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Biomedical subjects

Uwe Schneider

Publications and source records attributed to Uwe Schneider.

At least 19 recordsLinked to original sources

Intensity modulated photon and proton therapy for the treatment of head and neck tumors.

PURPOSE: A comparative treatment planning study has been performed between intensity modulated photon and proton therapy to investigate the ability of both modalities to spare organs at risk in the head and neck region while keeping target dose homogeneous. Additional advantage of reducing the spot size for IMPT was also investigated. The treatment planning comparison was extended by varying the number of fields to study its effect on the performance of each modality. Risks of secondary cancer induction were also calculated for all modalities. MATERIALS AND METHODS: Five planning CTs were selected for the study. Four different constraints were set to the organs at risk in order to measure the resulting dose homogeneity in the target volume. Five and nine field plans were made for IMXT and 3, 5 and 9 field plans were made for IMPT, for both spot sizes. Dose homogeneity as a function of the mean parotid dose was visualized using a 'pseudo' Pareto-optimal front approach. Risks of secondary cancer were estimated using the organ equivalent dose model. RESULTS: Critical organs were best spared using 3-field IMPT and, at least for IMPT, little advantage was seen with increasing field numbers. Reducing the spot size does give an advantage. In contrast, there was a significant advantage in going from 5 to 9 fields for IMXT. Secondary cancer risk was lowest for the IMPT plans with reduced spot size, for which normal tissue received the lowest integral dose. Interestingly, although integral dose remained the same, increasing the number of IMPT fields increased the secondary cancer risk, due to the increased volume of tissue irradiated to low dose. CONCLUSIONS: IMPT has a better ability to spare organs at risk than IMXT for the same dose homogeneity. It also significantly reduced the estimated risk of secondary cancer induction and the use of small numbers of fields further increased this advantage. Given that target homogeneity and normal tissue sparing were equally good with the 3 field IMPT, there appears to be a clear rationale to deliver small numbers of fields for IMPT.

Carcinoma, Squamous Cell↗

Is the risk for secondary cancers after proton therapy enhanced distal to the Planning Target Volume? A two-case report with possible explanations.

It is often assumed that radiation-induced secondary cancer after proton therapy forms preferentially close to the distal fall-off of the spread-out Bragg peak because of an increased relative biological effectiveness (RBE) with regard to cancer induction of low-energy protons. In this study we analyze to what extent dose gradients distal to the Planning Target Volume (PTV) may, independently from the RBE, contribute to enhanced radiation carcinogenesis. The study is based on two dogs which, out of 30 dogs treated with proton therapy at the Paul Scherrer Institute (PSI), developed a secondary cancer. Both dogs were originally diagnosed and treated for a fibrosarcoma and developed an osteosarcoma 48 and almost 60 months, respectively, after radiotherapy. From the dose distributions of the initial radiotherapy for both dogs three-dimensional maps of secondary cancer complication probability (SCCP) were computed. The SCCP maps were analyzed in the regions where the dogs developed a secondary cancer. The SCCP maps showed an enhanced risk in the regions of the femur where the secondary cancers were detected, as compared to the SCCP of the total femur. Excess risk of radiation-induced cancer at the distal part of proton radiation fields can thus be explained using SCCP calculations on the basis of the physical dose distributions. Therefore, the occurrence of secondary cancer close to the distal dose gradients of proton therapy is not necessarily due to an increased RBE of low-energy protons. More extensive studies based on more patients will be necessary to further elucidate the factors influencing the development of secondary tumors.

Animals↗

The impact of IMRT and proton radiotherapy on secondary cancer incidence.

