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Single-fraction Stereotactic Irradiation of Liver Metastases: Preliminary Results of a Phase I Trial
Digital Poster Discussion Abstracts S191
Volume 84 Number 3S Supplement 2012 Results: Groups I and II, with 34 and 25 patients respectively, had no significant demographic differences; tumor sizes ranged from 1.8-17.6 cm with mean tumor size 5.6 versus 6.4 cm in groups 1 and 2, respectively (p Z ns). Local control in this series is 58%. Overall, the median follow-up was 21 months and median overall survival was not reached in group 1 and 5.5 years in group II (p < 0.001). In group 2, 20 patients (80%) had first recurrences within the liver with median time to recurrence 10.5 months after resection; 2 patients had synchronous metastatic recurrence and were not included in further analysis. Eleven patients had only a single recurrent liver nodule and 12 patients recurred with multiple nodules synchronously. Nine of these 23 patients (39%) had tumor at or abutting the surgical margin. Microscopic margin was 2 cm for 92% versus 96% in groups 1 and 2, respectively (p Z ns). Four (17%) had recurrence within 2 cm of the surgical bed. Vascular invasion was correlated with recurrence (p Z 0.003) while the number of HCC lesions (p Z 0.076), margin status (p Z ns) and grade (p Z ns) were not significant correlates. None of the tumors ruptured at resection. Conclusions: In our series, upfront surgical resection had a local control of 58%. The majority of first recurrences (80%) were in the liver. Vascular invasion was a significant predictor for local recurrence with 17% occurring within 2 cm of the surgical bed. These patients may benefit from wider surgical margins, intra-operative radiation therapy, or adjuvant radiation. Author Disclosure: A. Kumar: None. G. El-Gazzaz: None. F. Aucejo: None. M. Abdel-Wahab: None.
1062 SBRT for Liver Metastases: Results on 173 Treated Lesions C. Menichelli,1 F. Casamassima,1 M. Panichi,2 G. Pastore,1 A. Fanelli,1 and E. Infusino1; 1Department of Radiotherapy-Ecomedica Institute, Empoli (Florence), Italy, 2UO Radioterapia Azienda OspedalieraUniversitaria Pisana, Pisa, Italy Purpose/Objective(s): The liver is a common site of metastatic spread for solid tumor and very often represents the only site of metastases. Some patients, however are not fit to surgery excision or other tumor ablation strategies (e.g., RFA and PEI), considered for limited disease. The purpose of this study is to assess efficacy of SBRT, as ablative therapy, to achieve local control and its relationship with type of primary tumor, dose prescription, and treatment delivery modalities. Materials/Methods: One hundred Patients (pts) (173 lesions) were treated by SBRT for liver metastases (primary was colon in 59 cases, breast in 18, lung in 7, and others in 16). Adopted inclusion criteria were no more than 5 metastases and no more than 6 cm in diameter. GTV was countered using CT data sets acquired at different respiratory phases to obtain an ITV in 17/ 100 pts and in 83/100 pts using Active Breathing Coordinator (ABC), both during CT acquisition and treatment delivery, to achieve a reduction of respiratory displacements. In 66 pts, gold fiducial markers as target surrogate were implanted. Target mean volume was 65.7 cc (range, 0.3-365 cc) and mean number of treated lesion was 1.7 (range, 1-5). Mean dose was 35 Gy (range, 25-48 Gy) prescribed to isocenter in 65/173 lesions and to the 67-70% isodose in 108 lesions delivered in three fractions. Treatment was delivered through multiple coplanar and no-coplanar arcs and DMLC by 6 MV LINAC. Isocenter position was verified before each fraction using CBCT co-registered to planning CT on diaphragm profile or gold fiducials. Local Control (CL), defined as no tumor regrowth in the irradiated volume, was evaluated by multiphasic CT at 2, 6, and 12 months after SBRT and every 6 months successively. Toxicity was evaluated according to CTCAE scale. Results: Median follow-up was 15 months (range, 2-63 months). The rate of LC at 6, 12, and 24 months was 92.8%, 78%, and 62%, respectively. On univariate analysis, the use of ABC system (p Z 0.0169), implanted fiducials (p Z 0.0006), low lesion volume (p Z 0.00768), higher delivered dose (p Z 0.00304) were correlated with better LC. No correlation was observed with tumor type, although there was a positive trend for breast secondary lesions. G1 toxicity in 12/100 patients and G2 (ulcera medically recovered) in 4 patients was observed.
