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S H Muller

Publications and source records attributed to S H Muller.

At least 19 recordsLinked to original sources

Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer.

In the MRISC study, women with an inherited risk for breast cancer were screened by a 6-month clinical breast examination (CBE) and yearly MRI and mammography. We found that the MRISC screening scheme could facilitate early breast cancer diagnosis and that MRI was a more sensitive screening method than mammography, but less specific. In the current study we investigated the contribution of MRI in the early detection of breast cancer in relation to tumor characteristics. From November 1999 to October 2003, 1909 women were included and 50 breast cancers were detected, of which 45 were evaluable and included in the current study. We compared the characteristics of tumors detected by MRI-only with those of all other (non-palpable) screen-detected tumors. Further, we compared the sensitivity of mammography and MRI within subgroups according to different tumor characteristics. Twenty-two (49%) of the 45 breast cancers were detected by MRI and not visible at mammography, of which 20 (44%) were also not palpable (MRI-only detected tumors). MRI-only detected tumors were more often node-negative than other screen-detected cancers (94 vs. 59%; P=0.02) and tended to be more often <or=1 cm (58 vs. 31%; P=0.11). MRI was more sensitive than mammography for a wide spectrum of invasive tumor characteristics i.e., size, nodal status, histology, grade and ER status. Half of the breast cancers detected in this study were visible by MRI only and these tumors were smaller and significantly more often node-negative than other screen-detected tumors, suggesting that MRI makes an important contribution to the early detection of hereditary breast cancer.

Breast Neoplasms↗

The correlation of mammographic-and histologic patterns of breast cancers in BRCA1 gene mutation carriers, compared to age-matched sporadic controls.

Breast cancers in BRCA1 gene mutation carriers often have specific histologic features: grade III tumors with pushing margins. Our purpose was to compare the mammographic and histologic features of breast cancers in carriers with those in age-matched sporadic controls. The features of breast cancers in 27 BRCA1 carriers found during annual surveillance were compared to those in 107 age-matched sporadic controls. The carriers had no (classic) spiculated mammographic lesions, a high percentage of well-defined masses and hardly any masses with microcalcifications, whereas the controls had significantly fewer well-defined ones and only in 27% spiculated lesions on the mammogram. The well-defined mammographic tumors correlated in 83% of the carriers and in 70% of the controls with histologic circumscribed tumor margins. Spiculated mammographic lesions in the controls were in 90% grade I or II tumors. DCIS with or without infiltration was seen in 22% of the carriers and in 45% of the controls. In conclusion, breast cancers diagnosed in BRCA1 carriers do not have classic malignant mammographic features. A minority of the young sporadic controls show the classic malignant lesion on the mammogram. Both carriers and controls generally show a good correlation between their mammographic- and histologic tumor pattern.

Adult↗

The physiological rationale of heat and moisture exchangers in post-laryngectomy pulmonary rehabilitation: a review.

Total laryngectomy results in a permanent disconnection of the upper and lower airways and inevitably leads to chronic pulmonary complaints like frequent involuntary coughing, increased sputum production and repeated daily forced expectoration to clean the airway. Heat and moisture exchangers (HMEs), applied in an attempt to compensate for the lost functions of the upper respiratory tract, have been found to diminish these symptoms and improve the quality of life significantly. An HME has three physical properties that might be responsible for these improvements. First, its heat and moisture exchanging capacity improves intra-airway preservation of heat and water. Since the condensation and evaporation of moisture are accompanied by the release and uptake of thermal energy, these parameters are inseparable. Secondly, the HME's resistance may reduce dynamic airway compression, thereby improving ventilation. Thirdly, to some extent, an HME might filter out particles, thereby cleaning inspiratory breathing air. This article summarizes our present knowledge of changes in respiratory physiology after total laryngectomy and the influence of the HME by reviewing the physiological impact of these three physical properties separately for in vitro and in vivo data.

Hot Temperature↗

Fusion of respiration-correlated PET and CT scans: correlated lung tumour motion in anatomical and functional scans.

