Biomedical subjects

M Flentje

Publications and source records attributed to M Flentje.

At least 73 records · Page 4Linked to original sources

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

[Pneumonitis after radiotherapy of bronchial carcinoma: incidence and influencing factors].

BACKGROUND: The most important side effect in radiotherapy of lung cancer is pneumonitis. The incidence of pneumonitis was evaluated in a retrospective study in the patient collective of the University of Heidelberg. Therapy related and therapy independent factors have been evaluated. PATIENTS AND METHODS: In 348 of 392 cases with lung cancer who were treated by local irradiation between January 1989 and January 1992 the patient's records were evaluable for response and toxicity. All patients were treated by megavolt equipment with a conventional fractionation in most cases. Standard target volumes were irradiated including the lymphatic drainage. From a dose of above 30 Gy a technique sparing the spinal cord was chosen. Retrospectively pneumonitis was classified into 4 grades starting from slight symptoms to respiratory insufficiency requiring O2. Grade I and II were summarized to slight, grade III and IV to severe pneumonitis. RESULTS: Regarding the treatment prior to irradiation patients with primary irradiation were affected in 26.5% (17% slight, 9.5% severe), with postoperative irradiation in 14% (9.3% slight, 4.7% severe), with radiochemotherapy of small cell lung cancer (SCLC) in 15.4% (12% slight, 3.4% severe) by this side effect. These differences were not significant (p = 0.32). The median onset of pneumonitis was 31 days after end of irradiation (severe 23 days, slight 44 days, p = 0.026). By a univariate analysis the total dose at the prescription point was the most important factor (30 to 50.5 Gy 11%, 52 to 59 Gy 15%, 60 to 74 Gy 26%, p = 0.007). High single doses (2.5 Gy) were only applied within a study of radiochemotherapy with a randomised sequential and alternating schedule. So that the increased rate of pneumonitis (42%) is not clearly separable from other influencing variables. A correlation between the applied techniques and the irradiated volume (measured by planimetric methods) was not demonstrable. Regarding the independent factors a high age, female sex and a low FeV1 were unfavourable. However, age and sex corrected FeV1 was not predictive. CONCLUSIONS: The observed incidence is within the range of literature. By a clinical point of view the total dose is an obvious factor. Also single doses above 2 Gy have to be seen critically (a total dose of 50 Gy). The results confirm the fact that patients with a low FeV1 are not suitable to a high dose irradiation of the chest. In this connection old patients and women also should be seen as patients at risk.

Adult↗

PubMed1997

[Prospective study on the prevention of heterotopic ossification after total hip replacement. Non-steroidal anti-inflammatory agents versus radiation therapy].

PURPOSE: Two prospective trials were undertaken to assess the comparative efficacy of early postoperative irradiation with different radiation doses versus the postoperative use of nonsteroidal antiinflammatory drugs (NSAID) for prevention of heterotopic ossification (HO) following prothetic total hip replacement (THP). PATIENTS AND METHOD: Between 1992 and 1994 585 patients received THP. These patients were randomed in two longitudinal studies each with 3 treatment arms comparing postoperative irradiation with 4 x 3 Gy (101 patients), 1 x 5 Gy (93 patients), 1 x 7 Gy (95 patients) and the postoperative use of the NSAID indometacin for 7 days (113 patients) respectively for 14 days (90 patients) und acetyl salicyl acid (ASS) for 14 days (93 patients). 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 analysed and defined as historical control group. RESULTS: Incidence of heterotopic ossification was 5% in the 4 x 3 Gy group (Brooker grade I 5%, grade II 0%, grade III 0%), 30.5% in the 1 x 5 Gy group (Brooker grade I 24.7%, grade II 4.1%, grade III 1.0%) and 10.5% in the 1 x 7 Gy group (Brooker grade I 10.5%, grade II 0%, grade III 0%). 15.9% of the indometacin-7 days-group developed heterotopic ossification (Brooker grade I 8%, grade II 6.2%, grade III 1.7%, grade IV 0%), 12.2% of the indometacin-14 days-group (Brooker grade I 8.9%, grade II 2.2%, grade III 1.1%) and 37.5% of the ASS-group (Brooker grade I 27.9%, grade II 4.3%, grade III 5.3%). The lowest incidence of heterotopic ossification was found for the 4 xx 3 Gy and the 1 x 7 Gy group, but no significant difference between these two different treatments was observed. CONCLUSION: Prophylactic irradiation of the operative site after hip replacement is more effective than the use of NSAID. Because no significant difference between the fractionated ingle dose irradiation was found and the latter is more comfortable for patients and more economical, irradiation with single 7 Gy fraction should be preferred.

