Balazs Nyiri

Helical tomotherapy for locoregional irradiation including the internal mammary chain in left-sided breast cancer: Dosimetric evaluation

PURPOSE To compare a standard 3- or 4-field technique to intensity modulated radiotherapy with helical tomotherapy (IMRT-HT) in the planning of locoregional breast radiation including the internal mammary chain (IMC). METHODS AND MATERIALS For 10 women with stage III left-sided breast cancer with a planning target volume (PTV) defined by the breast/chest wall and regional nodes, radiotherapy to a dose of 50 Gy in 25 fractions was planned using a standard 3- or 4-field technique and using IMRT-HT. Various metrics were extracted from dose-volume histograms, and were compared using the paired Students t-test. RESULTS The PTV receiving at least 95% of the prescribed dose did not differ between the two plans, but the VD115% was significantly lower with IMRT-HT. The dose conformality was significantly better with IMRT-HT. The cardiac V30(Gy) was reduced with IMRT-HT. The mean lungs dose was lower with IMRT-HT, as well the V20(Gy). With IMRT-HT, a greater volume of contralateral breast was irradiated to 5 Gy, but a smaller volume of soft tissue received dose above 50 Gy. CONCLUSIONS Compared to a standard technique, IMRT-HT provides similar target coverage, improves dose conformality and dose homogeneity within the PTV, decreases mean lung dose and spares heart, lung and soft tissue from high dose exposure.

Comparison of α/β estimates from homogeneous (individual) and heterogeneous (population) tumor control models for early stage prostate cancer

Radiobiological parameter estimates for prostate cancer are obtained from both a homogeneous (individual) and heterogeneous (population) tumor control model based on Poisson statistics and the linear quadratic model of cell survival. Parameter estimates for both models are highly correlated: statistically equivalent fits are achievable using either (1) linear quadratic (LQ) parameters with low numbers of radioresistant tumor stem cells, or (2) LQ parameters with corresponding larger number of radiosensitive tumor stem cells. A theoretical framework is developed to explain this correlation. A Monte Carlo error analysis based on binomial statistics is used to estimate confidence intervals for all parameter estimates. It was found that both the homogeneous and heterogeneous models produce approximately equivalent estimates of radiobiological parameters, including the α/β ratio. However, the 95% confidence interval for the α/β ratio derived from the heterogeneous model are considerably larger than those derived from the homogeneous model, which indicate the homogeneous model overestimates the statistical significance of the α/β estimate.

TCP isoeffect analysis using a heterogeneous distribution of radiosensitivity

A formula for the alpha/beta ratio is derived using the heterogeneous (population averaged) tumor control model. This formula is nearly identical to the formula obtained using the homogeneous (individual) tumor control model, but the new formula includes extra terms showing that the alpha/beta ratio, the ratio of the mean value of a divided by the mean value of beta that would be observed in a patient population, explicitly depends on the survival level and heterogeneity. The magnitude of this correction is estimated for prostate cancer, and this appears to raise the mean value of the ratio estimate by about 20%. The method also allows investigation of confidence limits for alpha/beta based on a population distribution of radiosensitivity. For a widely heterogeneous population, the upper 95% confidence interval for the alpha/beta ratio can be as high as 7.3 Gy, even though the population mean is between 2.3 and 2.6 Gy.

Raman micro-spectroscopy analysis of human lens epithelial cells exposed to a low-dose-range of ionizing radiation

Recent findings in populations exposed to ionizing radiation (IR) indicate dose-related lens opacification occurs at much lower doses (<2 Gy) than indicated in radiation protection guidelines. As a result, research efforts are now being directed towards identifying early predictors of lens degeneration resulting in cataractogenesis. In this study, Raman micro-spectroscopy was used to investigate the effects of varying doses of radiation, ranging from 0.01 Gy to 5 Gy, on human lens epithelial (HLE) cells which were chemically fixed 24 h post-irradiation. Raman spectra were acquired from the nucleus and cytoplasm of the HLE cells. Spectra were collected from points in a 3  ×  3 grid pattern and then averaged. The raw spectra were preprocessed and principal component analysis followed by linear discriminant analysis was used to discriminate between dose and control for 0.25, 0.5, 2, and 5 Gy. Using leave-one-out cross-validation accuracies of greater than 74% were attained for each dose/control combination. The ultra-low doses 0.01 and 0.05 Gy were included in an analysis of band intensities for Raman bands found to be significant in the linear discrimination, and an induced repair model survival curve was fit to a band-difference-ratio plot of this data, suggesting HLE cells undergo a nonlinear response to low-doses of IR. A survival curve was also fit to clonogenic assay data done on the irradiated HLE cells, showing a similar nonlinear response.

