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Dose-Volume Parameters of MRI Active Bone Marrow Versus Total Bone Marrow As Predictor of Hematologic Toxicity in Rectal Cancer Patients during Neoadjuvant Chemoradiation Therapy
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Volume 99 Number 2S Supplement 2017
2391
2392
Repeated Stereotactic Body Radiotherapy for Intra-Hepatic Recurrent Hepatocellular Carcinoma T. Kimura,1 K. Hioki,2 H. Aikata,3 K. Kubo,4 S. Takahashi,5 Y. Takeuchi,1 I. Takahashi,1 I. Nishibuchi,1 Y. Murakami,1 K. Chayama,3 and Y. Nagata1; 1Department of Radiation Oncology, Hiroshima University, Hiroshima, Japan, 2Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima, Japan, 3 Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan, 4Department of Radiation Oncology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan, 5 Department of Radiation Oncology, Kagawa University Hospital, Kagawa, Japan
Dose-Volume Parameters of MRI Active Bone Marrow Versus Total Bone Marrow As Predictor of Hematologic Toxicity in Rectal Cancer Patients during Neoadjuvant Chemoradiation Therapy L. Kuncman,1 M. Maslowski,2 J. Danielska,1 J. Łuniewska-Bury,3 and J. Fijuth1; 1Department of Radiotherapy, Medical University of Lodz, Lodz, Poland, 2Department of Teleradiotherapy, Regional Cancer Center, Copernicus Memorial Hospital of Lodz, Lodz, Poland, 3Department of Brachytherapy, Regional Cancer Center, Copernicus Memorial Hospital of Lodz, Lodz, Poland
Purpose/Objective(s): The safety and efficacy of stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) is well established. However, the effect of repeated SBRT for intra-hepatic recurrent HCC is unclear. This study aimed to retrospectively evaluate the safety and efficacy of repeated SBRT for intra-hepatic recurrent HCC. Materials/Methods: We enrolled 24 patients with 53 tumors who had undergone 2 two courses (median 2 times; range 2- 4 times). Sixteen patients (66.7%) had previously undergone surgery or ablation therapy, and 45 lesions (84.9%) underwent trans-arterial chemo-embolization using lipiodol before SBRT. Median tumor size was 17 mm (range 5- 47 mm). Child-Pugh (CP) scoring system was used to classify 20 and 4 patients (first course), and 18 and 6 patients (second course or beyond) into classes A and B, respectively. SBRT was performed using a 3dimensional conformal method which delivered a single high dose radiation to the tumor. Prescribed dose was evaluated at the isocenter in 27 lesions (median dose: 48 Gy in 4 fractions) and at D95% prescription in 26 lesions (median dose: 40 G y in 4 fractions) for the first and rest of the courses. Local progression was defined as growth of the irradiated tumor and early arterial enhancement remaining for more than 6 months on follow-up with dynamic CT. Treatment-related toxicities were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version. Results: The median follow-up duration was 42 months (range, 9- 79 months). The median interval between the first and the repeated SBRT was 21 months (range 4 - 61 months). Three- year overall survival rates, and local control rates for patients were 75.0 % (95 % CI: 56.0 - 94.0 %) and 97.4 % (95 % CI: 92.5 e 100 %), respectively. Grade 3 toxicities such as AST/ALT elevation, decreased platelet count, and ascites were observed in 4 patients (16.7 %) in the first course and 5 patients (20.8 %) in the second course or beyond. Seven patients developed grade 3 during all the courses, which was significantly higher in CP class B than in CP class A (pZ0.0196). All sessions were fused using deformable registration software (Velosity, Varian) to evaluate the median mean liver dose (MLD), 13.1 Gy (range, 5.5- 24.6 Gy) and the percentage of the uninvolved liver (liver volume other than GTV) volume exceeding 20 Gy (V20Gy), 20.7 % (range, 6.2- 48.3 %). There was no significant difference in MLD and V20Gy between patients with or without grade 3 toxicities. Conclusion: Repeated SBRT can be used safely and effectively for patients with intra-hepatic recurrent HCC. However, caution should be exercised in repeated SBRT usage for CP class B patients due to high rates of severe liver toxicities. Author Disclosure: T. Kimura: None. K. Hioki: None. H. Aikata: None. K. Kubo: None. S. Takahashi: None. Y. Takeuchi: None. I. Takahashi: None. I. Nishibuchi: None. Y. Murakami: None. K. Chayama: None. Y. Nagata: None.
