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Neoadjuvant Stereotactic Body Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: Prognostic Factors for Local Recurrence and Survival
E212
International Journal of Radiation Oncology Biology Physics
Results: A total of 16,933 IHC patients were identified, of which 1,493 patients met inclusion criteria. After excluding patients that had received their treatment past 3 months, 1,241 patients were eligible for analysis. The median age was 68 years (range, 25-90 years); 49% of patients were male and 86% were white. Of these patients, 719 (57.9%) received chemotherapy, 74 (5.9%) received chemo-radiation, and 448 (36%) received no treatment. Median follow-up was 29.7 months, which was not significantly different between the 3 groups. In patients receiving radiation, median dose was 50 Gy (range 32.4-60 Gy). Median OS was longer in patients receiving chemo-radiation compared to the no treatment group (12.6 months vs. 9.6 months, P Z 0.0428), with a trend for prolonged median OS in the chemo alone group (12.3 months vs. 9.6 months, P Z 0.053). Using the 6-month landmark analysis approach 1,032 patients were eligible for analysis. Of these patients, 623 (60.4%) received chemotherapy, 89 (8.6%) received chemo-radiation, and 320 (31%) received no treatment. There was a trend for longer median OS with chemo-radiation, which was not statistically significant (12m vs. 8.5 m, P Z 0.09). No OS benefit was observed in the chemo alone group. We also performed a Cox proportional hazard analysis adjusting for age and Charlson comorbidity score, and found the hazard ratios for the treatment groups were no longer statistically significant. Conclusion: The study results suggest that definitive chemo-radiation treatment may be associated with prolonged survival, which was not significant when adjusting for age and comorbidity score. Our data support further prospective trials, such as ongoing phase III trial NRG-GI001to delineate the role of radiation treatment in this setting. Author Disclosure: Z. Ghiassi-Nejad: None. E. Moshier: None. M. Schwartz: None. M. Buckstein: None.
paresthesia) toxicities. For SBRT, there were two grade 2 (fatigue, nausea), but no grade 3 toxicities. No late term toxicities attributable to bevacizumab or SBRT have been seen so far. Conclusion: In our pilot study, the combination of SBRT and Bevacizumab appeared to be feasible with an acceptable acute toxicity profile and no severe gastrointestinal toxicities. More research is needed to define biomarkers predicting for the potential benefit of this combination. Author Disclosure: P. Munoz Schuffenegger: None. Y. Ko: None. L. Milot: None. W. Chu: None. G. Czarnota: None. H.T. Chung: None.
2518 Combined Stereotactic Body Radiation Treatment and Bevacizumab as a Radiosensitizer for Colorectal Liver Metastases P. Munoz Schuffenegger,1,2 Y.J. Ko,3,4 L. Milot,5,6 W. Chu,1,2 G. Czarnota,1,2 and H.T. Chung1,2; 1Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 2Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 3Department of Medical Oncology, University of Toronto, Toronto, ON, Canada, 4Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 5 Department of Medical Imaging, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 6Department of Medical Imaging, University of Toronto, Toronto, ON, Canada Purpose/Objective(s): A recent review article expressed caution in the combination of stereotactic body radiation therapy and antiangiogenic agents in terms of risk of gastrointestinal toxicities. This is a prospective study evaluating the feasibility and toxicities of combining liver stereotactic body radiation therapy (SBRT) and bevacizumab in the treatment of colorectal liver metastases. Materials/Methods: This was a single-center, single-arm, open-label proof-of-concept study. Ethics approval was received by our institution. Eligible patients included any patient with metastatic colorectal cancer to liver (1-3 lesions) that was to receive SBRT. Patients received 2 doses of bevacizumab (5mg/kg) separated by 2 weeks. SBRT was commenced within 48 hours of the second dose of bevacizumab, and was up to 60 Gy in 6 fractions (alternating weekdays). Toxicities were assessed by NCI CTCAE v4.0. Efficacy of the SBRT was measured by CT and/or MRI and used RECIST v1.1 criteria. Results: This study enrolled 11 patients. One patient withdrew consent shortly after accrual. Ten patients and 11 liver lesions were treated. Median follow-up was 12.3 months (6.4-25.3 months). Median age was 70 years (44-94 years). There were 7 males and 4 females. All 10 patients completed bevacizumab without dose modifications. All 10 patients completed SBRT (median dose: 54 Gy, range 36-60) in 6 fractions. Median BED10 was 95.57. Acute adverse events attributable to bevacizumab included one grade 3 (hypertension) and two grade 2 (hypertension,
