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Chemotherapy Alone Versus Chemoradiation for Unresectable Pancreatic Cancer: A Meta-analysis
Volume 90 Number 1S Supplement 2014 ulcer, median V20 Z 2.00cc). The third patient with a grade 3 ulcer had a duodenal V15 of 9.4cc (upper limit Z 9cc; median 7.5cc). Conclusions: Grade 3 to 5 toxicity rates were low following SBRT for pancreatic cancer in this cohort. Duodenal V20 and V15 appear to be important in segregating patients at risk of late complications. Perhaps due to a low event rate, no significant correlation between observed high grade GI toxicity and individual SBRT dosimetric parameters emerged. Author Disclosure: O.Y. Mian: None. S. Moningi: None. J. Moore: None. A.J. Walker: None. A. Hacker-Prietz: None. T. McNutt: None. C. Wolfgang: None. T. Pawlik: None. M. Weiss: None. J.M. Herman: None.
2370 Preliminary Study of Daily Gastrointestinal Filling Impact on Tumor Targeting During Radiation Therapy for Pancreatic Cancer Patients Y. Liang, A.V. Kirichenko, and O. Gayou; Allegheny General Hospital, Pittsburgh, PA Purpose/Objective(s): Accurate targeting is critical to reduce radiation therapy toxicity in patients with pancreatic cancer due to the proximity of the pancreas to duodenum/stomach/small bowel. We hypothesize that gastrointestinal (GI) distension factors such as stomach and bowel filling can cause sufficient impact on pancreatic tumor displacement. The goal of this study was to compare the tumor location relative to bony anatomy under full and empty stomach conditions. Materials/Methods: Each patient enrolled in this Institutional Review Boardapproved single institution prospective study had 2 or 3 gold fiducial markers implanted at the tumor site via endoscopic ultrasound guidance. A free breathing planning CT simulation was acquired on empty stomach, followed by a 4D CT to estimate respiratory tumor motion. A 3 mm planning target volume margin was used. The patients were instructed to come for treatment shortly after eating (<1 hour and before bowel movement) for half the fractions in the “full” arm of the study, and long after eating (> 3 hours and after bowel movement) for half the fractions in the “empty” arm. This allowed for a paired comparison of tumor location within the patient. On each treatment day, the patients were initially positioned by aligning the skin marks to the room laser. A mega-voltage conebeam CT (MV-CBCT) was acquired and the patient position was corrected based on a fiducial marker registration. The patients were treated with intensity modulated radiation therapy (IMRT) with 36-54 Gy in 15-27 fractions. In an offline analysis, a second registration of the MV-CBCT images with the planning CT was performed based on bony anatomy. The difference between the bony anatomy- and the fiducial-based registrations represents the shift in tumor position relative to bony anatomy between simulation and treatment. The difference in this tumor location shift between “full” and “empty” conditions was analyzed for each patient using a paired t-test. Results: Five patients (88 fractions) were enrolled in the study. Four patients had tumor located in the head and one in the body of pancreas. Significant (p<0.05) differences in tumor location relative to bony anatomy between “empty” and “full” conditions were observed in two patients with tumor in the head of pancreas. The 3D displacement (mean SD) under “empty” vs “full” condition was 63mm vs 106mm for one patient and 134mm vs 42mm for the other. Conclusions: This preliminary study suggests that GI filling condition may cause significant impact on tumor location for some patients, and that controlling GI filling could lead to better targeting and sparing of surrounding organs. Further analysis with more patients is warranted to better understand the effect. Author Disclosure: Y. Liang: None. A.V. Kirichenko: None. O. Gayou: None.
