Publications by authors named "Jan Hrbacek"

47 Publications

Non-invasive recognition of eye torsion through optical imaging of the iris pattern in ocular proton therapy.

Phys Med Biol 2021 Jul 1;66(13). Epub 2021 Jul 1.

Paul Scherrer Institut, Switzerland.

The introduction of non-invasive imaging techniques such as MRI imaging for treatment planning and optical eye tracking for in-room eye localization would obviate the requirement of clips implantation for many patients undergoing ocular proton therapy. This study specifically addresses the issue of torsional eye movement detection during patient positioning. Non-invasive detection of eye torsion is performed by measuring the iris pattern rotations using a beams eye view optical camera. When handling images of patients to be treated using proton therapy, a number of additional challenges are encountered, such as changing eye position, pupil dilatation and illumination. A method is proposed to address these extra challenges while also compensating for the effect of cornea distortion in eye torsion computation. The accuracy of the proposed algorithm was evaluated against corresponding measurement of eye torsion using the clips configuration measured on x-ray images. This study involves twenty patients who received ocular proton therapy at Paul Scherrer Institute and it is covered by ethical approval (EKNZ 2019-01987).
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http://dx.doi.org/10.1088/1361-6560/ac0afbDOI Listing
July 2021

Characterization of the HollandPTC proton therapy beamline dedicated to uveal melanoma treatment and an interinstitutional comparison.

Med Phys 2021 Jun 5. Epub 2021 Jun 5.

Department of Radiotherapy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.

Purpose: Eye-dedicated proton therapy (PT) facilities are used to treat malignant intraocular lesions, especially uveal melanoma (UM). The first commercial ocular PT beamline from Varian was installed in the Netherlands. In this work, the conceptual design of the new eyeline is presented. In addition, a comprehensive comparison against five PT centers with dedicated ocular beamlines is performed, and the clinical impact of the identified differences is analyzed.

Material/methods: The HollandPTC eyeline was characterized. Four centers in Europe and one in the United States joined the study. All centers use a cyclotron for proton beam generation and an eye-dedicated nozzle. Differences among the chosen ocular beamlines were in the design of the nozzle, nominal energy, and energy spectrum. The following parameters were collected for all centers: technical characteristics and a set of distal, proximal, and lateral region measurements. The measurements were performed with detectors available in-house at each institution. The institutions followed the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice for absolute dose measurement, and the IAEA TRS-398 Code of Practice, its modified version or International Commission on Radiation Units and Measurements Report No. 78 for spread-out Bragg peak normalization. Energy spreads of the pristine Bragg peaks were obtained with Monte Carlo simulations using Geant4. Seven tumor-specific case scenarios were simulated to evaluate the clinical impact among centers: small, medium, and large UM, located either anteriorly, at the equator, or posteriorly within the eye. Differences in the depth dose distributions were calculated.

Results: A pristine Bragg peak of HollandPTC eyeline corresponded to the constant energy of 75 MeV (maximal range 3.97 g/cm in water) with an energy spread of 1.10 MeV. The pristine Bragg peaks for the five participating centers varied from 62.50 to 104.50 MeV with an energy spread variation between 0.10 and 0.70 MeV. Differences in the average distal fall-offs and lateral penumbrae (LPs) (over the complete set of clinically available beam modulations) among all centers were up to 0.25 g/cm , and 0.80 mm, respectively. Average distal fall-offs of the HollandPTC eyeline were 0.20 g/cm , and LPs were between 1.50 and 2.15 mm from proximal to distal regions, respectively. Treatment time, around 60 s, was comparable among all centers. The virtual source-to-axis distance of 120 cm at HollandPTC was shorter than for the five participating centers (range: 165-350 cm). Simulated depth dose distributions demonstrated the impact of the different beamline characteristics among institutions. The largest difference was observed for a small UM located at the posterior pole, where a proximal dose between two extreme centers was up to 20%.

Conclusions: HollandPTC eyeline specifications are in accordance with five other ocular PT beamlines. Similar clinical concepts can be applied to expect the same high local tumor control. Dosimetrical properties among the six institutions induce most likely differences in ocular radiation-related toxicities. This interinstitutional comparison could support further research on ocular post-PT complications. Finally, the findings reported in this study could be used to define dosimetrical guidelines for ocular PT to unify the concepts among institutions.
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http://dx.doi.org/10.1002/mp.15024DOI Listing
June 2021

Current antibiotic resistance patterns of rare uropathogens: survey from Central European Urology Department 2011-2019.

BMC Urol 2021 Apr 13;21(1):61. Epub 2021 Apr 13.

Department of Urology, 3rd Faculty of Medicine, Charles University and Thomayer University Hospital, Videnska 800, 140 59, Prague, Czech Republic.

Background: While the resistance rates of commonly detected uropathogens are well described, those of less frequent Gram-negative uropathogenic bacteria have seldom been reported. The aim of this study was to examine the resistance rates of less frequent uropathogenic Gram-negatives in a population of patients treated in a Department of Urology of a tertiary referral centre in Central Europe over a period of 9 years.

Methods: Data on all positive urine samples from urological in- and out-patients were extracted form the Department of Clinical Microbiology database from 2011 to 2019. Numbers of susceptible and resistant isolates per year were calculated for these uropathogens: Acinetobacter spp. (n = 74), Citrobacter spp. (n = 60), Enterobacter spp. (n = 250), Morganella morganii (n = 194), Providencia spp. (n = 53), Serratia spp. (n = 82) and Stenotrophomonas maltophilia (n = 27). Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin and colistin.

Results: Penicillin derivatives have generally poor effect except piperacillin/tazobactam. Cefuroxime is not efficient unlike cefotaxime (except against Acinetobacter spp. and S. maltophilia). Susceptibility to fluoroquinolones is limited. Amikacin is somewhat more efficient than gentamicine but susceptibilities for both safely exceed 80%. Nitrofurantoin shows virtually no efficiency. Cotrimoxazole acts well against Citrobacter spp., Serratia spp. and it is the treatment of choice for S. maltophilia UTIs. Among carbapenems, ertapenem was less efficient than meropenem and imipenem except for S. maltophilia whose isolates were mostly not suceptible to any carbapenems.

