disease (PD) in glioblastoma is according to the Response Assessment in Neuro-Oncology (RANO) criteria. Bevacizumab-treated patients may show pseudoresponse on postcontrast T1-weighted (T1w) MRI, and a more infltrative non-enhancing growth pattern on T2w/?uid attenuated inversion recovery (FLAIR) images. We investigated whether the RANO criteria remain the method of choice for assessing bevacizumab-treated recurrent glioblastoma when compared with various volumetric methods. Methods. Patients with assessable MRI data from the BELOB trial (n = 148) were included. Patients were treated with bevacizumab, lomustine, or both. At frst and second radiological follow-up (6 and 12 wk), PD was determined using the 2D RANO criteria and various volumetric methods based on enhancing tumor only and enhancing plus non-enhancing tumor. Differences in overall survival (OS) between PD and non-PD patients were assessed with the log-rank test and a Cox model. Hazard ratios (HRs) and their 95% CIs were determined. Results. For all patients together, all methods (except subtraction of non-enhancing from enhancing volume at frst follow-up) showed signifcant differences in OS between PD and non-PD patients (P <.001). The largest risk increase for death in case of PD at both frst and second follow-up was found with the RANO criteria: HR = 2.81 (95% CI, 1.92-4.10) and HR = 2.80 (95% CI, 1.75-4.49), respectively. In the bevacizumab-treated patients, all methods assessed showed signifcant differences in OS between PD and non-PD patients. There were no signifcant differences between methods. Conclusions. In the frst 12 weeks, volumetric methods did not provide signifcant improvement over the RANO criteria as a posttreatment prognostic marker

Identification of patients with recurrent glioblastoma who may benefit from combined bevacizumab and CCNU Therapy: A Report from the BELOB Trial

The results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva), a humanized monoclonal antibody against circulating VEGF-A, when added to CCNU chemotherapy in patients with recurrent glioblastoma (GBM). In this study, we performed gene expression profiling (DASL and RNA-seq) of formalin-fixed, paraffinembedded tumor material from participants of the BELOB trial to identify patients with recurrent GBM who benefitted most from bevaCCNU treatment. We demonstrate that tumors assigned to the IGS-18 or "classical" subtype and treated with bevaCCNU showed a significant benefit in progression-free survival and a trend toward benefit in overall survival, whereas other subtypes did not exhibit such benefit. In particular, expression of FMO4 and OSBPL3 was associated with treatment response. Importantly, the improved outcome in the bevaCCNU treatment arm was not explained by an uneven distribution of prognostically favorable subtypes as all molecular glioma subtypes were evenly distributed along the different study arms. The RNA-seq analysis also highlighted genetic alterations, including mutations, gene fusions, and copy number changes, within this well-defined cohort of tumors that may serve as useful predictive or prognostic biomarkers of patient outcome. Further validation of the identified molecular markers may enable the future stratification of recurrent GBM patients into appropriate treatment regimens