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Purpose: To investigate if a local dose-effect (LDE) relationship for perfusion loss improves the NTCP model fit for SBRT induced radiation pneumonitis (RP) compared to conventional LDEs., Methods and Materials: Multi-institutional data of 1015 patients treated with SBRT were analyzed. Dose distributions were converted to NTD with α/β = 3 Gy. The Lyman-Kutcher-Burman NTCP model was fitted to the incidence grade ≥2 RP by maximum likelihood estimation with mean lung dose (MLD), equivalent uniform doses (EUD) using three LDE functions (power-law (EUD power ), logistic with 2 free parameters (EUD log-free ) and logistic with fixed parameters describing local perfusion loss (EUD Perfusion )) and volume above a threshold dose (V x ). Models were compared with the Akaike weights (Aw) derived from the Akaike information criteria (AIC)., Results: The median time to grade ≥2 RP was 4.2 months and plateaued after 17 months at 5.4%. A strong dose-effect relationship for RP incidence was observed. The EUD Perfusion based NTCP model had the lowest AIC. The Aw were 0.53, 0.19, 0.11, 0.11, 0.05 for the EUD Perfusion , V x , MLD, EUD log-free and EUD power LDEs respectively., Conclusion: A LDE for perfusion loss provided modest improvement in NTCP model fit for SBRT induced radiation pneumonitis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To correlate radiotherapy (RT) dose to acute esophagitis (AE) by means of FDG-PET scans acquired after concurrent chemo-radiotherapy (cCRT) for locally advanced non-small-cell lung cancer (NSCLC)., Materials and Methods: Patients treated with 24 × 2.75 Gy were selected on presence of a post-RT PET (PET(post)) scan acquired within 3 months after cCRT. The value of PET(post) in relation to AE was evaluated by comparing the mean esophageal SUV of the highest 50% (mathematical left angle bracket SUV(50%) mathematical right angle bracket) between gr < 2 and gr ≥ 2AE. The local dose on the esophagus wall was correlated to the SUV and modeled using a power-law fit. The Lyman-Kutcher-Burman (LKB) model was used to predict gr ≥ 2AE. The local dose-response relation was used in the LKB model to calculate the EUD. Resulting prediction accuracy was compared to D(mean), V(35), V(55) and V(60)., Results: Eighty-two patients were included (gr < 2 = 25, gr ≥ 2=57). The mathematical left angle bracket SUV(50%) mathematical right angle bracket ≥ was significantly higher for gr ≥ 2AE (2.2 vs. 2.6, p < 0.01). The LKB parameters (95% CI) were n = 0.130 (0.120-0.141), m = 0.25 (0.13-0.85) and TD(50) = 50.4 Gy (37.5-55.4), which resulted in improved predictability of AE compared to other predictors., Conclusion: Esophageal uptake of FDG post-cCRT reflects AE severity. Predictability of grade ≥ 2AE was improved by using the local dose-SUV response model, with narrow confidence intervals for the optimized LKB parameters., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: To correlate acute esophageal toxicity with dosimetric and clinical parameters for non-small cell lung cancer (NSCLC) patients treated with radiotherapy (RT) alone or with chemo-radiotherapy (CRT)., Patients and Methods: We analyzed the data of 156 patients with medically inoperable or locally advanced NSCLC. Seventy-four patients were irradiated with high dose RT only, 45 patients with sequential CRT (Gemicitabine/Cisplatin) and 37 patients with concurrent CRT (Cisplatin daily 6 mg/m(2)). The radiation dose delivered ranged from 49.5 to 94.5 Gy (2.25-2.75 Gy per fraction) with an overall treatment time of 5-6 weeks. For all patients the maximal acute esophageal toxicity (RTOG/EORTC criteria) was scored and related to dose-volume parameters, as well as to clinical and treatment-related parameters. All parameters were tested univariable and multivariable in a binary logistic regression model. The toxicity data of a homogeneous subgroup was fitted to the Lyman-Kutcher-Burman model., Results: Grade 2 acute esophageal toxicity or higher occurred in 27% (n=42) of the patient population of which nine patients developed grade 3 toxicity and one patient grade 4. All 10 patients with grade>or=3 esophageal toxicity received concurrent CRT. At multivariable analysis, the most significant clinical parameter to predict acute esophageal toxicity was the concurrent use of CRT. The most significant dosimetric parameter was the esophagus volume that received at least 35 Gy. The data of the patients who did not receive concurrent CRT were well described by the Lyman-Kutcher-Burman normal tissue complication probability model. The optimal fit of the data of non-concurrent treated patients to this model was obtained using the following values for the parameters: TD(50)=47 Gy (41-60 Gy), n=0.69 (0.18-6.3) and m=0.36 (0.25-0.55) where the numbers between brackets denote the 95% confidence interval. Acute esophageal toxicity was not significantly increased for patients treated with sequential CRT., Conclusion: Both concurrent CRT and the volume that receives at least 35 Gy were predictors of acute esophageal toxicity.

