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Biomedical subjects

E B van Dieren

Publications and source records attributed to E B van Dieren.

12 recordsLinked to original sources
PubMed2000

Beam intensity modulation using tissue compensators or dynamic multileaf collimation in three-dimensional conformal radiotherapy of primary cancers of the oropharynx and larynx, including the elective neck.

INTRODUCTION: The treatment of midline tumors in the head and neck by conventional radiotherapy almost invariably results in xerostomia. This study analyzes whether a simple three-dimensional conformal radiotherapy (3D-CRT) technique with beam intensity modulation (BIM) (using a 10-MV beam of the MM50 Racetrack Microtron) can spare parotid and submandibular glands without compromising the dose distribution in the planning target volume (PTV). METHODS: For 15 T2 tumors of the tonsillar fossa with extension into the soft palate (To) and 15 T3 tumors of the supraglottic larynx (SgL), conventional treatment plans, consisting of lateral parallel opposed beams, were used for irradiation of both the primary tumor (70 Gy) and the elective neck regions (46 Gy). Separately, for each tumor a 3-D conformal treatment plan was developed using the 3-D computer planning system, CadPlan, and Optimize, a noncommercial program to compute optimal beam profiles. Beam angles were selected with the intention of optimal sparing of the salivary glands. The intensity of the beams was then modulated to achieve a homogeneous dose distribution in the target for the given 3D-CRT techniques. The dose distributions, dose-volume histograms (DVHs) of target and salivary glands, tumor control probabilities (TCPs), salivary gland volumes absorbing a biologically equivalent dose of greater than 40 or 50 Gy, and normal tissue complication probabilities (NTCPs) of each treatment plan were computed. The parameters of the 3D-CRT plans were compared with those of the conventional plans. RESULTS: In comparison with the conventional technique, the dose homogeneity in the target volume was improved by the conformal technique for both tumor sites. In addition, for the SgL conformal technique, the average volumes of the parotid glands absorbing a BED of greater than 40 Gy (V40) decreased by 23%, and of the submandibular glands by 7% (V40) and 6% (V50). Consequently, the average NTCPs for the parotid and submandibular glands were reduced by 7% and 6%, respectively. For the To conformal techniques, the V40 of the parotid glands was decreased on average by 31%, resulting in an average reduction of the NTCP by 49%. Both the average V50 and the NTCP of the submandibular glands were decreased by 7%. CONCLUSION: For primary tumors of the oropharynx, the parotid glands could be spared to a considerable degree with the 3D-CRT technique. However, particularly the ipsilateral submandibular gland could not be spared. For primary tumors of the larynx, the 3D-CRT technique allows sparing of all salivary glands to a considerable and probably clinically relevant degree. Moreover, the conformal techniques resulted in an increased dose homogeneity in the PTV of both tumor sites.

Feasibility Studies↗
PubMed2000

Detection of internal organ movement in prostate cancer patients using portal images.

Previous research has indicated that the appearance of large gas pockets in portal images of prostate cancer patients might imply internal prostate motion. This was verified with simulations based on multiple computed tomography (CT) data for 15 patients treated in supine position. Apart from the planning CT scan, three extra scans were made during treatment. The clinical target volume (CTV) and the rectum were outlined in all scans. Lateral portal images were simulated from the CT data and difference images were calculated for all possible combinations of CT scans per patient; each scan was used both as reference and repeat scan but gas pockets in the reference scan were removed. Gas pockets in a repeat CT scan then show up as black areas in a difference image. Due to gravity, they normally appear in the ventral part of the rectum. The distances between the ventral edge of a gas pocket in a difference image and the projection of the delineated ventral rectum wall in the reference scan were calculated. These distances were correlated with the "true" rectum wall shifts (determined from direct comparison of the rectum delineations in reference and repeat scan) and with CTV movements determined by three-dimensional chamfer matching. Gas pockets occurred in 23% of cases. Nevertheless, about 50% of rectum wall shifts larger than 5 mm could be detected because they were associated with gas pockets with a lateral diameter > 2 cm. When gas pockets were visible in the repeat scan, rectum wall shifts could be accurately detected by the ventral gas pocket edge in the difference images (r= 0.97). The shift of the rectum wall as detected from gas pockets also correlated significantly with the anterior-posterior shift of the center of mass of the CTV (r=0.88). In conclusion, the simulations showed that lateral pelvic images contain more information than the bony structures that are normally used for setup verification. If large gas pockets appear in those images, a quantitative estimate of the position of prostate and rectum wall can be obtained by determination of the ventral edge of the gas pocket.

