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Predictive Factors for Severe Toxicity after Thoracic Chest Wall Reirradiation
Proceedings of the 51st Annual ASTRO Meeting MRSI at 3 T was performed to measure metabolic parameters, such as lac/pyre and ala/pyr ratios, in both kidneys. Animals were anesthetized (isoflurane and O2) during the irradiation and imaging. Results: In our data at 15 Gy and both postirradiation times of 2-days and 21-days, 13C spectra in kidneys clearly show pyr and its downstream metabolic products lac and ala. Further analyses indicate lac/pyr is lower in irradiated kidney than the nonirradiated kidney in comparison to a normal rat. Conclusions: Our data imply that metabolic response due to radiation-induced alterations in renal tissues can be detectable and quantifiable by this novel metabolic imaging technique. Application of hyperpolarized 13C MRSI technique provides valuable tool to assess radiation-induced tissue damage. Author Disclosure: L. Senadheera, None; D. Mayer, None; M.M. Darpolor, None; Y. Yen, None; D.M. Spielman, None; L. Xing, None.
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Predictive Factors for Severe Toxicity after Thoracic Chest Wall Reirradiation
S. K. Nguyen1, D. Tremblay1, A. Dagnault1,2 1 De´partement de radio-oncologie de l’Hoˆtel-Dieu de Que´bec, Que´bec, QC, Canada, 2Centre de Recherche´ de L’Hoˆtel-Dieu de Que´bec, CHUQ, Que´bec, QC, Canada Purpose/Objective(s): To describe side effects after reirradiation (re-RT) of the thoracic chest wall, and to study associated predictive factors for severe toxicity in order to provide insight into chest wall re-RT tolerance. Materials/Methods: Between 1987 and 2007, a retrospective review of our experience identified 345 overlap regions in 257 patients who underwent re-RT of the thoracic chest wall. The biologically effective dose (BED) was calculated for acute toxicity with an a/b ratio of 10 and late toxicity with an a/b ratio of 3. Toxicities were graded and grouped into categories: severe, mild, and no toxicity until last follow-up. Cox stepwise regression analysis was used to determine factors associated with severe toxicity. Results: Breast cancer was the predominant histology at initial RT (78%) and re-RT (75%), followed by lung cancer and lymphoma. The total median dose was 45 Gy (±11 Gy) at initial irradiation (RT) and was 30 Gy (±12 Gy) at re-RT. Of the 345 regions, 92% were the result of one re-treatment, 7% of two re-treatments (3 consecutive courses) and 0.3% of 3 re-treatments (4 consecutive courses). Of the 257 patients, 74% had one overlap region, 20% had 2, 6% had 3, and 1% had 4 regions of overlap. The median cumulative dose to the overlap region was 78 Gy (±27 Gy3). The median interval to re-RT was 42 months (±88 months) for regions re-treated once. Median follow-up from re-RT for all regions was 10 months (±29 months). Acute and late severe toxicity occurred in 9 and 11 overlap regions, respectively, all within 60 months of follow-up. Moreover, severe toxicity only occurred in regions with a cumulative BED3 of 139 Gy3 or more. No Grade 4 or 5 toxicity was reported. On multivariate analysis, shorter interval between initial treatment and re-RT (p = 0.01) and cumulative BED10 (p \ 0.0001) were the most important factors for severe acute toxicity. Factors retained for late severe toxicity were presence of comorbidity (p = 0.0006), number of overlap regions per patient (p \ 0.0001) and cumulative BED3 (p \ 0.0001). Conclusions: Chest wall re-RT resulted in acceptable toxicity. Re-RT may be given with less concern in patients with fewer predictors. Late severe toxicity seems less probable if the cumulative biologically effective dose is #139 Gy3. Author Disclosure: S.K. Nguyen, None; D. Tremblay, None; A. Dagnault, None.