In this review of current clinical practice of set-up error verification by means of portal imaging, we firstly define the various types of set-up errors using a consistent nomenclature. The different causes of set-up errors are then summarized. Next, the results of a large number of studies regarding patient set-up verification are presented for treatments of patients with head and neck, prostate, pelvis, lung and breast cancer, as well as for mantle field/total body treatments. This review focuses on the more recent studies in order to assess the criteria for good clinical practice in patient positioning. The reported set-up accuracy varies widely, depending on the treatment site, method of immobilization and institution. The standard deviation (1 SD, mm) of the systematic and random errors for currently applied treatment techniques, separately measured along the three principle axes, ranges from 1.6-4.6 and 1.1-2.5 (head and neck), 1.0-3.8 and 1.2-3.5 (prostate), 1.1-4.7 and 1.1-4.9 (pelvis), 1.8-5.1 and 2.2-5.4 (lung), and 1.0-4.7 and 1.7-14.4 (breast), respectively. Recommendations for procedures to quantify, report and reduce patient set-up errors are given based on the studies described in this review. Using these recommendations, the systematic and random set-up errors that can be achieved in routine clinical practice can be less than 2.0 mm (1 SD) for head and neck, 2.5 mm (1 SD) for prostate, 3.0 mm (1 SD) for general pelvic and 3.5 mm (1 SD) for lung cancer treatment techniques.

Purpose: To assess for locoregional irradiation of breast cancer patients, the dependence of cardiac (cardiac mortality) and lung (radiation pneumonitis) complications on treatment technique and individual patient anatomy., Materials and Methods: Three-dimensional treatment planning was performed for 30 patients with left-sided breast cancer and various breast sizes. Two locoregional techniques (Techniques A and B) and a tangential field technique, including only the breast in the target volume, were planned and evaluated for each patient. In both locoregional techniques tangential photon fields were used to irradiate the breast. The internal mammary (IM)-medial supraclavicular (MS) lymph nodes were treated with an anterior mixed electron/photon field (Technique A) or with an obliquely incident mixed electron/photon IM field and an anterior electron/photon MS field (Technique B). The optimal IM and MS electron field dimensions and energies were chosen on the basis of the IM-MS lymph node target volume as delineated on CT-slices. The position of the tangential fields was adapted to match the IM-MS fields. Dose-volume histograms (DVHs) and normal tissue complication probabilities (NTCPs) for the heart and lung were compared for the three techniques. In the beam's eye view of the medial tangential fields the maximum distance of the heart contour to the posterior field border was measured; this value was scored as the Maximum Heart Distance., Results: The lymph node target volume receiving more than 85% of the prescribed dose was on average 99% for both locoregional irradiation techniques. The breast PTV receiving more than 95% of the prescribed dose was generally smaller using Technique A (mean: 90%, range: 69-99%) than using Technique B (mean: 98%, range: 82-100%) or for the tangential field technique (mean: 98%, range: 91-100%). NTCP values for excess cardiac mortality due to acute myocardial ischemia varied considerably between patients, with minimum and maximum values of 0.1 and 7.5% (Technique A), 0.1 and 5.8% (Technique B) and 0.0 and 6.1% (tangential tech.). The NTCP values were on average significantly higher (P<0.001) by 1.7% (Technique A) and 1.0% (Technique B) when locoregional breast irradiation was given, compared with irradiation of the left breast only. The NTCP values for the tangential field technique could be estimated using the Maximum Heart Distance. NTCP values for radiation pneumonitis were very low for all techniques; between 0.0 and 1.0%., Conclusions: Technique B results in a good coverage of the breast and locoregional lymph nodes, while Technique A sometimes results in an underdosage of part of the target volume. Both techniques result in a higher probability of heart complications compared with tangential irradiation of the breast only. Irradiation toxicity for the lung is low in all techniques. The Maximum Heart Distance is a simple and useful parameter to estimate the NTCP values for cardiac mortality for tangential breast irradiation.

