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Biomedical subjects

W Harms

Publications and source records attributed to W Harms.

At least 19 recordsLinked to original sources
PubMed2005

Daytime pulsed dose rate brachytherapy as a new treatment option for previously irradiated patients with recurrent oesophageal cancer.

The aim of this study was to evaluate the feasibility, effects, and toxicity of pulsed dose rate (PDR) brachytherapy for re-irradiation of oesophageal carcinoma. A total of 16 patients (median age 67 years) with inoperable recurrences from oesophageal cancer after primary radio-(chemo)-therapy (median 50 Gy) were re-irradiated using PDR brachytherapy ((192)Ir, 37 GBq). Treatment was carried out on an outpatient basis applying a weekly 5 Gy daytime schedule (0.5 Gy pulse(-1) h(-1), total dose 15-20 Gy). The dose was prescribed 10 mm from the mid-dwell position and encompassed the clipped tumour extension with 2 cm margins. The use of clips for delineation of tumour extent and catheter movement during irradiations was evaluated. All 61 PDR treatments were applied safely. The median catheter movement was 5 mm, range 2-12 mm. After a median follow-up of 8 months, three patients had a complete and five a partial remission. Body weight increased in 5 of 16 (31%) and was stable in 4 of 16 (25%) patients, respectively. The median grade 2 (RTOG/EORTC) dysphagia-free survival was 17 months. Seven patients experienced grade 1, five grade 2, and one grade 3 late toxicity. Three patients with uncontrolled locoregional disease showed grade 4 complications (oesophago-tracheal fistulae (n=2), fatal arterial bleeding (n=1). Daytime PDR brachytherapy proved to be feasible and provided effective palliation. Toxicity remains a major problem. Thus, total dose should be restricted to <15 Gy in this palliative situation.

Aged↗
PubMed2004

[Diagnosis with (18)F-FDG PET scan after larynx preservation by primary radiochemotherapy].

PATIENTS AND METHODS: In a group of 20 patients undergoing chemoradiation for larynx organ preservation after diagnosis of laryngeal and hypopharyngeal carcinoma, (18)F-fluordeoxyglucose positron emission tomography ((18)F-FDG-PET) was performed before the start of therapy. After i.v. application of 240 MBq FDG, a dynamic PET in 3-D-mode was performed over 90 min (Siemens CTI ECAT EXACT HR(+)). Analysis was done visually and semiquantitatively (60-90 min p.i.) following iterative reconstruction. Additional (18)F-FDG-PET investigations were done and correlated with the clinical outcome in 16/20 patients at 3 months and in 14/20 patients at 6 months after the end of therapy. RESULTS: In 17/20 patients (85%), the preclinical (18)F-FDG-PET correlated well with the histologically confirmed primary tumor. Three cases were false negatives. In one case this was due to an increased glucose value (203 mg%). After 3 months, 8/13 (62%) patients showed a positive correlation between clinical and PET results (sensitivity 100%, specificity 70%). After 6 months, 9/11 (82%) patients presented clinically normal PET results. PET results were false negative in one case (sensitivity 67%, specificity 88%). CONCLUSION: The data of our trial slightly reduce the enthusiasm of early (18)F-FDG-PET detection of residual disease after chemoradiation in resectable laryngeal or hypopharyngeal cancer. Further trials should optimize the calculation integrating the exact quantification of glucose metabolism with the aim of improving sensitivity and specificity.

Aged↗
PubMed2004

Intercomparison experiments of systems for the measurement of xenon radionuclides in the atmosphere.

Radioactive xenon monitoring is one of the main technologies used for the detection of underground nuclear explosions. Precise and reliable measurements of (131m)Xe, (133g)Xe, (133m)Xe, and (135g)Xe are required as part of the International Monitoring System for compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). For the first time, simultaneous testing of four highly sensitive and automated fieldable radioxenon measurement systems has been performed and compared to established laboratory techniques. In addition to an intercomparison of radioxenon monitoring equipment of different design, this paper also presents a set of more than 2000 measurements of activity concentrations of radioactive xenon made in the city of Freiburg, Germany in 2000. The intercomparison experiment showed, that the results from the newly developed systems agree with each other and the equipment fulfills the fundamental requirements for their use in the verification regime of the CTBT. For 24-h measurements, concentrations as low as 0.1 mBqm(-3) were measured for atmospheric samples ranging in size from 10 to 80 m(3). The (133)Xe activity concentrations detected in the ambient air ranged from below 1 mBqm(-3) to above 100 mBqm(-3).