2371 Monte Carlo Dose Evaluation for Pancreatic Stereotactic Body Radiation Therapy H. Gan,1 D. Zheng,1 Y. Lei,1 S. Li,1 Q. Zhang,1 S. Zhou,1 J. Li,2 and C. Lin1; 1University of Nebraska Medical Center, Omaha, NE, 2Fujian Provincial Cancer Hospital, Fujian, China Purpose/Objective(s): The high fractional dose applied in pancreatic stereotactic body radiation therapy (SBRT) demands high accuracy in dose
Poster Viewing Abstracts S363 calculation. Monte Carlo (MC) dose algorithm most accurately calculates heterogeneity correction where it is important for pancreatic SBRT due to inherent heterogeneity such as trapped air in the bowel and vertebral bone in the beam paths. In this study we applied MC dose calculation to reevaluate the dose volume data calculated by pencil beam (PB) algorithm for both planning target volume (PTV) and the most critical structure, i.e. duodenum. Materials/Methods: Under an IRB-approved protocol, 10 previously treated pancreatic SBRT patients were re-planned for a medical linear accelerator machine recently commissioned with both PB and MC algorithms in iPlan 4.5. The prescription dose for all patients is 40Gy in 5 fractions to > Z 95% PTV based on PB calculation. The dose distribution was re-calculated with MC on the same plans, with dose volume data collected for both PTV and duodenum. Statistical analysis was conducted to compare MC and PB with Wilcoxon signed rank sum test using Statistical Analysis System (SAS) software package, version 9.3. Results: Compared with MC (ground truth), the majority of PTV dose indexes, Dmean, Dmedian, D95%, D98% and Dmin, are calculated high by PB with p < 0.05, while Dmax is low at p Z 0.01.The difference of D2% is not significant. The mean values of Dmax, D2%, Dmean, D95%, and Dmin of PTV are 109.8%, 108.8%, 105.0%, 100.6, 94.0% of prescription dose for PB, and 110.8%, 108.6%, 104.4%, 99.7% and 92.5% for MC, respectively. The Paddick Conformality Index (IPCI) is significantly higher (P Z 0.002) while Homogeneity Index (HI) is significant lower (P Z 0.002) for PTV calculated with PB. The dose (Dmean) and volume (V5, V20, V35) of duodenum are significantly lower (p <0.05) with PB, with mean values of 19.9Gy, 69.0%, 56.4%, 18.5% of duodenum volume for PB and 20.4Gy, 70.4%, 57.5% and 19.7% for MC respectively. The PTV size was also found to impact the PTV dose volumetric data calculated with different algorithms. The difference of corresponding D95% and D98% of PTV between PB and MC is larger when PTV is larger than 125cc. The MC calculated dose distribution shows worse coverage than that of PB in superior and inferior direction, especially with larger PTV volume. Conclusions: MC re-evaluation of pancreatic SBRT dose calculation shows statistically significant differences in dose volume data of PTV and duodenum from PB calculation. PB tends to overestimate PTV dose while underestimating duodenum dose and volume. This could indicate in reality worse tumor control and critical organ (duodenum) sparing in current PBcalculated pancreatic SBRT, and warrants further investigation. Author Disclosure: H. Gan: None. D. Zheng: None. Y. Lei: None. S. Li: None. Q. Zhang: None. S. Zhou: None. J. Li: None. C. Lin: None.
