Biomedical subjects

V Rudat

Publications and source records attributed to V Rudat.

At least 37 records · Page 2Linked to original sources

PubMed1999

[Predictive value of serum levels of basic fibroblast growth factor, vascular endothelial growth factor and matrix metalloproteinase-2 in advanced carcinomas of the head and neck].

The objective of this trial was to analyse the predictive character of the angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase-2 (MMP-2) in the sera of patients with advanced carcinomas of the head and neck treated by primary radiochemotherapy. From 1992 to 1995, 25 patients with UICC stage cancers and one patient with stage III disease were treated in the departments of otolaryngology and radio-oncology of the University of Heidelberg according to a protocol of accelerated concomitant boost radiochemotherapy with carboplatin. The serum levels of VEGF, bFGF and MMP-2 were measured by enzyme-linked radiosorbent assay and data were correlated with followup findings (median time of follow up: 60 months). Patients with serum levels above normal were detected for VEGF in 4 patients, MMP-2 in 7 patients and for bFGF in 13 patients. An increase in bFGF serum levels above the upper limit of normal controls was significantly associated with a shorter time of locoregional control (P=0.036). In a covariate analysis bFGF proved to be independent of other prognostic factors, such as age, site, total tumor volume and response to therapy. No prognostic relevance of VEGF and MMP2 serum levels could be determined. The present suggest that bFGF is an independent prognostic factor for tumor control in advanced head and neck cancer after primary radiochemotherapy.

Adult↗

PubMed1999

[Prognostic significance of cell-cycle regulatory proteins for outcome after primary radiochemotherapy in patients with advanced head and neck cancer].

BACKGROUND: Primary radiochemotherapy is gaining increasing importance for the treatment of advanced head and neck squamous cell carcinomas. However, there is a lack of clinical factors concerning prognostic information in relation to treatment. In this pilot study, we examined whether molecular factors can provide such information. PATIENTS AND METHODS: The expression patterns and their possible prognostic relevance of the cell cycle regulatory proteins p53, p21(WAF/CIP1), Rb, p16(INK4A), CDK4 and Cyclin D1, MIB1 (Ki-67) and BCL-2 were analysed in pretreatment tumor biopsies from 43 patients with advanced carcinomas of the oropharynx (n = 26), hypopharynx (n = 10) and larynx (n = 7) by applying immunohistochemistry to paraffin sections of tumor specimens. All patients were treated by the same method of an accelerated "concomitant boost" radiochemotherapy with carboplatin in a phase II study. Median followup time was 56 months. RESULTS: No correlation was found between any of the markers and the remission rate, T-stage, N-stage, rate of loco-regional recurrences and distant metastases. However, independent of the tumor stage, patients with CDK4/cyclin-D1 overexpressing tumors had a significantly shortened overall survival (P = 0.014 and 0.026, respectively). CONCLUSION: The results of this pilot study indicate that CDK4 and cyclin D1 over-expression provide useful prognostic information about clinical outcome after primary radiochemotherapy of head and neck cancer patients.

Adult↗

PubMed1999

[Effect of primary radiochemotherapy on cellular and subcellular immunologic parameters].

PURPOSE: It is well known that chemotherapy and radiotherapy in other tumor sites than head and neck cause immunomodulating effects. The purpose of this trial was to assess the influence of radiochemotherapy in head and neck on cellular and subcellular immunity. PATIENTS AND METHODS: In a phase II/III-trial fifty patients with advanced squamous cell carcinoma of the head and neck were treated by simultaneously accelerated radiochemotherapy with Carboplatin (70 mg/sqm). Total radiation dose was 66 Gy/35 days. The following immunological parameters were investigated at several time points during therapy: total lymphocytes, total T-lymphocytes, CD4+ lymphocytes, CD8+ lymphocytes, monocytes, natural killer cells, interleukin-2-receptor-positive T-cells, MHC class II-positive B-cells, monocytes and T-cells, CD4/CD8-ratio; Cytokines: II-1, soluble II-1-receptor antagonist, II-2, soluble II-2-receptor, II-3, II-4, II-6, soluble II-6-receptor, II-8, interferon-alpha, granulocytes-macrophages-colony-stimulating-factor, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1. In addition, responses to the in vitro stimulation of lymphocytes by mitogens was tested. RESULTS: During therapy lymphocyte subpopulation counts decreased significantly but reversibly. Simultaneously, the function of lymphocytes was significantly but reversibly reduced. Also, II-8-concentration decreased significantly whereas concentrations of II-6 and soluble II-1-receptor antagonist significantly increased. CONCLUSIONS: The accelerated radiochemotherapy with Carboplatin induces a severe impairment of cellular immunity, followed by compensatory cytokine reaction.

