Search PubMed⌕ Search

Biomedical subjects

J V Lebesque

Publications and source records attributed to J V Lebesque.

At least 37 records · Page 2Linked to original sources
PubMed1999

A general methodology for three-dimensional analysis of variation in target volume delineation.

A generic method for three-dimensional (3-D) evaluation of target volume delineation in multiple imaging modalities is presented. The evaluation includes geometrical and statistical methods to estimate observer differences and variability in defining the Gross Tumor Volume (GTV) in relation to the diagnostic CT and MRI modalities. The geometrical method is based on mapping the 3-D shape of the target volume to a scalar representation, thus enabling a one-dimensional statistical analysis. The statistical method distinguishes observer and modality related uncertainties, which are expressed in terms of three error components: random observer deviations, systematic observer differences, and systematic modality differences. Monte Carlo simulations demonstrate that the standard errors of each of the three model parameters are inversely proportional to the square root of the product of the patient group size and the number of observers and proportional to the intraobserver variation. For 18 patients and 3 observers the standard errors of the estimated systematic modality and observer differences are 19% and 14% of the intraobserver standard deviation, respectively. A scalar representation of the shape of the prostate, delineated by 3 observers for 18 patients, was obtained by sampling the distance between the average center of gravity of the prostate in CT and the prostate surface for a large number of directions (2500), using polar coordinates. Observer variability and differences were obtained by applying the statistical method to the samples independently. The intraobserver variation for CT was largest in regions near the seminal vesicles (s.d: 3 mm) and the apex (s.d: 3 mm). The systematic observer variation in CT was largest in a region near the plexus Santorini, at the caudal-anterior side of the prostate (s.d.: 2 mm). The sensitivity for the choice of origin was tested by using the average center of gravity from axial MRI instead of CT. The results were almost identical. The polar map measures distances in the scanning directions. A correction procedure to get the variability in directions perpendicular to the surface of the prostate yielded variations that were a factor of 0.85 smaller for all directions. It is concluded that by separating the shape evaluation in a geometrical and a statistical part, the complexity of the analysis of 3-D shape differences can be significantly reduced. The method was successfully applied to a group of prostate patients, where we demonstrated that delineation variability is nonhomogeneous, with the largest variations occurring near the seminal vesicles and the apex.

Biophysical Phenomena↗
PubMed1999

Effect of radiotherapy and chemotherapy on pulmonary function after treatment for breast cancer and lymphoma: A follow-up study.

PURPOSE: To determine the changes in pulmonary function tests (PFTs) 0 to 48 months after treatment for breast cancer and lymphoma. PATIENTS AND METHODS: The alveolar volume (V(A)), vital capacity, forced expiratory volume in 1 second, and corrected transfer factor of carbon monoxide (T(L,COc)) were measured in 69 breast cancer and 41 lymphoma patients before treatment and 3, 18, and 48 months after treatment with radiotherapy alone or radiotherapy in combination with chemotherapy (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine; cyclophosphamide, epidoxorubicin, fluorouracil; cyclophosphamide, thiotepa, carboplatin; cyclophosphamide, methotrexate, fluorouracil). The three-dimensional dose distribution in the lung of each patient was converted to the mean lung dose. Statistical analysis was used to evaluate the changes in PFT values over time in relation to age, sex, smoking, chemotherapy, and the mean lung dose. RESULTS: After an initial reduction in PFT values at 3 months, significant recovery was seen at 18 months for all patients. Thereafter, no further improvement could be demonstrated. Reductions in spirometry values and V(A) were related to the mean lung dose only (0.9% per Gy at 3 months and 0.4% per Gy mean dose at 18 months). T(L,COc) decreased 1. 1% per Gy mean dose and additionally decreased 6% when chemotherapy was given after radiotherapy. Chemotherapy administered before radiotherapy reduced baseline T(L,COc) values by 8% to 21%. All patients showed an improvement of 5% at 18 months. CONCLUSION: On the basis of the mean lung dose and the chemotherapy regimen, the changes in PFT values can be estimated before treatment within 10% of the values actually observed in 72% to 85% of our patients with healthy lungs.

