Biomedical subjects

A Krüll

Publications and source records attributed to A Krüll.

At least 19 recordsLinked to original sources

PubMed2001

Split-course radiotherapy: where do we stand?

BACKGROUND: Split-course radiotherapy is only rarely applied in curative radiotherapy and there might be a number of arguments to believe that continuous radiotherapy is superior to split-course treatment. In order to point out the evidence current treatment practice is based on, the available randomized trials and some prominent retrospective analyses on split-course radiotherapy were critically assessed. MATERIAL AND METHODS: The analysis of the clinical results was based on published data only. Publications were searched in a Medline database. RESULTS: Assessment of 13 randomized trials, including the data of 2,112 patients, revealed no significant difference between continuous-course and split-course radiotherapy. Astonishingly, the outcome of 77 radiotherapy studies on split-course, most of which are retrospective, seems to depend on the year of publication, suggesting publication bias. CONCLUSIONS: No clinically relevant difference between continuous and split-course radiotherapy could be found. This, of course, does not proof that there are indeed no differences but the data do not allow to draw clear-cut conclusions in favor of or against split-course radiotherapy due to methodological shortcomings of the studies.

Dose Fractionation, Radiation↗

PubMed2001

Impact of treatment acceleration and its timing on the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation.

BACKGROUND AND PURPOSE: In clinical practice a concomitant boost is usually given as a second daily dose to a reduced field. The question arises which part of treatment should be accelerated to achieve optimal tumor control. An experiment was performed on tumor bearing rats to determine the optimal timing of treatment acceleration for this experimental tumor system. MATERIAL AND METHODS: Rhabdomyosarcoma R1H of the rat were treated applying 30 fractions in an overall treatment time of 40-42 days, up to total doses ranging from 67.5 to 97.5 Gy were administered. For control a standard treatment was given as continuous treatment applying one fraction per day. A boost of five additional fractions was given as a second fraction during 5 days. Three experimental arms received a boost either in the 1st, 4th, or in the last week of treatment. Treatment outcome was assessed using tumor control as endpoint. RESULTS: All experimental arms proved more effective than the standard treatment. Treatment was most effective when the boost was administered in the 1st week of treatment. A TCD37% of 87.1 Gy (95% CI: 82.8 ... 92.7 Gy), 96.5 Gy (89.9 ... 107.1), and 107.3 Gy (97.2 ... 131.0) was determined, when the boost was given in the 1st, 4th, or last week of treatment, respectively. The observed difference between the experimental arms was statistically significant (p = 0.004). CONCLUSIONS: Initially accelerated treatment schedules were found to be more effective for tumor control in an experimental tumor system.

Animals↗

PubMed2001

Comparison of total body irradiation vs busulfan in combination with cyclophosphamide as conditioning for unrelated stem cell transplantation in CML patients.

We compared fractionated total body irradiation (12 Gy)/cyclophosphamide (120 mg/kg) with busulfan (16 mg/kg)/cyclophosphamide (120 mg/kg) as preparative therapy in unrelated donor stem cell transplantation of CML patients. Fifty patients with CML (1.CP = 46; aP = 4) and a median age of 36 years (range 16-52) were enrolled in this sequential trial between 1994 and 1999. In both groups patients were well balanced with respect to age, disease status, stem cell source and CMV status. All patients received standard doses of cyclosporin A, methotrexate and anti-thymocyte globulin (ATG) as GVHD prophylaxis. No graft failures occurred in either group. The median day of leukocyte engraftment was earlier in the Bu/Cy than in the TBI/Cy group (day 15 vs 17; P = 0.006). The incidence of grade II-IV GVHD was 40% in the TBI/Cy and 36% in the Bu/Cy group, whereas severe grade III/IV GVHD was only observed in 12% of patients in both groups. The incidence of chronic GVHD (limited and extensive) at 1 year was higher in the Bu/Cy arm (65% vs 30%; P = 0.02). More toxicity grade I/II of the liver (88% vs 44%; P = 0.002) and more hemorrhagic cystitis (32% vs 8%; P = 0.02) were observed in the Bu/Cy regimen. Seven relapses in the TBI and no relapse in the Bu/Cy group were observed after a median follow-up of 44 and 15 months, respectively. The estimated 3 year OS and DFS was 72% (95% CI: 55-98%) and 58% (95% CI: 39-77%) in the TBI and 70% (95% CI: 51-89%) for DFS and OS in the Bu/Cy group. We conclude that the anti-leukemic effect of the Bu/Cy regimen seems to be at least as effective as the TBI/Cy combination in unrelated stem cell transplantation of CML patients, with no graft failures, but that it correlates with a higher incidence of liver toxicity, hemorrhagic cystitis and chronic GVHD. Longer follow-up is necessary to determine the late relapse rate and late toxicity.

