Does Bevacizumab Improve Outcomes After Ahmed Glaucoma Valve Implantation for Refractory Glaucoma?: A Meta-Analysis.

PRCIS: Mean intraocular pressure (IOP), complete and overall success, mean IOP-lowering medications, incidence of hypertensive phase, and complications were found to be comparable between patients undergoing Ahmed glaucoma valve implantation (AGVI) with adjunctive bevacizumab versus AGVI alone. OBJECTIVE: This meta-analysis aims to assess how adjunctive bevacizumab impacts the surgical outcomes of AGVI compared with AGVI alone in all subtypes of refractory glaucoma. METHODS: A systematic search of databases for relevant randomized controlled trials (RCTs) was performed in March 2023. Primary outcomes included mean IOP and success rates. Secondary outcomes were mean IOP-lowering medications, incidence of hypertensive phase, and complications. Qualitative assessment, meta-analysis, subgroup analyses, and sensitivity analysis were performed. RESULTS: Five RCTs comprising 203 eyes were included in the quantitative analysis. Initial meta-analysis showed a strong yet nonsignificant trend (all P > 0.05) favoring adjunctive bevacizumab in all outcomes of interest. Significant heterogeneity was observed for mean IOP and success outcomes at all time points (all I2 > 50%). Subgroup analysis of the administration route revealed a reduced incidence of hyphaema in the intravitreal bevacizumab subgroup (odds ratio: 0.10; 95% CI: 0.02 to 0.59; P = 0.01) with significant heterogeneity persisting in the intravitreal bevacizumab subgroup for all measures (all I2 > 50%). Post hoc sensitivity analysis of studies without concurrent pan-retinal photocoagulation for mean IOP and success outcomes demonstrated more conservative effect sizes with a corresponding decrease in heterogeneity for all measures (all I2 < 30%). CONCLUSION: Published studies investigating the role of adjunctive bevacizumab show a strong trend to improve outcomes but contain a relatively small number of participants. This analysis underpins the need for an adequately powered RCT to explore the role of anti-vascular endothelial growth factor agents in AGVI surgery.

Association of the CYP39A1 G204E Genetic Variant with Increased Risk of Glaucoma and Blindness in Patients with Exfoliation Syndrome.

PURPOSE: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation. DESIGN: Retrospective case study. PARTICIPANTS: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort. METHODS: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. MAIN OUTCOME MEASURES: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation. RESULTS: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001). CONCLUSIONS: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation.

Learning from the past: Mitomycin C use in trabeculectomy and its application in bleb-forming minimally invasive glaucoma surgery.

Trabeculectomy has been performed since the mid-1960s and remains the gold standard for glaucoma surgery. Newer surgical options have evolved, collectively referred to as minimally invasive glaucoma surgeries. Despite producing large intraocular pressure decreases, full-thickness procedures into the subconjunctival space may be limited by fibrosis. Mitomycin C (MMC) and 5-fluorouracil have been in use with trabeculectomy with good evidence of significantly increased success at the cost, however, of an increased risk of complications. Off-label MMC application can be found in almost all clinical trials, including in combination with minimally invasive glaucoma surgeries. We explore current evidence for MMC use in trabeculectomy and how this may differ for minimally invasive glaucoma surgery devices and analyze the range of agents and doses that are used. Although we found that most studies could not show any correlation between MMC dosage and the surgical outcome, the success rates with the Xen® microshunt seemed to be higher when using 20 mcg of MMC than when using 10 mcg. Certain important methodological considerations make this hard to confirm definitively, and other factors such as placement of the device may play a more substantial role. For the PreserFlo® microshunt, preliminary data suggest higher success rates with higher MMC dosage at the cost of higher device-related adverse events and reoperations. Although the ideal dose still needs to be established, it seems very likely that MMC provides significant improvement in outcomes in bleb-forming minimally invasive glaucoma procedures.

Image guidance and positioning accuracy in clinical practice: influence of positioning errors and imaging dose on the real dose distribution for head and neck cancer treatment.