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.

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.

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.

The first aim of this study was to quantify estimated translational setup deviations of patients treated with a wedged pair of oblique beams for parotid gland and tonsillar tumors, using portal imaging. The second aim was to design an off-line setup verification procedure, to improve the setup accuracy, if necessary. Thirty-one patients were treated with two conformal fields (anterior-oblique and posterior-oblique). The patients were immobilized with a head cast. For the last 10 patients, the rigidity of the cast was improved while, in addition, wax molds with metal markers were placed into the outer ear for image correlation. Portal images were acquired about weekly. Setup deviations were analyzed, using anatomical structures and, when available, metal markers for image matching. The consistency of the deviations was determined by the correlation between deviations in the cranio-caudal direction, as measured from both beams. When the deviations were consistent, the translational setup deviation during a treatment session could be described by a three-dimensional (3D) vector. A setup verification procedure was designed using a computer simulation. The statistics of the 3D setup deviations were used as input. The output consisted of the resulting setup accuracy and workload (i.e., the number of setup corrections and portal images). Using the anatomical structures for image correlation, the deviations in the cranio-caudal direction were not correlated, either for the old or the improved cast. However, by using the metal markers, the deviations were correlated and a 3D analysis could be performed. The standard deviations, averaged over the three directions, were equal to 1.8 and 1.4 mm for the distribution of systematic and random deviations, respectively. Application of a setup verification procedure, with 0.7 corrections on the average per patient, could potentially reduce the percentage of 3D systematic deviations larger than 4 mm from 30 to 2%. It can be concluded that it was not possible to obtain consistent translational setup deviations, due to rotations. To quantify 3D translational setup deviations, it was necessary to use additional metal markers, which were visible in the portal images of both beams. A further improvement of the setup accuracy is possible by using an off-line setup verification procedure.

Purpose: To predict the pulmonary function 3-4 months after irradiation for malignant lymphoma from the three-dimensional (3-D) dose distribution., Methods: Dose-effect relations for the relative reduction of local perfusion (Q) and local ventilation (V), were calculated in 25 patients, using correlated SPECT (Single Photon Emission Computed Tomography) and CT data. By combining the 3-D dose distribution of an individual patient with the dose-effect relations averaged over all patients, the average reduction of local Q and V (i.e., the overall response parameters) in the whole lung was estimated for each patient. Correlation coefficients were calculated between these overall response parameters and the change in standard lung function tests. In addition, the relation between the overall response parameters and the incidence of radiation pneumonitis was determined., Results: The overall response parameter for perfusion was correlated with the change in standard lung function tests, with correlation coefficients varying between 0.53 (p = 0.007) and 0.71 (p < 0.001) for the change of Vital Capacity and Forced Expiratory Volume at 1 s, respectively. For the overall response parameter for ventilation similar correlations were observed. Four out of the 25 patients developed radiation pneumonitis; in these four patients the overall response parameter for perfusion was on average somewhat higher (13.2 +/- 1.4% (1 standard error of the mean)) than in patients without radiation pneumonitis (10.5 +/- 1.0%), but this difference was not significant. A higher incidence of radiation pneumonitis was observed for larger values of the overall response parameter for perfusion; in patient groups with an overall response parameter for perfusion of 0-5%, 5-10%, 10-15%, and 15-20%, the incidence of radiation pneumonitis was 0 (0/1), 10 (1/10), 13 (1/8) and 33% (2/6), respectively., Conclusion: By combining the 3-D dose distribution with the average dose-effect relations for local perfusion or ventilation, an overall response parameter can be calculated prior to irradiation, which is predictive for the radiation-induced change in the overall pulmonary function, and possibly for the incidence of radiation pneumonitis, in this group of patients.