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

Rise of oxygenation in cervical lymph node metastasis during the initial course of radiochemotherapy.

It has been hypothesized that during radiation treatment a reoxygenation of hypoxic tumor tissue takes place. To test this hypothesis, we have investigated whether reoxygenation in lymph node metastases could be determined by invasive PO (2) measurements. Through a hypodermic needle inserted transcutaneously into tumor-positive lymph nodes, polarographic oxygen determinations were made in 18 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx. These measurements were performed before therapy and a week after the onset of radiotherapy or radiochemotherapy, respectively. Low PO (2) values before treatment (mean value of the patient's median was 12.6 mm Hg PO (2)) and a mean hypoxic fraction (PO (2) < 5 mm Hg) of 39.6% indicated manifest tumor hypoxia. After 1 week of treatment, a significant increase in the median PO (2) (mean value of shift: 7.3 mm Hg) and a reduction in the hypoxic fraction (mean value of shift: 13.4% PO (2) < 5 mm Hg, P < 0.03) were observed after both radiotherapy and radiochemotherapy. Thus invasive PO (2) histography fulfills the requirements for a method to confirm tumor hypoxia in head and neck tumors. The results obtained indicate that reoxygenation occurs during the initial phases of radiotherapy and radiochemotherapy, and they will form the basis for future comparative investigations on the possible influence of hypoxic parameters on tumor responsiveness toward radiation and radiochemotherapy.

Adult↗

PubMed1998

[Chronic laryngeal edema as a late reaction to radiochemotherapy].

In addition to mucositis and myelotoxicity as well known early reactions after radiotherapy or radiochemotherapy in advanced head and neck tumors, late toxicity following treatment is an often underestimated problem. Between 1992 and 1995, 68 patients with advanced oro- and hypopharyngeal tumors were treated primarily with accelerated concomitant boost radiochemotherapy (total dose irradiations of 66 Gy and carboplatin as chemotherapy). Ninety-three per cent of the patients had stage IV disease according to the UICC-TNM classification. Monitoring of follow-up included late toxicity with special attention given to laryngeal edema. In 37 patients (54%) edema of the larynx as a late complication of radiochemotherapy was observed by clinical investigation and CT scan. The median onset of laryngeal edema was found 121 days after completion of therapy, with a median time of observation of 250 days. Observations in these patients demonstrated the chronic character of this edema. An increase in the laryngeal edema in 5 cases resulted in tracheostomy. Laryngeal edema in 10 patients was associated with recurrence of tumor. These results show that after xerostomia laryngeal edema is the main late toxicity in the head and neck after radiochemotherapy and should lead to further investigations to exclude possible recurrent tumor.

Adult↗

PubMed1998

Trans-dominant inhibition of poly(ADP-ribosyl)ation leads to decreased recovery from ionizing radiation-induced cell killing.

Poly(ADP-ribosyl)ation is a post-translational modification of nuclear proteins catalysed by poly(ADP-ribose)polymerase (PARP). PARP is strongly activated by DNA strand breaks and is thought to be involved in DNA repair, and various chemical agents that inhibit poly(ADP-ribosyl)ation have radiosensitizing properties. An alternative, highly specific (trans-dominant) inhibition of PARP function has been made possible with a molecular genetic approach where CO60 hamster cells were transfected with the PARP DNA-binding domain (DBD) under the control of a Dexamethasone (Dex)-inducible promoter. Stable transfectants were incubated with or without Dex and the impact of poly(ADP-ribosyl)ation on cellular radiation response (clonogenic survival) was measured following irradiation at high or low dose-rate or when potentially lethal damage (PLD) recovery was allowed. For acute exposures the radiosensitizing effect of PARP inhibition could be confirmed and a large enhancement ratio (calculated from the respective mean inactivation doses) of 2.2 was found for plateau phase cells. Both cellular recovery phenomena (dose-rate sparing and PLD) were decreased in the presence of Dex, and particularly PLD-recovery was nearly completely abolished due to the inhibition of poly(ADP-ribosyl)ation. The latter finding strongly suggests an involvement of PARP in the repair of DNA double-strand breakage.