BACKGROUND: Modern radiotherapy offers the possibility of highly accurate tumor treatment. To benefit from this precision at its best, regular positioning verification is necessary. By the use of image-guided radiotherapy and the application of safety margins the influence of positioning inaccuracies can be counteracted. In this study the effect of additional imaging dose by set-up verification is compared with the effect of dose smearing by positioning inaccuracies for a collective of head-and-neck cancer patients. METHODS: This study is based on treatment plans of 40 head-and-neck cancer patients. To evaluate the imaging dose several image guidance scenarios with different energies, techniques and frequencies were simulated and added to the original plan. The influence of the positioning inaccuracies was assessed by the use of real applied table shifts for positioning. The isocenters were shifted back appropriately to these values to simulate that no positioning correction had been performed. For the single fractions the shifted plans were summed considering three different scenarios: The summation of only shifted plans, the consideration of the original plan for the fractions with set-up verification, and the addition of the extra imaging dose to the latter. For both effects (additional imaging dose and dose smearing), plans were analyzed and compared considering target coverage, sparing of organs at risk (OAR) and normal tissue complication probability (NTCP). RESULTS: Daily verification of the patient positioning using 3D imaging with MV energies result in non-negligible high doses. kV imaging has only marginal influence on plan quality, primarily related to sparing of organs at risk, even with daily 3D imaging. For this collective, sparing of organs at risk and NTCP are worse due to potential positioning errors. CONCLUSION: Regular set-up verification is essential for precise radiation treatment. Relating to the additional dose, the use of kV modalities is uncritical for any frequency and technique. Dose smearing due to positioning errors for this collective mainly resulted in a decrease of OAR sparing. Target coverage also suffered from the positioning inaccuracies, especially for individual patients. Taking into account both examined effects the relevance of an extensive IGRT is clearly present, even at the expense of additional imaging dose and time expenditure.

Imaging dose and secondary cancer risk in image-guided radiotherapy of pediatric patients.

BACKGROUND: Daily image-guided radiotherapy (IGRT) can contribute to cover extended body volumes with low radiation dose. The effect of additional imaging dose on secondary cancer development is modelled for a collective of children with Morbus Hodgkin. METHODS: Eleven radiotherapy treatment plans from pediatric patients with Hodgkin's lymphoma were retrospectively analyzed, including imaging dose from scenarios using different energies (kV/MV) and planar/cone-beam computed tomography (CBCT) techniques. In addition to assessing the effect of imaging dose on organs at risk, the excess average risk (EAR) for developing a secondary carcinoma of the lung or breast was modelled. RESULTS: Although the variability between the patients is relatively large due to the different target volumes, the additional EAR due to imaging can be consistently determined. For daily 6MV CBCT, the EAR for developing a secondary cancer at age 50 is over 3 cases per 104 PY (patient-years) for the female breast and 0.7-0.8 per 104 PY for the lungs. This can be decreased by using only planar images (< 1 per 104 PY for the breast and 0.1 for the lungs). Similar values are achieved by daily 360° kV CBCT (0.44-0.57 per 104 PY for the breast and 0.08 per 104 PY for the lungs), which is again reduced for daily 200° kV CBCT (0.02 per 104 PY for the lungs and 0.07-0.08 per 104 PY for the breast). These values increase if an older attained age is considered (e.g., for 70 years, by a factor of four for the lungs). CONCLUSIONS: Daily imaging can be performed with an additional secondary cancer risk of less than 1 per 104 PY if kV CBCT is applied. If MV modalities must be chosen, a similar EAR can be achieved with planar images. A further reduction in risk is possible if the imaging geometry allows for sparing of the breast by a partial rotation underneath the patient.

Image guidance in clinical practice - Influence of positioning inaccuracy on the dose distribution for prostate cancer.

BACKGROUND: In order to consider potential positioning errors there are different recipes for safety-margins for CTV-to-PTV expansion. The aim of this study is to simulate the effect of positioning inaccuracy with clinically realistic patient treatment plans. METHODS: For a collective of 40 prostate patients, the isocenter was shifted back appropriately to the applied table shifts after positioning verification, simulating that no positioning correction had been performed and the treatment plans were recalculated. All the treatment fractions with the appropriate isocenter-shifts were added to yield a new plan considering two scenarios:Afterwards all plans were analysed and compared with each other regarding target coverage, sparing of organs at risk (OAR) and normal tissue complication probability (NTCP). RESULTS: Dose distributions and especially DVH show a deterioration of the target-coverage caused by the positioning inaccuracy. Deviations in dose at a single point can reach values of over 10 Gy. In single cases minimum plan agreement only achieved 66% pass within 3% local dose for the realistic case. Organs at risk and NTCP analysis result in a slightly better sparing of the rectum. Measures of quality like homogeneity and conformity differ just minimally regarding the different scenarios. CONCLUSION: PTV-coverage suffers markedly by the positioning uncertainties, the shifted plans are in large parts clinically not acceptable. Surprisingly sparing of the OAR is not negatively affected by potential positioning errors for this prostate collective.

