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Background: A novel unconventional SBRT-based PArtial Tumor irradiation targeting HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal bystander (BE) and abscopal effects (AE) was developed by translating our preclinical findings to a clinic in 2016. In order to further improve BE/AE response rate, SBRT-PATHY was upgraded in 2018 by the sparing of peritumoral immune microenvironment as a new OAR, defined by its own dose-constraints. Considering the anti-tumor immune response homeostatic fluctuation, which is cyclically suppressed and incited ("switched off and on"), we synchronized SBRT-PATHY with its most excitable phase, in order to overcome tumor tolerance locally and systemically. The aim of this study, therefore, was to report on the initial results of our latest innovation aimed to further improve BE/AE response rate by testing the effectiveness of the time-synchronized immune-guided SBRT-PATHY.Materials and Methods: In order to serially map the homeostatic anti-tumor immune response-fluctuations, High Sensitive C-Reactive Protein (HS-CRP), Lactate Dehydrogenase (LDH) and Lymphocyte/Monocyte Ratio (LMR) were analyzed using high-order polynomial trend analysis as surrogate of immune system response. After the biomarker data analysis detected the immune fluctuations and related idiosyncratic immune cycle periodicity, we determined the "most favourable" and "least favourable" treatment time-positions in the immune cycle. In order to evaluate the impact of an idiosyncratic immune cycle on treatment outcomes, our first consecutive four patients were treated on the "most favourable" while the remaining four on the "least favourable" day.Results: The median follow-up was 11.8 months. The biomarker data analysis showed periodic immune response fluctuations of regular frequency. The "right" synchronization of SBRT-PATHY with the "most favorable day" of anti-tumor immune response was accompanied with improved clinical outcomes in terms of BE/AE-response rate.Conclusion: We believe the right synchronization of radiotherapy with the homeostatically oscillating immune response may improve the probability of inducing BE/AE. Present study has been retrospectively registered on 18th of October 2019 by the ethic committee for Austrian region "Kärnten "in Klagenfurt (AUT), under study number A 37/19. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Hydraulic dilatation is a novel method of cervical dilatation that is based on continuous controllable dilatation (CCBD) by the pumping of fluid into the balloon extension of the system. The main advantage of this procedure is that it allows control of and insight into the process of cervical dilatation. Methods: For the purposes of our research, we created a new and upgraded system for CCBD which consists of a programmed hydrostatic pump connected to a balloon extension. With regard to our aim to precisely measure and determine the location of the cervical resistance, we placed two pressure-measuring films, one on the top and one on the bottom of the balloon extension. This study included 42 patients in whom cervical resistance was measured before suction curettage. Results: Cervical dilatation and measurement of cervical resistance were successful in all patients. The analysis of the pressure-measuring films showed that the points of highest resistance were located in the zone of the internal cervical os and that these values were much higher than those in the zone of the external cervical os (0.402 versus 0.264 MPa at the upper pressure-sensitive film; 0.387 versus 0.243 MPa at the lower pressure-sensitive film). This study also showed that an increase in cervical resistance in the zone of the internal cervical os was followed by an increase in cervical resistance in the zone of the external cervical os. Conclusions: During CCBD, the internal cervical os is the centre of cervical resistance, and the values do not decline with the number of miscarriages or the number of previous births. Trial registration number: ISRCTN Registry identifier: ISRCTN30949871. Date of registration: 13 May 2015 [ABSTRACT FROM AUTHOR]

