Biomedical subjects

M Flentje

Publications and source records attributed to M Flentje.

At least 55 records · Page 3Linked to original sources

PubMed1999

Radiation-induced comet-formation in human skin fibroblasts from radiotherapy patients with different normal tissue reactions.

BACKGROUND: In clinical radiotherapy most patients tolerate the applied dosage with no or moderate side effects. However, 5 to 10% of all individuals show increased acute and/or late reactions. In-vitro test systems are investigated for their suitability for predictive purposes. This paper attempts a correlation between the induction and repair of DNA damage measured in the comet assay and the clinical observed reaction in order to evaluate the suitability of the comet assay for prediction of radiation sensitivity. PATIENTS AND METHODS: Skin fibroblasts of 30 patients with average tissue reactions or acute and/or late increased side effects and cell lines of 4 individuals carrying the heritable disease ataxia telangiectasia (AT) were irradiated in vitro. The induction and repair of DNA damage was measured at different time points after irradiation in the comet assay (single cell gel electrophoresis). These results were compared to the acute and late clinical reactions classified according to the RTOG grading system. RESULTS: The radiation induced DNA damage decreased over time reflecting DNA repair. Cells of the AT individuals showed an elevated damage induction and a reduced repair capacity compared to patients with average tissue reactions. Fibroblasts of patients with increased acute and late side effects exhibited slower DNA repair. In addition to the known lack of cell cycle control, our results indicate that AT cells show reduced DNA repair capacity. CONCLUSIONS: The comet assay seems to be able to detect some types of increased individual radiation sensitivity. In contrast to other predictive in-vitro tests, the comet assay needs less time and fewer cells, which would be useful in a clinical setting.

Ataxia Telangiectasia↗

PubMed1999

Curative-intent radiation therapy in anal carcinoma: quality of life and sphincter function.

In 22 colostomy-free survivors of curative-intent radiation therapy or chemoradiation for anal carcinoma, measurement of the Gastrointestinal Quality of Life Index (GIQLI) revealed a mean 114 of a maximum 144 points, as compared to 121 in healthy volunteers (n = 150) and 113 in patients with benign anorectal diseases (n = 325). Sixteen patients underwent anorectal manometry to determine anal sphincter length (SL), resting pressure (RP), maximum squeeze pressure (MSP), rectal compliance (RC) and relaxation of the internal anal sphincter (RIAS). SL, RP and MSP were significantly lower in anal carcinoma patients than in healthy volunteers. Complete continence was detected in 56% of patients.

Adult↗

PubMed1999

3D-recurrence-patterns of glioblastomas after CT-planned postoperative irradiation.

BACKGROUND AND PURPOSE: The introduction of computed-tomography as an advanced planning tool for the irradiation of intracranial tumours led to a controversial discussions about the optimal target-volume for the primary and postoperative treatment of malignant gliomas. This study analyses the three-dimensional tumour regrowth pattern relative to the treated volume which included the macroscopic preoperative tumour and 2-cm safety margin. MATERIALS AND METHODS: Seventy-nine patients with histologically-confirmed Glioblastoma multiforma and documented recurrence who were irradiated in our department between 1990 and 1996 were reviewed. With the help of a computer program written for this purpose, the PTV of the CT-based treatment plan was reconstructed and its spatial outline compared with the reconstructed volume of the recurrent tumour in the control CT-study. RESULTS: In 33 out 34 patients for which the CT-study showing tumour-recurrence was available the recurrence was completely situated within the original 90%-isodose. Only one tumour surpassed the outside surface of the PTV but was predominantly situated within the original tumourbed and suggests a tumour-regrowth within the high dose volume. CONCLUSIONS: The above results show that target-volumes based on the preoperative size of the enhanced tumour mass well cover the site of recurrence in nearly all cases. The findings suggest dose escalation to a more restricted volume.

Adult↗

PubMed1999

Prognostic impact of total tumor volume and hemoglobin concentration on the outcome of patients with advanced head and neck cancer after concomitant boost radiochemotherapy.

