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R Sauer

Publications and source records attributed to R Sauer.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Long term results following radiation therapy of locally recurrent and metastatic malignant melanoma].

The 20-year radiotherapy (RT) experience in patients with locally advanced, recurrent or metastatic malignant melanoma (MM) is analyzed with respect to different endpoints and prognostic factors. From 1977 to 1995, 2917 consecutive patients were entered in our MM registry. RT was indicated in 121 patients (56 females, 65 males) for palliation in advanced MM stages. The histology of the primary lesion was nodular in 51, superficial spreading in 35, acral-lentiginous in 8 and lentigo maligna in 4 patients); 22 were missing or could not be reclassified. Eleven patients had primary or recurrent lesions which were ineligible for surgery or had residual disease (R2) after resection of a primary or recurrent lesion (UICC IIB); 57 patients had lymph node (33) or in-transit metastases (24) (UICC III), 53 had distant organ metastases (7 M1a; 46 M1b) (UICC IV). Time from first diagnosis to on-study RT averaged 19 (median: 18; range: 3-186) months. In most cases conventional RT was applied (2-6 Gy single fractions) up to a mean total RT dose of 45 (median: 48; range: 20-66) Gy. At 3 months follow-up (FU), complete response (CR) was achieved in 7 (64%) and overall response (CR+PR) in all (100%) UICC IIB patients, in 25 (44%)/44 (77%) of 57 UICC III patients, and in 9 (17%)/26 (49%) of 53 UICC IV patients. Progression during RT occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median: 10 months) (p<0. 01). At last FU, 26 patients were alive: 6 (55%) UICC IIB, 17 (30%) UICC III, and 3 (6%) UICC IV patients (p<0.01). In univariate analysis following favorable prognostic factors for CR and long-term survival were identified: low UICC stage (p<0.001), primary site head and neck and total dose >40 Gy (all p<0).

Adult↗
PubMed1999

In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence.

PURPOSE: Cells undergoing apoptosis contribute to the regulation of activated mononuclear cells (Voll et al. 1997). Low-dose radiotherapy (LD-RT) is known to improve inflammatory symptoms, but the mechanism of action is still unclear. The aim of this study was to investigate the rate of apoptosis of peripheral blood mononuclear cells (PBMC) induced by LD-RT within the therapeutic dose range of anti-inflammatory RT. MATERIALS AND METHODS: PBMC were isolated from venous blood of ten healthy volunteers and were irradiated with single doses between 0.1 and 3.0 Gy. Apoptotic nuclei were detected by flow cytometry after propidium iodide (PI) triton staining, and apoptotic cells were detected by annexin V/PI staining and cell scatter analysis. Since apoptotic cells display increased cytoplasmatic granularity and concomitant reduced cell size, they can be distinguished from viable cells in forward/side scatter (FSC/SSC) histograms. Apoptotic PBMC were further subtyped by double staining with annexin V and directly labelled monoclonal antibodies recognizing the lineage-specific surface markers CD4, CD8, and CD19, respectively. The apoptosis rate of irradiated cells was analysed in a time and dose dependent fashion and was compared to a sham-irradiated control. RESULTS: After irradiation, a dose-dependent increase in apoptosis was observed, with a discontinuity (plateau or peak) between 0.3Gy and 0.7Gy in 9/10 donors (90%) and 59/80 samples (74%). 8/10 donors (80%) and 38/80 samples (47%) showed not only a discontinuous increase with a plateau but a relative maximum of apoptosis peaking within the dose range of 0.3 Gy and up to 0.7 Gy. CONCLUSION: LD-RT induces a relative maximum of apoptosis in PBMC in the does range between 0.3 Gy and 0.7 Gy. This may contribute to its anti-inflammatory effect observed clinically.

Adult↗
PubMed1998

Motor effects induced by a blockade of adenosine A2A receptors in the caudate-putamen.

Motor effects mediated through adenosine A2A receptors within the caudate-putamen were investigated in rats using bilateral microinfusions of MSX-3 (9 microg in 1 microl per side), a water-soluble phosphate prodrug of the selective A2A receptor antagonist MSX-2. Blockade of striatal A2A receptors produced a significant motor stimulation measured by an enhanced sniffing activity. Furthermore, catalepsy induced by systemic dopamine D1 (0.75 mg/kg SCH23390, i.p.) or dopamine D2 receptor blockade (1.5 mg/kg raclopride, i.p.) was potently reversed. These findings suggest that A2A receptors within the caudate-putamen are tonically activated by endogenous adenosine and that a striatal A2A receptor blockade produces motor stimulant effects, in particular in animals with dopamine hypofunction. The present results support the view that A2A receptor antagonists may be potentially useful therapeutics for the treatment of Parkinson's disease.