Adolescent↗
PubMed1998

Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients.

PURPOSE: To determine the relation between the incidence of radiation pneumonitis and the three-dimensional dose distribution in the lung. METHODS AND MATERIALS: In five institutions, the incidence of radiation pneumonitis was evaluated in 540 patients. The patients were divided into two groups: a Lung group, consisting of 399 patients with lung cancer and 1 esophagus cancer patient and a Lymph./Breast group with 78 patients treated for malignant lymphoma, 59 for breast cancer, and 3 for other tumor types. The dose per fraction varied between 1.0 and 2.7 Gy and the prescribed total dose between 20 and 92 Gy. Three-dimensional dose calculations were performed with tissue density inhomogeneity correction. The physical dose distribution was converted into the biologically equivalent dose distribution given in fractions of 2 Gy, the normalized total dose (NTD) distribution, by using the linear quadratic model with an alpha/beta ratio of 2.5 and 3.0 Gy. Dose-volume histograms (DVHs) were calculated considering both lungs as one organ and from these DVHs the mean (biological) lung dose, NTDmean, was obtained. Radiation pneumonitis was scored as a complication when the pneumonitis grade was grade 2 (steroids needed for medical treatment) or higher. For statistical analysis the conventional normal tissue complication probability (NTCP) model of Lyman (with n=1) was applied along with an institutional-dependent offset parameter to account for systematic differences in scoring patients at different institutions. RESULTS: The mean lung dose, NTDmean, ranged from 0 to 34 Gy and 73 of the 540 patients experienced pneumonitis, grade 2 or higher. In all centers, an increasing pneumonitis rate was observed with increasing NTDmean. The data were fitted to the Lyman model with NTD50=31.8 Gy and m=0.43, assuming that for all patients the same parameter values could be used. However, in the low dose range at an NTDmean between 4 and 16 Gy, the observed pneumonitis incidence in the Lung group (10%) was significantly (p=0.02) higher than in the Lymph./Breast group (1.4%). Moreover, between the Lung groups of different institutions, also significant (p=0.04) differences were present: for centers 2, 3, and 4, the pneumonitis incidence was about 13%, whereas for center 5 only 3%. Explicitly accounting for these differences by adding center-dependent offset values for the Lung group, improved the data fit significantly (p < 10(-5)) with NTD50=30.5+/-1.4 Gy and m=0.30+/-0.02 (+/-1 SE) for all patients, and an offset of 0-11% for the Lung group, depending on the center. CONCLUSIONS: The mean lung dose, NTDmean, is relatively easy to calculate, and is a useful predictor of the risk of radiation pneumonitis. The observed dose-effect relation between the NTDmean and the incidence of radiation pneumonitis, based on a large clinical data set, might be of value in dose-escalating studies for lung cancer. The validity of the obtained dose-effect relation will have to be tested in future studies, regarding the influence of confounding factors and dose distributions different from the ones in this study.

Dose-Response Relationship, Radiation↗
PubMed1998

Estimation of the incidence of late bladder and rectum complications after high-dose (70-78 GY) conformal radiotherapy for prostate cancer, using dose-volume histograms.