Conclusions: In our experience, SBRT for liver metastasis, as ablative treatment, lead to high rate of LC that appears, in our results, to be stable after two years (62%). The use of breath control systems and target surrogates improve LC rates. These results and low toxicity suggest the SBRT as a safe and effective treatment modality that can be offered to patients not suitable for other local ablative therapies. Author Disclosure: C. Menichelli: None. F. Casamassima: None. M. Panichi: None. G. Pastore: None. A. Fanelli: None. E. Infusino: None.
1063 Single-fraction Stereotactic Irradiation of Liver Metastases: Preliminary Results of a Phase I Trial J.J. Meyer,1 W. Rule,2 R. Schwarz,1 R.D. Sims,1 and R. Timmerman1; 1 University of Texas Southwestern Medical Center, Dallas, TX, 2Mayo Clinic Arizona, Phoenix, AZ Purpose/Objective(s): Multiple different stereotactic ablative radiation therapy fractionation schedules for the treatment of liver tumors are available and under study. We are conducting a dose-escalating phase I study to evaluate the safety of treatment with a single high dose of radiation for selected patients with liver metastases- true liver radiosurgery. We are now enrolling patients at the second dose level and report the toxicity results of the first dose level (35 Gy). Materials/Methods: Patients with five or fewer liver metastases (from solid tumor primaries) located outside of the central liver zone (defined as a 2 cm shell around the portal vein from its origin to its bifurcation) are eligible, as long as a critical volume liver constraint (700 mL receiving <9.1 Gy) can be met with the treatment plan. Seven to 15 patients are enrolled at each dose level. The prescription dose was 35 Gy (to the tumor periphery), in a single fraction, at dose level 1. Dose escalation will be in increments of 5 Gy (i.e., 40 Gy at dose level 2, 45 Gy at dose level 3). Dose-limiting toxicity is defined as (NCI Common Toxicity Criteria) treatment-related grade 3 gastrointestinal, genitourinary, or neurologic toxicity, as well as grade 4 or 5 hematologic, cardiac, pulmonary, soft tissue, or skin toxicity, and is assessed to 90 days post-treatment. Results: Seven patients (four women, three men) with a total of 10 metastatic lesions were enrolled to dose level 1 and have been followed through the DLT assessment period. Patient age range was 40-82 years old (median: 63 years old). A variety of solid tumor histologies was represented. Planning target volumes ranged from 4.1-60.2 mL (median: 22.1 mL). There were no grade 2 or higher adverse events. Three patients experienced grade 1 fatigue and 2 patients had grade 1 chills. No patient had grade 2 or higher liver enzyme elevation. At 3-month follow-up, for nine of the ten treated lesions assessable by MRI, there was one complete response and no patient had progression of treated lesions. Conclusions: Thirty-five Gy delivered in one fraction is a tolerable dose in selected patients with liver metastases with early indication of treatment activity. Enrollment in the study has continued at dose level 2. Author Disclosure: J.J. Meyer: None. W. Rule: None. R. Schwarz: F. Honoraria; Novartis. G. Consultant; Novartis. R.D. Sims: None. R. Timmerman: None.
