[18F]fluorodeoxyglucose positron emission tomography/computed tomography in combination with clinical data in predicting overall survival in non-small-cell lung cancer patients: A retrospective study.

INTRODUCTION: Positron emission tomography/computed tomography (PET/CT) has an established role in evaluating patients with lung cancer. The aim of this work was to assess the predictive capability of [18F]Fluorodeoxyglucose ([18F]FDG) PET/CT parameters on overall survival (OS) in lung cancer patients using an artificial neural network (ANN) in parallel with conventional statistical analysis. METHODS: Retrospective analysis was performed on a group of 165 lung cancer patients (98M, 67F). PET features associated with the primary tumor: maximum and mean standardized uptake value (SUVmax, SUVmean), total lesion glycolysis (TLG) metabolic tumor volume (MTV) and area under the curve-cumulative SUV histogram (AUC-CSH) and metastatic lesions (SUVmaxtotal, SUVmeantotal, TLGtotal, and MTVtotal) were evaluated. In parallel with conventional statistical analysis (Chi-Square analysis for nominal data, Student's t test for continuous data), the data was evaluated using an ANN. There were 97 input variables in 165 patients using a binary classification of either below, or greater than/equal to median survival post primary diagnosis. Additionally, phantom study was performed to assess the most optimal contouring method. RESULTS: Males had statistically higher SUVmax (mean: 10.7 vs 8.9; p = 0.020), MTV (mean: 66.5 cm3 vs. 21.5 cm3; p = 0.001), TLG (mean 404.7 vs. 115.0; p = 0.003), TLGtotal (mean: 946.7 vs. 433.3; p = 0.014) and MTVtotal (mean: 242.0 cm3 vs. 103.7 cm3; p = 0.027) than females. The ANN after training and validation was optimised with a final architecture of 4 scaling layer inputs (TLGtotal, SUVmaxtotal, SUVmeantotal and disease stage) and receiving operator characteristic (ROC) analysis demonstrated an AUC of 0.764 (sensitivity of 92.3%, specificity of 57.1%). CONCLUSION: Conventional statistical analysis and the ANN provided concordant findings in relation to variables that predict decreased survival. The ANN provided a weighted algorithm of the 4 key features to predict decreased survival. IMPLICATION FOR PRACTICE: Identification of parameters which can predict survival in lung cancer patients might be helpful in choosing the group of patients who require closer look during the follow-up.

Optimization of the regularization parameter in the Dual Annealing method used for the reconstruction of energy spectrum of electron beam generated by the AQURE mobile accelerator.

INTRODUCTION: The shape of the energy spectrum is an essential component of any electron beam Monte Carlo model. Due to specialized equipment and the long measurement time for the direct methods for determining the energy spectrum, attractive alternatives are backward spectrum reconstructions from the measured data. One such approach is solving the first-degree Fredholm integral equation with appropriate regularization. It makes it possible to calculate the depth distribution as the sum of the distributions from monoenergetic beams. This study aims to determine the optimal value of the regularization parameter for the problem of determining the spectrum of the electron beam produced by a mobile accelerator used during intraoperative radiotherapy. MATERIAL AND METHODS: The Geant4 package was used to generate the distributions of deep doses for monoenergetic beams for two models with different degrees of complexity, i.e. simple (theoretical) and full (for the mobile accelerator). The dose distributions for four different shapes of energy spectrum (for each model) were obtained similarly. They were established as the reference data for further calculations. The Dual Annealing optimization method was used to obtain the reconstructed spectrum. The multiple optimizations that differ by the regularization parameter (ranging from 0 to 1) were performed. For each reconstruction, similarity indicators of the energy spectrum and the dose distribution to the referenced data were calculated to determine the optimal regularization parameters. RESULTS: Optimal regularization parameters determined by similarity indicators for the spectrum and the dose distribution differ for geometry models considered in the study. The regularization parameter for the simple geometry ranged from 0.03 to 0.05, while for full geometry, they were from 0.05 to 0.06. The results for conventional linear accelerators found in the literature range from 0.5 to 1.1. CONCLUSION: The Dual Annealing optimization method can be effectively used to solve the Fredholm equation with Tikhonov regularization to reconstruct an electron beam's energy spectrum. The regularization parameter value depends on the beam-forming system. Its value for the mobile accelerator considered in the study ranges from 0.05 to 0.06, depending on the nominal beam energy value.