PURPOSE: To investigate whether Dose-Volume Histogram (DVH) parameters can be used to identify risk groups for developing late gastrointestinal (GI) and genitourinary (GU) complications after conformal radiotherapy for prostate cancer. METHODS AND MATERIALS: DVH parameters were analyzed for 130 patients with localized prostate cancer, treated with conformal radiotherapy in a dose-escalating protocol (70-78 Gy, 2 Gy per fraction). The incidence of late (>6 months) GI and GU complications was classified using the RTOG/EORTC and the SOMA/LENT scoring system. In addition, GI complications were divided in nonsevere and severe (requiring one or more laser treatments or blood transfusions) rectal bleeding. The median follow-up time was 24 months. We investigated whether rectal and bladder wall volumes, irradiated to various dose levels, correlated with the observed actuarial incidences of GI and GU complications, using volume as a continuous variable. Subsequently, for each dose level in the DVH, the rectal wall volumes were dichotomized using different volumes as cutoff levels. The impact of the total radiation dose, and the maximum radiation dose in the rectal and bladder wall was analyzed as well. RESULTS: The actuarial incidence at 2 years for GI complications > or =Grade II was 14% (RTOG/EORTC) or 20% (SOMA/LENT); for GU complications > or =Grade III 8% (RTOG/EORTC) or 21% (SOMA/LENT). Neither for GI complications > or =Grade II (RTOG/EORTC or SOMA/LENT), nor for GU complications > or =Grade III (RTOG/EORTC or SOMA/LENT), was a significant correlation found between any of the DVH parameters and the actuarial incidence of complications. For severe rectal bleeding (actuarial incidence at 2 years 3%), four consecutive volume cutoff levels were found, which significantly discriminated between high and low risk. A trend was observed that a total radiation dose > or = 74 Gy (or a maximum radiation dose in the rectal wall >75 Gy) resulted in a higher incidence of severe rectal bleeding (p = 0.07). CONCLUSIONS: These data show that dose escalation up to 78 Gy, using a conformal technique, is feasible. However, these data have also demonstrated that the incidence of severe late rectal bleeding is increased above certain dose-volume thresholds.

Dose-Response Relationship, Radiation↗
PubMed1998

Dose-effect relations for early local pulmonary injury after irradiation for malignant lymphoma and breast cancer.

PURPOSE: To quantify the influence of treatment- and patient-related factors on the severity of early local pulmonary injury and to establish whether regional differences are present for local dose-effect relations for early radiation-induced pulmonary injury. METHODS: Forty-two patients with malignant lymphoma and 40 breast cancer patients were examined prior to and 3 months after radiotherapy. The lymphoma patients were irradiated with mantle fields to an average dose of 38 Gy and the breast cancer patients were irradiated with internal mammary node fields with or without tangential breast fields to an average dose of 50 Gy. Dose-effect relations for local perfusion, ventilation and density changes were determined using correlated single photon emission computed tomography (SPECT) and CT data. A multivariate analysis was performed to study the influence of irradiated volume, chemotherapy (CMF and MOPP/ABV), smoking, age and gender. In addition, dose-effect relations for different regions in the lung were determined. RESULTS: A similar and almost linear increase of early functional changes as a function of radiation dose was observed for perfusion and ventilation, whereas the shape of the dose-effect relation and the magnitude of early structural changes were different for density. For the three end-points studied, regional differences in radiosensitivity could not be demonstrated. For the posterior lung region compared to the anterior lung region, however, a difference was observed, which could be attributed to a gravity-related effect in the measuring procedure. Local structural changes (density) were significantly smaller for smokers (P = 0.002) and young patients (P = 0.007), whereas the CMF chemotherapy regimen given after radiotherapy (P = 0.017) significantly increased the amount of functional changes (perfusion). The magnitude of local pulmonary changes was independent of the irradiated volume, the MOPP/ABV chemotherapy regimen and gender. CONCLUSION: The dose-effect relations for early radiation-induced local pulmonary changes were independent of the irradiated volume, MOPP/ABV, gender and lung region. CMF, smoking and age influenced the magnitude of early pulmonary changes and should be taken into account in dose-escalation protocols.

Adult↗
PubMed1998

Evaluation of two dose-volume histogram reduction models for the prediction of radiation pneumonitis.