PURPOSE: To identify prognostic clinical and treatment related factors for local control, distant metastasis-free survival, and survival by means of a multivariate analysis in patients with advanced squamous cell carcinoma of the head and neck after concomitant boost radiochemotherapy. PATIENTS AND METHODS: From 1992 to 1995, 68 patients with squamous cell cancer of the head and neck (93% stage IV disease) were treated with a simultaneous radiochemotherapy with Carboplatin using a concomitant boost technique. The total tumor volume (TTV) was quantitatively determined based on computed tomography scans in 56 patients. A Cox proportional hazards regression analysis was performed for each of the above endpoints and statistical significance of the Cox models was verified using the likelihood ratio test and Bonferroni correction for multiple testing. RESULTS: The survival and locoregional control rates at three years were 35 and 32%. The multivariate analysis revealed a significant association between the TTV and survival (P = 0.0008) and between the pretreatment serum hemoglobin concentration and locoregional control (P = 0.01) and survival (P = 0.05). The locoregional control was significantly associated with the N-stage (P = 0.007) and there was a good correlation between the N-stage and TTV in this study population. CONCLUSION: Our data corroborate the prognostic relevance of the tumor volume and hemoglobin concentration. In studies comparing the survival of patients with advanced cancer of the head and neck, the use of the TTV as a covariable may improve the statistical power.

Adult↗

PubMed1999

Acute and late toxicity, tumour control and intrinsic radiosensitivity of primary fibroblasts in vitro of patients with advanced head and neck cancer after concomitant boost radiochemotherapy.

BACKGROUND AND PURPOSE: The existence of hereditary factors influencing the cellular response to ionising radiation has led to the hypothesis that the inter-patient variability of clinical radiation reactions may, at least in part, be attributable to an individual, or intrinsic, radiosensitivity. Considerable effort has been spent in the development of test systems that would determine individual radiosensitivity before or early during radiotherapy to possibly predict treatment outcome, but the results are still conflicting. The present explorative study was therefore aimed at the detection of associations between acute and late radiation effects, tumour control and in vitro radiosensitivity of primary normal tissue fibroblasts. PATIENTS AND METHODS: Sixty-eight patients with squamous cell carcinoma of the head and neck (93% UICC stage IV) were treated with a simultaneous concomitant boost radiochemotherapy with Carboplatin as part of a prospective non-randomised multicenter study at the University of Heidelberg. Primary fibroblasts were obtained from skin biopsies prior to treatment from 25 unselected patients of this study and the SF2 was determined using the colony forming assay and high dose-rate irradiation. The median follow-up was 21 months (range 2.5-81 months). RESULTS: The locoregional control rate at three years was 32%. No significant association between acute (mucosa reaction grade 1 or 2 vs. grade 3 and 4), late radiation effects (subcutaneous fibrosis, osteonecrosis, larynx oedema), locoregional tumour control and SF2 of primary fibroblasts was found using Cox proportional hazards regression analysis, log-rank test and Mann-Whitney U-test. Although a steep dose-response relationship was observed for the radiation-induced severe larynx oedema, Cox proportional hazards regression analysis could not fully explain the occurrence of severe radiation-induced larynx oedema with the dose to the larynx (P = 0.09). In the subgroup of twenty-five patients, where the SF2 was determined, bivariate analysis revealed about the same non-significant influence of the dose to the larynx on the larynx oedema (P = 0.1) and no influence of the SF2 (P = 0.5). CONCLUSIONS: In our study of patients with advanced cancer of the head and neck, neither the normal fibroblast SF2 nor the severity of acute radiation effects were able to predict late radiation effects or locoregional tumour control.

Adult↗

PubMed1999

Long-term survival following postmastectomy locoregional recurrence of breast cancer.