Air Pollutants, Radioactive↗
PubMed2004

[Reirradiation of chest wall local recurrences from breast cancer].

OBJECTIVE: The aim of this article was to describe the radio-therapeutic treatment options in previously irradiated patients suffering from breast cancer local recurrences and to review the literature. MATERIAL AND METHODS: Reirradiation of the chest wall can be performed using electron beams or alternatively CLDR/PDR (continuous/pulsed low dose rate) brachytherapy techniques with large skin moulds. With both techniques high doses can be applied to the chest wall while deeper-seated organs (lung, heart) can be spared to a large extent. Electron-beam therapy is readily available and the depth of treatment can be easily controlled by selecting the appropriate energy. The protracted irradiation schedule of CLDR/PDR brachytherapy results due to radiobiological reasons in a broad therapeutic ratio and safe treatment time. RESULTS: In the literature, more than 250 cases being reirradiated for chest wall local recurrences have been published. After retreatment using electron beams complete remissions were obtained in 41-74 % of the patients (brachytherapy 79-82 %). Severe grade IV complications (RTOG/EORTC) occurred in less than 10 % of the patients. CONCLUSIONS: With regard to the limited treatment options reirradiation of chest wall local recurrences resulted in high local control rates while toxicity remained acceptable. These data weaken the radio-therapeutic dogma that reirradiation of the chest wall may not be possible.

Brachytherapy↗
PubMed2003

Preliminary evaluation of low-grade toxicity with conformal radiation therapy for prostate cancer on RTOG 9406 dose levels I and II.

PURPOSE: To evaluate the rates of low-grade late effects in patients treated for prostate cancer on Radiation Therapy Oncology Group (RTOG) 9406. MATERIALS AND METHODS: Between August 1994 and September 1999, 424 patients were entered on this dose escalation trial of three-dimensional conformal radiation therapy (3D-CRT) for localized adenocarcinoma of the prostate at doses of 68.4 Gy (level I) and 73.8 Gy (level II). We have previously reported Grade 3 or greater late toxicity of patients treated on the first two dose levels of this trial. This analysis examines the distribution of all late toxicities in these patients. All radiation prescriptions were a minimum dose to a planning target volume (PTV). Patients were stratified according to clinical stage and risk of seminal vesicle invasion (SVI) based upon Gleason score and presenting prostate-specific antigen. Group 1 includes patients with T1,2 disease with SVI risk < 15%, and Group 2 includes patients with T1,2 disease with SVI risk > 15%. Group 3 patients had T3 disease. Average months at risk after completion of therapy ranged from 21.4 to 40.1 months for patients treated at dose level I and 10.0 to 34.2 months for patients at dose level II. The frequency of all grades of late effects was compared with a similar group of patients treated in RTOG studies 7506 and 7706 with adjustments made for the interval from completion of therapy. The RTOG toxicity scoring scales for late effects were used for grading. RESULTS: The rate of Grade 3 or greater late toxicity continues to be low compared with RTOG historical controls. No Grade 4 or 5 late sequelae were reported in any of the 393 evaluable patients during the period of observation. The frequency of patients free of any complications was lower in RTOG 9406 than in historical controls. In the 73 Group 1 patients treated on dose level 1, there were 24 patients without sequelae compared with an expected rate of 39.7 (p = 0.013), and in 80 Group 3 patients at dose level II there were 24 patients without sequelae when 56.2 were expected (p < 0.0001). Other groups treated at these dose levels demonstrated a nonsignificant reduction in the rate of patients free of any side effects. These data suggest that the reduction in high-grade morbidity may be related to a shift of complications to lower grades. CONCLUSIONS: Morbidity of 3D-CRT in the treatment of prostate cancer is low. It is important to continue to closely examine late effects in patients treated in RTOG 9406. The primary objective of dose escalation without an increase rate of >/= Grade 3 sequelae has been achieved. However, the reduction in Grade 3 complications may have resulted in a higher incidence of Grade 1 or 2 late effects. Because Grade 2 late effects may have a significant impact on a patient's quality of life, it is important to reduce these complications as much as possible. Clinical trials should use quality-of-life measures to determine that trade-offs between severity and rates of toxicity are acceptable to patients.