Conclusions: Uropathogenic microorganisms covered in this report are noteworthy for their frequently multi-drug resistant phenotypes. Knowledge of resistance patterns helps clinicians choose the right empirical antibiotic treatment when the taxonomical assignment of the isolate is known but sensitivity results are pending.
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http://dx.doi.org/10.1186/s12894-021-00821-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042353PMC
April 2021

Combining rescanning and gating for a time-efficient treatment of mobile tumors using pencil beam scanning proton therapy.

Radiother Oncol 2021 07 9;160:82-89. Epub 2021 Apr 9.

Center for Proton Therapy, Paul Scherrer Institute (PSI), Villigen PSI, Switzerland. Electronic address:

Background And Purpose: Respiratory motion during proton therapy can severely degrade dose distributions, particularly due to interplay effects when using pencil beam scanning. Combined rescanning and gating treatments for moving tumors mitigates dose degradation, but at the cost of increased treatment delivery time. The objective of this study was to identify the time efficiency of these dose degradation-motion mitigation strategies for different range of motions.

Materials And Methods: Seventeen patients with thoracic or abdominal tumors were studied. Tumor motion amplitudes ranged from 2-30 mm. Deliveries using different combinations of rescanning and gating were simulated with a dense dose spot grid (4 × 4 × 2.5 mm) for all patients and a sparse dose spot grid (8 × 8 × 5 mm) for six patients with larger tumor movements (>8 mm). The resulting plans were evaluated in terms of CTV coverage and time efficiency.

Results: Based on the studied patient cohort, it has been shown that for amplitudes up to 5 mm, no motion mitigation is required with a dense spot grid. For amplitudes between 5 and 10 mm, volumetric rescanning should be applied while maintaining a 100% duty cycle when using a dense spot grid. Although gating could be envisaged to reduce the target volume for intermediate motion, it has been shown that the dose to normal tissues would only be reduced marginally. Moreover, the treatment time would increase. Finally, for larger motion amplitudes, both volumetric rescanning and respiratory gating should be applied with both spot grids. In addition, it has been shown that a dense spot grid delivers better CTV dose coverage than a sparse dose grid.

Conclusion: Volumetric rescanning and/or respiratory gating can be used in order to effectively and efficiently mitigate dose degradation due to tumor movement.
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http://dx.doi.org/10.1016/j.radonc.2021.03.041DOI Listing
July 2021

Good long-term visual outcomes of parapapillary choroidal melanoma patients treated with proton therapy: a comparative study.

Int Ophthalmol 2021 Feb 25;41(2):441-452. Epub 2020 Sep 25.

Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.

Purpose: To evaluate why small- and certain medium-sized parapapillary choroidal melanoma (pcM) patients treated with hypo-fractionated proton therapy (PT) retain excellent long-term visual acuity (VA) and assess the negative predictive factors for retaining good vision (≤ 0.2 logMAR (≥ 0.6 decimal) after 5 years.

Methods: This single-center, retrospective, comparative study recruited consecutive pcM patients that were treated with PT. Between 1984 and 2005, 609 patients received a total of 60 CGE, of whom 310 met the following inclusion criteria: posterior tumor border ≤ 2.5 mm from the optic disc, largest tumor diameter ≤ 17.9 mm, tumor thickness ≤ 5.2 mm and available follow-up data for at least 5 years.

Results: Mean follow-up was 120.8 ± 48.8 months (54.0-295.0). Out of 310 patients, 64 (21%) maintained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years following PT and were allocated to the "good visual outcome" (GVO) group, while the remaining 246 (79%) constituted the "poor visual outcome" (PVO) group, subdivided into 70 (22%) with a VA of 0.3-1.0 logMAR (0.1-0.5 decimal) and 157 (57%) patients with a VA > 1.0 logMAR (< 0.1 decimal). On multivariate analysis, older age (P = 0.04), tumor localization ≤ 0.5 mm to the fovea (P < 0.03), volume of the optic disc and macula receiving 50% of dose (30 CGE) (P = 0.02 and P < 0.001, respectively) were independent negative predictors of GVO.

Conclusions: Of 310 small- to medium-sized pcM patients successfully treated with PT, 21% retained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years. Strongest negative predictive factor for retaining good long-term vision was the volume of the macula irradiated with at least 30 Gy.
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http://dx.doi.org/10.1007/s10792-020-01594-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882567PMC
February 2021

Current Antibiotic Resistance Trends of Uropathogens in Central Europe: Survey from a Tertiary Hospital Urology Department 2011-2019.

Antibiotics (Basel) 2020 Sep 22;9(9). Epub 2020 Sep 22.

Department of Urology, 3rd Faculty of Medicine, Charles University and Thomayer Hospital, Videnska 800, 140 59 Prague, Czech Republic.

Monitoring of pathogen resistance profiles is necessary to guide empirical antibiotic therapy before culture and sensitivity results become available. The aim of this study was to describe current antibiotic resistance patterns of five most frequent causative uropathogens in a Department of Urology of a tertiary referral centre in Central Europe over a period of nine years. The Hospital Department of Clinical Microbiology database was used to extract data on all positive urine samples from inpatients in the Department of Urology between 2011 and 2019. Numbers of susceptible and resistant isolates per year were calculated for five most frequent uropathogens: spp., spp., , and spp. Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin, colistin, and vancomycin. High resistance rates of Gram-negative uropathogens were demonstrated to most common antimicrobials, with statistically significant increasing or decreasing trends in some cases. No carbapenem-resistant were isolated. Vancomycin-resistant spp. strains were rare in our population.
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http://dx.doi.org/10.3390/antibiotics9090630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559630PMC
September 2020

Potential and pitfalls of 1.5T MRI imaging for target volume definition in ocular proton therapy.

Radiother Oncol 2021 01 3;154:53-59. Epub 2020 Sep 3.

Paul Scherrer Institut (PSI), Center for Proton Therapy, Switzerland.

Introduction: Ocular proton therapy (OPT) for the treatment of uveal melanoma has a long and remarkably successful history. This is despite that, for the majority of patients treated, the definition of the eye anatomy is based on a simplified geometrical model embedded in the treatment planning system EyePlan. In this study, differences in anatomical and tumor structures from EyePlan, and those based on 1.5T magnetic resonance imaging (MRI) are assessed.