2519 Neoadjuvant Stereotactic Body Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: Prognostic Factors for Local Recurrence and Survival Z.D. Guss,1 L.M. Rosati,2 C.C. Hsu,3 A. Hacker-Prietz, PA-C,1 J. He,4 T.M. Pawlik,4 M.A. Makary,4 K. Hirose,4 A. De Jesus-Acosta,5 D.T. Le,5 L. Zheng,1 D.A. Laheru,5 J.L. Cameron,4 C.L. Wolfgang,4 M.J. Weiss,4 and J.M. Herman2; 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University School of Medicine, Department of Radiation Oncology & Molecular Radiation Sciences, Baltimore, MD, 3University of Arizona Department of Radiation Oncology, Tucson, AZ, 4Johns Hopkins University School of Medicine, Department of Surgery, Baltimore, MD, 5Johns Hopkins University School of Medicine, Department of Medical Oncology, Baltimore, MD Purpose/Objective(s): Surgical resection offers the greatest chance of cure for patients with adenocarcinoma of the pancreas (PCA), which has propensity for both local and distant recurrence. Refinements in neoadjuvant stereotactic body radiation therapy (SBRT) and multi-agent chemotherapy may offer opportunities for margin-negative resection (R0) of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. The purpose of our study was to identify factors associated with local recurrence and survival for BRPC or LAPC patients who underwent resection after neoadjuvant SBRT. Materials/Methods: A retrospective analysis was conducted for adult patients with BRPC or LAPC who received neoadjuvant SBRT (range: 25e33 Gy, in 5 fractions) to the pancreas and subsequently underwent surgical resection of their primary tumor. Local progression-free survival (LPFS), overall progression-free survival (PFS), and overall survival (OS) were calculated, with follow-up (FU) from the date of surgery. Log-rank test and Cox proportional hazards models were used to identify dichotomized risk factors associated with survival outcomes. Multivariate analysis (MA) adjusted for confounders including age 65, BRPC or LAPC, and pre-SBRT chemotherapy 4 months, margin status, node-negative (N0) resection, and 33 Gy SBRT. Results: For the 71 eligible patients with LAPC (52%) and BRPC (48%), median FU was 11 months (m) after surgery. Seventy-five percent of patients received 33 Gy SBRT; the remainder was dose-reduced. Eighty-two percent of patients had a R0 resection, and 28% had positive margins. Thirty percent of patients failed locally, 23% failed in regional nodes, 37% failed distantly, 48% experienced at least one type of failure, and 70% were alive at the time of last FU. Thirty-two percent of patients who failed experienced local failure as the site of first progression, and another 32% had both local and distant recurrence as the pattern of first failure. Oneyear OS was 73% (95% CI: 58-83%). R0 resection was associated with superior LPFS (HR 0.38, P Z 0.049) on univariate analysis (UA) and was the only significant factor (HR Z 0.37, P Z 0.046) after adjusting for confounders on MA. On MA, N0 resection was associated with improved PFS (HR 0.37, P<0.05), as was BRPC (HR 0.45, P Z 0.05). Improved OS was observed with 4m of pre-SBRT chemotherapy (HR 0.10, P<0.05) and 33 Gy SBRT (HR 0.11, P<0.05) on MA, while BRPC trended toward significance (HR 0.40, P Z 0.06) in the same model. Conclusion: The patients in our series demonstrated improved OS compared to historical figures. Although our results are encouraging, local recurrence remained a major source of treatment failure for patients with BRPC and LAPC. BRPC and N0 resection were associated with improved
Volume 96 Number 2S Supplement 2016 PFS, while a R0 resection conferred superior LPFS. Higher dose of RT, longer duration of chemotherapy, and BRPC were independently associated with an OS benefit. Most of these factors concern local disease, suggesting a role for intensified local therapy. Author Disclosure: Z.D. Guss: None. L.M. Rosati: None. C.C. Hsu: None. A. Hacker-Prietz, PA-C: None. J. He: None. T.M. Pawlik: None. M.A. Makary: None. K. Hirose: None. A. De Jesus-Acosta: None. D.T. Le: None. L. Zheng: None. D.A. Laheru: None. J.L. Cameron: None. C.L. Wolfgang: None. M.J. Weiss: None. J.M. Herman: Research Grant; Nucletron. Consultant; Merrimack Pharmaceuticals, Oncosil.