Adenocarcinoma↗
PubMed2002

Dose-dependent differential effects of low and pulsed dose-rate brachytherapy in a radioresistant syngenic rat prostate tumour model.

PURPOSE: To study the response of the Dunning prostate carcinoma (R3327-AT1 subline) to continuous low dose-rate (CLDR) and pulsed dose-rate (PDR) brachytherapy. MATERIALS AND METHODS: After subcutaneous tumour transplantation into the thigh of the Copenhagen rat, doses of 0, 20, 30, 40 and 50 Gy were applied to the tumour surface (tumour diameter 9+/-1mm). Eight animals were irradiated per dose group and exposure condition. Interstitial PDR ((192)Ir source, 37 GBq) and CLDR ((192)Ir seed, 150 MBq) brachytherapy were carried out with 0.75 Gy/pulse h(-1) and a dose-rate of 0.75Gyh(-1), respectively. Treatment response was assessed in terms of growth delay expressed as the time (T(5)) required for each tumour to reach five times the initial tumour volume. RESULTS: The median T(5) times for the CLDR groups (in the order: control, 20, 30, 40, 50 Gy) were 12 (12), 54.5 (21), 64.5 (31), 85.5 (51), and 65 (47.5) days. Values after PDR brachytherapy are given in parentheses and resulted in a significantly impaired tumour growth delay (log-rank test) in the 20Gy (p =0.006) and 30 Gy (p =0.036) groups. No significant difference was found in the 40-50 Gy dose range. CONCLUSIONS: In contrast to previous results and predictions of biological models we observed dose-dependent differential effects of PDR and CLDR brachytherapy with reduced efficacy of PDR in the lower dose range.

Animals↗
PubMed2002

[Computer-assisted reconstruction of coronary vessels].

End stage coronary artery disease with linear stenosis of the main vessels despite several coronary interventions is a current challenge for surgical treatment. As the long term results are mainly determined by the pathology of the coronary vessels a simple revascularisation with arterial or venous grafts provides no adequate solution of the problem. An exactly controlled 3D-reconstruction of the coronary vessels enabling selective thrombendarteriectomy (TEA) seems to be a new approach, that may be limited by neointimal hyperproliferation of the coronary vessels. Intraoperative brachytherapy may be a tool to inhibit this process.

Atherectomy, Coronary↗
PubMed2002

Daily patient set-up control in radiation therapy by coded light projection.

Advances in conformal radiation therapy to control disease via dose escalation are challenged by set-up uncertainties. Recently, techniques have been developed to use surface features to evaluate the patient's position and correct it where necessary. The aim of this study was to use the patient's surface as a tool for daily set-up control and monitoring. We use a surface scanner based on the projection of coded light to receive--in a daily routine--a large amount of surface points which enables us to register the CT-based planning data with the patients current position. By superimposing current and planned volumes, a volume of congruency was obtained. An error below 1 mm was considered acceptable. In cases where set-up was not satisfactory a map of the surface comparison was evaluated showing the areas of missing alignment. According to this information a manual repositioning was performed. This procedure was repeated until the error was acceptable. No more then 3 repetitions where necessary to obtain an acceptable result. The whole procedure including registration, calculation and visualization took about 20 sec for one repetition. The use of structured light projection in the daily set-up control and monitoring proved to be a noninvasive, easy, quick, inexpensive and reliable solution.

Data Collection↗
PubMed2001

Cooperative boundary populations: the evolution of cooperation on mortality risk gradients.