Background There is a strong interest in the investigation of extremely low frequency Electromagnetic Fields (EMF) in the clinic. While evidence about anticancer effects exists, the mechanism explaining this effect is still unknown. Methods We investigated in vitro, and with computer simulation, the influence of a 50 Hz EMF on three cancer cell lines: breast cancer MDA-MB-231, and colon cancer SW-480 and HCT- 116. After 24 h preincubation, cells were exposed to 50 Hz extremely low frequency (ELF) radiofrequency EMF using in vitro exposure systems for 24 and 72 h. A computer reactiondiffusion model with the net rate of cell proliferation and effect of EMF in time was developed. The fitting procedure for estimation of the computer model parameters was implemented. Results Experimental results clearly showed disintegration of cells treated with a 50 Hz EMF, compared to untreated control cells. A large percentage of treated cells resulted in increased early apoptosis after 24 h and 72 h, compared to the controls. Computer model have shown good comparison with experimental data. Conclusion Using EMF at specific frequencies may represent a new approach in controlling the growth of cancer cells, while computer modelling could be used to predict such effects and make optimisation for complex experimental design. Further studies are required before testing this approach in humans. [ABSTRACT FROM AUTHOR]

Background: Cervical dilation using mechanical dilators is associated with various complications, such as uterine perforation, cervical laceration, infections and intraperitoneal hemorrhage. To achieve safe and painless cervical dilation, we constructed a new medical device to achieve confident mechanical cervical dilation: a continuous controllable balloon dilator (CCBD). Methods: Controlled pumping of incompressible fluid into the CCBD increases the pressure and outer diameter of the CCBD, continuously dilating the cervical canal. The reliability of the CCBD was confirmed in vitro (testing for consistency and endurance, with no detected risk for breakage) and in vivo. A multi-center clinical study was conducted,with 120 pregnant women randomly assigned to one of three groups: Group I,control group, no dilation;Group II,mechanical dilation, Hegar dilator (HeD); and Group III,CCBD. The tissue material for histological evaluation was obtained from the endocervical mucosa before and after dilation using the HeD or CCBD. Results: The CCBD dilations were successful and had no complications in all 40 patients of Group III. The cervical tissue was markedly less damaged after CCBD dilation compared with HeD dilation (epithelium damage: 95% (HeD) vs. 45% (CCBD), P <0.001; basal membrane damage: 82.5% (HeD) vs. 27.5% (CCBD), P <0.001; stromal damage: 62.5% (HeD) vs. 37.5% (CCBD), P <0.01). Cervical hemorrhagia was observed in 90% of the patients after HeD dilation versus in 32.5% of the patients after CCBD dilation. Conclusions: The CCBD should be used as a replacement for mechanical dilators to prevent uterine and cervical injury during cervical dilation. Trial registration: ISRCTN54007498 [ABSTRACT FROM AUTHOR]

Lung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on radiotherapy as a major part of multi-modality care, and treatment-related toxicities, such as radiation-induced pneumonitis and/or lung fibrosis, are important dose limiting factors with direct impact on patient outcomes and quality of life. In this review, we summarize the current understanding of radiation-induced pneumonitis and pulmonary fibrosis, present predictive factors as well as recent diagnostic and therapeutic advances. Novel candidates for molecularly targeted approaches to prevent and/or treat radiation-induced pneumonitis and pulmonary fibrosis are discussed. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy-induced lymphopenia may be limiting the success of therapy and could also negatively affect the ability of immune system in mediating the bystander (BE) and abscopal effects (AE). A novel SBRT-based PArtial Tumor irradiation of HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal BE and AE by sparing the peritumoral immune microenvironment and regional circulating lymphocytes has been developed to enhance the radiotherapy therapeutic ratio of advanced lung cancer. The aim of this retrospective review of prospectively collected mono-institutional phase 2 study was to compare the outcomes between unconventional SBRT-PATHY and standard of care in unresectable stage IIIB/IV bulky NSCLC.Materials and Methods: Sixty patients considered inoperable or unsuitable for radical radio-chemotherapy were enrolled and treated using the following 3 regimens: SBRT-PATHY (group I, n = 20 patients), recommended standard of care chemotherapy (group II, n = 20 patients), and institutional conventional palliative radiotherapy (group III, n = 20 patients).Results: Median follow-up was 13 months. The 1-year overall survival was 75, 60, and 20% in groups 1, 2 and 3, respectively (p = 0.099). The 1-year cancer specific survival was 90, 60, and 20% in groups 1, 2, and 3, respectively (p = 0.049). Bulky tumor control rate was 95% for SBRT-PATHY compared with 20% in the other two groups. BE and AE were seen by SBRT-PATHY in 95 and 45% of patients, respectively. Multi-variate analysis for cancer specific survival was significant for treatment effect with SBRT-PATHY (p < 0.001) independent of age, sex, performance status, histology, stage, treated bulky site and tumor diameter. SBRT-PATHY resulted in lower toxicity (p = 0.026), and improved symptom control (p = 0.018) when compared to other two treatment options.Conclusion: SBRT-PATHY improved treatment outcomes in unresectable NSCLC and should be investigated in larger trials. Present study has been retrospectively registered on 8th of August 2019 by the ethic committee for Austrian region "Kärnten "in Klagenfurt (AUT), under study number A 31/19. [ABSTRACT FROM AUTHOR]

