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Increased Risk of Pelvic Fracture after Radiation Therapy in Rectal Cancer Survivors: A Propensity Matched Study
Poster Viewing E159
Volume 99 Number 2S Supplement 2017 effect of motion only grows, and enhanced motion mitigation could allow for significant widening of the therapeutic window. Author Disclosure: B.L. Jones: Research Grant; Varian Medical Systems. W. Campbell: Research Grant; Varian Medical Systems. K.A. Goodman: None. Y. Vinogradskiy: None. T. Schefter: Honoraria; Sirtex. Travel Expenses; Sirtex. M. Miften: None.
2382 Increased Risk of Pelvic Fracture after Radiation Therapy in Rectal Cancer Survivors: A Propensity Matched Study Y.M. Kang,1 T.H. Wang,2 T.F. Chao,3 and Y.W. Hu1; 1Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, 2Division of Radiation Oncology, Department of Oncology, China Medical University Hospital, Taichung, Taiwan, 3 Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Purpose/Objective(s): High-dose pelvic radiation is associated with increased pelvic fracture risk in cervical cancer and prostate cancer patients. However, it is not clear whether rectal radiotherapy would increase pelvic fracture risk in rectal cancer survivors. Materials/Methods: Rectal cancer patients who underwent curative surgery between 1996 to 2011 in Taiwan were retrospectively studied. Age, sex, comorbidities, Charlson comorbidity score, osteoporosis status, previous fracture status, radiotherapy, chemotherapy, and target therapy data were collected from National Health Insurance Research Database (NHIRD) of Taiwan. ICD-9 Codes 808, 805.4-805.7, 806.4-806.7, and 820 (including pelvic, sacrum, lumbar vertebral fracture, and femoral neck fracture) were defined as pelvic fracture in this study. Propensity scores for radiotherapy for each patient were used to perform one-to-one match between radiotherapy group and non-radiotherapy group. Incidences of pelvic fracture and arm fracture (as a control) were compared by multivariate Cox regression. Demographic sub-group analyses were also studied. Results: Of the 32689 patients studied, 7807 patients (23.9%) received radiotherapy, and 1616 patients suffered from pelvic fracture (incidence: 4.9%). After propensity score matching, 6952 patients in the radiotherapy group and 6952 patients in the non-radiotherapy group were analyzed. Radiotherapy was associated with increased risk of pelvic fracture in multi-variate Cox model (hazard ratio(HR): 1.216, 95% CI: 1.017-1.454, p Z0.032), but was not associated with increased risk of arm fracture (HR: 1.014, 95% CI: 0.819-1.254, pZ0.901). Previous fracture, older age, and female sex also showed increased risk of pelvic fracture and arm fracture. Subgroup analyses revealed radiotherapy was associated with higher risk of pelvic fracture in four types of patients: age over 60 years old (HR: 1.235, 95% CI: 1.021-1.495), females (HR: 1.39, 95% CI:1.091-1.771), those without previous fractures (HR: 1.257, 95% CI:1.02-1.55), and those who received chemotherapy (HR: 1.382, 95% CI: 1.049-1.681). Conclusion: Increased risk of pelvic fracture is noted in rectal cancer survivors who had received radiotherapy, especially in those who are elderly, female, without previous fracture experiences, and with chemotherapy. Author Disclosure: Y. Kang: None. T. Wang: None. T. Chao: None. Y. Hu: None.
Abstract 2382; Table
2383 Analysis of Threshold Doses for Radiation Induced Liver Parenchymal Changes on MRI after Real TimeeImage Gated Spot-Scanning Proton Beam Therapy of Hepatocellular Carcinomas N. Katoh,1,2 Y. Uchinami,3 S. Takao,4 K. Yasuda,2 K. Harada,1 T. Inoue,1,2 T. Matsuura,4,5 T. Hashimoto,6 S. Shimizu,2,3 and H. Shirato2,6; 1 Department of Radiation Oncology, Hokkaido University Hospital, Sapporo, Japan, 2Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan, 3Department of Radiation Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan, 4Proton Beam Therapy Center, Hokkaido University Hospital, Sapporo, Japan, 5Division of Quantum Science and Engineering, Faculty of Engineering, Hokkaido University, Sapporo, Japan, 6 Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Purpose/Objective(s): Radiation induced liver parenchymal changes after radiation therapy is depicted as a focal area of low signal intensity (FLSI) around the irradiated liver tumor on images of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). In 2014, we developed a real-time tumortracking function with two sets of fluoroscopic X-ray sources in the gantry and put it to use with spot-scanning proton beam therapy for moving tumors, we have called this real-time-image gated spot-scanning proton beam therapy (RGPT). The purpose of this study is to analyze the threshold dose (TD) for FLSI on Gd-EOB-DTPA-enhanced MRI after RGPT for hepatocellular carcinomas (HCC). Materials/Methods: We retrospectively reviewed patients with HCC treated by RGPT from December 2014 to October 2016 and followed this up with MRI using Gd-EOB-DTPA 3 months after the RGPT in our institution. We identified 10 patients with 11 lesions. Five patients had liver cirrhosis among the 10 patients. Before the RGPT, the median Child-Pugh score