Humans↗
PubMed1999

A simplified CT-based definition of the lymph node levels in the node negative neck.

INTRODUCTION AND PURPOSE: Using three dimensional (3D) conformal radiotherapy (CRT) techniques for elective neck irradiation (ENI) may allow for local disease control to be maintained while diminishing xerostomia by eliminating major salivary glands (or parts thereof) from the treatment portals. The standardization of CT based target volumes for the clinically negative (elective) neck is a prerequisite for 3DCRT. The aim of the present study was to substantially modify an existing ('original') CT-based protocol for the delineation of the neck target volume, into a more practical ('simplified') protocol. This will allow for rapid contouring and the implementation of conformal ENI in routine clinical procedures. MATERIAL AND METHODS: An earlier ('original') version of the CT-based definition for elective neck node regions 2-5 was re-evaluated, using 15 planning CT scans of previously treated patients. The contouring guidelines were simplified by (1) using a smaller number of easily identifiable soft tissue- and bony anatomical landmarks, which in turn had to be identified in only a limited number of CT slices, and (2) by subsequently interpolating the contoured lymph node regions. The adequacy of target coverage and the sparing using both 'original' and 'simplified' delineation protocols was evaluated by DVH analysis after contouring the primary tumor, the neck and the major salivary glands in a patient with supraglottic laryngeal (SGL) carcinoma who was treated using a 3DCRT technique. RESULTS: The BEV projections of the 'original' and the 'simplified' versions of the 3D elective neck target showed good agreement and were found to be reproducible. The DVH's of the target and parotid glands were not significantly different using both contouring protocols. CONCLUSIONS: The 'simplified' protocol for the delineation of the 3D elective neck target produced both comparable target coverage and sparing of the major salivary glands. When used together with an interpolation program, this 'simplified' protocol substantial reduced the contouring time and makes ENI with sparing of the major salivary glands a practical and achievable goal.

Head and Neck Neoplasms↗
PubMed1999

Verification of compensator thicknesses using a fluoroscopic electronic portal imaging device.

A method is presented for verification of compensator thicknesses using a fluoroscopic electronic portal imaging device (EPID). The method is based on the measured transmission through the compensator, defined by the ratio of the portal dose with the compensator in the beam and the portal dose without the compensator in the beam. The transmission is determined with the EPID by dividing two images, acquired with and without compensator inserted, which are only corrected for the nonlinear response of the fluoroscopic system. The transmission has a primary and a scatter component. The primary component is derived from the measured transmission by subtracting the predicted scatter component. The primary component for each point is only related to the radiological thickness of the compensator along the ray line between the focus and that point. Compensator thicknesses are derived from the primary components taking into account off-axis variations in beam quality. The developed method has been tested for various compensators made of a granulate of stainless steel. The compensator thicknesses could be determined with an accuracy of 0.5 mm (1 s.d.), corresponding to a change in the transmitted dose of about 1% for a 10 MV beam. The method is fast, accurate, and insensitive to long-term output and beam profile fluctuations of the linear accelerator.

Biophysical Phenomena↗
PubMed1996

Absorbed dose distribution of the auger emitters 67GA and 125I and the beta-emitters 67CU, 90Y, 131I, and 186RE as a function of tumor size, uptake, and intracellular distribution.

PURPOSE: The influence of tumor volume, uptake of radioactive compounds in cells of tumors and normal tissues, and characteristics of the emitted ionizing particles on the efficacy of systemic radiation were studied. METHODS AND MATERIALS: The influence of these variables was assessed using a point kernel approach combined with a distance histogram technique. Simulation calculations were performed to assess dose distributions for three tumor sizes (phi = 200 microns, 2 mm, or 2 cm) and six radionuclides: 67Ga, 125I, 67Cu, 90Y, 131I, and 186Re. RESULTS: The energy deposition patterns depended on the relation of the tumor size and range of the emitted particles. Selective uptake was especially important in cases where the range was short compared to the dimension of the tumor. CONCLUSION: To attain a high dose for treatment of micrometastases, the use of Auger and conversion electron emitters (67Ga and 125I) or beta-emitters with emission spectra including low energetic electrons (67Cu and 131I) was recommended. The results demonstrated the complementary nature of selectivity of energy deposition and crossfire. This implied that for tumor cells or areas with reduced uptake, crossfire from radioactivity in surrounding cells or areas with selective uptake would be provided by intermediate (conversion electrons) or long-range (beta-particles) emissions.