Lower lobe lung tumours in particular can move up to 2 cm in the cranio-caudal direction during the respiration cycle. This breathing motion causes image artefacts in conventional free-breathing computed tomography (CT) and positron emission tomography (PET) scanning, rendering delineation of structures for radiotherapy inaccurate. The purpose of this study was to develop a method for four-dimensional (4D) respiration-correlated (RC) acquisition of both CT and PET scans and to develop a framework to fuse these modalities. The breathing signal was acquired using a thermometer in the breathing airflow of the patient. Using this breathing signal, the acquired CT and PET data were grouped to the corresponding respiratory phases, thereby obtaining 4D CT and PET scans. Tumour motion curves were assessed in both image modalities. From these tumour motion curves, the deviation with respect to the mean tumour position was calculated for each phase. The absolute position of the centre of the tumour, relative to the bony anatomy, in the RCCT and gated PET scans was determined. This 4D acquisition and 4D fusion methodology was performed for five patients with lower lobe tumours. The peak-to-peak amplitude range in this sample group was 1-2 cm. The 3D tumour motion curve differed less than 1 mm between PET and CT for all phases. The mean difference in amplitude was less than 1 mm. The position of the centre of the tumour (relative to the bony anatomy) in the RCCT and gated PET scan was similar (difference <1 mm) when no atelectasis was present. Based on these results, we conclude that the method described in this study allows for accurate quantification of tumour motion in CT and PET scans and yields accurate respiration-correlated 4D anatomical and functional information on the tumour region.

Algorithms↗

The significance of circumscribed malignant mammographic masses in the surveillance of BRCA 1/2 gene mutation carriers.

Breast cancers in gene mutation carriers may escape mammographic detection because of rapid growth and tumor expansion. Therefore, they may mimic benign lesions on the mammogram. Twenty-nine BRCA 1/2 mutation carriers under surveillance developed 31 breast cancers between 1994 and 2001 at a mean age of 44.2 years. Controls were 63 women with 67 breast cancers in the same period at a mean age of 53.8 years, also under surveillance because of a life time risk of at least 15%. In 26% of the carriers vs. 48% of the controls, mammography was the method that first suspected a malignancy. Seven radiologists performed a retrospective review of the original mammograms to establish technical assessment, with special attention for circumscribed lesions and estimated probability of malignancy. In the mutation carriers seven (23%) circumscribed non-calcified mammographic masses were found and three in the controls (4.5%) P=0.01. These masses were proven to be malignant. In both groups around 70% of these fast-growing circumscribed lesions were detected by the patients. The masses were situated in breasts with a good interpretable breast pattern. BRCA 1/2 mutation carriers had a significantly higher percentage of circumscribed non-calcified mammographic masses that proved to be malignant. These mammographic lesions in women at high risk should be described as at least Birads 0 and worked-up with ultrasound and needle biopsy.

Adult↗

Reduction in the number of sentinel lymph node procedures by preoperative ultrasonography of the axilla in breast cancer.

Currently, breast cancer patients without clinically suspicious lymph nodes are candidates for sentinel lymph node procedures (SLNPs). The aims of this study were to investigate whether preoperative axillary ultrasonography and fine-needle aspiration cytology (FNA) can reduce the number of the more time-consuming SLNPs, and to identify a subset of quantitative nodal features to predict metastatic involvement. 268 axillae were ultrasonographically examined. FNA was performed on suspicious nodes (smallest diameter > or =5 mm or atypical cortex appearance). SLNP was omitted if a tumour-positive node was found on FNA. Length, width, maximum cortex thickness and appearance of cortex and hilus were ultrasonographically established. In 93 axillae (35%), at least one node was detected with ultrasound. FNA was performed once per axilla on 66 nodes; 37 (56%) contained tumour cells. 31% of all tumour-positive axillae (macro-+micrometastases) was found by ultrasound and FNA (37/121). 41% of all axillae containing macrometastases was found by ultrasound and FNA (36/87). SLNPs were reduced by 14% (37/268). Maximum cortex thickness is the main feature to predict metastatic involvement (area under Receiver Operating Characteristic (ROC) curve (A(Z))=0.87).

Adult↗

Displacement of breast tissue and needle deviations during stereotactic procedures.