4DCT-based evaluation of lung tumour motion during the breathing cycle.

The aim of this work was to quantify the variability in pre-treatment lung tumor motion during a single breathing period for 55 non-small cell lung cancer (NSCLC) targets. The influence of breathing on the volume and position of lung tumor was examined by comparing the information about tumor from respiratory-correlated four-dimensional computed tomography (4DCT) and three-dimensional computed tomography (3DCT) obtained without respiratory monitoring. The impact of age, gender, lung volume changes and immobilization device on tumor respiratory motion was evaluated. Based on the performed analysis, the significant differences were found between tumor volumes on 3DCT and 4DCT, although the comparison of volumes between 4DCT bins showed no statistically significant dependency. The significant differences between tumor centre of mass coordinates in the cranial-caudal (CC) and anterior-posterior (AP) directions were found. According to the results of statistical testing, there was no impact of gender and immobilization device on detected tumor respiratory motion. The impact was found for patient's age, lung volume changes, tumor volume and its location in different lung segments. The dominant lung cancer motion was observed for smaller tumors (up to 20 cc) located in posterior, caudal segments. This effect was also associated with a large variation in the lung volume during one respiratory cycle, observed for older patients. The important finding of the study is connected with the description of different patterns of tumor motion in AP and CC directions.

A review of cone-beam CT applications for adaptive radiotherapy of prostate cancer.

INTRODUCTION: The aim of this study was to systematize the information on adaptive radiotherapy based on cone-beam computed tomography (CBCT) imaging for patients with prostate cancers including the prostate gland only, or the prostate gland and seminal vesicles region. MATERIAL AND METHOD: A systematic literature search was carried out using the PubMed engine, based upon the following terms: adaptive radiotherapy, intensity modulated radiotherapy, volumetric modulated arc therapy and image-guided and dose-guided radiotherapy. Overall, 58 relevant studies were included: 31 about on-line strategies of adaptation, 6 about off-line strategies, and 21 that highlighted the technical aspects of CBCT usage. RESULTS: The off-line strategies provide a statistical prediction for each individual patient for the rest of treatment. The on-line strategies aim to resolve the potential disagreements between a planned and delivered dose directly before the specific fraction. Both strategies need information about the movements of the irradiated region relative to the target from treatment planning and the dose delivered relative to the planned dose. Quality of CBCT is very important for the accuracy of the adaptation procedures. While the errors caused by the insufficient quality of anatomy visualisation with CBCT are currently minimized, there are still problems with the proper dose computation. The most accurate methods are able to minimize the calculation error to 3%. CONCLUSION: CBCT plays a significant role in each step of adaptive radiation therapy of prostate cancers, starting from registration procedures through setting an appropriate CTV-to-PTV margin to fraction dose recalculations, and its cumulation/monitoring relative to the planned dose.

Actigraphy-measured nocturnal wrist movements and assessment of sleep quality in patients with bullous pemphigoid: a pilot case-control study.

BACKGROUND: Bullous pemphigoid (BP) is a distressing autoimmune bullous disease strongly associated with severe pruritus; however, data concerning pruritus in BP are still scarce. No clinical research evaluating the effect of BP on sleep quality has been conducted. AIM: To evaluate the intensity of pruritus measured by nocturnal wrist movements (NWMs) and the sleep quality in patients with BP using actigraphy in comparison with nonpruritic healthy controls (HCs) with subsequent correlations with an itch visual analogue scale (VAS) as a subjective measure, disease severity [Bullous Pemphigoid Disease Area Index (BPDAI), urticaria/erythema, erosions/blisters] and serum total IgE level. METHODS: In total, 31 patients with newly diagnosed BP (mean ± SD age 75.4 ± 12.3 years) and 40 nonpruritic HCs (age 73.5 ± 11.7 years) were recruited. All participants wore a sleep monitor (ActiSleep+) on the dominant wrist. RESULTS: For patients with BP, median VAS score was 5.5 and median BPDAI was 43 (urticaria/erythema BPDAI was 16, erosions/blisters BPDAI was 29). Scratching, defined as bouts of NWMs, was significantly (P < 0.001) more intensive in patients with BP than in controls. Characteristic of BP was that scratching bouts corresponded with the slowest wrist movements. There were no correlations with VAS, BPDAI or total IgE level. Compared with HCs, patients with BP presented significant (P < 0.001) sleep disturbances, as determined by sleep efficiency, waking after sleep onset and average duration of awakening, and these were strongly correlated with urticaria/erythema BPDAI. CONCLUSION: Nocturnal wrist movements measured by actigraphy are more intensive in patients with BP than in nonpruritic HCs, and characteristically slow movements. Actigraphy method showed very low sleep quality in patients with BP, thus severity of BP has a negative impact on sleep.