Only a few reports describe long-term survivors following locoregional recurrence of breast cancer after mastectomy. We analyzed 145 patients who were treated for an isolated postmastectomy breast cancer recurrence at our department between 1979 and 1992. All patients were free from distant metastases at the time of recurrence. Nineteen of these patients remained free from distant metastases after a follow-up of more than 10 years following recurrence. Clinical and histopathological characteristics of these 19 patients were analyzed. Primary tumors were small with almost all being T1 or T2 primaries. The majority of survivors had negative axillary node status (16/19 [84%]). Locoregional recurrences were mainly chest wall recurrences (16/19 [84%]) and all recurrences were smaller than 5 cm (19/19). Only 7 patients showed a typical scar recurrence. Sixteen patients had a single recurrent nodule. Early recurrences (<1 year after mastectomy) were rare (n=2). Treatment of recurrence consisted of tumor excision in all cases followed by radiotherapy in 16 patients (including 6 patients who had undergone elective irradiation following mastectomy), hormonal therapy in 6 and chemotherapy in 1 case. In all patients local control at the recurrence site was achieved. Cure after postmastectomy recurrence seems possible in a subgroup of patients (small primary tumor with negative axilla, small and solitary chest wall recurrence) provided adequate therapy is prescribed. Treatment of these patients should not be regarded as palliative therapy.

Journal Article↗

PubMed1999

Tumor volume and local control in primary radiotherapy of nasopharyngeal carcinoma.

An investigation of the effect of tumor volume and total dose on local control following primary radiotherapy for nasopharyngeal carcinoma was carried out in order to estimate the radiation dose necessary to control a specific tumor volume. Between 1983 and 1996 a total of 104 patients underwent radiation therapy for nasopharyngeal carcinoma at the Department of Radiation Oncology of the University of Wuerzburg. Total doses of between 8 and 80 Gy (5 fractions per week) were administered. Complete CT-data on primary tumor size, total tumor dose (calculated by 3D- or quasi 3D-CT-based radiation planning computer) and on local control status in the follow-up period were available for 63 patients. Lymph node metastases were present in 38 of these patients and they were also entered into the study. Thus this study is based on a total of 101 tumor regions. A Poisson probability-based model was used for calculating the dose-response relationship. Assuming a correlation between tumor volume and the total dose necessary to obtain local control, the individual tumor volumes were rescaled to a 1 ml volume by introducing a volume-dependent modification factor for the applied dose, in order to eliminate the influence of different individual tumor volumes. All dose values given are based on a fractionation scheme of 2 Gy single dose, 5 fractions per week. Nineteen tumors and 11 lymph nodes were considered locally uncontrolled or recurrent. Without dose-volume modification, a weak dose-response correlation was found and a typical shallow dose-response curve was calculated with a 50% response dose (RD50) of 60.2 Gy and a normalized dose-response gradient (gamma50) of 3.2+/-0.62. After dose-volume modification and rescaling to a 1 ml tumor volume, a steep dose-response curve with an RD50 of 40.9 Gy and gamma50 of 8.2. was found. Tumor volume is a very important factor influencing local control in nasopharyngeal carcinoma. The rescaling procedure to a reference volume of 1 ml used in this study revealed a very steep dose-response relationship. This result suggests that the clinically observed smooth dose-response relationships may be explained by interindividual tumor volume heterogeneity. The additional dose necessary to control a tumor of the double volume is close to 5 Gy. With a total dose of 72 Gy (5x2 Gy/week), tumor volumes larger than 64 ml are unlikely to be controlled.

Carcinoma↗

PubMed1999

Identification of ataxia telangiectasia heterozygotes, a cancer-prone population, using the single-cell gel electrophoresis (Comet) assay.

Heterozygotes of ataxia telangiectasia (AT) may comprise up to 1% of the general population. Because these individuals have no clinical expression of AT but may be highly radiosensitive and strongly predisposed for several forms of cancer, identification of AT carriers represents a considerable interest in cancer epidemiology and radiotherapy. We report a new approach for the in vitro identification of AT-heterozygotes based on the evaluation of the radiosensitivity and DNA damage repair ability of peripheral blood mononuclear cells using the single-cell gel electrophoresis (Comet) assay. The assay was performed on cells isolated from four different groups of individuals: (1) apparently healthy donors (n = 10); (2) patients with breast cancer showing a normal reaction to radiotherapy (n = 10); (3) a group of obligate AT carriers (parents of AT-homozygotes, n = 20); and (4) AT-homozygotes (n = 4). Cells irradiated with 3 Gy of x-rays were assayed for three parameters: (1) the initial and (2) residual DNA damage and (3) the kinetics of DNA damage repair. Both AT-heterozygotes' and AT-homozygotes' cells were found to be highly sensitive to x-irradiation. Quantitative evaluation of the single-cell electrophoregrams revealed that the average initial DNA damage in AT-heterozygous and AT-homozygous cells was almost three times higher than that in control non-AT cells. In addition, the DNA repair process in irradiated AT carrier cells was almost three times slower, and the extent of irreparable DNA damage in these cells was three times greater than in controls. Simultaneous assessment of the three parameters enabled correct identification of all tested AT carriers. This method seems to be a sensitive and useful tool for populational studies as a rapid prescreening test for a mutated AT status. The approach can also be extended for prediction of the in vivo radiosensitivity, which would enable optimization of individual radiotherapy schedules.