Animals↗

PubMed1997

Predictive value of the flow cytometric PCNA assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy.

PURPOSE: Proliferation of tumor cells during radiotherapy may limit tumor control, especially in rapidly proliferating tumors such as head and neck carcinomas. We present a flow cytometric method for detection of PCNA in solid head and neck tumors and how these data correlate with outcome. METHODS AND MATERIALS: Pretherapeutic biopsies of 20 inoperable patients with Stage IV squamous cell carcinoma were examined. Biparametric flow cytometry was done after anti-PCNA (PC10) and propidium iodine staining were performed. PCNA index (percentage PCNA positive cells), DNA index, and S phase fraction (SPF, euploid tumors only) were determined. The therapy consisted of an accelerated-hyperfractionated radiochemotherapy (66 Gy/5 weeks, concomitant boost of 1.6 Gy/day in weeks 4+5, Carboplatin 5 x 70 mg/m2 in weeks 1+5). The median follow-up time was 30 months. RESULTS: Fourteen patients suffered from disease progession and 12 died. Median actuarial, cause-specific survival, and disease-free survival (DFS) times were 17 and 9 months, respectively. PCNA indices ranged from 4 to 70% (median 9%); there were 7 aneuploid and 13 euploid tumors. SPF ranged from 4 to 14.5% (median 10.5%). Neither SPF nor ploidy had a significant influence on outcome. Patients were divided according to PCNA index in higher (n = 10) and lower (n = 10) than the median. Survival and DFS were 13 and 6 months for the group >9% and 20 and 15 months for the group <9%. The difference in DFS was significant (p = 0.03, log rank test). CONCLUSION: These results fall in line with other studies showing the influence of pretherapeutic proliferation on outcome after radiotherapy. Although the moderately accelerated therapy regimen certainly reduces the influence of proliferation on outcome, patients with faster proliferating tumors still have a worse outcome. DFS is the more relevant endpoint in this study because of effective salvage therapies, which influence survival.

Adult↗

PubMed1997

[The conformal radiotherapy of localized prostatic carcinoma: acute tolerance and early efficacy].

AIM: In a prospective trial early effectiveness and acute toxicity of conformal 3D-planned radiotherapy for localized prostate cancer was quantified using dose-volume-histogramms and evaluated with respect of treatment technique. PATIENTS AND METHOD: Thirty-two men (44 to 80 years old) with locally advanced carcinoma of the prostate (stage B2 or C) have been treated by 3D-planned conformal radiotherapy using high energy photons. In 28/32 men treatment technique was a monoaxial bisegmental rotation with irregular fields. With single doses of 2.0 Gy a mean total dose of 63.9 +/- 4.9 Gy according to ICRU was applied within 46 +/- 4 days. Maximum dose was in the mean 105.1% +/- 3.8%. 3D treatment volume was 274.1 +/- 113.4 cm3. Median follow-up is 1.8 years (15 to 34 months). Toxicity was evaluated according to RTOG-EORTC by patient interview and physical examination on a weekly basis during radiotherapy and by regular follow-up. RESULTS: Eleven patients had none, 15 mild (RTOG grade 1) and 6 moderate symptoms (RTOG grade 2, mainly diarrhoea, dysuria and polyuria). Acute complications leading to treatment interruption did not occur. In 16 patients symptoms disappeared within 6 weeks after radiotherapy. Only 2 men had symptoms which lasted longer than 3 months and were endoscopically examined. Up to now no late complications were detected. Incidence and severity of toxicity was significantly (p < 0.05) related to the size of treatment volume. Acute toxicity was found to depend statistically significant (p < 0.05) on the proportional volume of bladder and rectum, irradiated with more than 35 Gy. In 81% of the patients with pretherapeutic elevated PSA levels normalisation of PSA was observed. Overall mean PSA levels of 15.7 +/- 22.6 micrograms/l at the beginning of radiotherapy fell to 2.1 +/- 3.7 micrograms/l 6 weeks after irradiation. Only 1 Patient relapsed locally 22 months after radiation therapy. CONCLUSION: We conclude that due to modern 3D-planned conformal techniques with optimization of treatment dose and improved protection of critical organs such as urinary bladder and rectum, radiotherapy allows an effective and well tolerated therapy of localized prostatic carcinoma.

