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Biomedical subjects

V Strnad

Publications and source records attributed to V Strnad.

At least 19 recordsLinked to original sources
PubMed2002

High-dose intravascular beta-radiation after de novo stent implantation induces coronary artery spasm.

BACKGROUND: Intracoronary brachytherapy is effective in preventing restenosis after coronary interventions. However, in vitro and animal studies have shown that irradiation produces immediate and sustained endothelial dysfunction. This study assesses the clinical relevance of impaired vasomotoric function induced by brachytherapy. METHODS AND RESULTS: We analyzed the occurrence of postradiation coronary artery spasms in 1 animal study and 2 clinical trials investigating the effects of high-dose intracoronary beta-radiation after de novo coronary artery stenting. Irradiated segments (IRSs) proximal and distal to the stent were studied by quantitative coronary angiography after stenting, after radiation, and at the end of the procedure. There was an 67% overall incidence of coronary artery spasm in the IRSs immediately after beta-radiation compared with 9% after sham treatment (P<0.001). Whereas in most cases this phenomenon was only minor or moderate, in 12 cases, 4 (22%) animals and 8 (28%) patients, severe coronary spasm (>90% diameter stenosis) with significant ECG-changes or hemodynamic instability was observed. Relief of spasms was protracted (mean time until complete relief of spasm 423+/-122 seconds) and required repetitive intracoronary administration of nitroglycerin (mean dose: 1.2+/-0.6 mg). CONCLUSIONS: Vasoconstriction is a frequent reaction of coronary arteries after high-dose intracoronary beta-radiation, necessitating repetitive administration of vasodilators.

Animals↗
PubMed2001

Alteration of radiation-induced hematotoxicity by amifostine.

PURPOSE: To investigate whether amifostine can reduce radiation hematotoxicity. PATIENTS AND METHODS: Seventy-three patients undergoing radiotherapy for squamous cell carcinoma of the head and neck at the university clinics of Freiburg, Heidelberg, and Erlangen were evaluated. All received 60 Gy (50-70 Gy) at 5 x 2 Gy fractions per week employing standard techniques. Thirty-five were randomized to receive 200 mg/m(2) amifostine i.v. 30 min before radiation; 38 served as control patients. Blood counts (total n = 501) were determined before, during, and while completing radiotherapy. Changes of leukocyte, platelet, and hemoglobin levels were determined and compared using the t test. RESULTS: The blood hemoglobin level and the platelet count were not affected by irradiation, for either the amifostine-treated or control patients. Similarly, the leukocyte counts of amifostine-treated patients did not change during irradiation. However, control patients experienced a decrease in leukocyte count from 8.1 x 10(3)/mm(3) to 5.8 x 10(3)/mm(3) (difference: 2.3 x 10(3)/mm(3)). This seems to be line specific: Whereas amifostine does not affect lymphocyte count, a radiation-induced decrease of neutrophil granulocytes seems to be prevented. CONCLUSION: Amifostine protects from radiation hematotoxicity, particularly affecting the granulocytopoiesis. These data confirm results from our former study.

Amifostine↗
PubMed2001

Interstitial brachytherapy with Ir-192 low-dose-rate in the treatment of primary and recurrent cancer of the oral cavity and oropharynx. Review of 318 patients treated between 1985 and 1997.

