Showing papers by "Michael Baumann published in 2016"
TL;DR: There is an urgent need to improve reproducibility and translatability of preclinical data to fully exploit opportunities for molecular therapeutics involving radiation and radiochemotherapy and in vivo studies are necessary to confirm in vitro findings, further define mechanism of action, and address immunomodulation and treatment-induced modification of the microenvironment.
Abstract: There is an urgent need to improve reproducibility and translatability of preclinical data to fully exploit opportunities for molecular therapeutics involving radiation and radiochemotherapy. For in vitro research, the clonogenic assay remains the current state-of-the-art of preclinical assays, whereas newer moderate and high-throughput assays offer the potential for rapid initial screening. Studies of radiation response modification by molecularly targeted agents can be improved using more physiologic 3D culture models. Elucidating effects on the cancer stem cells (CSC, and CSC-like) and developing biomarkers for defining targets and measuring responses are also important. In vivo studies are necessary to confirm in vitro findings, further define mechanism of action, and address immunomodulation and treatment-induced modification of the microenvironment. Newer in vivo models include genetically engineered and patient-derived xenograft mouse models and spontaneously occurring cancers in domesticated animals. Selection of appropriate endpoints is important for in vivo studies; for example, regrowth delay measures bulk tumor killing, whereas local tumor control assesses effects on CSCs. The reliability of individual assays requires standardization of procedures and cross-laboratory validation. Radiation modifiers must be tested as part of clinical standard of care, which includes radiochemotherapy for most tumors. Radiation models are compatible with but also differ from those used for drug screening. Furthermore, the mechanism of a drug as a chemotherapeutic agent may be different from its interaction with radiation and/or radiochemotherapy. This provides an opportunity to expand the use of molecular-targeted agents. Clin Cancer Res; 22(13); 3138-47. ©2016 AACR.
69 citations
TL;DR: The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy, and this is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC.
Abstract: Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients’ quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects. This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week. The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects. Registered at ClinicalTrials.gov with Identifier NCT02731001
on 1 April 2016.
21 citations
7 citations
TL;DR: This poster presents a poster presented at the European Society for Medical Oncology Congress (ES congress) in Brussels on Wednesday, 5-7 June 2016 presenting the findings of the six-month study of radiolysis-guided cell reprograming of T-cells in the nucleus of the immune system.
3 citations
3 citations
TL;DR: It is feasible to simulate FMISO distributions that match the pimonidazole retention patterns observed in vivo, and good agreement was obtained for multiple tumor models by optimizing the oxygen consumption rate, M0, whose optimum value differed significantly between tumor models.
Abstract: Purpose:
To compare a dedicated simulation model for hypoxia PET against tumor microsections stained for different parameters of the tumor microenvironment. The model can readily be adapted to a variety of conditions, such as different human head and neck squamous cell carcinoma (HNSCC) xenograft tumors.
Methods:
Nine different HNSCC tumor models were transplanted subcutaneously into nude mice. Tumors were excised and immunoflourescently labeled with pimonidazole, Hoechst 33342, and CD31, providing information on hypoxia, perfusion, and vessel distribution, respectively. Hoechst and CD31 images were used to generate maps of perfused blood vessels on which tissue oxygenation and the accumulation of the hypoxia tracer FMISO were mathematically simulated. The model includes a Michaelis–Menten relation to describe the oxygen consumption inside tissue. The maximum oxygen consumption rate M0 was chosen as the parameter for a tumor-specific optimization as it strongly influences tracer distribution. M0 was optimized on each tumor slice to reach optimum correlations between FMISO concentration 4 h postinjection and pimonidazole staining intensity.
Results:
After optimization, high pixel-based correlations up to R2 = 0.85 were found for individual tissue sections. Experimental pimonidazole images and FMISO simulations showed good visual agreement, confirming the validity of the approach. Median correlations per tumor model varied significantly (p < 0.05), with R2 ranging from 0.20 to 0.54. The optimum maximum oxygen consumption rate M0 differed significantly (p < 0.05) between tumor models, ranging from 2.4 to 5.2 mm Hg/s.
Conclusions:
It is feasible to simulate FMISO distributions that match the pimonidazole retention patterns observed in vivo. Good agreement was obtained for multiple tumor models by optimizing the oxygen consumption rate, M0, whose optimum value differed significantly between tumor models.
2 citations
15 Apr 2016
15 Apr 2016
TL;DR: Eine zusätzliche Operation war abhängig von Tumorlokalisation and Verfügbarkeit, wobei insgesamt keine stärkeren Nebenwirkungen zu beobachten waren.
Abstract: Patienten und Methodik: Es wurden 57 Patienten mit lokalem Rhabdomyosarkom (21 Jahre oder jünger) oder metastasiertem embryonalen Rhabdomyosarkom (2–10 Jahre) zwischen Februar 2005 und August 2012 in die Studie eingeschlossen. Die Patienten erhielten entweder eine Chemotherapie mit Vincristin, Aktinomycin und Cyclophosphamid oder eine kombinierte erapie aus Vincristin, Actinomycin und Ifosfamid mit Protonentherapie. Eine zusätzliche Operation war abhängig von Tumorlokalisation und Verfügbarkeit. CTC-Kriterien (Version 3.0) wurden zur Graduierung der Nebenwirkungen verwendet. Ergebnisse: Nach einer medianen Nachbeobachtungszeit von 47 Monaten (Spanne 14–102 Monate) betrug in der gesamten Kohorte das krankheitsfreie Überleben nach 5 Jahren 69 %, das Gesamtüberleben 78 % und die lokale Kontrolle 81 %. Krankheitsfreies und Gesamtüberleben lagen nach 5 Jahren in der Niedrigrisiko-Gruppe bei 93 und 100 % und in der Gruppe mit intermediärem Risiko bei 61 und 70 % (jeweils: p = 0,04). Die lokale Kontrolle nach 5 Jahren lag bei 93 % für die Niedrigrisiko-Gruppe und bei 77 % für Patienten mit intermediärem Risiko (p = 0,20). Bei 13 Patienten ist eine akute Grad-3-Nebenwirkung und bei 3 Patienten eine Grad-3-Spättoxizität aufgetreten, wobei insgesamt keine stärkeren Nebenwirkungen zu beobachten waren.