PURPOSE: To evaluate the similarities between the mean lung dose and two dose-volume histogram (DVH) reduction techniques of 3D dose distributions of the lung. PATIENTS AND METHODS: DVHs of the lungs were calculated from 3D dose distributions of patients treated for malignant lymphoma (44), breast cancer (42) and lung cancer (20). With a DVH reduction technique, a DVH is summarized by the equivalent uniform dose (EUD), a quantity which is directly related to the normal tissue complication probability (NTCP). Two DVH reduction techniques were used. The first was based on an empirical model proposed by Kutcher et al. (Kutcher, G.J., Burman, C., Brewster, M.S., Goitein, M. and Mohan, R. Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations. Int. J. Radiat. Oncol. Biol. Phys. 21: 137-146, 1991), which needs a volume exponent n. Several values for n were tested. The second technique was based on a radiobiological model, the parallel functional subunit model developed by Niemierko et al. (Niemierko, A. and Goitein, M. Modeling of normal tissue response to radiation: the critical volume model. Int. J. Radiat. Oncol. Biol. Phys. 25: 135-145, 1993) and Jackson et al. (Jackson, A., Kutcher, G.J. and Yorke, E.D. Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation. Med. Phys. 20: 613-625, 1993), for which a local dose-effect relation needed to be specified. This relation was obtained from an analysis of perfusion and ventilation SPECT data. RESULTS: It can be shown analytically that the two DVH reduction techniques are identical, if the local dose-effect relation obeys a power-law relationship in the clinical dose range. Local dose-effect relations based on perfusion and ventilation SPECT data can indeed be fitted with a power-law relationship in the range 0-80 Gy, from which values of n = 0.8-0.9 were deduced. These correspond to the commonly used value of n = 0.87 for lung tissue and yielded EUDn=0.87 values which were almost identical to the mean lung doses. For other n values, for which no experimental data are present, differences exist between EUD and mean dose values. Six patients with malignant lymphoma (6/44) and none of the breast cancer patients (0/42) developed radiation pneumonitis. These cases occurred only at high values for the mean lung dose. CONCLUSION: The two DVH reduction techniques are identical for lung and are very similar to mean dose calculations. The two techniques are also relatively similar for other model parameter values.

Breast Neoplasms↗
PubMed1998

Prediction of overall pulmonary function loss in relation to the 3-D dose distribution for patients with breast cancer and malignant lymphoma.

PURPOSE: To predict the changes in pulmonary function tests (PFTs) 3-4 months after radiotherapy based on the three-dimensional (3-D) dose distribution and taking into account patient- and treatment-related factors. METHODS: For 81 patients with malignant lymphoma and breast cancer, PFTs (VA, VC, FEV1 and TL,COc) were performed prior to and 3-4 months after irradiation and dose-effect relations for early changes in local perfusion, ventilation and air-filled fraction were determined using correlated CT and SPECT data. The 3-D dose distribution of each patient was converted into four different dose-volume parameters, i.e. the mean dose in the lung and three overall response parameters (ORPs, which represent the average local injury over the complete lung). ORPs were determined using the dose-effect relations for early changes in local perfusion, ventilation and air-filled fraction. Correlation coefficients were calculated between these dose-volume parameters and the changes in PFTs. In addition, the impact of the variables chemotherapy (MOPP/ABV and CMF), tamoxifen, smoking, age and gender on the relation between the mean lung dose and the relative changes in PFTs following radiotherapy was studied using multiple regression analysis. RESULTS: The mean lung dose proved to be the easiest parameter to predict the reduction in PFTs 3-4 months following radiotherapy. For all patients the relation between the mean lung dose and the changes in PFTs could be described with one regression line through the origin and a slope of 1% reduction in PFT for each increase of 1 Gy in mean lung dose. Smoking and CMF chemotherapy influenced the reduction in PFTs significantly for VA and TL,COc, respectively. Patients treated with MOPP/ABV prior to radiotherapy had lower pre-radiotherapy PFTs than other patient groups, but did not show further deterioration after radiotherapy (at 3-4 months). CONCLUSIONS: The relative reduction in VA, VC, FEV1 and TL,COc 3-4 months after radiotherapy for breast cancer and malignant lymphoma can be estimated before radiotherapy based on the mean lung dose of each individual patient and taking into account the use of chemotherapy and smoking habits of the patient.