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SPECT-based Dose Rearrangement in Normal Lung to Minimize Loss of Function While Maintaining Physical Dose-based Iso-NTCP Limits
R. K. Ten Haken, D. L. McShan, K. Jee, D. S. Tatro, S. Yuan, F. Kong University of Michigan, Ann Arbor, MI Purpose/Objective(s): The prospective use of NTCP models facilitates individualization of patient tumor doses at safe (isoNTCP) levels. These models (and their derived parameters) generally assume contributions to ‘‘affect’’ metrics in proportion to physical volume (cm3) weighted dose. Thus, it is prudent (population-based safety concern) to proceed within these clinically established, physical volume-based, and dose limits/guidelines. However, lately, treatment planning considerations can include factors unrelated to equal weightings of doses by physical volume. Here, we investigate dose ‘‘rearrangement’’ in normal lung to minimize ‘‘functional volume’’ weighted dose while yet maintaining ‘‘physical volume’’ based NTCP limits. Materials/Methods: The IMRT dose distributions were obtained by first optimizing tumor coverage at fixed normal lung isoNTCP levels based on physical volume only and our existing NTCP model. Plans were then re-optimized to rearrange dose in the lung on a voxel-by-voxel basis to minimize the predicted loss of overall function (either lung perfusion or ventilation or V/ Q ratio) weighted dose, based on coregistered SPECT-CT studies, yet while maintaining target volume gEUD and the NTCP values at previously computed (from physical volume weighted dose) levels. This was accomplished using gEUD and NTCP based costlets directly in the optimization process within a multicriteria optimization scheme (lexicographic ordering) which categorized planning objectives into several, staged levels of priority; the final step being dose rearrangement based on function. Results: While preserving all physical volume-based PTV and normal lung metrics (such as NTCP or mean dose), dose functionalvolume histograms (DfVHs) generated after the last optimization step compared to those computed after the previous physical volume optimization step reveal reductions in ’’function-weighted’’ dose primarily for the mid- to low-dose values. This is reflected in corresponding reductions on the order of 10% in metrics such as mean function-weighted dose derived from the DfVHs. The dose rearrangements in areas away from the PTV introduced by the final step to preferentially reduce dose to voxels with higher SPECT intensities are easily illustrated when dose distributions are overlaid on coregistered V or Q scans. Conclusions: Multicriteria optimization, with its staged approach to plan objectives, permits the generation of IMRT treatment plans at traditional physical volume based iso-NTCP levels but, with the ability to rearrange dose after consideration of other factors. This staged, dose rearrangement in normal lung allows the potential for greater preservation of lung function as indicated by V/ Q SPECT at equivalent physical volume-based iso-NTCP levels. Author Disclosure: R.K. Ten Haken, None; D.L. McShan, None; K. Jee, None; D.S. Tatro, None; S. Yuan, None; F. Kong, None.
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103
Predictive Factors for Severe Toxicity after Thoracic Chest Wall Reirradiation
S. K. Nguyen1, D. Tremblay1, A. Dagnault1,2 1 De´partement de radio-oncologie de l’Hoˆtel-Dieu de Que´bec, Que´bec, QC, Canada, 2Centre de Recherche´ de L’Hoˆtel-Dieu de Que´bec, CHUQ, Que´bec, QC, Canada Purpose/Objective(s): To describe side effects after reirradiation (re-RT) of the thoracic chest wall, and to study associated predictive factors for severe toxicity in order to provide insight into chest wall re-RT tolerance. Materials/Methods: Between 1987 and 2007, a retrospective review of our experience identified 345 overlap regions in 257 patients who underwent re-RT of the thoracic chest wall. The biologically effective dose (BED) was calculated for acute toxicity with an a/b ratio of 10 and late toxicity with an a/b ratio of 3. Toxicities were graded and grouped into categories: severe, mild, and no toxicity until last follow-up. Cox stepwise regression analysis was used to determine factors associated with severe toxicity. Results: Breast cancer was the predominant histology at initial RT (78%) and re-RT (75%), followed by lung cancer and lymphoma. The total median dose was 45 Gy (±11 Gy) at initial irradiation (RT) and was 30 Gy (±12 Gy) at re-RT. Of the 345 regions, 92% were the result of one