First-in-human phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-ß2), in subjects with open-angle glaucoma undergoing glaucoma filtration surgery.

PURPOSE: To evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-ß2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; glaucoma filtration surgery). METHODS: In this prospective phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received a single intravitreal injection of ISTH0036 at the end of surgery in escalating total doses of 6.75 µg, 22.5 µg, 67.5 µg or 225 µg, resulting in calculated intraocular ISTH0036 concentrations in the vitreous humor of approximately 0.3 µM, 1 µM, 3 µM or 10 µM after injection, respectively. Outcomes assessed included: type and frequency of adverse events (AEs), intraocular pressure (IOP), numbers of interventions post trabeculectomy, bleb survival, visual acuity, visual field, electroretinogram (ERG), slit lamp biomicroscopy and optic disc assessment. RESULTS: In total, 12 patients were treated in the 4 dose groups. Main ocular AEs observed were corneal erosion, corneal epithelium defect, or too high or too low IOP, among others. No AE was reported to be related to ISTH0036. All other safety-related analyses did not reveal any toxicities of concern, either. The mean medicated preoperative IOP at decision time-point for surgery was 27.3 mmHg +/- 12.6 mmHg (SD). Mean IOP (±SD) for dose levels 1, 2, 3, and 4 were at Day 43 9.8 mmHg ± 1.0 mmHg, 11.3 mmHg ± 6.7 mmHg, 5.5 mmHg ± 3.0 mmHg and 7.5 mmHg ± 2.3 mmHg SD; and at Day 85 9.7 mmHg ± 3.3 mmHg, 14.2 mmHg ± 6.5 mmHg, 5.8 mmHg ± 1.8 mmHg and 7.8 mmHg ± 0.6 mmHg, respectively. In contrast to IOP values for dose levels 1 and 2, IOP values for dose levels 3 and 4 persistently remained below 10 mmHg throughout the observation period. CONCLUSION: This first-in-human trial demonstrates that intravitreal injection of ISTH0036 at the end of TE is safe. Regarding IOP control, single-dose ISTH0036 administration of 67.5 µg or 225 µg at the time of TE resulted in IOP values persistently < 10 mmHg over the three month postoperative observation period.

Abdominal imaging dose in radiology and radiotherapy - Phantom point dose measurements, effective dose and secondary cancer risk.

PURPOSE: To compare abdominal imaging dose from 3D imaging in radiology (standard/low-dose/dual-energy CT) and radiotherapy (planning CT, kV cone-beam CT (CBCT)). METHODS: Dose was measured by thermoluminescent dosimeters (TLD's) placed at 86 positions in an anthropomorphic phantom. Point, organ and effective dose were assessed, and secondary cancer risk from imaging was estimated. RESULTS: Overall dose and mean organ dose comparisons yield significantly lower dose for the optimized radiology protocols (dual-source and care kV), with an average dose of 0.34±0.01 mGy and 0.54±0.01 mGy (average ±â€¯standard deviation), respectively. Standard abdominal CT and planning CT involve considerably higher dose (13.58 ±â€¯0.18 mGy and 18.78±0.27 mGy, respectively). The CBCT dose show a dose fall-off near the field edges. On average, dose is reduced as compared with the planning or standard CT (3.79 ±â€¯0.21 mGy for 220° rotation and 7.76 ±â€¯0.37 mGy for 360°), unless the high-quality setting is chosen (20.30 ±â€¯0.96 mGy). The mean organ doses show a similar behavior, which translates to the estimated secondary cancer risk. The modelled risk is in the range between 0.4 cases per million patient years (PY) for the radiological scans dual-energy and care kV, and 300 cases per million PY for the high-quality CBCT setting. CONCLUSIONS: Modern radiotherapy imaging techniques (while much lower in dose than radiotherapy), involve considerably more dose to the patient than modern radiology techniques. Given the frequency of radiotherapy imaging, a further reduction in radiotherapy imaging dose appears to be both desirable and technically feasible.

Peptides of the variable IgG domain as potential biomarker candidates in primary open-angle glaucoma (POAG).