Imaging collective cell migration and hair cell regeneration in the sensory lateral line.

The accessibility of the lateral line system and its amenability to long-term in vivo imaging transformed the developing lateral line into a powerful model system to study fundamental morphogenetic events, such as guided migration, proliferation, cell shape changes, organ formation, organ deposition, cell specification and differentiation. In addition, the lateral line is not only amenable to live imaging during migration stages but also during postembryonic events such as sensory organ tissue homeostasis and regeneration. The robust regenerative capabilities of the mature, mechanosensory lateral line hair cells, which are homologous to inner ear hair cells and the ease with which they can be imaged, have brought zebrafish into the spotlight as a model to develop tools to treat human deafness. In this chapter, we describe protocols for long-term in vivo confocal imaging of the developing and regenerating lateral line.

Impact of the Intra- and Inter-observer Variability in the Delineation of Parotid Glands on the Dose Calculation During Head and Neck Helical Tomotherapy.

The intra- and inter-observer variability in delineation of the parotids on the kilo-voltage computed tomography (kVCT) and mega-voltage computed tomography (MVCT) were examined to establish their impact on the dose calculation during adaptive head and neck helical tomotherapy (HT). Three observers delineated left and right parotids for ten randomly selected patients with oropharynx cancer treated on HT. The pre-treatment kVCT and the MVCT from the first fraction of irradiation were selected to delineation. The delineation procedure was repeated three times by each observer. The parotids were delineated according to the institutional protocol. The analyses included intra-observer reproducibility and inter-structure, -observer and -modality variability of the volume and dose. The differences between the left and right parotid outlines were not statistically significant (p > 0.3). The reproducibility of the delineation was confirmed for each observer on the kVCT (p > 0.2) and on the MVCT (p > 0.1). The inter-observer variability of the outlines was significant (p < 0.001) as well as the inter-modality variability (p < 0.006). The parotids delineated on the MVCT were 10% smaller than on the kVCT. The inter-observer variability of the parotids delineation did not affect the average dose (p = 0.096 on the kVCT and p = 0.176 on the MVCT). The dose calculated on the MVCT was higher by 3.3% than dose from the kVCT (p = 0.009). Usage of the institutional protocols for the parotids delineation reduces intra-observer variability and increases reproducibility of the outlines. These protocols do not eliminate delineation differences between the observers, but these differences are not clinically significant and do not affect average doses in the parotids. The volumes of the parotids delineated on the MVCT are smaller than on the kVCT, which affects the differences in the calculated doses.

A dosimetric comparison of IMRT versus helical tomotherapy for brain tumors.

BACKGROUND AND PURPOSE: Helical tomotherapy (HT) can deliver highly conformal, uniform doses to the target volume. However, HT can only be delivered in a coplanar mode. The purpose of this study was to perform a dosimetric comparison of HT versus coplanar (cIMRT) and non-coplanar (n-cIMRT) beam arrangements on a conventional linear accelerator in a diverse group of brain tumors. MATERIALS AND METHODS: A total of 45 treatment plans were calculated retrospectively for 15 cases. For each case, 3 different delivery techniques (n-cIMRT, cIMRT and HT) were used. The treatment plans were compared using the parameters of the target coverage (conformity index; CI) and homogeneity (HI) for the planning target volume (PTV) and the maximum and mean doses for organs at risk (OARs). RESULTS: Median HI and CI were the best for HT plans and the worst for cIMRT. The largest reduction of maximum dose for lenses and mean dose for both eyes was achieved for n-cIMRT plans. Mean dose for chiasm and the ipsilateral optic nerve were the lowest for HT. The contralateral optic nerve was most spared with n-cIMRT. For D1% in the brain stem, there was no significant difference between HT and the IMRT plans. CONCLUSIONS: Both HT and n-cIMRT are capable of producing conformal and homogeneous treatment plans with a good sparing of OARs. However, due to the non-coplanar capabilities of IMRT, n-cIMRT led to a superior dose reduction to the lenses.