Materials And Methods: Thirty-three uveal melanoma patients treated with OPT at our institution were subject to eye MRI. The target volumes were manually delineated on those images by two radiation oncologists. The resulting volumes were geometrically compared to the clinical standard. In addition, the dosimetric impact of using different models for treatment planning were evaluated.

Results: Two patients (6%) presented lesions too small to be visible on MRI. Target volumes identified on MRI scans were on average smaller than EyePlan with discrepancies arising mostly from the definition of the tumor base. Clip-to-tumor base distances measured on MRI models exhibited higher discrepancy to ophthalmological measurements than EyePlan. For 53% of cases, treatment plans optimized for lesions identified on MRI only, failed to achieve sufficient target coverage for EyePlan volumes.

Discussion: The analysis has shown that 1.5T MRI might be more susceptible to misses of flat tumor extension of the clinical target volume than the current clinical standard. Thus, a proper integration of ancillary imaging modalities, leading to a better characterization of the full lesion, is required.
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http://dx.doi.org/10.1016/j.radonc.2020.08.023DOI Listing
January 2021

Outcomes of adolescents and young adults treated for brain and skull base tumors with pencil beam scanning proton therapy.

Pediatr Blood Cancer 2020 12 2;67(12):e28664. Epub 2020 Sep 2.

Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.

Background: The use of proton therapy (PT) in adolescents and young adults (AYAs) is becoming increasingly popular. This study aims to assess the outcomes and late toxicity consequences in AYAs (15-39 years) with brain/skull base tumors treated with pencil beam scanning proton therapy.

Methods: One hundred seventy six AYAs treated curatively at the Paul Scherrer Institute (PSI) were identified. Median age was 30 years (range 15-39) and median prescribed dose was 70.0 Gy (relative biological effectiveness [RBE]) (range 50.4-76.0). The most common tumors treated were chordomas/chondrosarcomas (61.4%), followed by gliomas (15.3%), and meningiomas (14.2%).

Results: After a median follow up of 66 months (range 12-236), 24 (13.6%) local only failures and one (0.6%) central nervous system (CNS) distant only failure were observed. The 6-year local control, distant progression-free survival, and overall survival were 83.2%, 97.4%, and 90.2%, respectively. The 6-year high-grade (≥grade [G] 3) PT-related late toxicity-free survival was 88.5%. Crude late toxicity rates were 26.2% G1, 37.8% G2, 12.2% G3, 0.6% G4, and 0.6% G5. The one G4 toxicity was a retinopathy and one G5 toxicity was a brainstem hemorrhage. The 6-year cumulative incidences for any late PT-related pituitary, ototoxicity, and neurotoxicity were 36.3%, 18.3%, and 25.6%; whilst high-grade (≥G3) ototoxicity and neurotoxicity were 3.4% and 2.9%, respectively. No secondary malignancies were observed. The rate of unemployment was 9.5% pre-PT, increasing to 23.8% post-PT. Sixty-two percent of survivors were working whilst 12.7% were in education post-PT.

Conclusions: PT is an effective treatment for brain/skull base tumors in the AYA population with a reasonable late toxicity profile. Despite good clinical outcomes, around one in four AYA survivors are unemployed after treatment.
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http://dx.doi.org/10.1002/pbc.28664DOI Listing
December 2020

Commissioning and Quality Assurance of a novel solution for respiratory-gated PBS proton therapy based on optical tracking of surface markers.

Z Med Phys 2020 Aug 20. Epub 2020 Aug 20.

Center for Proton Therapy, Paul Scherrer Institute, 5232 Villigen, Switzerland.

We present the commissioning and quality assurance of our clinical protocol for respiratory gating in pencil beam scanning proton therapy for cancer patients with moving targets. In a novel approach, optical tracking has been integrated in the therapy workflow and used to monitor respiratory motion from multiple surrogates, applied on the patients' chest. The gating system was tested under a variety of experimental conditions, specific to proton therapy, to evaluate reaction time and reproducibility of dose delivery control. The system proved to be precise in the application of beam gating and allowed the mitigation of dose distortions even for large (1.4cm) motion amplitudes, provided that adequate treatment windows were selected. The total delivered dose was not affected by the use of gating, with measured integral error within 0.15cGy. Analysing high-resolution images of proton transmission, we observed negligible discrepancies in the geometric location of the dose as a function of the treatment window, with gamma pass rate greater than 95% (2%/2mm) compared to stationary conditions. Similarly, pass rate for the latter metric at the 3%/3mm level was observed above 97% for clinical treatment fields, limiting residual movement to 3mm at end-exhale. These results were confirmed in realistic clinical conditions using an anthropomorphic breathing phantom, reporting a similarly high 3%/3mm pass rate, above 98% and 94%, for regular and irregular breathing, respectively. Finally, early results from periodic QA tests of the optical tracker have shown a reliable system, with small variance observed in static and dynamic measurements.
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http://dx.doi.org/10.1016/j.zemedi.2020.07.001DOI Listing
August 2020

Clinical outcomes of head and neck adenoid cystic carcinoma patients treated with pencil beam-scanning proton therapy.

Oral Oncol 2020 08 12;107:104752. Epub 2020 May 12.

Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Switzerland; Radiation Oncology Department, University Hospital Zürich, Zürich, Switzerland; Radiation Oncology Department, University Hospital Bern, Inselspital, Bern, Switzerland. Electronic address:

Objective: The aim of this study was to evaluate the outcome of patients with head and neck adenoid cystic carcinoma (ACC) treated using pencil beam scanning proton therapy (PBS PT) at our institution.

Materials And Methods: Thirty-five patients who underwent treatment with PBS PT for ACC between 2001 and 2017 were included. Local control (LC), distant control (DC), progression-free survival (PFS), overall survival (OS) and their prognostic factors were evaluated. Adverse effects were prospectively assessed.

