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Is There a Loss of Biological Effect in the Accelerated Partial Breast Irradiation (APBI) for Long Treatments Time?
I. J. Radiation Oncology d Biology d Physics
S704
Volume 72, Number 1, Supplement, 2008
were cultivated for 7 days after treatment until staining and evaluation. For gene expression analysis, RNA was isolated 6h after treatment and labeled for hybridization of a human whole transcriptome cDNA Microarray. Regulated genes were identified by statistical evaluations and affected biological processes by GO analysis (gene ontology). Results: Colony formation of primary endothelial cells is found to be more sensitive towards 12-C radiation than colony formation of primary fibroblasts. More genes are found to be regulated in fibroblasts compared to endothelial cells. Interestingly in fibroblasts there are more genes activated than repressed and in endothelial cells the opposite distribution is found, more genes are repressed than activated. Genes involved in e.g., nucleotide metabolism, DNA replication and cell division tend to be repressed in both cell cultures as response to all doses. Few genes are regulated in a rather dose dependent manner. Conclusions: We see a stronger effect of 12-C radiation on the clonogenic survival of endothelial cells than on fibroblast cells. In fibroblasts more genes are found to be regulated and specially activated. Thus, these genes differentially regulated within the two cell types can be the basis for in depth investigation of the improved survival of the fibroblasts. In addition this is an option to find target points for additional treatments in e.g., radiotherapy to avoid side effects on normal tissue. Author Disclosure: U. Wirkner, None; C. Rittmueller, None; S. Trinh, None; A. Abdollahi, None; P. Huber, None.
3191
Is There a Loss of Biological Effect in the Accelerated Partial Breast Irradiation (APBI) for Long Treatments Time?
D. A. Todor1,2, A. Bondal2, I. Barani1,2, P. Lin1,2, L. Cuttino1,2, D. Arthur1,2 1
Medical College of Virginia Hospitals and Physicians, Richmond, VA, 2Virginia Commonwealth University, Richmond, VA
Purpose/Objective(s): Interstitial multi-catheter (MC) brachytherapy and MammoSite (MS) balloon brachytherapy are the APBI delivery techniques associated with the most mature outcome data. The biologically effective dose (BED) for continuous low dose-rate implants has been shown to be affected by the dose rate. Modern APBI employs high dose-rate (HDR) delivery, usually administered over 10 treatment fractions. The total treatment time for an HDR fraction will vary with the source activity and with the number of dwell positions used, which in turn vary with treatment technique. This study uses accepted radiobiological formalisms and parameters to determine the effect of prolonged treatment times on the BED for MC and MS APBI. Materials/Methods: Two delivered treatment plans (one for each technique) were used to simulate treatment delivery with source strengths ranging from 3-10 Ci and treatment times ranging from 250-1,000 seconds. For each plan, the BED was calculated using the linear-quadratic formula for each voxel of the planning target volume (PTV). These individual values were then aggregated into an equivalent uniform BED (EUBED) for the entire PTV, essentially removing any effect from non-uniformity of the dose distribution. Two models were employed. EUBED0 accounted for the total dose, fraction size, and a/b ratio. EUBED1 also included repair and the actual delivery time sequence. The prescribed dose was 34.0 Gy in 10 fractions. The MS was an elliptical balloon with PTV = 86.3 cc and 10 dwell positions, while the MC implant had 16 catheters, 227 dwell time positions and PTV = 120.5 cc. Results: Using a/b = 4 Gy, the EUBED0 was 74.6 Gy for MC and 76.0 Gy for MS. When repair and the actual delivery time sequence were considered, EUBED1 for MC drops dramatically to 54.5 Gy, 39.5 Gy, and 36.4 Gy, for treatment times one, two and three times longer than the treatment time resulting from a source activity of 8.9 Ci. Similarly, for the MS, the values decreased to 56.1 Gy, 39.9 Gy, and 36.5 Gy. Conclusions: Although both MC and MS treatment are associated with excellent local control, these calculations suggest that there may be a loss of biological effect with HDR APBI with prolonged treatment times. The final EUBED is influenced non-linearly by the size of the PTV, number of dwell positions, dose distribution, source activity and treatment time. Based on these results, treatment time may impact clinical outcome and should be recorded along with other established dosimetric parameters. Author Disclosure: D.A. Todor, SenoRx, Inc., F. Consultant/Advisory Board; A. Bondal, None; I. Barani, None; P. Lin, None; L. Cuttino, None; D. Arthur, None.