2520 Gd-EOB-DTPA-Enhanced Liver Magnetic Resonance Imaging as Image Biomarker for Assessment of Liver Injury After External Beam Radiation Therapy X. Sun,1,2 L. Xing,3 S. Yan,1 J. Yu,4 X. Dong,4 S. Yuan,4 D. Wang,1 L. Bu,1 Z. Lu,1 X. Jiang,1 and G. Cao1; 1The 1st Affiliated Hospital College of Medicine Zhejiang University, Hangzhou, China, 2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 3Department of Radiation Oncology, Stanford University, Stanford, CA, 4Shan Dong Cancer Hospital, Shandong University, Jinan, China Purpose/Objective(s): Radiation-induced liver disease (RILD) is an important limiting factor for dose escalation and/or hypofractionation/ SBRT in liver radiation therapy (RT). An essential step toward successful liver RT with mitigated RILD is the establishment of an effective functional imaging strategy capable of determining the extent of liver injury. This work is aimed to investigate the clinical potential of emerging GdEOB-DTPA-enhanced MRI (EOB-MRI) and to determine the relationship between focal liver reaction (FLR) and the radiation dose in conventional fractionation scheme. Materials/Methods: Nine hepatocellular carcinoma (HCC) patients who underwent external beam RT. were enrolled into the pilot imaging study. Post RT EOB-MRI was performed for each of these patients. The median time of imaging from the patients’ RT was 35 days. The hepatobiliary phase of EOB-MRI was fused to the planning CT image overlaid with isodose lines. Correlation of the EOB-MR image intensity distribution and isodose lines was studied. In particular, the threshold doses for focal Liver Reaction (FLR) were derived with consideration of the patients’ pretreatment liver functional status as given by their Child-Pugh score. Results: Decreased uptake of Gd-EOB-DTPA, which was manifested by well-demarcated focal hypodensity of liver parenchyma or FLR to high dose of radiation, was observed in the irradiated areas in all nine patients. The threshold dose (TD) of causing decreased uptake of Gd-EOB-DTPA was determined to be 25 to 42 Gy. The TD value correlated significantly with baseline liver function: it was noted that the onset of hypodensity tends to be lower for those patients with poor pre-treatment Child-Pugh score. The media dose corresponding radiation image makers was found to be 35 Gy. Conclusion: EOB-MRI enables visualization of the functional loss of liver parenchyma and provides a valuable tool for therapeutic assessment and adaptive liver therapy with functional feedback. Author Disclosure: X. Sun: None. L. Xing: None. S. Yan: None. J. Yu: None. X. Dong: None. S. Yuan: None. D. Wang: None. L. Bu: None. Z. Lu: None. X. Jiang: None. G. Cao: None.