Impact of the Intra- and Inter-observer Variability in the Delineation of Parotid Glands on the Dose Calculation During Head and Neck Helical Tomotherapy.

The intra- and inter-observer variability in delineation of the parotids on the kilo-voltage computed tomography (kVCT) and mega-voltage computed tomography (MVCT) were examined to establish their impact on the dose calculation during adaptive head and neck helical tomotherapy (HT). Three observers delineated left and right parotids for ten randomly selected patients with oropharynx cancer treated on HT. The pre-treatment kVCT and the MVCT from the first fraction of irradiation were selected to delineation. The delineation procedure was repeated three times by each observer. The parotids were delineated according to the institutional protocol. The analyses included intra-observer reproducibility and inter-structure, -observer and -modality variability of the volume and dose. The differences between the left and right parotid outlines were not statistically significant (p > 0.3). The reproducibility of the delineation was confirmed for each observer on the kVCT (p > 0.2) and on the MVCT (p > 0.1). The inter-observer variability of the outlines was significant (p < 0.001) as well as the inter-modality variability (p < 0.006). The parotids delineated on the MVCT were 10% smaller than on the kVCT. The inter-observer variability of the parotids delineation did not affect the average dose (p = 0.096 on the kVCT and p = 0.176 on the MVCT). The dose calculated on the MVCT was higher by 3.3% than dose from the kVCT (p = 0.009). Usage of the institutional protocols for the parotids delineation reduces intra-observer variability and increases reproducibility of the outlines. These protocols do not eliminate delineation differences between the observers, but these differences are not clinically significant and do not affect average doses in the parotids. The volumes of the parotids delineated on the MVCT are smaller than on the kVCT, which affects the differences in the calculated doses.

Method for data analysis in different institutions: example of image guidance of prostate cancer patients.

Multi-institutional collaborations allow for more information to be analyzed but the data from different sources may vary in the subgroup sizes and/or conditions of measuring. Rigorous statistical analysis is required for pooling the data in a larger set. Careful comparison of all the components of the data acquisition is indispensable: identical conditions allow for enlargement of the database with improved statistical analysis, clearly defined differences provide opportunity for establishing a better practice. The optimal sequence of required normality, asymptotic normality, and independence tests is proposed. An example of analysis of six subgroups of position corrections in three directions obtained during image guidance procedures for 216 prostate cancer patients from two institutions is presented.

Evaluation of image-guidance strategies for prostate cancer.

In this study, set-up accuracy and time consumption of different image-guidance protocols used for prostate cancer patients were compared. Set-up corrections from 60 prostate cancer patients treated on helical tomotherapy (HT) were used to simulate four types of image-guidance protocols which were based on: (i) a limited number of imaging sessions (IG-1), (ii) reduced registration tasks during daily imaging (IG-2), or (iii) and (iv) mixed methods of imaging (IG-3, IG-4). Each protocol was evaluated for three referencing scenarios based on the first fraction, first three fractions and first five fractions. Residual set-up error, the difference between the average set-up correction and the actual correction required, was used to evaluate the accuracy of each protocol. The first five fractions referencing scenario provides the highest reduction of the margins for each image-guidance protocol evaluated in this study. The first type of protocol is the shortest way to the effective correction of the systematic component of set-up error. For the second type of the protocol, the control of the residual errors is better and, as a result, the reduction of the margins is more significant than that obtained for the first one. Moreover, the second type of the protocol provides the highest accuracy of delivered dose. The result obtained for the fourth type of protocol does not decrease the calculated margins or increase their accuracy in correspondence to the no image guidance scheme. The fourth type of the protocol is not recommended as a protocol to be used to increase the conformity of the dose. The choice of the rest protocols should be validated in the context of (i) institutional practice regarding patient set-up procedure and its time consumption, (ii) acceptable balance between the amount of the dose delivered to the organ at risk and the additional imaging dose and (iii) patient anatomical conditions.

Tomotherapy: implications on daily workload and scheduling patients based on three years' institutional experience.