Background: The goal of this study is to evaluate the status and future perspectives of clinical trials on positron emission tomography in prostate cancer for diagnostic or therapeutic as well as for surveillance purposes.Methods: The www.ClinicalTrials.gov database was searched on the 20th of January 2017 for all trials containing terms describing "prostate cancer" (prostate, prostatic, malignant, malignancy, cancer, tumor) and "positron emission tomography". In total 167 trials were identified. Trials that included diseases other than PCa were excluded (n = 27; 16%). Furthermore, we excluded trials (n = 4, 2%) withdrawn prior to first patient enrollment. The remaining trials (n = 137, 82%) were selected for further manual classification analysis.Results: One hundred thirty-seven trials were detected and analyzed. Majority of trials were in "active" recruitment status (n = 46, 34%) followed by trials that had been "completed" - (n = 34, 25%) and trials with "closed recruitment but active follow-up" (n = 23, 17%). Phase 1 and 2 comprised 46% of the complete trial portfolio. Locally confined disease was of major interest (n = 46, 34%), followed by metastatic disease - not otherwise specified (n = 43, 13%). Evaluation of PET was the primary goal of the trial in 114 (83%) cases. Most of the trials evaluated only one agent (n = 122, 89%). Choline and PSMA represented two major groups (total 50%) and they were equally distributed across trial portfolio with 25% (n = 34) each. PSMA trials showed the highest average annual growth rate of 56%. The trials were conducted in 17 countries.Conclusion: The scientific community is showing a strong and ever-growing interest in the field and we expect that in the coming years, more phase III trials will be initiated ultimately delivering the required Level 1 evidence. [ABSTRACT FROM AUTHOR]

Background: Hydraulic dilatation is a novel method of cervical dilatation that is based on continuous controllable dilatation (CCBD) by the pumping of fluid into the balloon extension of the system. The main advantage of this procedure is that it allows control of and insight into the process of cervical dilatation.Methods: For the purposes of our research, we created a new and upgraded system for CCBD which consists of a programmed hydrostatic pump connected to a balloon extension. With regard to our aim to precisely measure and determine the location of the cervical resistance, we placed two pressure-measuring films, one on the top and one on the bottom of the balloon extension. This study included 42 patients in whom cervical resistance was measured before suction curettage.Results: Cervical dilatation and measurement of cervical resistance were successful in all patients. The analysis of the pressure-measuring films showed that the points of highest resistance were located in the zone of the internal cervical os and that these values were much higher than those in the zone of the external cervical os (0.402 versus 0.264 MPa at the upper pressure-sensitive film; 0.387 versus 0.243 MPa at the lower pressure-sensitive film). This study also showed that an increase in cervical resistance in the zone of the internal cervical os was followed by an increase in cervical resistance in the zone of the external cervical os.Conclusions: During CCBD, the internal cervical os is the centre of cervical resistance, and the values do not decline with the number of miscarriages or the number of previous births.Trial Registration Number: ISRCTN Registry identifier: ISRCTN30949871 . Date of registration: 13 May 2015. [ABSTRACT FROM AUTHOR]