Adult↗

PubMed1997

[Polarographic detection of reoxygenation of lymph node metastases in the initial phase of primary radio- and radiochemotherapy in patients with advanced squamous epithelial carcinomas of the head and neck].

The therapeutic effect of radiotherapy depends amongst other things on the degree of oxygenation of tumour tissue. Epithelial carcinomas of the head-neck region exhibit considerable hypoxic areas which vary markedly between individuals and not encompassed by current staging and grading. It is assumed that during radiation treatment a reoxygenation of hypoxic tumour cells takes place. It was investigated wether the occurrence of reoxygenation could be determined by invasive oxygen partial pressure measurements in lymph node metastases. Using a needle probe inserted transcutaneously into a lymph node polarographic oxygen determinations (Eppendorf pO2-Histiograph) were made on 13 patients with advanced oro- and hypopharyngeal carcinomas before therapy and after a week of accelerated radio- or radiochemotherapy. Low pO2 values before treatment (median 13.5 mmHg, average 20.3 mmHg) and a hypoxic fraction (pO2 < 10 mmHg) of 45.2% indicated manifest tumour hypoxia. After the first week of treatment a significant increase in the median- (24.1 mmHg) and the average pO2 (28.2 mmHg) as well as a reduction in the hypoxic fraction (27%) were observed. Invasive pO2 histiography fulfils the requirements for a method to confirm tumour hypoxia in head-neck tumours. The results obtained indicate that reoxygenation occurs during the initial phases of radio- and radio-chemotherapy.

Adult↗

PubMed1997

In vitro radiosensitivity of primary human fibroblasts. Lack of correlation with acute radiation toxicity in patients with head and neck cancer.

BACKGROUND AND PURPOSE: There is a considerable hope among clinicians and radiobiologists to detect genetically radiosensitive patients prior to radiotherapy. A predictive assay would enable adjustment of the total irradiation dose to the individual at a constant risk of normal tissue complications. In this prospective study, the clonogenic survival assay for primary human fibroblasts to determine radiosensitivity in vitro was evaluated and then correlated with clinically observed acute radiation reactions. MATERIALS AND METHODS: One hundred twenty-five independent survival experiments with primary fibroblasts derived from 63 biopsies from 55 cancer and non-cancer patients were performed. RESULTS: A wide variation of cell survival between biopsies was detected. Statistical analysis revealed a highly significantly larger interindividual than intraindividual variation of SF2 values. However, a considerable scatter of SF2 values in repeated experiments was observed in individual cases. Age, gender, disease status (cancer patient, non-cancer patient) and origin of fibroblasts (skin, periodontal tissue) were demonstrated not to be statistically significant confounding factors on the intrinsic radiosensitivity in vitro. In a prospective study, no correlation of the SF2 and acute reactions in 25 patients with head and neck cancer treated with a primary accelerated radiochemotherapy was detected. CONCLUSION: Our data show that the clonogenic assay is able to distinguish between intrinsic radiosensitivities of primary human fibroblasts if a statistical approach is used but does not predict acute radiation toxicity.

Acute Disease↗

PubMed1997

Prognostic significance of color Doppler findings in head and neck tumors.

We examined whether or not the degree of tumor vascularity in lymph node metastases as depicted by color Doppler is associated with a patient's prognosis. Cervical lymph node metastases in 25 patients with head and neck cancer were examined before combined accelerated radiotherapy and chemotherapy. The findings were quantified using a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD) and the color hues, which are numerically expressed by the mean color value (MCV). We found that, in the patient group with a CPD below median, the median survival was 958 days and, in the group with a higher CPD, it was 423 days (p = 0.05). The time to detection of distant metastases was 18 months with a low CPD, and 6 months with a high CPD (p = 0.05). However, the time to local or nodal progression was not different between the groups. The MCV was not correlated with prognostic data. These results indicate that, in patients with metastatic head and neck cancer, highly vascularized lymph nodes detected with color Doppler sonography may indicate a shorter survival and earlier occurrence of distant metastases.

Blood Flow Velocity↗

PubMed1996

Combined error of patient positioning variability and prostate motion uncertainty in 3D conformal radiotherapy of localized prostate cancer.

