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Biomedical subjects

W De Neve

Publications and source records attributed to W De Neve.

At least 73 records · Page 4Linked to original sources

On-line portal imaging: image quality defining parameters for pelvic fields--a clinical evaluation.

PURPOSE: A test of several image enhancement techniques, performed on on-line portal images in real clinical circumstances, is presented. In addition a score system enabling us to evaluate image quality on pelvic fields is proposed and validated. METHODS AND MATERIALS: Localization images (n = 546) generated by an on-line portal imaging system during the treatment of 13 patients on pelvic fields were obtained by delivering a radiation dose of 6-8 cGy by an 18 MV photon beam, and recorded with a silicon intensified target video camera with adjustable gain, kV- and black level. Set-up errors were corrected before continuing irradiation. A scoring system based on the number of visible bone-soft tissue edges and transformed to a scale 0 to 5 was developed to judge image quality. A validation of this classification of images was performed with the use of transsectional bone-densities (bone-density*radiological path length) specified at the score defining landmarks. A high pass filter was used on all images, additional on-line open field subtraction was performed on 242 fields. Off-line study was performed in which a panel consisting of two groups (one composed of three radiation oncologists, the other of three radiotherapy technologists), scored 470 pelvic fields without further enhancement, and the same images with Contrast Limited Adaptive Histogram Equalization (CLAHE) (Pizer et al.). Two different clipping levels (3.0 and 5.0) were studied. RESULTS: Gender and transsectional bone-densities were the most defining patient-related factors influencing image quality. Camera settings, gantry angle, and image post-processing were important non-patient-related factors. All investigators judged CLAHE to ameliorate low contrast images and to deteriorate good quality images (p < 0.001).

Humans↗

Interactive use of on-line portal imaging in pelvic radiation.

We have evaluated a fluoroscopic on-line portal imaging system in routine clinical radiotherapy, involving the treatment of 566 pelvic fields on 13 patients. The image was typically generated by delivering a radiation dose of 6-8 cGy. Comparison between portal image and simulator film was done by eye and all visible errors were corrected before continuing irradiation. If possible, these corrections were performed from outside the treatment room by moving the patient couch by remote control or by changing collimator parameters. Adjustments were performed on 289/530 (54.5%) evaluable fields or 229/278 (82.4%) evaluable patient set-ups. The lateral couch position was most frequently adjusted (n = 254). The absolute values of the adjustments were 6.8 mm mean (SD 6.6 mm) with a maximum of 40 mm. All absolute values of adjustments exceeding 25 mm were recorded in one patient and those exceeding 15 mm were observed in two patients. Both patients were obese females. Adjustments exceeding 5 mm were observed in all 13 patients. Related to the use of on-line portal imaging, treatment time was increased by a median of 36.5% (mean 45.8%; SD 42.1%). The range was 7.7 to 442%. The fraction of the total treatment time to perform corrections was 22.7% median (mean: 26.0; SD: 11.8%). Statistically significant systematic in-plane errors were found in 7/13 patients. A systematic error was detected on the lateral position of the field in five patients. In one patient a systematic error of the longitudinal field position and in one patient a rotational error was detected. For adjustments in the lateral direction the present method does not allow to detect lateral shifts of less than 2 mm. For adjustments in the longitudinal direction the sensitivity could not be estimated but the available data suggest that 80% of errors < or = 5 mm were not adjusted. In obese patients, random errors may be surprisingly large.

Evaluation Studies as Topic↗

Origin and differentiation of hepatic natural killer cells (pit cells).

Liver sinusoids contain a population of large granular lymphocytes or natural killer cells, originally termed pit cells. After isolation and purification, these cells were separated into a low-density and a high-density fraction. The liver low-density fraction differs significantly in morphology and function from cells of the blood, whereas the liver high-density fraction shows intermediate properties. In this study we demonstrate that this morphological and functional heterogeneity is based on subsequent steps of differentiation of the large granular lymphocytes within the liver. When cell proliferation was suppressed by sublethal total body irradiation, the life span of the hepatic large granular lymphocytes could be determined: high-density and low-density populations were totally depleted within 1 and 2 wk after irradiation, respectively. By using intravenous asialo-GM1 anti-serum to deplete animals of asialo-GM1-positive cells, we found that the depletion of the asialo-GM1-positive cells preceded the depletion of asialo-GM1-negative hepatic low-density large granular lymphocytes by approximately 1 wk. Direct evidence that the asialo-GM1-positive high-density large granular lymphocytes are precursors of the low-density large granular lymphocytes was given by adoptive transfer experiments with fluorescent-labeled high-density cells. Three days after their injection, labeled large granular lymphocytes were found in the hepatic low-density fraction of the recipient rat, and these cells had developed morphological characteristics of low-density large granular lymphocytes. It is concluded therefore that marginating blood large granular lymphocytes differentiate through high-density large granular lymphocytes into the typical liver specific low-density large granular lymphocytes or pit cells.