The purpose of this study was to investigate the accuracy of field matching in patients treated by irradiation of the breast and adjacent lymph nodes. Field matching is performed by the radiographers during each session on a match line drawn on the patient's skin. Field edge positions were assessed in the cranial match plane of tangential breast fields and supraclavicular-axillary fields using an electronic portal imaging device and match line markers placed on the skin of the patients. The mean gap/overlap of the four fields for individual patients during each treatment session, derived from 374 marker projections, was +0.5 mm indicating that no systematic gap or overlap was observed. The uncertainty in the position of the four fields with respect to the match plane ranges from 3.1 to 5.1 mm (1 SD) for the individual patients. Gaps and overlaps between fields were also related to an absolute match line position, found by comparison of simulator and portal images, showing a small systematic uncertainty of 2.4 mm and a standard deviation of 3.3 mm. It can be concluded that the use of an electronic portal imaging device in combination with match line markers is a good method to quantify the accuracy of field matching in vivo. The results showed good stability and reproducibility in the field matching region for this treatment technique of breast cancer irradiation.

Purpose: To estimate the dose-effect relations for local functional (ventilation and perfusion) and structural (density) changes of the lung, 3-4 months after irradiation., Methods: Twenty-five patients with malignant lymphoma were irradiated with a (modified) mantle field to an average dose of 38 Gy, given in 21 fractions. Single photon emission computed tomography (SPECT) ventilation (V) and perfusion (Q) scans, and CT scans were performed before and 3-4 months after radiation treatment. The three-dimensional dose distribution was calculated using the CT data. After correlation of SPECT and CT data sets, the average post-treatment value of V, Q and lung density per voxel was calculated relative to the pre-treatment value, per dose interval of 4 Gy. Subsequently, the dose-effect relations in each patient were normalized to the average value per voxel in the dose interval of 0-12 Gy. In addition, in each dose interval of 4 Gy the fraction of patients with changes larger than 20% was calculated for all three parameters. The dose-effect relations for perfusion and ventilation normalized to the low-dose regions, and the dose-incidence curves for the fraction of patients with changes larger than 20% were fitted for all three parameters, using a logistic model., Results: Marked changes in the distribution of V and Q were found after irradiation. Prior to normalization to the low-dose regions, a change in V and Q was found in most patients in the dose interval of 0-12 Gy, varying from an increase of 37% to a decrease of 10%, which was followed by a decreasing trend at higher doses. The increase in the low-dose regions indicated a redistribution phenomenon, the magnitude of which was dependent of the irradiated volume. The logistic fit of the dose-effect relations for Q and V, normalized to the low-dose regions, resulted in values for D50 of 51 Gy and 54 Gy (given in 21 fractions on average), respectively, and for the steepness parameter k of 4.2 and 4.0, respectively. The logistic fit for the dose-incidence curves for Q, V and lung density resulted in values for D50 and k of 38 Gy, 37 Gy, 44 Gy and 10.3, 7.8 and 9.4, respectively., Conclusions: With the combined use of SPECT and CT scans, we have obtained dose-effect relations for local functional and structural damage in the lung, 3-4 months after irradiation.

Purpose: The purpose of this study was to quantify the correlation between irradiated small bowel volume and late occurring small bowel complications., Methods: Small bowel volumes in the high-dose region were measured using orthogonal barium films for 203 patients treated for rectal carcinoma with pelvic postoperative radiotherapy to 50 Gy in an EORTC multicentric study., Results: The 5-year estimate of late pelvic small bowel obstruction requiring surgery was 11%. No correlation between the irradiated small bowel volume and obstruction was detected. The actuarial 5-year estimate of chronic diarrhea varied from 31% in patients with irradiated small bowel volumes below 77 cm3 to 42% in patients with volumes over 328 cm3. This correlation was significant in the univariate and multivariate analysis (p = 0.025). The type of rectal surgery significantly influenced the incidence of chronic diarrhea and malabsorption, the actuarial 5-year estimate being 49% and 26% after low anterior resection and abdominoperineal resection, respectively (p = 0.04)., Conclusions: This study demonstrated that there is a volume-effect in radiation-induced diarrhea at a dose of 50 Gy in 25 fractions. No volume-effect for small bowel obstruction was detected at this dose-level in pelvic postoperative radiotherapy. A review of the literature data on small bowel obstruction indicates that the volume effect at this dose level can only be demonstrated in patients who were treated with extended field radiotherapy (estimated small bowel volume 800 cm3) after intra-abdominal surgery.