Aged↗

PubMed1997

[Intracavitary afterloading therapy as a new technique of boost irradiation in anal canal carcinoma].

PURPOSE: There are different techniques of boost irradiation in the treatment of patients with anal carcinoma. A new system of applicators is presented, which can be used for an intracavitary afterloading therapy. MATERIAL AND METHODS: Three different applicators are available, the first with a central catheter (K1), a second with 5 semicircular fixed catheters (K2) and an eccentric shield, a third with 8 circular fixed catheters and a central shield (K3). RESULTS: The adequate choice of applicator and catheters takes into consideration the individual localisation and extension of anal carcinoma in planning therapy. Thus, in circular growing tumors, an irradiation of the whole circumference of the anal canal is possible. In non-circular growing tumors, the dose applied in the non-affected part of the anal canal can be reduced to a quarter of the dose applied at the tumor. CONCLUSION: The new system of intracavitary afterloading therapy is a good alternative to previous techniques of boost irradiation in the treatment of anal carcinoma. By means of this technique, irradiation can be highly individualized, the tumor better included and non-affected sections of the anal canal saved.

Anus Neoplasms↗

PubMed1997

[The locoregional recurrence of rectal carcinoma. A computed tomographic analysis and a target volume concept for adjuvant radiotherapy].

BACKGROUND: In the adjuvant postoperative radiotherapy of rectal carcinoma the knowledge of the predominant areas of recurrences is of major importance for the definition of the target volume. We analysed the pattern and locations of tumor recurrences in the CT scans of 155 patients and correlated the findings with the primary tumor location (above and below the peritoneal duplication) and the operating method (abdominoperineal extirpation, anterior resection. Hartmann procedure). PATIENTS AND METHOD: Hundred and fifty-five patients with the diagnosis of rectal carcinoma recurrences were treated in our institution between 1980 and 1995. To determine the extension of the recurrent tumor within the pelvic levels (presacral levels S1-S5, precoccygeal, pelvic floor level and perineal level) and the tumor infiltration of pelvic organs and muscles we analysed the pretherapeutic CT images. The lymph node recurrences were classified as: pararectal, presacral, iliac internal, iliac external, iliac communis and para-aortal recurrences. RESULTS: Sixty-one percent of the patients with rectum extirpation and 66% with anterior resection showed a combined local and nodal recurrence. Isolated lymph node recurrences were rare (4% and 5%) (Tables 2 and 3). The local recurrence was mostly situated in the presacral pelvis, predominantly there was an infiltration of the presacral space at the level of S4, S5 and os coccygis regardless of the operating method and the primary tumor location (Figure 1). The anastomosis was involved in the tumor recurrence in 93% of the anteriorly resected patients (Table 3). In 9 out of 96 patients after rectum extirpation the pelvic region caudal of the tip of the coccyx was the origin of the recurrent tumor (Table 2, Figure 2). Primarily all 9 patients had a deep-seated carcinoma (< 6 cm ab ano). Only 2 patients showed an isolated perineal recurrence after rectum extirpation (Table 2. Figure 2). Two thirds of the deep-seated tumors showed a vaginal involvement (Figures 3 and 4). The incidence of iliac internal and presacral nodal recurrence was 47 to 59% (Figures 3 and 4). The incidence of iliac external lymph node recurrences was 7% after rectum extirpation and 2% after anterior resection/Hartmann procedure. CONCLUSION: Our data demonstrate that 2/3 of the patients with tumor-bed recurrences also show lymph node recurrences predominantly in the iliac internal and presacral groups. This has to be considered in the definition of the boost target volume. The target volume must also include the dorsal wall of the urogenital organs. A ventral extension of target volume up to iliac external lymph nodes is not necessary.

