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Biomedical subjects

Rita Engenhart-Cabillic

Publications and source records attributed to Rita Engenhart-Cabillic.

14 recordsLinked to original sources

Accuracy of single-session extracranial radiotherapy for simple shaped lung tumor or metastasis using fast 3-D CT treatment planning.

BACKGROUND: This study is situated in the area of measuring set-up accuracy and time periods of single-session extracranial radiotherapy (SSRT) for simple-shaped targets (e.g., spherical or rotational symmetrical) definitively located in the peripheral lung. METHODS AND MATERIALS: After adaptation of the stereotactic body frame, the patient has to remain in the vacuum pillow during planning computed tomography (CT), fast three-dimensional (3-D) treatment planning, and direct irradiation after verification. Fast preplanning is performed by using virtual simulation software to accelerate the method. RESULTS: In our new procedure, SSRT is applied in approximately 1.5 h. The mean setup accuracy vector was 2.4+/-0.7 mm in the range of 1.34 to 4 mm. Mean intrafractional patient movement in the stereotactic body frame before and after radiation was 0.70 mm+/-0.5 mm and 0.76+/-0.76 mm in the range of 0 to 2.8 mm. Mean time period steps were measured at (1) planning CT with 3-D treatment planning: 76+/-12 min; (2) irradiation and verification: 33+/-7 min; and (3) complete procedure duration: 109+/-11 min (range, 89-169). CONCLUSIONS: The main difference between the positioning technique of SSRT and that of conventional extracranial radiosurgery is the tighter patient fixation, which guarantees minimal patient movement. The main advantages are procedure acceleration and omission of CT simulation. SSRT is a preliminary stage of real-time treatment.

Aged↗

Stereotactic radiotherapy of meningiomas: symptomatology, acute and late toxicity.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery (SRS) is well established in the treatment of skull base meningiomas, but this therapy approach is limited to small tumors only. The fractionated stereotactic radiotherapy (SRT) offers an alternative treatment option. This study aims at local control, symptomatology, and toxicity. PATIENTS AND METHODS: Between 1997-2003, 224 patients were treated with SRT (n = 183), hypofractionated SRT (n = 30), and SRS (n = 11). 95/224 were treated with SRT/SRS alone. 129/224 patients underwent previous operations. Freedom from progression and overall survival, toxicity, and symptomatology were evaluated systematically. Additionally, tumor volume (TV) shrinkage was analyzed three-dimensionally within the planning system. RESULTS: The median follow-up was 36 months (range, 12-100 months). Overall survival and freedom from progression for 5 years were 92.9% and 96.9%. Quantitative TV reduction was 26.2% and 30.3% 12 and 18 months after SRT/SRS (p < 0.0001). 95.9% of the patients improved their symptoms or were stable. Clinically significant acute toxicity (CTC III degrees ) was rarely seen (2.5%). Clinically significant late morbidity (III degrees -IV degrees ) or new cranial nerve palsies did not occur. CONCLUSION: SRT offers an additional treatment option of high efficacy with only few side effects. In the case of large tumor size (> 4 ml) and adjacent critical structures (< 2 mm), SRT is highly recommended.

Adult↗

Clinicopathologic features of aggressive meningioma emphasizing the role of radiotherapy in treatment.

BACKGROUND AND PURPOSE: Although meningiomas are typically benign, they occasionally behave in an aggressive fashion and carry a less favorable prognosis. The aim of this study was to review the clinical, radiologic and histopathologic features of these aggressive variants as well as the outcome after multimodality therapy. PATIENTS AND METHODS: 16 patients with atypical meningiomas (n = 11) and anaplastic meningiomas (n = 5) were treated in the Departments of Neurosurgery and Radiation Oncology at the University Hospital of Philipps University Marburg, Germany, between 1997 and 2003. Tumor grading was based on new WHO criteria. There were eleven men and five women with a mean age of 54 years. The median follow-up period was 34 months. RESULTS: A total of 24 surgical procedures were performed for these 16 patients. Only seven patients underwent postoperative fractionated stereotactic radiotherapy. Patients with atypical meningioma received radiotherapy only for the recurrent disease. Six patients (37.5%) experienced tumor recurrence after a mean period of 27.2 months in spite of gross total resection. Radiographic findings suggestive of aggressiveness were observed mostly with WHO grade III meningiomas. By comparing the proliferation rate in four cases with atypical meningioma operated twice, the recurrent tumor had a higher proliferation rate than the first tumor in three cases. A special proliferation pattern was noticed in MIB-1 with anaplastic meningiomas. The mean overall survival period was 66.5 months. There was no mortality among patients with atypical meningioma, while four out of five patients with anaplastic meningioma died during follow-up. CONCLUSION: Considering the higher rate of recurrence in aggressive meningiomas even after radical surgical excision and the possibility that the recurrent tumor is more aggressive than the original one, surgery should be combined with postoperative fractionated radiotherapy to improve local tumor control. The peculiar focal expression patterns of anaplastic meningioma in MIB-1 might be a marker of such malignant development.