Results: The median patient follow-up was 30 months. Prior to PT, 26 patients (74.3%) underwent surgery with R0/R1/R2 outcome in 5, 13 and 8 cases, respectively. Nine patients (25.7%) presented with inoperable disease. The 2-year LC, DC, PFS and OS was 92.2%, 77.8%, 74.3% and 88.8%, respectively. LC was influenced by patient age (p = 0.002) with a significant difference between local and distant failure (median 61.3 vs. 42.3 years, p = 0.005). Tumor T stage was a significant risk factor for PFS (p = 0.045) and tumor prognostic group affected OS (p = 0.049). No significant survival advantage for operable vs. inoperable disease could be identified. The acute and late grade 3 toxicity rates were 14.3% and 6.1%, respectively. No acute or late grade 4/5 toxicities were observed.

Conclusions: PBS PT is an effective and safe treatment for patients with head & neck ACC in both definitive and adjuvant setting. Distant metastases are the main pattern of failure. Age, tumor stage and clinical stage had a significant negative impact on LC, OS and PFS.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104752DOI Listing
August 2020

Practice Considerations for Proton Beam Radiation Therapy of Uveal Melanoma During the Coronavirus Disease Pandemic: Particle Therapy Co-Operative Group Ocular Experience.

Adv Radiat Oncol 2020 Jul-Aug;5(4):682-686. Epub 2020 Apr 23.

Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.

Uveal melanoma (UM) is a rare but life-threatening cancer of the eye. In light of the coronavirus disease (COVID-19) pandemic, hospitals and proton eye therapy facilities must analyze several factors to ensure appropriate treatment protocols for patients and provider teams. Practice considerations to limit COVID-19 transmission in the proton ocular treatment setting for UM are necessary. The Particle Therapy Co-Operative Group is the largest international community of particle/proton therapy providers. Participating experts have current or former affiliation with the member institutions of the Particle Therapy Co-Operative Group Ocular subcommittee with long-standing high-volume proton ocular programs. The practices reviewed in this document must be taken in conjunction with local hospital procedures, multidisciplinary recommendations, and regional/national guidelines, as each community may have its unique needs, supplies, and protocols. Importantly, as the pandemic evolves, so will the strategies and recommendations. Given the unique circumstances for UM patients, along with indications of potential ophthalmologic transmission as a result of health care providers working in close proximity to patients and intrinsic infectious risk from eyelashes, tears, and hair, practice strategies may be adapted to reduce the risk of viral transmission. Certainly, providers and health care systems will continue to examine and provide as safe and effective care as possible for patients in the current environment.
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http://dx.doi.org/10.1016/j.adro.2020.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179507PMC
April 2020

Technical Note: Benchmarking automated eye tracking and human detection for motion monitoring in ocular proton therapy.

Med Phys 2020 Jun 10;47(5):2237-2241. Epub 2020 Mar 10.

Paul Scherrer Institut (PSI), Center for Proton Therapy, 5232, Villigen PSI, Switzerland.

Purpose: Ocular proton therapy is an effective therapeutic option for patients affected with uveal melanomas. An optical eye-tracking system (ETS) aiming at noninvasive motion monitoring was developed and tested in a clinical scenario.

Materials And Methods: The ETS estimates eye position and orientation at 25 frames per second using the three-dimensional position of pupil and cornea curvature centers identified, in the treatment room, through stereoscopic optical imaging and infrared eye illumination. Its capabilities for automatic detection of eye motion were retrospectively evaluated on 60 treatment fractions. Then, the ETS performance was benchmarked against the clinical standard based on visual control and manual beam interruption.

Results: Eye-tracking system detected eye position successfully in 97% of all available frames. Eye-tracking system-based eye monitoring during therapy guarantees quicker response to involuntary eye motions than manual beam interruptions and avoids unnecessary beam interruptions.

Conclusions: Eye-tracking system shows promise for on-line monitoring of eye motion. Its introduction in the clinical workflow will guarantee a swifter treatment course for the patient and the clinical personnel.
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http://dx.doi.org/10.1002/mp.14087DOI Listing
June 2020

Benchmarking a commercial proton therapy solution: The Paul Scherrer Institut experience.

Br J Radiol 2020 Mar 30;93(1107):20190920. Epub 2020 Jan 30.

Zentrum für Protonentherapie, Paul Scherrer Institut, Villigen, Switzerland.

Objective: For the past 20 years, Paul Scherrer Institut (PSI) has treated more than 1500 patients with deep-seated tumors using PSI-Plan, an in-house developed treatment planning system (TPS) used for proton beam scanning proton therapy, in combination with its home-built gantries. The goal of the present work is to benchmark the performance of a new TPS/Gantry system for proton therapy centers which have established already a baseline standard of care.

Methods And Materials: A total of 31 cases (=52 plans) distributed around 7 anatomical sites and 12 indications were randomly selected and re-planned using Eclipse™. The resulting plans were compared with plans formerly optimized in PSI-Plan, in terms of target coverage, plan quality, organ-at-risk (OAR) sparing and number of delivered pencil beams.

Results: Our results show an improvement on target coverage and homogeneity when using Eclipse™ while PSI-Plan showed superior plan conformity. As for OAR sparing, both TPS achieved the clinical constraints. The number of pencil beams required per plan was on average 3.4 times higher for PSI-Plan.

Conclusion: Both systems showed a good capacity to produce satisfactory plans, with Eclipse™ being able to achieve better target coverage and plan homogeneity without compromising OARs.

Advances In Knowledge: A benchmark between a clinically tested and validated system with a commercial solution is of interest for emerging proton therapy, equipped with commercial systems and no previous experience with proton beam scanning.
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http://dx.doi.org/10.1259/bjr.20190920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066977PMC
March 2020

Use of Prostate Specific Antigen Density Combined with Multiparametric Magnetic Resonance Imaging Improves Triage for Prostate Biopsy.

Urol Int 2019 8;103(1):33-40. Epub 2019 May 8.

Department of Urology, Thomayer Hospital, Prague, Czechia,

Background: Multi-parametric magnetic resonance imaging (mpMRI)-directed biopsy for prostate cancer (PC) diagnosis improves the detection of clinically significant prostate cancer (CSPC) and decreases the rate of over-diagnosis of insignificant disease. The aim of this study was to investigate the value of mpMRI combined with prostate specific antigen density (PSAD) in the decision making related to the biopsy.