2521 Adjuvant Radiation Therapy Improves Overall Survival in Resected Gastric Adenocarcinoma: A National Cancer Data Base Analysis P.K. Stumpf,1 A. Amini,1 K.A. Goodman,2 T. Schefter,2 and C.G. Rusthoven1; 1Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 2Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO
Poster Viewing E213 Purpose/Objective(s): For patients with resectable gastric adenocarcinoma, perioperative chemotherapy and adjuvant chemoradiation are both considered standard options. We used the National Cancer Data Base (NCDB) to compare overall survival (OS) for patients receiving perioperative chemotherapy vs adjuvant chemotherapy and radiation (RT). Materials/Methods: From 2004-2012 patients who underwent gastrectomy for non-metastatic gastric adenocarcinoma were divided into groups of perioperative chemotherapy without RT vs adjuvant chemotherapy and RT (45-50.4 Gy). Survival was estimated using the Kaplan-Meier method and compared using univariate and multivariate Cox proportional hazards models adjusted for age, sex, race, T stage (1-4), nodal status (+ vs -), surgical margin status (+ vs -), and Charlson-Deyo comorbidity scores. Subset analyses were performed for three factors chosen a priori, including T stage, nodal status, and surgical margins and potential interactions between treatment and covariates were assessed using Cox models. Results: A total of 3,669 patients with resected gastric adenocarcinoma were identified, of which 1,884 (51%) underwent perioperative chemotherapy and 1,785 (49%) received postoperative chemotherapy and RT. By stage, 29.1% were stage I, 53.1% stage II, and 17.8% stage III. Median follow-up was 28 months, and median age was 62 years. Analyses of the entire cohort demonstrated improved OS with adjuvant RT on both univariate (median OS 51 vs 42 months, P Z 0.011) and multivariate analyses (HR 0.895, 95% CI 0.810-0.988, P Z 0.028). On subset analyses adjusted for all factors, a significant interaction was observed between the survival impact of adjuvant RT and surgical margins with a greater benefit of RT for margin-positive disease (Margin (+) vs Margin (-); HR with RT, 0.657 vs 0.982; interaction-P<0.001). Differences in the impact of adjuvant RT by nodal status (Node (+) vs Node (-); HR with RT, 0.809 vs 0.929; interaction-P Z 0.505) and T stage (T1-4; interaction-P Z 0.242) did not reach statistical significance. Conclusion: In this NCDB analysis, the use of adjuvant RT in addition to chemotherapy was associated with a significant OS advantage for patients with resected gastric cancer. The relative survival benefit from adjuvant RT was particularly evident among patients with positive surgical margins, whereas the impact of RT was not significantly modified by nodal status or T stage. Author Disclosure: P.K. Stumpf: None. A. Amini: None. K.A. Goodman: None. T. Schefter: None. C.G. Rusthoven: None.
2522 Neoadjuvant Stereotactic Body Radiation Therapy Dosimetric Parameters Predict for Pathologic Outcomes and Survival in Pancreas Adenocarcinoma L. Chen,1 Y. Cao,1 A. Narang,1 Z. Cheng,1 L.M. Rosati,2 O.Y. Mian,3 S.P. Robertson,3 T.R. McNutt,3 A. Hacker-Prietz, PA-C,1 and J.M. Herman2; 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University School of Medicine, Department of Radiation Oncology & Molecular Radiation Sciences, Baltimore, MD, 3Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) for pancreas ductal adenocarcinoma (PDA) is thought to improve local control through hypofractionated doses. We reviewed outcomes of borderline and locally advanced PDA patients treated with neoadjuvant chemotherapy and SBRT prior to surgical resection. We aimed to evaluate dosimetric predictors of surgical pathologic outcomes and patient survival outcomes. Materials/Methods: Patient charts were retrospectively reviewed. Radiation treatment plans and dosimetry were restored. Survival analysis was conducted using multivariate Cox proportional hazard models with covariates including patient age, FOLFIRINOX (FFX)-based chemotherapy, chemotherapy duration, surgical margin status, surgical lymph node status, pathologic complete response, and radiation planning tumor volume (PTV)
International Journal of Radiation Oncology Biology Physics