Adult↗

How to successfully implement E-learning for both students and teachers.

RATIONALE AND OBJECTIVES: Electronic learning (e-learning) may provide a means to enhance learning efficacy. However, introduction of e-learning often fails. We describe a strategy of how an e-learning curriculum was successfully implemented. MATERIALS AND METHODS: The curriculum was designed based on published evidence. It consists of self-directed learning, an online discussion forum, and discussion rounds. The e-content in nuclear medicine and radiotherapy was produced by the k-MED team of medical authors, web designers, and psychologists. The online courses were delivered via a dedicated learning management system. The e-content for diagnostic radiology and physics was provided as PDF/HTML script by the respective teachers who objected to participate in the k-MED project. The exam was taken online. Online evaluation of the curriculum by the students was taken at the end of the course. RESULTS: The new curriculum proved very effective. The time for the preparation for the clinical part of the radiology course could be reduced from 4 to 2 weeks. The students particularly enjoyed the self-directed learning. Although the material provided by k-MED received 90%-99% positive scores, the HTML and PDF scripts scored worse (13%-67% positive ratings). The positive results of the evaluation convinced the teachers responsible for physics and diagnostic radiology to participate in k-MED. CONCLUSIONS: As our example shows, new e-learning curricula can successfully be introduced. The strategy of implementation should be based on the existing evidence from the literature. The new curriculum helped to increase the efficacy of teaching and save time as the duration of the respective part of the course could be reduced by half.

Computer-Assisted Instruction↗

Expression of p53 and p21 in primary glioblastomas.

BACKGROUND AND PURPOSE: Primary glioblastomas (GBMs) are highly radioresistant, and in contrast to secondary GBMs, they bear wild-type (wt) p53 protein, which is stabilized in a proportion of these tumors. Therefore, it was investigated in vivo whether p53 expression has prognostic value in patients undergoing radiochemotherapy. Additionally, the authors tried to identify, in vitro, subgroups of primary GBM with different susceptibilities to irradiation, on the basis of their p53 and p21 responses to ionizing radiation. MATERIAL AND METHODS: Tumor tissue samples from 31 patients suffering from primary GBM undergoing a combined radiochemotherapy with topotecan were investigated. The percentage of cells expressing p53 protein was determined immunohistochemically. Additionally, primary cultures from eleven primary GBMs were established and investigated. p53 and p21 expressions were evaluated before irradiation with 10 Gy and at 2 and 8 h after irradiation. p53 protein expression was measured by Western analysis and p21 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The percentage of p53-positive cells within the tumor specimens obtained from the 31 patients ranged from 0% to 28%, the median value being 4.3%. No significant correlation with disease-free survival or overall survival was found. In vitro, p53 protein was detected in seven of eleven cultures from primary GBM. After irradiation a decrease in p53 protein expression was seen in six of the seven p53-positive cultures. Half of the cultures (two of four) without basal p53 expression showed an increase in p53 expression after irradiation. Basal overexpression of p21 was detected in six of the eleven cultures; in four out of six irradiation led to a decrease in p21 expression. In all cell lines (five of eleven) initially showing absent p21 expression, irradiation induced p21 expression. Despite these responses, G1 arrest was not detectable in any of the GBM cultures. CONCLUSION: p53 protein expression in vivo does not correlate with the outcome of patients with primary GBM. Therefore, p53 protein content per se does not appear to be a helpful prognostic factor for prognosis-adapted therapy in primary GBM. By contrast, primary GBM cells in vitro show different and independent responses in their p53 and p21 pathways to ionizing radiation. The failure of G1 arrest seems to be due to a functional defect in the p53 pathway, either because p21 was not induced or because of an unidentified defect downstream from p21.

