Modeling of Acute Rectal Toxicity to Compare Two Patient Positioning Methods for Prostate Cancer Radiotherapy: Can Toxicity Modeling be Used for Quality Assurance?

PURPOSE: Intensity Modulated Radiation Therapy (IMRT) allows for significant dose reductions to organs at risk in prostate cancer patients. However, the accurate delivery of IMRT plans can be compromised by patient positioning errors. The purpose of this study was to determine if the modeling of grade ≥ 2 acute rectal toxicity could be used to monitor the quality of IMRT protocols. MATERIALS AND METHODS: 79 patients treated with Image and Fiducial Markers Guided IMRT (FMIGRT) and 302 patients treated with trans-abdominal ultrasound guided IMRT (USGRT) was selected for this study. Treatment plans were available for the FMIGRT group, and hand recorded dosimetric indices were available for both groups. We modeled toxicity in the FMIGRT group using the Lyman Kutcher Burman (LKB) and Univariate Logistic Regression (ULR) models, and we modeled toxicity in USGRT group using the ULR model. We performed Receiver Operating Characteristics (ROC) analysis on all of the models and compared the Area under the ROC curve (AUC) for the FMIGRT and the USGRT groups. RESULTS: The observed Incidence of grade ≥ 2 rectal toxicity was 20% in FMIGRT patients and 54% in USGRT patients. LKB model parameters in the FMIGRT group were TD50=56.8 Gy, slope m=0.093, and exponent n=0.131. The most predictive indices in the ULR model for the FMIGRT group were D25% and V50 Gy. AUC for both models in the FMIGRT group was similar (AUC=0.67). The FMIGRT URL model predicted less than a 37% incidence of grade ≥ 2 acute rectal toxicity in the USGRT group. A fit of the ULR model to USGRT data did not yield a predictive model (AUC=0.5). CONCLUSION: Modeling of acute rectal toxicity provided a quantitative measure of the correlation between planning dosimetry and this clinical endpoint. Our study suggests that an unusually weak correlation may indicate a persistent patient positioning error.

Current insights into the aetiology of adolescent idiopathic scoliosis.

Scoliosis occurs in about 0.2-0.6% of the general population. In the majority of cases the cause of this entity remains mostly unidentified. The search for the causes covers almost all aspects of its possible origin. We collected and systematised the contemporary theories and concepts concerning the aetiology of adolescent idiopathic scoliosis. Genetic and hereditary factors are commonly accepted as possible causes; however, the identification of the single gene responsible for the development of this condition seems impossible, which suggests multifactorial mechanism of its formation. Dysfunctions of the nervous system are recognised risks related to the development of scoliosis, but they are classified as belonging to a separate aetiological category. Scoliosis develops at the quickest rate during the child's growth spurt, which prompted the research on the role of the growth hormone in scoliosis aetiology. Melatonin is another hormone that is studied as a possible factor involved in development of this entity. In cases of progressive scoliosis, increased activity of calmodulin-a protein that regulates the levels of calcium ions-has been observed. The scientists have characterised numerous qualitative and quantitative changes in the composition of the tissue of intervertebral discs, spinal ligaments and paraspinal muscles. Some of the theories, explaining the nature of this entity, presented in this review seem to have only a purely theoretical value; their proliferation only confirms the fact that the actual nature of this condition has not been unveiled yet, and suggests its multifactorial aetiology.

WE-G-BRCD-09: Assessment of Quantitative Differences Between Different Deformable Image Registration Algorithms for Image Guided Radiotherapy of Head and Neck Cancer Patients.

PURPOSE: DIR algorithms differ by physical principles employed in their design which in turn determines complexity of the transformation that the algorithm allows. Indiscriminate application of different algorithms without regard for their limitations may lead to significant discrepancies in research results and in clinical procedures. We compare two different algorithms in Head and Neck (H&N) patients to assess what aspects of DIR use are most sensitive to differences between algorithms. METHODS: H&N patients are enrolled in a protocol which acquires weekly FBCT and daily double CBCT. Each FBCT study is contoured by the same physician. Two DIR algorithms are compared: Small Deformation Inverse-Consistent Linear Elastic (SICLE), and the ITK Diffeomorphic Demons (ITKDD) as implemented in the ITK package. Both algorithms employ significantly different physical principles in their design and consequently impose different restrictions on the complexity of transformation they allow. We compare Jacobian Volume Histograms (JVH), Spatial Discrepancy Volume Histograms (SDVH), BED and physical dose accumulation results and resulting plan evaluation indices. RESULTS: Analysis of mean Jacobian shows that both algorithms are able to detect changes in structure volumes, though they differ quantitatively from one another and from the ground truth as established by the analysis of changes in contours. Width of Jacobian distributions is very different indicating that Jacobian should not be used as a measure of volume change at a voxel level without independent validation. Analysis of SDVHs shows that dose lookup points implied by both algorithms are separated by 5mm - 10mm over approximately 30% of most volumes. These differences translate into clearly visible though not very significant differences in BED and dose accumulation. We further observe that physical dose accumulation in external beam H&N patients is a good proxy for direct BED accumulation. CONCLUSIONS: Different DIR algorithms may have to be applied selectively in different areas of treatment planning. Acknowledgments: Supported by NIH Grant P01 CA11602.