Adenocarcinoma↗

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

CT planning of boost irradiation in radiotherapy of breast cancer after conservative surgery.

BACKGROUND AND PURPOSE: A study was performed to compare the accuracy of clinical treatment set-up and CT planning of boost irradiation in radiotherapy of breast cancer. MATERIAL AND METHODS: Between September 1993 and October 1994, 45 women who underwent breast conserving surgery and irradiation containing a boost to the tumour bed were investigated. Prospective evaluation of CT planning of the boost was carried out. The target volume/boost field, electron energy and treatment set-up had been defined on the basis of clinical examination, initial and postsurgical mammograms by one radiotherapist. Next, a planning CT was performed in treatment position and a CT-based treatment plan was calculated according to a target volume defined by another radiotherapist. The clinical treatment set-up was imported into our computer planning system and the resulting isodose plots were compared with those from CT planning and reviewed critically. RESULTS: The clinically defined treatment set-up had to be modified in 80% of the patients. Most discrepancies observed were related to the size of the boost field itself and the chosen electron energy. Minor changes had to be made with respect to angle of table and gantry. CONCLUSIONS: Critical review of the isodose plots from both methods showed clear advantages for CT planning. Guidelines for target definition in CT planning of boost irradiation and subgroups of patients benefiting from this technique are described.

Breast Neoplasms↗

PubMed1997

Three dimensional variability in patient positioning using bite block immobilization in 3D-conformal radiation treatment for ENT-tumors.

BACKGROUND AND PURPOSE: The aim of this prospective study was to analyze the three-dimensional (3D) reproducibility of the isocenter position and of patient positioning with the use of bite block immobilization by means of a simple verification procedure for a complex beam arrangement applied for ENT-tumors. MATERIALS AND METHODS: We analyzed the positioning data of 29 consecutive patients treated for ENT-tumors at the Department of Radiotherapy and Oncology of the University of Wurzburg. A total of 136 treatment sessions were analyzed. Patients were positioned and immobilized using an individualized bite block system and a head and neck support. A complex beam arrangement was applied combining two offset rotational and two oblique wedge fields on a 5 MV linear accelerator. Orthogonal verification films were taken once weekly. Four to six film pairs per patient were obtained (during 4-6 weeks) with a mean number of 4.7 film pairs per patient. These were compared to the corresponding orthogonal simulator films taken during primary simulation. Deviations of the verified isocenter from the isocenter on the simulator film were measured and analyzed in three dimensions in terms of overall, systematic and random categories. A 3D-deviation vector was calculated from these 3D data as well as a 2D-deviation vector (for comparison with literature data) from the lateral verification films. RESULTS: The overall setup deviation showed standard deviations (SD) of 2.5, 2.7 and 3.1 mm along the cranio-caudal, anterior-posterior and medio-lateral axes, respectively. The random component ranged from SD 1.9 to 2.1 mm and the systematic component ranged from SD 1.8 to 2.2 mm. The mean length of the 3D-vector was 3.1 mm for the systematic as well as the random component. Ninety percent of 3D systematic and random deviations were less than 5 mm. The mean length of the 2D-vector was 2.4 mm for the random component and 2.2 mm for the systematic component. Ninety percent of 2D-random and systematic variations were less than 4 mm. CONCLUSIONS: The presented individualized bite block immobilization device provides an accurate and reproducible patient positioning for 3D-conformal radiation therapy in the head and neck. Random and systematic deviations in each of the three directions are in the range of +/-4 mm (2 SD, comprising 95% of the deviations) and are within the range or even less than deviations described for most thermoplastic or PVC-mask fixation devices. These deviations should be taken into account during definition of planning target volume in head and neck tumors.