RATIONALE AND OBJECTIVES: The aim of this study was to quantify the displacement of breast tissue and the inaccuracy of needle positioning for biopsy (14-gauge) and localization (19.5-gauge) needles. METHODS: For displacement of breast tissue, differences between the coordinates of identifiable microcalcifications in the images before (baseline) and after needle positioning were analyzed (n = 52). For accuracy of needle positioning, differences between the coordinates of the needle tip and the target were analyzed in breast tissue (n = 97) and in air (n = 246). RESULTS: Average target displacement was 2.1 mm for biopsy needles (95% prediction interval [PI] 0.6-7.8) and 1.0 mm (95% PI 0.3-3.9) for localization needles. Mean inaccuracy of needle positioning in breast tissue was 1.1 mm (95% PI 0.4-3.0) and 1.8 mm (95% PI 0.7-4.6) for biopsy and localization needles, respectively. CONCLUSIONS: Tissue and needle displacements cause a total positioning error of 2.4 mm in stereotactic core biopsy, which will limit the attainable diagnostic accuracy.

Biopsy, Needle↗

Improved sentinel node visualization in breast cancer by optimizing the colloid particle concentration and tracer dosage.

Faint lymph uptake may hamper sentinel node (SN) identification by scintigraphy and subsequent gamma probe localization. The aim of the present study was to evaluate an adjustment in the colloid particle concentration and tracer dosage to optimize mammary lymphoscintigraphy. Scintigraphy was performed in 151 patients with a palpable breast carcinoma and clinically negative axilla: for the first 75 patients (group A) a standard labelling of 0.5 mg nanocolloid with 99Tcm was performed, for the subsequent 76 patients (group B) the labelling dilution volume was reduced from 4 to 2 ml. For both groups the volume of injection was 0.2 ml. Lymph node uptake was evaluated by a 4-step visual score (from 0 = absent to 3+ = very intense), and by count quantification of at 4 h in the first draining SN. The SN visualization rate increased from 93% (70/75) in group A (mean dosage 93.4 MBq, range 57-130 MBq) to 99% (75/76) in group B (mean dosage 106.5 MBq, range 74-139 MBq). The percentage of patients with uptake 3+ was significantly higher (P = 0.001) in group B (51% vs 35% in group A). SN counts were significantly higher for group B (P<0.001). The percentage of patients with less than 2000 counts/node diminished from 45% in group A to 9% in group B (P = 0.001). In group B (P = 0.033) more lymph channels (53% vs 35% in group A) were visualized and for a longer time (26% vs 4% at 4 h). Axillary drainage was seen in 96% in group A and 98% in group B whereas non-axillary drainage was observed in 19% and 25%, respectively. Intraoperative SN identification rate was 97% in group A and 100% in group B. SN metastases were found in 41% of group A and 47% of group B. It is concluded that enhancement of colloid particle concentration and adjustment of tracer dosage led to improved SN identification by substantial increase in lymph node uptake and lymph vessel depiction. A significant reduction of cases with faint SN uptake enables better surgical efficacy.

Adult↗

Changes in local pulmonary injury up to 48 months after irradiation for lymphoma and breast cancer.

PURPOSE: To assess the recovery from early local pulmonary injury after irradiation and to determine whether regional differences exist. METHODS: For 110 patients treated for breast cancer or malignant lymphoma, single photon emission computed tomography (SPECT) perfusion and ventilation scans and CT scans were made before, 3, 18, and 48 months after radiotherapy. Dose-effect relations for changes in local perfusion, ventilation, and density were determined for each individual patient using spatially correlated SPECT and CT data sets, for each follow-up period. Average dose-effect relations for both subgroups were determined, as well as dose-effect relations for different regions. RESULTS: In general, partial improvement of local pulmonary injury was observed between 3 and 18 months for each of the three endpoints. After 18 months, no further improvement was seen. Patients with breast cancer and malignant lymphoma showed a similar improvement (except for the perfusion parameter), which was attributed to a recovery from the early radiation response and could not be explained by contraction effects of fibrosis of lung parenchyma. No regional differences in radiosensitivity 18 months after treatment were observed, except for the dorsal versus ventral region. This difference was attributed to a gravity-related effect in the measuring procedure. CONCLUSION: For all patients, a partial recovery from early local perfusion, ventilation, and density changes, was seen between 3 and 18 months after radiotherapy. After 18 months, local lung function did not further improve (lymphoma patients).

Adolescent↗

Radiation dose-effect relations and local recovery in perfusion for patients with non-small-cell lung cancer.