Autoantibody profiling has gained increasing interest in the research field of glaucoma promising the detection of highly specific and sensitive marker candidates for future diagnostic purposes. Recent studies demonstrated that immune responses are characterized by the expression of congruent or similar complementarity determining regions (CDR) in different individuals and could be used as molecular targets in biomarker discovery. Main objective of this study was to characterize glaucoma-specific peptides from the variable region of sera-derived immunoglobulins using liquid chromatography--mass spectrometry (LC-MS)-based quantitative proteomics. IgG was purified from sera of 13 primary open-angle glaucoma patients (POAG) and 15 controls (CTRL) and subsequently digested into Fab and Fc by papain. Fab was further purified, tryptic digested and measured by LC-MS/MS. Discovery proteomics revealed in total 75 peptides of the variable IgG domain showing significant glaucoma-related level changes (P < 0.05; log2 fold change ≥ 0.5): 6 peptides were high abundant in POAG sera, whereas 69 peptides were low abundant in comparison to CTRL group. Via accurate inclusion mass screening strategy 28 IgG V domain peptides were further validated showing significantly decreased expression levels in POAG sera. Amongst others 5 CDR1, 2 CDR2 and 1 CDR3 sequences. In addition, we observed significant shifts in the variable heavy chain family distribution and disturbed κ/λ ratios in POAG patients in contrast to CTRL. These findings strongly indicate that glaucoma is accompanied by systemic effects on antibody production and B cell maturation possibly offering new prospects for future diagnostic or therapy purposes.

A prospective, randomised, placebo-controlled, double-masked, three-armed, multicentre phase II/III trial for the Study of a Topical Treatment of Ischaemic Central Retinal Vein Occlusion to Prevent Neovascular Glaucoma - the STRONG study: study protocol for a randomised controlled trial.

BACKGROUND: Neovascular glaucoma (NVG) is rare, comprising only 3.9% of all glaucoma cases. The most common cause of NVG is ischaemic central retinal vein occlusion (iCRVO). NVG frequently results in blindness and painful end-stage glaucomatous damage leading to the need for enucleation. Currently, there is no preventive therapy for NVG following iCRVO. Rescue treatments have severe drawbacks. Accordingly, there is a great need for preventing the often visually devastating outcomes of NVG. The STRONG study is designed to test whether the topically active anti-angiogenic agent aganirsen is able to inhibit the formation of neovascularisation leading to the development of secondary NVG in eyes with iCRVO. At the same time, STRONG will provide important information on the natural course of iCRVO and NVG in a large and well-characterised cohort of such patients. METHODS/DESIGN: This protocol describes a phase II/III, prospective, randomised, placebo-controlled, double-masked, three-armed multicentre study for the investigation of aganirsen, a new topical treatment for iCRVO in order to prevent NVG. The study will evaluate the efficacy of two different doses of this newly developed antisense oligonucleotide formulated in an eye emulsion to avoid new vessel formation by blocking insulin receptor substrate-1 (IRS)-1. This leads to subsequent down-regulation of both angiogenic as well as proinflammatory growth factors such as vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF). Eligible patients (n = 333) will be treated with topical aganirsen or placebo for a period of 24 weeks. They will also be invited to participate in substudies involving analysis of gonioscopic images, detection of biomarkers for NVG and risk factors for iCRVO. DISCUSSION: The STRONG study has the potential to offer a new treatment modality for patients suffering from iCRVO with a high risk of developing NVG. The topical administration can reduce patients' burden and risk related to rescue treatment, such as destructive laser treatment or enucleation, but requires a high level of patient compliance. TRIAL REGISTRATION: EudraCT: 2014-000239-18; ClinicalTrials.gov, ID: NCT02947867 . (Registered on 15 October 2016); see also http://strong-nvg.com .

Influence of daily imaging on plan quality and normal tissue toxicity for prostate cancer radiotherapy.