Adolescent↗
PubMed1998

Dosimetric verification of the 95% isodose surface for a conformal irradiation technique.

In the treatment planning of conformal radiotherapy, field shapes are often designed in such a way that a high-value isodose surface fully encompasses the target volume. Therefore, knowledge about the accuracy with which the treatment planning system calculates the position of that isodose surface is essential to prevent field shapes which are either too large or too small. To determine this accuracy for a conformal multi-field technique, the dose in the high-dose region must be measured with a high spatial resolution. A method is presented to reconstruct and evaluate the experimental high-dose region from a set of water phantom scans. This method, which assesses combined dose profiles for multi-field irradiation techniques, can be used for the commissioning and/or quality assurance of a 3-D treatment planning system. For a specific conformal technique, the measured and calculated 95% isodose positions along lines in several directions have been compared. It is shown that different dose values of single beam profiles determine the resulting 95% isodose position, which is important to recognize for quality assurance of treatment planning calculations. It is further found that the uncertainty in the calculated 95% isodose surface can be described by a standard deviation in dose value, which relates to a positional uncertainty through the local dose gradient. Thus the confidence region of the calculated 95% isodose can be indicated in the treatment plan by plotting isodoses at the 95% level plus and minus its standard deviation. Such a procedure is recommended instead of plotting the 95% isodose with a constant width. In addition, restrictions for the cumulative dose-volume histogram of acceptable treatment plans can be formulated, based on the sensitivity of the actual target coverage on the uncertainty with which the prescribed isodose surface is calculated.

Brachytherapy↗
PubMed1998

Automatic registration of pelvic computed tomography data and magnetic resonance scans including a full circle method for quantitative accuracy evaluation.

The purpose of this study is to develop a method for registration of CT and MR scans of the pelvis with minimal user interaction and to obtain a means for objective quantification of the registration accuracy of clinical data without markers. CT scans were registered with proton density MR scans using chamfer matching on automatically segmented bone. A fixed threshold was used to segment CT, while morphological filters were used to segment MR. The method was tested with transverse and coronal MR scans of 18 patients and sagittal MR scans of 8 patients. The registration accuracy was estimated by comparing (triangulating) registrations of a single CT scan with MR in different orientations in a "full circle." For example, CT is first matched on transverse MR, next transverse MR is matched independently on coronal MR, and finally coronal MR is matched independently on CT. The product of the three transformations is the identity if all matching steps are perfect. Deviations from identity occur both due to random errors and due to some types of systematic errors. MR was registered on MR (to close the "circle") by minimization of rms voxel value differences. CT-MR registration takes about 1 min, including user interaction. The random error for CT-MR registration with transverse or coronal MR was 0.5 mm in translation and 0.4 degree in rotation (standard deviation) for each axis. A systematic registration error of about 1 mm was demonstrated along the MR frequency encoding direction, which is attributed to the chemical shift. In conclusion, the presented algorithm efficiently and accurately registers pelvic CT and MR scans on bone. The "full circle" method provides an estimate of the registration accuracy on clinical data.

Algorithms↗
PubMed1998

Automatic three-dimensional matching of CT-SPECT and CT-CT to localize lung damage after radiotherapy.

UNLABELLED: The aim of this study was to develop a fast and clinically robust automatic method to register SPECT and CT scans of the lungs. METHODS: CT and SPECT scans were acquired in the supine position from 20 patients with healthy lungs. After partial irradiation of the lungs by radiotherapy, the scans were repeated. Two matching methods were compared: a conventional method with external skin markers and a new method using chamfer matching of the lung contours. In the latter method, a unique value for the SPECT threshold, needed for segmentation of the SPECT lungs, was determined by iteratively applying the chamfer matching algorithm. RESULTS: The new technique for CT-SPECT matching could be implemented in a fully automatic manner and required less than 2 min. No large systematic shifts or rotations were present between the matches obtained with the marker method and the lung contour method for healthy or partially irradiated lungs. For healthy lungs, the number of ventilation SPECT counts outside the CT-defined lung was taken as a measure for a good match. This number of outside counts was slightly lower for the new method than for the conventional method, which indicates that the accuracy of the new method is at least comparable to the conventional method. For ventilation, a systematic difference between the results of the matching methods, a small translation in the anterior --> posterior direction, could be attributed to an inconsistency of the marker positions (2 mm). For perfusion, a somewhat larger anterior --> posterior shift was found, which was attributed to the gravity force. CT-CT correlation on the lung contours using chamfer matching was tested with the same dataset. For accurate matching, the CT slices encompassing the diaphragm had to be deleted. CONCLUSION: The new method based on lung contour matching is a fast, automatic procedure and allows accurate clinical follow-up.