Helical tomotherapy (HT) was introduced at the Greater Poland Cancer Centre (GPCC) in April 2009. Retrospective analysis included data from the treatments performed for the first 656 patients treated with HT between May 2009 and May 2012 at the GPCC. In order to evaluate the implications on daily workload and scheduling of patients, stepwise regression and time analysis for each component of the overall treatment time, such as positioning, imaging, registration, and irradiation were performed. A detailed analysis included: (1) learning curves and optimized time needed for positioning and registration; (2) relation between irradiation time and parameters used for plan creation; and (3) average time of daily imaging. The irradiation component has the highest influence on the overall treatment time (R = 0.911). The lowest influence was observed for the imaging (R = 0.670). The learning curve for positioning was 7 months while the reduction of the average daily time needed for registration was observed even after two years. The irradiation time strongly depends on the planning parameters. Changing the pitch from 0.215 to 0.287 for pelvic cancer cases decreased the average daily beam-on time per patient by about 2 minutes. Similar changes for head and neck reduced this time by 1.3 minutes. The limitation in the usage of 1 cm field width only for complex cases, lower than 10 cm in the cranio-caudal direction, reduced the beam-on time per patient by 2 minutes. The average overall treatment time decreased from 21.5 minutes per patient in the first year of the HT usage to 13.8 minutes per patient in current practice. Our current practice shows that for a group of patients including mainly those with pelvis and head and neck cancers, the HT treatment takes approximately 15 minutes per patient allowing 40 patients to be treated within 10 hours.

Optimization of treatment planning parameters used in tomotherapy for prostate cancer patients.

BACKGROUND AND PURPOSE: Tomotherapy treatment planning depends on parameters that are not used conventionally such as: field width (FW), pitch factor (PF) and modulation factor (MF). The aim of this study is to analyze the relationship between these parameters and their influence on the quality of treatment plans and beam-on time. MATERIAL AND METHODS: Ten prostate cancer patients were included in the study. For each patient, two cases of irradiation were considered depending on the target volume: PTV1 included the prostate gland, seminal vesicles, pelvic lymph nodes and a 1 cm margin, whereas PTV2 included only the prostate gland with a 1 cm margin. For each patient and each case of irradiation (PTV1 and PTV2) 8 treatment plans were created - all consisted of a different combination of planning parameters (FW = 1.05, 2.5, 5 cm; PF = 0.107, 0.215, 0.43; MF = 1.5, 2.5, 3.5). Default values used in this study were FW = 2.5 cm, PF = 0.215 and MF = 2.5. Hence, for plans with different FWs, parameters of PF and MF were 0.215 and 2.5, respectively; for different PFs, FW and MF were 2.5 and 2.5, respectively; finally for different MFs, FW and PF were 2.5 and 0.215, respectively. The reference plan was optimized for FW = 1.05 cm, PF = 0.107 and MF = 3.5, which was assumed to result in the best dose distribution and the longest treatment time. As a result, 160 plans were created. Each plan was analyzed for dose distribution and execution time. RESULTS AND CONCLUSION: : Treatment plans with FW of 5 cm resulted in the shortest execution time compromising the dose distribution. Moreover, the dose fall off in the longitudinal direction was not sharp. FW of 1.05 cm and PF of 0.107 were not recommended for routine prostate plans due to long execution time, which was 3 times longer than for plans with FW = 5 cm. There was no substantial decrease of irradiation time when PF was increased from 0.215 to 0.43 for both cases (PTV1 and PTV2); however, the dose distribution was slightly compromised. Finally, decreasing MF from 2.5 to 1.5 was useless because it did not change the beam-on time; however, it did remarkably decrease the dose distribution. Nevertheless, increasing MF up to 3.5 could be considered. The lowest EUD for the rectum and intestines, could be observed for PF = 0.107. For the other plans the differences were rather small (the EUD was almost the same). By reducing PF from 0.43 to 0.107 or FW from 5 to 1.05 the EUD for bladder (in PTV1 case) decreased by 3.13% and 2.60%. When PTV2 was a target volume, the EUD for bladder decreased by 4.54% and 3.43% when FW was changed from 5 to 1.05 and MF from 1.5 to 3.5, respectively. For optimal balance between beam-on time and dose distribution in OARs for routine patients, the authors would suggest to use: FW = 2.5, PF = 0.215 and MF = 2.5.

B-Spline registration based on new concept of an intelligent masking procedure and GPU computations for the head and neck adaptive tomotherapy.