Adolescent↗

PubMed1999

[Autocrine activation of fibroblasts following irradiation].

BACKGROUND: The most important limitation of thoracic radiotherapy is radio-toxicity of the normal lung. We distinguish the pneumonitis with acute clinical onset, histologically characterised by infiltration of inflammatory cells to alveoli and interstitium, from fibrosis, which is slowly progressive and characterised by fibroblast proliferation and collagen deposition in the interstitium. Radiogenetic fibrosis can occur without evidence of alveolitis, an active role of mesenchymal lung cells in the pathogenesis of this special disorder is assumed. METHODS: Human lung fibrobasts were irradiated in vitro with single doses of 4, 7 and 10 Gy and afterwards observed or incubated together with non-irradiated cells in a co-culture system. After 3, 6, 9, and 12 days cells were counted, and TGF beta 1 and fibronectin was measured in supernatants. RESULTS: Cell growth of irradiated fibroblasts was inhibited as expected. In contrast, we observed a significant stimulation of cell growth of the non-irradiated fibroblasts, which were incubated together with the irradiated cells. This effect was obvious from day 1 until day 9 following irradiation and was dose dependent. In irradiated cells TBF beta 1 was increased in culture supernatants up to five-fold compared to sham-irradiated cells from day 6 until day 12. Fibronectin was elevated in dose dependent manner. CONCLUSION: Irradiation of fibroblasts in vitro induces synthesis of substances which stimulate cell growth. TGF beta 1 and fibronectin may be involved in this act of "self-activation".

Cell Division↗

PubMed1998

Preoperative irradiation versus the use of nonsteroidal anti-inflammatory drugs for prevention of heterotopic ossification following total hip replacement: the results of a randomized trial.

PURPOSE: Previous studies showed the effectiveness of early preoperative (4 h before operation) irradiation for prevention of heterotopic ossification (HO) after total hip replacement. This procedure can result in logistic problems, if there is a great distance between the department of radiotherapy and the orthopedic clinic. To avoid these organizational problems a prospective study was undertaken to analyze the effectiveness of preoperative irradiation on the day preceding surgery (16-20 h before operation). METHODS AND MATERIALS: Between 1995 and 1996, 100 patients were randomized to receive a prophylactic therapy for prevention of heterotopic ossification. Forty-six patients were irradiated with 7 Gy single dose within 16-20 h before operation. Fifty-four patients were treated with nonsteroidal anti-inflammatory drugs (NSAID) (Voltaren resinat 2 x 75 mg/day for 2 weeks). Heterotopic ossification was scored according to the Brooker Grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992 were analyzed and defined as the historical control group. RESULTS: Incidence of heterotopic ossification was 47.8% in the 7 Gy preoperative group (Brooker Score I: 36.9%; II: 8.7%; III: 2.2%; IV: 0%) and 11.1% in the NSAID group (Brooker Score I: 9.3%; II: 1.8%; III: 0%; IV: 0%). Regarding overall heterotopic ossification there was a significant difference between the NSAID group and the 7 Gy group (p < 0.01). Analyzing the clinically significant heterotopic ossification (Brooker Score III and IV) there was no significant difference between the two treatment arms (p > 0.05). In the untreated historical control group the incidence of heterotopic ossification was 65% (Brooker Score I: 26%; II: 15%; III: 19%; IV: 5%). Referring to overall and to clinically relevant heterotopic ossification the incidence of HO was greater in the control group than in the prophylactically treated groups (p < 0.05). CONCLUSION: Irradiation within 16-20 h before operation and use of NSAID (Voltaren resinat) can reduce the incidence of clinically relevant heterotopic ossification after total hip replacement.