Adolescent↗

PubMed2001

Impact of pulmonary metastases of the R1H-tumour on radiation tolerance of rat lung.

PURPOSE: The aim was to investigate the influence of pulmonary metastases of the rhabdomyosarcoma R1H on the radiation response of the lung of the WAG/Rij rat. MATERIAL AND METHODS: Three groups of animals were investigated: metastases-free animals treated with fractionated irradiation of the lungs; metastases-bearing animals receiving no irradiation; and metastases-bearing animals treated with fractionated irradiation initiated 14, 21 or 28 days after induction of pulmonary metastases of the R1H-tumour by i.v. injection of viable tumour cells. Metastases were thus treated at various well-defined sizes. Total doses of 20-60Gy were applied in fractions of 2 Gy within 11 days. Complication rate and survival time were used as endpoints. RESULTS: About 2 months after onset of irradiation treatment, animals had to be sacrificed because of severe respiratory distress either caused by irradiation-induced lung damage (median 57 days, range 36-77 days), or because of development of lung metastases (65, 20-160 days). A decrease of the ED(50) (dose required to induce lethal lung damage in 50% of irradiated animals) was determined for metastases-bearing animals. This effect increased with metastatic volume. CONCLUSIONS: The results suggest that the presence of tumours in the lung decreased the lung tolerance to radiation. This effect can hardly be explained by a reduction in functional lung volume by metastatic volume.

Animals↗

PubMed2000

Influence of dose per fraction and overall treatment time on the response of pulmonary micrometastases of the R1H-tumour to fractionated irradiation.

BACKGROUND AND PURPOSE: Macroscopic subcutaneously growing R1H-tumours have been shown to respond almost independently of the dose per fraction when treated under ambient conditions. In addition decelerated repopulation during fractionated irradiation has been shown for this experimental tumour. The aim of the present study was to investigate whether this is also the case for pulmonary micrometastases which are assumed to be fully oxygenated or whether differences in the oxygenation status of the tumour possibly alters its response to fractionation. The influence of the dose per fraction and overall treatment time on the response of micrometastases to fractionated irradiation was studied. MATERIALS AND METHODS: Pulmonary metastases were induced by i.v. injection of viable tumour cells. Treatment was started 14 days later, when metastases reached an average size of four cells. Total doses of 16 to 28 Gy were administered within an overall treatment time of 11 or 25 days, using doses per fraction of 1, 2, or 4 Gy. Tumour response was quantified by metastatic control (MCD(37%)). RESULTS: Fractionation had a significant influence on local control (P=0.009). After application of 1, 2, or 4 Gy and an overall treatment time of 11 days the MCD(37%) was 25.4 (95% C.I.: 21.5-32.0) Gy, 20.7 (17. 0-24.0) Gy, and 18.5 (14.9-21.6) Gy, respectively. When overall treatment time was prolonged to 25 days the MCD(37%) increased to 25. 5 (21.3-33.5) Gy when fractions of 2 Gy where applied, but this difference was not significant (P=0.13). The doubling time of 12.8 days determined for the metastatic clonogenic tumour cells during fractionated irradiation was significantly longer than the 4.1 days observed for untreated metastases (P=0.006). CONCLUSIONS: The results show a strong influence of fractionation on treatment outcome and a decelerated repopulation during fractionated irradiation treatment for well oxygenated pulmonary metastases of the R1H-tumour.