The purpose of this study was to analyse whether the intended patient setup, based on a CT scan, was different from the setup at the simulator. Furthermore, we investigated how these possible transfer errors between the planned patient setup and the actual simulator setup affected the resulting overall treatment setup accuracy. Two groups, of 15 prostate patients each, were studied. For one group (group II), the simulation time was about twice as large as for the other (group I), since digitally reconstructed radiographs (DRRs) were used to get a good visual agreement between the intended and the simulator setup. For the purpose of this study DRRs were also calculated for the patients in group I, and for both groups DRRs were matched with the simulator images to obtain quantitative data of the transfer errors. The resulting overall treatment setup accuracy was determined by comparing the DRRs with portal images. For group I, the standard deviations (SD) of the differences between the DRRs and the simulator images ('transfer errors') were 1.5 mm and 4.5 mm in the lateral (x) and cranio-caudal (y) direction, respectively. For group II the SDs were smaller: 1.4 mm and 1.5 mm in the x- and y-direction, respectively. For both groups, the magnitude of the overall mean was less than 1.3 mm. For group I, the SDs of the resulting overall setup deviations during treatment were 1.6 mm and 4.1 mm in the x- and y-direction, respectively. For group II, these figures were 2.4 mm and 2.6 mm, respectively. For both groups, the magnitude of the overall mean was less than 1.0 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

A method is described to determine accurately skin redness during a course of radiotherapy using reflectance spectroscopy utilizing information from across the visible spectrum according to the L*a*b* color coordinate system. The method was used to quantify the development of skin erythema during and after electron beam irradiation of the chest wall following mastectomy. A number of factors were identified which could influence the wide variation in response seen between patients. These were: intra- and inter-observer variation; intra- and inter-patient variation and variation in the actual dose delivered. Statistical analysis, including an analysis of variance of inter- and intra-patient variation, revealed that the major factor that accounts for the observed difference between patients is a true inter-patient variation, with a coefficient of variation, corrected for intra-patient variation, of 43%. Within the narrow dose range administered in this study, there was no demonstrable dose-effect relationship, raising questions about the role of cell death in the basal layer of the epidermis in the pathogenesis of radiation induced erythema.

The purpose of this study was to establish which level of geometrical accuracy can be obtained during radiotherapy, using portal image analysis, with a minimum number of patient set-up measurements and corrections. A set-up verification and correction procedure using decision rules for improving the set-up of a patient during radiotherapy was investigated by means of a computer simulation. In this simulation study, set-up deviations were assumed to be the sum of random and systematic deviations and varying ratios of random and systematic deviations were studied. The distribution of random deviations (SD equal to sigma) was assumed to be equal for all patients of a specific treatment site. Set-up deviations are measured during the first N consecutive fractions after the start of the treatment or after a patient set-up correction. A set-up is corrected when the deviation averaged over these measurements is larger than an N-dependent action level. This action level is specified by alpha/square root of N, in which alpha is a variable initial action level parameter. After the start of the treatment or after each correction, Nmax measurements are made to decide on a possible (further) correction. By varying alpha and Nmax, the relation between the overall accuracy and the workload has been analyzed. It was possible to obtain a resulting overall accuracy level which is almost independent of the initial distribution of systematic deviations.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: To determine dose-effect relations for regional lung-function changes after radiotherapy., Methods: Single Photon Emission Computed Tomography (SPECT) was performed to quantify regional ventilation and perfusion. CT scans were used to calculate the three-dimensional (3-D) dose distribution. Both SPECT and CT scans were performed prior to radiotherapy and 5 months after the start of the treatment. To obtain combined 3-D information on ventilation, perfusion and dose, the SPECT data were correlated with the corresponding CT data. The relative changes in ventilation and perfusion were calculated in each SPECT voxel (voxel size about 6 x 6 x 6 mm) and related to the dose in that voxel. The average relative changes were determined per dose interval of 4 Gy. This procedure was evaluated using the data from five patients treated for Hodgkin's disease with mantle field irradiation with a prescribed total dose of 40-42 Gy., Results: Dose-effect relations for perfusion were observed in all patients, while in four of the five patients, a dose-effect relation was found for ventilation. The maximal uncertainty of the calculated radiation dose was 11%: a difference between the position of the patient during treatment and during CT scanning caused a maximal dose uncertainty of 6%, while the accuracy of the dose calculation algorithm itself was estimated to be within 5%., Conclusion: The results indicate that the combined use of SPECT and CT information is an effective method for determining dose-effect relations for regional lung function parameters in each individual patient.