Aged↗

PubMed1998

Abdominal irradiation in unilateral nephroblastoma and its impact on local control and survival.

PURPOSE: The influence of abdominal radiotherapy was analyzed in 122 patients with unilateral Wilms tumor eligible for local irradiation according to postoperative SIOP-stage. MATERIAL & METHODS: 122 of 454 children with Wilms tumor diagnosed between January 1989 and March 1994 in Germany were eligible for abdominal irradiation after preoperative chemotherapy and tumor resection according to SIOP9/GPOH protocol. There were 88 children with standard histology (SH; local Stage IIN+ and III) and 34 children with unfavorable histology (UH; anaplastic, clear cell and rhabdoid, local Stages II and III). Local irradiation was given postoperatively parallel to polychemotherapy according to protocol with appropriate dose reductions of Actinomycin D (dactinomycin) during the course of radiotherapy. Fifteen Gy to the tumor bed were prescribed in standard histology, with 30 Gy to regional lymph nodes, if histologically positive. Thirty Gy were given in unfavorable histology. Boost doses up to 15 Gy were possible for macroscopic residuals. Ages ranged between 6 months and 21 years (median 4.2 years). RESULTS: Only 98 of 122 eligible children were irradiated. Reasons for ommission of radiotherapy were: Stage III only due to intraoperative biopsy (n = 6), due to resected cava thrombus (n = 5); young age (n = 2); undergrading/understaging (n = 7); other reasons (n = 4). There were 19 abdominal recurrences (4 of 88 with SH; 15 of 34 UH). In 5 patients, local recurrence was the only site of failure. There were 6 local failures in 24 nonirradiated but eligible children (25%) vs. 13 of 98 in irradiated children (13%); p = 0.15. In SH 0 of 15 nonirradiated vs. 4 of 73 treated children (p = NS) and in UH 6 of 8 nonirradiated vs. 9 of 26 irradiated children developed local recurrence (p < 0.05). Of 19 children with local recurrence as one site of failure, 18 have died. This comprises 67% of 27/122 children with fatal outcome in the observation period. In the patients eligible for abdominal radiotherapy, projected 3-year relapse-free survival is 85% for the group of children with standard histology and 41% for the children with unfavorable histology. CONCLUSION: Despite impressive overall results for this multicenter trial in unilateral nephroblastoma, local recurrence remains a grave prognostic parameter. Evaluation of irradiated vs. eligible but not irradiated children suggests that radiotherapy to the tumor bed is of considerable impact for local control in the risk groups eligible for abdominal irradiation as defined in the SIOP9/GPOH protocol.

Adolescent↗

PubMed1998

[3D-Ct-planned interstitial HDR brachytherapy + percutaneous irradiation and chemotherapy in inoperable pancreatic carcinoma. Methods and clinical outcome].

PURPOSE: Clinical experiences in interstitial 192-iridium HDR brachytherapy for the treatment of unresectable pancreatic carcinoma are presented. Brachytherapy has been used as boost irradiation in a multimodality treatment concept together with external radiotherapy and simultaneous chemotherapy. Practicability during clinical routine, tolerability and toxicity of treatment are investigated. PATIENTS AND METHODS: Nineteen patients (9 female, 10 male, median age 67 years) with unresectable carcinoma of the pancreas have been treated with interstitial brachytherapy. Distribution according to UICC stages showed 4, 10 and 5 patients in stage II to IV respectively. In all cases afterloading technique with 192-iridium in HDR-modus was used. A total dose of 10 to 34 Gy to the reference isodose was delivered (single dose 1.88 to 5 Gy, median 2.5 Gy). Brachytherapy was followed by external radiotherapy, delivering an additional dose of 40 to 58 Gy. Nine patients received simultaneous chemotherapy (5-fluorouracil, leucovorin). Treatment planning was performed based on CT scans, allowing spatial correlation of isodose curves to the patient's anatomy. RESULTS: Median survival time was 6 months. A trend of lower survival rates with advanced stage of disease (median survival stage IV 4 months, stage II and III 6.5 months) was seen. Local control rate was 70%. Brachytherapy treatment was well tolerated, severe acute side effects were not observed. One patient developed pancreatic fistulae 4 months and 1 patient a gastric ulcer 7 months after treatment. Pain release was achieved in all patients. CONCLUSIONS: 192-iridium HDR-brachytherapy is an effective tool in the treatment of unresectable pancreatic carcinoma with a high rate of local control and a low rate of side effects and is comparable IORT or seed implantation.