Animals↗

PubMed1999

[Results of radiotherapy for vertebral hemangioma].

PURPOSE: Assessment of treatment results of symptomatic vertebral hemangiomas and review of the literature (Table 3). PATIENTS AND METHODS: Ten patients treated between 1974 to 1997 were retrospectively analyzed. Efficacy of treatment was determined according to improvement of pain and/or neurological symptoms (Table 1). RESULTS: Improvement was achieved in 8 of 10 patients. The initially existing neurological symptoms of 3 patients disappeared completely in 2 cases and improved in 1 case. Acute side effects were slight. Late side effects were not seen. A dose-effect relationship could not be assessed. There was no relapse. CONCLUSION: Radiotherapy with 30 Gy for symptomatic vertebral angioma as primary therapy is indicated. In case of neurological symptoms a radiotherapy after operative therapy is recommendable even if the patient is free of symptoms to prevent progress or relapse.

Adult↗

PubMed1998

[Radiotherapy of soft tissue sarcomas].

Soft tissue sarcomas are uncommon neoplasms that represent approximately 1% of all malignancies. It is clear that sarcomas require a therapeutic approach that establishes local control and thereby eliminates the potential of metastasis for patients with truly limited disease. Localized sarcomas are generally treated by surgery. Excision must be complete, with a wide margin of normal tissue, and along anatomic planes, or recurrence will almost certainly follow. Amputations are still occasionally required, although limb salvage procedures are being used increasingly, particularly in the context of multimodality therapy with irradiation or chemotherapy. Radiotherapy can be highly effective for improving local control and is used as adjuvant therapy, either preoperatively or postoperatively. In case of non-in-sano-resection a salvage surgery is indicated. Use of adjuvant postoperative radiotherapy allows for more conservative surgery without compromising local control, and therefore often may allow limb salvage where amputation might otherwise be necessary, e.g. in case of R1- or R2-resection without a new resection, a close margin or large tumors with histologic G2 or G3 grading and in case of local relapses. Local control rate of 90% are reported for the combination of pre- and postoperative radiotherapy. Prognosis is still limited by distant metastases. In case of unresectable tumors neutron radiotherapy results in 50% local control. New approaches e.g. hyperfractionated-accelerated radiotherapy, interoperative radiotherapy and chemoradiotherapy are promising perspectives, which are being evaluated in clinical studies. Desmoid tumors benefit of postoperative radiotherapy in case of R1-resection or relapse.

Combined Modality Therapy↗

PubMed1998

Neutron therapy in malignant salivary gland tumors: results at European centers.

Malignant salivary gland tumors are relatively rare and account for only 3%-4% of all head and neck cancers. Especially in adenoid cystic carcinoma, the incidence of local recurrence and distant metastases is influenced by the perineural spread of tumor. In advanced salivary gland tumors, surgery alone has a high incidence of local failure. The results of conventional radiotherapy are suboptimal in inoperable or not completely resected salivary gland tumors and in recurrent disease. The pooled data of some international series for low linear energy transfer radiation show a local control of only 28%. Especially in advanced salivary gland tumors, neutron therapy can improve local control. In Europe at least 570 patients with salivary gland tumors have been treated with neutrons alone or with combined modalities. The clinical data of different centers in Europe and the United States result in a similar local control rate of 67% in gross disease. An analysis of different European series shows on average a complication rate of 10.6% for severe radiation-related morbidity. Modern neutron machines and the use of three-dimensional treatment planning systems are now available in a few institutions and may further reduce side effects.

Aged↗

PubMed1998

European results of neutron therapy in soft tissue sarcomas.