Adult↗

Open-label simultaneous radio-chemotherapy of glioblastoma multiforme with topotecan in adults.

BACKGROUND: Due to its radioresistance, the prognosis of glioblastoma multiforme (GBM) remains poor. Therefore, we investigated the impact of simultaneous radio-chemotherapy with topotecan (Hycamtin) on clinical outcome, tolerability and quality of life. PATIENTS AND METHODS: In this multicenter trial, 60 patients (19 females, 41 males) with histologically proven (5x biopsy, 31x subtotal resection, 24x total resection) GBM were included. Radio-Chemotherapy was performed with daily doses of 2.0 Gy (total, 60 Gy), and 0.5 mg (absolute dose) of topotecan intravenously 1 h prior to irradiation. Toxicity was assessed using common toxicity criteria (CTC). General condition and quality of life were assessed at baseline, at the end of therapy, and 6 weeks post-therapy. Local control and length of survival were compared with an historical control group of 67 patients only treated with postoperative radiotherapy following stereotactic biopsy (15x), subtotal resection (39x), or total resection (13x). RESULTS: 57 patients completed the therapy. Median radiation dose was 60 Gy (range 16-76 Gy). Median cumulative topotecan dose was 15 mg (range 7.5-18.5 mg). CTC toxicity grade 3 was observed in six patients and grade 4 toxicity in two patients (three events). Two patients died of septic disease. Mean Karnofsky index was 87% at baseline, 81% at the end of therapy, and 80% at 6 weeks post-therapy. Median survival time was 15 months, significantly longer than the 11 months seen in the control group (P < 0.002). Extent of tumour resection or patient age did not have a significant effect on survival. CONCLUSION: This multimodal approach is well tolerated, and quality of life remains preserved. The relatively long median survival time is promising but a further randomised double blind placebo controlled parallel designed clinical trial should be performed to confirm these results.

Adolescent↗

Methodology of continuous extracranial radiosurgery for lung cancer using EXOMIO 3-D CT simulation.

BACKGROUND: It is well known that precision can be achieved using radiosurgery for brain tumors. This method can be extended to treat localized lung tumors and lung metastases. MATERIAL AND METHODS: The conventional procedure of extracranial radiosurgery is contained in the following steps: adaptation of the vacuum mattress, planning CT, three-dimensional (3-D) treatment planning, CT repositioning, and irradiation. In the new procedure of continuous extracranial radiosurgery, a short treatment planning is often used for simple target shapes (spherical, rotation-symmetrical), and the irradiation follows directly after the planning procedure. During continuous extracranial radiosurgery, the patient has to lie still in the body frame from the planning CT to irradiation. Fast treatment planning is performed by using multileafs and EXOMIO (Medintec, Bochum, Germany), a software for CT simulation. The high quality of the digitally reconstructed radiographs (DRRs) of each field enables a high precision in dose application by the comparison with the verification radiograph and the DRR (Elekta iView, Hamburg, Germany). RESULTS: In five lung cancer patients the average time for the complete procedure from planning CT to irradiation was 107 min (range: 91-124 min). The mean positioning accuracy of the patient in the vacuum bed (total shift) was 3.3 mm (range: 2.9-4.7 mm). CONCLUSION: Continuous extracranial radiosurgery can be performed for small peripheral lung tumors or metastases and is optimizing the conventional procedure. It is of special interest to clinics with restricted CT capacity.

Equipment Design↗

Evaluation of a laser system for CT software simulation (EXOMIO) in patients with breast cancer.

PURPOSE: To develop a manually movable laser system connected to the CT table for alignment of the isocenter cross of irradiation fields on the patient's skin directly after CT software simulation. MATERIAL AND METHODS: The specially designed laser system was constructed in the authors' department, and the mean focusing accuracy of isocenter translations was analyzed using Alderson phantom measurements. The mean overall accuracy from setup to treatment of the whole procedure of CT software simulation was measured by the comparison of bone structures and mamma contour of the digitally reconstructed radiograph (DRR) with the verification film. The time taken for the different setup procedure steps was evaluated for 70 breast cancer patients who were treated using tangential fields. RESULTS: The mean focusing accuracy of the manually movable laser system after defined isocenter translation was measured as 0.8 +/- 0.5 mm, the mean patient movement on the CT table as 2.0 +/- 1 mm, and the mean positioning accuracy of the first treatment after patient positioning corresponding to the skin alignments as 3.9 +/- 1.5 mm. The time periods for the different steps of the CT software simulation were measured, and the total duration was found to be 35.8 +/- 3.3 min. CONCLUSION: In general, the main advantage of well-known CT software simulation when compared to conventional simulation is the relief of the real X-ray simulator which is feasible with fast planning software (EXOMIO) and the presented movable laser system.