Cooperative or altruistic behavior is known to be vulnerable to destructive exploitation in the absence of spatial segregation and perceptual discrimination on the part of cooperators. In this study, a non-standard, agent-based, spatially explicit model of the evolution of cooperation shows that spatial gradients of increasing individual mortality risk can allow cooperative subpopulations to persist among players randomly matched for one-shot Prisoner's Dilemma. Further, the dynamically stable cooperator population formed on the gradient at the boundary of the survivable non-cooperative range provides ideal conditions for the evolution of discriminating strategies such as tit-for-tat. It is suggested that such gradients may commonly exist at the boundaries of the ranges of existing populations, providing a new basic mechanism for the evolution of cooperation.

Animals↗
PubMed2001

Characterization of human myocardial fibroblasts immortalized by HPV16 E6--E7 genes.

Human myocardial fibroblasts (HMF) have proved to be useful as a species specific cell culture system in various studies on myocarditis and cardiac remodelling. However, their use is limited, since they are hard to obtain and lifespan is short due to replicative senescence. To overcome these disadvantages, we transfected primary HMF with the E6 and E7 genes of the oncogenic human papillomavirus (HPV) 16. Successful transfection was demonstrated in 3 of 12 experiments by detection of E6-E7 gene transcription with nucleic acid sequence based amplification (NASBA). No significant change of phenotype was noted in the emerging cell lines (HMF(1226D), HMF(1321D), HMF(1226K)), but their in vitro lifespan was increased by 20 to 30 population doublings until cells entered crisis. A single subclone of HMF(1226K) had a transformed phenotype and continued to proliferate indefinitely. This subclone (HMF(1226K/I)) was considered to be immortalized and telomerase activity was detected. Despite the increased risk of mutations due to abrogation of p53 function, HMF(1226K/I) and the HMF lines with an increased lifespan retained the properties of primary HMF cells, as they expressed fibroblast markers (prolyl-4-hydroxylase, vimentin), cytokines (interleukin 1 alpha, 6, 8), and angiotensin II receptors and still were permissive for coxsackievirus B3 infection.

Cell Line↗
PubMed2001

Results of chest wall reirradiation using pulsed-dose-rate (PDR) brachytherapy molds for breast cancer local recurrences.

PURPOSE: We report in a retrospective study on the effect and toxicity of chest wall reirradiation using pulsed-dose-rate (PDR) afterloading molds. METHODS AND MATERIALS: Between 1993 and 1999, a total of 58 patients were treated. All patients presented with locally recurrent breast cancer (31 patients had concomitant distant metastases) after mastectomy and a previously completed course of radiation therapy (median, 54 Gy; range, 36-70). Indication for reirradiation was a progressive macroscopic skin recurrence in 30 cases and an incomplete surgical resection in 28 patients. Standard treatment consisted of a split course with two fractions of 20 Gy (interval, 31 days). The reference dose was prescribed to the skin surface at 5 mm distance from the source. PDR brachytherapy (37 GBq, (192)Ir) was carried out after geometric distance optimization with 0.5-1 Gy/pulse/h. The irradiated median area was 423 cm(2) (range, 100-919). The median follow-up was 18 months (range, 7-84). RESULTS: The actuarial 1-, 2- and 3-year local recurrence-free survival rates in patients treated for macroscopic disease (microscopic disease in parenthesis) were 89% (96%), 81% (85%), and 75% (71%). Local control was obtained in 24/30 (22/28) patients. Twenty-nine of the 34 patients (85%) who deceased during follow-up were locally controlled. 9/58 patients experienced Grade III acute toxicity, 35/58 patients Grade III (29/58 telangiectasia, 6/58 contracture), and 4/58 Grade IV late toxicity (RTOG/EORTC). CONCLUSION: Reirradiation of the chest wall using PDR brachytherapy molds is effective and provides a high local control rate with acceptable toxicity.

Adult↗
PubMed2000

Treatment of primary tracheal carcinoma. The role of external and endoluminal radiotherapy.