Animals↗

Dialysis in patients over 65 years of age.

In 44 patients with end-stage renal disease, 24 on hemodialysis and 20 on CAPD, the survival was calculated using the life table method. Median survival for CAPD was 19 months and for hemodialysis 47 months. Using Cox's proportional hazards model, treatment modality and performance score were significant determinants of survival. Performance score was influenced by age and kidney disease. When survival was analyzed separately for patients with a good or a bad performance score, the survival was better in the hemodialysis group only in patients with a bad score (ECOG 3 and 4). Patients with a good score had similar prognoses, irrespective of treatment modality.

Aged↗

Determination of vinca alkaloids in mouse tissues by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the determination of vinblastine in various normal mouse tissues, such as lung, heart, liver, kidney and muscles, and in implanted MO4 tumours. Vincristine was used as the internal standard. Freshly obtained mouse tissue or tumour tissue was frozen at -20 degrees C and then lyophilized. After lyophilisation, the dry tissues were pulverized and homogeneously mixed, and an aliquot was suspended in 0.1 M hydrochloric acid. The drugs of interest were then isolated from this suspension using ion-pair extraction at pH 3 with octylsulphate as counter-ion. The obtained extracts were analysed on a reversed-phase system with a cyanopropyl stationary phase. The detection limit was 1 ng/l in plasma and 10 ng/g in tissue. The extraction recoveries of vincristine and vinblastine were between 45 and 67%, and there were no interferences from blank components. Preliminary pharmacokinetic data for different mouse tissues and tumour implanted in muscle tissue are presented.

Animals↗

Routine clinical on-line portal imaging followed by immediate field adjustment using a tele-controlled patient couch.

We have evaluated the fluoroscopic on-line portal imaging (OPI) system developed by Siemens (Beamview-1, Concord, CA, U.S.A.) in routine clinical radiotherapy, involving the treatment of 883 fields (559 patient set-ups for treatment) on 21 patients. The image was typically generated by delivering 10 monitor units when used in single exposure or 1-2 monitor units on a large open field followed by 8-10 monitor units on the actual field when double exposure was used. Comparison between the portal image and the simulator film was done by eye. A region of tolerance was drawn on the simulator film and the field edges on the portal image had to project within this region. If this criterion was not met, adjustments followed by verification portal images were done before the remaining field dose was delivered. If possible, these adjustments were performed by moving the patient couch by remote control. The image quality was insufficient for evaluation in 75/883 (8.5%) fields. The abovementioned criterion was not met in 95/808 (11.8%) of the evaluable fields (26/559 patient set-ups were not evaluable). Of the 533 evaluable patient set-ups, 92 had to be adjusted (17.2%) including three (pelvic irradiations) set-ups that were adjusted on both field irradiated during the same radiotherapy session. In one case an incorrect tray (with wrong blocks) was detected and replaced. In one case (a 5.5 x 6.0 cm rectangular larynx field) the x and y axis of the field were interswitched. In one case incorrect focusing of a block was shown by the portal image. To make adjustments, the couch longitudinal position was changed 20 times (range -10 to +15 mm). The lateral position was changed 73 times (range -15 to +16 mm). The height position was changes 6 times (range -7 to +6 mm). Diaphragma rotation changes were performed 5 times (1 degree). The fraction of treatment time that was related to the use of OPI was 30.7% median (mean 32.4%, S.D. 14.1%). The range was 4.1 to 78.6%. On the basis of calculations assuming no OPI would have been used, field treatment time was increased by a median of 44.2% (mean 55.8%; S.D. 41.2%) by using OPI. The fraction of monitor units (fraction of the dose) to generate a satisfactory image was 10% median.(ABSTRACT TRUNCATED AT 400 WORDS)

Head and Neck Neoplasms↗

T1 and T2 carcinoma of the urinary bladder: long term results with external, preoperative, or interstitial radiotherapy.