was 5 (range: 5-7) and nine patients were evaluated as Child -Pugh class A, with one as class B. The mean gross tumor volume was 33 37 ml. Five patients received 76 Gy (relative biological effectiveness: RBE) in 20 fractions, three 72.6 Gy (RBE) in 22 fractions, and two patients with three lesions 66 Gy (RBE) in 10 fractions. We defined the FLSI as the low signal intensity area around the irradiated liver tumors on images in the hepatobiliary phase of Gd-EOBDTPA-enhanced MRI 3 months after RGPT. The FLSI and the whole liver 3 months after RGPT were visually delineated. When we calculated the threshold dose (TD) for FLSI using a dose volume histogram, we adopted the non-FLSI liver volume (whole liver volume 3 months after RGPT minus the FLSI volume) to mitigate the impact of the shrinkage of the irradiated tumor and liver parenchyma within the FLSI. To analyze the TD among three treatment regimens, we used the equivalent dose in 2 Gy (RBE) fractions using a linear-quadratic model, assuming an a/b of 3. Results: The mean liver volume before and after RGPT were 1278 218 ml and 1218 221 ml, respectively. The mean FLSI volume and non-FLSI liver volume were 143 108 ml and 1061 244 ml, respectively. The mean TD in 2Gy (RBE) fractions was 36.9 11.0 Gy (RBE). The mean TD for patients with and without liver cirrhosis were 38.2 10.8 Gy (RBE) and 34.9 12.6 Gy (RBE), respectively (p Z 0.673). Conclusion: The threshold dose for FLSI after RGPT on Gd-EOB-DTPAenhanced MRI could be estimated in the RGPT planning for HCC. This
Multivariate Cox regression after propensity score match Pelvic fracture HR (95% CI)
Radiotherapy Osteoporosis Previous fracture Age (>Z60 y vs. <60 y) Sex (Male vs. Female)
1.216 1.264 2.190 1.085 0.498
(1.017-1.454) (1.002-1.595) (1.777-2.712) (1.075-1.096) (0.414-0.600)
Arm fracture P value 0.032 0.048 <0.001 <0.001 <0.001
HR (95% CI) 1.014 1.009 1.969 1.024 0.393
(0.819-1.254) (0.740-1.376) (1.499-2.586) (1.014-1.034) (0.315-0.491)
P value 0.901 0.955 <0.001 <0.001 <0.001
Volume 99 Number 2S Supplement 2017 effect of motion only grows, and enhanced motion mitigation could allow for significant widening of the therapeutic window. Author Disclosure: B.L. Jones: Research Grant; Varian Medical Systems. W. Campbell: Research Grant; Varian Medical Systems. K.A. Goodman: None. Y. Vinogradskiy: None. T. Schefter: Honoraria; Sirtex. Travel Expenses; Sirtex. M. Miften: None.
2382 Increased Risk of Pelvic Fracture after Radiation Therapy in Rectal Cancer Survivors: A Propensity Matched Study Y.M. Kang,1 T.H. Wang,2 T.F. Chao,3 and Y.W. Hu1; 1Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, 2Division of Radiation Oncology, Department of Oncology, China Medical University Hospital, Taichung, Taiwan, 3 Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Purpose/Objective(s): High-dose pelvic radiation is associated with increased pelvic fracture risk in cervical cancer and prostate cancer patients. However, it is not clear whether rectal radiotherapy would increase pelvic fracture risk in rectal cancer survivors. Materials/Methods: Rectal cancer patients who underwent curative surgery between 1996 to 2011 in Taiwan were retrospectively studied. Age, sex, comorbidities, Charlson comorbidity score, osteoporosis status, previous fracture status, radiotherapy, chemotherapy, and target therapy data were collected from National Health Insurance Research Database (NHIRD) of Taiwan. ICD-9 Codes 808, 805.4-805.7, 806.4-806.7, and 820 (including pelvic, sacrum, lumbar vertebral fracture, and femoral neck fracture) were defined as pelvic fracture in this study. Propensity scores for radiotherapy for each patient were used to perform one-to-one match between radiotherapy group and non-radiotherapy group. Incidences of pelvic fracture and arm fracture (as a control) were compared by multivariate Cox regression. Demographic sub-group analyses were also studied. Results: Of the 32689 patients studied, 7807 patients (23.9%) received radiotherapy, and 1616 patients suffered from pelvic fracture (incidence: 4.9%). After propensity score matching, 6952 patients in the radiotherapy group and 6952 patients in the non-radiotherapy group were analyzed. Radiotherapy was associated with increased risk of pelvic fracture in multi-variate Cox model (hazard ratio(HR): 1.216, 95% CI: 1.017-1.454, p Z0.032), but was not associated with increased risk of arm fracture (HR: 1.014, 95% CI: 0.819-1.254, pZ0.901). Previous fracture, older age, and female sex also showed increased risk of pelvic fracture and arm fracture. Subgroup analyses revealed radiotherapy was associated with higher risk of pelvic fracture in four types of patients: age over 60 years old (HR: 1.235, 95% CI: 1.021-1.495), females (HR: 1.39, 95% CI:1.091-1.771), those without previous fractures (HR: 1.257, 95% CI:1.02-1.55), and those who received chemotherapy (HR: 1.382, 95% CI: 1.049-1.681). Conclusion: Increased risk of pelvic fracture is noted in rectal cancer survivors who had received radiotherapy, especially in those who are elderly, female, without previous fracture experiences, and with chemotherapy. Author Disclosure: Y. Kang: None. T. Wang: None. T. Chao: None. Y. Hu: None.