BACKGROUND AND PURPOSE: In a retrospective study the role of radiation therapy for the treatment of primary tracheal carcinoma was investigated. PATIENTS AND METHODS: Between 1984 and 1997, 25 patients with primary tracheal carcinoma were treated with external beam radiotherapy (17 squamous-cell carcinoma [SCC], 8 adenoid cystic carcinoma [ACC], median dose SCC 60 Gy. ACC 55 Gy). An additional brachytherapy boost was carried out in 10/25 patients (median dose SCC 18 Gy, ACC 15 Gy). Ten patients underwent operative treatment. RESULTS: The median survival (Kaplan-Meier) for patients with SCC was 33 months (ACC 94.2). The 1-, 2- and 5-year survival rates (Kaplan-Meier) for patients with SCC were 64.7% (ACC 85.7%), 64.7% (ACC 85.7%), and 26% (ACC 85.7%). Patients with ACC and patients with a complete remission after treatment had a significantly better survival probability (log rank test, p < 0.05). An excellent or good relief of clinical symptoms was achieved in 88% of the patients with SCC (ACC 88%). Eleven patients were locally controlled at last follow-up (SCC: 5/17; ACC: 6/8). Grade 1 to 2 toxicity (RTOG/EORTC) occurred in 12% (SCC: 2/17, ACC: 1/8) and Grade 3 to 4 toxicity in 8% (SCC: 0/17, ACC: 2/8) of the patients. Persistent or progressive local disease caused complications in 5 patients (fatal hemorrhage n = 2, esophagotracheal fistula n = 2, tracheal necrosis n = 1). CONCLUSION: Radiation therapy is an effective treatment for primary tracheal neoplasms. Surgery followed by adjuvant radiotherapy and primary radiotherapy in inoperable cases represent potentially curative treatment options. Prospective multicenter studies are needed to determine the optimal radiotherapeutic approach.

Adult↗
PubMed2000

Effect and toxicity of endoluminal high-dose-rate (HDR) brachytherapy in centrally located tumors of the upper respiratory tract.

AIM: To assess effect and toxicity of high-dose-rate afterloading (HDR) alone or in combination with external beam radiotherapy (EBRT) in centrally located tumors of the upper respiratory tract. PATIENTS AND METHODS: From 1987 to 1996, 55 patients were treated. Twenty-one patients (group A1: 17 non-small-cell lung cancer [NSCLC], A2: 4 metastases from other malignancies) were treated using HDR alone due to a relapse after external beam irradiation. In 34 previously untreated and inoperable patients (group B1: 27 NSCLC, B2: 7 metastases from other malignancies) HDR was given as a boost after EBRT (30 to 60 Gy, median 50). HDR was carried out with a 192Ir source (370 GBq). The brachytherapy dose (group A: 5 to 27 Gy, median 20; B: 10 to 20 Gy, median 15) was prescribed to 1 cm distance from the source axis. A distanciable applicator was used in 39/55 patients. RESULTS: In group A1, a response rate (CR, PR) of 53% (group B1: 77%) was reached. The median survival (Kaplan-Meier) was 5 months in group A1 (B1: 20 months). The 1-, 3- and 5-year local progression free survival rates (Kaplan-Meier) were 66% (15%), 52% (0%), and 37% (0%) in group B1 (group A1). Prognostic favorable factors in group B1 were a tumor diameter < 20 mm, the lack of radiological mediastinal involvement, a complete remission, and a Karnofsky performance status > 70. Grade-1 or 2 toxicity (RTOG/EORTC) occurred in 0% in group A and in 6% in group B. We observed no Grade-3 or 4 toxicity. Complications caused by persistent or progressive local disease occurred in 3 patients in group A (fatal hemorrhage, tracheomediastinal fistula, hemoptysis) and in 2 patients in group B (fatal hemorrhage, hemoptysis). CONCLUSIONS: HDR brachytherapy is an effective treatment with moderate side effects. In combination with external beam irradiation long-term remissions can be reached in one third of the patients.

Adult↗
PubMed2000

Long-term results of pulsed irradiation of skin metastases from breast cancer. Effectiveness and sequelae.