Results: A total of 16,933 IHC patients were identified, of which 1,493 patients met inclusion criteria. After excluding patients that had received their treatment past 3 months, 1,241 patients were eligible for analysis. The median age was 68 years (range, 25-90 years); 49% of patients were male and 86% were white. Of these patients, 719 (57.9%) received chemotherapy, 74 (5.9%) received chemo-radiation, and 448 (36%) received no treatment. Median follow-up was 29.7 months, which was not significantly different between the 3 groups. In patients receiving radiation, median dose was 50 Gy (range 32.4-60 Gy). Median OS was longer in patients receiving chemo-radiation compared to the no treatment group (12.6 months vs. 9.6 months, P Z 0.0428), with a trend for prolonged median OS in the chemo alone group (12.3 months vs. 9.6 months, P Z 0.053). Using the 6-month landmark analysis approach 1,032 patients were eligible for analysis. Of these patients, 623 (60.4%) received chemotherapy, 89 (8.6%) received chemo-radiation, and 320 (31%) received no treatment. There was a trend for longer median OS with chemo-radiation, which was not statistically significant (12m vs. 8.5 m, P Z 0.09). No OS benefit was observed in the chemo alone group. We also performed a Cox proportional hazard analysis adjusting for age and Charlson comorbidity score, and found the hazard ratios for the treatment groups were no longer statistically significant. Conclusion: The study results suggest that definitive chemo-radiation treatment may be associated with prolonged survival, which was not significant when adjusting for age and comorbidity score. Our data support further prospective trials, such as ongoing phase III trial NRG-GI001to delineate the role of radiation treatment in this setting. Author Disclosure: Z. Ghiassi-Nejad: None. E. Moshier: None. M. Schwartz: None. M. Buckstein: None.
paresthesia) toxicities. For SBRT, there were two grade 2 (fatigue, nausea), but no grade 3 toxicities. No late term toxicities attributable to bevacizumab or SBRT have been seen so far. Conclusion: In our pilot study, the combination of SBRT and Bevacizumab appeared to be feasible with an acceptable acute toxicity profile and no severe gastrointestinal toxicities. More research is needed to define biomarkers predicting for the potential benefit of this combination. Author Disclosure: P. Munoz Schuffenegger: None. Y. Ko: None. L. Milot: None. W. Chu: None. G. Czarnota: None. H.T. Chung: None.
2518 Combined Stereotactic Body Radiation Treatment and Bevacizumab as a Radiosensitizer for Colorectal Liver Metastases P. Munoz Schuffenegger,1,2 Y.J. Ko,3,4 L. Milot,5,6 W. Chu,1,2 G. Czarnota,1,2 and H.T. Chung1,2; 1Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 2Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 3Department of Medical Oncology, University of Toronto, Toronto, ON, Canada, 4Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 5 Department of Medical Imaging, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 6Department of Medical Imaging, University of Toronto, Toronto, ON, Canada Purpose/Objective(s): A recent review article expressed caution in the combination of stereotactic body radiation therapy and antiangiogenic agents in terms of risk of gastrointestinal toxicities. This is a prospective study evaluating the feasibility and toxicities of combining liver stereotactic body radiation therapy (SBRT) and bevacizumab in the treatment of colorectal liver metastases. Materials/Methods: This was a single-center, single-arm, open-label proof-of-concept study. Ethics approval was received by our institution. Eligible patients included any patient with metastatic colorectal cancer to liver (1-3 lesions) that was to receive SBRT. Patients received 2 doses of bevacizumab (5mg/kg) separated by 2 weeks. SBRT was commenced within 48 hours of the second dose of bevacizumab, and was up to 60 Gy in 6 fractions (alternating weekdays). Toxicities were assessed by NCI CTCAE v4.0. Efficacy of the SBRT was measured by CT and/or MRI and used RECIST v1.1 criteria. Results: This study enrolled 11 patients. One patient withdrew consent shortly after accrual. Ten patients and 11 liver lesions were treated. Median follow-up was 12.3 months (6.4-25.3 months). Median age was 70 years (44-94 years). There were 7 males and 4 females. All 10 patients completed bevacizumab without dose modifications. All 10 patients completed SBRT (median dose: 54 Gy, range 36-60) in 6 fractions. Median BED10 was 95.57. Acute adverse events attributable to bevacizumab included one grade 3 (hypertension) and two grade 2 (hypertension,