Rapid palliative radiotherapy: comparing IG-IMRT with more conventional approaches

Purpose: To assess the efficiency of an integrated imaging, planning, and treatment delivery system to provide image-guided intensity-modulated radiotherapy (IG-IMRT) for patients requiring palliative radiotherapy (PRT). Methods: Between December 2006 and May 2008, 28 patients requiring urgent PRT were selected to undergo single-session megavoltage computed tomography (MV-CT) simulation, IMRT treatment planning, position verification and delivery of the first faction of radiotherapy on a helical Tomotherapy ® unit. The time required to complete each step was recorded and compared to our standard approach of using either fluoroscopic or CT-based simulation, simplified treatment planning and delivery on a megavoltage unit. Results: Twenty-eight patients were treated with our integrated IG-IMRT protocol. The median age was 72 years, with 61% men and 39% women. The indications for PRT were: painful bone and soft tissue metastasis (75%); bleeding lesions (14%); and other reasons (11%). The areas treated included the following: hip and/or pelvis (42%); spine (36%); and other areas (21%). The most commonly used dose prescription was 20 Gy in five fractions. Average times for the integrated IG-IMRT processes were as follows: image acquisition, 15 minutes; target delineation, 16 minutes; IMRT treatment planning, 9 minutes; treatment position verification, 10 minutes; and treatment delivery, 12 minutes. The average total time was 62 minutes compared to 66 minutes and 81 minutes for fluoroscopic and CT-simulation-based approaches, respectively. The IMRT dose distributions were also superior to simpler plans. Conclusions: PRT with an integrated IG-IMRT approach is efficient and convenient for patients, and has potential for future applications such as single-fraction radiotherapy.

Poster - 57: Statistical analysis of setup correction for radical IMRT lung patients on a treatment couchtop with six degrees of freedom

Purpose: To characterize the distributions of setup corrections for radical IMRT lung patients treated on a couchtop with six degrees of freedom (6DOF). Methods: Translational and rotational setup corrections were retrospectively analyzed for patients treated on the HexaPODTM 6DOF couchtop. Conventional and hypo-fractioned radical IMRT lung treatments were included, for a total of 152 patients and 2,042 fractions. The distribution of setup corrections was analyzed for each DOF. Potential correlations between pairs of corrections were examined and possible causes identified. Intra-patient variability of setup corrections was characterized. Results: For lateral, longitudinal and vertical setup corrections, the mean ± 1 S.D. (in mm) were: −0.6 ± 3.8, 2.8 ± 5.1, and 1.1 ± 3.9. Each of the three means is statistically significant from the theoretical population mean of zero (p<0.01). For rotations, the means were within 0.1° from zero, with a standard deviation of 1.3°. Moderate correlation (r = −0.45) was observed between longitudinal and pitch corrections, which can be caused by changes in the spinal column position, to which registration is mostly done. The standard deviation for intra-patient corrections varies among patients: 2 – 10 mm for translations and 0.5 – 3° for rotations. Intra-patient variability in translations has a positive correlation with that in rotations. Conclusions: In 6DOF setup corrections for lung patients, systematic translational corrections were observed, with moderate correlation between longitudinal and pitch corrections. Careful setups and custom immobilization may help reduce such offsets, correlations, and intra-patient setup variability.

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 09: Impact of the distance of reflective markers from linac isocenter on the positional accuracy of an infrared tracking system

Purpose: The HexaPOD™ six degree of freedom couchtop is equipped with an optical tracking system, consisting of a stereoscopic camera and a reference frame (RF) carrying infrared reflective markers. The manufacturer recommends placing the RF within 50 cm from linac isocenter (ISO), which is a serious limitation since the RF does not fit around the shoulders of most brain patients. This study quantifies the impact of extended RF distances from ISO on positional accuracy. Methods: An in-house tool with an estimated resolution of 0.3 mm and 0.1° was used. It is a large cube and a mathematical model of HexaPOD motion to determine the intersection of room lasers with the ruled cube edges. Combinations of translations (±1 and ±3 cm) and rotations (±2.5°) were executed on two HexaPOD couchtops for multiple RF distances from ISO (35 to 77 cm). For each combination, ten laser readings were fed into a least squares algorithm to determine the executed translations and rotations while minimizing operator reading errors. Results: The usable tracking volume is up to an RF distance of 82 cm from ISO. Positional accuracy of the HexaPOD/iGuide system is 0.6 mm and 0.1° (95% confidence). Positional accuracy variations versus RF distance from ISO are statistically insignificant (p = 0.05). Our results generally confirm recent internal estimates by the manufacturer (for future release). Conclusions: RF distances up to 77 cm from ISO are clinically acceptable, provided performing a patient safety study with a verification scan.