Adenocarcinoma↗

PubMed1998

[Cosmetic results of breast conserving therapy for breast carcinoma. Treatment results from the Heidelberg Radiation Clinic in the years 1984 to 1992].

PURPOSE: In this study we retrospectively analyzed local control, survival rate and late cosmetic results of women with early breast cancer receiving breast conserving therapy. PATIENTS AND METHODS: All patients (1984 through 1992) of the Department of Radio-Oncology (University of Heidelberg), who received breast conserving therapy consisting of conservative surgery followed by radiotherapy, were interviewed and asked to come. Subjective estimation of the cosmetic results of therapy was evaluated by means of a questionnaire. Cosmesis, circumferences and temperatures of different mammary regions were assessed and measured. Side effects and late sequelae were valued by the EORTC/RTOG-score. RESULTS: Mean follow-up time of 192 women (pT1: 71.9%, pT2: 28.1%) was 4.5 years (median: 4.0 years). 26.6% of them were nodal positive. Positive nodal status correlated with high tumor grading (p = 0.0001). Ten patients developed distant metastases; one of them subsequent to having suffered a loco-regional failure. Eight loco-regional failures occurred, 3 of them before radiotherapy (salvage). Following radiotherapy altogether 5 loco-regional failures (= 2.6%) were found; 3 women concerning were pre-, 2 postmenopausal. Three of these patients died, in 1 case occurred distant metastasis. Seventeen patients died, 3 of them presenting loco-regional failure, 8 of them showing distant metastasis. Sixty-four women were examined for cosmesis with the following result: a poor result was observed twice, a fair result 13 times, a good result 34 and an excellent result 15 times. Self-assessment was significantly better than observer's assessment. Third-degree late sequelae were found once, second-degree was seen 11 times, first-degree 38 times and no visible late sequelae were observed 14 times. The use of wedges was followed with borderline significance (p = 0.06) either by a better cosmesis and fewer late sequelae. Neither the type of surgery nor the width of the fields nor the quality of radiation (Co60 or 6 MVX) nor boost-application influenced the cosmetic result. Measured circumferences and distances showed no significant differences in the groups of the patients with poor or fair and good or excellent cosmesis. The temperature of the seized and contralateral breast showed no significant difference as well. With increasing distance from primary therapy the cosmetic results deteriorated. CONCLUSION: Breast conserving therapy consisting of conservative surgery followed by radiotherapy causes predominantly excellent to good cosmetic results combined with an acceptable amount of late side effects. The decreased rate of good and excellent cosmetic long-term results is biological interesting and requires further studies.

Aged↗

PubMed1998

DNA double-strand breaks in mammalian cells exposed to gamma-rays and very heavy ions. Fragment-size distributions determined by pulsed-field gel electrophoresis.

