Index of content:
Volume 33, Issue 6, June 2006
- Therapy Scientific Session: Room 230 A
- Radiobiology II
33(2006); http://dx.doi.org/10.1118/1.2241963View Description Hide Description
Purpose: Dose‐volume metrics have often been correlated with outcomes and are often used to evaluate treatment plans. Unfortunately, when used for IMRTtreatment planning, dose‐volume metrics are computationally complex (non‐convex) and can warp DVHs near the constraint dose. We investigate whether the generalized equivalent uniform dose (gEUD) can be made to highly correlate with different parts of the DVH curve by tuning the exponential parameter. If so, gEUD may be a smooth and computationally attractive replacement for dose‐volume metrics in treatment planning and evaluation. Method and Materials: We correlated gEUD with various values of its parameter a and clinically applicable dose‐volume constraints. Three datasets were used: lung, esophagus, and prostate, with 219, 263, and 291 patient plans, respectively. We tested values of a between −10 and 10 by intervals of 0.2 and in some cases tested values as low as −40. The dose‐volume constraints tested include: V10, V20, and V30 for lung, V55 for esophagus, and D95 for prostate PTV and lung PTV. Results: For all cases tested, we found a Spearman correlation between 0.917 and 0.989 (mean correlation 0.956) with negligible (<1×10−6) p‐values. Values of a ranged from 0.4 to 3.2 for volume metrics and −7.8 to −27.2 for lung PTV and prostate PTV dose metrics (respectively). Conclusion: There is a significant and strong correlation between dose‐volume metrics and gEUD for the datasets tested. The practical application of this is that for a particular dose‐volume metric, we can find the value of a (the gEUD parameter) with the highest correlation and use the convex gEUD function in place of the non‐convex dose‐volume constraint in the IMRT optimization, thereby allowing optimization to be faster and more able to efficiently achieve a global optimum. Conflict of Interest: Partially supported by NIH grant R01 CA85181 and a grant from TomoTherapy, Inc.
33(2006); http://dx.doi.org/10.1118/1.2241964View Description Hide Description
Purpose: To quantify the loss in effective dose resulting from prolongation of treatment fraction delivery times associated with IMRT, and investigate the corresponding effects for neutronIMRT.Method and Materials: The effect of treatment fraction delivery time prolongation was investigated in vitro using human PC3 prostate and HGL21 and U373 glioblastoma tumor cell lines. Cells were maintained at 37 degrees Celsius and irradiated with photons from a conventional linac and with d(48.5)+Be fast neutrons. The delivery time for simulated, multiple‐port fractions was varied from acute to 60 minutes for photonirradiation, and acute to 120 minutes for neutron irradiation. Physical dose ranges for cell survival analysis were 0.5–6 Gy and 0.16–2 Gy for photons and neutrons, respectively. Results: Prolonging photon delivery time (from initiation to completion of irradiation) from 5 to 45 minutes resulted in a loss in effective dose of 6% and 11% in the PC3 and HGL21 cell lines, respectively. A loss of <1% in effective dose was observed for similar prolongation of neutron irradiation of PC3 and HGL21, and photonirradiation of U373 cells. More clinically common prolongations of 5 to 30 and 5 to 15 minutes resulted in effective dose reductions of 4% and 1.5% for PC3, and 6% and 2.5% for HGL21. Application of typical dose response gradients would result in even larger percentage reductions in calculated TCP. Conclusions: This work indicates that prolonged fraction delivery times may have a significant impact on treatment outcome for tumors with a low α/β ratio and short repair half‐time. These effects are significant at delivery times commonly associated with IMRT and are highly variable with cell type. Fraction delivery time should therefore be minimized to achieve the most predictable radiobiological effect. This work also demonstrates that the biological effect of neutronradiotherapy is independent of fraction delivery time.