The deformable image registration (DIR) procedure has been optimized for helical tomotherapy. The data on registration shifts obtained on matching planning image with pre-treatment megavoltage CT are used in our software for acceleration of the first step (rigid registration) of the DIR procedure and for implementation of the B-Spline algorithm with intelligent masking. Priorities of the masks were automatically calculated based on disagreement detected during rigid registration. Evaluation tasks included: (a) comparison of accuracy and rate for schemes of pre-registered and non-registered images; (b) qualification of the effectiveness of the intelligent masking process, and (c) determination of acceleration of achievable with GPU computing. A specially designed head and neck phantom used for evaluation included structures with controlled changes of position, volume, density, and shape. Re-contouring procedures were performed with an Adaptive Planning software (Tomotherapy Inc.). No statistical difference was observed in accuracy of DIR based on structure position match on the tomotherapy unit and non pre-registered images (p > 0.7). Using pre-registered data reduces the total time required for execution of the elastic registration procedure by 5%. These data are also necessary for intelligent masking procedure during B-Spine registration. Intelligent masking procedure increases accuracy of the registration for a masked structure (p < 0.04) without decreasing the accuracy in non-masked tissues and additionally reduces the total time by 13%. GPU computations speed up procedure 30 times. GPU computing of the DIR in current status of our investigation could be realized in a relatively short time after pre-treatment imaging. The proposed approach can be used in the routine assessment of anatomic changes occurring in healthy tissue during the course of radiotherapy. Further developments will be concentrated on the full integration of DIR computations in the imaging and treatment process of helical tomotherapy.

Evaluating acute medical admissions through emergency departments in Hong Kong: can one adjust for case-mix variation?

BACKGROUND: Healthcare systems are under pressure to efficiently and safely reduce acute care admissions to hospital. There is a need to develop a standardised system for assessing emergency department performance which takes into account case-mix variation. The objective of this study was to derive and validate a standardised tool for assessing variations in medical admissions through emergency departments in Hong Kong. METHODS: Retrospective study of patients attending emergency departments of 14 acute hospitals in Hong Kong. Data were retrieved from a centralised administrative database. RESULTS: Of 2,531,225 patients who attended emergency departments between 1 January 2001 and 31 December 2003, 780,444 (30.8%) were admitted to medical wards. A model derived from 2001 data shows well-calibrated admission probabilities, with an area under the receiver operating characteristic curve for probability of admission of 90.3 (95% CI ±0.11). The areas under the receiver operating characteristic curves for 2002 and 2003 validation sets were 89.9 (95% CI ±0.11) and 89.0 (95% CI ±0.12), respectively. With an averaged benchmark, reductions in medical admissions of up to 19% could be achieved, while under the most optimistic assumption, reductions of up 36% could be achieved. CONCLUSIONS: A tool for benchmarking hospital medical admissions and minimising case-mix variation has been derived and validated in Hong Kong, but it requires further validation in other healthcare systems given the wide variations in admission thresholds internationally. This may be used as one potential method to evaluate the performance of emergency departments against a common standard.

Feasibility of reducing the irradiation dose in regions of active neurogenesis for prophylactic cranial irradiation in patients with small-cell lung cancer.

Prophylactic cranial irradiation (PCI) is performed on patients with limited or extensive small-cell lung cancer to reduce incidence of brain metastases and prolong survival. PCI may induce neurocognitive impairment. Decreasing irradiation of neural stem cells (NSC) might reduce PCI-induced toxicity. We tested the feasibility of reducing irradiation doses to neural stem cell (NSC) regions while maintaining prescribed doses to the planned target volume (PTV). Irradiation plans utilizing intensity-modulated radiotherapy (IMRT), helical TomoTherapy, and RapidArc for 10 consecutive lung cancer patients were evaluated. The dose distribution, dose-volume histograms, and dose homogeneity indexes were analyzed. Planned and actual dose distributions were compared by dosimetric analysis. Both helical tomotherapy and LINAC-based IMRT reduced the radiation dose to the NSC regions by approximately 45% while maintaining the full dose to the rest of brain. Measured dose distributions matched the planned dose distributions.Protecting the regions of active neurogenesis is technically feasible. Whether reducing the dose by 35% to 45% is sufficient to reduce treatment toxicity, however, can only be addressed in a randomized study. Further reducing the dose within the NSC region might also significantly decrease the dosage to the PTV.