Adult↗

Effectiveness of radiochemotherapy on lymph node metastases in patients with stage IV oropharyngeal cancer.

Radiochemotherapy plays a leading role in the treatment of patients with advanced squamous cell carcinomas (SCC) of the oropharynx. The aim of the present study was to estimate its effectiveness on lymph node (LN) metastases. Seventeen patients with advanced UICC stage IV oropharyngeal SCC (1xT2, 4xT3, 12xT4, 2xN1, 15xN2) were observed prospectively. They were treated with radiochemotherapy (total radiation doses 60-70.6 Gy). One to four months after neck dissection (ND) was performed. Specimens were histologically examined for metastases according to the neck levels obtained from. Local control was achieved in 14/17 (82.4%) patients and regional-in 10/17 (58.8%) patients. Of 566 LN studied, 29 exhibited signs of involvement. Two from 29 were found in neck level I, 20/29 in II, 6/29 in III and 1/29 in IV. In 13/29 LN the metastases had completely regressed under treatment whereas 16/29 LN (7 patients) contained vital tumoral tissue. The observed high incidence of vital LN metastases, which abide the radiochemotherapy, advocates further studies, concerning the value of planed ND after radiochemotherapy.

Adult↗

Assessment of the accuracy of a conventional simulation for radiotherapy of head and skull base tumors.

In this prospective study we investigated the absolute accuracy of the conventional simulation in head and skull base tumors. 41 isocenters in 40 consecutive patients with tumors of the head and skull base were included. In all cases a rigid stereotactic mask system was used for non-invasive fixation. The stereotactic ("calculated") coordinates of the isocenter were defined by the treatment planning computer. Each patient underwent a physical simulation using exclusively anatomical reference points to define the "preliminary" isocenter. The displacement between its coordinates and those of the stereotactic target point was recorded in X-, Y- and Z-direction with help of the targeting device, and the spatial error was calculated. Additionally, the patients were stratified by basal or calvarial tumor site to estimate the importance of the basal bone structures in the simulation accuracy. The influence of the learning effect on simulation accuracy was also determined. The results showed an accuracy of set-up at the linac within 1 mm in all three directions as calculated from orthogonal portal films. Mean shift of the isocenter coordinates obtained from physical simulation compared to the calculated stereotactic coordinates was 2.15 mm, 2.54 mm, and 2.69 mm for X-, Y-, and Z-direction, respectively. Mean spatial displacement amounted 5.06 mm, and the median was 4.50 mm. No significant difference could be noted between basal and calvarial location of the isocenter. A significant "learning effect" was observed with a decrease in spatial shift with increasing patient numbers. This effect was stronger in basal lesions, whereas calvarial lesions showed only a minor, insignificant effect. In conclusion, a physical simulation requires a safety margin of 5 mm in PTV definition in addition to other factors, e.g. organ movement.

Head and Neck Neoplasms↗

[The effectiveness of radiation treatment in comparison with extracorporeal shockwave therapy (ESWT) in supraspinatus tendon syndrome].