2372 Chemotherapy Alone Versus Chemoradiation for Unresectable Pancreatic Cancer: A Meta-analysis M. Bernstein, A. Kaubisch, M. Rosenstein, S. Aparo, M.K. Garg, S. Kalnicki, C. Guha, and N. Ohri; Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY Purpose/Objectives(s): Patients with unresectable pancreatic cancer face a dismal prognosis. Optimal management for these patients remains controversial. Here, we perform an up-to-date meta-analysis and systematic review of randomized studies comparing chemotherapy (CT) versus chemoradiation (CRT) for patients diagnosed with locally-advanced unresectable pancreatic cancer. Materials/Methods: We reviewed relevant MEDLINE citations as well as abstracts from major scientific meetings through January 2014. All randomized clinical trials comparing CT alone to CRT were included. Hazard ratios (HR) describing the impact of CRT on overall survival (OS) were extracted directly from the original studies or extrapolated from survival curves. Pooled estimates were obtained using the inverse variance method. A random effects model was used in cases of significant effect heterogeneity (p<0.10 using Q test). Additional analyses were performed for subsets of studies using relatively uniform treatment techniques. Results: Six randomized trials with a total of 673 patients met inclusion criteria for analysis. Four of these studies have been published in peerreviewed journals, and two were only available in abstract form. Meta-analysis
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International Journal of Radiation Oncology Biology Physics
revealed no significant survival benefit for patients receiving CRT compared to CT alone (random effects model HR Z 0.88, 95% CI Z 0.67-1.15; p Z 0.351). Repeat analysis after excluding one study in which patients were treated with an unusually high dose of radiation therapy demonstrated a trend in favor of CRT (random effects model HR Z 0.82, 95% CI Z 0.62-1.08; p Z 0.148). Lastly, subgroup analysis including the two studies that tested radiation therapy given concurrently with gemcitabine chemotherapy revealed significantly improved outcomes for CRT over CT (fixed effects model HR Z 0.69, 95% CI Z 0.56-0.86; p<0.001). Conclusions: CT and CRT are acceptable treatment strategies for locallyadvanced pancreatic cancer. When used appropriately, CRT may confer a survival benefit over CT for this patient population, particularly when gemcitabine is used as a radiosensitizer. Additional studies to optimize the implementation of CRT and identify patients most likely to benefit from combined-modality treatment are needed. Author Disclosure: M. Bernstein: None. A. Kaubisch: None. M. Rosenstein: None. S. Aparo: None. M.K. Garg: None. S. Kalnicki: None. C. Guha: None. N. Ohri: None.
5.07 mm, 0.07 - 5.89mm, and 0.61 - 7.82 mm in the LR, AP and SI directions respectively. Conclusions: Our study shows that inter-fraction shifts from free-breathing spine to ABC breath-hold target can be as high as 8 mm. Values that deviate significantly from this limit should be investigated to rule out potential problems such as bowel gas or fiducial shift prior to proceeding with treatment. Author Disclosure: R. Teboh Forbang: None. S. Srinivasan: None. S. Ellsworth: None. E. Shin: None. M. Khashab: None. A. O’BroinLennon: None. T. Pawlik: None. C. Wolfgang: None. D. Laheru: None. J. Herman: None.
2373 Patient Setup Management for Pancreatic Stereotactic Body Radiation Therapy: Interfraction Adjustment Between Spine Alignment and the Pancreatic Fiducial During Breath-Hold kV Imaging R. Teboh Forbang, S. Srinivasan, S. Ellsworth, E. Shin, M. Khashab, A. O’Broin-Lennon, T. Pawlik, C. Wolfgang, D. Laheru, and J. Herman; Johns Hopkins University, Baltimore, MD Purpose/Objective(s): Active Breathing Coordinator (ABC) is a widely used motion management strategy for the radiation therapy of mobile tumors. During treatment, aligning the patient based on spine alone does not automatically lead to an acceptable alignment with respect to soft tissue targets and adjustment is necessary. Determining the magnitude of such an adjustment is an important quality assurance measure that will guide expectations for each treatment site. It will also allow creation of guidelines to determine acceptable shifts between the spine and a given target (fiducial) for a given site. Estimating the magnitude of this adjustment for pancreatic cancer stereotactic body radiation therapy (SBRT) was the purpose of this work. Materials/Methods: This was a retrospective study of nineteen (n Z 19) pancreatic SBRT patients, average age 65y (range 47 - 88y), treated between 12/2012 - 6/2013. Radio-opaque fiducial markers were implanted by endoscopic guidance into or adjacent to the pancreatic tumor to