Dose-Response Relationship, Radiation↗
PubMed1996

Radiotoxic effect and dosimetry of 67GA in multicellular spheroids as compared to single cells of the lymphoma cell line U715.

PURPOSE: The purpose of the present study was to investigate if there were differences between U715 spheroids and single cells in the radiotoxic effect of 67Ga on cell growth and clonogenic capacity in vitro and to generate dosimetric approaches for the multicellular tumor model. METHODS AND MATERIALS: Human lymphoma U715 cells were cultured in vitro as single cells and multicellular spheroids, grown with the use of a combination of fibrin clot technique, spinner flasks, and liquid-overlay culture. Cells were incubated with 2.96-8.88 MBq/ml 67Gallium for 4 days. Spheroids were dispersed to single cells by treatment with plasmin. Residual proliferative and clonogenic capacity after 67Ga incubation were assayed using the MTT-test and clonogenic test, respectively. Autoradiography was performed with 1 microm sections and Ilford L4 liquid photographic emulsion. Dosimetric approaches were made, based on the MIRD-approach. RESULTS: During 67Ga incubation proliferation was inhibited. The residual proliferative or clonogenic capacity was inhibited by 8.88 MBq/ml for 39 and 88%, respectively. For single cells with 6.66 MBq/ml these inhibitions were 64 and 96%, respectively. Autoradiography showed an homogeneous distribution of 67Ga in spheroids and single cells. In single cells a 2.1-3.5 times higher 67Ga uptake/cell than in spheroids produced an equitoxic effect. The uptake parameters were implemented in new dosimetric approaches and showed that the efficacy of intracellular 67Ga was two times higher in spheroid clusters than in single cells due to energy deposition of internal conversion electrons within the cell clusters with a mean diameter size of nine cells. Both for proliferative and clonogenic capacity the exponential survival curves were superimposed. CONCLUSIONS: With the new approaches made in our dosimetric model the discrepancy found between 67Ga accumulation and radiotoxic effect in spheroids as compared to single cells can be explained by additional effects of the crossfire of internal conversion electrons within clusters of about nine cells in diameter in spheroids. Only twice as much 67Ga was needed to reach equitoxic absorbed doses in spheroids than was needed in single cells. Such might be important for the use of 67Ga treatment of small metastasis of malignant lymphoma.

Autoradiography↗
PubMed1996

Bone marrow absorbed dose of rhenium-186-HEDP and the relationship with decreased platelet counts.

UNLABELLED: Rhenium-186(Sn)-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) has been used for palliation of metastatic bone pain. The purpose of this study was to find a relationship between the bone marrow absorbed dose and the toxicity, expressed as the percentage decrease in the peripheral blood platelet count. METHODS: The bone marrow absorbed dose was calculated according to the MIRD model using data obtained from ten treatments of patients suffering from metastatic prostate cancer; noninvasive and pharmacokinetic methods were used. The bone marrow doses were related to toxicity using the pharmacodynamic sigmoid Emax model. RESULTS: The mean bone marrow absorbed doses using the noninvasive and pharmacokinetic methods were in a close range to each other (1.07 mGy/MBq and 1.02 mGy/MBq, respectively). There was a good relationship between the toxicity and the bone marrow absorbed dose (r = 0.80). Furthermore, the EDrm50 (i.e., the bone marrow absorbed dose producing a 50% platelet decrease) to bone marrow for 186Re-HEDP was on the order of 2 Gy. CONCLUSION: Although the function of normal bone marrow is affected by metastases in patients with metastatic bone disease, the MIRD model can be used to relate toxicity to the bone marrow absorbed dose after a therapeutic dosage of 186Re-HEDP.

Aged↗
PubMed1994

A dosimetric model for intrathecal treatment with 131I and 67Ga.