1064 Individualized High Precision Radiation Therapy for Liver Tumors Based on 4D List Mode PET/CT I. Ernst,1 C. Moustakis,1 F. Buether,2 J. Dullat,1 S. Scobioala,1 N. Willich,1 U. Haverkamp,1 and H.T. Eich1; 1Westfaelic Wilhelm University, Muenster, Germany, 2European Institute of Molecular Imaging, Muenster, Germany Purpose/Objective(s): Individual target motion is a major problem in high precision radiation therapy techniques. Four-dimensional list mode PET/CT can solve this problem for PET visible lesions by valid detection of movements. This study evaluates our clinical experience using 4D list mode- based target delineation in free breathing stereotactic body radiation therapy (SBRT) of liver tumors. Materials/Methods: Eighty-five patients were enrolled. They suffered from metastases (n Z 76; one to four lesions), Klatskin tumor (n Z 7) or
Volume 84 Number 3S Supplement 2012 Results: Groups I and II, with 34 and 25 patients respectively, had no significant demographic differences; tumor sizes ranged from 1.8-17.6 cm with mean tumor size 5.6 versus 6.4 cm in groups 1 and 2, respectively (p Z ns). Local control in this series is 58%. Overall, the median follow-up was 21 months and median overall survival was not reached in group 1 and 5.5 years in group II (p < 0.001). In group 2, 20 patients (80%) had first recurrences within the liver with median time to recurrence 10.5 months after resection; 2 patients had synchronous metastatic recurrence and were not included in further analysis. Eleven patients had only a single recurrent liver nodule and 12 patients recurred with multiple nodules synchronously. Nine of these 23 patients (39%) had tumor at or abutting the surgical margin. Microscopic margin was 2 cm for 92% versus 96% in groups 1 and 2, respectively (p Z ns). Four (17%) had recurrence within 2 cm of the surgical bed. Vascular invasion was correlated with recurrence (p Z 0.003) while the number of HCC lesions (p Z 0.076), margin status (p Z ns) and grade (p Z ns) were not significant correlates. None of the tumors ruptured at resection. Conclusions: In our series, upfront surgical resection had a local control of 58%. The majority of first recurrences (80%) were in the liver. Vascular invasion was a significant predictor for local recurrence with 17% occurring within 2 cm of the surgical bed. These patients may benefit from wider surgical margins, intra-operative radiation therapy, or adjuvant radiation. Author Disclosure: A. Kumar: None. G. El-Gazzaz: None. F. Aucejo: None. M. Abdel-Wahab: None.
1062 SBRT for Liver Metastases: Results on 173 Treated Lesions C. Menichelli,1 F. Casamassima,1 M. Panichi,2 G. Pastore,1 A. Fanelli,1 and E. Infusino1; 1Department of Radiotherapy-Ecomedica Institute, Empoli (Florence), Italy, 2UO Radioterapia Azienda OspedalieraUniversitaria Pisana, Pisa, Italy Purpose/Objective(s): The liver is a common site of metastatic spread for solid tumor and very often represents the only site of metastases. Some patients, however are not fit to surgery excision or other tumor ablation strategies (e.g., RFA and PEI), considered for limited disease. The purpose of this study is to assess efficacy of SBRT, as ablative therapy, to achieve local control and its relationship with type of primary tumor, dose prescription, and treatment delivery modalities. Materials/Methods: One hundred Patients (pts) (173 lesions) were treated by SBRT for liver metastases (primary was colon in 59 cases, breast in 18, lung in 7, and others in 16). Adopted inclusion criteria were no more than 5 metastases and no more than 6 cm in diameter. GTV was countered using CT data sets acquired at different respiratory phases to obtain an ITV in 17/ 100 pts and in 83/100 pts using Active Breathing Coordinator (ABC), both during CT acquisition and treatment delivery, to achieve a reduction of respiratory displacements. In 66 pts, gold fiducial markers as target surrogate were implanted. Target mean volume was 65.7 cc (range, 0.3-365 cc) and mean number of treated lesion was 1.7 (range, 1-5). Mean dose was 35 Gy (range, 25-48 Gy) prescribed to isocenter in 65/173 lesions and to the 67-70% isodose in 108 lesions delivered in three fractions. Treatment was delivered through multiple coplanar and no-coplanar arcs and DMLC by 6 MV LINAC. Isocenter position was verified before each fraction using CBCT co-registered to planning CT on diaphragm profile or gold fiducials. Local Control (CL), defined as no tumor regrowth in the irradiated volume, was evaluated by multiphasic CT at 2, 6, and 12 months after SBRT and every 6 months successively. Toxicity was evaluated according to CTCAE scale. Results: Median follow-up was 15 months (range, 2-63 months). The rate of LC at 6, 12, and 24 months was 92.8%, 78%, and 62%, respectively. On univariate analysis, the use of ABC system (p Z 0.0169), implanted fiducials (p Z 0.0006), low lesion volume (p Z 0.00768), higher delivered dose (p Z 0.00304) were correlated with better LC. No correlation was observed with tumor type, although there was a positive trend for breast secondary lesions. G1 toxicity in 12/100 patients and G2 (ulcera medically recovered) in 4 patients was observed.
