Sarah M. McGuire

A methodology for incorporating functional bone marrow sparing in IMRT planning for pelvic radiation therapy.

BACKGROUND AND PURPOSE The purpose of this study was to design a radiation therapy treatment planning approach that would spare hematopoietically active bone marrow using [(18)F]FLT PET imaging. MATERIALS AND METHODS We have developed an IMRT planning methodology to incorporate functional PET imaging using [(18)F]FLT scans. Plans were generated for two simulated cervical cancer patients, where pelvic active bone marrow regions were incorporated as avoidance regions based on the ranges: SUV4 ≥ 4; 4>SUV3 ≥ 3; and 3 > SUV2 ≥ 2. Dose objectives were set to reduce bone marrow volume that received 10 (V(10)) and 20 (V(20))Gy. RESULTS Active bone marrow regions identified by [(18)F]FLT with an SUV ≥ 2, SUV ≥ 3, and SUV ≥ 4 represented an average of 43.0%, 15.3%, and 5.8%, respectively of the total osseous pelvis for the two cases studied. Improved dose-volume histograms for all identified bone marrow SUV volumes and decreases in V(10), and V(20) were achieved without clinically significant changes to PTV or OAR doses. CONCLUSIONS Incorporation of [(18)F]FLT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in pelvic malignancies.

3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.

PURPOSE To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. METHODS AND MATERIALS Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. RESULTS After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. CONCLUSION Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested.

Spatial mapping of functional pelvic bone marrow using FLT PET

The purpose of this study was to determine the ability of regions identified with bony landmarks on CT imaging to accurately represent active bone marrow when compared to FLT PET imaging. These surrogate regions could then be used to create a bone marrow sparing radiation therapy plan when FLT PET imaging is not available. Whole body (WB) FLT PET images were obtained of 18 subjects prior to chemoradiation therapy. The FLT image of each subject was registered to a CT image acquired for that subject to obtain anatomic information of the pelvis. Seventeen regions were identified based on features of the pelvic bones, sacrum, and femoral heads. The probability of FLT uptake being located in each of 17 different CT‐based regions of the bony pelvis was calculated using Tukeys multiple comparison test. Statistical analysis of FLT uptake in the pelvis indicated four distinct groups within the 17 regions that had similar levels of activity. Regions located in the central part of the pelvis, including the superior part of the sacrum, the inner halves of the iliac crests, and the L5 vertebral body, had greater FLT uptake than those in the peripheral regions (p‐value < 0.05). We have developed a method to use CT‐defined pelvic bone regions to represent FLT PET‐identified functional bone marrow. Individual regions that have a statistically significant probability of containing functional bone marrow can be used as avoidance regions to reduce radiation dose to functional bone marrow in radiation therapy planning. However, because likely active bone marrow regions and pelvic targets typically overlap, patient‐specific spatial detail may be advantageous in IMRT planning scenarios and may best be provided using FLT PET imaging. PACS number: 87.57.ukThe purpose of this study was to determine the ability of regions identified with bony landmarks on CT imaging to accurately represent active bone marrow when compared to FLT PET imaging. These surrogate regions could then be used to create a bone marrow sparing radiation therapy plan when FLT PET imaging is not available. Whole body (WB) FLT PET images were obtained of 18 subjects prior to chemoradiation therapy. The FLT image of each subject was registered to a CT image acquired for that subject to obtain anatomic information of the pelvis. Seventeen regions were identified based on features of the pelvic bones, sacrum, and femoral heads. The probability of FLT uptake being located in each of 17 different CT-based regions of the bony pelvis was calculated using Tukeys multiple comparison test. Statistical analysis of FLT uptake in the pelvis indicated four distinct groups within the 17 regions that had similar levels of activity. Regions located in the central part of the pelvis, including the superior part of the sacrum, the inner halves of the iliac crests, and the L5 vertebral body, had greater FLT uptake than those in the peripheral regions (p-value < 0.05). We have developed a method to use CT-defined pelvic bone regions to represent FLT PET-identified functional bone marrow. Individual regions that have a statistically significant probability of containing functional bone marrow can be used as avoidance regions to reduce radiation dose to functional bone marrow in radiation therapy planning. However, because likely active bone marrow regions and pelvic targets typically overlap, patient-specific spatial detail may be advantageous in IMRT planning scenarios and may best be provided using FLT PET imaging. PACS number: 87.57.uk.

Bone marrow sparing in intensity modulated proton therapy for cervical cancer: Efficacy and robustness under range and setup uncertainties

BACKGROUND AND PURPOSE This study evaluates the potential efficacy and robustness of functional bone marrow sparing (BMS) using intensity-modulated proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic toxicity. MATERIAL AND METHODS IMPT plans with prescription dose of 45 Gy were generated for ten patients who have received BMS intensity-modulated X-ray therapy (IMRT). Functional bone marrow was identified by (18)F-flourothymidine positron emission tomography. IMPT plans were designed to minimize the volume of functional bone marrow receiving 5-40 Gy while maintaining similar target coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with ±3% range uncertainty errors and/or ±3 mm translational setup errors in all three principal dimensions. RESULTS In the static scenario, the median dose volume reductions for functional bone marrow by IMPT were: 32% for V(5Gy), 47% for V(10Gy), 54% for V(20Gy), and 57% for V(40Gy), all with p<0.01 compared to IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for V(5Gy), 37% for V(10Gy), 41% for V(20Gy), and 39% for V(40Gy), all with p<0.01. CONCLUSIONS The potential sparing of functional bone marrow by IMPT for cervical cancer is significant and robust under realistic systematic range uncertainties and clinically relevant setup errors.