Abstract 2382; Table
2383 Analysis of Threshold Doses for Radiation Induced Liver Parenchymal Changes on MRI after Real TimeeImage Gated Spot-Scanning Proton Beam Therapy of Hepatocellular Carcinomas N. Katoh,1,2 Y. Uchinami,3 S. Takao,4 K. Yasuda,2 K. Harada,1 T. Inoue,1,2 T. Matsuura,4,5 T. Hashimoto,6 S. Shimizu,2,3 and H. Shirato2,6; 1 Department of Radiation Oncology, Hokkaido University Hospital, Sapporo, Japan, 2Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan, 3Department of Radiation Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan, 4Proton Beam Therapy Center, Hokkaido University Hospital, Sapporo, Japan, 5Division of Quantum Science and Engineering, Faculty of Engineering, Hokkaido University, Sapporo, Japan, 6 Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Purpose/Objective(s): Radiation induced liver parenchymal changes after radiation therapy is depicted as a focal area of low signal intensity (FLSI) around the irradiated liver tumor on images of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). In 2014, we developed a real-time tumortracking function with two sets of fluoroscopic X-ray sources in the gantry and put it to use with spot-scanning proton beam therapy for moving tumors, we have called this real-time-image gated spot-scanning proton beam therapy (RGPT). The purpose of this study is to analyze the threshold dose (TD) for FLSI on Gd-EOB-DTPA-enhanced MRI after RGPT for hepatocellular carcinomas (HCC). Materials/Methods: We retrospectively reviewed patients with HCC treated by RGPT from December 2014 to October 2016 and followed this up with MRI using Gd-EOB-DTPA 3 months after the RGPT in our institution. We identified 10 patients with 11 lesions. Five patients had liver cirrhosis among the 10 patients. Before the RGPT, the median Child-Pugh score was 5 (range: 5-7) and nine patients were evaluated as Child -Pugh class A, with one as class B. The mean gross tumor volume was 33 37 ml. Five patients received 76 Gy (relative biological effectiveness: RBE) in 20 fractions, three 72.6 Gy (RBE) in 22 fractions, and two patients with three lesions 66 Gy (RBE) in 10 fractions. We defined the FLSI as the low signal intensity area around the irradiated liver tumors on images in the hepatobiliary phase of Gd-EOBDTPA-enhanced MRI 3 months after RGPT. The FLSI and the whole liver 3 months after RGPT were visually delineated. When we calculated the threshold dose (TD) for FLSI using a dose volume histogram, we adopted the non-FLSI liver volume (whole liver volume 3 months after RGPT minus the FLSI volume) to mitigate the impact of the shrinkage of the irradiated tumor and liver parenchyma within the FLSI. To analyze the TD among three treatment regimens, we used the equivalent dose in 2 Gy (RBE) fractions using a linear-quadratic model, assuming an a/b of 3. Results: The mean liver volume before and after RGPT were 1278 218 ml and 1218 221 ml, respectively. The mean FLSI volume and non-FLSI liver volume were 143 108 ml and 1061 244 ml, respectively. The mean TD in 2Gy (RBE) fractions was 36.9 11.0 Gy (RBE). The mean TD for patients with and without liver cirrhosis were 38.2 10.8 Gy (RBE) and 34.9 12.6 Gy (RBE), respectively (p Z 0.673). Conclusion: The threshold dose for FLSI after RGPT on Gd-EOB-DTPAenhanced MRI could be estimated in the RGPT planning for HCC. This
Multivariate Cox regression after propensity score match Pelvic fracture HR (95% CI)
Radiotherapy Osteoporosis Previous fracture Age (>Z60 y vs. <60 y) Sex (Male vs. Female)
1.216 1.264 2.190 1.085 0.498
(1.017-1.454) (1.002-1.595) (1.777-2.712) (1.075-1.096) (0.414-0.600)
Arm fracture P value 0.032 0.048 <0.001 <0.001 <0.001
HR (95% CI) 1.014 1.009 1.969 1.024 0.393
(0.819-1.254) (0.740-1.376) (1.499-2.586) (1.014-1.034) (0.315-0.491)
P value 0.901 0.955 <0.001 <0.001 <0.001