PURPOSE: To determine local dose-effect relations for lung perfusion and density changes due to irradiation for patients with non-small-cell lung cancer (NSCLC) and to quantify the effect of reperfusion. METHODS AND MATERIALS: For 25 NSCLC patients and a reference group of 81 patients with healthy lungs, registered single photon emission computed tomography (SPECT) lung perfusion and CT scans were made, before and after radiotherapy. Average dose-effect relations for perfusion and CT-density changes were calculated and compared with the dose-effect relation of the reference group. On the basis of these dose-effect relations, the post-RT perfusion was predicted for each patient and compared to the measured post-RT perfusion. RESULTS: Well-perfused lung regions of the NSCLC patients showed the same dose-effect relation as the reference patients. By comparing predicted and measured post-treatment perfusion scans, regions of reperfusion could be determined for 18 of 25 NSCLC patients but for none of the reference patients. CONCLUSION: Well-perfused lung tissue of patients with NSCLC behaves like healthy lung tissue with respect to radiation. The dose-effect relation for perfusion and CT density was extended for doses up to 80 Gy. Radiation damage in poorly perfused lung regions was less than predicted as a consequence of local reperfusion.

Algorithms↗

Reliability of lymphoscintigraphy in indicating the number of sentinel nodes in melanoma patients.

BACKGROUND: This study was undertaken to establish the reliability of lymphoscintigraphy in indicating the number of sentinel nodes in patients with melanoma. METHODS: Lymphoscintigraphy was performed with dynamic imaging after injection of 60 MBq 99mTc-nanocolloid (1.6 mCi) and static imaging after 2 hours in 200 patients with clinically localized primary melanoma of the skin. The following day, sentinel nodes were retrieved with the blue dye technique and a gamma detection probe (Neoprobe 1000/1500). The discrepancies between the number of sentinel nodes indicated by lymphoscintigraphy and the actual number of sentinel nodes as established by the surgeon were evaluated. RESULTS: Lymphoscintigraphy showed drainage to 393 sentinel nodes in 255 lymphatic fields in 199 patients. In 48 lymphatic fields (19%) in 46 patients (23%), the number of sentinel nodes was different from the number that was visualized with scintigraphy. Additional sentinel nodes were found by the surgeon because a lymphatic vessel was not seen on the lymphoscintigraphy (43%), because a sentinel node was not visualized separately from other hot nodes or vessels or the injection site (36%), or because a sentinel node was blue and not hot (4%). Fewer sentinel nodes were found than suggested by scintigraphy because a lymphangioma was mistaken for a sentinel node (4%) or because a single elongated node was depicted as two hot spots (6%). CONCLUSIONS: Although lymphoscintigraphy is indispensable for lymphatic mapping, the predicted number of sentinel nodes is accurate in only 81% of lymph node fields. The limited discriminating power of the gamma camera is an important cause of discrepancies.

Adolescent↗

The accuracy of image registration for the brain and the nasopharynx using external anatomical landmarks.

We investigated the accuracy of 3D image registration using markers that are repeatedly applied to external anatomical landmarks on the head. The purpose of this study is to establish a lower limit of the errors that would occur in, for instance, MRI-SPECT matching, which in some situations can only be achieved using external landmarks. Marker matching was compared with (single-modality) volume matching for 20 MRI scans. The results were compared with a published expression for the target registration error (TRE) which gives the 3D distribution of the mismatch between both scans. It was found that the main error source is reapplying the external markers on the anatomical landmarks. The published expression describes the relative distribution of the TRE in space well, but tends to underestimate the actual registration error. This deviation is due to anisotropy in the error distribution of the marker position (errors in the direction perpendicular to the skin surface are in general much smaller than errors in other directions). A simulation of marker matching with anisotropy in the errors confirmed this finding. With four reapplied markers, the TRE is 6 mm or smaller in most regions of the head.

Brain↗

Evaluation of mammary lymphoscintigraphy by a single intratumoral injection for sentinel node identification.