Between January 1974 and December 1984, 273 consecutive patients with cancer of the urinary bladder, Stages T1 or T2, any N, M0, were referred to the radiotherapy department of the Catharina Hospital at Eindhoven, The Netherlands and 265 were treated in a non-randomized fashion according to one of the three following schedules: 137 patients (67 T1, 70 T2) received radiotherapy only; 96 (44 T1, 52 T2) had preoperative radiotherapy followed by cystectomy and diversion according to the Bricker technique in 94/96; 32 patients (13 T1, 19 T2) had low total dose (12 Gy median) external radiotherapy followed by an interstitial cesium implant. The external radiotherapy fields included the pelvic structures. Total dose was 64 Gy median in the radiotherapy-only group and 40 Gy median in the preoperative irradiated group. The median follow-up in survivors was 81 months (range: 15-203). Locoregional relapse was observed in 50% in the group treated by external radiotherapy alone versus 17% in the group treated by preoperative radiation plus surgery and 28% of the patients who received cesium implant. During follow-up, 106/137 (77%), 67/96 (70%) and 13/32 (41%) patients died. In the radiotherapy-alone group, 38 died from intercurrent diseases, 36 from bladder cancer, two from therapy-related complications and cause of death was unknown in 30 patients. In the preoperative radiation group, the figures were 17 for intercurrent deaths, 26 related to progressive bladder cancer, 14 died due to perioperative complications and cause of death was unknown in 10. Cause of death was intercurrent in six and due to bladder cancer in seven patients treated by cesium implant. Probability of survival (calculated from the date of histological diagnosis) for the whole group, with censoring death to intercurrent disease was 53% at 5 years (56% for T1; 51% for T2) and 41% (40% for T1; 43% for T2) at 10 years. No significant difference was observed between T1 and T2 (p = 0.76). Survival in the treatment subgroups was, for patients treated by external radiotherapy only: 50% at 5 years and 33% at 10 years; for patients treated by external radiotherapy and surgery: 49% at 5 years and 42% at 10 years; for patients treated by cesium implant: 76% at 5 years and 76% at 10 years. Survival of patients in the cesium implant group was significantly better than in the other groups (p = 0.0001). Following variables were analyzed using the Cox proportional hazards model: age, gender, T1 or T2 stage, grade, cesium implant or not, and surgery or not.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Incompletely resected rectum, recto-sigmoid, or sigmoid carcinoma: results of postoperative radiotherapy and prognostic factors.

Postoperative radiotherapy was given in 40 patients with gross or microscopic pathologically proven residual disease after surgical resection of rectum, recto-sigmoid, or sigmoid carcinoma. The radiotherapy target volume included the pelvis with (9 patients) or without (31 patients) the perineum. Median total dose of radiation was 50 Gy (range 30-60). One patient received 30 Gy, 10 received greater than 30 to 40 Gy, 13 received greater than 40 to 50 Gy, and 16 patients received greater than 50 to 60 Gy. The median follow-up in the survivors (16 patients) was 53 months (range: 16-85). Probability of survival with censoring for death due to intercurrent disease was 36% at 5 years. Survival for patients with microscopic residual disease (21 patients) was 40% at 5 years compared to 12% for those with gross residual disease (19 patients) (p = 0.09). Twenty-five patients relapsed. All but one relapse occurred earlier than 50 months after radiotherapy. Approximately half (12/25) of the relapses were observed within 6 months after radiotherapy. Local relapse inside the radiotherapy portals was observed in 9/40 (22%) patients. Therapy-related urogenital complications occurred in no patient and gastro-intestinal complications in three patients (7%). In one patient they were scored WHO grade 4 and in two patients WHO grade 3. Prognostic factors were analyzed using the Cox proportional hazards model. For survival differentiation, grade (p less than 0.001), stage (p = 0.04), and perineal irradiation (p = 0.03) were independent prognostic factors. With relapse-free survival as the endpoint, only stage (p = 0.003) was a statistically significant prognostic factor. There was a trend toward a better relapse-free survival when the perineum was included in the radiation portals (p = 0.09).