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PubMed1998

Efficacy of radiochemotherapy with platin derivatives compared to radiotherapy alone in organ-sparing treatment of bladder cancer.

PURPOSE: Presently, for muscle-invasive bladder cancer, radical cystectomy is considered to be the standard treatment. Bladder preservation, in the interest of quality of life, is secondary to the primary treatment goal of curing the patient. We present a 14-year multivariate analysis of prognostic factors influencing survival and bladder preservation after transurethral resection of the bladder (TURB) and radiotherapy (RT) +/- chemotherapy. METHODS AND MATERIALS: From May 1982 to May 1996, sequential cohorts of 333 patients with bladder cancer (mean age: 66 years) were treated by either RT alone (128 patients), or with platin-based concomitant radiochemotherapy (RCT, 205 patients) after TURB. Patients (282) with muscle-invasive or T1 high-risk cancers (Grade III, residual tumor after TURB, multifocality, tumor diameter > 5 cm, associated Tis or Ta, multiple recurrences or lymph node metastases), who received a minimal target dose of 45 Gy were selected for analysis (med. follow-up = 7.5 years): after October 1985, 115 patients received cisplatin (25 mg/m2) and 69 patients carboplatin (65 mg/m2) before every treatment fraction (1.8 Gy) on Days 1-5 and 29-33 of conventional fractionated RT. RESULTS: Complete remission rate was 20% (55 of 282 patients) after radical TURB, 57% (56 of 98) after TURB plus postoperative RT, and 80% (145 of 181 patients) after TURB plus RCT (85% after concomitant cisplatin and 70% after RCT plus carboplatin). These differences were significant in multivariate analysis (p = 0.003-0.05). The strongest impact on initial response had T-category (p < 0.0001) and R-status after TURB (p < 0.0003). Cause-specific survival (CSS) was 59 and 43% after 5 and 10 years; 79% of patients survived with preserved bladder. Five-year CSS after RT, RCT-Cis, and RCT-Carbo was 40, 64, and 54%, 10-year CSS 31, 48, and 27%, respectively (p = 0.04-0.045, univariate). R-status after TURB was the only independent prognostic factor for survival and bladder preservation. For relapsed patients after cystectomy, the 5- and 10-year CSS were 40 and 33%. CONCLUSIONS: TURB followed by RT/RCT is an alternative treatment option to primary cystectomy for patients with muscle-invading bladder cancer. Compared to historic controls, the addition of cisplatin or carboplatin leads to significantly more complete remissions and better survival. Survival rates are similar to those achieved by primary cystectomy and possibly even better for selected subjects, such as patients with T3b and T4 tumors. Cystectomy should be restricted to only those patients who fail after RCT.

Adult↗
PubMed1998

Transoral laser surgery of supraglottic cancer: follow-up of 141 patients.

OBJECTIVE: To determine the role of transoral laser resection of supraglottic carcinomas. DESIGN: Retrospective unicenter study of the oncologic results of transoral carbon dioxide laser microsurgery for supraglottic carcinomas performed between February 1979 and December 1993. Median follow-up was 37 months. SETTING: University hospital academic tertiary referral center. PATIENTS: We reviewed the medical records of 141 patients (a consecutive sample of 131 men and 10 women; mean age, 60 years) with histologically proven supraglottic carcinomas undergoing transoral laser surgery, possibly in combination with neck dissection or radiotherapy. Stage distribution of patients was as follows: stage I, 23.4%; stage II, 25.5%; stage III, 16.3%; and stage IV, 34.8% (according to the Union Internationale Contre le Cancer staging system). MAIN OUTCOME MEASURES: Recurrence-free survival rates and local and regional recurrence rates. RESULTS: Five-year recurrence-free survival rates were as follows: the whole case load, 65.7%; stage I, 85.0%; stage II, 62.6%; stage III, 74.2%; and stage IV, 45.3%, according to the Union Internationale Contre le Cancer staging system. The local and regional recurrence rates were 16.3% and 9.9%, respectively. CONCLUSIONS: The oncologic results of transoral carbon dioxide laser surgery are satisfying if clean surgical margins (R0 resection) can be reached. In patients in whom tumor-free margins are not achieved (R1 and R2 resection) and transoral revision is not possible, transcervical procedures (partial or total laryngectomy) should be performed. The indication for transoral supraglottic laryngectomy in T3 lesions should be considered with restraint.

Adult↗
PubMed1998

Schedule-dependent interaction of paclitaxel (Taxol) and irradiation in vitro.