MO-F-BRA-02: Evaluation of 4D CT to 4D Cone-Beam CT Deformable Image Registration for Lung Cancer Adaptive Radiation Therapy.

PURPOSE: To evaluate two deformable image registration (DIR) algorithms for the purpose of contour mapping to support image guided adaptive radiotherapy (IGART) with 4D cone beam CT (4DCBCT). METHODS: Eleven locally advanced non-small cell lung cancer (NSCLC) patients underwent one planning 4D fan- beam CT (4DFBCT) and seven weekly 4DCBCT scans. Gross tumor volume (GTV) and carina were delineated by a physician in all 4D images. For day to day registration, the end of inspiration 4DFBCT phase was deformably registered to the corresponding phase in each 4DCBCT image. For phase to phase registration, the end of inspiration phase from each 4D image was registered to end of expiration phase. The delineated contours were warped using the resulting transforms and compared to the manual contours through Dice similarity coefficient (DSC), false positive and false negative indices, and, for carina, target registration error (TRE). Two DIR algorithms were tested: 1) small deformation, inverse consistent linear elastic (SICLE) algorithm and 2) Insight Toolkit diffeomorphic demons (DEMONS). RESULTS: For day to day registrations, the mean DSC was 0.59 ± 0.16 after rigid registration, 0.72 ± 0.13 with SICLE and to 0.66 ± 0.18 with DEMONS. SICLE and DEMONS reduced TRE to 4.1 ± 2.1 mm and 5.8 ± 3.7 mm respectively, from 6.2 ± 3.5 mm; and reduced false positive index to 0.27 and 0.26 respectively from 0.46. Registration with the cone beam as the fixed image resulted in higher DSC than with the fan beam as fixed (p < 0.001). SICLE and DEMONS increased the DSC on average by 10.0% and 8.0% and reduced TRE by 2.8 mm and 2.9 mm respectively for phase to phase DIR. CONCLUSIONS: DIR achieved more congruent mapping of target structures to delineations than rigid registration alone, although DIR performance varied with algorithm and patient. This work was supported by National Cancer Institute Grant No. P01 CA 116602.

A comparison of HDR brachytherapy and IMRT techniques for dose escalation in prostate cancer: a radiobiological modeling study.

A course of one to three large fractions of high dose rate (HDR) interstitial brachytherapy is an attractive alternative to intensity modulated radiation therapy (IMRT) for delivering boost doses to the prostate in combination with additional external beam irradiation for intermediate risk disease. The purpose of this work is to quantitatively compare single-fraction HDR boosts to biologically equivalent fractionated IMRT boosts, assuming idealized image guided delivery (igIMRT) and conventional delivery (cIMRT). For nine prostate patients, both seven-field IMRT and HDR boosts were planned. The linear-quadratic model was used to compute biologically equivalent dose prescriptions. The cIMRT plan was evaluated as a static plan and with simulated random and setup errors. The authors conclude that HDR delivery produces a therapeutic ratio which is significantly better than the conventional IMRT and comparable to or better than the igIMRT delivery. For the HDR, the rectal gBEUD analysis is strongly influenced by high dose DVH tails. A saturation BED, beyond which no further injury can occur, must be assumed. Modeling of organ motion uncertainties yields mean outcomes similar to static plan outcomes.

Quantification of the impact of MLC modeling and tissue heterogeneities on dynamic IMRT dose calculations.

This study quantifies the dose prediction errors (DPEs) in dynamic IMRT dose calculations resulting from (a) use of an intensity matrix to estimate the multi-leaf collimator (MLC) modulated photon fluence (DPE(IGfluence) instead of an explicit MLC particle transport, and (b) handling of tissue heterogeneities (DPE(hetero)) by superposition/convolution (SC) and pencil beam (PB) dose calculation algorithms. Monte Carlo (MC) computed doses are used as reference standards. Eighteen head-and-neck dynamic MLC IMRT treatment plans are investigated. DPEs are evaluated via comparing the dose received by 98% of the GTV (GTV D 98%), the CTV D 95%, the nodal D 90%, the cord and the brainstem D 02%, the parotid D 50%, the parotid mean dose (D (Mean)), and generalized equivalent uniform doses (gEUDs) for the above structures. For the MC-generated intensity grids, DPE(IGfluence) is within +/- 2.1% for all targets and critical structures. The SC algorithm DPE(hetero) is within +/- 3% for 98.3% of the indices tallied, and within +/- 3.4% for all of the tallied indices. The PB algorithm DPE(hetero) is within +/- 3% for 92% of the tallied indices. Statistical equivalence tests indicate that PB DPE(hetero) requires a +/- 3.6% interval to state equivalence with the MC standard, while the intervals are < 1.5% for SC DPE(hetero) and DPE(IGfluence). Overall, these results indicate that SC and MC IMRT dose calculations which use MC-derived intensity matrices for fluence prediction do not introduce significant dose errors compared with full Monte Carlo dose computations; however, PB algorithms may result in clinically significant dose deviations.

