Purpose/Objectives(s) 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 (radiotherapy plus cisplatin, 5FU/MMC or cisplatin/5FU/cetuximab) or less myelotoxic treatment (capacitabine-radiotherapy or no concurrent chemotherapy). Patients underwent MR imaging and venipuncture at baseline, mid-treatment, and post-treatment visits. We performed mixed effects modeling of the mean proton density fat fraction (PDFF(%)) by linear-time, treatment, and vertebral column region (L4-S2 vs. T10-L3 vs. C3-T9), while controlling for cumulative mean dose and other confounders. Spearman rank correlations were performed by blood cell counts versus the difference in PDFF(%) pre- and post-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 difference in WBC versus the difference in PDFF(%) overall and within T10-S2 ranged from 0.69-0.78 (p<0.05). Rank correlations of the inverse log difference in ANC versus the difference in PDFF(%) overall and within L4-S2 ranged from 0.79-0.81 (p<0.05). Conclusion MRI fat quantification is sensitive to marrow composition changes that result from (chemo)radiotherapy. 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.

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Background and Purpose We compared [18F]fluoro-2-deoxy-2-D-glucose (FDG) versus 3′-deoxy-3′-[18F]fluorothymidine (FLT) for the purpose of identifying active pelvic bone marrow (BM), quantifying its locational variation, and determining which technique is likely to be better for BM-sparing radiation planning. Material and Methods We sampled 41 patients, of which 25 underwent FDG-PET/CT only, 7 underwent FLT-PET/CT only, and 9 underwent both. Active BM subvolumes were defined as subsets of the pelvic BM with the highest standardized uptake values comprising 40%, 50%, and 60% of the total pelvic BM volume. We used the Dice similarity coefficient to quantify the percent overlap of active BM volumes of equal size. Differences in the spatial distribution of active BM were assessed using a region-growing algorithm. Results For patients with both modalities, the mean Dice coefficients for the 40%, 50%, and 60% subvolumes were 0.683, 0.732, and 0.781 respectively. Comparing individual active BM subvolumes to the mean subvolume, Dice coefficients varied from 0.598–0.889 for FDG and 0.739–0.912 for FLT. Region growing analysis showed FLT-PET defined more highly clustered active BM subvolumes. Conclusions Within the limitations of a small sample size, we found significant agreement between FDG-PET and FLT-PET; however, FLT-PET had significantly less individual variation and is likely to be superior to FDG-PET for BM-sparing radiotherapy.

SummaryWe performed an international phase II trial to test the Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. hypothesis that intensity modulated radiation therapy (IMRT) would reduce the acute toxicity for locoregionally advanced cervical cancer. For the 83 patients enrolled, acute gastrointestinal toxicity was significantly reduced with both IMRT and positron emission tomography-guided bone marrow sparing IMRT (IG-IMRT) compared with historical controls. The incidence of neutropenia was significantly reduced in patients who underwent IG-IMRT. We conclude that IMRT reduces acute toxicity compared with standard treatment in this population and that IG-IMRT warrants testing in randomized trials.Methods and Materials: We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade !3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life. Results: From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (PZ.012). The incidence of grade !3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (nZ48), those treated with IG-IMRT (nZ35) had a significantly lower incidence of grade !3 neutropenia (8.6% vs 27.1%; 2-sided c 2 PZ.035) and nonsignificantly lower incidence of grade !3 leukopenia (25.7% vs 41.7%; PZ.13) and any grade !3 hematologic toxicity (31.4% vs 43.8%; PZ.25). Conclusions: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia. Ó

Objectives Image-guided radiation therapy (IGRT) improves setup accuracy and reduces treatment margins, potentially improving efficacy while decreasing long-term toxicity of whole breast irradiation (WBI). This study quantifies intraparenchyma fiducial motion and utility during the course of WBI. Methods On a prospective IRB-approved protocol, textured gold fiducials were placed intraoperatively at the periphery of the surgical bed in 25 patients who then received 3D conformal conventional WBI. Free breathing and 4D CT image sets were obtained at pre-treatment simulation and at 6 weeks of treatment. Respiration-induced motion was assessed by comparing fiducials' position between inspiration and expiration. Fiducial migration and setup variation were determined by comparing the relative positions of each marker from the preand post-treatment megavoltage and 4D CT image sets. Results Average intrafraction respiratory motion on 4D CT image sets was 0.1 mm. Variation in separation between fiducial pairs compared to simulation CT was on average 0.7 mm. The position of the seroma center was stable with respect to the center of mass (COM) of the fiducials throughout treatment. Based on daily megavoltage portal images, the average variation in the fiducial COM relative to the vertebral body landmark was 9.4 mm. The average variation of the seroma relative to fiducial COM from the 4D CT data was 6.2 mm. Conclusions Fiducial position was stable during treatment, and there was minimal respiration-induced motion. Using IGRT may improve the accuracy of daily setup and reduce PTV margins in WBI. Better tumor bed localization and reduced margin size will decrease the volume of normal tissue treated, which may translate into improved outcomes and lower toxicity.