BACKGROUND: Modern radiotherapy offers various possibilities for image guided verification of patient positioning. Different clinically relevant IGRT (image guided radiotherapy) scenarios were considered with regard to their influence on dosimetric plan quality and normal tissue complication probability (NTCP). METHODS: This study is based on treatment plans of 50 prostate patients. We evaluate the clinically performed IGRT and simulate the influence of different daily IGRT scenarios on plan quality. Imaging doses of planar and cone-beam-CT (CBCT) images for three different energies (6 MV, 1 MV and 121 kV) were added to the treatment plans. The plan quality of the different scenarios was assessed by a visual inspection of the dose distribution and dose-volume-histogram (DVH) and a statistical analysis of DVH criteria. In addition, an assessment of the normal tissue complication probability was performed. RESULTS: Daily 1MV-CBCTs result in undesirable high dose regions in the target volume. The DVH shows that the scenarios with actual imaging performed, daily kV-CBCT and daily 6MV imaging (1x CBCT, 4x planar images per week) do not differ exceedingly from the original plan; especially imaging with daily kV-CBCT has little influence to the sparing of organs at risk. In contrast, daily 1MV- CBCT entails an additional dose of up to two fraction doses. Due to the additional dose amount some DVH constraints for plan acceptability could no longer be satisfied, especially for the daily 1MV-CBCT scenario. This scenario also shows increased NTCP for the rectum. CONCLUSION: Daily kV-CBCT has negligible influence on plan quality and is commendable for the clinical routine. If no kV-modality is available, a daily IGRT scenario with one CBCT per week and planar axial images on the other days should be preferred over daily MV-CBCT.

mARC Treatment of Hypopharynx Carcinoma with Flat and Flattening-Filter-Free Beam Energies - A Planning Study.

BACKGROUND: The recently implemented mARC-rotation-technique is capable to deliver high dose rate bursts. For the case of hypopharynx cancer plans we evaluate whether the mARC can achieve an advantage in treatment time in comparison to IMRT. These plans consider two arcs with flat and flattening filter free (FFF) beam energies. MATERIALS AND METHODS: For 8 hypopharynx-cancer patients step-and-shoot-IMRT and mARC plans were created retrospectively using flat and FFF beam energy. The comparison of the plan scenarios considered measures of quality for PTV coverage and sparing of organs at risk. All plans were irradiated on an anthromorphic phantom equipped with thermoluminescent dosimeters to measure scattered dose and treatment times. RESULTS: A visual comparison of the dose distribution did not show a marked preference for either technique or energy. The statistical evaluation yielded significant differences in favor of the mARC technique and the FFF energy. Scattered dose could be decreased markedly by the use of the mARC technique. Treatment times could be reduced up to 3 minutes with the use of mARC in comparison to IMRT. The high dose rate energy results in another time advantage of about 1 minute. CONCLUSIONS: All four plan scenarios yielded equally good quality plans. A combination of the mARC technique with FFF 7 MV high dose rate resulted in a decrease of treatment times from about 9 minutes to 5-6 minutes in comparison to 6 MV IMRT.

mARC prostate treatment planning with Varian Eclipse for flat vs. FFF beams.

PURPOSE: The modulated arc (mARC) technique as an alternative to VMAT is a rotational IMRT irradiation with burst mode delivery. Varian has recently implemented an option for mARC-planning into the Eclipse treatment planning system (TPS) and so far mARC-planning with this TPS has not been evaluated systematically. Therefore, for prostate treatment with Eclipse we compare mARC with IMRT using flat (6MV) and flattening-filter-free (FFF, 7MV) beam energies. METHODS: For ten prostate cancer patients standardized re-contouring and re-planning was performed with a prescription of 76Gy to the complete planning-target-volume (PTV). IMRT and mARC plans (6MV vs. FFF 7MV) were compared pairwise considering indices for plan quality. All plans were delivered on an anthromorphic phantom equipped with thermoluminescent dosimeters to measure out-of-field dose and treatment times. RESULTS: Regarding PTV coverage, there was no marked preference for either technique or energy. The evaluation of organs at risk showed improved bladder sparing of the mARC plans up to about 75Gy; above this dose the IMRT plans achieved significant better sparing. The use of the FFF-beam-energy and mARC-technique resulted in a significant decrease in out-of-field dose. This combination also led to a drastic reduction of treatment time by factor of three in comparison with 6MV IMRT. CONCLUSION: While highly conformal treatment plans could be created by the use of all modalities, the combination of the high dose rate with mARC appears to be the preferable option as it benefits from a marked decrease in treatment time and out-of-field dose.

Set-up errors and planning margins in planar and CBCT image-guided radiotherapy using three different imaging systems: A clinical study for prostate and head-and-neck cancer.