provide a target for accurate localization. For each fraction, a free-breathing CBCT was registered to a reference breath-hold CT for alignment to spine. Then, two perpendicular breath-hold kV projection images were acquired and compared with corresponding reference digitally reconstructed radiographs (DRR) to further fine-tune the alignment with the fiducial marker. By comparing the breath-hold kV projection images from subsequent treatment fractions with those from fraction 1, 3D variability of the fiducial position was derived. A 2D-to-2D image registration code was written that registered each day’s 2D projection image to the projection image from day 1. We applied normalized cross-correlation for this registration where the template was chosen at the spine. After fusing the two images at the spine region, the inter-fraction variability of the anatomical breath-hold state was then derived by analyzing the relative position of the fiducials from day n (n>1) compared to day 1 images. Results: We observed an average inter-fraction reproducibility of 1.73 0.84 mm, 1.98 1.42 mm, and 3.19 2.49 mm in the LR, AP and SI directions, respectively. The average excursion from free breathing spine alignment to breath-hold fiducial alignment was 1.51 1.38 mm, 2.05 1.91 mm, and 3.01 2.04 mm in the LR, AP and SI directions, respectively. The range of excursions which can be interpreted as the average expected adjustment required after spine alignment was observed as 0.18 -
2374 Interpreting Baseline and Follow-Up 18-Fluorodeoxyglucose-PET Total Lesion Glycolysis in Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer S. Moningi, A.S. Dholakia, S. Raman, R. Lange, A. Hacker-Prietz, PA-C, M. Griffith, R. Assadi, K. Oteiza, E. Fishman, M. Chaudhry, R. Wahl, and J.M. Herman; Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objectives(s): Pancreatic cancer is the fourth leading cause of cancer death and patients with unresectable disease continue to have a low 5-year survival of less than 5%. Positron emission tomography (PET) is a useful modality in the diagnosis, staging and surveillance of patients with pancreatic cancer. Recent studies have shown associations between SUVmax and overall survival and progression free survival; however, the role of follow-up PET parameters in prognosis of pancreatic cancer is yet to be well determined. Materials/Methods: Thirty-eight patients from a single institution with locally advanced or borderline PDA who received chemotherapy and either hypofractionated stereotactic body radiation therapy (SBRT) or intensity modulated radiation therapy (IMRT) and a baseline and follow-up PET scan following radiation were retrospectively analyzed. Total lesion glycolysis (TLG) and maximum and peak standardized uptake values (SUVmax and SUVpeak) on baseline and follow-up PET scans were calculated using in-house software. Disease was measured at a threshold based on the liver SUV using the equation Livermean+(2*Liversd). TLG was defined as the volume of tumor tissue that demonstrated metabolic activity at or above the calculated threshold of disease measurability multiplied by the mean SUV within the volume. Changes in the values of PET parameters were assessed for their prognostic potential through Cox regression analyses. Results: Of 38 patients (35 locally advanced and 3 borderline) with pre- and post-treatment PET scans analyzed, 31 patients (82%) received SBRT (23 patients 6.6 Gyx5fractions, 8 patients 5Gyx5fractions) and 7 patients received IMRT (total dose range 30-50.4 Gy, fraction size 2.5). Median overall survival (OS) was 22.7 months for the entire group. Median time from baseline PET scan to radiation therapy was 0.89 months (range 0.10-4.24 months) and 3.67 months (range .99-12.82 months) from the end of radiation therapy to the follow-up PET scan. Patients with a baseline TLG of 20 cm3 or greater had inferior OS compared to patients with a TLG less than 20 cm3 (HR 5.7, 95% CI Z 1.3-25.9, p Z 0.02); however, a decrease in TLG on post-RT PET scans was associated with inferior OS compared to patients with an increase in TLG (HR 3.5, 95% CI Z 1.2-10.4, p Z 0.2). Conclusions: Pre-radiation PET parameters can potentially be predictive for OS in patients with locally advanced and borderline resectable pancreatic cancer. Lower baseline metabolic activity might be a prognostic indicator for better OS, whereas increased PET metabolic activity following radiation might be due to local response from treatment and not likely due to disease progression. Author Disclosure: S. Moningi: None. A.S. Dholakia: None. S. Raman: None. R. Lange: None. A. Hacker-Prietz, PA-C: None. M. Griffith: None. R. Assadi: None. K. Oteiza: None. E. Fishman: None. M. Chaudhry: None. R. Wahl: None. J.M. Herman: None.