Humans↗
PubMed1997

The potential impact of CT-MRI matching on tumor volume delineation in advanced head and neck cancer.

PURPOSE: To study the potential impact of the combined use of CT and MRI scans on the Gross Tumor Volume (GTV) estimation and interobserver variation. METHODS AND MATERIALS: Four observers outlined the GTV in six patients with advanced head and neck cancer on CT, axial MRI, and coronal or sagittal MRI. The MRI scans were subsequently matched to the CT scan. The interobserver and interscan set variation were assessed in three dimensions. RESULTS: The mean CT derived volume was a factor of 1.3 larger than the mean axial MRI volume. The range in volumes was larger for the CT than for the axial MRI volumes in five of the six cases. The ratio of the scan set common (i.e., the volume common to all GTVs) and the scan set encompassing volume (i.e., the smallest volume encompassing all GTVs) was closer to one in MRI (0.3-0.6) than in CT (0.1-0.5). The rest volumes (i.e., the volume defined by one observer as GTV in one data set but not in the other data set) were never zero for CT vs. MRI nor for MRI vs. CT. In two cases the craniocaudal border was poorly recognized on the axial MRI but could be delineated with a good agreement between the observers in the coronal/sagittal MRI. CONCLUSIONS: MRI-derived GTVs are smaller and have less interobserver variation than CT-derived GTVs. CT and MRI are complementary in delineating the GTV. A coronal or sagittal MRI adds to a better GTV definition in the craniocaudal direction.

Adenocarcinoma↗
PubMed1997

An analysis of the effect of ovoid shields in a selectron-LDR cervical applicator on dose distributions in rectum and bladder.

PURPOSE: A disadvantage of ovoid shields in a Fletcher-type applicator is that these shields cause artifacts on postimplant CT images. CT images, however, make it possible to calculate the dose distribution in the rectum and the bladder. To be able to estimate the possible advantage of having CT information over the use of ovoid shields without having CT information, we investigated the influence of shielding segments in a Fletcher-type Selectron-LDR applicator on the dose distribution in rectum and bladder. METHODS AND MATERIALS: Contours of rectum and bladder were delineated on transaxial CT slices of 15 unshielded applications. Of the volumes contained within these structures dose-volume histograms (DVHs) were calculated. In a similar way, DVHs of simulated shielded applications were calculated. The reduction, due to shielding, of the dose to the 2 cm3 (D2) and 5 cm3 (D5) volume of the cumulative DVHs of rectum and bladder, were determined. An isodose pattern in the sagittal plane through the center of each applicator was plotted to compare the location of the shielded area with the location of maximum dose in rectum and bladder in the unshielded situation. In two cases local dose reductions to the rectal wall were determined by calculating the dose in points at 10-mm intervals on the rectal contours. RESULTS: For the rectum, the reduction of D2 ranged from 0 to 11.1%, with an average of 5.0%; the reduction of D5 ranged from 2.3 to 12.1%, with an average of 6.4%. The reduction of D2 and D5 for the bladder ranged from 0 to 11.9% and from 0 to 11.6%, with average values of 2.2 and 2.6%, respectively. In 8 out of 15 cases the rectal maximum dose was located inferior to the shielded area. In all cases except one the bladder maximum dose was located superior to the shielded area. Local dose reductions on the rectal wall can be as high as 30% or more in an optimally shielded area. CONCLUSIONS: Reductions of D2 and D5 to rectum and bladder due to shielding are rather small, because the shielded area does usually not coincide with the high dose region and even if it does, the shielded area is too small to result in large reductions of these values. Because local dose reductions vary largely, one should proceed with caution when calculating the dose in just one rectal or bladder reference point. Because large overall dose reductions cannot be achieved with shielding, it is safe to use an unshielded applicator when post implant CT images are used to realize optimized dose distributions.