The spatial distribution of DNA double-strand breaks (DSB) was assessed after treatment of mammalian cells (V79) with densely ionizing radiation. Cells were exposed to beams of heavy charged particles (calcium ions: 6.9 MeV/u, 2.1.10(3) keV/microm; uranium ions: 9.0 MeV/u, 1.4.10(4) keV/microm) at the linear accelerator UNILAC of GSI, Darmstadt. DNA was isolated in agarose plugs and subjected to pulsed-field gel electrophoresis under conditions that separated DNA fragments of size 50 kbp to 5 Mbp. The measured fragment distributions were compared to those obtained after gamma-irradiation and were analyzed by means of a convolution and a deconvolution technique. In contrast to the finding for gamma-radiation, the distributions produced by heavy ions do not correspond to the random breakage model. Their marked overdispersion and the observed excess of short fragments reflect spatial clustering of DSB that extends over large regions of the DNA, up to several mega base pairs (Mbp). At fluences of 0.75 and 1.5/microm2, calcium ions produce nearly the same shape of fragment spectrum, merely with a difference in the amount of DNA entering the gel; this suggests that the DNA is fragmented by individual calcium ions. At a fluence of 0.8/microm2 uranium ions produce a profile that is shifted to smaller fragment sizes in comparison to the profile obtained at a fluence of 0.4/microm2; this suggests cumulative action of two separate ions in the formation of fragments. These observations are not consistent with the expectation that the uranium ions, with their much larger LET, should be more likely to produce single particle action than the calcium ions. However, a consideration of the greater lateral extension of the tracks of the faster uranium ions explains the observed differences; it suggests that the DNA is closely coiled so that even DNA locations several Mbp apart are usually not separated by less than 0. 1 or 0.2 microm.

Animals↗

PubMed1998

Combined effects of ionizing radiation and 4-hydroperoxyfosfamide in vitro.

BACKGROUND AND PURPOSE: Combined radiochemotherapy has gained increasing interest in clinical applications. The effects of combined exposure of ionizing radiation and 4-hydroperoxyifosfamide (4HOOIF) on cell survival were investigated in vitro. MATERIALS AND METHODS: Clonogenic survival of log phase V79, Caski (squamous carcinoma), Widr (colon carcinoma) and MRI-221 cells (human melanoma) was determined after combined exposure to 4HOOIF and radiation. Measurement of cell survival for different cell cycle phases was performed after mitotic shake-off (V79) or appropriate intervals after serum stimulation of plateau phase cells (Widr). Control of cell cycle distribution was performed using flow cytometry. RESULTS: In all cell lines tested, a combined exposure resulted in cell killing that was greater than for independent action. While this type of radiosensitization was of minor magnitude for log-phase cells or cells in G1 substantial radiosensitization was detected for S-phase cells with enhancement ratios (calculated from the respective mean inactivation doses) of up to 1.5. CONCLUSIONS: The results demonstrate the interaction of 4HOOIF and radiation-induced cell damage with marked cell cycle specificity. Since the largest combination effect was observed for the most radioresistant S-phase cells, damage interaction could be mediated by an interference of 4HOOIF with the repair/fixation pathway of radiation-induced potentially lethal damage.

Animals↗

PubMed1998

Lethal pulmonary toxicity after autologous bone marrow transplantation/peripheral blood stem cell transplantation for hematological malignancies.

BACKGROUND AND PURPOSE: Retrospective evaluation of the incidence of lethal pulmonary complications (LPC) with special emphasis on interstitial pneumonia (IP) in a large group of patients homogeneously treated with hyperfractionated total body irradiation (HTBI) before autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) for hematological malignancy. The factors influencing IP are discussed. MATERIALS AND METHODS: Of 260 patients (maximum follow-up 137 months) that were treated with ABMT or PBSCT for hematological neoplasms between 1982 and 1994, 209 patients received HTBI and could be evaluated with respect to lethal pulmonary complications and especially lethal interstitial pneumonia. For most patients (n = 155), the HTBI dose was 14.4 Gy (lung dose 9-9.5 Gy) given in 12 fractions over 4 days. Twenty-one patients received a total dose of > or =15 Gy with pulmonary doses of 9-10.5 Gy. RESULTS: The actuarial overall 5-year survival for all 209 patients evaluated was 44 +/- 4%, enabling valid evaluation with respect to lethal pulmonary toxicity. The actuarial incidence of all LPC during the first year was calculated as being 8 +/- 2%. The actuarial incidence of lethal IP is certainly lower and was estimated to be between 3 and 5% for all patients. The overall treatment-related mortality was 12% in 188 patients that received a total dose of <15 Gy and 24% among the patients treated with a total dose of > or =15 Gy. CONCLUSION: ABMT/PBSCT, like other transplant modalities without significant graft versus host disease (GvHD), has a low transplant-related mortality, a very small rate of overall LPC and a low incidence of lethal IP after HTBI. Doses up to 14.4 Gy with lung doses of 9-9.5 Gy can be administered safely. For total doses of > or =15 Gy with lung doses of 9-10.5 Gy, the risk of serious transplant-related complications cannot yet be finally assessed but such higher doses should be considered with caution because of the possibility of increasing toxicity in organs other than the lung.

