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Biomedical subjects

R P Müller

Publications and source records attributed to R P Müller.

At least 19 recordsLinked to original sources
PubMed2001

Low-dose radiation is sufficient for the noninvolved extended-field treatment in favorable early-stage Hodgkin's disease: long-term results of a randomized trial of radiotherapy alone.

PURPOSE: To show that radiotherapy (RT) dose to the noninvolved extended field (EF) can be reduced without loss of efficacy in patients with early-stage Hodgkin's disease (HD). PATIENTS AND METHODS: During 1988 to 1994, pathologically staged patients with stage I or II disease who were without risk factors (large mediastinal mass, extranodal lesions, massive splenic disease, elevated erythrocyte sedimentation rate, or three or more involved areas) were recruited from various centers. All patients received 40 Gy total fractionated dose to the involved field areas but were randomly assigned to receive either 40 Gy (arm A) or 30 Gy (arm B) total fractionated dose for the clinically noninvolved EF. No chemotherapy was given. RT films were prospectively reviewed for protocol violations and recurrences retrospectively related to the applied RT. RESULTS: Of 382 recruited patients, 376 were eligible for randomized comparison, 190 in arm A and 186 in arm B. Complete remission was attained in 98% of patients in each arm. With a median follow-up of 86 months, 7-year relapse-free survival (RFS) rates were 78% (arm A) and 83% (arm B) (P =.093). The upper 95% confidence limit for the possible inferiority of arm B in RFS was 4%. Corresponding overall survival rates were 91% (arm A) and 96% (arm B) (P =.16). The most common causes of death (n = 27) were cardiorespiratory disease/pulmonary embolisms (seven), second malignancy (six), and HD (five). Protocol violation was associated with significantly poorer RFS. Nonirradiated nodes were involved in 42 of 52 reviewed relapses, infield areas in 18, marginal areas in 17, and extranodal sites in 16. CONCLUSION: EF-RT alone attains good survival rates in favorable early-stage HD. The 30-Gy dose is adequate for clinically noninvolved areas. Protocol violation worsens the subsequent prognosis. Relapse patterns suggest that systemic therapy can reduce the 20% long-term relapse rate.

Adolescent↗
PubMed2000

[Prognostic value of hemoglobin level for primary radiochemotherapy of head-neck carcinomas].

The pretherapeutic hemoglobin level (Hb) has been postulated to constitute a prognostic marker for outcome after primary chemoradiation of patients with advanced cancer of the head and neck. However, this hypothesis has not been tested systematically in large study samples. In the years 1992-1997, 125 patients with advanced head and neck cancer (stages III/IV UICC) were treated with primary chemoradiation in two different prospective multicentric trials, 62 patients in trial A (phase II, 1992-1995), and 63 in trial B (phase III, 1995-1997). Beside initial Hb, other pretherapeutic parameters with potential prognostic relevance were assessed and correlated with clinical outcome after 43-months follow-up: total tumor volume (TTV; calculated in initial CT scans), tumor oxygenation (polarographic measurements with Eppendorf histography), TNM, tumor localization, age, and performance status. The evaluation of the clinical end points (progression-free and overall survival and local tumor control) revealed that Hb and TTV were independent parameters with strong predictive character of outcome after primary chemoradiation in both trials (n = 125). Bivariate analysis showed < median (13.5 g/dl) a hazard ratio of 2.1 (P = 0.002) for Hb; and > median (98 ml) a Hazard ratio of 2.0 (P = 0.006) for TTV. Severe anemia (Hb < 10 g/dl) was an adverse factor in three patients. Hypoxia was associated with poorer initial therapeutical response but was not predictive of clinical outcome. Furthermore, tumor oxygenation showed no correlation with Hb. The other parameters examined failed to show prognostic significance. Our results indicate a high prognostic value of initial Hb for outcome after primary chemoradiation in advanced head and neck cancer and imply a therapeutic benefit of Hb substitution or erythropoietin administration. We propose to test this in randomized clinical trials.

Adult↗
PubMed2000

Computer simulation of cytotoxic and vascular effects of radiosurgery in solid and necrotic brain metastases.