2519 Neoadjuvant Stereotactic Body Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: Prognostic Factors for Local Recurrence and Survival Z.D. Guss,1 L.M. Rosati,2 C.C. Hsu,3 A. Hacker-Prietz, PA-C,1 J. He,4 T.M. Pawlik,4 M.A. Makary,4 K. Hirose,4 A. De Jesus-Acosta,5 D.T. Le,5 L. Zheng,1 D.A. Laheru,5 J.L. Cameron,4 C.L. Wolfgang,4 M.J. Weiss,4 and J.M. Herman2; 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University School of Medicine, Department of Radiation Oncology & Molecular Radiation Sciences, Baltimore, MD, 3University of Arizona Department of Radiation Oncology, Tucson, AZ, 4Johns Hopkins University School of Medicine, Department of Surgery, Baltimore, MD, 5Johns Hopkins University School of Medicine, Department of Medical Oncology, Baltimore, MD Purpose/Objective(s): Surgical resection offers the greatest chance of cure for patients with adenocarcinoma of the pancreas (PCA), which has propensity for both local and distant recurrence. Refinements in neoadjuvant stereotactic body radiation therapy (SBRT) and multi-agent chemotherapy may offer opportunities for margin-negative resection (R0) of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. The purpose of our study was to identify factors associated with local recurrence and survival for BRPC or LAPC patients who underwent resection after neoadjuvant SBRT. Materials/Methods: A retrospective analysis was conducted for adult patients with BRPC or LAPC who received neoadjuvant SBRT (range: 25e33 Gy, in 5 fractions) to the pancreas and subsequently underwent surgical resection of their primary tumor. Local progression-free survival (LPFS), overall progression-free survival (PFS), and overall survival (OS) were calculated, with follow-up (FU) from the date of surgery. Log-rank test and Cox proportional hazards models were used to identify dichotomized risk factors associated with survival outcomes. Multivariate analysis (MA) adjusted for confounders including age 65, BRPC or LAPC, and pre-SBRT chemotherapy 4 months, margin status, node-negative (N0) resection, and 33 Gy SBRT. Results: For the 71 eligible patients with LAPC (52%) and BRPC (48%), median FU was 11 months (m) after surgery. Seventy-five percent of patients received 33 Gy SBRT; the remainder was dose-reduced. Eighty-two percent of patients had a R0 resection, and 28% had positive margins. Thirty percent of patients failed locally, 23% failed in regional nodes, 37% failed distantly, 48% experienced at least one type of failure, and 70% were alive at the time of last FU. Thirty-two percent of patients who failed experienced local failure as the site of first progression, and another 32% had both local and distant recurrence as the pattern of first failure. Oneyear OS was 73% (95% CI: 58-83%). R0 resection was associated with superior LPFS (HR 0.38, P Z 0.049) on univariate analysis (UA) and was the only significant factor (HR Z 0.37, P Z 0.046) after adjusting for confounders on MA. On MA, N0 resection was associated with improved PFS (HR 0.37, P<0.05), as was BRPC (HR 0.45, P Z 0.05). Improved OS was observed with 4m of pre-SBRT chemotherapy (HR 0.10, P<0.05) and 33 Gy SBRT (HR 0.11, P<0.05) on MA, while BRPC trended toward significance (HR 0.40, P Z 0.06) in the same model. Conclusion: The patients in our series demonstrated improved OS compared to historical figures. Although our results are encouraging, local recurrence remained a major source of treatment failure for patients with BRPC and LAPC. BRPC and N0 resection were associated with improved
Volume 96 Number 2S Supplement 2016 PFS, while a R0 resection conferred superior LPFS. Higher dose of RT, longer duration of chemotherapy, and BRPC were independently associated with an OS benefit. Most of these factors concern local disease, suggesting a role for intensified local therapy. Author Disclosure: Z.D. Guss: None. L.M. Rosati: None. C.C. Hsu: None. A. Hacker-Prietz, PA-C: None. J. He: None. T.M. Pawlik: None. M.A. Makary: None. K. Hirose: None. A. De Jesus-Acosta: None. D.T. Le: None. L. Zheng: None. D.A. Laheru: None. J.L. Cameron: None. C.L. Wolfgang: None. M.J. Weiss: None. J.M. Herman: Research Grant; Nucletron. Consultant; Merrimack Pharmaceuticals, Oncosil.