An electronic portal imaging device (EPID) was used to detect patient setup displacement during the course of a 3-field pelvic irradiation of two groups of patients: 10 rectal and 10 prostate carcinomas. These patients were irradiated with conventional treatment techniques in routine clinical practice. A total of 469 portal images and 60 simulator films were used to determine the values of setup deviations in the X- Y- and Z-directions of a fixed coordinate system, corresponding to the medio-lateral, cranio-caudal and antero-posterior direction, respectively. The absolute displacement averaged over all setups and patients ranged between 0.4 mm and 1.4 mm with a standard deviation (S.D.) of 1.6-3.9 mm. The overall distribution along each direction could be separated into a distribution of random deviations (S.D.s ranging from 1.2 to 2.8 mm) around the mean deviation of each patient and a distribution of the means themselves: the distribution of systematic deviations (S.D.s ranging from 1.0 to 2.6 mm). Significant gradual displacement as a function of time was detected in 5 out of the 20 patients, 2 in the rectum and 3 in the prostate group. This "time trend" was found along each of the 3 directions specified. The magnitude of the time-dependent displacement throughout the course of treatment ranged between 4 and 11 mm. It can be concluded that for treatments requiring a high level of precision, portal images should be made and analyzed during the whole treatment course in order to detect and correct significant time trends.

Between 1984 and 1988, 206 patients were treated with pelvic radiotherapy after macroscopically complete surgery for rectal or (recto)sigmoid cancer. Depending on an estimation of the amount of small bowel in the intended treatment volume a total dose was, in general, 45 or 50 Gy. An additional boost of 10 Gy was given to 6 patients because of microscopically involved surgical margins. For tumor stage B a statistically significant trend (p = 0.017) for higher local control with higher total dose was observed comparing patients treated with a total dose of 45 Gy or less, with more than 45 Gy but less than 50 Gy or with a total dose of 50 Gy or more. This finding illustrates the impact of total dose on local control for postoperative radiotherapy for rectal carcinoma.

A design procedure of a patient setup verification protocol based upon frequent digital acquisition of portal images is demonstrated with an application for conformal prostatic boost fields. The protocol aims at the elimination of large systematic deviations in the patient setup and includes decision rules which indicate when correction of the patient setup is needed. The decision rules were derived from the results of a theoretical and quantitative analysis of patient setup variations measured in three pelvic fields (one anterior-posterior and two lateral fields) of 105 fractions for nine patients. Deviations in the patient positioning, derived from one field, were quantified as two-dimensional (2-D) displacement vectors in the plane perpendicular to the beam axis by alignment of anatomical features in the portal and the simulator image. The magnitude of the overall setup variations along the anterior-posterior, superior-inferior and lateral directions varied between 2.6 and 3 mm (1 S.D.). Inter- and intra-treatment variations could be separated, both having equal magnitudes of 1.7 to 2.2 mm (1 S.D.). In addition, intra-treatment variations appeared to be predictable which was a prerequisite for the development of the decision rules. The 2-D setup deviations, measured in the three fields of one fraction were strongly correlated and a 3-D displacement vector was calculated. Utilization of this 3-D vector in a setup verification protocol may lead to an early detection of systematic setup deviations.

The simultaneous boost technique in radiotherapy consists of delivering the boost treatment (additional doses to reduced volumes) simultaneously with the basic (large-field) treatment for all treatment sessions. Both the dose per fraction delivered by the basic-treatment fields and by the boost-treatment fields have to be reduced to end up with the same total dose in the boost volume as in the original schedule, where the basic treatment preceded the boost treatment. These dose reductions and corresponding weighting factors have been calculated using the linear-quadratic (LQ) model and the concept of Normalized Total Dose (NTD). Relative Normalized Total Dose (RNTD) distributions were computed to evaluate the dose distributions resulting for the simultaneous boost technique with respect to acute and late normal tissue damage and tumor control. For the example of the treatment of prostatic cancer the weighting factors were calculated on the basis of the NTD for late normal tissue damage. For the treatment of oropharyngeal cancer the NTD for acute normal tissue damage was used to determine the weighting factors. In this last example a theoretical sparing of late normal tissue damage can be demonstrated. A second advantage of the simultaneous boost technique is that the megavoltage images of the large basic-treatment fields facilitates the determination of the position of the patient with respect to the small boost-treatment fields.