PURPOSE: Solid and necrotic brain tumors respond to radiosurgery, although necrotic lesions often contain a significant proportion of hypoxic cells which cannot become reoxygenated during the short overall treatment time of single dose application. In addition to the direct cytotoxic action, delayed vascular occlusion followed by ischemic tumor cell death could contribute to the effect of radiosurgery. MATERIALS AND METHODS: In order to determine the impact of the two possible effects on tumor response, a 3-dimensional computer simulation was developed and fitted to response data obtained from 90 patients who were treated by LINAC radiosurgery for 1-3 brain metastases with median marginal doses of 20 Gy. Complete response rates were as follows: small, solid lesions (diameter 0.4-1 cm), 52% (12/23); large solid lesions (1.1-5.2 cm), 28% (17/60); large necrotic lesions, 12% (6/50). The 3-dimensional computer model simulated the growth of small solid and large, solid or necrotic tumors situated in a vascularized stroma. Oxygen supply, tumor cell division (cell cycle time 5 days), neovascularization, tumor cell kill by single dose irradiation (linear-quadratic model, alpha/beta=10 Gy, oxygen enhancement ratio 3.0) and time-dependent vascular occlusion (alpha/beta=3 Gy) were modeled by Monte-Carlo simulation techniques. RESULTS: In the presence of neovascularization, solid tumors with a hypoxic fraction of 1-2% developed. Without neoangiogenesis, central necrosis occurred, and tumors had a hypoxic fraction of 20-25%. Assuming a pure cytotoxic effect of radiosurgery, neither the dose-response relationship for the solid lesions of different size nor that for the large lesions with solid or necrotic appearance could be reproduced for any given level of radiosensitivity. This was only possible by introducing a vascular effect that led to the occlusion of >/=99% of the vessels at the border of the target volume within 1 year after irradiation. In the presence of the vascular effect, the apparent radiosensitivity of the tumor cells was increased by 50-100%. Calculations of the dose-equivalent for the vascular effect show that it contributes 19-33% of the overall effect of single dose radiosurgery. CONCLUSION: This simulation study suggests that the therapeutic effect of single radiosurgery in malignant brain tumors cannot be understood without the consideration of vascular effects. The computer model might serve as a basis for exploring new treatment modalities that modify both cytotoxic and vascular effects of radiosurgery.

Blood Vessels↗
PubMed2000

On isocentre adjustment and quality control in linear accelerator based radiosurgery with circular collimators and room lasers.

We have developed a densitometric method for measuring the isocentric accuracy and the accuracy of marking the isocentre position for linear accelerator based radiosurgery with circular collimators and room lasers. Isocentric shots are used to determine the accuracy of marking the isocentre position with room lasers and star shots are used to determine the wobble of the gantry and table rotation movement, the effect of gantry sag, the stereotactic collimator alignment, and the minimal distance between gantry and table rotation axes. Since the method is based on densitometric measurements, beam spot stability is implicitly tested. The method developed is also suitable for quality assurance and has proved to be useful in optimizing isocentric accuracy. The method is simple to perform and only requires a film box and film scanner for instrumentation. Thus, the method has the potential to become widely available and may therefore be useful in standardizing the description of linear accelerator based radiosurgical systems.

Algorithms↗
PubMed2000

Dosimetric analysis at ICRU reference points in HDR-brachytherapy of cervical carcinoma.

In vivo dosimetry in bladder and rectum as well as determining doses on suggested reference points following the ICRU report 38 contribute to quality assurance in HDR-brachytherapy of cervical carcinoma, especially to minimize side effects. In order to gain information regarding the radiation exposure at ICRU reference points in rectum, bladder, ureter and regional lymph nodes those were calculated (digitalisation) by means of orthogonal radiographs of 11 applications in patients with cervical carcinoma, who received primary radiotherapy. In addition, the doses at the ICRU rectum reference point was compared to the results of in vivo measurements in the rectum. The in vivo measurements were by factor 1.5 below the doses determined for the ICRU rectum reference point (4.05 +/- 0.68 Gy versus 6.11 +/- 1.63 Gy). Reasons for this were: calibration errors, non-orthogonal radiographs, movement of applicator and probe in the time span between X-ray and application, missing connection of probe and anterior rectal wall. The standard deviation of calculations at ICRU reference points was on average +/- 30%. Possible reasons for the relatively large standard deviation were difficulties in defining the points, identifying them on radiographs and the different locations of the applicators. Although 3 D CT, US or MR based treatment planning using dose volume histogram analysis is more and more established, this simple procedure of marking and digitising the ICRU reference points lengthened treatment planning only by 5 to 10 minutes. The advantages of in vivo dosimetry are easy practicability and the possibility to determine rectum doses during radiation. The advantages of computer-aided planning at ICRU reference points are that calculations are available before radiation and that they can still be taken into account for treatment planning. Both methods should be applied in HDR-brachytherapy of cervical carcinoma.