Adolescent↗

PubMed1998

Radiation-induced micronucleus formation in human skin fibroblasts of patients showing severe and normal tissue damage after radiotherapy.

PURPOSE: Treatment schedule and total dosage in radiation therapy is based on the tumoricidal doses and the tolerance dose of the perifocal normal tissue. Since large-scale variations occur between the patients concerning the side effects, one of the major goals of radiation research recently has been the development of a predictive in vitro assay. This paper is a contribution to that effort. MATERIALS AND METHODS: Skin fibroblasts of patients with normal-tissue reactions or acute and/or late increased side effects and cell lines of four individuals carrying the heritable disease ataxia telangiectasia were irradiated in vitro. The formation of micronuclei was chosen as biological endpoint and the results were compared with the clinically observed side effects. RESULTS: In general, a radiation dose-dependent increase in micronucleus frequency was found. The cells of the majority of the sensitive patients, as well as those of homozygous and heterozygous ataxia telangiectasia individuals, showed a higher micronucleus induction than the average of the donors with normal sensitivity. CONCLUSIONS: The micronucleus test seems to be a very promising tool in the evaluation of radiation sensitivity prior to therapy. However, larger studies are needed to confirm these findings and to optimize the methodology, and it is presumed that a final predictive assay will consist of a combination with other test systems.

Adult↗

PubMed1997

Randomized trial comparing early postoperative irradiation vs. the use of nonsteroidal antiinflammatory drugs for prevention of heterotopic ossification following prosthetic total hip replacement.

PURPOSE: A randomized trial was undertaken to assess the comparative efficacy of early postoperative irradiation with either 5 or 7 Gy vs. the use of nonsteroidal antiinflammatory drug (NSAID) for prevention of heterotopic ossification (HO) following prosthetic total hip replacement (THP). METHODS AND MATERIALS: Between 1993 and 1994, 301 patients were randomized to receive postoperative irradiation (5 or 7 Gy) or NSAID. One hundred and thirteen patients were treated with NSAID (indomethacin 2 x 50 mg/day for 1 week), 93 patients were irradiated with a single 7 Gy fraction, 95 patients with a single 5 Gy fraction. The treatment volume included the soft tissues between the periacetabular region of pelvis and the intertrochanteric portion of the femur. X-rays of treated hips were obtained immediately and 6 months after surgery. Heterotopic ossification was scored according to the Brooker Grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992, were analyzed and defined as historical control group. RESULTS: Incidence of heterotopic ossification was 16.0% in NSAID-group (Brooker Score I: 8.0%; II: 6.2%; III: 1.8%; IV: 0%), 30.1% in 5 Gy group (Brooker Score I: 24.7%; II: 4.3%; III: 1.1%; IV: 0%), and 11.1% in 7 Gy group (Brooker Score I: 11.6%; II: 0%; III: 0%; IV: 0%). Regarding overall heterotopic ossification there was a significant difference between the NSAID group and the 5 Gy group (p < .015), respectively, between the 7 Gy group and the 5 Gy group (p < .0001). No significant difference was noted in the influence of overall HO between the NSAID and the 7 Gy group (p > 0.3). Analyzing the clinically significant HO (Brooker Score III and IV) patients irradiated with 7 Gy developed less HO than those treated with NSAID (p = 0.003). Incidence of HO was greater in the untreated historical control group (Brooker Score I: 26%; II: 15%; III: 19%; IV: 5%) than in all three prophylacticly treated groups. CONCLUSION: Prophylactic irradiation of the operative site after hip replacement with single a 7 Gy fraction is the most effective postoperative treatment schedule in prevention of clinically significant heterotopic ossification. This therapy modality is more effective than irradiation with a single 5 Gy fraction or use of NSAID.

Aged↗