Head and Neck Neoplasms↗

PubMed1997

CT simulation in stereotactic brain radiotherapy--analysis of isocenter reproducibility with mask fixation.

BACKGROUND AND PURPOSE: CT verification and measurement of isocenter deviation using repeated mask fixation in linac-based stereotactic high dose radiotherapy of brain metastases were performed in this study. MATERIALS AND METHODS: For stereotactic radiotherapy of brain metastases a commercial head mask fixation device based on thermoplastic materials (BrainLAB) was used. A two-step planning-treatment procedure was performed. Immediately before treatment the patient was relocated in the mask and a verification CT scan of the radiopaque marked isocenter was performed and if necessary its position was corrected. The verification procedure is described in detail. Twenty-two CT verifications in 16 patients were analyzed. Deviations were measured separately for each direction. A 3D-deviation vector was calculated. Additionally the average amount of deviation in each of the three dimensions was calculated. RESULTS: The mean deviation and standard deviation (SD) of the isocenter was 0.4 mm (SD 1.5 mm) in the longitudinal direction, -0.1 mm (SD 1.8 mm) in the lateral direction and 0.1 mm (SD 1.2 mm) in the anterior-posterior direction. The mean three-dimensional distance (3D-vector) between the verified and the corrected isocenter was 2.4 mm (SD 1.3 mm). The average deviation (without consideration of direction) was 1.1 mm (SD 1.1 mm), 1.3 mm (SD 1.3 mm) and 0.8 mm (SD 0.9 mm) in the longitudinal, lateral and sagittal directions, respectively. No correlation was found between 3D-deviation and the distance of the isocenter from the reference plane nor between deviation and the position of metastases in the brain (central versus peripheral or between different lobes), or the date of treatment. CONCLUSION: Reproducibility of the isocenter using the presented mask fixation is in the range of positioning reproducibility reported for other non-invasive fixation devices for stereotactic brain treatment. Our results underline the importance of CT verification as a quality assurance method in stereotactic radiotherapy. Under the condition of a preceding CT verification the mask can be used for single dose stereotactic radiotherapy. For fractionated stereotactic irradiation of small target volumes we recommend repeated CT verifications to assure reproducibility.

Brain Neoplasms↗

PubMed1997

PDR brachytherapy with flexible implants for interstitial boost after breast-conserving surgery and external beam radiation therapy.

BACKGROUND AND PURPOSE: For radiobiological reasons the new concept of pulsed dose rate (PDR) brachytherapy seems to be suitable to replace traditional CLDR brachytherapy with line sources. PDR brachytherapy using a stepping source seems to be particularly suitable for the interstitial boost of breast carcinoma after breast-conserving surgery and external beam irradiation since in these cases the exact adjustment of the active lengths is essential in order to prevent unwanted skin dose and consequential unfavorable cosmetic results. The purpose of this study was to assess the feasibility and morbidity of a PDR boost with flexible breast implants. MATERIALS AND METHODS: Sixty-five high risk patients were treated with an interstitial PDR boost. The criteria for an interstitial boost were positive margin or close margin, extensive intraductal component (EIC), intralymphatic extension, lobular carcinoma, T2 tumors and high nuclear grade (GIII). Dose calculation and specification were performed following the rules of the Paris system. The dose per pulse was 1 Gy. The pulse pauses were kept constant at 1 h. A geometrically optimized dose distribution was used for all patients. The treatment schedule was 50 Gy external beam to the whole breast and 20 Gy boost. PDR irradiations were carried out with a nominal 37 GBq 192-Ir source. RESULTS: The median follow-up was 30 months (minimum 12 months, maximum 54 months). Sixty percent of the patients judged their cosmetic result as excellent, 27% judged it as good, 11% judged it as fair and 2% judged it as poor. Eighty-six percent of the patients had no radiogenous skin changes in the boost area. In 11% of patients minimal punctiform telangiectasia appeared at single puncture sites. In 3% (2/65) of patients planar telangiectasia appeared on the medial side of the implant. The rate of isolated local recurrence was 1.5%. In most cases geometrical volume optimization (GVO) yields improved dose distributions with respect to homogeneity and compensation of underdosage at the margins of the implant. Only in 9% of patients was the dose distribution impaired by GVO. However, GVO causes a number of substantial changes of the dose distribution which have consequences for its application. CONCLUSIONS: The interstitial CLDR boost of the breast can be replaced by the PDR technique without severe acute and late complications and without deterioration of the cosmetic results.