Optimization and it's influence on value of doses in HDR and PDR brachytherapy.

The aim of this work is to examine the influence of the dose optimization procedure on the value of radiation doses in organs of risk and to compare value of doses measured in healthy tissues according to chosen different PDR brachytherapy (PDRBT) and HDR brachytherapy (HDRBT) fractionation schedule. Fifty one patients treated with PDRBT were qualified for calculations. This group included patients with head and neck cancer, brain tumor, breast cancer, sarcoma, penile cancer and rectal cancer. The doses were calculated in chosen critical points in surrounded healthy tissues. For all treatment plans the doses were compared with the use of the BED (Biologically Equivalent Dose) formula and PDR along with HDR values were calculated. Differences among total doses in PDRBT and different schemas of HDRBT in critical points before and after dose point and volume optimization, were analyzed. The same dependences were examined also for BEDs. One ascertained that in biologic equivalent (to PDR) HDRBT the increase of fraction dose from 4 Gy to 10 Gy caused the necessity of decrease of total dose in treatment area (p<0,001). The use of HDR instead of PDR essentially lowered physical and biological doses in examined organs of risk. In many examined critical points in organs of risk where biological equivalence dose in the treatment area was the same, one ascertained the decrease of total physical HDR dose according to the growth of the fraction dose. Similar dependences appeared also for biologically equivalent doses. The optimization process in PDRBT improved the dose homogeneity in the treatment area, but simultaneously induced unprofitable (essential statistically) increase of dose in some healthy organs of risk, what makes an increase risk for radiation-induced complications. The use of biologically equivalent HDRBT instead of PDRBT makes for the decrease of physical doses in the treatment area and the decrease of physical and biologically equivalent doses in healthy organs of risk.

Prediction of radiation pneumonitis: dose-volume histogram analysis in 62 patients with non-small cell lung cancer after three-dimensional conformal radiotherapy.

The purpose of the study was to determine the relation between the incidence of radiation pneumonitis (RP) and available parameters from a dose-volume histogram (DVH) in patients with non-small cell lung cancer (NSCLC) who underwent three-dimensional conformal radiotherapy treatment. Between January 1999 and August 2003 in the Greatpoland Cancer Center, 62 patients with NSCLC were treated using three-dimensional conformal radiotherapy (3D CRT). All patients were treated 5 days per week with daily fractionation of 2 Gy to total dose of 60 Gy. All patients were available for analysis for symptomatic RP. Radiation pneumonitis was graded according to the RTOG/EORTC morbidity scoring classification. Logistic regression analysis was performed to test the association between RP and the following DVH parameters: mean lung dose (MLD), volume of lung receiving > or =20 Gy (V20 ) and > or =30 Gy (V30) and normal tissue complication probability (NTCP). Additionally, correlation of the following clinical factors such as: age, sex, tumor site, performance status (KPS), and additional therapy (chemotherapy) with incidence of the RP were performed. Moreover, correlation between DVH parameters were tested using Spearman method. Thirty out of 62 patients (48%) developed RP grade 0 or 1 (0 grade -- 12%, 1 grade -- 36%) and 32 (52%) grade 2 or 3 (2 grade -- 47%, 3 grade -- 5%). In the logistic regression analysis, all DVH parameters were associated with RP (p in range from 0.004 to 0.007). The strongest association was observed for NTCP and V30 (p=0.004). On the other hand, a weak association was found for V20 (p=0.007). The correlations between all DVH parameters for lung were sufficient (r Spearman in range from 0.87 to 0.93). The best correlation among DVH parameters were observed between V20 and NTCP (r=0.93, p<0.001). On the other hand, the least but sufficient association was found for V30 and V20 (r=0.87, p<0.001). There was no association between clinical factors and RP. NTCP and V30 parameters were the best predictors of symptomatic radiation pneumonitis for patients after three-dimensional conformal radiotherapy of non-small cell lung cancer.

Advanced tracheal carcinoma--a therapeutic significance of HDR brachytherapy in palliative treatment.