Brachytherapy↗
PubMed1999

[Quality assurance in radio-oncology/radiotherapy: basic considerations].

Since 1994 the German Radiooncological Society has established a special commission for quality assurance in radiation oncology. The working agenda covers guidelines for dosimetry, infrastructure and organisation of a radiooncological department. The efforts are in close cooperation with the quality assurance programs of the EORTC. Corresponding guidelines are being published. They can be applied to create a quality assurance system in a radiooncological department. They are not considered definitive and are still receptive to benefit from further modifications.

Germany↗
PubMed1998

[Radiotherapy of follicle center lymphoma. Results of a German multicenter and prospective study. Members of the Study Group "NHL-early stages"].

PURPOSE: Follicle centre lymphoma grade I, II (REAL) or centroblastic-centrocytic lymphoma (Kiel classification) present a well defined clinical entity from a clinical point of view. These lymphomas are not curable by chemotherapy in early or advanced stages. They are treated by radiation therapy in early stages, but up to now the curative potency of radiotherapy has not been confirmed by prospective clinical trials. PATIENTS AND METHODS: Between January 1986 and August 1993 117 adults with follicle centre lymphoma were recruited from 24 institutions to enter the multicentric prospective, not randomised clinical trial. Patients with histologically proven nodal follicle centre lymphoma of stages I, II and limited III were included. They were treated by a standardised radiotherapy regimen, in stage I by extended field and in stages II and III by total nodal irradiation. Dose per fraction was 1.8 to 2.0 Gy, in the abdominal bath 1.5 Gy up to a total dose of 26 Gy in adjuvant situation and 36 Gy to enlarged lymphoma. RESULTS: All patients developed a complete remission at the end of radiotherapy. Median follow-up is 68 months. Overall survival of all patients in 86 +/- 3% at 5 and 8 years. Stage adjusted survival at 5 and 8 years was 89% for stage I, 86% for stage II and 81% for III. Patients in stages I and II < 60 years had survival rates of 94% at 5 and 8 years, patients > 60 years 63% (p < 0.0001). Recurrence free survival of all patients is 70% at 5 and 60 +/- 5% at 8 years. The number of recurrences is high with 29% at 5 and 41% at 8 years. All recurrences were seen within 7 years. The probability of localised nodal in-field recurrences is 11% and 22% at 5 and 8 years, respectively. Adverse prognostic factors were identified by multivariate analysis: age > 60 years, treatment breaks > or = 7 days and dose deviations > 20% from prescribed doses. Acute side effects of extended field irradiation were moderate. CONCLUSIONS: On the basis of these results radiotherapy is a potentially curative therapeutic approach in stages I, II and limited III of follicle centre lymphoma. The optimal technique is total lymphoid irradiation with doses of 30 Gy in the adjuvant situation and 40 to 44 Gy in enlarged lymphomas. The number of local recurrences leads to the assumption, that the extension of radiotherapy to the total lymphoid system might reduce their frequency.

Adult↗
PubMed1998

External beam radiation in patients suffering from exudative age-related macular degeneration. A matched-pairs study and 1-year clinical follow-up.

BACKGROUND: The aim of this prospective study was to ascertain whether external beam irradiation is effective in patients with subretinal neovascularization (SRN) due to age-related macular degeneration (AMD). METHODS: All patients had subfoveal SRN due to AMD as verified by fluoresceinangiography. Two hundred and eighty-seven patient-eyes were treated by external beam irradiation (total dose of 16 Gy in 2-Gy fractions, 5 times a week) from January 1996. The analysis was restricted to those 73 patients with a minimum follow-up of 11 months. Eighteen patients with subfoveal SRN who refused treatment served as control group (CG). 18 patients of the treatment group (TG) were matched for visual acuity, refraction and extent of SRN. The statistical analysis was performed with the unpaired t-test. RESULTS: The mean age of the CG was 73.9 years (range 66.9-81.3 years) and of the TG 75.6 years (range: 65.7-80.6 years). The median follow-up was 13.5 months (range 11.9-18.4 months) in the CG and 12.9 months (range 11-13.9 months) in the TG. The initial visual acuity (VA) was 20/80 in both groups. After 7 months the follow-up revealed median VA of 20/400 in the CG and 20/160 in the TG (P=0.0335). The final median VA was 20/400 in both groups, with a range from 20/40 to 20/1000 in the CG and from 20/63 to 20/500 in the TG (P=0.2433). The SRN doubled in size during this time in both groups. CONCLUSION: These results suggest that external beam irradiation applied in 2-Gy fractions 5 times a week slows down the visual loss in exudative AMD for a short time. Nevertheless, the patients' reading vision could not be saved in the long term.