BACKGROUND AND AIM: Supraspinatus tendinitis is usually treated by antiinflammatoric drugs, local injections, physiotherapy or low-dose irradiation. A novel approach is the use of Extracorporeal Shock Wave Therapy (ESWT) if conservative therapies have failed. So far there has been no controlled study comparing the effectiveness of ESWT with an established conservative method of therapy such as X-ray stimulation radiotherapy. PATIENTS AND METHOD: 30 patients with chronic supraspinatus tendinitis were admitted into the prospective randomized study. After randomization the patients were treated either with X-ray stimulation radiotherapy with 6 x 0.5 Gy on the ICRU reference point (1 fraction/day) with cobalt 60 gamma rays or three times with 2000 pulses (energy flux density ED+ 0.1 mJ/mm2) in 1 week intervals using a Storz Minilith SL1. Primary endpoint was the age-corrected constant score 3 months after intervention. RESULTS: Acute side effects caused by the irradiation were not observed, as expected. One patient described pain and one patient showed a moderate skin irritation after ESWT. In the radiotherapy group average the age-corrected constant score improved from 47.6 through 79.5 points to 87.4 points. In the ESWT group it rose from 50.1 points before ESWT to 91.4 points after 12 weeks and 97.8 after 52 weeks. CONCLUSION: No statistically significant differences were proven between ESWT and radiotherapy. ESWT appears to be equivalent but not superior to radiotherapy in treating chronic supraspinatus tendinitis syndrome. A comprehensive randomized study is, however, necessary to ensure the equivalence of ESWT.

Adult↗

[Precision of conventional simulation: which extent of accuracy is reachable in head and neck region?].

PURPOSE: In this prospective investigation we tested the absolute accuracy of a conventional localization of the isocenter obtained from a three-dimensional treatment plan in conformal radiotherapy of head and neck tumors. PATIENTS AND METHODS: 41 isocenters in 41 consecutive patients with histologically proven tumors of the brain or head and neck region were included into this investigation. In all cases a stereotactic mask (Stryker-Leibinger) was made for fixation and positioning of the patients. The stereotactically guided fractionated radiotherapy was carried out on the base of CT and MRI. The stereotactic coordinates were defined by an external localization system. Afterwards each patient underwent a conventional simulation using exclusively anatomical reference points. Additionally, the patients were adjusted to the linac isocenter using a stereotactic targeting device. Deviations between the simulated and the external adjusted target point coordinates were recorded in X-, Y- and Z-direction and spatial error was calculated. RESULTS: Mean deviation was 2.15, 2.54, and 2.69 mm for X-, Y-, and Z-direction, respectively. The largest deviation was found in Z-direction with a maximum of over 11 mm. The spatial deviation per patient amounted 1.3-12.2 mm with a mean of 5.1 and a median value of 4.5 mm. That means that in half of the cases a deviation of 5 up to over 12 mm occurs in conventional simulation. Only in a quarter of the sample the deviation was 4 mm or below. CONCLUSION: The planning target volume definition requires a consideration of the inaccuracy of the conventional simulation. A reduction of the safety margin in the planning target volume assumes the use of the stereotactic target positioner. This is to postulate especially for the treatment of benign lesions or lesions or lesions adjacent to critical structures.

Brain Neoplasms↗

Phase I study of oral uracil and Tegafur plus leucovorin and pelvic radiation in patients with recurrent rectal cancer.

Continuous 5-fluorouracil (5-FU) infusion during radiation therapy is superior to the application of bolus 5-FU schedules. As an oral therapy, that provides prolonged fluoropyrimidine exposure, uracil and Tegafur (UFT) plus leucovorin (LV) has shown favorable activity with only moderate toxicity in colorectal cancer. The present study was designed to evaluate the safety of UFT+LV combined with pelvic radiation to determine the maximum-tolerated dose (MTD) in recurrent rectal cancer. Patients with recurrent rectal cancer received escalating doses of UFT (starting at 250 mg/m /day with 50 mg/m /day increments between consecutive cohorts) and fixed doses of LV (90 mg). The UFT+LV combination was given 5 days per week simultaneously to a 5-week course of irradiation up to a total dose of 50.4 Gy, 1.8 Gy daily fractions followed by a boost of 5.4 or 9.0 Gy to the gross tumor volume. Nineteen patients were treated and 14 received the full chemotherapy with delivery of all planned radiotherapy. The MTD of UFT was 400 mg/m /day due to the occurrence of dose-limiting diarrhea and emesis. Toxicities were mild and manageable on the lower dose levels. Treatment was feasible mainly on an outpatient base. We conclude that combined chemoradiation with oral UFT+LV is feasible and well tolerated for recurrent rectal cancer patients undergoing pelvic radiation. The safety profile appears comparable to that of i.v. dosing without requiring any i.v. port systems. The recommended doses for further phase II chemoradiation trials are 350 mg/m /day UFT+90 mg LV.

Administration, Oral↗