Methods: mpMRI and mpMRI/transrectal ultrasound fusion targeted biopsies with subsequent systematic biopsies were performed in 397 patients (223 biopsy-naïve and 174 with a previous biopsy). Detection rates of (CSPC) and insignificant PC were stratified using the PIRADS score, and the number of avoidable biopsies and missed (CSPC) were plotted against PSAD values of 0.1-0.5 ng/mL2.

Results: PIRADS <3 and PSAD <0.2 ng/mL2 were the safest criteria for not performing a biopsy. When applied to the biopsy-naïve group, 21.5% (48/223) of the biopsies could have been avoided and 3.7% (3/82) of CSPC would have been missed. In the repeat biopsy group, 12.6% (22/174) of biopsies could have been avoided and 6.9% (4/58) of (CSPC) would have been missed.

Conclusions: A combination of mpMRI and PSAD might reduce the number of biopsies performed with the cost of missing <4% of CSPC.
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http://dx.doi.org/10.1159/000500350DOI Listing
February 2020

Evaluation of the ray-casting analytical algorithm for pencil beam scanning proton therapy.

Phys Med Biol 2019 03 18;64(6):065021. Epub 2019 Mar 18.

Centre for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland. Department of Physics, ETH Zurich, Zurich, Switzerland.

For pencil beam scanned (PBS) proton therapy, analytical dose calculation engines are still typically used for the optimisation process, and often for the final evaluation of the plan. Recently however, the suitability of analytical calculations for planning PBS treatments has been questioned. Conceptually, the two main approaches for these analytical dose calculations are the ray-casting (RC) and the pencil-beam (PB) method. In this study, we compare dose distributions and dosimetric indices, calculated on both the clinical dose calculation grid and as a function of dose grid resolution, to Monte Carlo (MC) calculations. The analysis is done using a comprehensive set of clinical plans which represent a wide choice of treatment sites. When analysing dose difference histograms for relative treatment plans, pencil beam calculations with double grid resolution perform best, with on average 97.7%/91.9% (RC), 97.9%/92.7% (RC, double grid resolution), 97.6%/91.0% (PB) and 98.6%/94.0% (PB, double grid resolution) of voxels agreeing within  ±5%/±  3% between the analytical and the MC calculations. Even though these point-to-point dose comparison shows differences between analytical and MC calculations, for all algorithms, clinically relevant dosimetric indices agree within  ±4% for the PTV and within  ±5% for critical organs. While the clinical agreement depends on the treatment site, there is no substantial difference of indices between the different algorithms. The pencil-beam approach however comes at a higher computational cost than the ray-casting calculation. In conclusion, we would recommend using the ray-casting algorithm for fast dose optimization and subsequently combine it with one MC calculation to scale the absolute dose and assure the quality of the treatment plan.
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http://dx.doi.org/10.1088/1361-6560/aafe58DOI Listing
March 2019

Automated Knowledge-Based Intensity-Modulated Proton Planning: An International Multicenter Benchmarking Study.

Cancers (Basel) 2018 11 2;10(11). Epub 2018 Nov 2.

Cancer Center Amsterdam, Department of Radiation Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

Radiotherapy treatment planning is increasingly automated and knowledge-based planning has been shown to match and sometimes improve upon manual clinical plans, with increased consistency and efficiency. In this study, we benchmarked a novel prototype knowledge-based intensity-modulated proton therapy (IMPT) planning solution, against three international proton centers. A model library was constructed, comprising 50 head and neck cancer (HNC) manual IMPT plans from a single center. Three external-centers each provided seven manual benchmark IMPT plans. A knowledge-based plan (KBP) using a standard beam arrangement for each patient was compared with the benchmark plan on the basis of planning target volume (PTV) coverage and homogeneity and mean organ-at-risk (OAR) dose. PTV coverage and homogeneity of KBPs and benchmark plans were comparable. KBP mean OAR dose was lower in 32/54, 45/48 and 38/53 OARs from center-A, -B and -C, with 23/32, 38/45 and 23/38 being >2 Gy improvements, respectively. In isolated cases the standard beam arrangement or an OAR not being included in the model or being contoured differently, led to higher individual KBP OAR doses. Generating a KBP typically required <10 min. A knowledge-based IMPT planning solution using a single-center model could efficiently generate plans of comparable quality to manual HNC IMPT plans from centers with differing planning aims. Occasional higher KBP OAR doses highlight the need for beam angle optimization and manual review of KBPs. The solution furthermore demonstrated the potential for robust optimization.
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http://dx.doi.org/10.3390/cancers10110420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266684PMC
November 2018

Personalized Anatomic Eye Model From T1-Weighted Volume Interpolated Gradient Echo Magnetic Resonance Imaging of Patients With Uveal Melanoma.

Int J Radiat Oncol Biol Phys 2018 11 14;102(4):813-820. Epub 2018 May 14.

Radiology Department, Lausanne University Hospital, Lausanne, Switzerland; Medica Image Analysis Laboratory, Centre d'Imagerie BioMédicale, University of Lausanne, Lausanne, Switzerland; Signal Processing Laboratory, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Purpose: We present a 3-dimensional patient-specific eye model from magnetic resonance imaging (MRI) for proton therapy treatment planning of uveal melanoma (UM). During MRI acquisition of UM patients, the point fixation can be difficult and, together with physiological blinking, can introduce motion artifacts in the images, thus challenging the model creation. Furthermore, the unclear boundary of the small objects (eg, lens, optic nerve) near the muscle or of the tumors with hemorrhage and tantalum clips can limit model accuracy.

Methods And Materials: A dataset of 37 subjects, including 30 healthy eyes of volunteers and 7 eyes of UM patients, was investigated. In our previous work, active shape model was successfully applied to retinoblastoma eye segmentation in T1-weighted 3T MRI. Here, we evaluate this method in a more challenging setting, based on 1.5T MRI acquisition and different datasets of awake adult eyes with UM. The lens and cornea together with the sclera, vitreous humor, and optic nerve were automatically segmented and validated against manual delineations of a senior ocular radiation oncologist, in terms of the Dice similarity coefficient and Hausdorff distance.

