J.A. Hayman

Impact of Intensity Modulated Radiation Therapy on Acute Toxicity in Locally Advanced Lung Cancer: Results of a Large Statewide Multi-center Cohort

Secondary analysis of RTOG 0617 has shown lower rates of pneumonitis and less decline in patient quality of life with the use of intensity modulated radiation therapy (IMRT) vs. three-dimensional conformal external beam radiation therapy (3D-CRT) in locally advanced non-small cell lung cancer patients undergoing definitive radiation therapy. In a large statewide radiation oncology quality consortium, we sought to evaluate impact of IMRT vs. 3D-CRT treatment technique on acute esophagitis & pneumonitis.

Impact of Comorbidities on Acute Toxicity in Patients Receiving Radiation Therapy for Locally Advanced Lung Cancer

Radiation Therapy for Locally Advanced Lung Cancer MR McFarlane1, Y Sun2, M Schipper1-2, C Maurino1, AM Laucis1, A Saripalli1, R Ten-Haken1, FM Kong4, M Matuszak1, DE Spratt1, L Pierce1, J Hayman1, P Paximadis5, S Jolly1 Departments of 1Radiation Oncology, 2Biostatistics and 3Pulmonary Medicine, University of Michigan, Ann Arbor; 4Department of Radiation Oncology, Indiana University, Indianapolis; 5Lakeland Radiation Oncology, St. Joseph

TU-F-CAMPUS-T-03: Commissioning of a Custom Fetal Lead Shield for Radiotherapy

Purpose: To evaluate the peripheral dose (PD) to a fetus during radiation therapy of pregnant patients when using a newly designed fetal lead shield (FLS). Methods: A custom FLS has been designed and fabricated for our department. The FLS (1.1 TVLs for 6 MV) is mounted on a mobile frame and can be adjusted vertically with a motor actuator. PD measurements were acquired for multiple simple square fields and for a variety of potential treatment sites a pregnant patient may be treated for including brain, head and neck (H&N) and thorax. For measurements of the brain, H&N, and thorax, an ionization chamber and OSLDs were positioned on average at a distance of 48, 29 and 26 cm, respectively, from the edge of treatment fields to mimic the approximate position of the fundus. Results: Based on our measurements, applying a 90° collimator rotation and using tertiary MLCs to define the field aperture in combination with jaws resulted in an average dose reduction of 60%. When using these planning strategies in combination with the FLS, on average, the PD was reduced by additional 25% for simple square fields and 20% for clinical plans. Conclusion: The custom FLS is a safe, effective, and relatively easy system to position. Commissioning measurements have demonstrated that the PD to the fetus can be significantly reduced when using the FLS. The comprehensive dataset obviates the need for individual patient pre-treatment dose measurements as long as the geometry falls within the commissioning limits.

SU‐E‐T‐245: A Physics Database for a Multi‐Institutional Quality Consortium

Purpose: A collaborative quality initiative (CQI) has been developed in the state of Michigan to assess physician and patient reported outcomes to compare conformal and IMRT techniques for a specific cohort of breast and lung cancer patients. Here, we present a web‐based database that was designed to collect planning and delivery information to facilitate analysis of outcomes for the CQI. Methods: A web‐based database was built to capture key physics information, including dose that may be related to acute toxicities. An annual institutional questionnaire captures the technology available for these patients. A patient‐specific survey collects simulation, planning, and delivery information. To overcome differences in DVH file formats, a simple interface was developed where the user selects from a structure list, submits numeric data, and reviews the data summary. To analyze the delivery type, DICOM‐RT plan files are uploaded via a web interface. The data are anonymized and displayed for the user to verify that no protected health information is submitted. Results: Initial partner institutions tested and provided feedback on all aspects of the physics data collection. Institutions have shared customized programs for extracting DVH and DICOM‐RT data and documents for electronic workflow. Data submission began via the web portal in April 2012. There are 4 planning systems represented among the 14 institutions. Delivery techniques include static, dynamic and segmental MLC, Tomotherapy, and VMAT. As of February, data have been submitted for approximately 80% of the 815 eligible cases. Centers will be audited for data quality once per year. Conclusion: A system has been designed to capture high integrity simulation, plan, and delivery data for a CQI focused on breast and lung cancer. This information will be used to quantitatively evaluate the use of IMRT techniques in the state of Michigan and to permit dose‐based correlations to physician and patient‐rated toxicities. This work was funded by Blue Cross Blue Shield of Michigan.