BACKGROUND AND PURPOSE: There is concern about the increase of radiation-induced malignancies with the application of modern radiation treatment techniques such as intensity-modulated radiotherapy (IMRT) and proton radiotherapy. Therefore, X-ray scatter and neutron radiation as well as the impact of the primary dose distribution on secondary cancer incidence are analyzed. MATERIAL AND METHODS: The organ equivalent dose (OED) concept with a linear-exponential and a plateau dose-response curve was applied to dose distributions of 30 patients who received radiation therapy of prostate cancer. Three-dimensional conformal radiotherapy was used in eleven patients, another eleven patients received IMRT with 6-MV photons, and eight patients were treated with spot-scanned protons. The treatment plans were recalculated with 15-MV and 18-MV photons. Secondary cancer risk was estimated based on the OED for the different treatment techniques. RESULTS: A modest increase of 15% radiation-induced cancer results from IMRT using low energies (6 MV), compared to conventional four-field planning with 15-MV photons (plateau dose-response: 1%). The probability to develop a secondary cancer increases with IMRT of higher energies by 20% and 60% for 15 MV and 18 MV, respectively (plateau dose-response: 2% and 30%). The use of spot-scanned protons can reduce secondary cancer incidence as much as 50% (independent of dose-response). CONCLUSION: By including the primary dose distribution into the analysis of radiation-induced cancer incidence, the resulting increase in risk for secondary cancer using modern treatment techniques such as IMRT is not as dramatic as expected from earlier studies. By using 6-MV photons, only a moderate risk increase is expected. Spot-scanned protons are the treatment of choice in regard to secondary cancer incidence.

Dose-Response Relationship, Radiation↗

Evaluation of a commercial electron treatment planning system based on Monte Carlo techniques (eMC).

A commercial electron beam treatment planning system on the basis of a Monte Carlo algorithm (Varian Eclipse, eMC V7.2.35) was evaluated. Measured dose distributions were used for comparison with dose distributions predicted by eMC calculations. Tests were carried out for various applicators and field sizes, irregular shaped cut outs and an inhomogeneity phantom for energies between 6 Me V and 22 MeV Monitor units were calculated for all applicator/energy combinations and field sizes down to 3 cm diameter and source-to-surface distances of 100 cm and 110 cm. A mass-density-to-Hounsfield-Units calibration was performed to compare dose distributions calculated with a default and an individual calibration. The relationship between calculation parameters of the eMC and the resulting dose distribution was studied in detail. Finally, the algorithm was also applied to a clinical case (boost treatment of the breast) to reveal possible problems in the implementation. For standard geometries there was a good agreement between measurements and calculations, except for profiles for low energies (6 MeV) and high energies (18 Me V 22 MeV), in which cases the algorithm overestimated the dose off-axis in the high-dose region. For energies of 12 MeV and higher there were oscillations in the plateau region of the corresponding depth dose curves calculated with a grid size of 1 mm. With irregular cut outs, an overestimation of the dose was observed for small slits and low energies (4% for 6 MeV), as well as for asymmetric cases and extended source-to-surface distances (12% for SSD = 120 cm). While all monitor unit calculations for SSD = 100 cm were within 3% compared to measure-ments, there were large deviations for small cut outs and source-to-surface distances larger than 100 cm (7%for a 3 cm diameter cut-out and a source-to-surface distance of 10 cm).

Algorithms↗

Complexity of heart rate fluctuations in near-term sheep and human fetuses during sleep.

We investigated how the complexity of fetal heart rate fluctuations (fHRF) is related to the sleep states in sheep and human fetuses. The complexity as a function of time scale for fetal heart rate data for 7 sheep and 27 human fetuses was estimated in rapid eye movement (REM) and non-REM sleep by means of permutation entropy and the associated Kullback-Leibler entropy. We found that in humans, fHRF complexity is higher in non-REM than REM sleep, whereas in sheep this relationship is reversed. To show this relation, choice of the appropriate time scale is crucial. In sheep fetuses, we found differences in the complexity of fHRF between REM and non-REM sleep only for larger time scales (above 2.5 s), whereas in human fetuses the complexity was clearly different between REM and non-REM sleep over the whole range of time scales. This may be due to inherent time scales of complexity, which reflect species-specific functions of the autonomic nervous system. Such differences have to be considered when animal data are translated to the human situation.

