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Volker Budach

Publications and source records attributed to Volker Budach.

24 records · Page 2Linked to original sources
PubMed2002

Selective inactivation of DNA-dependent protein kinase with antisense oligodeoxynucleotides: consequences for the rejoining of radiation-induced DNA double-strand breaks and radiosensitivity of human cancer cell lines.

The inhibition of DNA-dependent protein kinase activity with antisense-oligodeoxynucleotide (As-ODN) and its consequences for the rejoining of DNA-double-strand breaks (Dsbs) and radiation sensitivity was studied in human non-small cell lung cancer (NSCLC) cell lines. Cells were transfected with As-ODNs specific for the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). In comparison, cells were treated with Wortmannin, a potent but nonspecific inhibitor of DNA-PK activity. As-ODN efficiently reduced the kinase activity with an IC50 of about 100-200 IC50 of Wortmannin was at approximately 5-10 micro M. Treatment of cells with 300 nM As-ODN increased the fraction of residual Dsb at 4 h after irradiation by a factor of 4.4, 2.6, and 1.7 in A549, H460, and H661 cells, respectively. The respective values after treatment with 20 micro M Wortmannin were 5.3, 4.3, and 2.2. Inhibition of DNA-PK activity by As-ODN and Wortmannin also decreased the surviving fraction of the NSCLC cell lines. These data show that kinase activity of DNA-PKcs can be specifically inhibited with As-ODN as effective as Wortmannin and results in marked inhibition of DNA-Dsb rejoining and radiosensitization of NSCLC cell lines.

Androstadienes↗
PubMed2002

Intraindividual comparison of conventional three-dimensional radiotherapy and intensity modulated radiotherapy in the therapy of locally advanced non-small cell lung cancer a planning study.

BACKGROUND: Local failure is the one of the most frequent cause of tumor related death in locally advanced non-small cell lung cancer (LAD-NSCLC). Dose escalation has the promise of increased loco-regional tumor control but is limited by the tolerances of critical organs. PATIENTS AND METHODS: To evaluate the potential of IMRT in comparison to conventional three-dimensional conformal planning (3DCRT) dose constraints were defined: Maximum dose (D(max)) to spinal cord < 48 Gy, mean lung dose </= 24 Gy, D(max) esophagus > 70 Gy in not more than 5 cm of the total length. For ten patients two plans were compared: (1) 3DCRT with 5 weekly fractions (SD) of 2 Gy to a total dose (TD) of 50 Gy to the planning target volume of second order (PTV2). If the tolerance of the critical organs was not exceeded, patients get a boost plan with a higher TD to the PTV1. (2) IMRT: concomitant boost with 5 weekly SD of 2 Gy (PTV1) and 1.5 Gy to a partial (p)PTV (pPTV=PTV2 profile of a line PTV1) to a TD of 51 Gy to the pPTV and 68 Gy to the PTV1. If possible, patients get a boost plan to the PTV1 with 5 weekly SD of 2 Gy to the highest possibly TD. RESULTS: Using 3DCRT, 3/10 patients could not be treated with TD > 50 Gy, but 9/10 patients get higher TD by IMRT. TD to the PTV1 could be escalated by 16% on average. The use of non-coplanar fields in IMRT lead to a reduction of the irradiated lung volume. There is a strong correlation between physical and biological mean lung doses. CONCLUSION: IMRT gives the possibility of further dose escalation without an increasing mean lung dose especially in patients with large tumors.

Adult↗
PubMed2002

High dose rate brachytherapy of localized prostate cancer.

OBJECTIVE: We evaluated the safety and efficacy of high dose rate (HDR) brachytherapy using Iridium-192 (Ir 192) and 3D conformal external beam radiotherapy in patients with localized prostate cancer. METHODS: A total of 444 patients with localized prostate cancer underwent combined radiotherapy with interstitial Ir 192 and 3D conformal external beam radiotherapy between December 1992 and March 2001. The 230 patients, treated between December 1992 and December 1997 were analyzed. All patients underwent laparoscopic pelvic lymph node dissection to exclude patients with lymphatic involvement. Ir 192 was delivered twice with a 1-week interval in HDR remote control technique. The interstitial dose from December 1992 to December 1993 was 10Gy, after December 1993 the dose was reduced to 9Gy per treatment session. The interstitial application was followed by external beam radiation of 45Gy for cT1-cT2 and 50.4Gy for cT3 tumor (40Gy from December 1992 to December 1993). Progression was defined as biochemical failure according to ASTRO criteria, e.g. three consecutive PSA rises following the PSA nadir. RESULTS: The median PSA value decreased from 12.8 to 0.93ng/ml 12 months after treatment. Median PSA value was 0.47 after 24 months, 0.30ng/ml after 36 months and 0.18ng/ml after 60 months. 68% of the biopsies were negative 24 months after therapy. Progression-free rate was 100% for cT1 tumors, 75% for cT2 and 60% for stage-cT3 on 5-year follow-up. Five-year overall survival was 93%, 5-year disease-specific survival was 98%. Initial PSA value <10ng/ml, low stage and low grade were significantly related to 5-year progression-free survival. CONCLUSIONS: Combined HDR brachytherapy with Ir 192 is an alternative treatment option especially for patients with cT3 prostate cancer. Initial PSA value, stage and grade, are important prognostic factors.