Purpose/Objective(s): Studies investigating active bone marrow (BMact) as organ at risk (OAR) present promising results. Main limitations are small samples size and no comparison to conventional total bone marrow (BMtot) delineation. The purpose is to determine if dose-volume parameters of BMact (delineated on basis of T1 weighted MRI) and BMtot correlate with hematologic toxicity (HT) in rectal cancer patients during neoadjuvant chemoradiotherapy (CRT). Materials/Methods: Twenty-five patients (13 women (W), 12 men (M)) with stage II-III rectal adenocarcinoma prospectively enrolled to analysis received neoadjuvant CRT to 50,4 Gy with concurrent 5-Fluorouracil/ Leucovorin and underwent pretreatment 1,5T MRI which were fused with planning CT. As proposed in prior studies regions with signal intensity equal or slightly higher than that of muscle on T1 weighted MRI were delineated as BMact. BMtot in pelvic region was contoured based on CT. White blood cells counts (WBC), platelets counts (PLT), red blood cells counts (RBC), absolute neutrophils count (ANC), absolute Lymphocyte Count (ALC) were collected before, weekly during and at the end of CRT. Dose-volume metrics of BMact and BMtot and other potential predictors of acute HT (gender, age, BMI, ECOG status, cancer clinical stage, volume of BMtot, pretreatment WBC, PLT, RBC ANC, ALC) were correlated with WBC, PLT, RBC ANC, ALC nadirs (described as percentage of baseline). Univariate, multivariate linear models and Mann-Whitney U test were used to test associations between variables (if not indicated p<0,05). Results: Lymphopenia stage 3 (CTCAE v.4.03) occurred in 8 patients (32%), most commonly in the fifth week of treatment (52%). Univariate analysis revealed PLT nadirs were correlated with V5-V10 for both BMact (rZ0,41) and BMtot (rZ0,40-0,41), ALC nadirs were correlated with V5V40 for both BMact (rZ0,41-0,56) and BMtot (rZ0,41-0,60). Women had lower volume of BMtot (M 1889,6cc W 1396,4cc p<0,001) thus worse dosevolume metrics of V5-V40 and ANC nadirs (M 29% W 22%). Multivariate linear regression models including listed above potential predictors of HT were performed separately for BMact and BMtot for ANC nadirs. ANC nadir regression model for BMtot was significant and highly predictive (p<0,01, R2Z0,95 adjusted R2Z0,84) and revealed ANC nadir was correlated with baseline ANC (p<0,01), volume of BMtot (p<0,05) V10-BMtot, V15BMtot, V50-BMtot (p<0,01) and ECOG (p<0,01). In contrary ANC nadir for BMact was insignificant, revealed no significant predictors. Conclusion: Dose-volume metrics of BMact and BMtot may be correlated with ANC nadirs in CRT for rectal cancer. Multivariate regression model for BMtot seems to be more predictive of HT than model for BMact. Author Disclosure: L. Kuncman: None. M. Maslowski: None. J. Danielska: None. J. Łuniewska-Bury: V-ce Head of Brachytherapy Department; Wojewo´dzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi. Medical Director-Oncology; Wojewo´dzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi. J. Fijuth: Head of Radiotherapy Department; Wojewo´dzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi, Department of Radiotherapy, Medical University of Ło´dz.
Volume 99 Number 2S Supplement 2017
2391
2392
Repeated Stereotactic Body Radiotherapy for Intra-Hepatic Recurrent Hepatocellular Carcinoma T. Kimura,1 K. Hioki,2 H. Aikata,3 K. Kubo,4 S. Takahashi,5 Y. Takeuchi,1 I. Takahashi,1 I. Nishibuchi,1 Y. Murakami,1 K. Chayama,3 and Y. Nagata1; 1Department of Radiation Oncology, Hiroshima University, Hiroshima, Japan, 2Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima, Japan, 3 Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan, 4Department of Radiation Oncology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan, 5 Department of Radiation Oncology, Kagawa University Hospital, Kagawa, Japan
Dose-Volume Parameters of MRI Active Bone Marrow Versus Total Bone Marrow As Predictor of Hematologic Toxicity in Rectal Cancer Patients during Neoadjuvant Chemoradiation Therapy L. Kuncman,1 M. Maslowski,2 J. Danielska,1 J. Łuniewska-Bury,3 and J. Fijuth1; 1Department of Radiotherapy, Medical University of Lodz, Lodz, Poland, 2Department of Teleradiotherapy, Regional Cancer Center, Copernicus Memorial Hospital of Lodz, Lodz, Poland, 3Department of Brachytherapy, Regional Cancer Center, Copernicus Memorial Hospital of Lodz, Lodz, Poland
Purpose/Objective(s): The safety and efficacy of stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) is well established. However, the effect of repeated SBRT for intra-hepatic recurrent HCC is unclear. This study aimed to retrospectively evaluate the safety and efficacy of repeated SBRT for intra-hepatic recurrent HCC. Materials/Methods: We enrolled 24 patients with 53 tumors who had undergone 2 two courses (median 2 times; range 2- 4 times). Sixteen patients (66.7%) had previously undergone surgery or ablation therapy, and 45 lesions (84.9%) underwent trans-arterial chemo-embolization using lipiodol before SBRT. Median tumor size was 17 mm (range 5- 47 mm). Child-Pugh (CP) scoring system was used to classify 20 and 4 patients (first course), and 18 and 6 patients (second course or beyond) into classes A and B, respectively. SBRT was performed using a 