re-treatment, 7% of two re-treatments (3 consecutive courses) and 0.3% of 3 re-treatments (4 consecutive courses). Of the 257 patients, 74% had one overlap region, 20% had 2, 6% had 3, and 1% had 4 regions of overlap. The median cumulative dose to the overlap region was 78 Gy (±27 Gy3). The median interval to re-RT was 42 months (±88 months) for regions re-treated once. Median follow-up from re-RT for all regions was 10 months (±29 months). Acute and late severe toxicity occurred in 9 and 11 overlap regions, respectively, all within 60 months of follow-up. Moreover, severe toxicity only occurred in regions with a cumulative BED3 of 139 Gy3 or more. No Grade 4 or 5 toxicity was reported. On multivariate analysis, shorter interval between initial treatment and re-RT (p = 0.01) and cumulative BED10 (p \ 0.0001) were the most important factors for severe acute toxicity. Factors retained for late severe toxicity were presence of comorbidity (p = 0.0006), number of overlap regions per patient (p \ 0.0001) and cumulative BED3 (p \ 0.0001). Conclusions: Chest wall re-RT resulted in acceptable toxicity. Re-RT may be given with less concern in patients with fewer predictors. Late severe toxicity seems less probable if the cumulative biologically effective dose is #139 Gy3. Author Disclosure: S.K. Nguyen, None; D. Tremblay, None; A. Dagnault, None.
104
SPECT-based Dose Rearrangement in Normal Lung to Minimize Loss of Function While Maintaining Physical Dose-based Iso-NTCP Limits
R. K. Ten Haken, D. L. McShan, K. Jee, D. S. Tatro, S. Yuan, F. Kong University of Michigan, Ann Arbor, MI Purpose/Objective(s): The prospective use of NTCP models facilitates individualization of patient tumor doses at safe (isoNTCP) levels. These models (and their derived parameters) generally assume contributions to ‘‘affect’’ metrics in proportion to physical volume (cm3) weighted dose. Thus, it is prudent (population-based safety concern) to proceed within these clinically established, physical volume-based, and dose limits/guidelines. However, lately, treatment planning considerations can include factors unrelated to equal weightings of doses by physical volume. Here, we investigate dose ‘‘rearrangement’’ in normal lung to minimize ‘‘functional volume’’ weighted dose while yet maintaining ‘‘physical volume’’ based NTCP limits. Materials/Methods: The IMRT dose distributions were obtained by first optimizing tumor coverage at fixed normal lung isoNTCP levels based on physical volume only and our existing NTCP model. Plans were then re-optimized to rearrange dose in the lung on a voxel-by-voxel basis to minimize the predicted loss of overall function (either lung perfusion or ventilation or V/ Q ratio) weighted dose, based on coregistered SPECT-CT studies, yet while maintaining target volume gEUD and the NTCP values at previously computed (from physical volume weighted dose) levels. This was accomplished using gEUD and NTCP based costlets directly in the optimization process within a multicriteria optimization scheme (lexicographic ordering) which categorized planning objectives into several, staged levels of priority; the final step being dose rearrangement based on function. Results: While preserving all physical volume-based PTV and normal lung metrics (such as NTCP or mean dose), dose functionalvolume histograms (DfVHs) generated after the last optimization step compared to those computed after the previous physical volume optimization step reveal reductions in ’’function-weighted’’ dose primarily for the mid- to low-dose values. This is reflected in corresponding reductions on the order of 10% in metrics such as mean function-weighted dose derived from the DfVHs. The dose rearrangements in areas away from the PTV introduced by the final step to preferentially reduce dose to voxels with higher SPECT intensities are easily illustrated when dose distributions are overlaid on coregistered V or Q scans. Conclusions: Multicriteria optimization, with its staged approach to plan objectives, permits the generation of IMRT treatment plans at traditional physical volume based iso-NTCP levels but, with the ability to rearrange dose after consideration of other factors. This staged, dose rearrangement in normal lung allows the potential for greater preservation of lung function as indicated by V/ Q SPECT at equivalent physical volume-based iso-NTCP levels. Author Disclosure: R.K. Ten Haken, None; D.L. McShan, None; K. Jee, None; D.S. Tatro, None; S. Yuan, None; F. Kong, None.
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