Algorithms↗

Fetal heart rate variability in growth restricted fetuses.

Intrauterine growth restriction (IUGR) remains a major problem in perinatal medicine because of the variety of its underlying causes and the prediction of its outcome. Characteristics of heartbeat interval patterns are associated with neuro-vegetative and humoral regulatory processes. Fetal magnetocardiography allows non-invasive assessment of these processes with high precision throughout the second half of gestation. The aim of our study was the analysis of linear and non-linear parameters of fetal heart rate fluctuations to distinguish between IUGR fetuses and a cohort of normal subjects, both pre-selected from heart-rate traces representing a quiet state of activity in the third trimester of gestation.

Algorithms↗

Radiation risk estimates after radiotherapy: application of the organ equivalent dose concept to plateau dose-response relationships.

Estimates of secondary cancer risk after radiotherapy are becoming more important for comparative treatment planning. Modern treatment planning systems provide accurate three-dimensional (3D) dose distributions for each individual patient. The dose distributions can be converted into organ equivalent doses to describe radiation-induced cancer after radiotherapy (OED(rad-ther)) in the irradiated organs. The OED(rad-ther) concept assumes that any two dose distributions in an organ are equivalent if they cause the same radiation-induced cancer risk. In this work, this concept is applied to dose-response relationships, which are leveling off at high dose. The organ-dependent operational parameter of this dose-response relationship was estimated by analyzing secondary cancer incidence data of patients with Hodgkin's disease. The dose distributions of a typical radiotherapy treatment plan for treating Hodgkin's disease was reconstructed. Dose distributions were calculated in individual organs from which cancer incidence data were available. The model parameter was obtained by comparing dose and cancer incidence rates for the individual organs.

Body Burden↗

Quantification of the response of circulating epithelial cells to neodadjuvant treatment for breast cancer: a new tool for therapy monitoring.

INTRODUCTION: In adjuvant treatment for breast cancer there is no tool available with which to measure the efficacy of the therapy. In contrast, in neoadjuvant therapy reduction in tumour size is used as an indicator of the sensitivity of tumour cells to the agents applied. If circulating epithelial (tumour) cells can be shown to react to therapy in the same way as the primary tumour, then this response may be exploited to monitor the effect of therapy in the adjuvant setting. METHOD: We used MAINTRAC analysis to monitor the reduction in circulating epithelial cells during the first three to four cycles of neoadjuvant therapy in 30 breast cancer patients. RESULTS: MAINTRAC analysis revealed a patient-specific response. Comparison of this response with the decline in size of the primary tumour showed that the reduction in number of circulating epithelial cells accurately predicted final tumour reduction at surgery if the entire neoadjuvant regimen consisted of chemotherapy. However, the response of the circulating tumour cells was unable to predict the response to additional antibody therapy. CONCLUSION: The response of circulating epithelial cells faithfully reflects the response of the whole tumour to adjuvant therapy, indicating that these cells may be considered part of the tumour and can be used for therapy monitoring.

Antineoplastic Combined Chemotherapy Protocols↗

Alkylchlorotins grafted to cross-linked polystyrene beads by a -(CH2)n- spacer (n=4, 6, 11): selective, clean and recyclable catalysts for transesterification reactions.

Insoluble polystyrene grafted compounds of the type (P-H)(1-t){P-(CH2)n SnBu(p)Cl(3-p)}(t), (P-H)(1-t){P-(CH2)n SnBuO}(t) and (P-H)(1-t)[{P-(CH2)n SnBuCl}2O](t/2), in which (P-H) is a cross-linked polystyrene; n=4, 6, and 11; p=0 and 1; and t the degree of functionalisation, were synthesised from Amberlite XE-305, a polystyrene cross-linked with divinylbenzene. The compounds were characterised by using elemental analysis, and IR, Raman, solid-state 117Sn NMR, and 1H and 119Sn high-resolution MAS NMR spectroscopy. The influence of the spacer length and the tin functionality on the catalytic activity of these compounds, as well as their recycling ability, was assessed in the transesterification reaction of ethyl acetate with various alcohols. These studies showed significant differences in the activity of the catalysts interpreted in terms of changes in the mobility of the catalytic centres. Some of the supported catalysts could be recycled at least seven times without noticeable loss of activity. The residual tin content in the reaction products was found to be as low as 3 ppm.

