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Purpose: For stereotactic radiosurgery, the AAPM Report No. 54 [AAPM Task Group 42 (AAPM, 1995)] requires the overall stability of the isocenter (couch, gantry, and collimator) to be within a 1 mm radius. In reality, a rotating system has no rigid axis and thus no isocenter point which is fixed in space. As a consequence, the isocenter concept is reviewed here. It is the aim to develop a measurement method following the revised definitions. Methods: The mechanical isocenter is defined here by the point which rotates on the shortest path in the room coordinate system. The path is labeled as "isocenter path." Its center of gravity is assumed to be the mechanical isocenter. Following this definition, an image-based and radiation-free measurement method was developed. Multiple marker pairs in a plane perpendicular to the assumed gantry rotation axis of a linear accelerator are imaged with a smartphone application from several rotation angles. Each marker pair represents an independent measuring system. The room coordinates of the isocenter path and the mechanical isocenter are calculated based on the marker coordinates. The presented measurement method is by this means strictly focused on the mechanical isocenter. Results: The measurement result is available virtually immediately following completion of measurement. When 12 independent measurement systems are evaluated, the standard deviations of the isocenter path points and mechanical isocenter coordinates are 0.02 and 0.002 mm, respectively. Conclusions: The measurement is highly accurate, time efficient, and simple to adapt. It is therefore suitable for regular checks of the mechanical isocenter characteristics of the gantry and collimator rotation axis. When the isocenter path is reproducible and its extent is in the range of the needed geometrical accuracy, it should be taken into account in the planning process. This is especially true for stereotactic treatments and radiosurgery. [ABSTRACT FROM AUTHOR]

Background: Induction chemotherapy followed by definitive chemoradiotherapy is an intensified treatment approach for locally advanced squamous cell carcinoma of the head and neck (HNSCC) that might be associated with high rates of toxicity.Materials and Methods: The data of 40 consecutive patients who underwent induction chemotherapy with docetaxel-containing regimens followed by intensity-modulated radiotherapy (IMRT) and concomitant systemic therapy for unresectable locally advanced HNSCC were retrospectively analyzed. Primary objectives were RT-related acute and late toxicity. Secondary objectives were response to induction chemotherapy, locoregional recurrence-free survival (LRRFS), overall survival (OS), and influencing factors for LRRFS and OS.Results: The median follow-up for surviving patients was 21 months (range, 2-53 months). Patients received a median of three cycles of induction chemotherapy followed by IMRT to 72 Gy. Three patients died during induction chemotherapy and one during chemoradiotherapy. Acute RT-related toxicity was of grade 3 and 4 in 72 and 3 % of patients, respectively, mainly dysphagia and dermatitis. Late RT-related toxicity was mainly xerostomia and bone/cartilage necrosis and was of grade 3 and 4 in 15 % of patients. One- and 2-year LRRFS and OS were 72 and 49 % and 77 and 71 %, respectively.Conclusion: Induction chemotherapy followed by chemoradiotherapy using IMRT was associated with a high rate of severe acute and late RT-related toxicities in this selected patient cohort. Four patients were lost because of fatal complications. Induction chemotherapy did not compromise the delivery of full-dose RT; however, the use of three cycles of concomitant cisplatin was impaired. [ABSTRACT FROM AUTHOR]

Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cell­extracellular matrix (ECM) interactions are thought to mediate drug and radiation resistance. Dependence of cell survival, β1-integrin expression and cell cycling on the ECM proteins and &betal;1-integrin ligands fibronectin (FN) and laminin (LA) were examined in malignant and normal cells exposed to the cytotoxic drug Ukrain plus/minus irradiation. FN and LA reduced the cytotoxic effect of single Ukrain treatment compared with polystyrene and BSA. FN and LA also abolished Ukrain-dependent radiosensitization in A549 cells and decreased the radiosensitivity of MDA231 and HSF1 cells. Single Ukrain exposure on polystyrene significantly reduced β1-integrin expression and promoted G2-phase accumulation of A549 cells. In contrast, Ukrain-treated MDA231 and HSF1 cells showed elevated β1-integrin expression and no Ukrain-specific cell cycle effect. Under Ukrain-radiation exposure, irradiation, FN or LA abolished Ukrain-mediated reduction of β1-integrin expression and G2-phase accumulation in A549 cells, whereas in MDA231 cells and fibroblasts β1-integrin expression and cell cycle distribution were stabilized. Cell adhesion to FN or LA was significantly impaired (A549) or improved (MDA231, HSF1) upon Ukrain treatment. The data corroborate the findings of other groups that cell adhesion-mediated resistance to either single or combined drug and radiation exposure is tightly correlated to specific ECM proteins. By demonstrating a strong modulatory impact of FN and LA on the radiosensitivity-modifying activity of the drug Ukrain, these findings are also highly important for the assessment of drug and radiation effects within in vitro cytotoxicity studies. The data give the first mechanistic insights into specific FN- and LA-modulated cellular resistance mechanisms as well as into the important role for β1-integrins using the unique cytotoxic and radiosensitivity-modifying drug Ukrain. [ABSTRACT FROM AUTHOR]

Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Treatment of low grade glioma of the visual pathway in children poses a challenge to the neuro-ophthalmologist and radio-oncologist owing to their low incidence and the lack of consensus about 'optimal' treatments. Objectives: To define the role of radiotherapy in present and future treatment approaches. Methods: Reports in the literature spanning 6o years of radiation therapy, including orthovoltage, megavoltage, and recent modern high-precision treatment techniques, were reviewed with respect to the impact on visual function, survival, treatment techniques, and consequences of treatment. Based on these experiences, future swategies in the management of childhood low grade g ioma are discussed. Results: Although the efficacy of radiation therapy, has been well known for more than 60 years. there are still many open questions. Location and extent of disease often precludes aggressive surgery and a conservanve approach is used today with the aim of preserving visual function, Evaluation of published reports is difficult because of short follow-up periods and the failure to present findings and results in a comparable way. Even with the shortcomings of the reports available in the literature primarily concerning indications, dose-response effects, timing, and use of 'optimal' treatment fields, fractionated radiation therapy plays an important role m the management of low grade gliomas. Improved or stable visual function is obtained in approximately 9o% of the cases. With doses of 45-54Gy with standard fractionation and limited treatment fields high local tumor control in up to 8o% and more can be achieved. Past series comprising children younger than 5 years of age, however, have reported high rares of severe late effects when using large treatment fields and inadequat fractionation schemes. There is consent today to employ radiotherapy in progressive disease only and that newer technologies, such as [SUB3]D treatmemt planning (conformal radiotherapy),... [ABSTRACT FROM AUTHOR]

Purpose: Ukrain[sup ®], an alkaloid thiophosphoric acid derivative of Chelidonium majus L., has demonstrated a promising impact on chemotherapy in a variety of malignancies. The effects of the drug on cell survival, alteration of the cell cycle and induction of apoptosis were examined without and in combination with ionizing radiation (IR). The TP53 status of the cell lines used was also investigated. Materials and methods: Exponentially growing human tumour cell lines MDA-MB-231 (breast), PA-TU-8902 (pancreas), CCL-221 (colorectal), U-138MG (glioblastoma), and human skin and lung fibroblastic cells, HSF1, HSF2 and CCD32-LU were studied by colony assay, flow cytometry (cell-cycle, annexin-V staining for