The purpose of this publication is to review the data of European neutron therapy facilities in the treatment of soft tissue sarcoma. In the past locally advanced soft tissue sarcoma was a common indication for neutron therapy in several European centers. Data from 1171 patients treated at 11 centers were analysed on the basis of published data or personal communication. Neutron therapy was of benefit especially for patients with primary radiotherapy of inoperable tumors, and with macroscopic disease after surgery. Local control was about 50% in these patients. These results are superior to those from photon therapy from the literature. Results for postoperative neutron therapy after R0- and R1-resection are similar to those from photon therapy. The incidence of late side effects was considerably high in some neutron series. This is influenced by the treatment of most patients with first-generation machines of limited technical standard, and that in most cases large treatment volumes were irradiated.

Humans↗

PubMed1998

Use of neutron therapy in the management of locally advanced nonresectable primary or recurrent rectal cancer.

Inoperable locally advanced or inoperable recurrent rectal cancer is a difficult problem. Tenesmus, discharge, bleeding and pelvic pain are frequently present and often are associated with infiltration of the sacral plexus. The value of radiotherapy in managing such patients is being appreciated, although up to 40% of the treated patients have no symptomatic response. Improvement in tumor response and control has been scored through efforts to overcome the radio resistance of the hypoxic tumor cells by neutron irradiation. This article is an account of the activity of neutron radiotherapy in such patients. Over 350 patients were entered in studies comparing neutrons used alone and neutrons used in a mixed-beam treatment schedule. At present no therapeutic gain for long-lasting survival has been achieved; however, local control and pain improvement seems to be better with neutrons than with photons.

Humans↗

PubMed1998

Long-term disease-free survival of patients with advanced mantle-cell lymphoma following high-dose chemotherapy.

In advanced stage mantle cell lymphoma, conventional chemotherapy yields a complete remission rate below 40%, and the median survival rate is only about 3 years. Between 1991 and 1996 we treated nine such patients (six male; three female) with high-dose chemotherapy (six of these also with 12 Gy fractionated total body irradiation (TBI)) and peripheral stem cell support (n = 8) or allogeneic bone marrow transplantation (n = 1). The median age was 47 years (range, 28-61). At the time of high-dose chemotherapy, five patients were in first complete remission (CR), two in first partial remission (PR) and two in second remission (CR = 1; PR = 1). High-dose chemotherapy included TBI (12 Gy), etoposide and cyclophosphamide (patients 1-5), TBI and cyclophosphamide (patient 7), busulfan, etoposide and cyclophosphamide (patients 6 and 9), cyclophosphamide and busulfan (patient 8). The patterns of toxicity according to the Bearman score were usually mild (mucositis grade 2, n = 7; renal grade I, n = 2) with no therapy-related fatality. Only one patient developed hepatic toxicity grade III (veno-occlusive disease) but recovered completely. The median time to neutrophil engraftment was 10 days (range, 8-15). After high-dose chemotherapy all patients achieved complete remission. After a median follow-up of 22 months (range, 9.4-64) all patients remain in continuous complete remission. These encouraging results suggest that high-dose chemotherapy can be applied safely and leads to long-term disease-free survival in otherwise incurable disease.

Adult↗

PubMed1997

[Salvage therapy of advanced squamous cell carcinoma of the mouth cavity and oropharynx. Results of interstitial high-dose-rate brachytherapy combined with ablative tumor surgery].

PURPOSE: The clinical effect of high-dose-rate (HDR) interstitial brachytherapy combined with tumor resection was investigated in this retrospective study on patients with recurrent oral and oropharyngeal squamous cell carcinoma. PATIENTS AND METHODS: Oral and oropharyngeal squamous cell carcinoma in 38 patients were treated over a period of 7 years (1988-1994) by HDR interstitial brachytherapy using Gammamed 12i equipment. Pretreatment of patients in terms of irradiation and surgery differed (33 irradiated with a total dose between 60.0 and 75.6 Gy, including 8 patients with additional surgery; 1 patient with surgery alone, and 4 patients without any pretreatment). Indications for interstitial brachytherapy differed according to individual responses to treatment and medical histories. RESULTS: Interstitial brachytherapy was successful in the majority of patients, i.e. complete remission: 12, partial remission: 19, no change: 2, progression: 5. Local control and overall survival including patients with surgical treatment was 59% and 81% at 6 months and 47% and 49% after 12 months, respectively. CONCLUSION: Interstitial HDR brachytherapy with Iridium 192 is recommended in patients with local recurrences or second primary carcinomas after previous external radiotherapy in the head and neck region. Combination of interstitial brachytherapy and surgery is preferable for these patients.