Journal Article↗

Estimation of radiation-induced cancer from three-dimensional dose distributions: Concept of organ equivalent dose.

PURPOSE: Estimates of secondary cancer risk after radiotherapy are becoming more important for comparative treatment planning. Modern treatment planning systems provide accurate three-dimensional dose distributions for each individual patient. These data open up new possibilities for more precise estimates of secondary cancer incidence rates in the irradiated organs. We report a new method to estimate organ-specific radiation-induced cancer incidence rates. The concept of an organ equivalent dose (OED) for radiation-induced cancer assumes that any two dose distributions in an organ are equivalent if they cause the same radiation-induced cancer incidence. METHODS AND MATERIALS: The two operational parameters of the OED concept are the organ-specific cancer incidence rate at low doses, which is taken from the data of the atomic bomb survivors, and cell sterilization at higher doses. The effect of cell sterilization in various organs was estimated by analyzing the secondary cancer incidence data of patients with Hodgkin's disease who were treated with radiotherapy in between 1962 and 1993. The radiotherapy plans used at the time the patients had been treated were reconstructed on a fully segmented whole body CT scan. The dose distributions were calculated in individual organs for which cancer incidence data were available. The model parameter that described cell sterilization was obtained by analyzing the dose and cancer incidence rates for the individual organs. RESULTS: We found organ-specific cell radiosensitivities that varied from 0.017 for the mouth and pharynx up to 1.592 for the bladder. Using the two model parameters (organ-specific cancer incidence rate and the parameter characterizing cell sterilization), the OED concept can be applied to any three-dimensional dose distribution to analyze cancer incidence. CONCLUSION: We believe that the concept of OED presented in this investigation represents a first step in assessing the potential risk of secondary cancer induction after the clinical application of radiotherapy.

Dose-Response Relationship, Radiation↗

Prenatal diagnosis of a long QT syndrome by fetal magnetocardiography in an unshielded bedside environment.

OBJECTIVE: The potentially life threatening long QT syndrome should be diagnosed during pregnancy to improve perinatal care. METHODS: A patient with a family history for a hereditary long QT syndrome presented at 30 weeks of her first pregnancy with fetal bradycardia and a narrow oscillation bandwidth on cardiotocography without structural abnormalities of the fetal heart. Fetal magnetocardiography was performed with a prototype biomagnetometer/gradiometer device in a magnetically unshielded environment. The cardiac time intervals were determined in the averaged PQRST complex. RESULTS: The QT time and the frequency-corrected QTc showed a marked prolongation to 380 ms and 0.52 s, respectively. The findings were confirmed in the postnatal electrocardiogram after spontaneous term delivery in a perinatal center. The causative mutation on chromosome 11 had been passed on to the newborn from his mother. CONCLUSION: Bedside fetal magnetocardiography revealed the exact diagnosis of the long QT syndrome in a period of the gestation when the fetus was electrically isolated by the vernix caseosa that hinders electrocardiography. To patients at risk of fetal cardiac abnormalities, magnetocardiography can be offered as a non-invasive diagnostic bedside procedure. The diagnosis should trigger closer surveillance and delivery in a perinatal center.

Adult↗

A simple dose-response relationship for modeling secondary cancer incidence after radiotherapy.