2520 Gd-EOB-DTPA-Enhanced Liver Magnetic Resonance Imaging as Image Biomarker for Assessment of Liver Injury After External Beam Radiation Therapy X. Sun,1,2 L. Xing,3 S. Yan,1 J. Yu,4 X. Dong,4 S. Yuan,4 D. Wang,1 L. Bu,1 Z. Lu,1 X. Jiang,1 and G. Cao1; 1The 1st Affiliated Hospital College of Medicine Zhejiang University, Hangzhou, China, 2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 3Department of Radiation Oncology, Stanford University, Stanford, CA, 4Shan Dong Cancer Hospital, Shandong University, Jinan, China Purpose/Objective(s): Radiation-induced liver disease (RILD) is an important limiting factor for dose escalation and/or hypofractionation/ SBRT in liver radiation therapy (RT). An essential step toward successful liver RT with mitigated RILD is the establishment of an effective functional imaging strategy capable of determining the extent of liver injury. This work is aimed to investigate the clinical potential of emerging GdEOB-DTPA-enhanced MRI (EOB-MRI) and to determine the relationship between focal liver reaction (FLR) and the radiation dose in conventional fractionation scheme. Materials/Methods: Nine hepatocellular carcinoma (HCC) patients who underwent external beam RT. were enrolled into the pilot imaging study. Post RT EOB-MRI was performed for each of these patients. The median time of imaging from the patients’ RT was 35 days. The hepatobiliary phase of EOB-MRI was fused to the planning CT image overlaid with isodose lines. Correlation of the EOB-MR image intensity distribution and isodose lines was studied. In particular, the threshold doses for focal Liver Reaction (FLR) were derived with consideration of the patients’ pretreatment liver functional status as given by their Child-Pugh score. Results: Decreased uptake of Gd-EOB-DTPA, which was manifested by well-demarcated focal hypodensity of liver parenchyma or FLR to high dose of radiation, was observed in the irradiated areas in all nine patients. The threshold dose (TD) of causing decreased uptake of Gd-EOB-DTPA was determined to be 25 to 42 Gy. The TD value correlated significantly with baseline liver function: it was noted that the onset of hypodensity tends to be lower for those patients with poor pre-treatment Child-Pugh score. The media dose corresponding radiation image makers was found to be 35 Gy. Conclusion: EOB-MRI enables visualization of the functional loss of liver parenchyma and provides a valuable tool for therapeutic assessment and adaptive liver therapy with functional feedback. Author Disclosure: X. Sun: None. L. Xing: None. S. Yan: None. J. Yu: None. X. Dong: None. S. Yuan: None. D. Wang: None. L. Bu: None. Z. Lu: None. X. Jiang: None. G. Cao: None.