3dimensional conformal method which delivered a single high dose radiation to the tumor. Prescribed dose was evaluated at the isocenter in 27 lesions (median dose: 48 Gy in 4 fractions) and at D95% prescription in 26 lesions (median dose: 40 G y in 4 fractions) for the first and rest of the courses. Local progression was defined as growth of the irradiated tumor and early arterial enhancement remaining for more than 6 months on follow-up with dynamic CT. Treatment-related toxicities were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version. Results: The median follow-up duration was 42 months (range, 9- 79 months). The median interval between the first and the repeated SBRT was 21 months (range 4 - 61 months). Three- year overall survival rates, and local control rates for patients were 75.0 % (95 % CI: 56.0 - 94.0 %) and 97.4 % (95 % CI: 92.5 e 100 %), respectively. Grade 3 toxicities such as AST/ALT elevation, decreased platelet count, and ascites were observed in 4 patients (16.7 %) in the first course and 5 patients (20.8 %) in the second course or beyond. Seven patients developed grade 3 during all the courses, which was significantly higher in CP class B than in CP class A (pZ0.0196). All sessions were fused using deformable registration software (Velosity, Varian) to evaluate the median mean liver dose (MLD), 13.1 Gy (range, 5.5- 24.6 Gy) and the percentage of the uninvolved liver (liver volume other than GTV) volume exceeding 20 Gy (V20Gy), 20.7 % (range, 6.2- 48.3 %). There was no significant difference in MLD and V20Gy between patients with or without grade 3 toxicities. Conclusion: Repeated SBRT can be used safely and effectively for patients with intra-hepatic recurrent HCC. However, caution should be exercised in repeated SBRT usage for CP class B patients due to high rates of severe liver toxicities. Author Disclosure: T. Kimura: None. K. Hioki: None. H. Aikata: None. K. Kubo: None. S. Takahashi: None. Y. Takeuchi: None. I. Takahashi: None. I. Nishibuchi: None. Y. Murakami: None. K. Chayama: None. Y. Nagata: None.
Purpose/Objective(s): Studies investigating active bone marrow (BMact) as organ at risk (OAR) present promising results. Main limitations are small samples size and no comparison to conventional total bone marrow (BMtot) delineation. The purpose is to determine if dose-volume parameters of BMact (delineated on basis of T1 weighted MRI) and BMtot correlate with hematologic toxicity (HT) in rectal cancer patients during neoadjuvant chemoradiotherapy (CRT). Materials/Methods: Twenty-five patients (13 women (W), 12 men (M)) with stage II-III rectal adenocarcinoma prospectively enrolled to analysis received neoadjuvant CRT to 50,4 Gy with concurrent 5-Fluorouracil/ Leucovorin and underwent pretreatment 1,5T MRI which were fused with planning CT. As proposed in prior studies regions with signal intensity equal or slightly higher than that of muscle on T1 weighted MRI were delineated as BMact. BMtot in pelvic region was contoured based on CT. White blood cells counts (WBC), platelets counts (PLT), red blood cells counts (RBC), absolute neutrophils count (ANC), absolute Lymphocyte Count (ALC) were collected before, weekly during and at the end of CRT. Dose-volume metrics of BMact and BMtot and other potential predictors of acute HT (gender, age, BMI, ECOG status, cancer clinical stage, volume of BMtot, pretreatment WBC, PLT, RBC ANC, ALC) were correlated with WBC, PLT, RBC ANC, ALC nadirs (described as percentage of baseline). Univariate, multivariate linear models and Mann-Whitney U test were used to test associations between variables (if not indicated p<0,05). Results: Lymphopenia stage 3 (CTCAE v.4.03) occurred in 8 patients (32%), most commonly in the fifth week of treatment (52%). Univariate analysis revealed PLT nadirs were correlated with V5-V10 for both BMact (rZ0,41) and BMtot (rZ0,40-0,41), ALC nadirs were correlated with V5V40 for both BMact (rZ0,41-0,56) and BMtot (rZ0,41-0,60). Women had lower volume of BMtot (M 1889,6cc W 1396,4cc p<0,001) thus worse dosevolume metrics of V5-V40 and ANC nadirs (M 29% W 22%). Multivariate linear regression models including listed above potential predictors of HT were performed separately for BMact and BMtot for ANC nadirs. ANC nadir regression model for BMtot was significant and highly predictive (p<0,01, R2Z0,95 adjusted R2Z0,84) and revealed ANC nadir was correlated with baseline ANC (p<0,01), volume of BMtot (p<0,05) V10-BMtot, V15BMtot, V50-BMtot (p<0,01) and ECOG (p<0,01). In contrary ANC nadir for BMact was insignificant, revealed no significant predictors. Conclusion: Dose-volume metrics of BMact and BMtot may be correlated with ANC nadirs in CRT for rectal cancer. Multivariate regression model for BMtot seems to be more predictive of HT than model for BMact. Author Disclosure: L. Kuncman: None. M. Maslowski: None. J. Danielska: None. J. Łuniewska-Bury: V-ce Head of Brachytherapy Department; Wojewo´dzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi. Medical Director-Oncology; Wojewo´dzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi. J. Fijuth: Head of Radiotherapy Department; Wojewo´dzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi, Department of Radiotherapy, Medical University of Ło´dz.