SU‐F‐500‐02: Early Prediction of Brain Metastases Response to Radiation Therapy by Combination of Changes in Tumor Vascular and Cellularity Properties

PURPOSE To investigate the impact of combining image-based measurements related to alterations of vascular and cellularity properties of brain metastases for early prediction of tumor response to radiation therapy (RT). METHODS 24 patients undergoing treatment for metastases had perfusion (DCE) and diffusion MRI scans. Tumor subvolumes with high regional cerebral blood volume (rCBV) and high Gd-DTAP transfer constant (Ktrans) were extracted. The apparent diffusion coefficient (ADC) histograms of the tumor volume were categorized into low, normal and high ADC subvolumes. Changes in different tumor subvolumes and their combination from pre-RT to week 2 after start of radiation were evaluated in differentiation of responsive, stable and progressive tumors for patients treated by either whole brain radiation therapy (WBRT, 28 lesions) alone or combined with Bortezomib as a radiation sensitizer (39 lesions). Receiver Operating Characteristic (ROC) analysis compared a combined perfusion/diffusion prediction model with changes in gross tumor volume (GTV) within the same time interval. RESULTS For lesions treated with WBRT alone, a decrease in both high cellularity and edema subvolumes were associated with response. A decrease in the tumor subvolumes with high cellularity and vascularity was associated with response in lesions treated with RT combined with Bortezomib. In ROC analysis, areas under curve (AUCs) of 0.96 (WBRT alone) and 0.96 (WBRT + Bortezomib) were seen in prediction of non-responsive lesions when changes in different subvolumes were combined. Also, GTV changes could predict the non-responsive lesions treated with WBRT alone (AUC = 0.91) but failed to predict the response in lesions treated with WBRT combined with Bortezomib (AUC = 0.57). CONCLUSION Combining the changes in tumor cellularity and vascularity could be used for early prediction of brain metastases response to RT and perform better than the GTV changes, suggesting that physiological changes could occur earlier than the morphological changes. (Support: NIH RO1NS064973) NIH grant ROl NS064973.

WE‐C‐BRA‐05: Physiological Imaging‐Defined Response‐Driven Subvolumes of a Tumor

Purpose: To develop an image analysis framework to delineate the physiological imaging‐defined subvolumes of a tumor in relating to treatment response and outcome. Methods: Our proposed approach is designed to delineate subvolumes of a tumor based upon its heterogeneous distributions of physiological imaging parameters. The method assigns each voxel a probabilistic membership function belonging to the physiological parameter classes based upon a sample of tumors, and then calculates the related subvolumes for each tumor. We applied our approach to regional cerebral blood volume (rCBV) and Gd‐DTAP transfer constant (Ktrans) images of patients who had brain metastases and were treated by whole brainradiation therapy (WBRT). Forty five lesions were included in the analysis. Changes in the rCBV (or Ktrans)‐defined subvolumes of the tumors from pre RT to 2 weeks (2W) after the start of WBRT were evaluated for differentiation of responsive, stable and non‐responsive tumors using Mann‐Whitney U test. Performance of the newly developed metrics for predicting tumor response to WBRT was evaluated by Receiver Operating Characteristic (ROC) analysis. Results: The percentage decrease in the high‐CBV defined subvolumes of the tumors from pre‐RT to 2W was significantly greater in the group of responsive tumors than in the group of stable and nonresponsive ones (p<0.007). The change in the high‐CBV defined subvolumes of the tumors from pre‐RT to 2W was a predictor for post‐RT response significantly better than the change in gross tumor volume observed during the same time interval (p=0.0124), suggesting the physiological change occurs prior to the volumetric change. Also, Ktrans did not add significant discriminatory information for assessing response with respect to rCBV. Conclusions: The physiological imaging‐defined subvolumes of the tumors delineated by our method have the potential to be a new imaging response‐predictor and a candidate for intensified treatment. NIH grant RO1 NS064973

Use of increase in esophageal FDG SUV during radiotherapy to predict radiation esophagitis.

e17509 Background: Esophageal uptake of FDG is commonly seen in patients with non-small cell lung cancer (NSCLC), but the relationship of the uptake to radiation esophagitis has not been delineated. Since esophageal mucosa is sensitive to the effect of radiation, we hypothesized that: (1) esophageal FDG activity changes during fractionated radiotherapy (RT), (2) these changes are associated with radiation esophagitis. Methods: Patients with stage I-III NSCLC were prospectively enrolled and received >60 Gy RT. FDG-PET/CT scans were acquired prior to and during RT after the delivery of 45 Gy. Normalized standardized uptake values (NSUV), defined by the esophageal maximum SUV relative to intravascular background within the aortic arch, were measured at the levels of the primary tumor, sternal notch, aortic arch, carina, and gastro-esophageal junction. Grade ≥2 radiation esophagitis was defined as an event. Results: 16 of 50 patients had radiation esophagitis event. Clinical stage, concurrent chemotherapy, ma...