PURPOSE: Calculations were performed of absorbed dose distributions of the beta-emitter 131I and the Auger emitter 67Ga for intrathecal administration. METHODS AND MATERIALS: The proposed dosimetric model accounts for the macroscopic distribution of the activity, by means of a Medical Internal Radiation Dose Committee approach, and for the microscopic distribution of activity, by means of a point kernel technique. This point kernel approach was used in combination with a distance histogram technique, to study in more detail the absorbed dose distribution in the cerebro-spinal fluid, in the surface of the central nervous system, and in tumor sites. We simulated decreased uptake, as well as highly selective uptake in free-floating tumor cells and in meningeal lesions (1-16 cells thick). RESULTS: In case of limited access to lesions adherent to the pia mater, the beta-emitter 131I provides crossfire from the CSF, resulting in a higher absorbed dose (Gy/MBq) in these lesions as compared with the Auger emitter 67Ga. In case of increasing radionuclide uptake, the increment of the absorbed dose in the adherent lesions and the free floating cells from 67Ga is considerable because of the local deposition of energy by this radionuclide. CONCLUSIONS: The model might be useful to select the optimal emission characteristics of radionuclides applicable for intrathecal therapy, which is demonstrated in a comparison of the Auger emitter 67Ga and the beta-emitter 131I.

Gallium Radioisotopes↗
PubMed1994

Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies.

Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium-111-OV-TL-3 F(ab')2]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for 111In-OV-TL-3 and between 0.13 and 0.68 mGy/MBq for 131I-16.88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation.

Bone Marrow↗
PubMed1993

Gallium-67 radiotoxicity in human U937 lymphoma cells.

Promising clinical results have been obtained with radiolabeled antibodies in lymphoma patients. The higher uptake by lymphomas of 67Gallium (67Ga) compared with monoclonal antibodies makes selective radiotherapy by the widely available 67Ga appealing. However, the gamma radiation of 67Ga used in scintigraphy is considered to be almost non-toxic to lymphoma cells. However, in addition to photon radiation 67Ga emits low energy Auger electrons and 80-90 keV conversion electrons which could be cytotoxic. The objective of the present study was the assessment of radiotoxicity of 67Ga on a lymphoid cell line: U937. Proliferation (MTT-assay) and clonogenic capacity (CFU-assay) were measured after 3 and 6 days incubation with 10, 20 and 40 microCi ml-1 67Ga. Growth inhibition was 36% after 3 days incubation and 63% after 6 days incubation with 40 microCi 67Ga ml-1. Clonogenic capacity was reduced by 51% after 3 days and 72% after 6 days incubation with 40 microCi ml-1 67Ga. A survival curve showed an initial shoulder and became steeper beyond 200-250 pCi cell-1 (low linear energy transfer type). Iso-effect doses of 67Ga and 90Yttrium (90Y) were determined. The iso-effect dose of 40 microCi 67Ga ml-1 (cumulative dose of conversion electrons 306 cGy) was 2.5 microCi 90Y ml-1 (cumulative dose 494 cGy) and the iso-effect dose of 80 microCi 67Ga ml-1 was 5.0 microCi 90Y/ml. The main cytotoxic effect of 67Ga seems to be induced by the 80 keV conversion electrons. We conclude that the conversion electrons of 67Ga have a cytotoxic effect on U937 cells and that in our experiments a 16-fold higher microCi-dose of 67Ga than of 90Y was needed for the same cytotoxic effect. We believe that 67Ga holds promise for therapeutic use.

Cell Division↗
PubMed1992

Kinetics and dosimetry of iodine-131-labelled antibody fragments after local administration in patients with rectal cancer.

In 11 patients with rectal cancer, a mixture of F(ab')2 fragments of anti-carcinoembryonic antigen and anti-CA 19.9 labelled with a diagnostic dose of iodine-131 (3-10 MBq) was administered submucosally around the tumour. In this study, the local kinetics in and the dose to the rectal wall, the whole body kinetics and the effective dose equivalent are presented. The early disappearance of the activity from the injection spot was characterized by a T1/2 of 21 h. Initially, about 50% of the plasma activity was due to free 131I. After 4 h, the plasma activity was almost completely protein bound (86%). Maximum plasma activity was observed after the 2nd day. From 72 h p.i., the plasma activity decreased with a T1/2 of 53 h. In the first 24 h, 14% of the injected dose was excreted in the urine and within 4 days about half of the administered activity. The absorbed radiation dose to the rectal wall was estimated to be 0.2 Gy/MBq, presuming a 20 cm3 distribution volume. The dose to the bone marrow was 0.2 mGy/MBq or 0.4 mGy/MBq, assuming a homogeneous tracer distribution or equal blood and bone marrow activity concentrations, respectively. The effective dose equivalent is 1.9 mSv/MBq, mainly determined by the dose to the rectal wall and to a lesser extent by the dose to the remaining body. Postulating comparable kinetics, 123I- or 111In- or 99mTc-labelled fragments would result in 4-25-fold lower effective dose equivalents.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