2370 Preliminary Study of Daily Gastrointestinal Filling Impact on Tumor Targeting During Radiation Therapy for Pancreatic Cancer Patients Y. Liang, A.V. Kirichenko, and O. Gayou; Allegheny General Hospital, Pittsburgh, PA Purpose/Objective(s): Accurate targeting is critical to reduce radiation therapy toxicity in patients with pancreatic cancer due to the proximity of the pancreas to duodenum/stomach/small bowel. We hypothesize that gastrointestinal (GI) distension factors such as stomach and bowel filling can cause sufficient impact on pancreatic tumor displacement. The goal of this study was to compare the tumor location relative to bony anatomy under full and empty stomach conditions. Materials/Methods: Each patient enrolled in this Institutional Review Boardapproved single institution prospective study had 2 or 3 gold fiducial markers implanted at the tumor site via endoscopic ultrasound guidance. A free breathing planning CT simulation was acquired on empty stomach, followed by a 4D CT to estimate respiratory tumor motion. A 3 mm planning target volume margin was used. The patients were instructed to come for treatment shortly after eating (<1 hour and before bowel movement) for half the fractions in the “full” arm of the study, and long after eating (> 3 hours and after bowel movement) for half the fractions in the “empty” arm. This allowed for a paired comparison of tumor location within the patient. On each treatment day, the patients were initially positioned by aligning the skin marks to the room laser. A mega-voltage conebeam CT (MV-CBCT) was acquired and the patient position was corrected based on a fiducial marker registration. The patients were treated with intensity modulated radiation therapy (IMRT) with 36-54 Gy in 15-27 fractions. In an offline analysis, a second registration of the MV-CBCT images with the planning CT was performed based on bony anatomy. The difference between the bony anatomy- and the fiducial-based registrations represents the shift in tumor position relative to bony anatomy between simulation and treatment. The difference in this tumor location shift between “full” and “empty” conditions was analyzed for each patient using a paired t-test. Results: Five patients (88 fractions) were enrolled in the study. Four patients had tumor located in the head and one in the body of pancreas. Significant (p<0.05) differences in tumor location relative to bony anatomy between “empty” and “full” conditions were observed in two patients with tumor in the head of pancreas. The 3D displacement (mean SD) under “empty” vs “full” condition was 63mm vs 106mm for one patient and 134mm vs 42mm for the other. Conclusions: This preliminary study suggests that GI filling condition may cause significant impact on tumor location for some patients, and that controlling GI filling could lead to better targeting and sparing of surrounding organs. Further analysis with more patients is warranted to better understand the effect. Author Disclosure: Y. Liang: None. A.V. Kirichenko: None. O. Gayou: None.