Estimates of secondary cancer risk after radiotherapy are becoming more important for comparative treatment planning. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at doses higher than 4 Gy. The purpose of this report is to determine a simple dose-response relationship for secondary cancer incidence after radiotherapy treatment which can be used for comparative treatment planning. In this report a simple one-parameter model to estimate the complication probability of secondary cancer was fitted to literature data on secondary cancer incidence after radiotherapy. The results showed a linear dose-response relationship in the low-dose part and an exponentially decreasing one after a maximum at around 10 Gy. The observed dose-response relationship and the literature data used to fit the dose-response indicate that cell death effects are important for the explanation of secondary cancer incidence. Even using a dose and dose-rate effectiveness factor (DDREF) of two (instead of one), a cancer incidence maximum is observed at around 10 Gy, with decreasing incidence at higher doses.

Dose-Response Relationship, Radiation↗

Patient specific optimization of the relation between CT-hounsfield units and proton stopping power with proton radiography.

The purpose of this work is to show the feasibility of using in vivo proton radiography of a radiotherapy patient for the patient individual optimization of the calibration from CT-Hounsfield units to relative proton stopping power. Water equivalent tissue (WET) calibrated proton radiographs of a dog patient treated for a nasal tumor were used as baseline in comparison with integrated proton stopping power through the calibrated CT of the dog. In an optimization procedure starting with a stoichiometric calibration curve, the calibration was modified randomly. The result of this iteration is an optimized calibration curve which was used to recalculate the dose distribution of the patient. One result of this experiment was that the mean value of the deviations between WET calculations based on the stoichiometric calibration curve and the measurements was shifted systematically away from zero. The calibration produced by the optimization procedure reduced this shift to around 0.4 mm. Another result was that the precision of the calibration, reflected as the standard deviation of the normally distributed deviations between WET calculation and measurement, could be reduced from 7.9 to 6.7 mm with the optimized calibration. The dose distributions based on the two calibration curves showed major deviations at the distal end of the target volume.

Animals↗

Laparoscopic and vaginal repair of uterine scar dehiscence following cesarean section as detected by ultrasound.

INTRODUCTION AND OBJECTIVE: Cesarean section (CS) is the most common operation in obstetrics, with rising incidence in most countries. As a result of this operation late scar dehiscence may occur, which may lead to uterine rupture in a subsequent pregnancy. In this case series we have described sonographic detection of scar dehiscence after CS and feasibility of vaginal or combined laparoscopic and vaginal scar excision and uterine repair. METHODS: Five consecutive patients underwent vaginal or laparoscopic assisted vaginal approach for repair of suspected scar dehiscence following CS, during a 5 year period. In all cases, transvaginal sonography detected suspicious features of scar dehiscence over the anterior uterine wall. Except of one, all patients had reported recurrent pelvic pain and/or irregular menstrual bleedings. Furthermore all patients planned for a further pregnancy. RESULTS: Resection of the uterine defect and re-constitution of the uterine wall was successfully achieved in all five patients. There were no intra-operative complications and none of the patients required blood transfusion. The mean operation time was 117 min (27-192). Presence of scar tissue was confirmed on histology in all specimens. Four patients remained free of symptoms with no evidence of recurrent scar dehiscence on sonography over a median follow up of 30 months (3-46). One patient had an uneventful pregnancy 24 months after scar removal and was delivered by repeat CS at 39 weeks' gestation. CONCLUSION: Patients with a history of CS should undergo transvaginal sonography of the scar region in order to detect latent scar dehiscence in combination with uterine wall thinning prior to planning further pregnancy. In suspected cases, a combined laparoscopic - vaginal or vaginal approach can be employed to repair the defect.

Adult↗

Neutron dose from prostheses material during radiotherapy with protons and photons.

The purpose of this investigation is to measure the impact of Ti-alloy-prostheses on the neutron dose during proton and photon radiotherapy. Such unwanted neutron dose to the patient should be kept as low as possible (ALARA principle), as such additional dose can create secondary malignancies. For this purpose we performed neutron dose measurements using etch track detectors under the same conditions on a proton and a photon beam line used for radiotherapy. We found no influence of the prostheses material on the neutron dose both for proton and photon treatment.

Alloys↗