Aged↗
PubMed1998

Radiation-induced hyposalivation and its treatment with oral pilocarpine.

OBJECTIVE: The aim of this study was to determine the effects of radiation on the secretion of saliva from mucous salivary glands in comparison with serous salivary glands. STUDY DESIGN: The minor salivary glands of the palate were used as an example of mucous glands, while the parotid glands were used as an example of a serous secretion organ. Serial flow rate measurements of the parotid and palatal glands were taken over a period of approximately 9 months in 13 patients who suffered from malignancies of the head and neck region. Twelve patients consented to take part in a second study in which salivary flow was stimulated by oral pilocarpine before and at the conclusion of radiotherapy and 7 months later. Complaints and symptoms were recorded at each time of measurement. RESULTS: After radiotherapy, the secretory performance of the parotid glands dropped off rapidly and irreversibly. Salivary secretion from the palatal glands was not totally diminished as a result of radiation. Clinical complaints and histologic findings indicate a serious alteration of the tissues irradiated; however, residual secretion from the remaining parenchyma of the mucous glands still remains. Pilocarpine produced a clinically significant increase of salivary flow from the palatal glands before and 7 months after radiation. Secretory performance of the parotid glands could not be sufficiently increased by stimulation with pilocarpine after radiotherapy. Clinical side effects and risks for the treatment of symptomatic postradiation xerostomia with pilocarpine were minimal. CONCLUSIONS: These findings emphasize the greater resistance and recoverability of the mucous secreting minor palatal glands in comparison with the serous secreting parotid glands. They also indicate the significant postradiation ability of the mucous secreting glands to be stimulated by pilocarpine.

Carcinoma, Squamous Cell↗
PubMed1998

Computerized optimization of multiple isocentres in stereotactic convergent beam irradiation.

A method for the fully computerized determination and optimization of positions of target points and collimator sizes in convergent beam irradiation is presented. In conventional interactive trial and error methods, which are very time consuming, the treatment parameters are chosen according to the operator's experience and improved successively. This time is reduced significantly by the use of a computerized procedure. After the definition of target volume and organs at risk in the CT or MR scans, an initial configuration is created automatically. In the next step the target point positions and collimator diameters are optimized by the program. The aim of the optimization is to find a configuration for which a prescribed dose at the target surface is approximated as close as possible. At the same time dose peaks inside the target volume are minimized and organs at risk and tissue surrounding the target are spared. To enhance the speed of the optimization a fast method for approximate dose calculation in convergent beam irradiation is used. A possible application of the method for calculating the leaf positions when irradiating with a micromultileaf collimator is briefly discussed. The success of the procedure has been demonstrated for several clinical cases with up to six target points.

Arteriovenous Malformations↗
PubMed1998

Emergency stenting of malignant obstruction of the upper airways: long-term follow-up with two types of silicone prostheses.

We report on 10 patients with severe malignant "mixed-type" obstruction of the proximal trachea or distal trachea plus both main stem bronchi. They had far-advanced inoperable tumors (esophageal cancer in 4 patients, lung cancer in 3, and recurrent laryngeal, uvular, and thyroid cancers in 1 each). Emergency treatment consisted of a dilating bougie maneuver followed by the insertion of a large one-way (4 patients) or Y-shaped (6) silicone prosthesis. Subsequent to the intervention, there was long-lasting clinical improvement. The median survival from stent insertion was 8 months for all patients irrespective of tumor type; it was 5 months for lung carcinoma patients and 8 months for those with esophageal cancer. The results are in accordance with those of other studies using different therapeutic modalities. Stent exchange proved necessary in 5 patients. The main reasons were continuing tumor growth beyond the proximal and distal boundaries and recurrent productive bronchial infection. Patients died of pneumonia (4 patients), pulmonary lymphangitic spread (1), heart failure (2, one of whom also had pneumonia), and fatal hemorrhage (1). As of December 1995, 3 patients were still alive, 2, 5, and 8 months after stent implantation. As evidenced by clinical efficacy and length of palliation, endoscopic placement of silicone-based one-way and bifurcated prostheses in far-advanced tumor of the central airways is technically feasible and ethically justifiable.