Results: Leave-one-out cross validation (mixing both volunteers and UM patients) yielded median Dice similarity coefficient values (respective of Hausdorff distance) of 94.5% (1.64 mm) for the sclera, 92.2% (1.73 mm) for the vitreous humor, 88.3% (1.09 mm) for the lens, and 81.9% (1.86 mm) for the optic nerve. The average computation time for an eye was 10 seconds.

Conclusions: To our knowledge, our work is the first attempt to automatically segment adult eyes, including patients with UM. Our results show that automated active shape model segmentation can succeed in the presence of motion, tumors, and tantalum clips. These results are promising for inclusion in clinical practice.
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http://dx.doi.org/10.1016/j.ijrobp.2018.05.004DOI Listing
November 2018

Automated Treatment Planning System for Uveal Melanomas Treated With Proton Therapy: A Proof-of-Concept Analysis.

Int J Radiat Oncol Biol Phys 2018 07 13;101(3):724-731. Epub 2018 Feb 13.

Centre for Proton Therapy, Paul Scherrer Institut, Villigen, Switzerland.

Purpose: By precalculation of an entire set of planning solutions for protons, penalizing them and providing a graphical navigator tool (Automated Treatment Planning [ATP]), we aim to improve the efficiency of the planning procedure for uveal melanoma (UM) and make it independent of treatment planner experience.

Methods And Materials: A phase space of plans is evaluated by transforming the eye model in each gaze angle, calculating cumulative dose-volume histograms for each position, and defining a dose-volume constraint for each considered structure. The final result is a map of the plan phase space, displaying how many criteria are fulfilled for each gaze angle.

Results: To test its usability and performance, ATP was used retrospectively on 48 UM patients treated with protons. In 36 of 48 cases (75%), the planning result was either the same (13 of 48, 27%) or comparable (23 of 48, 48%). In 11 of 48 evaluated cases (23%), ATP plans showed improvements. In 1 case (2%) the patient's visual acuity had been impaired, and an optimization was not possible.

Conclusions: We have developed a dose calculation and planning engine that prepares a set of treatment plans covering a wide range of theoretical clinically feasible gaze angles for a given patient, by precalculating the dose distributions for each gaze angle. By considering different structures and adapting their constraints, the identification of the optimal gaze angle can be realized. With a better understanding of the dose-volume constraints and the development of strategies to react to the trade-offs between considered structures, ATP may lead to a complete automation of the planning process for UM treated with proton therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2018.02.008DOI Listing
July 2018

Range resolution and reproducibility of a dedicated phantom for proton PBS daily quality assurance.

Z Med Phys 2018 Dec 13;28(4):310-317. Epub 2018 Mar 13.

Centre for Proton Therapy, Paul Scherrer Institut, 5232 Villigen, Switzerland.

Purpose: Wedge phantoms coupled with a CCD camera are suggested as a simple means to improve the efficiency of quality assurance for pencil beam scanning (PBS) proton therapy, in particular to verify energy/range consistency on a daily basis. The method is based on the analysis of an integral image created by a pencil beam (PB) pattern delivered through a wedge. We have investigated the reproducibility of this method and its dependence on setup and positional beam errors for a commercially available phantom (Sphinx, IBA Dosimetry) and CCD camera (Lynx, IBA Dosimetry) system.

Material And Methods: The phantom includes 4 wedges of different thickness, allowing verification of the range for 4 energies within one integral image. Each wedge was irradiated with a line pattern of clinical energies (120, 150, 180 and 230MeV). The equipment was aligned to the isocenter using lasers, and the delivery was repeated for 5 consecutive days, 4 times each day. Range was computed using the myQA software (IBA Dosimetry) and inter- and intra-setup uncertainty were calculated. Dependence of range on energy was investigated delivering the same pencil beam pattern but with energy variations in steps of ±0.2MeV for all the nominal energies, up to ±1.0MeV. Possible range uncertainties, caused by setup and positional errors, were then simulated including inclination of the phantom, pencil beam and couch shifts.

Results: Intra position setup (based on in-room laser system) shows a maximum in plane difference within 1.5mm. Range reproducibility (standard deviation) was less than 0.14mm. Setup and beam errors did not affect significantly the results, except for a vertical shift of 10mm which leads to an error in the range computation.

Conclusion: Taking into account different day-to-day setup and beam errors, day-to-day determination of range has been shown to be reproducible using the proposed system.
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http://dx.doi.org/10.1016/j.zemedi.2018.02.001DOI Listing
December 2018

Noninvasive eye localization in ocular proton therapy through optical eye tracking: A proof of concept.

Med Phys 2018 May 23;45(5):2186-2194. Epub 2018 Mar 23.

Center for Proton Therapy, Paul Scherrer Institut, Villigen, PSI, 5232, Switzerland.

Purpose: Over the last four decades, Ocular Proton Therapy has been successfully used to treat patients affected by intraocular lesions. For this, treatment geometry verification is routinely performed using radiographic images to align a configuration of fiducial radiopaque markers implanted on the sclera outer surface. This paper describes the clinical application of an alternative approach based on optical eye tracking for three-dimensional noninvasive and automatic eye localization. An experimental protocol was designed to validate the optical-based eye referencing against both radiographic imaging system and the clinically used EYEPLAN treatment planning system.

Methods: The eye tracking system (ETS) was installed in the OPTIS 2 treatment room at PSI to acquire eye motions during the treatment of nine patients. The pupil position and the cornea curvature center were localized by segmenting the pupil contour and corneal light reflections on the images acquired by a pair of calibrated optical cameras. After calibration of the ETS, a direct comparison of radiopaque markers position, and consequentially eye position and orientation, provided by the ETS, radiographs and EYEPLAN was performed.

Results: Nineteen out of thirty total monitored fractions were excluded from the study due to poor visibility of corneal reflection, resulting in a success rate of acquisition of 37%. For these data, overall median agreement between ETS-based and x-ray-based markers position assessment were 0.29 mm and 0.94° for translations and rotations, respectively. Small discrepancies were also measured in the eye center estimates of the ETS and EYEPLAN. Conversely, variations in measured eye orientation were higher, with interquartile range (IQR) between 4.39° and 7.58°. Nonetheless, dosimetric evaluation of the consequence of ETS uncertainties showed that the target volume would still be covered by more than 95% of the dose in all cases.