AIM: To evaluate the impact of postoperative interstitial brachytherapy with and without external radiotherapy in the treatment of primary and recurrent squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Between 1985 and 1997, a total of 318 patients were treated by interstitial Ir-192 low-dose-rate brachytherapy as part of their primary (n = 236) or recurrent treatment (n = 82). There were 263 male (83%) and 55 (17%) female patients. The distribution of UICC (1997) stages was as follows: I (61 patients, 19%), II (71 patients, 22%), III (58 patients, 18%), IV (128 patients, 40%). The primary tumor site was located in the oral cavity in 201 patients (63%), in the oropharynx in 86 patients (27%), lower lip in 19 patients (6%) and other regions in twelve cases (4%). Treatment concepts did not vary over the time and were dictated by the initial tumor extension: a total of 175 patients (55%) received a combination of surgery, interstitial brachytherapy (23-25 Gy) and external radiotherapy (50-60 Gy), 60 patients (19%) surgery and interstitial brachytherapy (45-55 Gy) alone. Advanced disease not amenable to primary surgery was either treated by radiochemotherapy and interstitial brachytherapy in 39 patients (12%) or a combination of interstitial brachytherapy, external radiotherapy and interstitial hyperthermia in 44 patients (14%). RESULTS: Overall survival rates following primary and recurrent treatment were 50 +/- 4% and 29 +/- 5%, respectively, at 5 years (p < 0.0001). A significant impact on overall survival rate was noted for UICC stage: patients in stage I/II had survival rates of 64 +/- 5% and 57 +/- 10%, respectively, while patients in stage III/IV had survival rates of 39 +/- 5% and 15 +/- 5%, respectively, at 5 years (p < 0.0001). In addition, grading (p = 0.01) and hemoglobin levels (p = 0.05) had a significant influence on overall survival. Local tumor control rates for all patients were 74 +/- 3% and 57 +/- 7% at 5 years following primary and recurrent treatment (p = 0.01), respectively. The 145 patients treated for primary disease by a uniform concept of surgery, interstitial brachytherapy and external radiotherapy achieved excellent local control rates with 92 +/- 4% (stage I/II) and 65 +/- 6% (stage III/IV) at 5 years. Late treatment-related toxicity with soft tissue necrosis and/or osteonecrosis requiring mandibular resection was 7.5%. CONCLUSION: Local tumor excision followed by postoperative interstitial brachytherapy with and without external radiotherapy is associated with excellent locoregional control, a low risk of chronic sequelae and may therefore considered as a new approach avoiding mutilating radical surgery.

Brachytherapy↗
PubMed2000

Protective effect of amifostine on dental health after radiotherapy of the head and neck.

PURPOSE: The cytoprotective agent amifostine has been shown to reduce the radiation-induced acute and chronic xerostomia in head and neck cancer patients. The purpose of this study was to evaluate whether or not amifostine also reduces the incidence of dental caries associated with the radiation-induced xerostomia. METHODS AND MATERIALS: The dental status before and 1 year after radiotherapy was retrospectively compared in 35 unselected patients treated as part of the prospective randomized and multicenter open-label Phase III study (WR-38) at the University Hospitals of Heidelberg, Freiburg, and Erlangen. The WR-38 study compared radiotherapy in head and neck cancer with and without concomitant administration of amifostine. RESULTS: Patient and treatment characteristics (particularly the radiation dose and percentage of parotids included in the treatment volume) were equally distributed between the patients who received (n = 17) or did not receive (n = 18) amifostine. Fifteen patients of the amifostine group showed no deterioration of the dental status 1 year after radiotherapy as compared to 7 patients who did not receive the cytoprotector (p = 0. 015, two-tailed Fisher exact test). CONCLUSION: Our data suggest a protective effect of amifostine on the dental health after radiotherapy of the head and neck. The dental status should be used as a primary endpoint in future studies on amifostine.

Adult↗
PubMed2000

Phase III randomized trial of amifostine as a radioprotector in head and neck cancer.

PURPOSE: Radiotherapy for head and neck cancer causes acute and chronic xerostomia and acute mucositis. Amifositine and its active metabolite, WR-1065, accumulate with high concentrations in the salivary glands. This randomized trial evaluated whether amifostine could ameliorate these side effects without compromising the effectiveness of radiotherapy in these patients. PATIENTS AND METHODS: Patients with previously untreated head and neck squamous cell carcinoma were eligible. Primary end points included the incidence of grade > or =2 acute xerostomia, grade > or =3 acute mucositis, and grade > or =2 late xerostomia and were based on the worst toxicity reported. Amifostine was administered (200 mg/m(2) intravenous) daily 15 to 30 minutes before irradiation. Radiotherapy was given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 Gy. Whole saliva production was quantitated preradiotherapy and regularly during follow-up. Patients evaluated their symptoms through a questionnaire during and after treatment. Local-regional control was the primary antitumor efficacy end point. RESULTS: Nausea, vomiting, hypotension, and allergic reactions were the most common side effects. Fifty-three percent of the patients receiving amifostine had at least one episode of nausea and/or vomiting, but it only occurred with 233 (5%) of 4,314 doses. Amifostine reduced grade > or =2 acute xerostomia from 78% to 51% (P<.0001) and chronic xerostomia grade > or = 2 from 57% to 34% (P=.002). Median saliva production was greater with amifostine (0.26 g v 0.10 g, P=.04). Amifostine did not reduce mucositis. With and without amifostine, 2-year local-regional control, disease-free survival, and overall survival were 58% versus 63%, 53% versus 57%, and 71% versus 66%, respectively. CONCLUSION: Amifostine reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.