33(2006); http://dx.doi.org/10.1118/1.2241965View Description Hide Description
Purpose: To investigate whether IMRToptimization based on generalize equivalent uniform dose1 (gEUD) objectives for target volumes and organs at risk (OAR) alike can lead to superior plans as oppose to multiple dosevolume (D&V) based objectives plans, for head and neck (H&N) and postmastectomy chest wall (CW) treatment sites. Methods and Materials: We applied gEUD—based optimization to obtain IMRT plans for H&N and CW cancer patients and compared them with the corresponding plans a) optimized with stringent multiple D&V objectives and b) optimized with the standard in‐house physician requested (phys) D&V objective. The D&V optimized plans were created with objectives based on the resultant gEUD plans with the same weight of importance, in order to drive the optimization as close to the gEUD plan as possible. The plan comparison at this point was based on DVH analysis. Results: For all H&N and CW cancer patient in the study, we found that gEUD‐based optimization led to superior sparing of OARs, even beyond the specified requirements, with the same or better target coverage when compared to either the phys‐based or D&V‐based plans respectively. In order to avoid dose inhomogeneities in the target volumes created by the gEUD‐based optimization, use additional D&V objectives just for targets needed to be employed. Conclusions: The general conclusion drawn from our investigation is that the EUD objective function uses smaller number of parameters compared to the D&V and, allows a larger number of solutions with different DVHs but the same EUD. Thus, a better plan was delivered with EUD compared to multiple D&V objectives optimization for either the H&N or CW treatment sites. The use of EUD can allow the plan evaluation to be based on both DVHs and EUD. Details of the method will be discussed. 1Niemierko A. Med. Phys. 26 (abstract), 1100 (1999).
33(2006); http://dx.doi.org/10.1118/1.2241966View Description Hide Description
Purpose: The zebrafish, Danio rerio has in recent years become a preferred model to study human disease. Our aim was to test the new micro‐irradiator for its capability to perform basic radiobiology experiments, in particular to investigate relationship between radiation, apoptosis and inflammatory response. Materials and Methods: A novel micro‐irradiator, which enables high dose radiation of biological samples below 1 mm, was used to irradiate zebrafish embryos at different age postfertilization. Two experiments were performed — total body irradiation and partial body irradiation. In total body irradiation, the embryos were irradiated up to 40 Gy and the amount of surviving neutrophils as a function of time was analyzed. In partial‐body irradiation, only zebrafish embryo tails were irradiated to 20 Gy and time‐dependent apoptotic and inflammatory response was assessed. FITS‐labeled neutrophil‐specific antibody protein myeloperoxidase was used for neutrophil labeling and TUNEL assays were used for apoptosis labeling. Results: In total body irradiation experiments, little effect was observed at earlier time points post irradiation, but a sharp decrease in the number of neutrophils was observed at 72 hours post irradiation (hpi) suggesting that inflammatory cells can be completely ablated. In partial body irradiation experiments the inflammatory response seems to follow apoptotic response. Significant apoptotic and inflammatory activity was observed at few hours after irradiation, which slowly decreased to almost no activity as early as 24 hpi. Conclusions: Our new micro‐irradiator can perform unique radiobiological experiments. Preliminary results investigating relation between irradiation, apoptosis and inflammation indicated severe posttreatment cell ablation effects for total body irradiation and early apoptotic and inflammatory response within 24 hours post irradiation.
TH‐E‐230A‐05: Development of An Integrated Software Platform for Treatment Documentation and Outcome Analysis for IGRT33(2006); http://dx.doi.org/10.1118/1.2241967View Description Hide Description
Purpose:Information generated in IGRT is tremendous. The long‐term goal of this work is to develop a software package (named RAPID, Research Analysis Platform and IGRTDatabases) that is capable of storing patient diagnostic, treatment and follow‐up data for IGRT, which documents treatment outcome, and allows dose‐response analysis based on biophysical models. Presented here are several key components of this development. Method and Materials: The RAPID consists of a database,software tools and auxiliary applications. The database, developed using FileMaker software, includes modules for storing demographics, diagnosis, treatment, and follow up data. Diagnostic and planning images of different modalities (e.g., CT, PET, MR, US) and treatment verification images (e.g., CT,US, radiography) can be stored in DICOM format. Using an integrated auxiliary application these images can be brought into the desktop. The database is integrated with another software package, CERR, developed at Washington University, allowing display of contours and dose distributions on planning images. Various software tools are developed to perform dose response analysis that is linked to documented treatment outcome. For example, treatment related toxicity definitions for a given anatomic site were incorporated into the database, allowing standardized documentation of toxicity which, in turn, facilitates dose‐response analysis. Calculations of EUD, TCP and NTCP are enabled based on 3D dose distributions. Results: The newly developed RAPID is found to be useful. Patient data collected in our clinic for two anatomic sites have been entered into the system. Analysis of treatment and follow‐up toxicity was effectively carried out using the RAPID. With a FileMaker server installed to host the database, users can access password‐protected information remotely.