2371 Monte Carlo Dose Evaluation for Pancreatic Stereotactic Body Radiation Therapy H. Gan,1 D. Zheng,1 Y. Lei,1 S. Li,1 Q. Zhang,1 S. Zhou,1 J. Li,2 and C. Lin1; 1University of Nebraska Medical Center, Omaha, NE, 2Fujian Provincial Cancer Hospital, Fujian, China Purpose/Objective(s): The high fractional dose applied in pancreatic stereotactic body radiation therapy (SBRT) demands high accuracy in dose
Poster Viewing Abstracts S363 calculation. Monte Carlo (MC) dose algorithm most accurately calculates heterogeneity correction where it is important for pancreatic SBRT due to inherent heterogeneity such as trapped air in the bowel and vertebral bone in the beam paths. In this study we applied MC dose calculation to reevaluate the dose volume data calculated by pencil beam (PB) algorithm for both planning target volume (PTV) and the most critical structure, i.e. duodenum. Materials/Methods: Under an IRB-approved protocol, 10 previously treated pancreatic SBRT patients were re-planned for a medical linear accelerator machine recently commissioned with both PB and MC algorithms in iPlan 4.5. The prescription dose for all patients is 40Gy in 5 fractions to > Z 95% PTV based on PB calculation. The dose distribution was re-calculated with MC on the same plans, with dose volume data collected for both PTV and duodenum. Statistical analysis was conducted to compare MC and PB with Wilcoxon signed rank sum test using Statistical Analysis System (SAS) software package, version 9.3. Results: Compared with MC (ground truth), the majority of PTV dose indexes, Dmean, Dmedian, D95%, D98% and Dmin, are calculated high by PB with p < 0.05, while Dmax is low at p Z 0.01.The difference of D2% is not significant. The mean values of Dmax, D2%, Dmean, D95%, and Dmin of PTV are 109.8%, 108.8%, 105.0%, 100.6, 94.0% of prescription dose for PB, and 110.8%, 108.6%, 104.4%, 99.7% and 92.5% for MC, respectively. The Paddick Conformality Index (IPCI) is significantly higher (P Z 0.002) while Homogeneity Index (HI) is significant lower (P Z 0.002) for PTV calculated with PB. The dose (Dmean) and volume (V5, V20, V35) of duodenum are significantly lower (p <0.05) with PB, with mean values of 19.9Gy, 69.0%, 56.4%, 18.5% of duodenum volume for PB and 20.4Gy, 70.4%, 57.5% and 19.7% for MC respectively. The PTV size was also found to impact the PTV dose volumetric data calculated with different algorithms. The difference of corresponding D95% and D98% of PTV between PB and MC is larger when PTV is larger than 125cc. The MC calculated dose distribution shows worse coverage than that of PB in superior and inferior direction, especially with larger PTV volume. Conclusions: MC re-evaluation of pancreatic SBRT dose calculation shows statistically significant differences in dose volume data of PTV and duodenum from PB calculation. PB tends to overestimate PTV dose while underestimating duodenum dose and volume. This could indicate in reality worse tumor control and critical organ (duodenum) sparing in current PBcalculated pancreatic SBRT, and warrants further investigation. Author Disclosure: H. Gan: None. D. Zheng: None. Y. Lei: None. S. Li: None. Q. Zhang: None. S. Zhou: None. J. Li: None. C. Lin: None.
2372 Chemotherapy Alone Versus Chemoradiation for Unresectable Pancreatic Cancer: A Meta-analysis M. Bernstein, A. Kaubisch, M. Rosenstein, S. Aparo, M.K. Garg, S. Kalnicki, C. Guha, and N. Ohri; Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY Purpose/Objectives(s): Patients with unresectable pancreatic cancer face a dismal prognosis. Optimal management for these patients remains controversial. Here, we perform an up-to-date meta-analysis and systematic review of randomized studies comparing chemotherapy (CT) versus chemoradiation (CRT) for patients diagnosed with locally-advanced unresectable pancreatic cancer. Materials/Methods: We reviewed relevant MEDLINE citations as well as abstracts from major scientific meetings through January 2014. All randomized clinical trials comparing CT alone to CRT were included. Hazard ratios (HR) describing the impact of CRT on overall survival (OS) were extracted directly from the original studies or extrapolated from survival curves. Pooled estimates were obtained using the inverse variance method. A random effects model was used in cases of significant effect heterogeneity (p<0.10 using Q test). Additional analyses were performed for subsets of studies using relatively uniform treatment techniques. Results: Six randomized trials with a total of 673 patients met inclusion criteria for analysis. Four of these studies have been published in peerreviewed journals, and two were only available in abstract form. Meta-analysis