Conclusion: An ETS was successfully installed in a clinical ocular proton therapy treatment room and used to monitor eye position and orientation in a clinical scenario. First results show the potential of such a system as an eye localization device. However, the low success rate prevents straightforward clinical application and needs further improvements aimed at increasing corneal reflection visibility.
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http://dx.doi.org/10.1002/mp.12841DOI Listing
May 2018

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy.

Phys Med Biol 2018 03 1;63(5):055005. Epub 2018 Mar 1.

Paul Scherrer Institute (PSI), Center for Proton Therapy, 5232 Villigen PSI, Switzerland. Department of Physics, ETH Zurich, 8092 Zurich, Switzerland.

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6[Formula: see text] layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with [Formula: see text]5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.
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http://dx.doi.org/10.1088/1361-6560/aaad1eDOI Listing
March 2018

The meaning of sampling density in multiple repeat prostate biopsies.

Cent European J Urol 2016 30;69(4):347-352. Epub 2016 Nov 30.

Department of Urology, 1 Faculty of Medicine and General Teaching Hospital, Charles University Praha, Czech Republic.

Introduction: Extended transrectal ultrasound-guided prostate biopsy is a state-of-the-art tool for prostate cancer detection. Nevertheless, approximately 1/3 of cancers are missed when using this method and repeat biopsy sessions are often required. The aim of this study was to investigate how sampling density (a compound variable reflecting the number of biopsy cores and prostate volume) impacts on detection rate in multiple repeat TRUS-biopsies.

Material And Methods: A total of 1007 consecutive patients undergoing their 1, 2, 3 and any further repeat prostate biopsies were included. The relationship between sampling density and other clinical variables (age, prostate-specific antigen level, free/total PSA ratio, digital rectal examination, number of previous biopsies) and cancer detection rate were assessed by interaction analysis.

Results: There were 562 primary re-biopsies, 267 second re-biopsies and 178 third and further re-biopsies included in the study. Detection rate was 25.4%, 25.8% and 25.3%, respectively. Interaction of sampling density with age was demonstrated in patients undergoing their first repeat biopsy (but not further re-biopsies). No interaction was observed with other variables investigated.

Conclusions: A more extensive prostate sampling leads to a higher cancer detection rate on repeat prostate biopsies, as shown previously. However, this effect seems to be particularly pronounced in men younger than 65 years undergoing their first repeat prostate biopsy.
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http://dx.doi.org/10.5173/ceju.2016.910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260465PMC
November 2016

Comparison of MicroRNA Content in Plasma and Urine Indicates the Existence of a Transrenal Passage of Selected MicroRNAs.

Adv Exp Med Biol 2016 ;924:97-100

Department of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General Faculty Hospital in Prague, Prague, Czech Republic.

MicroRNAs (miRNAs) in urine are examined as potential biomarkers. We examined the urine samples from 70 individuals (45 males, 25 females, mean age 65 years, range 20-84 years). Of the urine donors, 15 were healthy volunteers, 5 were patients with non-cancer diseases, 50 were patients with different stages of bladder cancer. To examine the spectrum of miRNAs in the cell-free fraction of urine, TaqMan Human miRNA Array Card A v.2.1 was used. A set of 30 miRNAs were found that are constantly present in urine supernatants independently of sex, age and health status of the subjects. We compared this set with miRNAs found in plasma, expressed in kidney and genito-urinary tract. Our results indicate that some miRNA could be transferred from the circulation into urine.
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http://dx.doi.org/10.1007/978-3-319-42044-8_18DOI Listing
September 2017

Oncological Outcomes of Patients with Concomitant Bladder and Urethral Carcinoma.

Urol Int 2016 28;97(2):134-41. Epub 2016 Jul 28.

Department of Urology, University of Michigan, Ann Arbor, Mich., USA.

Introduction: The study aimed to investigate oncological outcomes of patients with concomitant bladder cancer (BC) and urethral carcinoma.

Methods: This is a multicenter series of 110 patients (74 men, 36 women) diagnosed with urethral carcinoma at 10 referral centers between 1993 and 2012. Kaplan-Meier analysis was used to investigate the impact of BC on survival, and Cox regression multivariable analysis was performed to identify predictors of recurrence.

Results: Synchronous BC was diagnosed in 13 (12%) patients, and the median follow-up was 21 months (interquartile range 4-48). Urethral cancers were of higher grade in patients with synchronous BC compared to patients with non-synchronous BC (p = 0.020). Patients with synchronous BC exhibited significantly inferior 3-year recurrence-free survival (RFS) compared to patients with non-synchronous BC (63.2 vs. 34.4%; p = 0.026). In multivariable analysis, inferior RFS was associated with clinically advanced nodal stage (p < 0.001), proximal tumor location (p < 0.001) and synchronous BC (p = 0.020).

Conclusion: The synchronous presence of BC in patients diagnosed with urethral carcinoma has a significant adverse impact on RFS and should be an impetus for a multimodal approach.
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http://dx.doi.org/10.1159/000448335DOI Listing
April 2017

Practice Patterns Analysis of Ocular Proton Therapy Centers: The International OPTIC Survey.

Int J Radiat Oncol Biol Phys 2016 May 28;95(1):336-343. Epub 2016 Jan 28.

Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.

Purpose: To assess the planning, treatment, and follow-up strategies worldwide in dedicated proton therapy ocular programs.

Methods And Materials: Ten centers from 7 countries completed a questionnaire survey with 109 queries on the eye treatment planning system (TPS), hardware/software equipment, image acquisition/registration, patient positioning, eye surveillance, beam delivery, quality assurance (QA), clinical management, and workflow.