The optimal dose and schedule of paclitaxel in combination with irradiation have not been determined yet. The aim of this study was to compare the in vitro cytotoxicity and enhancement of radiation sensitization as a function of single vs. fractionated paclitaxel exposure. A fibroblast cell line (B14) in exponential growth phase was used. The clonogenic assay was applied to determine cell survival. Flow cytometric measurements were performed to study cell cycle DNA distribution. Cytotoxicity of Taxol was examined at concentrations varying from 2 to 50 microM. Single (1 x 0 microM) vs. fractionated (2 microM/day, days 1-5) exposure of Taxol was investigated. The combination of Taxol plus irradiation as single and fractionated treatment was accomplished with 10 microM Taxol on day 1 plus 10 Gy irradiation on day 1 vs. Taxol 2 microM/day, days 1-5, plus irradiation 2 Gy/day, days 1-5. One-, 9-, and 24-hr intervals between end of incubation and irradiation were defined. Control populations demonstrated an average plating efficiency of 93%. Single Taxol exposure showed an average clonogenic survival of 84%. No significant difference between concentrations varying from 2 to 50 microM was observed. Single dose irradiation (1 x 10 Gy) led to clonogenic survival of 3%. Single exposure of Taxol plus single dose irradiation led to clonogenic survival of 4%. Fractionated radiation showed an average clonogenic survival of 41%. Fractionated Taxol treatment led to an average clonogenic survival of 63%. The combination of fractionated Taxol treatment (2 microM/day, days 1-5) plus fractionated irradiation (2 Gy/day, days 1-5) showed an average clonogenic survival of 15%. No significant difference between the chosen intervals was demonstrated. Flow cytometric measurements did not indicate any significant alterations in cell cycle DNA distribution. In conclusion, the data demonstrate a potential beneficial effect by combining fractionated Taxol exposure with fractionated irradiation without evidence for G2/M arrest in DNA analysis.

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PubMed1998

Sphincter preservation with chemoradiation in anal canal carcinoma: abdominoperineal resection in selected cases?

PURPOSE: This study contained herein assessed long-term results, toxicity, and prognostic variables following combined modality therapy of patients with International Union Against (Cancer Classification T1-4, N0-3, M0 squamous-cell carcinoma of the anal canal. PATIENTS AND METHODS: Between 1985 and 1996, 62 patients completed treatment with combined modality therapy. A median total dose of 50 Gy was given to the primary, perirectal, presacral, and inguinal nodes followed by a local boost in selected cases. 5-Fluorouracil was scheduled as a continuous infusion of 1,000 mg/m2 per 24 hours on days 1 to 5 and 29 to 33 and mitomycin C as a bolus of 10 mg/m2 on days 1 and 29. Routinely processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferating cell nuclear antigen and MIB1 (Ki-67) antigen to determine the labeling index. In addition, DNA ploidy was assessed after Feulgen staining. RESULTS: Actuarial cancer-related survival, no evidence of disease survival, and colostomy-free survival rates at five years were 81, 76, and 86 percent, respectively. In univariate analysis, T category (T1/2 vs. T3/4) was predictive for no evidence of disease survival (87 vs. 59 percent; P = 0.03) and colostomy-free survival (94 vs. 73 percent; P = 0.05). N category (N0 vs. N1-3) influenced actuarial cancer-related survival (85 vs. 58 percent; P = 0.002) and no evidence of disease survival (80 vs. 53 percent; P = 0.02). A higher proliferative potential as measured by the MIB1 labeling index was associated with a better colostomy-free survival (90 vs. 50 percent; P = 0.04). In multivariate analysis, actuarial cancer-related survival was only influenced by the N category (P = 0.03) and no evidence of disease survival by N category (P = 0.03) and mitomycin C dose (P = 0.04). Salvage abdominoperineal resection achieved long-term control in only four of seven patients with local failures. CONCLUSION: Treatment with a combination of radiotherapy and chemotherapy is safe and effective for patients with anal canal carcinoma. Abdominoperineal resection is indicated as a salvage procedure in nonresponding and recurrent lesions and may be of benefit in a small subgroup of patients with poor prognostic factors.

Adult↗
PubMed1998

[The age correction of survival probabilities in cancer studies].

PURPOSE: Survival of elder oncological patients may depend on the tumor disease, on reasons not related to the underlying disease or simply on patient's age. Therefore patient' age has to be taken into account if the objective of an oncological study is the disease-related survival. Basically, there are 3 different approaches: multivariate statistical modelling, estimation of disease-related survival after censoring of cases with cause of death not due to the tumor disease, and consideration of demographical data in the general population. PATIENTS AND METHODS: Our paper deals with the age correction using the data from the 1986/88 census in Germany. We have written a computer program based on SPSSWIN, which allows an automated age correction. Using clinical data of radiotherapy after surgical therapy of bladder cancer, we illustrate the method. RESULTS: The estimated 5-year-survival using the age correction was--dependent on patient's age in the sample--10% up to 15% higher than the uncorrected rate. In the whole sample of 333 unselected patients, 5-year-survival was corrected from 47% to 59%. In the normal population adjusted for age- and sex-distribution, the expected survival rate was 80%. CONCLUSIONS: The age correction has substantial influence on survival analysis of male patients elder than 60 years and female patients elder than 70 years. It should therefore be used in oncological studies investigating long-term survival of patients in these age-groups.