Artifacts↗
PubMed1996

High-precision prostate cancer irradiation by clinical application of an offline patient setup verification procedure, using portal imaging.

PURPOSE: To investigate in three institutions, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis [AvL]), Dr. Daniel den Hoed Cancer Center (DDHC), and Dr, Bernard Verbeeten Institute (BVI), how much the patient setup accuracy for irradiation of prostate cancer can be improved by an offline setup verification and correction procedure, using portal imaging. METHODS AND MATERIALS: The verification procedure consisted of two stages. During the first stage, setup deviations were measured during a number (Nmax) of consecutive initial treatment sessions. The length of the average three dimensional (3D) setup deviation vector was compared with an action level for corrections, which shrunk with the number of setup measurements. After a correction was applied, Nmax measurements had to be performed again. Each institution chose different values for the initial action level (6, 9, and 10 mm) and Nmax (2 and 4). The choice of these parameters was based on a simulation of the procedure, using as input preestimated values of random and systematic deviations in each institution. During the second stage of the procedure, with weekly setup measurements, the AvL used a different criterion ("outlier detection") for corrective actions than the DDHC and the BVI ("sliding average"). After each correction the first stage of the procedure was restarted. The procedure was tested for 151 patients (62 in AvL, 47 in DDHC, and 42 in BVI) treated for prostate carcinoma. Treatment techniques and portal image acquisition and analysis were different in each institution. RESULTS: The actual distributions of random and systematic deviations without corrections were estimated by eliminating the effect of the corrections. The percentage of mean (systematic) 3D deviations larger than 5 mm was 26% for the AvL and the DDHC, and 36% for the BVI. The setup accuracy after application of the procedure was considerably improved (percentage of mean 3D deviations larger than 5 mm was 1.6% in the AvL and 0% in the DDHC and BVI), in agreement with the results of the simulation. The number of corrections (about 0.7 on the average per patient) was not larger than predicted. CONCLUSION: The verification procedure appeared to be feasible in the three institutions and enabled a significant reduction of mean 3D setup deviations. The computer simulation of the procedure proved to be a useful tool, because it enabled an accurate prediction of the setup accuracy and the required number of corrections.

Feasibility Studies↗
PubMed1996

Phase II study of intensive chemotherapy with autologous bone marrow transplantation in patients in complete remission of disseminated breast cancer.

BACKGROUND: This trial studied the disease-free survival after high-dose chemotherapy in patients in complete remission of metastatic breast cancer. PATIENTS AND METHODS: Thirty women, mean age 42.2 years (range 33-55) with metastatic breast cancer, received high-dose chemotherapy in a phase II study. Patients were eligible if they were < or = 55 years of age, had achieved complete remission within 6 months of the initiation of chemotherapy, and had a WHO performance scale of 0 or 1. The high-dose regimen consisted of melphalan 180 mg/m2 and mitoxantrone 60 mg/m2 both divided over 3 days. On day 7 bone marrow and/or peripheral stem cells were infused. After bone marrow recovery, external beam radiation was administered to sites of previous metastatic disease in 15 patients. RESULTS: Apart from leuko- and thrombocytopenia, mucositis was the major side effect. One patient died during the bone marrow transplant period due to an aspergillus infection. The median follow-up since high-dose chemotherapy is 25 months (range 13 to 56 months). The median disease-free survival since high-dose chemotherapy is 27 months and the disease free survival is still 43% with an overall survival of 53% at 3 years. In two patients tumor relapse occurred only in the brain; in one patient the only relapse sign was a meningeal carcinosis. At the moment 17 patients are disease-free (13(+)-56+) months after high-dose chemotherapy. CONCLUSION: Until now this high-dose regimen in selected patients with complete remission after induction chemotherapy for metastatic breast cancer has a promising disease free survival.

