Browsing by Author "Jeremic, Branislav (7005009126)"

The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed. © 2017 The Author(s).

Although conventional fractionated (CF) radiotherapy (RT) became the most common non-surgical approach delivering 66-70 Gy in 33-35 daily fractions (fx) in 6.5-7 weeks several decades ago due to a good local control (LC) with low normal tissue complication rates, recent decades also brought altered fractionated RT regimens based on better understanding of radiobiology. Of these, split course RT is largely abandoned due to inferior results caused by the treatment gap, which led to inferior local control rates and consequently survival. Hyperfractionated (Hfx) RT and various forms of accelerated (Acc) RT had consistently shown improvement in the treatment outcome, given either alone or with concurrent chemotherapy (CHT). Hfx RT was most consistently superior to CF and frequently to Acc RT, while moderate Acc RT also holds promise to be used more often in daily clinical practice. The use of Hfx RT may face the challenge of applicability in busy radiotherapy departments around the world despite unequivocally having been proven as superior regarding both local/regional tumor control and overall survival. With concurrent CHT, although results favor it, risks of accompanying toxicity rise and should be considered when planning such intensified treatment approach. © 2020, Turkish Society for Radiation Oncology.

Meta-analyses of chemotherapy in Head and Neck Cancer (MAC-HNC) showed that adding chemotherapy (CHT) to locoregional treatment improves the treatment outcome. However, it was observed only with concurrent administration of radiotherapy (RT) and CHT. Among many drugs used in this setting, cisplatin (CDDP) has most consistently been used as a single-agent with radical RT. The two most common administrations of CDDP included 100 mg/sqm every three weeks and 40 mg/sqm weekly, both during the course of RT. While a direct comparison of the two modes of CDDP administration in the definitive treatment of locally advanced squamous cell (SQC) HNC is basically lacking, recent summary brought somewhat conflicting results. Questions largely unexplored is the total CDDP dose deemed necessary when administered concurrently with radical RT. Subset analyses from various prospective randomized trials and meta-analyses seem to indicate that one may not need a total CDDP dose of significantly higher than 200 mg/sqm if at all higher than that, irrespective of the type of RT administered and seemingly unnecessary in HPV+ oropharyngeal cancer patients. Due to presumably lower but still effective threshold level of total CDDP given with RT may depend on other factors, such as frequency of CDDP administration or RT fractionation pattern and be closely interrelated with an-ticipated toxicity, researchers continue with their quest to find optimal approach in this setting. Large clinical trials should detect small differences between treatment options in an era when “old” but effective drugs still dominate the research arena of SQC HNC. © 2020, Turkish Society for Radiation Oncology.

Background: To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. Methods: The records of 175,538 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. Results: In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3%) followed by low dose rate (LDR) (42.0%). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1%) followed by breast cancer (17.0%). BT was rarely the primary investigated treatment modality for cervical cancer (6.8%). Conclusion: Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future. © 2016 Cihoric et al.