TH‐C‐351‐08: Clustering Analysis of Dynamic 11C‐Methionine PET in GBM for RT Target Definition

Purpose: To assess tumor differentiation in patients with glioblastoma multiforme (GBM) using dynamic 11C‐methionin (D‐MET) PET and fuzzy c‐means (FCM) clusteringanalysis; and to evaluate the added value of D‐MET PET in radiation therapy (RT) target definition. Method and Materials: D‐MET PETimages were obtained prior to RT in 25 patients with GBM. Each scan was composed of 15 phases acquired at 0–50 minutes following injection. Conventional MRI was also acquired before RT for target volume definition and after RT for evaluation of treatment outcome. D‐MET PET data were normalized to the mean uptake of each individuals cerebellum. Volume of interest (VOI) for the analysis was defined based on pre‐RT FLAIR‐MRI and extended to incorporate regions of high uptake of MET. Time‐activity curves of MET uptake in the VOI were classified using a FCM clustering algorithm with spatial constraints. The optimal number of clusters was determined for each dataset by calculating several clustering validity indices. The results of classification were reviewed by experts; and were also correlated to the patterns of local failure after RT. Results: Using the FCM clustering algorithm, time‐activity curves of MET uptake in the VOI were successfully partitioned into tumor, normal braintissue, inflammation response, surgical cavity and edema. Heterogeneous MET uptake in the tumor was also differentiated. In 15 of the 25 patients who had tumor progression, the pre‐RT PET in the clusters correspondent to the locations of recurrence had a median uptake value of 1.47 (last dynamic phase), which involves clusters beyond the hottest ones. Conclusion: This study demonstrated that dynamic MET‐PET is capable of differentiating active tumors in patients with GBM. It is also promising in providing extra information for RT target definition. Supported by NIHP01CA59827.

SU‐FF‐J‐34: Can Functional Imaging Be Used to Individualize Adaptive Radiation Therapy for Non‐Small Cell Lung Cancer?

Background/purpose: To determine the changes in tumor and lung function during the course of radiation and their potentials in adaptive radiation therapy for non‐small cell lungcancer(NSCLC).Materials/Methods: FDG‐PET‐CT and Ventilation/perfusion (V/Q) SPECT were acquired prior to and after the delivery of 45 Gy during the course of radiation in 15 patients with NSCLC.Tumor activity was measured by relative standard uptake value (RSUV). V/Q SPECT was evaluated blindly by radiobiologist, through comparing to healthy normal controls. Results: After 45 Gy radiation, the mean RSUV decreased from 4.6±1.9 to 2.1±1.0 for primary tumors (p<0.0001) and from 3.2+1.3 to 1.7+0.5 for nodal diseases (p=0.0008). Mean reduction in PET tumor volume was 78% (67–100%). There was 28% (4/15) and 0% (0/15) complete responders on PET and CT, respectively. Three patients achieved a complete CT response at 3 month follow‐up, all of them were PET complete responders at 45 Gy. Boosting after 45 Gy, normal tissue complication probability (NTCP) could be reduced by 50%, V20 by 28%, and mean lungdose by 29% while keeping the total dose constant. Keeping the NTCP constant, dose could be escalated by 50%. Lung functional mapping also changed remarkably at 45 Gy during radiation. Fifteen of 15 patients had V/Q defects at or adjacent to tumor on the baseline SPECT, while 14/15 patients had at least one defect located remotely from tumor. For those defects located adjacent to tumor, 79% improved remarkably, while only 7.9% of the others had notable change (p<0.001). Lung NTCP adjusted by V/Q SPECT obtained during radiation was significantly different from those generated from the pretreatment V/Q SPECT and simulating CT.Conclusions:Tumor and lung functional imaging during the course of radiation may provide useful information for adaptive radiation therapy in patients with NSCLC.