Jakub Pritz

Fat Composition Changes in Bone Marrow During Chemotherapy and Radiation Therapy

PURPOSE To quantify changes in bone marrow fat fraction and determine associations with peripheral blood cell counts. METHODS AND MATERIALS In this prospective study, 19 patients received either highly myelotoxic treatment (radiation therapy plus cisplatin, 5-fluorouracil mitomycin C [FU/MMC], or cisplatin/5-FU/cetuximab) or less myelotoxic treatment (capecitabine-radiation therapy or no concurrent chemotherapy). Patients underwent MR imaging and venipuncture at baseline, midtreatment, and posttreatment visits. We performed mixed effects modeling of the mean proton density fat fraction (PDFF[%]) by linear time, treatment, and vertebral column region (lumbar [L]4-sacral [S]2 vs thoracic [T]10-L3 vs cervical[C]3-T9), while controlling for cumulative mean dose and other confounders. Spearman rank correlations were performed by white blood cell (WBC) counts versus the differences in PDFF(%) before and after treatment. RESULTS Cumulative mean dose was associated with a 0.43% per Gy (P=.004) increase in PDFF(%). In the highly myelotoxic group, we observed significant changes in PDFF(%) per visit within L4-S2 (10.1%, P<.001) and within T10-L3 (3.93%, P=.01), relative to the reference C3-T9. In the less myelotoxic group, we did not observe significant changes in PDFF(%) per visit according to region. Within L4-S2, we observed a significant difference between treatment groups in the change in PDFF(%) per visit (5.36%, P=.04). Rank correlations of the inverse log differences in WBC versus the differences in PDFF(%) overall and within T10-S2 ranged from 0.69 to 0.78 (P<.05). Rank correlations of the inverse log differences in absolute neutrophil counts versus the differences in PDFF(%) overall and within L4-S2 ranged from 0.79 to 0.81 (P<.05). CONCLUSIONS Magnetic resonance imaging fat quantification is sensitive to marrow composition changes that result from chemoradiation therapy. These changes are associated with peripheral blood cell counts. This study supports a rationale for bone marrow-sparing treatment planning to reduce the risk of hematologic toxicity.

Validating Fiducial Markers for Image-Guided Radiation Therapy for Accelerated Partial Breast Irradiation in Early-Stage Breast Cancer

PURPOSE Image-guided radiation therapy (IGRT) may be beneficial for accelerated partial breast irradiation (APBI). The goal was to validate the use of intraparenchymal textured gold fiducials in patients receiving APBI. METHODS AND MATERIALS Twenty-six patients were enrolled on this prospective study that had three or four textured gold intraparenchymal fiducials placed at the periphery of the lumpectomy cavity and were treated with three-dimensional (3D) conformal APBI. Free-breathing four-dimensional computed tomography image sets were obtained pre- and posttreatment, as were daily online megavoltage (MV) orthogonal images. Intrafraction motion, variations in respiratory motion, and fiducial marker migration were calculated using the 3D coordinates of individual fiducials and a calculated center of mass (COM) of the fiducials. We also compared the relative position of the fiducial COM with the geometric center of the seroma. RESULTS There was less than 1 mm of intrafraction respiratory motion, variation in respiratory motion, or fiducial marker migration. The change in seroma position relative to the fiducial COM was 1 mm ± 1 mm. The average position of the geometric seroma relative to the fiducial COM pretreatment compared with posttreatment was 1 mm ± 1 mm. The largest daily variation in displacement when using bony landmark was in the anteroposterior direction and two standard deviations (SD) of this variation was 10 mm. The average variation in daily separation between the fiducial pairs from daily MV images was 3 mm ± 3 mm therefore 2 SD is 6 mm. CONCLUSION Fiducial markers are stable throughout the course of APBI. Planning target volume margins when using bony landmarks should be 10 mm and can be reduced to 6 mm if using fiducials.

Providing a fast conversion of total dose to biological effective dose (BED) for hybrid seed brachytherapy

Optimization of permanent seed implant brachytherapy plans for treatment of prostate cancer should be based on biological effective dose (BED) distributions, since dose does not accurately represent biological effects between different types of sources. Currently, biological optimization for these plans is not feasible due to the amount of time necessary to calculate the BED distribution. This study provides a fast calculation method, based on the total dose, to calculate the BED distribution. Distributions of various numbers of hybrid seeds were used to calculate total dose distributions, as well as BED distributions. Hybrid seeds are a mixture of different isotopes (in this study 125I and 103Pd). Three ratios of hybrid seeds were investigated: 25/75, 50/50, and 75/25. The total dose and BED value from each voxel were coupled together to produce graphs of total dose vs. BED. Equations were then derived from these graphs. The study investigated four types of tissue: bladder, rectum, prostate, and other normal tissue. Equations were derived from the total dose – BED correspondence. Accuracy of conversion from total dose to BED was within 2 Gy; however, accuracy of conversion was found to be better for high total dose regions as compared to lower dose regions. The method introduced in this paper allows one to perform fast conversion of total dose to BED for brachytherapy using hybrid seeds, which makes the BED‐based plan optimization practical. The method defined here can be extended to other ratios, as well as other tissues that are affected by permanent seed implant brachytherapy (i.e., breast). PACS number: 87.55.de

Calculating prescription doses for new sources by biologically effective dose matching