Carcinoma↗

Interaction between flavone acetic acid (LM-975, NSC 349512) and radiation in Glasgow's osteogenic sarcoma in vivo.

Flavone acetic acid (FAA) is a new anticancer agent in Phase II trials in Europe. In preclinical testing FAA showed broad activity against murine solid tumors and minimal activity against murine leukemias. Our interest in studying the combination of FAA and radiation was based on two of its biological effects which might modify radiation damage. First, FAA depletes ATP and inhibits macromolecular synthesis which are needed to repair radiation-induced DNA strand breaks; and second, inhibition of tumor blood flow by FAA could lead to radiobiological hypoxia. Various schedules of FAA (170 mg/kg I.V.) (n = 9, SF = 0.44) and radiation (10 Gy) (n = 9, SF = 0.37) were investigated against s.c. implanted Glasgow osteogenic sarcoma. In the same model we studied both the kinetics of ATP depletion by 31P-Nuclear Magnetic Resonance Spectroscopy and the repair of radiation induced single and double strand breaks by alkaline elution. The combined response was not significantly different from log-additive when radiation was given 24, 5 or 1 hr before FAA. When FAA was given immediately before radiation an increase in tumor response, significantly different from log-additive (p = 0.03) was observed. This enhancement disappeared when radiation was delayed for between 1 and 48 hr after FAA. While decreased ATP levels and increased response to radiation occurred within minutes after FAA administration, no effect of FAA at either 180 or 200 mg/kg was observed on the repair of radiation induced single or double strand breaks (10 and 50 Gy, respectively; 5 hr after FAA) in spite of significant ATP depletion in the tumors.

Adenosine Triphosphate↗

Quantitative study of liver metastases from colon cancer in rats after treatment with cyclosporine A.

Liver metastases were produced in syngeneic BD IX rats by intraportal injection of colon cancer cell aggregates. The cells originated from the DHD/K12 cell line, derived from a 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colon adenocarcinoma in BD IX rats. The animals received either cyclosporine A (CSA) or the excipients alone (control) through daily gastric intubation during 6 weeks. Multiple and very large hepatic metastases were observed early in 100% of the CSA-treated rats. The mean tumor volume was approximately 2,000 times higher in the CSA-treated group than in the controls (P less than .01). Survival time in the CSA-treated group was shortened (P less than .01) by generalized metastatic disease. Easy production of metastasis from colon cancer in 100% of the animals and precise estimation of tumor volume may prove useful for future therapeutic studies of secondary hepatic disease.

Adenocarcinoma↗

The influence of the ambient temperature on tumour growth, metastasis and survival in mice.

The effect of ambient temperature was analysed on the behaviour of MO4 cells which are malignant, invasive and metastasizing C3H mouse fibroblastic cells when implanted in the tail of the syngeneic animal. Raising the ambient temperature to 28 degrees C increases growth of the primary tumour, incidence of metastases and shortens survival. Lowering the ambient temperature to 13 degrees C prevents all these phenomena. Measurements at the implantation site show that the temperature of the tail remains in a range +/- 2-3 degrees C in accordance with the environment. From these results we conclude that room temperature may be important when experiments are performed in vivo.

Animals↗

[Intensity modulated radiotherapy with dynamic multileaf collimator. Technique and clinical experience].

Since early 1997, dynamic multileaf collimators (DMLCs) have been used in our division for intensity modulated radiotherapy (IMRT). We have used IMRT to: irradiate concave targets (head and neck, paraspinal tumors); combine beams with shallow hinge angles (mediastinum, lung tumors); deliver intentionally inhomogeneous dose distributions (prostate, paranasal sinuses, brain tumors). IMRT is now our standard treatment for locoregional relapse (after high-dose radiotherapy) for head and neck cancer and for radical treatment of localized prostate cancer. For a variety of other tumors, conventional 3D-plans are compared with IMRT-plans, the latter being clinically implemented if superior. We developed a geometry based IMRT planning strategy to create assemblies of static intensity modulated (IM)-beams which consist of uniform (unmodulated) segments. By a translator program, segments are combined in a single prescription which allows delivery under computer control. Cost-containment is further improved by automation of the planning. After manual or semi-automated contouring of PTV and the organs at risk, prostate IMRT plans, based on a class solution, are generated and optimized by a computer. IMRT for pharyngeal relapses and most other tumor sites is planned semi-automatically. IMRT replaces gradually conventional treatments in our division. Interesting dose distributions generated by IMRT allow a better sparing of normal tissues with decreased acute and late toxicity, and offer a window for further dose escalation.

