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Stefan Lang

Publications and source records attributed to Stefan Lang.

15 recordsLinked to original sources
PubMed2006

Uncertainties when using only one MRI-based treatment plan for subsequent high-dose-rate tandem and ring applications in brachytherapy of cervix cancer.

BACKGROUND AND PURPOSE: This retrospective study compares individual MRI based 3D treatment planning for each intracavitary applicator insertion and the use of only one MRI treatment plan for cervical cancer brachytherapy. MATERIALS AND METHODS: GTV, high risk (HR) CTV and OAR were delineated and analysed for 14 patients. Data using the individual approach were taken from the actual irradiated plans. The "single plan procedure" was simulated by matching the dose distribution of the first plan to the MRI datasets of each subsequent implantation. Total doses from brachytherapy were added up and normalized to 2Gy fractionation (EQD2). RESULTS: The mean D90 for HR CTV was 6Gy higher when using one plan than when using individual treatment plans. The D(2cc) increased 3.5Gy for the bladder, 4.2Gy for the rectum and 5.8Gy for the sigmoid. The use of only one treatment plan would have resulted in 2, 1 and 5 extra cases exceeding total D(2cc) constraints for bladder (90Gy), rectum (75Gy) and sigmoid (75Gy), respectively. CONCLUSION: The use of only one treatment plan for several applications results in higher dose to target and OAR structures. CT, clinical examination and X-ray findings can help to reduce certain situations of overdosage, when individual MRI based treatment planning is not available for each fraction.

Brachytherapy↗
PubMed2006

The Vienna applicator for combined intracavitary and interstitial brachytherapy of cervical cancer: clinical feasibility and preliminary results.

PURPOSE: The aims of this study were to investigate the clinical feasibility and to report on preliminary treatment outcomes of combined intracavitary/interstitial brachytherapy, using a novel applicator and magnetic resonance imaging (MRI)-based treatment planning in patients with locally advanced cervical cancer. METHODS AND MATERIALS: A total of 22 cervical cancer patients with insufficient response and/or unfavorable topography after external-beam irradiation were included in this study. Parametrial extent of the disease in these patients was judged to exceed the coverage limit of intracavitary brachytherapy alone. A modified tandem/ring (T/R) applicator for guidance of parametrial needles (N) was used to perform high-dose-rate-brachytherapy with MRI-based treatment planning. Clinical feasibility and preliminary treatment outcomes were assessed. RESULTS: A total of 44 interstitial needle implants were performed. The spatial relations between the T/R + N applicator, high-risk clinical target volume, and organs at risk were visible clearly in all cases. Accurate and reproducible needle placement could be achieved in the majority of cases. No severe adverse events were caused by the intervention. The mean follow-up period was 20 months (range, 5-35 months). No G3 to G4 early or persistent late side effects were observed. Complete remission was achieved in 21 patients (95%). One local recurrence was observed within the high-risk clinical target volume area during follow-up. CONCLUSIONS: Our preliminary clinical experience indicates that combined intracavitary and interstitial MRI-based brachytherapy in patients with significant residual disease after external-beam therapy extending up to the distal third of parametria is feasible and allows excellent local control and a low rate of morbidity.

Adult↗
PubMed2006

The Vienna applicator for combined intracavitary and interstitial brachytherapy of cervical cancer: design, application, treatment planning, and dosimetric results.

PURPOSE: To present a combined intracavitary and interstitial dedicated applicator and magnetic resonance imaging (MRI) treatment planning for cervical cancer brachytherapy. METHODS AND MATERIALS: A modified ring applicator allows interstitial needles to be implanted in parallel to the intrauterine tandem. MRI treatment planning based on a standard loading pattern with stepwise dwell weight adaptation and needle loading is performed to achieve optimal dose coverage and sparing of organs at risk. Dose constraints are applied for dose-volume histogram parameters. RESULTS: The use of additional interstitial needles provides prescription dose up to 15 mm lateral to point A. Twenty-two patients with high-risk clinical target volumes of mean 44 cm3 were treated with a mean prescribed total dose of 85 Gy (biologically equivalent to 2 Gy fractionation, alpha/beta = 10 Gy) and 93% coverage (V100). The dose to organs at risk was within standard limits for intracavitary brachytherapy alone. CONCLUSIONS: A combined interstitial-intracavitary applicator results in reproducible implants for cervical cancer brachytherapy. MRI-based treatment planning based on a target concept, dose-volume constraints, and limitations for the relative dwell weight allows for an increase in target coverage, treated volume, and total dose without increasing the dose to critical structures.