apoptosis) and Western blotting. Ukrain was used in concentrations from 0.1 to 50 μg ml[sup -1] for 1, 3 and 24 h and radiation as single doses of 1-10Gy. Combined drug-radiation exposure employed 1 μg ml[sup -1] Ukrain for 24h plus 2-8 Gy. Results: Ukrain cytotoxicity was time- and dose-dependent. The combination of Ukrain plus IR gave enhanced toxicity in CCL-221 and U-138MG cells, but not in MDA-MB-231 and PA-TU-8902 cells. Most strikingly, a radioprotective effect was found in normal human skin and lung fibroblasts. Flow-cytometry analyses supported the differential and cell line-specific cytotoxicity of Ukrain. CCL-221 and U-138MG cells accumulated in G2 after 24-h Ukrain treatment, whereas no alterations were detected in the other tumour cells and normal fibroblasts tested. Western blotting of TP53 demonstrated non-functional overexpression in all tumour cell lines without a ffecting p21. HSF1 presented wild-type TP53 and a p21 response after IR. Flowcytometric analyses of annexin-V staining showed no induction of apoptosis after Ukrain treatment in comparison with untreated controls. Conclusions: Differential effects of Ukrain in modulating radiation toxicity of human cancer cell lines and its protective effect in normal human fibroblasts suggest that this alkaloid may have potential properties for clinical radiochemotherapy. [ABSTRACT FROM AUTHOR]

Aim: Optimal dose and schedule of paclitaxel in combined drug-irradiation treatment could not be determined for most of tumors yet. The aim of this study was to compare in vitro cytotoxicity and radiosensitizing abilities as a function of single paclitaxel (Taxol) exposure in tumor and fibroblastic cells using different drug incubation irradiation intervals.Material and Method: A lung-carcinoma (SK-LU-1), glioblastoma (U-138 MG) and rodent fibroblast cell line (HyB14FAF28) were used. The clonogenic assay was applied for survival investigation. alpha beta-values were calculated using the linear-quadratic model (log S = -alpha D - beta D2). Cytotoxicity of Taxol was examined at 0 to 50 microM. Combined Taxol-radiotherapy exposure was accomplished with 10 microM Taxol plus 10 Gy irradiation (RT) following after a 1-hour and 9-hour interval. For controls cells were exposed to Cremophor EL/ethanol (CEL/eth) and a phosphate buffered saline (PBS).Results: Single Taxol exposure (10 microM) resulted in 0.54/0.50/0.84 (3-hours incubation) and 0.094/0.48/0.82 (15-hours incubation) survival of SK-LU-1, U-138 MG and HyB14FAF28 cells, respectively. Taxol concentrations from 2 to 50 microM only had cytotoxic effect in tumor cells. Single dose RT (10 Gy) led to cell survival of 0.0006/0.006/0.03. The diluent CEL/eth also showed cytotoxic activity. Taxol plus RT led to cell survival of 0.00025/0.0014/0.042 (1 hour) and 0.0004/0.0019/0.04 (9 hours) without significant difference between chosen time intervals. alpha beta-values showed great variation lacking evidence for definite radiosensitization. alpha increase after Taxol and alpha decrease after CEL/eth exposure were detected.Conclusions: The data presented demonstrate a potential beneficial effect, described as co-operation, by combining Taxol and RT in human tumor cells and rodent fibroblasts. High intrinsic alpha components of the tumor cells as well as CEL/eth's antagonizing actions could be likely to disturb and influence paclitaxel's abilities leading to radiosensitization. [ABSTRACT FROM AUTHOR]

The SAKK 09/10 phase 3 trial showed that dose-intensified salvage radiotherapy (SRT) was not superior to conventional dose SRT for biochemically recurrent prostate cancer (PCa) after radical prostatectomy (RP). We previously reported on the validation of the 22-gene genomic classifier as prognostic in this trial but did not observe an interaction with RT dose. Herein, we examine the PORTOS classifier, an expression signature of 24 DNA damage repair and immune pathway genes, previously shown to predict benefit from postoperative radiotherapy, to test its predictive ability to SRT dose. The SAKK 09/10 trial (NCT01272050) was a multicenter, randomized phase 3 trial that included PCa patients with biochemical progression after RP (PSA > 0.1 to 2 ng/mL at randomization). Patients were randomized to 64Gy vs 70Gy to the prostate