3192
a/b Ratio of Human Lung Determined Based on Reaction on Ct Image for Carbon Ion Beam
T. Sugawara Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan Purpose/Objective(s): For planning safety carbon therapy for human lung cancer, the minimum (threshold) dose to generate lung reaction on CT image was investigated at various fraction regimen. To evaluate the a/b ratio of human lung for carbon ion beam was our goal. Materials/Methods: From 1995 January to 2003 December, 44 patients with stage I non-small-cell lung cancer who were treated with carbon ion beams of various fractions (1-12 fractions a port) and total doses (28-90 GyE). Out of those, 78 irradiated fields were classified into the two groups: the reaction positive and the reaction negative according to the changes on CT image within 6 months. About every fractionation schedule of 1-, 2-, 4-, and 9-fractions, the dose-response curves between the positive rate of lung reaction and the total dose, and then the isoeffect doses to produce 50% positive on lung reaction were calculated. The a/b ratio was determined based on the plot of the reciprocal numbers of the isoeffect doses and doses per fraction. Results: Fifty percent positive doses as the isoeffect doses on lung reaction were 17.5, 27.1, 27.3, and 39.2 GyE, respectively 1-, 2-, 4-, and 9-fractions. The a/b ratio resolved from the regression line was 10.0 GyE. Conclusions: This a/b ratio was too big compared with ones of X-ray which had reported ever, and seem to be useful to estimate lung injuries prospectively in various fractionation schedule besides singe-dose irradiation in safety carbon ion beam therapy. Author Disclosure: T. Sugawara, None.
S704
Volume 72, Number 1, Supplement, 2008
were cultivated for 7 days after treatment until staining and evaluation. For gene expression analysis, RNA was isolated 6h after treatment and labeled for hybridization of a human whole transcriptome cDNA Microarray. Regulated genes were identified by statistical evaluations and affected biological processes by GO analysis (gene ontology). Results: Colony formation of primary endothelial cells is found to be more sensitive towards 12-C radiation than colony formation of primary fibroblasts. More genes are found to be regulated in fibroblasts compared to endothelial cells. Interestingly in fibroblasts there are more genes activated than repressed and in endothelial cells the opposite distribution is found, more genes are repressed than activated. Genes involved in e.g., nucleotide metabolism, DNA replication and cell division tend to be repressed in both cell cultures as response to all doses. Few genes are regulated in a rather dose dependent manner. Conclusions: We see a stronger effect of 12-C radiation on the clonogenic survival of endothelial cells than on fibroblast cells. In fibroblasts more genes are found to be regulated and specially activated. Thus, these genes differentially regulated within the two cell types can be the basis for in depth investigation of the improved survival of the fibroblasts. In addition this is an option to find target points for additional treatments in e.g., radiotherapy to avoid side effects on normal tissue. Author Disclosure: U. Wirkner, None; C. Rittmueller, None; S. Trinh, None; A. Abdollahi, None; P. Huber, None.
3191
Is There a Loss of Biological Effect in the Accelerated Partial Breast Irradiation (APBI) for Long Treatments Time?