Aged↗
PubMed1997

Extended field and total central lymphatic radiotherapy in the treatment of early stage lymph node centroblastic-centrocytic lymphomas: results of a prospective multicenter study. Study Group NHL-frühe Stadien.

BACKGROUND: A prospective multicenter trial was performed to evaluate survival, patterns of relapse, and toxicity for clinically staged patients with lymph node centroblastic-centrocytic (cb/cc) lymphomas in Stages I-IIIA after large extended field irradiation (EFI) or total central lymphatic irradiation (TCLI). METHODS: Between January 1986 and August 1993, 117 adults with clinical Stage I-IIIA lymph node cb/cc lymphoma (Kiel classification) were recruited. Patients in Stages I or II with mediastinal, hilar, periaortic, iliac, or mesenteric involvement and in Stage IIIA received TCLI, whereas patients with more peripherally located cb/cc lymphomas were treated with EFI. TCLI and EFI were administered to a total dose of 26 gray (Gy) with 2 Gy per daily fraction, with the exception of the whole abdomen, which was irradiated to a total dose of 25.5 Gy with 1.5 Gy per fraction. A boost of 10 Gy with 2 Gy per fraction was administered to enlarged and involved lymph nodes at the start of radiotherapy. RESULTS: Sixty, 40, and 17 patients had Stage I, II, and limited IIIA disease (no bulk and less than 6 involved lymph node regions), respectively. Overall survival was 86% at 5 and 7 years; median follow-up was 68 months. The probabilities of relapse at any site, recurrences in lymph nodes, and in-field lymph node recurrences after TCLI were 17% in Stage I; 56%, 43%, and 40% in Stage II, respectively; and 44%, 35%, and 35% in Stage IIIA, respectively. The risk of disseminated extralymphatic relapses was 9% at 7 years. The most important adverse prognostic factor for in-field lymph node recurrences was a deviation of >20% from the assigned total radiation dose. After EFI, patients in Stage I had a significantly lower risk of recurrences in adjuvant irradiated lymph node regions than in unirradiated lymph node regions. Acute toxicity of EFI and TCLI was moderate. CONCLUSIONS: In-field lymph node recurrences remained the main risk after TCLI, and a deviation of >20% from the assigned radiation dose was the major risk factor for in-field recurrences. From these data, a total dose of 40-44 Gy in conventional fractionation for the treatment of macroscopic cb/cc lymphomas and 30 Gy for the treatment of subclinical disease is recommended. A randomized study comparing TCLI with EFI is now being organized by this group.

Adult↗
PubMed1997

Risk analysis of LINAC radiosurgery in patients with arteriovenous malformation (AVM).

The purposes of this analysis were the evaluation of the toxicity of stereotactic single dose irradiation in patients with an arteriovenous malformation (AVM) and the comparison of the authors' own results with already existing risk prediction models. Computed-tomography (CT) or magnetic-resonance (MR) images, and clinical data of patients treated with linear accelerator radiosurgery for an AVM were analysed retrospectively. Using the Cox proportional hazards model (1), the relevance of treatment parameters and dose-volume relationships to the occurrence of radiation-induced tissue changes (oedema and localised blood-brain-barrier breakdown) were assessed. The 81 patients selected for analysis had a mean follow-up of 28.9 months (range: 9.0-65.7 months). Radiation-induced tissue changes (22 out of 81 i.e. 27.2%) were documented on CT or MR images 6.3-33.8 months after radiosurgery (median time: 12.8 months). The actuarial risk at 2 years was 32.1% for the development of neuroradiological changes and 20.1% for the development of symptomatic tissue alteration. The coefficient of total volume receiving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model. These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.

Actuarial Analysis↗
PubMed1997

[Development of guidelines in radiation oncology].

BACKGROUND: On a national and international level many scientific and health political efforts are undertaken to develop specific guidelines for various medical disciplines. They are thought to improve the transparency of the medical health system and guarantee an improvement and special care for the individual patients. Besides other medical disciplines radiation oncology also has to develop and establish such guidelines. METHODS: After a specific definition of the different terms "standard", "guidelines" and "recommendation" a general description of the principle process involved in the development of guidelines is given. Furthermore, the current activities of the special working group "Quality Control in Radiation Oncology" of the German Radiation Oncology Society are elaborated. RESULTS: A detailed set of guidelines is expected to be completed by the end of 1997.

Consensus Statements as Topic↗