PURPOSE: To measure the patient positioning and prostate motion variability and to estimate its influence on the calculated 3D dose distribution in 3D conformal radiotherapy of patients with localized prostate carcinoma. METHODS AND MATERIALS: Patient positioning variability was determined retrospectively by comparing 54 orthogonal simulator films with 125 corresponding portal films from 27 patients. Prostate motion variability was determined by 107 computed tomography (CT) examinations with a CT simulator in 28 patients during radiotherapy. RESULTS: In each observed direction, the patient positioning variability and prostate motion showed a normal distribution. This observation enabled the calculation of a combined error of both components. The standard deviation (1 SD) of the patient positioning error in three directions ranged from 3.1 to 5.4 mm; the prostate motion variability was significantly greater in the anterior-posterior direction (1 SD = 2.8 mm) than in the mediolateral direction (1 SD = 1.4 mm). The 1 SD of the estimated combined error was in the anterior-posterior direction 6.1 mm and in mediolateral direction 3.6 mm. CONCLUSION: The range of patient positioning variability and prostate motion were statistically predictable under the patient setup conditions used. Dose-volume histograms demonstrating the influence of the combined error of both components on the calculated dose distribution are presented.

Humans↗

PubMed1996

[Accelerated hyperfractionated simultaneous radiochemotherapy in advanced head-neck carcinomas in comparison: split course and concomitant boost concept].

PATIENTS: Between 1989 and 1992, 38 patients with advanced squamous cell carcinomas of the head and neck were treated by an accelerated hyperfractionated split-course radiochemotherapy (SCRC). This therapy was carried out at the ENT department and department of radiooncology of the University of Heidelberg. Within 51 days, 70.2 Gy were applied in three courses. In every course, simultaneous chemotherapy with cisplatin (60 mg/m2/week)/5 Fu (bolus: 350 mg/m2/d)/Leucovorin (bolus: 50 mg/m2 + 100 mg/m2/24 h) was carried out. Between 1992 and 1994, 50 patients suffering from advanced head and neck cancer (stage III, V) were also treated with an accelerated hyperfractionated concomitant-boost radiochemotherapy (CBRC) at the same departments. A total dose of 66 Gy, was applied within 33 days. The patients were also treated with simultaneous chemotherapy with carboplatin (70 mg/m2/24 h) in the first and fifth week. RESULTS: In about 50% of the patients treated with SCRC, the therapy was more than 10 days longer than the scheduled period. The lack of compliance due to toxicity was considered as one of the main reasons for this delay. After the first course of SCRC, eight of 38 patients showed mucositis of the upper aerodigestive tract (WHO grade > 3); after the second course, 11 of 38 patients; and after the third course, 15 of 38 patients. Fifty-two percent of the patients developed emesis, 10% leucopenia < 1 nl, 10% nephrotoxicity, 3% pancreatitis, 3% thrombosis, 3% gastritis, and 3% auditory threshold shifts of about more than 10 dB. In about 7.5% of the patients treated with CBRC, the therapy was more than 10 days longer than the scheduled period. The mucositis of the upper aerodigestive tract (50% of the patients showed WHO-grade > 3) was considered to be the main reason for this. In four patients a neutropenia < 1 nl was detected, in one patient anemia < 7 g/dl and n 33 patients thrombocytopenia < 100/nl. CONCLUSIONS: In conclusion, the concomitant boost radiochemotherapy showed a lower toxicity and higher acceptance than the split-course radiochemotherapy. This is documented in lower protocol delays and better results in the two-years survival time in case of concomitant boost radiotherapy.

Adult↗

PubMed1995

[The problem of radiogenic and chemotherapy-induced mucositis of the mouth and and oropharynx exemplified by accelerated radiochemotherapy with carboplatin in patients with inoperable squamous epithelial carcinomas of the head-/neck area. Heidelberg experiences].

Despite numerous treatment measures mucositis of the mouth and pharynx due to radiochemotherapy frequently remains refractory to therapy. In most cases high doses of pain medications are till required. However, mucositis as a strong early reaction may be controllable by limiting cancer therapy. Within the current framework of accelerated radiochemotherapy with carboplatin, 50 patients with inoperable squamous cell carcinomas of the head and neck were followed from 1992 to 1994. Acute toxicity was documented from the first through eighth week after starting therapy. From the fifth week on, the degree of mucositis found was > 3 (WHO scale) in 24 patients. The extent of mucositis in 5 patients required interrupting therapy for 10 days on average. In 14 cases the average stay in hospital had to be prolonged by 10.2 days because of severe inflammation. In all, the average duration of mucositis after the end of the therapy amounted to 9.6 weeks. Twenty patients required bypass feedings with transnasal stomach tubes or percutaneous gastrostomy (PEG) tubes that were later removed. In addition, the incidences of dysphagia, xerostomia, hoarseness, skin reactions, nausea or vomitus and myelotoxicity were recorded. Descriptions of the supportive care concepts used at the University of Heidelberg are given and the supportive care concepts available scientific literature is updated.