Brachytherapy↗
PubMed2006

Systematic evaluation of MRI findings in different stages of treatment of cervical cancer: potential of MRI on delineation of target, pathoanatomic structures, and organs at risk.

PURPOSE: To compare magnetic resonance imaging (MRI) findings at different stages of cervix cancer treatment and to define the potential of MRI to delineate the gross tumor volume (GTV), clinical target volume (CTV), pathoanatomic structures, and organs at risk (OAR) in brachytherapy. METHODS AND MATERIALS: Forty-nine patients underwent MRI at diagnosis and at brachytherapy. The ability to discriminate anatomic structures on MRI was assessed (quality factor: 0 = inability to discriminate; 1 = fair discrimination; 2 = good discrimination; 3 = excellent discrimination). The overall ability to visualize (percentage of patients with quality factors greater than 0) and the overall discrimination quality score (mean quality factors of all patients) were estimated for the applicator, GTV at diagnosis (GTV(D)), GTV at brachytherapy (GTV(BT))/"gray zones," cervix rim/uterine corpus, OAR, vaginal wall, and parametria. RESULTS: The overall ability to visualize the applicator on MRI at brachytherapy was 100%; for the GTV(BT)/"gray zones," cervix rim/uterine corpus, OAR, and vaginal wall, visualization was 98% (overall discrimination quality factors: 1.2, 2.9, 2.1, 1.9, 1.7, and 2.6). Three of 4 borders of parametrial space were defined in more than 98% (discrimination quality factors: 2.9, 2.1, and 1.2). CONCLUSION: Magnetic resonance imaging provides appropriate information for definition of the applicator, GTV, CTV, pathoanatomic structures, and OAR that enables precise delineation for cervix cancer brachytherapy.

Adult↗
PubMed2006

Intercomparison of treatment concepts for MR image assisted brachytherapy of cervical carcinoma based on GYN GEC-ESTRO recommendations.

PURPOSE: To perform a multicentre intercomparison study of treatment concepts for MRI assisted brachytherapy of cervix cancer based on recommendations of the Gynaecological GEC-ESTRO Working Group. METHODS: Each participating centre (IGR Paris, University Hospital Leuven, Medical University of Vienna) contributed data of one patient with comparable clinical features. GTV, High Risk CTV (HR CTV), Intermediate Risk CTV (IR CTV) and organ walls of bladder, rectum and sigmoid colon were delineated at the time of each brachytherapy fraction on axial MR images with the applicator in place. Dose-volume histograms were calculated to evaluate doses to tumour, target volumes and organs at risk. Dose values were biologically normalised to equivalent doses in 2 Gy fractions (EQD(2), equivalent to 50 cGy/h low dose rate) applying the linear-quadratic model. RESULTS: Total doses to point A from external beam therapy plus brachytherapy ranged from 85 to 91 Gy and were close to the dose covering 90% of HR CTV (D90=85-87 Gy). D90 of IR CTV was within 69-73 Gy. Doses to organs at risk were comparable. CONCLUSIONS: This study indicates the feasibility of the GEC-ESTRO recommendations. Despite different treatment concepts, biologically normalised total doses to tumour, target volumes and organs at risk were comparable.

Brachytherapy↗
PubMed2006

Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology.