Aged↗
PubMed2002

Interstitial hyperthermia using self-regulating thermoseeds combined with conformal radiation therapy.

OBJECTIVE: The combination of hyperthermia and radiation in the treatment of malignancies is based on a variety of experimental data which have proven the synergistic effects of these two treatment modalities. We planned a phase II trial in a special hyperthermia research group (SFB 273) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) to determine feasibility, acute toxicity and efficacy of this combination for prostate cancer. METHODS: A total of 57 patients with localized prostate cancer were treated with interstitial hyperthermia using cobalt-palladium thermoseeds and conformal radiation between July 1997 and December 2000. Thermoseeds were placed into the prostate homogeneously. Hyperthermia was created using a magnetic field and was delivered in six sessions once weekly. 3D-conformal radiotherapy of 68.4Gy was given simultaneously in daily fractions of 1.8Gy. RESULTS: Intra-prostatic temperatures were between 42 and 46 degrees C. No major side effects were observed during hyperthermia. Median follow-up was 12 months (range: 3-26 months). Median prostate specific antigen (PSA) value decreased from 11.6 to 2.4 ng/ml 3 months after treatment, to 1.3ng/ml 12 months after treatment and to 0.55 ng/ml 2 years after the therapy. CONCLUSION: Interstitial hyperthermia is feasible, well tolerated and led to a steep decrease of PSA values. Our current follow-up is too short to comment about efficacy. Combining effective interstitial hyperthermia with conformal radiotherapy may be an exciting innovative treatment option for prostate cancer.

Aged↗
PubMed2002

Influence of amifostine on toxicity of CHOP in elderly patients with aggressive non-Hodgkin's lymphoma--a phase II study.

Due to concerns about toxicity, many elderly patients with aggressive non-Hodgkin's lymphoma (NHL) are not considered candidates for standard chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). The cytoprotective agent amifostine has the potential to reduce toxicity when added to chemotherapy. The purpose of the current study was to examine the toxicity of CHOP combined with amifostine in elderly patients with aggressive NHL. A prospective phase II study was performed in patients aged 60 years and older. Patients with stage I/II disease received 4 cycles of CHOP followed by involved-field irradiation. Patients with stage III/IV received 6-8 cycles of CHOP. Amifostine (740 mg/m(2)) was administered as a 15-min i.v. infusion immediately before chemotherapy. Forty-one (median age 69.5 years, range 60-87) of 49 consecutive previously untreated patients, aged 60 years and older, with aggressive NHL seen in our center were included in the study. Twenty-one patients had stage I/II disease and 20 had stage III/IV disease. The patients received a total of 207 cycles of amifostine-CHOP. Infusion of amifostine caused mild to moderate transient side effects, including a drop of systolic blood pressure >20 mmHg in 54 cycles and nausea/vomiting in 36 cycles. Hematotoxicity of CHOP consisted of leukopenia grade 4 in only 15.4% of cycles. There were two cases of grade 3 anemia. No thrombocytopenia higher than grade 2 occurred. Febrile neutropenia was rare, occurring in 4.3% of cycles. One patient died after the first CHOP administration because of anthracycline-related acute cardiomyopathy (corresponding to a toxic death rate of 2.4%). The complete response rates were 85 and 75% in stage I/II and stage III/IV patients, respectively. After median follow-up of 33 months (range 17-50 months) the median overall survival was not reached in patients with stage I/II and was found to be 32 months in patients with stage III/IV. At 2 years, 76% of patients with stage I/II and 70% with stage III/IV were alive. Twelve of the 15 patients who died were aged older than 70. Amifostine pre-treatment was associated with a low toxicity of CHOP in elderly patients with aggressive NHL treated with curative intent. Treatment outcomes appeared not to be impaired by the addition of amifostine to CHOP. This schedule merits further testing in a randomized trial.

Aged↗