Conclusion: We have developed a software platform, RAPID, to facilitate storage and analysis of IGRT clinical outcome data.
TH‐E‐230A‐06: Comparison of Correction and Model Based Dose Algorithms in Lung Cancer Retrospective Dose Recalculation and Treatment Outcome Evaluation33(2006); http://dx.doi.org/10.1118/1.2241968View Description Hide Description
Purpose: To perform a systematic comparison of the Monte Carlo(MC), convolution/superposition (CS), and equivalent path length (EPL)‐based dose calculation algorithms for the purposes of outcomes modeling in lungcancertreatment planning.Methods: Several treatment plans (originally planned using EPL) from a large database of patients treated on a lungdose escalation protocol were retrospectively recalculated using MC and CS. Doses were computed in the homogeneous (unit‐density) and heterogeneous geometries; homogeneous calculations were used to elicit differences in the beam models To evaluate algorithmic differences due to heterogeneity effects, beam model differences were minimized by adjusting beam weights in the homogeneous plans to achieve the same prescribed dose with each algorithm. These beam weights were then applied to the heterogeneous geometries. Absolute dose distributions were compared using: color‐wash dose difference displays, isodose lines, EUD (for the target) and mean lungdose (MLD) and NTCP (for the normal lungs).Results: For the target, MC and CS‐computed EUDs were in good agreement for both homogeneous and heterogeneous cases, with maximum dose differences of 1.2 Gy noted. Differences between EPL and MC (or CS) were generally much larger, in the heterogeneous plans extending up to 6 Gy. Differences in MLD computed with MC and CS ranged between 2% and 15% in the heterogeneous plans. These differences were similar in the corresponding homogeneous geometries, illustrating the importance of beam model disparities. For EPL, differences in the MLD and NTCP (relative to MC or CS) were much larger in the heterogeneous plans indicating systematic differences in the normal lungdose prediction. Conclusion: Evidence thus far is suggestive that discrepancies in dose computed with EPL and MC (or CS) will lead to differences in correlations of dose with outcome with respect to the target as well as normal tissue complications (radiation induced pneumonitis) and calculated NTCP.
TH‐E‐230A‐07: Estimate of Radiobiological Parameters From Clinical Data for Treatment Planning of Liver Irradiation33(2006); http://dx.doi.org/10.1118/1.2241969View Description Hide Description
Purpose: Several different dose fractionation regimens are being developed in clinical trials for liver irradiation. For example, RTOG is initiating a new hypofractionation regimen (RTOG 0438) to treatlivercancer patients. To evaluate the radiobiological equivalence between different regimens, which is useful in the design of these trials, requires reliable radiobiological parameters. The purpose of this work is to estimate a plausible set of such parameters for livertumor based on published clinical data. Method and Materials: A phenomenological expression inspired by the linear‐quadratic (LQ) formalism was developed to fit a series of clinical survival data for radiotherapy of hepatocellular carcinoma patients. The data are from different institutes using different fractionation (e.g., 1.5, 1.8 or 4.88 Gy). The phenomenological expression consists of 6 fitting parameters including radiosensitivity parameters α and α/β, potential doubling time Tb, and clonogenic cell number K. The expression considers the prescription dose,dose per fraction, overall treatment time and the elapsed time at which the survival data were collected. We have developed an algorithm to take into account the tumor cell repopulation during the elapsed time. Results: The newly developed phenomenological expression was found to fit well to the available clinical data. Based on the fitting, we have estimated a set of plausible radiobiological parameters for livertumor: α/β = 12.8 ± 1.0 Gy, α 0.013 ± 0.002 Gy, the potential doubling time: 123 ± 9 days, and colonogenic cell number: 1302 ± 47. Using this set of parameters we have calculated a series of dose fractionation regimens that are biologically equivalent based on BED. Conclusion: A plausible set of radiobiological parameters have been obtained based on clinical data. These parameters may be used for radiation treatment planning of livertumor, in particular, for the design of new treatment regimens aimed for dose escalation.