Renal toxicity in patients with multiple myeloma receiving zoledronic acid vs. ibandronate: A retrospective medical records review

Aims : This retrospective study investigated the rates of renal impairment in patients with multiple myeloma treated with zoledronic acid and ibandronate. Materials and Methods : We retrospectively reviewed medical records in a German oncology clinic, from May 2001 to December 2005. Creatinine measurements were analyzed from baseline (before zoledronic acid or ibandronate treatment) to last evaluation for each patient. A total of 84 patients were included. Results : Zoledronic acid increased the risk of renal impairment by approximately 3-fold compared with ibandronate (renal impairment rates: zoledronic acid 37.7% vs. ibandronate 10.5%, relative risk [RR]=3.6, P=0.0029 serum creatinine [SCr]; 62.3% vs. 23.7%, RR=2.6, P=0.0001 glomerular filtration rate [GFR]). Ibandronate-treated patients switched from zoledronic acid had a significantly higher risk of renal impairment than patients receiving ibandronate monotherapy (zoledronic acid over ibandronate 39.1% vs. ibandronate monotherapy 6.7%, RR= 5.9, P=0.028 [SCr]; 65.2% vs 26.7%, RR=2.4, P=0.022 [GFR]). Multivariate analysis found significantly higher hazard ratios for zoledronic acid over ibandronate (SCr: Cox = 4.38, P=0.01; Andersen-Gill=8.22, P < 0.01; GFR: Cox = 4.31, P < 0.01; Andersen-Gill = 3.71, P < 0.01). Conclusions : Overall, this retrospective study suggests that multiple myeloma patients are more likely to experience renal impairment with zoledronic acid than with ibandronate. The risk of renal impairment increased if patients had received prior therapy with zoledronic acid

Retrospective Analysis of Treatment Pathways in Patients With BRAFV600E-mutant Metastatic Colorectal Carcinoma - MORSECRC.

BACKGROUND/AIM Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland. PATIENTS AND METHODS Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-line treatment using descriptive statistics. RESULTS Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy. CONCLUSION Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Interaktiver Kleingruppenunterricht für Medizinstudenten der Klinischen Semester in einer onkologischen Gemeinschaftspraxis [Interactive medical education for medical students in an oncology group practice]