S364
International Journal of Radiation Oncology Biology Physics
revealed no significant survival benefit for patients receiving CRT compared to CT alone (random effects model HR Z 0.88, 95% CI Z 0.67-1.15; p Z 0.351). Repeat analysis after excluding one study in which patients were treated with an unusually high dose of radiation therapy demonstrated a trend in favor of CRT (random effects model HR Z 0.82, 95% CI Z 0.62-1.08; p Z 0.148). Lastly, subgroup analysis including the two studies that tested radiation therapy given concurrently with gemcitabine chemotherapy revealed significantly improved outcomes for CRT over CT (fixed effects model HR Z 0.69, 95% CI Z 0.56-0.86; p<0.001). Conclusions: CT and CRT are acceptable treatment strategies for locallyadvanced pancreatic cancer. When used appropriately, CRT may confer a survival benefit over CT for this patient population, particularly when gemcitabine is used as a radiosensitizer. Additional studies to optimize the implementation of CRT and identify patients most likely to benefit from combined-modality treatment are needed. Author Disclosure: M. Bernstein: None. A. Kaubisch: None. M. Rosenstein: None. S. Aparo: None. M.K. Garg: None. S. Kalnicki: None. C. Guha: None. N. Ohri: None.
5.07 mm, 0.07 - 5.89mm, and 0.61 - 7.82 mm in the LR, AP and SI directions respectively. Conclusions: Our study shows that inter-fraction shifts from free-breathing spine to ABC breath-hold target can be as high as 8 mm. Values that deviate significantly from this limit should be investigated to rule out potential problems such as bowel gas or fiducial shift prior to proceeding with treatment. Author Disclosure: R. Teboh Forbang: None. S. Srinivasan: None. S. Ellsworth: None. E. Shin: None. M. Khashab: None. A. O’BroinLennon: None. T. Pawlik: None. C. Wolfgang: None. D. Laheru: None. J. Herman: None.
2373 Patient Setup Management for Pancreatic Stereotactic Body Radiation Therapy: Interfraction Adjustment Between Spine Alignment and the Pancreatic Fiducial During Breath-Hold kV Imaging R. Teboh Forbang, S. Srinivasan, S. Ellsworth, E. Shin, M. Khashab, A. O’Broin-Lennon, T. Pawlik, C. Wolfgang, D. Laheru, and J. Herman; Johns Hopkins University, Baltimore, MD Purpose/Objective(s): Active Breathing Coordinator (ABC) is a widely used motion management strategy for the radiation therapy of mobile tumors. During treatment, aligning the patient based on spine alone does not automatically lead to an acceptable alignment with respect to soft tissue targets and adjustment is necessary. Determining the magnitude of such an adjustment is an important quality assurance measure that will guide expectations for each treatment site. It will also allow creation of guidelines to determine acceptable shifts between the spine and a given target (fiducial) for a given site. Estimating the magnitude of this adjustment for pancreatic cancer stereotactic body radiation therapy (SBRT) was the purpose of this work. Materials/Methods: This was a retrospective study of nineteen (n Z 19) pancreatic SBRT patients, average age 65y (range 47 - 88y), treated between 12/2012 - 6/2013. Radio-opaque fiducial markers were implanted by endoscopic guidance into or adjacent to the pancreatic tumor to provide a target for accurate localization. For each fraction, a free-breathing CBCT was registered to a reference breath-hold CT for alignment to spine. Then, two perpendicular breath-hold kV projection images were acquired and compared with corresponding reference digitally reconstructed radiographs (DRR) to further fine-tune the alignment with the fiducial marker. By comparing the breath-hold kV projection images from subsequent treatment fractions with those from fraction 1, 3D variability of the fiducial position was derived. A 