bed. No patients received concurrent androgen suppression or pelvic nodal radiotherapy. After central review, the highest-grade tumors were profiled using the Decipher whole-transcriptome assay (Veracyte, San Diego, CA) to generate PORTOS. The independent prognostic ability and interaction effects were examined for the biochemical progression, clinical progression-free survival (CPFS), receipt of salvage hormone therapy, and metastasis-free survival endpoints with Cox multivariable and interaction analyses (MVA). Categorical analyses used the published threshold for PORTOS radiotherapy response (high vs low). Of the 226 trial patients with transcriptome data, 16% had high PORTOS radiation response compared to 84% with lower PORTOS. Patients with high PORTOS were well balanced between the randomization arms. PORTOS was not prognostic for the endpoints in MVA with the trial stratification factors. A high PORTOS, however, was predictive for improved outcomes in patients receiving dose-intensified SRT. Patients with high PORTOS that received 70Gy dose had 5-year CPFS of 94% compared to 49% with the 64Gy dose (log-rank p=0.006). In interaction analysis, PORTOS had a statistically significant interaction with RT dose for multiple endpoints: freedom from biochemical progression (interaction p=0.04), clinical progression-free survival (interaction p=0.003) and metastasis-free survival (interaction p=0.037). In a phase 3 trial testing SRT dose intensification after RP, patients with high PORTOS had significantly better outcomes with dose-intensified treatment, suggesting that higher doses should be considered in this subgroup. Further studies are warranted to validate PORTOS as the first predictive biomarker to help personalize dose prescription in the postoperative setting. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Presalvage PSA is an important prognostic and a predictive factor for salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) post-prostatectomy. GC can independently prognosticate prostate cancer outcomes and may help individualize treatment intervention. Herein, we assessed the role of the GC in patients treated within a contemporary phase 3 trial.Materials/methods: The SAKK 09/10 trial (NCT01272050) is an open-label, multicenter, randomized phase 3 trial performed in 24 centers in Switzerland, Germany, and Belgium. Patients with biochemical progression (PSA > 0.1 to 2 ng/mL at randomization) were randomized to 64 Gy vs 70 Gy to the prostate bed. No patients received ADT or pelvic nodal radiotherapy. A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. GC score range is 0 to 1, with locked cut points of < 0.45, 0.45-0.6, > 0.6 for low, intermediate, and high, respectively. In this sub-analysis, the primary endpoint was freedom from biochemical progression (FFBP) according to PSA at randomization (≤0.5 vs > 0.5, a trial stratification variable). Cox multivariable analysis (MVA) adjusting for age, T-category, Gleason score, persistent PSA after RP, and randomization arm were performed. Secondary endpoints included clinical progression-free survival (CPFS) and time to salvage ADT.Results: Of 233 patients with tissue available, 1 was ineligible and 6 failed QC. The remaining 226 were included for analysis with a median follow-up of 6.3 years (IQR 6.0-7.2). High- vs. low/intermediate-GC had an HR of 2.22 (95% CI 1.37-3.58, P = 0.001) for FFBP, 2.29 (95% CI 1.32-3.98, P = 0.003) for CPFS, and 2.99 (95% CI 1.50-5.95, P = 0.002) for use of salvage ADT. In patients with PSA ≤0.5 ng/mL (165/226, 73%), the 5-year FFBP was 74% [95% CI 66-82] for low-intermediate GC compared to 59% [95% CI 43-74] in patients with high-GC. High-GC patients had 5-year FFBP of 13% [95% CI 0-32] when SRT was delivered at PSA > 0.5 ng/mL compared to 59% [95% CI 43-74] when PSA ≤0.5 ng/mL.Conclusion: In a contemporary phase 3 trial, patients with a high-GC were more than twice as likely than patients with low/intermediate-GC to experience biochemical and clinical progression and receive salvage ADT. High-GC patients who received SRT with PSA > 0.5 ng/mL had nearly 90% risk of recurrence by 5-years post-SRT. This data validates the clinical utility of the GC for tailoring treatment in the salvage setting. [ABSTRACT FROM AUTHOR]