The impact of customized beam shaping was studied for five patients with parotid tumors treated with a paired wedged field technique. For each patient two plans were generated. The standard plan had unblocked portals with field sizes defined by the largest target contour found in any CT slice. In the second plan customized beam's eye view (BEV) designed blocks were added to both beams. The differences in the dose distributions between the two types of plans were evaluated using dose-volume histograms (DVH). As expected, the dose distribution within the target volume showed no difference. However, a considerable sparing of normal tissue was observed for the plans with customized blocks. The volume of unnecessary exposed normal tissue that received more than 90% of the prescribed dose, was reduced by a factor of about 4: from 165 to 44% on average, if the volume is expressed as a percentage of the target volume in each patient. In particular, the homolateral mandible showed a mean decrease of 21% of integral dose when blocks were used. Normal tissue complication probabilities (NTCP) were calculated. For a tumor dose of 70 Gy, the average bone necrosis probability was reduced from 8.4% (no blocks) to 4.1% (blocks). For other normal tissues such as nervous tissue, other soft tissues and bones a substantial reduction of integral dose was found for all patients when individual blocks were used.

The effects of the volume of irradiated small bowel on late small-bowel tolerance was studied, taking into account the equivalent total dose and type of pre-irradiation surgical procedure. A method was developed to estimate small-bowel volumes in the high-dose region of the radiation treatment using CT-scans in the treatment position. Using this method small-bowel volumes were measured for three-field and AP-PA pelvic treatments (165 cm3 and 400 cm3, respectively), extended AP-PA pelvic treatment (790 cm3), AP-PA treatment of para-aortic nodes (550 cm3) and AP-PA treatment of para-aortic and iliac nodes (1000 cm3). In a retrospective study of 111 patients irradiated after surgery for rectal or recto-sigmoid cancer to a dose of 45-50 Gy in 5 weeks, extended AP-PA pelvic treatment (n = 27) resulted in a high incidence of severe small-bowel complications (37%), whereas for limited (three-field) pelvic treatment (n = 84) the complication rate was 6%. These complication data together with data from the literature on postoperative radiation-related small-bowel complications were analysed using the maximum likelihood method to fit the data to the logistic form of the dose-response relation, taking the volume effect into account by a power law. The analysis indicated that the incidence of radiation-related small-bowel complications was higher after rectal surgery than after other types of surgery, which might be explained by the development of more adhesions. For both types of surgery a volume exponent of the power-law of 0.26 +/- 0.05 was established. This means that if the small-bowel volume is increased by a factor of 2, the total dose has to be reduced by 17% for the same incidence of small-bowel complications.

In radiation therapy of breast cancer several photon fields are used. Proper matching of the fields and minimizing the irradiated lung volume can be obtained by suitable beam blocking and appropriate angulation of the gantry, collimator and turntable. To facilitate the simulation procedure a new general method has been developed to calculate these angles, the position of the beam blocks and the field dimensions exactly.

The response of mouse kidneys to multifractionation irradiation using the [51Cr]EDTA clearance method was re-analysed. As previously published, a series of schedules was investigated giving 1,2,4,8,16,32 and 64 equal X-ray doses in an overall treatment time of 3 weeks, using doses per fraction in the range of 0.9 to 17 Gy. The kidney function was assessed from 19 to 55 weeks after irradiation. The decrease of the clearance with time could be characterized by a new, relevant parameter: the relative rate constant for the development of late damage. These rate constants showed well defined dose-response relationships for each fractionation schedule with an estimated maximum rate constant of 0.15 wk-1. Making use of the logistic transformation of the relative rate constant data, the validity of the linear-quadratic (LQ) model was tested directly using proper statistical methods. We showed that only the higher fraction number data (16,32 and 64) could be described by the LQ-model (alpha/beta = 5.0 +/- 0.5 Gy). The deviations from the LQ-model could not be explained by incomplete or slow repair and we concluded that the expression of the clonogenic survival of target cells in the kidney is not sufficiently described by a linear and a quadratic term.