Results: Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014. Most centers treated a vast number of ocular patients (1729 to 6369). Three centers treated fewer than 200 ocular patients. Most commonly, the centers treated uveal melanoma (UM) and other primary ocular malignancies, benign ocular tumors, conjunctival lesions, choroidal metastases, and retinoblastomas. The UM dose fractionation was generally within a standard range, whereas dosing for other ocular conditions was not standardized. The majority (80%) of centers used in common a specific ocular TPS. Variability existed in imaging registration, with magnetic resonance imaging (MRI) rarely being used in routine planning (20%). Increased patient to full-time equivalent ratios were observed by higher accruing centers (P=.0161). Generally, ophthalmologists followed up the post-radiation therapy patients, though in 40% of centers radiation oncologists also followed up the patients. Seven centers had a prospective outcomes database. All centers used a cyclotron to accelerate protons with dedicated horizontal beam lines only. QA checks (range, modulation) varied substantially across centers.

Conclusions: The first worldwide multi-institutional ophthalmic proton therapy survey of the clinical and technical approach shows areas of substantial overlap and areas of progress needed to achieve sustainable and systematic management. Future international efforts include research and development for imaging and planning software upgrades, increased use of MRI, development of clinical protocols, systematic patient-centered data acquisition, and publishing guidelines on QA, staffing, treatment, and follow-up parameters by dedicated ocular programs to ensure the highest level of care for ocular patients.
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http://dx.doi.org/10.1016/j.ijrobp.2016.01.040DOI Listing
May 2016

With Gaze Tracking Toward Noninvasive Eye Cancer Treatment.

IEEE Trans Biomed Eng 2016 09 4;63(9):1914-1924. Epub 2015 Dec 4.

We present a new gaze tracking-based navigation scheme for proton beam radiation of intraocular tumors and we show the technical integration into the treatment facility. Currently, to treat a patient with such a tumor, a medical physicist positions the patient and the affected eye ball such that the radiation beam targets the tumor. This iterative eye positioning mechanism requires multiple X-rays, and radio-opaque clips previously sutured on the target eyeball. We investigate a possibility to replace this procedure with a noninvasive approach using a 3-D model-based gaze tracker. Previous work does not cover a comparably extensive integration of a gaze tracking device into a state-of-the-art proton beam facility without using additional hardware, such as a stereo optical tracking system. The integration is difficult because of limited available physical space, but only this enables to quantify the overall accuracy. We built a compact gaze tracker and integrated it into the proton beam radiation facility of the Paul Scherrer Institute in Villigen, Switzerland. Our results show that we can accurately estimate a healthy volunteer's point of gaze, which is the basis for the determination of the desired initial eye position. The proposed method is the first crucial step in order to make the proton therapy of the eye completely noninvasive.
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http://dx.doi.org/10.1109/TBME.2015.2505740DOI Listing
September 2016

Urinary Cell-Free DNA Quantification as Non-Invasive Biomarker in Patients with Bladder Cancer.

Urol Int 2016 3;96(1):25-31. Epub 2015 Sep 3.

Department of Urology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.

Introduction: Concentration of urinary cell-free DNA (ucfDNA) belongs to potential bladder cancer markers, but the reported results are inconsistent due to the use of various non-standardised methodologies. The aim of the study was to standardise the methodology for ucfDNA quantification as a potential non-invasive tumour biomarker.

Material And Methods: In total, 66 patients and 34 controls were enrolled into the study. Volumes of each urine portion (V) were recorded and ucfDNA concentrations (c) were measured using real-time PCR. Total amounts (TA) of ucfDNA were calculated and compared between patients and controls. Diagnostic accuracy of the TA of ucfDNA was determined.

Results: The calculation of TA of ucfDNA in the second urine portion was the most appropriate approach to ucfDNA quantification, as there was logarithmic dependence between the volume and the concentration of a urine portion (p = 0.0001). Using this methodology, we were able to discriminate between bladder cancer patients and subjects without bladder tumours (p = 0.0002) with area under the ROC curve of 0.725. Positive and negative predictive value of the test was 90 and 45%, respectively.

Conclusion: Quantification of ucf DNA according to our modified method could provide a potential non-invasive biomarker for diagnosis of patients with bladder cancer.
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http://dx.doi.org/10.1159/000438828DOI Listing
December 2016

External validation of extended prostate biopsy nomogram.

Cent European J Urol 2015 18;68(2):148-52. Epub 2015 May 18.

Department of Urology, 2 Faculty of Medicine and Motol University Hospital, Charles University Praha, Czech Republic.

Introduction: Historical nomograms for the prediction of cancer on prostate biopsy, developed in the sextant biopsy era are no more accurate today. The aim of this study was an independent external validation of a 10-core biopsy nomogram by Chun et al. (2007).

Material And Methods: A total of 322 patients who presented for their initial biopsy in a tertiary care center and had all the necessary data available were included in the retrospective analysis. To validate the nomogram, receiver operator characteristic (ROC) curves and calibration plots were constructed.

Results: Area under the ROC curve calculated for our data using the nomogram was 0.773, similar to that reported originally. However, the nomogram systematically overestimated prostate cancer risk, which, for our data, could be resolved by subtracting 24 points from the total number of points of the nomogram.

Conclusions: The nomogram yielded overall good predictive accuracy as measured by the area under the ROC curve, but it systematically overestimated PC probability in individual patients. However, we showed how the nomogram could easily be adapted to our patient sample, resolving the bias issue.
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http://dx.doi.org/10.5173/ceju.2015.610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526620PMC
August 2015

Prognostic factors and outcomes in primary urethral cancer: results from the international collaboration on primary urethral carcinoma.

World J Urol 2016 Jan 17;34(1):97-103. Epub 2015 May 17.

USC/Norris Comprehensive Cancer Center, Institute of Urology, Los Angeles, CA, USA.

Purpose: To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC).

Methods: A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death.

Results: Median age at definitive treatment was 66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p = 0.001), whereas clinical nodal stage was the only independent predictor for OS (p = 0.026).

Conclusions: These data suggest that clinical nodal stage is a critical parameter for outcomes in PUC.
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http://dx.doi.org/10.1007/s00345-015-1583-7DOI Listing
January 2016

Firing at a fly with a shotgun.

Authors:
Jan Hrbáček

Cent European J Urol 2015 ;68(1):95

Department of Urology, Charles University - 2 Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.

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http://dx.doi.org/10.5173/ceju.2015.01.e92DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408399PMC
April 2015
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