Adult↗
PubMed2000

Early results of pulsed-dose-rate interstitial brachytherapy for head and neck malignancies after limited surgery.

PURPOSE: The aim of this study was to evaluate the relative incidence of toxicity and local control in patients with head and neck malignancies who underwent interstitial pulsed-dose-rate (PDR) brachytherapy (iBT). PATIENTS AND METHODS: From October 1997 to December 1998, 61 patients underwent interstitial PDR brachytherapy procedures in our department; 47 were patients with head and neck cancer. Forty patients received brachytherapy as part of their curative treatment regimen, and 7 patients were implanted for palliative purposes and excluded from the analysis of therapy efficacy. Twenty-four patients had interstitial brachytherapy procedures alone with D(REF) = 50 Gy; in 23 patients, iBT procedures were performed with D(REF) = 24 Gy in combination with external radiation. A dose per pulse (dp) of 0.5 Gy was prescribed for 38/47 patients, and a dp = 0.7 Gy for 9/47 patients. The pulses were delivered 24 h a day, with a time interval of 1 h between two pulses, resulting in an effective dose rate of 0.5 Gy/h or 0.7 Gy/h. A follow-up of the patients was done to analyze acute and delayed toxicity, local control, and survival. The analysis was performed after median follow-up of 12 months (5-18 months). RESULTS: After a median follow-up of 12 months, soft tissue necrosis was seen in one patient and bone necrosis in another. No other serious side effects were observed. Permanent locoregional tumor control was achieved in 37 of 40 patients. No distant metastases were observed. CONCLUSIONS: PDR interstitial brachytherapy with 0.5-0.7 Gy/h is a safe therapy. These preliminary results suggest that PDR interstitial brachytherapy of head and neck cancer is comparable with low-dose-rate (LDR) brachytherapy.

Adult↗
PubMed1997

[Regression of Yoshida sarcoma during normoxia and hypoxia after fractionated irradiation].

PURPOSE: Tumor regression is one of the most important factors determinating the tumor control probability after radiotherapy. The changes in the regression of tumors during fractionated radiotherapy and the application of different radioprotectors or radiosensitizers make render to assess their effectivity. MATERIAL AND METHOD: The effect of hypoxic breathing (8.1% O2) on the tumor regression of Yoshida sarcoma was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. RESULTS: No significant changes in the tumor regression after radiotherapy in any group in any time independent from respiratoric hypoxia were recorded. The tumor regression rate was significantly influenced by treatment schedule (p < 0.0005). CONCLUSIONS: Our results support the hypothesis of hypoxy-radiotherapy: The acute hypoxic hypoxia, caused due the breathing of hypoxic gas mixture with 8 to 10% oxygen, did not influence the radiation induced tumor regression in animal experiment. For this criterium no protection can be shown. The influence of hypoxy-radiotherapy on the local tumor control is necessary to evaluate in further experiments.

Acute Disease↗
PubMed1997

[Oxygen pressure distribution in lymph node metastases and the changes during acute respiratory hypoxia].

PURPOSE: The radiosensitivity of tissues is essentially influenced by hypoxia. Based on the oxygen effect a new therapeutic modality has been developed to protect healthy tissues while hypoxic breathing during irradiation. PATIENTS AND METHOD: The effect of hypoxic breathing (8.1% O2) on the pO2 in metastatic lymph nodes was studied in 14 patients. Tissue oxygenation was assessed using a polarographic electrode system. RESULTS: The median pO2 was 19.6 mm Hg prior to hypoxic breathing with a great intra- and intertumoral variability. The relative frequency of pO2-values < 5 mm Hg was between 0 and 88%. During hypoxic breathing we registered no significant changes in the mean, the median or the pO2 values < 5 mm Hg. CONCLUSIONS: In metastatic lymph nodes can be found chronic hypoxia with great inter- and intratumoral pO2 variability. The hypoxic breathing (8.1% O2) shows no significant modifications of the tumor oxygenation with increased pO2 variability. This fact explains the experimental and clinical experience, that the hypoxic breathing (8 to 10% O2) protects the healthy tissue without changes in the radiosensitivity of chronic hypoxic tumor tissue.

Acute Disease↗
PubMed1996

[Radiochemotherapy and simultaneous hormonal therapy of locally advanced prostatic carcinoma].