PURPOSE: The purpose of this work is to compare the positioning accuracy achieved by three different imaging techniques and planar vs. CBCT imaging for two common IGRT indications. METHODS: A collective of prostate cancer and head-and-neck cancer patients treated at our institution during the year 2013 was retrospectively analyzed. For all treatment fractions (3078 in total), the kind of acquired set-up image and the performed couch shift before treatment were assessed. The distribution of couch corrections was compared for three different imaging systems available at our institution: the treatment beam line operating at 6 MV, a dedicated imaging beam line of nominally 1 MV, and the kVision system at 70-121 kV. Shifts were analyzed for planar and cone-beam CT images. Based on the set-up corrections, CTV to PTV expansion margins were calculated. RESULTS: The difference in set-up corrections performed for the three energies and both techniques (planar vs. CBCT) was not significant for head-and-neck cancer patients. For prostate cancer all shifts had equal variance. Averages ranged from -0.7 to +0.7 mm. The set-up margins calculated on the basis of the observed shifts are 4.0 mm (AP) and 3.8 mm (SI, LR) for the head-and-neck PTV and 6.6 mm (SI), 6.7 mm (AP) and 7.9 mm (LR) for the prostate cancer patients. CONCLUSIONS: For three different linac-based imaging energies and planar/CBCT imaging, no relevant differences in set-up shifts were observed. The suggested set-up margins for these indications are of the order of 4 mm for head-and-neck and 6-8 mm for prostate treatment.

mARC vs. IMRT radiotherapy of the prostate with flat and flattening-filter-free beam energies.

BACKGROUND: There as yet exists no systematic planning study investigating the novel mARC rotational radiotherapy technique, which is conceptually different from VMAT. We therefore present a planning study for prostate cancer, comparing mARC with IMRT treatment at the same linear accelerator equipped with flat and flattening-filter-free (FFF) photon energies. METHODS: We retrospectively re-contoured and re-planned treatment plans for 10 consecutive prostate cancer patients. Plans were created for a Siemens Artiste linear accelerator with flat 6 MV and FFF 7 MV photons, using the Prowess Panther treatment planning system. mARC and IMRT plans were compared with each other considering indices for plan quality and dose to organs at risk. All plans were exported to the machine and irradiated while measuring scattered dose by thermoluminescent dosimeters placed on an anthropomorphic phantom. Treatment times were also measured and compared. RESULTS: All plans were found acceptable for treatment. There was no marked preference for either technique or energy from the point of view of target coverage and dose to organs at risk. Scattered dose was significantly decreased by the use of FFF energies. While mARC and IMRT plans were of very similar overall quality, treatment time could be markedly decreased both by the use of mARC and FFF energy. CONCLUSIONS: Highly conformal treatment plans could be created both by the use of flat 6 MV and FFF 7 MV energy, using IMRT or mARC. For all practical purposes, the FFF 7 MV energy and mARC plans are acceptable for treatment, a combination of both allowing a drastic reduction in treatment time from over 5 minutes to about half this value.

Comparison of the effects of different lens-cleaning solutions on the protein profiles of human conjunctival cells.

BACKGROUND: Many contact lens wearers suffer from dry eye syndrome. Previous studies show significant changes in the protein composition of the tears depending on the lens-cleaning solution used. Therefore, the aim of this study was to detect the influence of different lens solutions on conjunctival cells, cells also involved in tear film composition. METHODS: Conjunctival epithelium cells (HCjE; IOBA-NHC) were exposed to medium containing Complete® Multipurpose Solution Easy Rub® Formula (Complete) (AMO) or Opti-Free® Express Multipurpose Disinfecting Solution (Opti-Free) (Alcon) in different concentrations (0.1, 0.5, 1, 2.5 %) for 12 and 24 h. Apoptosis and necrosis using FACS and protein profiles of the cells using SELDI-TOF-MS and MALDI-TOF-MS were measured. Multivariate statistics were calculated to detect the most significant changes. RESULTS: Complex protein profiles were measured with SELDI-TOF-MS and MALDI-TOF-MS. Significant differences of protein profiles between control and treatment cells were detected after 12 and 24 h, although cells incubated with Complete showed significantly fewer changes than cells incubated with Opti-Free, also showing concentration-dependent changes of some significantly changed proteins, e.g., protein at 6,736 Da (p > 0.002). Cells incubated with Complete showed significantly less apoptosis or necrosis in comparison to control cells (p < 0.05), whereas cells incubated with Opti-Free showed significantly more (p < 0.05). CONCLUSIONS: We were able to demonstrate that Complete shows very little effect on the protein profiles of conjunctival cells in comparison to Opti-Free, where the cells showed very large protein profile changes, and apoptosis and necrosis of the cells was increased. These results are in concordance to clinical studies showing that the use of Complete solution made the tear film proteins similar to those of people not wearing contact lenses. Therefore, we believe that Complete is less aggressive and should provoke fewer side-effects, such as dry eye syndrome, for the users.