The purpose of this study was to determine the benefit of high dose rate endotracheal brachytherapy as an exclusive palliative treatment of obstructive tracheal cancer. Thirty-five patients with advanced tracheal carcinoma were treated between May 1999 and March 2001 in Greatpoland Cancer Center. They were qualified for brachytherapy due to life-threatening situations. Fourteen patients were irradiated using three fractions 7.5 Gy each one every week, six patients received three fractions 10 Gy each one every week and fifteen patients received one fraction of 10 Gy. Survival time was compared with chosen clinical factors (age, sex, Karnofsky status, tumor location, lymph nodes involvement and percent of obturation) and prescribed dose. The median survival (Kaplan-Meier) for all patients was 6.6 months. Patients with an endoscopically controlled complete remission 4 weeks after the treatment had a significantly better survival in comparison to patients with a partial remission or no change of tumor size (p=0.0003). Univariate analysis revealed significant difference between patients with Karnofsky score equal with 60 or lower (28/35, 80%) and higher than 60 (7/35, 20.0%) (p=0.005). Difference between the grade of tumor obturation (more than 60% of tracheal lumen (27/35, 77.1%), 60% or lower (8/35, 22.9%) was found in univariate analysis (p=0.04). In multivariate analysis statistically important prognostic factor for survival was Karnofsky score (p=0.04). Statistical analysis revealed no differences in survival according to sex and age (p=0.43 for age, p=0.19 for sex), tumor localization (p=0.13), lymph node involvement (p=0.48) or fractionation scheme (p=0.62). Exclusive HDR brachytherapy of advanced tracheal carcinoma was a safe palliative method of treatment and caused in many patients prolonged survival and improved quality of life. Most important prognostic factor for survival, confirmed in both univariate and multivariate analysis, was Karnofsky score.

The comparison of radiotherapy techniques for treatment of the prostate cancer: the three-field vs. the four-field.

Our purpose was to compare the three-field and the four-field planning techniques in patients with localized prostate cancer. Twenty patients with localized prostate cancer stage (T1-T2N0M0) were chosen for the analysis of treatment plans. Simulation and CT planning were performed in all cases in the supine position with a "comfortably" full bladder. The planning treatment volume (PTV) was defined as the prostate gland with a 10 mm margins around the clinical target volume (CTV), except for the posterior margin (prostate gland - the anterior part of rectum wall), where a 5 mm margin was applied. The clinical target volume (CTV) was defined as prostate gland. For each patient the following organs at risk (OAR) were outlined: rectum, bladder, and right femoral head. The following three-field and four-field plans were made: 3 field techniques with beam angles orientations 0 degree, 120 degrees, 240 degrees and 0 degree, 90 degrees, 270 degrees, and 4 field technique (0 degree, 90 degrees, 180 degrees, 270 degrees). Two versions of treatment plans were also made including different range of applied energy of photons (6 MV or 20 MV) for the therapeutic machine - Clinac 2300 CD. Beam portals were conformal by shaped by a multileaf collimator (MLC). The daily fractionation dose 1.8 Gy and the total dose 73.8 Gy were applied in each case. One hundred and twenty treatment plans were made and compared according to the following parameters: the mean total dose (MTD) in the target, the tumor control probability (TCP), the mean total dose (MTD) in the OAR (rectum, bladder, and right femoral head), the normal tissue complication probabilities (NTCP), and the volume of OARs which received arbitrary chosen fraction (%) of the total prescribed dose (73.8 Gy=100%). ANOVA statistical methods to verify the significance of differences between the treatment plans were used. There were no significant differences in the distribution of MTD and TCP in the PTV for the evaluated treatment plans. There were no significant differences in the MTD, NTCP, V80, and V90 distribution in bladder. The distribution of MTD, NTCP, and V80 for rectum indicated that lower parameters were achieved in the case of the three-field technique with the orientation of beams 0 degree, 90 degrees, 270 degrees. The distribution of MTD, NTCP, and V70 in right femoral head for each treatment plan was below the tolerance dose. The study has shown that the three-field technique (an anterior and two opposing lateral fields with the portals orientation 0 degree, 90 degrees, 270 degrees) and applied energy photons 20 MV, provides the best rectal protection. All evaluated plans according to the dose distribution in the target (PTV) have not indicated any significant differences. None of the techniques has shown any significant advantages in sparing bladder. The risk of morbidity in the femoral heads for all the applied techniques, in a dose up to 73.8 Gy was not a therapeutic problem. However, the three-field technique with beams orientation 0 degree, 120 degrees, 240 degrees gave the best sparing effect for femoral heads.