The second part of the GYN GEC ESTRO working group recommendations is focused on 3D dose-volume parameters for brachytherapy of cervical carcinoma. Methods and parameters have been developed and validated from dosimetric, imaging and clinical experience from different institutions (University of Vienna, IGR Paris, University of Leuven). Cumulative dose volume histograms (DVH) are recommended for evaluation of the complex dose heterogeneity. DVH parameters for GTV, HR CTV and IR CTV are the minimum dose delivered to 90 and 100% of the respective volume: D90, D100. The volume, which is enclosed by 150 or 200% of the prescribed dose (V150, V200), is recommended for overall assessment of high dose volumes. V100 is recommended for quality assessment only within a given treatment schedule. For Organs at Risk (OAR) the minimum dose in the most irradiated tissue volume is recommended for reporting: 0.1, 1, and 2 cm3; optional 5 and 10 cm3. Underlying assumptions are: full dose of external beam therapy in the volume of interest, identical location during fractionated brachytherapy, contiguous volumes and contouring of organ walls for >2 cm3. Dose values are reported as absorbed dose and also taking into account different dose rates. The linear-quadratic radiobiological model-equivalent dose (EQD2)-is applied for brachytherapy and is also used for calculating dose from external beam therapy. This formalism allows systematic assessment within one patient, one centre and comparison between different centres with analysis of dose volume relations for GTV, CTV, and OAR. Recommendations for the transition period from traditional to 3D image-based cervix cancer brachytherapy are formulated. Supplementary data (available in the electronic version of this paper) deals with aspects of 3D imaging, radiation physics, radiation biology, dose at reference points and dimensions and volumes for the GTV and CTV (adding to [Haie-Meder C, Pötter R, Van Limbergen E et al. Recommendations from Gynaecological (GYN) GEC ESTRO Working Group (I): concepts and terms in 3D image-based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235-245]). It is expected that the therapeutic ratio including target coverage and sparing of organs at risk can be significantly improved, if radiation dose is prescribed to a 3D image-based CTV taking into account dose volume constraints for OAR. However, prospective use of these recommendations in the clinical context is warranted, to further explore and develop the potential of 3D image-based cervix cancer brachytherapy.

Brachytherapy↗
PubMed2005

Blockade of interleukin-13-mediated cell activation by a novel inhibitory antibody to human IL-13 receptor alpha1.

Interleukin-13 (IL-13) is a cytokine with a crucial role in the development of allergic asthma. The IL-13 receptor shares the IL-4Ralpha subunit with the IL-4R system, but contains as a specific component the IL-13Ralpha1 chain. Blocking signal release by IL-13 without affecting IL-4 function is a potentially interesting therapeutical option for the treatment of asthma. Employing genetic immunization, we generated a set of novel monoclonal antibodies to the IL-13Ralpha1 receptor that proved very specific and efficient inhibitors of human IL-13 activity. Receptor binding antibodies were identified by their specific reactivity with both human monocytes and a murine pro-B cell line overexpressing human IL-13Ralpha1 by flow cytometry and cell ELISA. A luciferase reporter cell system based on STAT6-mediated promoter activation in murine Ba/F3 cells was employed to screen the antibodies for IL-13 antagonistic properties. Inhibitory antibody effects were quantified by interference with IL-13-dependent proliferation of TF-1 cells. The capability of blocking IL-13-driven responses of primary, inflammation-relevant cells was tested by Western blot analysis of STAT6 tyrosine phosphorylation and expression of 15-lipoxygenase in monocytes from fresh blood. The most potent inhibitory antibody identified, GM1E7, inhibited IL-13-driven gene activation and cell proliferation in immune cell lines with IC(50) values in the low nanomolar range. Both short-term (STAT6 activation) and long-term (15-LO induction) responses of primary human blood cells to IL-13 were almost entirely blocked, whereas IL-4 effects remained virtually unaffected. GM1E7 is superior to available agents interfering with IL-13 activity in terms of specificity and efficiency and offers potential novel therapeutic perspectives for the treatment of allergic asthma.

Antibodies, Monoclonal↗
PubMed2005

The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi.

The high-mobility group transcription factor Sox10 exerts many different roles during development of the neural crest and nervous system. To unravel its complex transcriptional functions, we have started to look for interaction partners. Here, we identify an association of Sox10 with the N-myc interactor Nmi, which was mediated by the high-mobility group of Sox10 and the central region of Nmi. In vivo relevance of this interaction is indicated by the fact that both proteins were co-expressed in glial cells, gliomas and in the spinal cord. Additionally, subcellular localization of Nmi in C6 glioma depended on the presence of Sox10 such that nuclear Nmi was more frequent in Sox10-expressing cells. Importantly, Nmi modulated the transcriptional activity of Sox10 in reporter gene assays. Nmi effects varied between different Sox10 target gene promoters, indicating that Nmi function in vivo may be promoter-specific.

Cell Line↗
PubMed2005

Dose and volume parameters for MRI-based treatment planning in intracavitary brachytherapy for cervical cancer.