PURPOSE: The results of radiotherapy alone in the prostate cancer stage T3-T4 are not satisfactory. We investigated, whether the combination of radio-chemotherapy with hormone therapy, possible most effective therapy in stage III, will be tolerated without serious side effects. PATIENTS AND METHODS: Eight patients with prostate cancer T3/T4 were treated with concurrent radio-chemotherapy and hormone therapy. The mean doses in reference point was 61.7 Gy, the single dose was 1.8 Gy. The patients received epirubicin 20 mg/m2 and 5-fluorouracil 800 mg/m2 on day 1 to 5 and 29 to 33 of radiotherapy. The hormone therapy began before the radio-chemotherapy started. RESULTS: Only the hematological side effects were relevant. Three out of 8 patients had leucopenia grade III and 1 of 8 patients leucopenia grade IV according WHO. Other serious complications could not be observed. CONCLUSION: The concurrent radio-chemotherapy with epirubicin and 5-fluorouracil in the combination with hormone therapy was tolerated well. The effectiveness of this new treatment should be examined prospectively in prostate cancer stage T3-T4.

Adenocarcinoma↗
PubMed1996

[Hypoxyradiotherapy: changes in the oxygen partial pressure distribution in the tumor and in the healthy tissue under acute respiratory hypoxia].

PURPOSE: Based on the oxygen effect a new therapeutic modality has been developed to protect healthy tissues while breathing hypoxic gas mixture during irradiation. MATERIAL AND METHODS: The effect of breathing hypoxic gas mixture (8.1% O2) on pO2 in Yoshida sarcoma and muscle was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. Tissue oxygenation was assessed with a polarographic electrode system. RESULTS: The median pO2 in Yoshida sarcoma was 10 mm Hg. 21% of pO2-values were lower than 5 mm Hg. During breathing of hypoxic gas mixture no significant changes in median tumor pO2 or radiobiologic hypoxic values (< or = 5 mm Hg) were recorded. The median pO2 in muscle was 30 mm Hg. During breathing of gas hypoxic mixture a significant decrease of the median to the value 12 mm Hg and an increase of the radiobiologic hypoxic values (p < 0.00001) were observed. The changes of pO2-values were constant independent from fractionation. CONCLUSIONS: Between tumor and healthy tissue exists a significant difference regarding changes in the radiobiologic fraction during breathing of hypoxic gas mixture. This fact explains the experimental and clinical experience, that the breathing hypoxic gas mixture protects the healthy tissue without changes in the radiosensibility of chronic hypoxic tumor tissue.

Acute Disease↗
PubMed1996

[Reoxygenation in Yoshida sarcoma during different fractionated radiotherapy].

PURPOSE: Tumor reoxygenation is one of the most important factors determining the tumor control probability after radiotherapy. In experimental studies reoxygenation has been measured preferably after single dose irradiation. Only few data exist about changes in the hypoxic tumor fraction during fractionated radiotherapy. MATERIAL AND METHODS: The changes in the pO2 during fractionated radiotherapy were studied in Yoshida sarcoma transplanted to Wistar rats. Tissue oxygenation was assessed using a polarographic electrode system at the beginning, in the middle and at the end of radiation therapy. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. RESULTS: In the statistical analysis significant changes emerged in the mean, median, 10%-percentile and 0 to 2.5 mm Hg and 0 to 5.0 mm Hg values dependent on time. The tumors were significantly more hypoxic at the end of therapy. This trend became more pronounced with decreasing dose per fraction. CONCLUSIONS: The Yoshida sarcoma has no effective reoxygenation during fractionated radiotherapy.

Animals↗
PubMed1995

[Adjuvant radiotherapy of breast carcinoma].

Adjuvant postoperative radiotherapy for breast conserving treatment is well established. Contraindications against breast conservation are macroscopic tumor residues, multicentric disease, diffuse microcalcifications or inflammatory carcinoma because of the necessary radiation (dose) which exceeds the tolerance of the breast. Treatment results are comparable for skillful excision and quadrantectomy or segmentectomy. The impact of postoperative radiotherapy is debated for very favourable situations--clinical evidence of significant prognostic factors is the aim of prospective randomized studies. Postoperative radiotherapy after mastectomy diminishes five fold the local recurrence rate. This strategy does improve the quality of life. Prognostic factors for local relapse are T3-, T4-tumors, extensive axillary involvement, multifocal or multicentric disease, extensive lymphangiosis and extensive intraductal carcinoma. New clinical protocols confirm the value of radiotherapy of the regional lymph nodes. The results show a promising impact not only on the regional but also on the distant relapse free time and the overall survival.

Breast Neoplasms↗