Adult↗

PubMed1995

[The belly-board technic for the sparing of the small intestine. Studies on positioning accuracy taking into consideration conformational irradiation technics].

BACKGROUND: The immobilization error of patients positioned on the open table-top device in prone position as well as the movement of the small bowel out of the pelvis by this positioning technique was determined. The positioning error is of special importance for the 3-dimensional treatment planning for conformational radiotherapy. PATIENTS AND METHODS: The positioning error was determined by superpositioning 106 portal films with the corresponding simulator films from 21 patients with carcinoma of the rectum who-received 3D-planned conformational radiotherapy (3-field technique with irregular blocks). The movement of the small bowel out of the pelvis was studied by comparing simulator films after barium swallow in supine and open table-top position as well with 3D-treatment plans of the same patient in both positions in 3 cases. RESULTS: The positioning error along the medio-lateral, dorso-ventral and cranio-caudal axis was 1.4/0.6/1.8 mm and the standard deviation 4.4/6.8/6.3 mm, respectively. In comparison to the supine position more rotation errors in the sagittal view were observed (37% and 9% respectively) with a median of 5.1 degrees. Six out of 22 patients showed no adhesions of the small bowel and a complete movement out of the treatment field was achieved. 14 out of 16 Patients with adhesions revealed a partial movement of the small bowel out of the treatment field. Comparing 3D-treatment plans in both positions again demonstrated a marked reduction of the irradiated small bowel volume with the use of the open table-top device. CONCLUSIONS: The open table-top device positioning technique is a simple and cheap positioning support to reduce small bowel obstructions by radiation therapy of pelvic and retroperitoneal tumors. For the radiation treatment planning the data suggest a safety margin to compensate positioning errors of approximately 1.5 cm referring to the 95% confidence interval.

Administration, Oral↗

PubMed1995

[Three-dimensional planned radiotherapy in rectal cancer. Feasibility study and preliminary clinical results].

PURPOSE: Since 1991 the use of three-dimensional planned radiation therapy for rectal cancer was evaluated as a part of a clinical project funded by the Deutsche Krebshilfe at the Radiological Department of the University of Heidelberg. First clinical experiences are reported. PATIENTS AND METHODS: 32 patients who were irradiated loco-regional for rectal cancer were analysed retrospectively. Radiation therapy techniques: patient's position was prone by the use of a belly board. Three-dimensional treatment (3D) planning system was voxelplan. The radiation therapy was started using a 3-field-box technique modified by 3D-technique after 22 to 42 Gy, depending on therapeutic concept. RESULTS: On average 92% of the planning target volume were encompassed with the 80% isodose. The average maximum dose was 108% (isocenter = 100%), of the small bowel volume received less than 34% of the dose, 70% of the bladder volume less than 40% respectively. Total average dose was 52.4% Gy. Irregular fields were used in all patients, a non-coplanar field was used to optimize dose-distribution in 41% of the patients, 21 patients received chemotherapy simultaneously. Acute side effects according to gastrointestinal tract reached grade 1 (WHO) in 9 patients, grade 2 in 2 patients. Side effects according to bladder reached grade 1 in 5 patients grade 2 in 1 patient respectively. In 4 patients suffered from acute side effects concerning the bladder. In one patient acute side effects grade 1 concerning gastrointestinal tract was observed. Portal films were analysed to evaluate precision of radiation therapy. On average the error was 3.1/4.5/4.0 mm in the x/y/z direction respectively. The standard deviation was 4.4/6.8/6.3 mm for x/y/z respectively. A median time of 2 hours was necessary for all planning procedures. CONCLUSIONS: Three-dimensional treatment planning optimizes dose-distribution in a relevant number of patients. Its clinical use for treatment of large targets or in order to applicate high doses is justified. Planning target volume should cover the clinical target volume with a margin of 1.5 cm.

Feasibility Studies↗