We investigated whether chemotherapy with the presence or absence of antibiotics against different kinds of cancer changed the gastrointestinal microbiota.
Feces of 17 ambulant patients receiving ...chemotherapy with or without concomitant antibiotics were analyzed before and after the chemotherapy cycle at four time points in comparison to 17 gender-, age- and lifestyle-matched healthy controls. We targeted 16S rRNA genes of all bacteria, Bacteroides, bifidobacteria, Clostridium cluster IV and XIVa as well as C. difficile with TaqMan qPCR, denaturing gradient gel electrophoresis (DGGE) fingerprinting and high-throughput sequencing. After a significant drop in the abundance of microbiota (p = 0.037) following a single treatment the microbiota recovered within a few days. The chemotherapeutical treatment marginally affected the Bacteroides while the Clostridium cluster IV and XIVa were significantly more sensitive to chemotherapy and antibiotic treatment. DGGE fingerprinting showed decreased diversity of Clostridium cluster IV and XIVa in response to chemotherapy with cluster IV diversity being particularly affected by antibiotics. The occurrence of C. difficile in three out of seventeen subjects was accompanied by a decrease in the genera Bifidobacterium, Lactobacillus, Veillonella and Faecalibacterium prausnitzii. Enterococcus faecium increased following chemotherapy.
Despite high individual variations, these results suggest that the observed changes in the human gut microbiota may favor colonization with C. difficile and Enterococcus faecium. Perturbed microbiota may be a target for specific mitigation with safe pre- and probiotics.
Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric ...randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3⁻20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%,
= 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436⁻671 versus control: 568 days, 95% CI: 349⁻680;
= 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.
Objectives
Although guidelines recommend normalization of platelet counts as an appropriate endpoint for treatment in high‐risk essential thrombocythemia (ET), retrospective studies could not prove a ...correlation of diagnostic platelet counts with an increased thrombotic rate. There is, however, an increasing evidence that leukocytosis is an important risk factor for arterial thrombosis in myeloproliferative neoplasms.
Methods
This study considers the Austrian cohort of a European registry regarding the platelet‐lowering therapeutic anagrelide. Influence of platelet and white blood cell (WBC) counts on thrombotic risk was assessed.
Results
Using the calculated cutoffs of 574.5 G/L for platelets and 8.48 G/L for WBC counts, respectively, the Cox regression analysis revealed a clear influence of elevated platelets (P = 0.008) and WBC counts (P = 0.011) on the occurrence of major thrombotic events. The time to a major thrombotic event was shortest (P < 0.001) and the frequency related to 100 patient‐years was highest (P = <0.001) when both platelet and WBC counts ranged above the calculated cutoffs.
Conclusion
Our data add evidence to the impact of platelet and WBC counts on thrombosis in ET. We suspect a particular interaction between platelets and WBC which might be based on a biological interplay depending on particular cell counts.
Understanding the impact of induction and maintenance therapy on patients’ quality of life (QoL) is important for treatment selection. This study aims to compare patient‐reported QoL between patients ...treated with KTd or KRd induction therapy and K maintenance therapy or observation. QoL was assessed using the EORTC QOL‐C 30 and QOL‐MY20 questionnaires in the AGMT‐02 study, in which 123 patients with newly diagnosed transplant ineligible multiple myeloma were randomized to nine cycles of either KTd or KRd induction therapy, followed by 12 cycles of K maintenance therapy, or observation. Longitudinal assessments showed statistically significant improvements in global health‐related QoL, various disease symptoms and pain for both treatment regimens. KTd improved insomnia and fatigue, and KRd improved physical functioning. Cross‐sectional comparisons indicated a “slight” superiority of KTd over KRd in several scales, with the exception of higher neuropathy scores with KTd. During maintenance, longitudinal comparisons showed no statistically significant changes. Cross‐sectional comparisons revealed a “slight” improvement in cognitive functioning during carfilzomib therapy, but a worsening in most other QoL scales. Induction therapy led to improvements in most QoL items, while maintenance therapy with K maintenance was associated with “slight” or “moderate” impairments in several QoL scales compared with the observation group.
Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. ...The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 10
CD34
cells/kg for a single or ≥5 × 10
CD34
cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34
cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34
cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 10
CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19
and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.
Colorectal cancer Zhang, Cheng; Stampfl-Mattersberger, Margarete; Ruckser, Reinhard ...
Wiener medizinische Wochenschrift
173, Issue:
9-10
Journal Article
Peer reviewed
Being one of the most common tumor entities worldwide, the colorectal carcinoma accounts for approximately 10% of all tumor-related deaths. With screening programs such as preventive colonoscopy, ...a decreasing incidence and mortality rate can be seen in the last decades. Many risk factors, which favor or prevent the development of colorectal carcinoma, can be traced back to lifestyle choices. Many patients with localized disease can be cured through tumor resection and adjuvant chemotherapy, in systemic disease, targeted therapy and immunotherapy have improved survival in the last years. This article aims to provide an overview on the basic epidemiologic, diagnostic and therapeutic principles of colorectal carcinoma, as well as a short excerpt of the newest therapeutic developments.
Zusammenfassung
Als eine der häufigsten Tumorentitäten weltweit ist das kolorektale Karzinom für etwa 10 % aller malignom-assoziierten Todesfälle verantwortlich. Durch Screening Programme wie die ...Vorsorgekoloskopie sehen wir in den letzten Jahrzehnten eine fallende Inzidenz sowie Mortalität. Viele Risikofaktoren, welche die Entwicklung eines kolorektalen Karzinoms begünstigen, aber auch verhindern, lassen sich auf Faktoren des Lebensstils zurückführen.
Durch Tumorresektion und adjuvante Chemotherapie kann ein Teil der Betroffenen im lokalisierten Stadium der Erkrankung geheilt werden, im fortgeschrittenen Stadium gab es durch neue gezielte Therapie und Immuntherapie in den letzten Jahren eine Verbesserung des Überlebens.
Das Ziel des vorliegenden Artikels ist es, einen kurzen Überblick über die Grundlagen der Epidemiologie, Diagnostik und Therapie des kolorektalen Karzinoms zu verschaffen, und auch einen kurzen Auszug aus den aktuellen Therapieentwicklungen wiederzugeben.
Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching ...provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.
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