PURPOSE: The concept of pulsed brachytherapy suggested by Brenner and Hall requires an unusual fractionation scheme. Effectiveness and sequelae of this new irradiation method were observed in patients with disseminated cutaneous metastases of breast cancer. PATIENTS AND METHODS: A flexible, reusable skin mold (weight 110 g) was developed for use with a pulsed dose rate (PDR) afterloader. An array of 18 parallel catheters (2 mm diameter) at equal distances of 10 or 12 mm was constructed by fixation of the catheters in a plastic wire mesh. The array is sewn between 2 foam rubber slabs of 5 mm thickness to provide a defined constant distance to the skin. Irradiations are possible up to a maximum field size of 20 x 23.5 cm using a nominal 37 GBq Ir-192 source. Pulses of 1 Gy reference dose at the skin surface are applied at a rate of 1 pulse every 1.2 hours (0.8 Gy per hour). The dose distribution is geometrically optimized to provide a homogeneous skin dose (100% +/- 10%). The 80% dose level lies at 5 mm below the skin surface. Between April 1994 and December 1997, 52 patients suffering from cutaneous metastases at the thoracic wall were treated with 54 fields and total doses of 38 to 50 Gy (median 42 Gy) applying 2 PDR courses with a pause of 4 to 5 weeks. RESULTS: Forty-six patients (48 fields) were eligible for evaluation in June 1998. The median follow-up was 16 months (range 7.1 to 46.2 months). Local control was achieved in 40 out of 48 fields (83%) or 41 of 46 patients (89%), respectively. Moist desquamation occurred in 52% of the patients. Late reactions were judged after a minimum follow-up of 6 months. Thirty-two fields had been previously irradiated with external beam therapy to doses of 40 to 60 Gy. Regardless of whether the skin was preirradiated or not all patients surviving long enough developed telangiectasia within 2 years after PDR irradiation. In preirradiated patients (n = 32) skin contractures and/or skin necrosis occurred in 12% each. In newly irradiated patients (n = 14) no contractures or skin necrosis were observed. CONCLUSIONS: Pulsed brachytherapy is an effective and time-sparing method for the treatment of cutaneous metastases from breast cancer. Skin reactions are comparable to the sequelae of orthovoltage therapy. Two sessions of approximately 20 Gy PDR were tolerated on preirradiated skin without severe sequelae.

Brachytherapy↗
PubMed1999

Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC)

PURPOSE: To identify a clinically relevant and available parameter upon which to identify non-small cell lung cancer (NSCLC) patients at risk for pneumonitis when treated with three-dimensional (3D) radiation therapy. METHODS AND MATERIALS: Between January 1991 and October 1995, 99 patients were treated definitively for inoperable NSCLC. Patients were selected for good performance status (96%) and absence of weight loss (82%). All patients had full 3D treatment planning (including total lung dose-volume histograms [DVHs]) prior to treatment delivery. The total lung DVH parameters were compared with the incidence and grade of pneumonitis after treatment. RESULTS: Univariate analysis revealed the percent of the total lung volume exceeding 20 Gy (V20), the effective volume (Veff) and the total lung volume mean dose, and location of the tumor primary (upper versus lower lobes) to be statistically significant relative to the development of > or = Grade 2 pneumonitis. Multivariate analysis revealed the V20 to be the single independent predictor of pneumonitis. CONCLUSIONS: The V20 from the total lung DVH is a useful parameter easily obtained from most 3D treatment planning systems. The V20 may be useful in comparing competing treatment plans to evaluate the risk of pneumonitis for our individual patient treatment and may also be a useful parameter upon which to stratify patients or prospective dose escalation trials.

Adult↗
PubMed1999

HDR-brachytherapy boost for residual tumour after external beam radiotherapy in patients with tracheal malignancies.

Seven inoperable patients with tracheal neoplasms received a high dose rate (HDR) brachytherapy boost (median 15 Gy, single dose 3-5 Gy) for residual tumour after external beam radiotherapy (median 50 Gy, 5 x 2 Gy/week). The median actuarial survival was 34.3 months. The 1-, 2- and 3-year actuarial survival rates were 85.7%, 85.7% and 32%. Local control was obtained in 5/7 patients. Late toxicity occurred in three patients (stenosis n = 2, hemorrhage n = 1). Our data indicate, that a HDR brachytherapy boost is effective and feasible.

Actuarial Analysis↗