PURPOSE: Magnetic resonance imaging (MRI)-based treatment planning in intracavitary brachytherapy allows optimization of the dose distribution on a patient-by-patient basis. In addition to traditionally used point dose and volume parameters, dose-volume histogram (DVH) analysis enables further possibilities for prescribing and reporting. This study reports the systematic development of our concept applied in clinical routine. METHODS AND MATERIALS: A group of 22 patients treated with 93 fractions using a tandem-ring applicator and MRI-based individual treatment planning for each application was analyzed in detail. High-risk clinical target volumes and gross tumor volumes were contoured. The dose to bladder, rectum, and sigma was analyzed according to International Commission of Radiation Units and Measurements (ICRU) Report 38 and DVH parameters (e.g., D(2cc) represents the minimal dose for the most irradiated 2 cm(3)). Total doses, including external beam radiotherapy and the values for each individual brachytherapy fraction, were biologically normalized to conventional 2-Gy fractions (alpha/beta 10 Gy for target, 3 Gy for organs at risk). RESULTS: The total prescribed dose was about 85 Gy(alphabeta10), which was mainly achieved by 45 Gy external beam radiotherapy plus 4 x 7 Gy brachytherapy (total 84 Gy(alphabeta10)). The mean value was 82 Gy(alphabeta10) for the point A dose (left, right) and 84 cm(3) for the volume of the prescribed dose. The average dose to the clinical target volume was 66 Gy(alphabeta10) for the minimum target dose, 87 Gy(alphabeta10) for the dose received by at least 90% of the volume, with a mean volume treated with at least the prescribed dose of 89%. The mean D(2cc) for the bladder was 83 Gy(alphabeta3), the ICRU point dose was 75 Gy(alphabeta3), and the dose at the ICRU point plus 1.5 cm cranially was 100 Gy(alphabeta3). The average dose to the rectum was 64 Gy(alphabeta3) for D(2cc) and at ICRU point 69 Gy(alphabeta3). The sigma D(2cc) was 63 Gy(alphabeta3). CONCLUSION: A standard loading pattern should be used as the starting point for MRI-based optimization. Individual changes of active dwell positions and dwell weights are guided by a concept of DVH constraints for target and organs at risk. In our clinical routine, the dose to point A and dose received by at least 90% of the volume for the clinical target volume are both comparable to the prescribed dose. The DVH constraints for organs at risk allow reproducible treatment plans, helping to detect and avoid severe overdosage.

Brachytherapy↗
PubMed2005

Locally adaptive function estimation for binary regression models.

In this paper we present a nonparametric Bayesian approach for fitting unsmooth or highly oscillating functions in regression models with binary responses. The approach extends previous work by Lang et al. for Gaussian responses. Nonlinear functions are modelled by first or second order random walk priors with locally varying variances or smoothing parameters. Estimation is fully Bayesian and uses latent utility representations of binary regression models for efficient block sampling from the full conditionals of nonlinear functions.

Bayes Theorem↗
PubMed2005

Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV.

BACKGROUND AND PURPOSE: Brachytherapy (BT) plays a crucial role in the management of invasive cervix cancer from stage I to IV. Intracavitary techniques are based on afterloading devices, with different types of applicators. CT and/or MRI compatible applicators allow a sectional image based approach with a better assessment of gross tumour volume (GTV) and definition and delineation of target volume (CTV) compared to traditional approaches. Accurate and reproducible delineation of GTV, CTV and PTV, as well as of critical organs has a direct impact on BT treatment planning, especially if it is possible to adapt the pear-shape isodose by optimisation using DVH analysis. When introducing a 3D image based approach for GTV and CTV assessment, there is a need for a common language to describe the concepts and to define the terms which are to be used. METHODS: In 2000, GEC-ESTRO decided to support 3D imaging based 3D treatment planning approach in cervix cancer BT with the creation of a Working Group. The task was to describe basic concepts and terms and to work out a terminology enabling various groups working in this advanced field to use a common language. The recommendations described in this report were proposed based on clinical experience and dosimetric concepts of different institutions (IGR, Leuven, Vienna) and were stepwise validated against the background of different clinical experience. CONCLUSIONS: As GTV and CTV for BT change significantly during treatment, time frame for assessment of GTV and CTV for BT is specified in this report: at time of diagnosis GTV(D), CTV(D) and at time of BT GTV(B), CTV(B). Furthermore, CTV for BT is defined related to risk for recurrence: high risk CTV and intermediate risk CTV. Beside verbal descriptions detailed examples are given, partly in form of schematic drawings.