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

Invasive thymoma: treatment with postoperative radiation therapy.

PURPOSE: To assess radiation therapy and chemotherapy in the treatment of invasive thymoma and thymic carcinoma. MATERIALS AND METHODS: In 1981-1995, 43 patients received irradiation after total (n = 23) or subtotal (n = 20) resection. Tumors were thymic carcinoma (n = 10) or invasive thymoma (n = 33). Masaoka stage was II in 10 patients, III in 14, and IV in 19. Median total dose applied was 50 Gy (range, 10-72 Gy). Seventeen patients (five with stage III and 12 with stage IV) also received chemotherapy. RESULTS: Patients with thymic carcinoma had a median survival of 9.5 months, compared with 50 months for patients with invasive thymoma (P = .008). Patients' median survival and 5-year survival rates were 97 months and 90% for stage II, 65 months and 67% for stage III, and 32.5 months and 30% for stage IV tumors (P = .024). Overall control rate within the radiation field was 81% (35 patients) and overall local control rate within the thorax was 74% (32 patients). Of the 17 patients who received chemotherapy and radiation therapy, nine had thymic carcinoma and a median survival of 12 months (range, 1.4-23.0 months). CONCLUSION: With total doses of 45-50 Gy, local control is achievable after radical resection. Whether patients with completely resected stage II thymomas should receive radiation after surgery remains uncertain, as does the role of chemotherapy in the treatment of thymoma.

Adult↗

PubMed1997

[Bone metastasis in breast carcinoma].

113278891978 and 1988 278 patients with metastatic disease of breast cancer were treated at the Clinic of Radiotherapy of the University of Würzburg. 192 of these patients developed skeletal metastases. Particularly the skeletal axis was affected. In 58.3 percent (162 patients) skeletal metastasis was the first metastasis. The median age of the patients was 62.5 years at time of diagnosis of skeletal metastasis. Median interval between primary diagnosis of breast cancer and diagnosis of skeletal metastasis was 2.9 years. Median survival of patients with skeletal metastasis was 1.7 years. Skeletal metastases could not worse survival time, if other metastases already existed. Because of the relatively good prognosis we have to improve and combine the local and systemic therapy.

Bone Neoplasms↗

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

Differential effects of dose rate and superfractionation on survival and cell cycle of V79 cells from spheroid and monolayer culture.