Algorithms↗

Increasing peak levels of vinblastine given in repeated divided doses.

Pharmacokinetics of vinblastine were assayed in 9 patients, using a high pressure liquid chromatography method. Patients were treated in three different ways: the first 3 patients received bolus injections of vinblastine at a fixed dose of 2 mg/day for 5 consecutive days. Three other patients were treated with 3 mg/m2 vinblastine as a bolus injection on day 1, day 3 and day 8. The remaining 3 patients received a bolus injection of vinblastine of 6 mg/m2 on day 1, day 8 and 15. Blood samples were taken on days 1, 3 and 5 for the first group and on every treatment day for the other groups. The early phase peak levels obtained during the 5 day-treatment increased progressively during repeated treatments, probably due to decreased central compartment volumes and not to drug accumulation. There was no relation between vinblastine levels and orosomucoid levels. The rise in peak level was less predictable during the other methods of treatment (once or twice weekly). This observation calls attention to the necessity of performing drug level monitoring at very early time points, as increasing peak levels during repeated administration may explain unexpected toxicities.

Adult↗

Not the presence but the synthesis of HSPS correlates with thermotolerance in a fibrosarcoma MO4 cell-line.

This study reports the induction of heat shock proteins (hsps) and thermotolerance in a MO4 cell line. An enhanced synthesis of hsp68, hsp70 and hsp90 was observed. After 6 hrs, the synthesis of hsp68 and hsp70 decreased to the control value. Hsp90 synthesis was absent after 10 hrs. However, hsps were found to be stable for longer periods of time (more than 48 hrs). A coupled study of hsps and SF demonstrated that an induction of hsps were followed by a change in the slope of the survival curve. Thermotolerance, as expressed by the observed SF after a second heating, is only present during the first 4 hrs and decayed between 4 and 8 hrs. We could not find a correlation between the presence of hsps and thermotolerance, but only between the synthesis of hsps and thermotolerance in MO4 cells.

Animals↗

The effect of pentagastrin on the directional migration of colon adenocarcinoma cells in vitro.

The centrifugal spreading of multicellular aggregates from a DMH induced colon adenocarcinoma cell line from rats was observed in vitro. Various concentrations of pentagastrin were added to the culture medium. Controls included medium alone or culture medium containing different concentrations of either NH4OH or NaOH that were needed to dissolve the pentagastrin. The migration index, the total surface area occupied by the cells after 7 days, and the cell density of the culture were measured. Using 10 micrograms/ml of pentagastrin, the migration idex and the area covered by the cells were increased (P less than 0.01) while the cell density was not. Inhibition of cell division through addition of 5 fluoro-uracil to the culture medium abolished the stimulating effect of pentagastrin although the centrifugal migration was not suppressed by the antimetabolite. These data indicate that a supraphysiological concentration of pentagastrin can stimulate the spreading of colon cancer cell aggregates in vitro by enhanced proliferation.

Adenocarcinoma↗

[Epidural metastases at the spinal level. Clinical study of 82 cases].

This is a retrospective review of 82 cases of spinal epidural metastasis. A warning vertebral or radicular pain was present in 85% of the cases. In 33% of the patients, who complained only of pain without any neurological deficit, a complete myelographic block was already present. It is thus of prime importance not to neglect a vertebro-radicular pain in cancer patients, and even in patients without known cancer since the epidural metastasis was the first manifestation of the neoplasm in 30% of our cases. The indications for myelography are defined. The functional result (i.e. ability to walk) after treatment depends on the neurological state before treatment. In our series, total paraplegia was always irreversible. Early diagnosis and treatment are thus very important. The surgical treatment alone is judged insufficient. We were not able to prove the superiority of one of the following therapeutic modalities: laminectomy followed by radiotherapy or radiotherapy alone. Radiotherapy is indicated in all cases, often as the sole treatment. The indications for surgery are defined; they are based on our own experience and the literature. High dose steroids are indicated as adjuvant therapy.

Adolescent↗