2D-to-2D image registration code was written that registered each day’s 2D projection image to the projection image from day 1. We applied normalized cross-correlation for this registration where the template was chosen at the spine. After fusing the two images at the spine region, the inter-fraction variability of the anatomical breath-hold state was then derived by analyzing the relative position of the fiducials from day n (n>1) compared to day 1 images. Results: We observed an average inter-fraction reproducibility of 1.73 0.84 mm, 1.98 1.42 mm, and 3.19 2.49 mm in the LR, AP and SI directions, respectively. The average excursion from free breathing spine alignment to breath-hold fiducial alignment was 1.51 1.38 mm, 2.05 1.91 mm, and 3.01 2.04 mm in the LR, AP and SI directions, respectively. The range of excursions which can be interpreted as the average expected adjustment required after spine alignment was observed as 0.18 -
2374 Interpreting Baseline and Follow-Up 18-Fluorodeoxyglucose-PET Total Lesion Glycolysis in Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer S. Moningi, A.S. Dholakia, S. Raman, R. Lange, A. Hacker-Prietz, PA-C, M. Griffith, R. Assadi, K. Oteiza, E. Fishman, M. Chaudhry, R. Wahl, and J.M. Herman; Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objectives(s): Pancreatic cancer is the fourth leading cause of cancer death and patients with unresectable disease continue to have a low 5-year survival of less than 5%. Positron emission tomography (PET) is a useful modality in the diagnosis, staging and surveillance of patients with pancreatic cancer. Recent studies have shown associations between SUVmax and overall survival and progression free survival; however, the role of follow-up PET parameters in prognosis of pancreatic cancer is yet to be well determined. Materials/Methods: Thirty-eight patients from a single institution with locally advanced or borderline PDA who received chemotherapy and either hypofractionated stereotactic body radiation therapy (SBRT) or intensity modulated radiation therapy (IMRT) and a baseline and follow-up PET scan following radiation were retrospectively analyzed. Total lesion glycolysis (TLG) and maximum and peak standardized uptake values (SUVmax and SUVpeak) on baseline and follow-up PET scans were calculated using in-house software. Disease was measured at a threshold based on the liver SUV using the equation Livermean+(2*Liversd). TLG was defined as the volume of tumor tissue that demonstrated metabolic activity at or above the calculated threshold of disease measurability multiplied by the mean SUV within the volume. Changes in the values of PET parameters were assessed for their prognostic potential through Cox regression analyses. Results: Of 38 patients (35 locally advanced and 3 borderline) with pre- and post-treatment PET scans analyzed, 31 patients (82%) received SBRT (23 patients 6.6 Gyx5fractions, 8 patients 5Gyx5fractions) and 7 patients received IMRT (total dose range 30-50.4 Gy, fraction size 2.5). Median overall survival (OS) was 22.7 months for the entire group. Median time from baseline PET scan to radiation therapy was 0.89 months (range 0.10-4.24 months) and 3.67 months (range .99-12.82 months) from the end of radiation therapy to the follow-up PET scan. Patients with a baseline TLG of 20 cm3 or greater had inferior OS compared to patients with a TLG less than 20 cm3 (HR 5.7, 95% CI Z 1.3-25.9, p Z 0.02); however, a decrease in TLG on post-RT PET scans was associated with inferior OS compared to patients with an increase in TLG (HR 3.5, 95% CI Z 1.2-10.4, p Z 0.2). Conclusions: Pre-radiation PET parameters can potentially be predictive for OS in patients with locally advanced and borderline resectable pancreatic cancer. Lower baseline metabolic activity might be a prognostic indicator for better OS, whereas increased PET metabolic activity following radiation might be due to local response from treatment and not likely due to disease progression. Author Disclosure: S. Moningi: None. A.S. Dholakia: None. S. Raman: None. R. Lange: None. A. Hacker-Prietz, PA-C: None. M. Griffith: None. R. Assadi: None. K. Oteiza: None. E. Fishman: None. M. Chaudhry: None. R. Wahl: None. J.M. Herman: None.