Internal fixation systems in the surgical treatment of spondylolisthesis.

The authors of this article describe the surgical procedure for fixation of spondylolisthesis using transpedicular fixation, and offer a comparative evaluation of the DERO, CD, C-CD, SOCON, and STRYKER systems.
The evaluation involved 36 patients operated in the Rehabilitation Clinic at the Lublin Academy of Medicine during the period 1994-2000. In 11 cases the DERO fixation system was used; in 5 cases, fixation with CD or C-CD instrumentation; in 15 cases, using the SOCON system; and in 5 cases with the STRYKER instrumentation.
Indications for surgery included pain and symptoms of nerve root irritation with sciatic neuralgia. The concomitant neurological symptoms resulted from the displacement into the vertebral canal of fragments of the nucleus pulposus, or from bone-related stenosis of the vertebral canal and intervertebral foramina.
Surgical treatment involved decompression of the nerve elements and internal fixation. In all the cases reported here posterior and postero-lateral spondylodesis was performed, while in 20 cases interbody spondylodesis was additionally performed, in 14 cases using interbody plugs.
The authors analyze the reasons for complications, such implants working loose and fatigue fractures.

Internal fixation of the spine in the surgical treatment of scoliosis.

Progressive idiopathic scoliosis, despite the good effects of treatment by kinesitherapy and corrective corsets, continues to pose a complicated problem in planning surgical procedure. On the one hand, the steady growth and improvement of systems for three-plane correction and fixation of scoliosis improves the radiological and clinical outcome; on the other hand, three arises the necessity to choose the surgical procedure and system of implants appropriate for the given type, localization, and angular dimensions of the curvature. The problems faced by the operating surgeon include not only making the right choice of implants, but also arranging the transpedicular screws and hooks at the proper strategic points along the curvature of the spine.
On the basis of clinical material from 200 patients surgically treated for idiopathic scoliosis, the authors present surgical solutions and analyze various implant systems (CD-HORIZON, DERO, STRYKER), made of steel or titanium, for three-plane correction and fixation of the spine. Attention is called to the application in the lumbar spine of transpedicular screws, which improve the correction and fixation of the spine and reduce the amount of instrumentation needed, while assuring the essential horizontal arrangement of the lower lumbar vertebrae.
The authors' own experience shows that modern systems for three-plane correction and fixation of the spine in scoliosis exceeding 750, despite spondylodesis, do not assure the proper correction and biomechanical value, in comparison to the Wisconsin method, which combines BW distraction with Luque intersegmentary fixation.

Effect of metal reconstruction plates on cobalt-60 dose distribution: a predictive formula and clinical implications.

PURPOSE: We sought to create a predictive formula for the dose perturbations caused by head and neck reconstruction plates in the delivery of postoperative radiotherapy with 60Co beams. MATERIALS AND METHODS: The dose perturbation effects of Vitallium and Titanium reconstruction plates and flat metal plates of aluminum (13Al), stainless steel (26Fe), tin (50Sn) and lead (82Pb) irradiated with a 60Co beam were measured in polystyrene phantoms using a film dosimetry system. We then used these results to create formulas to predict the effect of a metal reconstruction plate dependent upon its effective atomic number. RESULTS: Percentage dose increases secondary to back scattering were 10% at 1 mm in front of the Vitallium plate and 40% at the plate while the percentage dose decrease was 29% at the plate and 10% 1 mm behind the plate. For the Titanium plate, the percentage dose increase was 5% at 1 mm in front the plate and 25% at the plate while the percentage dose decrease was 20% at the plate and 5% 1 mm behind the plate. For flat plates the percentage dose increases and decreases, respectively, at the plate surfaces were: 13Al (8%, 6%), 26Fe (35%, 16%), 50Sn (60%, 24%), and 82Pb (85%, 13%). A second order polynomial predicting the back scatter and shadowing effects was created, Y = a + bZ + cZ2, where Z is the effective atomic number of the plate while a, b, and c are the following constants: for back scatter a = 0.854 +/- 0.082, b = 0.0212 +/- 0.0044, c = -0.00011 +/- 0.00004 and for shadowing a = 1.108 +/- 0.021, b = -0.0141 +/- 0.0011, c = 0.00014 +/- 0.00001. CONCLUSIONS: It is possible to predict the effect of a metal reconstruction plate upon the delivered postoperative radiotherapy dose. The dose perturbations around the plate only exist for a few millimeters, but this is substantially greater than the thickness of a normal tissue or tumor cell. Perhaps a coating of a low effective atomic number, biologically inert, substance might allow for greater dose homogeneity and decrease the risks of plate failure or tumor recurrence.