Adult↗
PubMed1996

Target margins for random geometrical treatment uncertainties in conformal radiotherapy.

In this study we investigate a method for positioning the margin required around the clinical target volume (CTV) to account for the random geometrical treatment uncertainties during conformal radiotherapy. These uncertainties are introduced by patient setup errors and CTV motion within the patient. Three-dimensional dose distributions are calculated for two four-field box techniques and a three-field technique, using rectangular fields. In addition, dose calculations are performed for four prostate cases, treated with a three-field conformal technique. The effects of random rotational and translational deviations on the delivered dose are described as a convolution of the "static" dose with the distribution of the deviations. For the rectangular field techniques, these convolutions are performed with a range of standard deviations (SDs) of the distribution of random translations (0-7 mm in the three directions) and rotations (0 degree-5 degrees around the main axes). Two centers of rotation are considered: the isocenter and a position that is 3.5 cm shifted with respect to the isocenter. For the prostate cases, the random deviations are estimated by combining the results from organ motion and setup accuracy studies. The required margin is defined as the change in the position of the static 95% isodose surface by the convolution and it is approximated by a morphological erosion operator, applied to the static 95% isodose surface. When the center of rotation coincides with the isocenter the change in the position of the static 95% isodose surface can accurately be described by an erosion operator. For the rectangular field techniques, the margin is equal to about 0.7 SD of the distribution of translations, independent of the distribution of rotations. When the center of rotation does not coincide with the isocenter and rotations are considerable, the margin is strongly place dependent, and the accuracy of the approximation by an erosion operator is much lower. In conclusion, margins for random uncertainties can be approximated by a dilation operator (inverse of an erosion operator) when the center of rotational deviations coincides with the isocenter. The size of the margin is about 0.7 SD of the distribution of translations. When rotational deviations are present and the center of rotation does not coincide with the isocenter, the margin can become strongly place dependent and the convolution computation should be incorporated in the planning system.

Biophysical Phenomena↗
PubMed1996

Recovery of overall and local lung function loss 18 months after irradiation for malignant lymphoma.

PURPOSE: To determine the local and overall pulmonary injury 3 to 18 months after irradiation and to investigate whether the changes in overall lung function can be predicted using the three-dimensional (3-D) dose distribution in combination with dose-effect relations for local injury; and to study the influence of chemotherapy on the injury. PATIENTS AND METHODS: Local perfusion (Q), ventilation (V), and tissue density were measured in 25 patients treated for malignant lymphoma, before, 3 to 4 months after, and 18 months after irradiation. Dose-effect relations for local injury, calculated using correlated single-photon emission computed tomographic (SPECT) and computed tomographic (CT) data, were combined with the 3-D dose distribution, to calculate the estimated mean local changes over the complete lung for each patient. The result was correlated with the actual changes in pulmonary function. RESULTS: A dose-dependent increase with injury was observed at 3 to 4 months after irradiation, which at 18 months had recovered by approximately 50% to 60%. The estimated mean relative reduction of local Q predicted the change in overall lung function within 10% of the actually observed values in 63% to 73% of patients. Chemotherapy given before radiotherapy enhanced radiation-induced reduction of local Q significantly, with dose-modifying factors of 1.22 and 1.37 at 3 to 4 months and 18 months, respectively. CONCLUSION: Partial recovery of radiation-induced reduction of local and overall lung function was observed at 18 months after irradiation. The overall functional outcome of most patients could be well predicted, based on the estimated mean local injury over the complete lung. Chemotherapy given before radiotherapy enhanced the radiation-induced reduction of local Q.

Adolescent↗