UNLABELLED: The aim of this study was to evaluate the findings of mammary lymphoscintigraphy by a single intratumoral injection in 150 patients with breast carcinoma: 100 patients (group A) investigated in the validation phase of the study and 50 (group B) studied after the tracer dose was optimized. METHODS: Immediately after injection of 99mTc-nanocolloid using a 25-gauge needle and a 0.2-mL volume, simultaneous anterior and lateral images were acquired with a dual-head gamma camera during 20 min followed by sequential static anterior and prone lateral breast images after 30 min and after 2 and 4 h. 57Co-assisted skin marking defined the sentinel node location for subsequent gamma probe, blue dye-guided sentinel node biopsy. RESULTS: In group A (mean dose, 61.6 MBq; range, 42-88 MBq) scintigraphy revealed lymph nodes in 83 patients (83%), with an increase in the rate of visualization from 72% for the first 40 patients to 90% for the last 60; patient age (P = 0.01) and administered tracer dose (P = 0.04) were found to be significant factors for visualization, with optimal results obtained from doses higher than 65 MBq. Lymph nodes were visible in 34 patients (41%) during the first 30 min after injection, whereas in 49 patients appearance occurred at 2-4 h. A total of 97 lymphatic basins were visualized (80 axillary, 3 clavicular, 14 internal mammary). In group B (mean dose, 90.8 MBq; range, 68-124 MBq), the visualization rate was 94%, with early lymph node appearance in 27 patients (57%) and a total of 53 basins (45 axillary, 8 internal mammary). In combination with intraoperative blue dye mapping and y probing, the identification rate increased to 90% in group A and 98% in group B. Prone lateral images contributed to identification of intramammary lymph nodes in a total of 14 patients and axillary nodes close to the injection site in 8 other patients. CONCLUSION: Mammary lymphoscintigraphy by single intratumoral injection is a valid method for lymphatic mapping and identification of both axillary and nonaxillary sentinel nodes. Lymph node visualization appears to be improved with higher tracer doses. The compactness of the injection site enables high-quality additional lateral images that can depict intramammary or axillary lymph nodes adjacent to the injection site.

Adult↗

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↗

[Contribution of nuclear medicine to lymphatic mapping and sentinel node identification in oncology].

An overview of the current applications of nuclear medicine for lymphatic mapping and sentinel node identification is given. The validation of the sentinel node concept in oncology has led to the rediscovery of lymphoscintigraphy. By combining preoperative lymphatic mapping with intraoperative gamma probe detection this nuclear medicine procedure is increasingly used to identify and detect the sentinel node in melanoma, breast cancer, and in other malignancies such as penile cancer and vulvar cancer. In melanoma, the adequate combination of dynamic and static gamma camera images enables lymph node visualization with identification of the sentinel node in more than 97% of the cases. The variability in drainage in areas such as trunk, head and neck makes lymphoscintigraphy indispensable in protocols of sentinel node biopsy. The reproducibility of lymphoscintigraphy for sentinel node detection varies from 85% to 88% and the method appears to have a high interobserver agreement. In contrast to the procedure of lymphoscintigraphy for melanoma, for which the only dilemma remaining is probably the choice of the tracer, in breast cancer there has not yet been reached a consensus for many topics such as tracer characteristics, injection volume, and principally the site of administration. Lymphoscintigraphy by subdermal tracer administration is able to detect axillary lymph nodes in 98% of the cases but the method is accompanied by a low visualization incidence (2%) of drainage outside the lower axilla such as the internal mammary chain. This latter aspect appears to occur in 16% to 35% in the series using peri- or intratumoural administration with an axillary rate of visualization of 75% to 98%. Although peritumoural administration is predominantly associated with late lymph node detection, the early appearance observed after subdermal and intratumoural tracer injection justifies the obtention of early gamma camera images. The strategies of identification of the sentinel node depend strongly on the results of lymphoscintigraphy. In melanoma, the rapid lymphatic drainage and the visualization of afferent lymphatic vessels enables sentinel node identification by lymphoscintigraphy in almost the totality of the cases and intraoperative probe detection may subsequently be performed. In breast cancer, the slower drainage pattern may hamper image interpretation and diagnostic conclusion. Considering the first appearing node and the visualization of an afferent lymphatic vessel as the major criteria to identify the sentinel node, scintigraphy may be considered conclusive in approximately 75% of the cases, and not conclusive in about a fourth part of the cases in which 2 or more lymph nodes appear simultaneously without lymph vessel delineation. When lymphoscintigraphy is not conclusive, additional lymphatic mapping with blue dye is recommended to definitively identify the sentinel node. The use of nuclear medicine techniques for the sentinel node procedure will become an important part of clinical work in the nuclear medicine and surgical oncology practice of the next years. Principally mammary lymphoscintigraphy demands from the nuclear medicine community and allied disciplines a prompt standardization of the technique to solving some controversial aspects such as tracer requirements, administration route and interpretation criteria.

Biopsy↗

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↗

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↗

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↗