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Targeting the P13K/mTOR and ATR/Chk1 Pathways to Improve Radiation Efficacy for Cancer Therapy
The purpose of the present thesis was to better understand the effect of targeting key biological mechanisms in order to improve radiotherapy response. Two important and distinct pathways were targeted using novel agents: (1) the phosphoinoside-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway; (2) the ataxia telangiectasia-mutated-Rad3-related (ATR)/Chkl pathway. The role of the PI3K1mTOR signalling pathway in tumour radiosensitivity and tumour microerivlronment (TME) was examined using three, recently-developed signalling inhibitors obtained from Novartis Pharma: NVP-BEZ235 (dual PI3K1mTOR inhibitor), NVP-BGT226 (dual PI3K1mTOR inhibitor) and NVP-BKM120 (single PI3K inhibito...
A 25-year Retrospective, Single Center Analysis of 343 WHO Grade II/III Glioma Patients: Implications for Grading and Temozolomide Therapy
Purpose: Classification and treatment of WHO grade II/III gliomas have dramatically changed. Implementing molecular markers into the WHO classification raised discussions about the significance of grading and clinical trials showed overall survival (OS) benefits for combined radiochemotherapy. As molecularly stratified treatment data outside clinical trials are scarce, we conducted this retrospective study. Methods: We identified 343 patients (1995-2015) with newly diagnosed WHO grade II/III gliomas and analyzed molecular markers, patient characteristics, symptoms, histology, treatment, time to treatment failure (TTF) and OS. Results: IDH-status was available for all patients (259 mutant, 84 IDH1-R132H-non-mutant). Molecular subclassification was possible in 173 tumors, resulting in diagnosis of 80 astrocytomas and 93 oligodendrogliomas. WHO grading remained significant for OS in astrocytomas/IDH1-R132H-non-mutant gliomas (p)
RADIANCE - Radiochemotherapy with Or Without Durvalumab in the Treatment of Anal Squamous Cell Carcinoma: a Randomized Multicenter Phase II Trial
Abstract: Purpose Anal squamous cell carcinomas (ASCC) are increasing in frequency across the developed world. The 3-year disease-free survival (DFS) in patients with locally-advanced disease is approximately 60% after primary radiochemotherapy (RCT). There is a strong rationale for combining immunotherapy with RCT in patients with ASCC due to its association with human papilloma virus (HPV) infection. Methods/design RADIANCE is an investigator initiated, prospective, multicenter, randomized phase II trial testing the addition of Durvalumab, a PD-L1 immune checkpoint inhibitor, to standard RCT in 178 patients with locally advanced ASCC (T2 ≥ 4 cm Nany, cT3-4 and/or cN+). In the control arm...
Tumors of the Central Nervous System, Volume 11
Like the ten preceding volumes in the series Tumors of the Central Nervous System, this book is distinguished for its comprehensive approach, its distinguished roster of some 93 contributors representing 8 different countries and its embrace of leading-edge technology and methods. Volume 11: Imaging, Glioma and Glioblastoma, Stereotactic Radiotherapy, Spinal Cord Tumors, Meningioma, and Schwannomas concentrates on the diagnosis, prognosis and therapy of four types of tumors, namely Glioblastoma, Meningioma, Schwannoma and Spinal Tumors. The book offers an in-depth survey of a range of new technologies and their applications to tumor diagnosis, treatment and therapy assessment. The contributors explain in thorough detail a range of current and newly developed imaging methods, including molecular imaging and PET scan. Also covered is molecular profiling of brain tumors to select therapy in clinical trials of brain tumors. Discussion includes a review of such surgical treatments as resection and the application of non-invasive stereotactic radiosurgery for treating high-risk patients with brain metastasis. Additional discussion is devoted to tumor seeding.