2521 Adjuvant Radiation Therapy Improves Overall Survival in Resected Gastric Adenocarcinoma: A National Cancer Data Base Analysis P.K. Stumpf,1 A. Amini,1 K.A. Goodman,2 T. Schefter,2 and C.G. Rusthoven1; 1Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 2Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO
Poster Viewing E213 Purpose/Objective(s): For patients with resectable gastric adenocarcinoma, perioperative chemotherapy and adjuvant chemoradiation are both considered standard options. We used the National Cancer Data Base (NCDB) to compare overall survival (OS) for patients receiving perioperative chemotherapy vs adjuvant chemotherapy and radiation (RT). Materials/Methods: From 2004-2012 patients who underwent gastrectomy for non-metastatic gastric adenocarcinoma were divided into groups of perioperative chemotherapy without RT vs adjuvant chemotherapy and RT (45-50.4 Gy). Survival was estimated using the Kaplan-Meier method and compared using univariate and multivariate Cox proportional hazards models adjusted for age, sex, race, T stage (1-4), nodal status (+ vs -), surgical margin status (+ vs -), and Charlson-Deyo comorbidity scores. Subset analyses were performed for three factors chosen a priori, including T stage, nodal status, and surgical margins and potential interactions between treatment and covariates were assessed using Cox models. Results: A total of 3,669 patients with resected gastric adenocarcinoma were identified, of which 1,884 (51%) underwent perioperative chemotherapy and 1,785 (49%) received postoperative chemotherapy and RT. By stage, 29.1% were stage I, 53.1% stage II, and 17.8% stage III. Median follow-up was 28 months, and median age was 62 years. Analyses of the entire cohort demonstrated improved OS with adjuvant RT on both univariate (median OS 51 vs 42 months, P Z 0.011) and multivariate analyses (HR 0.895, 95% CI 0.810-0.988, P Z 0.028). On subset analyses adjusted for all factors, a significant interaction was observed between the survival impact of adjuvant RT and surgical margins with a greater benefit of RT for margin-positive disease (Margin (+) vs Margin (-); HR with RT, 0.657 vs 0.982; interaction-P<0.001). Differences in the impact of adjuvant RT by nodal status (Node (+) vs Node (-); HR with RT, 0.809 vs 0.929; interaction-P Z 0.505) and T stage (T1-4; interaction-P Z 0.242) did not reach statistical significance. Conclusion: In this NCDB analysis, the use of adjuvant RT in addition to chemotherapy was associated with a significant OS advantage for patients with resected gastric cancer. The relative survival benefit from adjuvant RT was particularly evident among patients with positive surgical margins, whereas the impact of RT was not significantly modified by nodal status or T stage. Author Disclosure: P.K. Stumpf: None. A. Amini: None. K.A. Goodman: None. T. Schefter: None. C.G. Rusthoven: None.
2522 Neoadjuvant Stereotactic Body Radiation Therapy Dosimetric Parameters Predict for Pathologic Outcomes and Survival in Pancreas Adenocarcinoma L. Chen,1 Y. Cao,1 A. Narang,1 Z. Cheng,1 L.M. Rosati,2 O.Y. Mian,3 S.P. Robertson,3 T.R. McNutt,3 A. Hacker-Prietz, PA-C,1 and J.M. Herman2; 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University School of Medicine, Department of Radiation Oncology & Molecular Radiation Sciences, Baltimore, MD, 3Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) for pancreas ductal adenocarcinoma (PDA) is thought to improve local control through hypofractionated doses. We reviewed outcomes of borderline and locally advanced PDA patients treated with neoadjuvant chemotherapy and SBRT prior to surgical resection. We aimed to evaluate dosimetric predictors of surgical pathologic outcomes and patient survival outcomes. Materials/Methods: Patient charts were retrospectively reviewed. Radiation treatment plans and dosimetry were restored. Survival analysis was conducted using multivariate Cox proportional hazard models with covariates including patient age, FOLFIRINOX (FFX)-based chemotherapy, chemotherapy duration, surgical margin status, surgical lymph node status, pathologic complete response, and radiation planning tumor volume (PTV)