SU-F-J-222: Using PET Imaging to Evaluate Proliferation and Blood Flow in Irradiated and Non-Irradiated Bone Marrow 1 Year After Chemoradiation Therapy

PURPOSE To compare proliferation and blood flow in pelvic and thoracic bone marrow 1 year after pelvic chemoradiation. METHODS Sixteen pelvic cancer patients were enrolled in an IRB-approved protocol to acquire FLT PET images during radiation therapy simulation (baseline) and 1 year after chemoradiation therapy. Three subjects also had optional O-15 water PET images acquired 1 year after chemoradiation therapy. Baseline FLT PET images were used to create IMRT plans to spare pelvic bone marrow identified as regions with FLT SUV ≥ 2 without compromising PTV coverage or OAR sparing. Marrow VOIs were defined using a 50% maximum pixel value threshold on baseline FLT PET images (VIEW, PMOD version 3.5) in the sacrum and thoracic spine representing irradiated and non-irradiated regions, respectively. FLT PET and O-15 water PET images acquired 1 year after therapy were co-registered to baseline images (FUSION PMOD) and the same VOIs were used to measure proliferation (FLT SUV) and blood flow (O-15 water uptake). Separate image-based input functions were used for blood flow quantitation in each VOI. RESULTS Mean 1 year FLT SUV in sacral and thoracic VOIs for were 1.1 ± 0.4 and 6.5 ± 1.7, respectively for N = 16 subjects and were 1.2 ± 0.2 and 5.6 ± 1.6, respectively for N = 3 subjects who also underwent O-15 water imaging. Blood flow measures in equivalent sacral and thoracic marrow regions (N = 3) were 21.3 ± 8.7 and 18.3 ± 4.9 mL/min/100mL respectively. CONCLUSION Decreased bone marrow proliferation measured by FLT SUV does not appear to correspond to decreased blood flow as measured by O-15 water PET imaging. Based on this small sample at a single time point, reduced blood supply does not explain reductions in bone marrow proliferative activity 1 year after chemoradiation therapy.

Comparative analysis of uptake for 18F-fluorodeoxyglucose (FDG) versus 18F-fluorodeoxythymidine (FLT) PET scans in rectal cancer.

657 Background: FLT PET is a novel metabolite for imaging cellular proliferation and has shown promise for treatment response monitoring. The utility of FLT PET imaging in rectal adenocarcinomas (RA) has not previously been established. We set out to compare FDG and FLT uptake in RA and correlate FLT response during treatment to tumor regression. Methods: We evaluated 6 patients with RA who were treated on an institutional prospective clinical trial (NCT01717391). Patients were treated neoadjuvantly with concurrent chemoradiation therapy per standard of care. Patients had both FDG and FLT PET scans prior to starting treatment and FLT scans after 1 and 2 weeks of radiotherapy. Tumor volumes and pelvic lymph nodes measuring greater than 6 mm were contoured on the simulation CT scan and adjusted for bladder and rectal filling based on the attenuation correction CT for each PET scan. FLT and FDG SUVs were collected from a total of 40 lymph nodes among the six patients. Pretreatment and change in tumor FLT SUV...

SU‐E‐J‐94: FLT PET Imaging for Evaluating Bone Marrow Recovery after Chemoradiation Therapy in Cervical Cancer Patients

Purpose: To evaluate the ability of FLT PET imaging to measure bone marrow recovery from chemoradiation therapy in cervical cancer patients. Methods: Two cervical cancer patients were enrolled in an IRB approved protocol to obtain FLT PET images at simulation, during chemoradiation, and ∼30 days post chemoradiation therapy. WBC counts and bone marrow FLT uptake change inside and outside the radiation therapy (RT) field were measured to correlate with recovery measured with FLT uptake 30 days post‐therapy. Bone marrow response and recovery was measured within the RT field in 1 Gy/week dose volumes and outside the field within the lumbar vertebral bodies. Results: Each subject was unique in her bone marrow recovery due to chemoradiation therapy when compared to pre‐therapy values. Inside the RT field, subject 1 bone marrow that received 6 Gy/week recovered at least 50% of pre‐therapy FLT uptake 30 days post‐therapy. However, subject 2 bone marrow that received 6 Gy/week recovered ∼35% of pre‐therapy FLT uptake. Outside the RT field, subject 1 L1 FLT mean SUV increased over initial values 60.6% after 3 weeks of RT and 59.1% 30 days post‐therapy. Subject 2 L1 FLT mean SUV increased over initial values only 18.5% after 3 weeks of RT and 10.6% 30 days post‐therapy. Pre‐therapy bone marrow activity may also influence bone marrow recovery. Subject 1 had lower initial WBCs and FLT uptake than subject 2 (5.3 vs. 12.2 K/mm3 and 10.4 vs. 13.6 max SUV). Conclusion: This preliminary data shows that bone marrow recovery, pre‐therapy FLT uptake, and compensatory response can be quantified with FLT PET. These metrics may be valuable in correlating pre‐, during, and post‐therapy response to radiationdose and long‐term systemic toxicity.