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Biomedical subjects

W Harms

Publications and source records attributed to W Harms.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1995

The cumulative verification image analysis tool for offline evaluation of portal images.

PURPOSE: Daily portal images acquired using electronic portal imaging devices contain important information about the setup variation of the individual patient. The data can be used to evaluate the treatment and to derive correction for the individual patient. The large volume of images also require software tools for efficient analysis. This article describes the approach of cumulative verification image analysis (CVIA) specifically designed as an offline tool to extract quantitative information from daily portal images. METHODS AND MATERIALS: The user interface, image and graphics display, and algorithms of the CVIA tool have been implemented in ANSCI C using the X Window graphics standards. The tool consists of three major components: (a) definition of treatment geometry and anatomical information; (b) registration of portal images with a reference image to determine setup variation; and (c) quantitative analysis of all setup variation measurements. The CVIA tool is not automated. User interaction is required and preferred. Successful alignment of anatomies on portal images at present remains mostly dependent on clinical judgment. Predefined templates of block shapes and anatomies are used for image registration to enhance efficiency, taking advantage of the fact that much of the tool's operation is repeated in the analysis of daily portal images. RESULTS: The CVIA tool is portable and has been implemented on workstations with different operating systems. Analysis of 20 sequential daily portal images can be completed in less than 1 h. The temporal information is used to characterize setup variation in terms of its systematic, random and time-dependent components. The cumulative information is used to derive block overlap isofrequency distributions (BOIDs), which quantify the effective coverage of the prescribed treatment area throughout the course of treatment. Finally, a set of software utilities is available to facilitate feedback of the information for treatment plan recalculation and to test various decision strategies for treatment adjustment. CONCLUSIONS: The CVIA tool provides comprehensive analysis of daily images acquired with electronic portal imaging devices. Its offline approach allows characterization of the nature of setup variation for the individual patient that would have been difficult to deduce using only a few daily or weekly portal images. Distribution of the tool will help establish an important database of setup variation from many clinics. The information derived from CVIA can also serve as the foundation to integrate treatment verification, treatment planning, and treatment delivery.

Computer Peripherals↗
PubMed1995

Three-dimensional treatment planning and conformal radiation therapy: preliminary evaluation.

Preliminary clinical results are presented for 209 patients with cancer who had treatment planned on our three-dimensional radiation treatment planning (3-D RTP) system and were treated with external beam conformal radiation therapy. Average times (min) for CT volumetric simulation were: 74 without or 84 with contrast material; 36 for contouring of tumor/target volume and 44 for normal anatomy; 78 for treatment planning; 53 for plan evaluation/optimization; and 58 for verification simulation. Average time of daily treatment sessions with 3-D conformal therapy or standard techniques was comparable for brain, head and neck, thoracic, and hepatobiliary tumors (11.8-14 min and 11.5-12.1, respectively). For prostate cancer patients treated with 3-D conformal technique and Cerrobend blocks, mean treatment time was 19 min; with multileaf collimation it was 14 min and with bilateral arc rotation, 9.8 min. Acute toxicity was comparable to or lower than with standard techniques. Sophisticated 3-D RTP and conformal irradiation can be performed in a significant number of patients at a reasonable cost. Further efforts, including dose-escalation studies, are necessary to develop more versatile and efficient 3-D RTP systems and to enhance the cost benefit of this technology in treatment of patients with cancer.

Bile Duct Neoplasms↗
PubMed1994

Design of a fully integrated three-dimensional computed tomography simulator and preliminary clinical evaluation.

PURPOSE: We describe the conceptual structure and process of a fully integrated three-dimensional (3-D) computed tomography (CT) simulator and present a preliminary clinical and financial evaluation of our current system. METHODS AND MATERIALS: This is a preliminary report on 117 patients treated with external beam radiation therapy alone on whom a 3-D simulation and treatment plan and delivery were carried out from July 1, 1992, through June 30, 1993. The elements of a fully integrated 3-D CT simulator were identified: (a) volumetric definition of tumor volume and patient anatomy obtained with a CT scanner, (b) virtual simulation for beam setup and digitally reconstructed radiographs, (c) 3-D treatment planning for volumetric dose computation and plan evaluation, (d) patient-marking device to outline portal on patient's skin, and (e) verification (physical) simulation to verify portal placement on the patient. Actual time-motion (time and effort) recording was made by each professional involved in the various steps of the 3-D simulation and treatment planning on computer-compatible forms. Data were correlated with the anatomic site of the primary tumor being planned. Cost accounting of revenues and operation of the CT simulator and the 3-D planning was carried out, and projected costs per examination, depending on case load, were generated. RESULTS: Average time for CT volumetric simulation was 74 min without or 84 min with contrast material. Average times were 36 min for contouring of tumor/target volume and 44 min for normal anatomy, 78 min for treatment planning, 53 min for plan evaluation/optimization, and 58 min for verification simulation. There were significant variations in time and effort according to the specific anatomic location of the tumor. Portal marking of patient on the CT simulator was not consistently satisfactory, and this procedure was usually carried out on the physical simulator. Based on actual budgetary information, the cost of a volumetric CT simulation (separate from the 3-D treatment planning) showed that 1500 examinations per year (six per day in 250 working days) must be performed to make the operation of the device cost effective. The same financial projections for the entire 3-D planning process and verification yielded five plans per day. Some features were identified that will improve the use of the 3-D simulator, and solutions are offered to incorporate them in existing devices. CONCLUSIONS: Commercially available CT simulators lack some elements that we believe are critical in a fully integrated 3-D CT simulator. Sophisticated 3-D simulation and treatment planning can be carried out in a significant number of patients at a reasonable cost. Time and effort and therefore cost vary according to the anatomic site of the tumor being planned and the number of procedures performed. Further efforts are necessary, with collaboration of radiation oncologists, physicists, and manufacturers, to develop more versatile and efficient 3-D CT simulators, and additional clinical experience is required to make this technology cost effective in standard radiation therapy of patients with cancer.

Adult↗