Recent developments concerning brachytherapy suggest conditions for an equivalence between the common continuous low dose rate (CLDR) exposure and pulsed irradiation regimens (PDR), provided that total dose is administered in the same overall time. The respective theoretical considerations have been based solely on the phenomenon of sublethal damage recovery. The present study, therefore, aimed to assess a possible influence of growth state/cell cycle progression when CLDR and different super fractionation protocols are compared. The respective experiments were performed with V79 cells that can be grown as a rapidly proliferating monolayer culture or as small spheroids (without hypoxia) where most of the cells are out of cycle. Differential changes in cell cycle distribution occurring during the compared exposure schemes and their impact on cell survival were expected to be expressed most clearly with this model system because of the short G1 phase. Cell irradiations were performed with brachytherapy sources either continuously (137Cs) or with high dose rate pulses (192Ir) at different (1 h and 4 h) pulse repetitions whereby the overall dose rate was kept constant to approximately 1 Gy/h. Cell survival curves were generated by sampling cells at different exposure times or number of pulses, respectively. For spheroid cells an unequivocal decrease of effectivity was demonstrated with decreasing dose per pulse, and the dose effect relation obtained with hourly pulses of 1 Gy was indistinguishable from the CLDR response. For monolayer cells, on the contrary, the scheme of hourly pulses was significantly more effective than the CLDR irradiation. As measured by flow cytometry, this different behaviour could be attributed to the accumulation of cycling cells in the radiosensitive G2/M phase (G2 block) during protracted exposure which was drastically more pronounced for the pulsed scheme compared to the CLDR condition. The observed principle phenomenon of a block to cell cycle progression from high dose rate pulses (at low overall dose rate) may be less expressed in (human) cells having a long G1 period, but if applicable to a clinical situation, an increase of acute effectiveness of a superfractionated brachytherapy protocol has to be considered.

Animals↗

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↗

PubMed1996

Migration patterns in pulsed-field electrophoresis of DNA restriction fragments from log-phase mammalian cells after irradiation and incubation for repair.

An assay system was developed to detect changes of restriction fragment profiles obtained after pulsed-field gel electrophoresis (PFGE) for DNA from mammalian cells that were irradiated and incubated for repair. DNA was prepared from irradiated log-phase human melanoma cells (MRI 221) after incubation for repair (6 h) and was digested with the rare-cutting restriction enzyme NotI (RE) prior to PFGE separation. DNA-fragment size distributions were compared to the respective PFGE profiles from unirradiated controls. After doses of 5 and 10 Gy (plus a 6-h incubation for repair), the relative amount of DNA retained in the plug during PFGE was increased. For higher doses (30 and 60 Gy), this phenomenon was superimposed by the residual fragmentation (25-30% of the initial breakage of 0.42 dsb/100 Mbp/Gy). Since irradiated cells accumulated in S phase during incubation for repair, a correction for the reduced electrophoretic migration of DNA from S-phase cells was necessary, and a 0.5% increase in DNA retention per 1% S-phase increment was found. However, the % retention for the 5 Gy plus repair sample was significantly higher than for the S-phase adjusted control (p < 0.01). Radiation induced DNA-protein crosslinks cannot account for the observed phenomenon because of the extensive proteolysis in DNA preparation, and also a loss of restriction enzyme recognition sites appear to be an unlikely explanation from simple quantitative considerations. Based on the recent observation of misrejoining during dsb repair, it is proposed that the incorrect joining of DNA ends also causes a more random distribution of replicating DNA in restriction fragments derived from cells in S phase after incubation for repair. This process would necessarily increase the proportion of DNA unable to migrate in PFGE.

DNA Repair↗

PubMed1996

Fotemustine given simultaneously with total brain irradiation in multiple brain metastases of malignant melanoma: report on a pilot study.

Melanoma patients with multiple brain metastases not amenable to surgery or stereotactic radiotherapy were treated with total brain irradiation in fractions of 2.5 Gy four times weekly, up to 40 Gy. At days 1, 8, and 25100 mg/m2 fotemustine was infused 4 h before irradiation. Of 12 evaluable patients, four showed partial remission and three stabilization in the brain. The median survival in these two groups of patients was 6 months; the survival of the other patients was 2 months. Severe haematological side effects were observed in 6/13 patients. In conclusion, the combination of fotemustine and total brain irradiation seems to be more effective than either treatment alone, but bears the risk of additional bone-marrow toxicity.

Adolescent↗