Adult↗

PubMed1997

Combination of fractionated irradiation with nicotinamide and carbogen in R1H-tumours of the rat and its pulmonary metastases.

BACKGROUND AND PURPOSE: The combination of radiotherapy with nicotinamide and carbogen is a promising method to improve treatment outcome. The aim of the present study was to investigate its effect on rat lungs, the R1H-tumour and its pulmonary metastases. MATERIALS AND METHODS: Subcutaneous tumours and artificially induced pulmonary metastases of the rhabdomyosarcoma R1H of the rat were treated either with fractionated irradiation alone or in combination with nicotinamide and carbogen. Local metastatic control, net growth delay and lethal lung damage were used as endpoints. RESULTS: Radiosensitivity of the lungs of WAG/Rij rats increased by a factor of 1.13, while no positive effect of the combined treatment either on subcutaneous R1H-tumours or on pulmonary metastases could be detected. This resulted in a therapeutic loss of 18% (P = 0.003). CONCLUSION: The results indicate that deleterious effects of the combination of radiotherapy with nicotinamide and carbogen cannot be excluded under all circumstances.

Animals↗

PubMed1996

Neutrontherapy in soft tissue sarcomas: a review of European results.

The purpose of this publication is to review the data on European neutrontherapy facilities in the treatment of soft tissue sarcoma. Data on 1171 patients treated at 11 centers were analyzed. Neutrontherapy was of advantage especially for patients with primary radiotherapy of inoperable tumors, and those with macroscopic disease after surgery. Local control was about 50% in these groups. Results for postoperative neutrontherapy after R0 and R1 resection were similar to those for photon therapy. The incidence of late side effects was considerable. This was influenced by the fact that most patients were treated with first-generation machines.

Disease-Free Survival↗

PubMed1996

European results in neutron therapy of malignant salivary gland tumors.

In Europe to date, 501 patients with salivary gland tumors have been treated with neutrons alone or with combined modalities. The most common histological types are adenoid cystic carcinomas, mucoepidermoid carcinomas and malignant mixed tumors. The results of conventional radiotherapy are suboptimal in inoperable or incompletely resected salivary gland tumors and in recurrent disease. The pooled data of some international series for low linear energy transfer radiation show a local control of 28%. Especially in advanced tumors neutron therapy can improve local control and should be the treatment of choice. The clinical data from different therapy centers in Europe show local control of 67% in gross disease.

Carcinoma, Adenoid Cystic↗

PubMed1996

[Results of radiotherapy in recurrences of soft tissue sarcomas].