PURPOSE In current clinical practice, single isotopes, such as (125)I or (103)Pd, are used as single sources in prostate seed implants. A mixture of two radionuclides in the seeds has been proposed for prostate cancer treatment. This study investigates a method for determining the prescription dose for these new seeds using the biological effective dose (BED). METHODS Ten prostate cancer cases previously treated using single radionuclide seeds were selected for this study. The BED distribution for these cases was calculated. Plans using other radionuclides were then calculated based on this BED distribution. Prescription values could then be obtained for the calculated plans. The method was verified by calculating the prescription dose for (103)Pd and (125)I and comparing to clinical values. The method was then applied to a hybrid seed that consisted of a mixture of (125)I and (103)Pd radionuclides, which deliver equal dose to 1cm from the source in water (50/50D@1 cm). A prescription BED value was also calculated. RESULTS A prescription BED of 110 Gy was found to correlate to a prescription dose of 145, 120, and 137 Gy for (125)I, (103)Pd, and 50/50D@1 cm hybrid seeds, respectively. CONCLUSION The method introduced in this article allows one to calculate the prescription dose for new and novel sources in brachytherapy. The method was verified by calculating a prescription dose for (125)I and (103)Pd radionuclides that coincides with values used clinically.

WE‐C‐WAB‐06: Effects of Radiation On Functional Bone Marrow in Patients with Pelvic Malignancies

PURPOSE To test the hypothesis that pelvic bone marrow fat fraction (FF) (i.e., quantity of fat relative to water) varies with glucose metabolism and radiation dose in patients undergoing pelvic radiotherapy. METHODS 34 patients with pelvic malignancies were enrolled from 2009-2012 on prospective trials; 31 received concurrent chemotherapy. All patients underwent baseline 18 F-FDG-PET and quantitative MRI with IDEAL-IQ. 9 patients underwent PET/CT simulation, 15 PET/CT, and 10 PET-only. 18 and 14 patients underwent IDEAL-IQ at mid-treatment and 1-3 weeks post-treatment, respectively. PET-only scans were rigidly registered to the planning CT (pCT). PET/CT and IDEAL-IQ scans were deformably registered to the pCT (Velocity AI, Atlanta, GA). Each image was resampled to the pCT, creating a database of FF, dose, and body weight-standardized uptake value (SUVbw) for each voxel. Analyses were performed on pelvic bone from L5 to ischia. Spearman rank correlation coefficients (SRCC) were estimated comparing SUVbw and dose vs. FF1 , ΔFF21 , and ΔFF31 . FF1 represents FF at baseline and ΔFF21 and ΔFF31 represent change in FF from baseline to mid-and post-treatment, respectively. Mean SRCCs were tested for significance using a 2-sided t-test. RESULTS Data analysis was completed for 15 patients (13 gynecologic, 7 anal cancer). We observed a significant negative correlation between SUVbw and FF1, and significant positive correlations between SUVbw and ΔFF21 and ΔFF31 (Table), indicating that high metabolic activity correlated with lower FF (a surrogate for red marrow) and increased conversion to fat (yellow marrow) during radiotherapy. We observed significant positive correlations between radiation dose and ΔFF21 and ΔFF31 , indicating that regions of higher dose were more likely to convert to fat (Table). No correlation was observed between dose and FF1. CONCLUSION Preliminary results suggest that red marrow has higher metabolic activity, and is more likely to convert to yellow marrow during radiotherapy, in a dose-dependent manner. Funding has been provided by NIH R21 Research Grant (#CA162718-01) and by the American Society of Clinical Oncology.

SU‐E‐T‐653: Dosimetric Evaluation of Prostate Brachytherapy Using Single Isotope and Hybrid Seeds

Purpose: Clinically, single isotope, such as I‐125 or Pd‐103, is commonly used in the seeds in brachytherapy for prostate cancer. A mixture of two isotopes in the seeds has been proposed for prostate cancer treatment. This study investigates the differences in biological effective dose (BED) between the treatment plans of such hybrid sources and plans of single isotope. Methods: Five prostate cancer cases previously treated using single isotope seeds were selected for this study. Hybrid seed plans of a 50/50 mixture of I‐125 and Pd‐103 and a single isotope Pd‐103 were generated based on the original I‐125 plans. Number and location of seeds were the same between the plans. A numerical approach was implemented in the BED calculation. Dose and BED homogeneity in PTV, mean BED in organs at risk (OAR) and hot BED to OAR were compared between the plans. Results: To achieve the same BED (110 Gy) to cover 90% of PTV, the corresponding dose is 145, 120 and 136 Gy for I‐125, Pd‐103 and 50/50 hybrid seeds respectively. The hybrid plans demonstrated the most homogeneous dose and BED in PTV. The mean highest BED delivered to a 1.0 cc volume of rectal tissue by the I‐125, Pd‐103, and 50/50 hybrid modality was 49.85±30.24, 93.73±38.33, and 82.52±34.08 Gy respectively, delivered to a 1.0 cc volume of bladder was 41.6±19.5, 66.8±27.9 and 61.6±25.2 Gy respectively, and to other normal tissue was 303.41±63.84, 363.95±197.29, and 319.14±146.72 Gy respectively Conclusions: The prescription dose to cover 90% PTV by a BED of 110 Gy is 145, 120 and 136 Gy for I‐125, Pd‐103 and 50/50 hybrid seeds respectively. Based on the BED data, the best OAR sparing occurs with I‐125 treatment plans, followed by the 50/50 hybrid plans, and finally the Pd‐103 plans.