SU-F-J-52: A Novel Approach to X-Ray Tube Quality Assurance for CBCT Systems in Order to Better Assess the Patient Imaging Dose in a Large, Multi-Unit Treatment Facility

PURPOSE To standardize the tube calibration for Elekta XVI cone beam CT (CBCT) systems in order to provide a meaningful estimate of the daily imaging dose and reduce the variation between units in a large centre with multiple treatment units. METHODS Initial measurements of the output from the CBCT systems were made using a Farmer chamber and standard CTDI phantom. The correlation between the measured CTDI and the tube current was confirmed using an Unfors Xi detector which was then used to perform a tube current calibration on each unit. RESULTS Initial measurements showed measured tube current variations of up to 25% between units for scans with the same image settings. In order to reasonably estimate the imaging dose, a systematic approach to x-ray generator calibration was adopted to ensure that the imaging dose was consistent across all units at the centre and was adopted as part of the routine quality assurance program. Subsequent measurements show that the variation in measured dose across nine units is on the order of 5%. CONCLUSION Increasingly, patients receiving radiation therapy have extended life expectancies and therefore the cumulative dose from daily imaging should not be ignored. In theory, an estimate of imaging dose can be made from the imaging parameters. However, measurements have shown that there are large differences in the x-ray generator calibration as installed at the clinic. Current protocols recommend routine checks of dose to ensure constancy. The present study suggests that in addition to constancy checks on a single machine, a tube current calibration should be performed on every unit to ensure agreement across multiple machines. This is crucial at a large centre with multiple units in order to provide physicians with a meaningful estimate of the daily imaging dose.

SU‐E‐T‐602: Investigation of Target Motion for Serially Delivered TMI Treatments

Purpose: Total marrow irradiation (TMI) delivered via helical TomoTherapy (HT) presents a unique challenge for organ localization because the entire target structure (skeletal bone) cannot be imaged and registered with the planning CT accordingly. Therefore a few surrogates must be used to determine the position of many structures along the entire length of the patient. We investigated the CTV to PTV margin sizes required in order to maintain common target coverage requirements. Methods: Three patients were immobilized in full‐body Vac‐locs with a thermoplastic mask to cover the head and shoulders. Patients were initially aligned to the head and neck anatomy and to the pelvic girdle in upper body and lower body plans, respectively. Both plans were interrupted during delivery to determine the position of different anatomy (the T10 vertebrae in the upper body plan and the ankle region in the lower body plan) and to realign the patient. Results: Intrafraction motion in the S/I direction was within the uncertainty of the measurement. The positions of the same anatomy separated by up to 40 min correlate well (R>8) indicating that intrafraction motion is small. The standard deviations of the systematic setup errors were all under 2mm, and were marginally smaller in the upper body plan. The standard deviations of the random setup errors were twice as large in the L/R directions than in the A/P directions for both the upper and lower body plans. We determined the width of the blurred dose distribution penumbra specific to the interrupt locations. Conclusions: The resultant margins in the A/P directions and L/R directions were similar in both plans, under 8mm. The data presented only applies to the limited number of patients and interrupt positions chosen, and requires further investigation at many different anatomical sites in order to be applied over the whole body.

Poster — Thur Eve — 31: Optimum Frequency of Spatial Registration in Image Guided Radiation Therapy for TMI

Purpose: To assess the influence of the frequency of spatial registration in total marrow irradiation using Helical Tomotherapy to correct for intrafraction variations. Methods: The analysis was performed using TCP and NTCP models in a phantom study. Different cases were investigated: one treatment per fraction (no‐junction), and splitting the treatment along Y‐axis (SUP‐INF direction) into 2 or 3 independent sub‐treatments (one/two‐junction), which allows 2 or 3 spatial registrations per treatment fraction. Linearly increasing margins were added to expand the CTV (ribs and spine) and OARs (lungs) with increasing distance from the registration point (iPTV and iPRV). Margin increases of 5, 10 and 15 mm were analyzed. The prescription was for 95% of the iPTV to receive 20 Gy. Results: The dose to the iPRVs was reduced when the treatment was split; D20 to lung was 22, 16.2 and 13.4 Gy for no‐junction, one‐junction and two‐junction cases respectively. However the dose received by the iPTV also decreased; the volume of the iPTV receiving the prescription was 93.9%, 90.5% and 88.4% respectively. The probability of uncomplicated cure TCP(1‐NTCP) increased 3% from no‐junction to two‐junction cases for a maximum margin of 5 mm. The corresponding difference for maximum margin of 15 mm was 22%. Larger margins combined with splitting the treatment to perform additional patient registrations showed benefit, mainly due to lower NTCP. Conclusion: Increasing uncertainties can be reduced by splitting large treatments and realigning the patient prior to each sub‐treatment. This technique reduces the NTCP and marginal misses of the PTV.