D. A. Todor1,2, A. Bondal2, I. Barani1,2, P. Lin1,2, L. Cuttino1,2, D. Arthur1,2 1
Medical College of Virginia Hospitals and Physicians, Richmond, VA, 2Virginia Commonwealth University, Richmond, VA
Purpose/Objective(s): Interstitial multi-catheter (MC) brachytherapy and MammoSite (MS) balloon brachytherapy are the APBI delivery techniques associated with the most mature outcome data. The biologically effective dose (BED) for continuous low dose-rate implants has been shown to be affected by the dose rate. Modern APBI employs high dose-rate (HDR) delivery, usually administered over 10 treatment fractions. The total treatment time for an HDR fraction will vary with the source activity and with the number of dwell positions used, which in turn vary with treatment technique. This study uses accepted radiobiological formalisms and parameters to determine the effect of prolonged treatment times on the BED for MC and MS APBI. Materials/Methods: Two delivered treatment plans (one for each technique) were used to simulate treatment delivery with source strengths ranging from 3-10 Ci and treatment times ranging from 250-1,000 seconds. For each plan, the BED was calculated using the linear-quadratic formula for each voxel of the planning target volume (PTV). These individual values were then aggregated into an equivalent uniform BED (EUBED) for the entire PTV, essentially removing any effect from non-uniformity of the dose distribution. Two models were employed. EUBED0 accounted for the total dose, fraction size, and a/b ratio. EUBED1 also included repair and the actual delivery time sequence. The prescribed dose was 34.0 Gy in 10 fractions. The MS was an elliptical balloon with PTV = 86.3 cc and 10 dwell positions, while the MC implant had 16 catheters, 227 dwell time positions and PTV = 120.5 cc. Results: Using a/b = 4 Gy, the EUBED0 was 74.6 Gy for MC and 76.0 Gy for MS. When repair and the actual delivery time sequence were considered, EUBED1 for MC drops dramatically to 54.5 Gy, 39.5 Gy, and 36.4 Gy, for treatment times one, two and three times longer than the treatment time resulting from a source activity of 8.9 Ci. Similarly, for the MS, the values decreased to 56.1 Gy, 39.9 Gy, and 36.5 Gy. Conclusions: Although both MC and MS treatment are associated with excellent local control, these calculations suggest that there may be a loss of biological effect with HDR APBI with prolonged treatment times. The final EUBED is influenced non-linearly by the size of the PTV, number of dwell positions, dose distribution, source activity and treatment time. Based on these results, treatment time may impact clinical outcome and should be recorded along with other established dosimetric parameters. Author Disclosure: D.A. Todor, SenoRx, Inc., F. Consultant/Advisory Board; A. Bondal, None; I. Barani, None; P. Lin, None; L. Cuttino, None; D. Arthur, None.
3192
a/b Ratio of Human Lung Determined Based on Reaction on Ct Image for Carbon Ion Beam
T. Sugawara Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan Purpose/Objective(s): For planning safety carbon therapy for human lung cancer, the minimum (threshold) dose to generate lung reaction on CT image was investigated at various fraction regimen. To evaluate the a/b ratio of human lung for carbon ion beam was our goal. Materials/Methods: From 1995 January to 2003 December, 44 patients with stage I non-small-cell lung cancer who were treated with carbon ion beams of various fractions (1-12 fractions a port) and total doses (28-90 GyE). Out of those, 78 irradiated fields were classified into the two groups: the reaction positive and the reaction negative according to the changes on CT image within 6 months. About every fractionation schedule of 1-, 2-, 4-, and 9-fractions, the dose-response curves between the positive rate of lung reaction and the total dose, and then the isoeffect doses to produce 50% positive on lung reaction were calculated. The a/b ratio was determined based on the plot of the reciprocal numbers of the isoeffect doses and doses per fraction. Results: Fifty percent positive doses as the isoeffect doses on lung reaction were 17.5, 27.1, 27.3, and 39.2 GyE, respectively 1-, 2-, 4-, and 9-fractions. The a/b ratio resolved from the regression line was 10.0 GyE. Conclusions: This a/b ratio was too big compared with ones of X-ray which had reported ever, and seem to be useful to estimate lung injuries prospectively in various fractionation schedule besides singe-dose irradiation in safety carbon ion beam therapy. Author Disclosure: T. Sugawara, None.