[english] Background: The education of medical students to become qualified medical doctors should be improved in Germany. Reasons for this are medical teachers not properly trained in education, a lack of quality control and low esteem of medical education, too large groups, no intensive relationship between students and academic teachers and the triad for medical teachers at university hospitals to qualify in their discipline, to perform science and lecture medical students. At the same time experienced associate professors who left university are not integrated optimally in medical education programs. Pilotproject: Since 1998 we are performing weekend seminars for advanced medical students. 3 students are educated by 1 teacher. The topics of the training are differential diagnosis of anaemia, polyglobulinaemia, leukocytopenia, leukocytosis, thrombocytopenia, thrombocytosis, training in morphology, diagnosis and treatment of leukaemia and lymphoma and principles of communication skills. Patient cases are presented in a problem oriented learning manner using patient files, a video microscope and a computer based learning programme for interactive purposes.Results: So far 320 students have participated in our seminars. Systematic quality evaluation of the teaching reveals excellent marks for practical relevance, learning atmosphere, didactics and effectiveness. Impressions of the routine work in an oncology group practice widens the experience of the students.Conclusion: Academical training for medical students is feasable and successful in an oncology group practice. This teaching model enables external associate professors to give their education in the environment where they are working and may relieve the University personally and financially.[german] Hintergrund: Die Ausbildung von Medizinstudenten zu guten Ärzten ist in Deutschland verbesserungsbedürftig. Die Gründe für ein suboptimales Studium sind die häufig fehlende Vernetzung von Theorie und Praxis, die mangelnde didaktische Ausbildung der akademischen Lehrer, die fehlende Wertschätzung einer guten Lehre, zu große Gruppen, fehlende fachliche und persönliche Beziehungen zwischen Lehrern und Studierenden, und immer noch die Triade, die von den Ärzten der Unikliniken verlangt ihre Facharztweiterbildung, Grundlagenforschung und den Studentenunterricht simultan zu leisten. Gleichzeitig wird die Erfahrung und Kompetenz der großen Zahl von erfahrenen, habilitierten Hochschuldozenten, die die Universität verlassen haben, nicht optimal genutzt.Pilotprojekt: Seit 1998 führen wir in unserer Gemeinschaftspraxis zweimal pro Semester ein Blockseminar für Studierende der klinischen Semester durch. Die maximale Gruppenstärke beträgt 3 Studenten pro Dozent. Die Unterrichtsinhalte umfassen die Anämiediagnostik, Differentialdiagnose der Leukozytopenie, Leukozytose, Thrombozytose, Thrombozytopenie, Diagnostik und Systematik der Leukämien und Lymphome, Morphologieunterricht sowie die Grundprinzipien der ärztlichen Gesprächsführung. Methodisch steht das problemorientierte Lernen unter Verwendung von Patientenakten, einem Videomikroskop sowie eine von uns entwickelte Differentialdiagnose CD im Mittelpunkt.Ergebnisse: Bisher haben 320 Studenten an unseren Seminaren teilgenommen. Die systematische Evaluation des Unterrichtes durch die Studenten ergibt Bestnoten für Praxisrelevanz, Unterrichtsatmosphäre, Didaktik und Effektivität. Einblicke in die Möglichkeiten des ärztlichen Arbeitens im Niedergelassenen Bereich erweitern den studentischen Erfahrungshorizont.Schlussfolgerung: Der akademische Unterricht von Medizinstudenten in einer Gemeinschaftspraxis ist auf hohem Qualitätsniveau möglich. Durch dieses Lehrmodell wird externen Hochschuldozenten der Unterricht erleichtert, gleichzeitig kann die Universität personell und finanziell entlastet werden

Determination of Choline Concentration in Breast Lesions:Quantitative Multivoxel Proton MR Spectroscopy as a Promising Noninvasive Assessment Tool to Exclude Benign Lesions

Purpose: To determine the optimal cutoff of choline (Cho) concentration in quantitative multivoxel magnetic resonance (MR) spectroscopic data to safely prove benignancy in breast lesions. Materials and Methods: The study was institutional review board approved, and informed consent was obtained from each patient. Between July 2009 and July 2010, multivoxel MR spectroscopy was performed in 24 consecutive patients with 25 breast lesions assessed as Breast Imaging Reporting and Data System 3 or 4 and larger than 1 cm in diameter at mammography. Two-dimensional point-resolved spatially localized spectroscopy chemical shift imaging was first performed without signal suppression (repetition time msec/echo time msec, 1500/30) as reference measurement and was performed subsequently with suppression of water and fat signals (1500/135) to detect Cho. Differences in mean and highest Cho concentration in the breast lesions were tested for significance by using the independent sample t test. The final diagnosis was confirmed with pathologic findings. Results: Fourteen of 25 breast lesions were malignant. The mean Cho concentration varied between 0.3 and 1.3 mmol/L (0.84 mmol/L +/- 0.32 [ standard deviation]) in benign lesions and between 1.3 and 9.5 mmol/L (3.10 mmol/L +/- 2.21) in malignant lesions. The highest Cho concentrations in benign and malignant lesions were 0.4-1.5 mmol/L (1.19 mmol/L +/- 0.33) and 1.7-11.8 mmol/L (4.08 mmol/L +/- 2.81), respectively. Mean and highest Cho concentrations in benign and malignant breast lesions differed significantly (P =.02 for both). Conclusion: The study, in a relatively small patient population, shows that quantitative multivoxel MR spectroscopy can be applied to exclude benign breast lesions from further invasive diagnostic work-up with the implementation of a Cho concentration of 1.5 mmol/L or lower as a cutoff. Further larger studies will be needed to confirm these results. (C) RSNA, 2011COUNSELOR