PURPOSE: Published data for radiotherapy in soft tissue sarcomas refer in most of the cases to the use of irradiation for primary tumors. Experiences of radiotherapy in local recurrences are limited. The own treatment results of a multimodal treatment approach in a large number of patients will be analyzed for local tumor control rates, survival rates, side effects and prognostic factors and will be compared to the literature. PATIENTS AND METHODS: At the University Hospital Hamburg-Eppendorf a total of 98 patients with local recurrences of soft tissue sarcomas were irradiated between 1980 and 1993. The median age of the patients was 55 years. There was a large variety of different histologies. Grading was evaluable in 95 cases: G1 24 patients, G2 21 patients and G3 50 patients. Localisation was dominated by the extremities with 64.3%. Recurrences were reclassified: 21 patients had rT1-tumors and 77 patients had rT2-tumors. Twelve cases showed lymph node metastases and 9 patients distant metastases. Generally treatment included surgery and postoperative irradiation. R-classification showed R0 in 25, R1 in 20 and R2 in 48 cases. Neutrontherapy was prefered in 57 cases and neutron- and photontherapy in 22 cases. Local tumor control rates and survival rates were calculated using the Kaplan-Meier method. Side effects were scored using the RTOG/EORTC scoring system. Univariate and multivariate analyses were applied to evaluate prognostic factors. RESULTS: Local tumor control rates at 5 years were 56.4%, for G1 75.2%, G2 52.5%, G3 47.1%, rT1 66.0%, rT2 53.6%, R0 63.4%, R1 42.3% and R2 53.2%, N0 61.1% vs. N1 31.7%. Survival rates at 5 years were 45.2%, for G1 64.8%, G2 66.9%, G3 25.0%, rT1 60.0%, rT2 41.5%, R0 64.2%, R1 49.3% and R2 32.7%. Acute side effects were scored as grade 1 and grade 2. The rate of grade 3 and 4 late effects was about 6%. Lymph node status was a significant factor for local control. Grade, residual tumor status, type of irradiation and the applied neutron dose were significant factors for survival. CONCLUSIONS: Nowadays no standard treatment exists for local recurrences of soft tissue sarcomas. Treatment should be interdisciplinary. Local recurrences should be avoided by the consequent use of surgery and radiotherapy. It is important that local recurrences should be detected early. Neutrontherapy may bring advantages for local control of recurrences with macroscopic tumor residuals.

Adolescent↗

PubMed1995

Interstitial high-dose rate brachytherapy with iridium-192 in patients with oral squamous cell carcinoma.

Thirty-four patients with recurrent oral and oropharyngeal carcinomas were treated over a period of 4 years, by interstitial high-dose rate (HDR) brachytherapy (BT) using an iridium-192 source (Gammamed 2i and 12i equipment, Sauerwein, Germany) and fractionated application (1 up to 3 times, weekly recovery phases, single maximum dose 10 Gy). Pretreatment characteristics of patients in terms of irradiation (RT) and surgery differed (22 had external RT alone, with a total dose between 60.0 and 75.6 Gy; RT and surgery: 7; surgery alone: 1). The initial TNM-stages (UICC, Hermanek et al., 1987) of patients were: I = 2, II =3, III = 7, IV = 22. In the majority of cases, clinical indications for HDR-BT included tumour recurrence or progression following external RT, and second primary tumours of the oral cavity. Therapy was successful in most cases, i.e. complete remission: 11, partial remission: 16, no change: 2, progression: 5. Local control and overall survival rates, including patients surgically treated after BT, were at 6 months 58% and 62%, and 44% and 53% at 12 months, respectively. This type of treatment is recommended in patients with local recurrence or second primary tumours after previous external RT in the head and neck region. However, the benefit of interstitial HDR-BT remains questionable, particularly in patients with large tumours and lymph node metastases.

Adult↗

PubMed1995

[Results of neutron therapy in recurrent malignant salivary gland tumors in the head and neck area].

PURPOSE: The records of 33 patients of recurrent salivary gland tumors of the head and neck regions were analysed. PATIENTS AND METHODS: 33 patients with recurrent salivary gland tumors were treated with fast neutrons of a 14 MeV DT generator. All patients had been operated several times. 10 patients had been irradiated before with photons or electrons. 24 patients had macroscopic tumor. In many cases advanced tumors were treated. RESULTS: The median follow-up of our patients is 33 months. 6 patients are still alive without disease. 5 patients are alive with local recurrence or tumor progression. The calculated survival rate for all patients is 45% at 5 years. The calculated control rate for all patients is 43% at 5 years. Most of the late side effects according to the RTOG/EORTC-score were moderate. Only in one case severe late side effects could be observed. CONCLUSION: According to the literature advanced recurrences of salivary gland tumors should be treated with fast neutrons.

Adult↗