Adult↗
PubMed1998

Cytotoxicity of fractionated paclitaxel (Taxol) administration in vitro.

PURPOSE: Paclitaxel (Taxol) is a new anticancer agent with a novel mechanism of action. It has demonstrated broad clinical activity in a variety of malignancies. Several aspects of paclitaxel's usage remain to be clarified, including the optimal treatment schedule. Furthermore, the diluent of paclitaxel, Cremophor EL/ethanol, alone has shown to be markedly active in tumor samples. MATERIAL AND METHODS: The in-vitro cytotoxicity of paclitaxel (Taxol) due to single dose (1 x 10 microM/day, day 1 incubation time: 3 h and 15 h) and fractionated exposure (5 x 2 microM/day, day 1 to 5 incubation time: 3 h/day) was evaluated, measuring surviving fraction (clonogenic assay) and DNA distribution (flow cytometric analysis). In the control population, the diluent Cremophor EL/ethanol or a phosphate buffered salt solution (PBS) were applied using identical doses and schedules. A mammalian fibroblast cell line (HyB14FAF28) was used. RESULTS: Fractionated application of paclitaxel (Taxol) produced a significant lower clonogenic survival (0.63) in comparison with single dose exposure for 3 h (0.84) and 15 h (0.82). DNA analysis showed no evidence for a significant difference in DNA distribution of the paclitaxel-specific G2/M phase over a 10-day period. Controls with the diluent Cremophor EL/ethanol showed a clonogenic survival of 0.87 (3 h exposure) and 0.88 (15 h exposure) versus 0.65 after fractionated drug administration (5 x 2 microM/day, day 1 to 5, incubation time: 3 h/day). PBS controls and untreated controls did not show any significant effect. CONCLUSIONS: It seems that clonogenic survival after Taxol exposure of this mammalian fibroblast cell line varies with treatment schedule through a yet unknown process that does not involve G2/M arrest. The results indicate the treatment effects to be mainly based on the diluent combination without any further benefit induced by paclitaxel.

Animals↗
PubMed1998

[Use of G-CSF (Neupogen) in multimodal treatment in radiotherapy].

BACKGROUND: Therapy-induced leukopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen). PATIENTS AND METHODS: In this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neuropogen) was already given at leukocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It administered subcutaneously every other day, based on body weight until reaching normal leucocyte levels. RESULTS: In 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treated with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light "flu like" symptoms in 14% of the patients, no side effects were observed. CONCLUSIONS: When a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.

Adult↗
PubMed1998

[Effects of fractionation and dose rate in PDR brachytherapy of B14 cells].

PURPOSE: Present radiobiological studies for different cell lines in vitro demonstrate the equivalence and efficacy of continuous low-dose-rate brachytherapy (LDR-BT) and pulsed dose rate brachytherapy (PDR-BT) when using small and frequent dose pulses. The aim of this study was to examine monolayer fibroblast cultures in vitro to examine the biological effects of different pulse doses and dose rates under clinically conditions. MATERIAL AND METHODS: B14 cells, Hy B14 FAF 28, peritoneal fibroblasts, were cultured in multi-well plates and exposed to a PDR radiation source at a distance of 9 mm. The following PDR-schemes were compared: dose per pulse: 1 Gy, 2.5 Gy and 5 Gy to a total dose of 5 Gy/5 h (overall time), 10 Gy/10 h, 20 Gy/20 h and 30 Gy/30 h. The pulse duration for the examination of dose rate effects was 20 min, 30 min or 52 min corresponding by dye pulse dose rate of 300 cGy/h, 200 cGy/h or 115 cGy/h. Treatment endpoints were cell measured by dye exclusion test and clonogenic cell survival. RESULTS: Cell survival decreased for pulse doses of 5 Gy compared to 2.5 Gy or 1 Gy per pulse (mean dose rate 200 to 300 cGy/h). No differences were observed with dose rates during irradiation of 300 cGy/h, 200 cGy/h or 115 cGy/h (20 Gy/1 Gy). CONCLUSION: Radiobiological effects of PDR-RT are dependent on the dose per pulse, with differences in biological effects only with a dose per pulse of more than 2.5 Gy, considering the described in-vitro conditions. More examinations with a more pronounced difference in dose rate will be continued for evaluation of dose rate effects.

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