Brachytherapy↗
PubMed2003

Non-parametric regression with BayesX: a flexible estimation of trends in human physical stature in 19th century America.

The recently developed computer program BayesX provides a Bayesian approach to the estimation of non-parametric additive models. Such models can be useful in applications when the effect of metrical covariates (such as time) are to be estimated while controlling for other factors. In an application of this methodology, trends in the height of West Point cadets in the 19th century are estimated. The results indicate that the biological standard of living of the "middle class" increased relative to the rest of the American society during the Antebellum years.

Adult↗
PubMed2002

Perioperative small-dose S(+)-ketamine has no incremental beneficial effects on postoperative pain when standard-practice opioid infusions are used.

UNLABELLED: Several studies report that when small-dose racemic ketamine, an N-methyl-D-aspartate receptor antagonist, is administered perioperatively, opioid consumption is reduced postoperatively. S(+)-ketamine has a higher affinity for the N-methyl-D-aspartate receptor and less-serious side effects than racemic ketamine. Thirty patients scheduled for elective arthroscopic anterior cruciate ligament repair were enrolled in this randomized, double-blinded clinical trial designed to determine the preemptive effect of S(+)-ketamine on postoperative analgesia requirements in a setting of clinically relevant perioperative analgesia. Total IV anesthesia was induced and maintained with remifentanil (0.125-1.0 microg x kg(-1) x min(-1)) and a propofol target-controlled infusion (target 2-4 microg/mL). The Ketamine group received a bolus of 0.5 mg/kg S(+)-ketamine before incision, followed by a continuing infusion of 2 microg x kg(-1) x min(-1) until 2 h after emergence from anesthesia. The Control group received NaCl in the same sequence. After IV morphine provided pain relief down to < or =3 on a visual analog scale scored from 0 to 10, patients were connected to a patient-controlled analgesia device. There were no significant differences between the two groups in terms of total morphine consumption or VAS scores, either at rest or with movement. In our study, S(+)-ketamine did not contribute to postoperative pain reduction, possibly because of the clinically routine perioperative opioid analgesia. IMPLICATIONS: Small-dose S(+)-ketamine had no positive effect on postoperative analgesia when administered perioperatively for elective arthroscopic anterior cruciate ligament repair. Unlike investigations of the racemic mixture of ketamine, our study methods included timely standard-practice perioperative opioid analgesia, which seems to make supplemental analgesia unnecessary.

Adult↗
PubMed2000

Requirement of cyclin D1 in mesangial cell mitogenesis.

Abstract. Hyperplasia of mesangial cells (MC) is a frequent finding in glomerulonephritis. The control and function of cyclin D1, a regulator of cell cycle progression, in MC proliferation in vivo and in vitro were investigated. In a rat model of mesangioproliferative glomerulonephritis, increases in the number of cyclin D1-positive MC nuclei were prominent on day 5 of the disease, preceding the peak of MC hyperplasia. In growth-arrested rat MC in culture, mitogenic stimulation with serum or platelet-derived growth factor (PDGF) led to rapid increases in cyclin D1 protein expression. Transforming growth factor-beta1 inhibited PDGF induction of cyclin D1 protein at 12 h. In an examination of the subcellular distribution of cyclin D1, it was observed that stimulation of MC with PDGF for 6 h caused translocation of cyclin D1 from the cytoplasm into the nucleus. Coincubation with PDGF and transforming growth factor-beta1 completely inhibited this effect, without altering the cellular cyclin D1 protein abundance at that time point. To test whether reduction of cyclin D1 protein levels was sufficient to inhibit mitogenesis, MC were transfected with antisense oligonucleotides (ODN) complementary to rat cyclin D1 mRNA. Antisense ODN against cyclin D1 reduced the serum- or PDGF-induced protein expression of cyclin D1 to 27 or 10% of control levels, respectively. These inhibitory effects were correlated with diminished cyclin-dependent kinase 4 activity. Antisense ODN against cyclin D1 also decreased the PDGF-induced increase in p21(Waf-1) protein levels. The MC proliferation caused by serum or PDGF was markedly inhibited by antisense ODN against cyclin D1, as measured by [(3)H]thymidine uptake and cell counts. It is concluded that increased cyclin D1 protein expression of MC is required for MC proliferation. Targeting cyclin D1 expression may represent an effective means to inhibit MC proliferation in vitro and in vivo.

Animals↗