Conclusions: In our experience, SBRT for liver metastasis, as ablative treatment, lead to high rate of LC that appears, in our results, to be stable after two years (62%). The use of breath control systems and target surrogates improve LC rates. These results and low toxicity suggest the SBRT as a safe and effective treatment modality that can be offered to patients not suitable for other local ablative therapies. Author Disclosure: C. Menichelli: None. F. Casamassima: None. M. Panichi: None. G. Pastore: None. A. Fanelli: None. E. Infusino: None.
1063 Single-fraction Stereotactic Irradiation of Liver Metastases: Preliminary Results of a Phase I Trial J.J. Meyer,1 W. Rule,2 R. Schwarz,1 R.D. Sims,1 and R. Timmerman1; 1 University of Texas Southwestern Medical Center, Dallas, TX, 2Mayo Clinic Arizona, Phoenix, AZ Purpose/Objective(s): Multiple different stereotactic ablative radiation therapy fractionation schedules for the treatment of liver tumors are available and under study. We are conducting a dose-escalating phase I study to evaluate the safety of treatment with a single high dose of radiation for selected patients with liver metastases- true liver radiosurgery. We are now enrolling patients at the second dose level and report the toxicity results of the first dose level (35 Gy). Materials/Methods: Patients with five or fewer liver metastases (from solid tumor primaries) located outside of the central liver zone (defined as a 2 cm shell around the portal vein from its origin to its bifurcation) are eligible, as long as a critical volume liver constraint (700 mL receiving <9.1 Gy) can be met with the treatment plan. Seven to 15 patients are enrolled at each dose level. The prescription dose was 35 Gy (to the tumor periphery), in a single fraction, at dose level 1. Dose escalation will be in increments of 5 Gy (i.e., 40 Gy at dose level 2, 45 Gy at dose level 3). Dose-limiting toxicity is defined as (NCI Common Toxicity Criteria) treatment-related grade 3 gastrointestinal, genitourinary, or neurologic toxicity, as well as grade 4 or 5 hematologic, cardiac, pulmonary, soft tissue, or skin toxicity, and is assessed to 90 days post-treatment. Results: Seven patients (four women, three men) with a total of 10 metastatic lesions were enrolled to dose level 1 and have been followed through the DLT assessment period. Patient age range was 40-82 years old (median: 63 years old). A variety of solid tumor histologies was represented. Planning target volumes ranged from 4.1-60.2 mL (median: 22.1 mL). There were no grade 2 or higher adverse events. Three patients experienced grade 1 fatigue and 2 patients had grade 1 chills. No patient had grade 2 or higher liver enzyme elevation. At 3-month follow-up, for nine of the ten treated lesions assessable by MRI, there was one complete response and no patient had progression of treated lesions. Conclusions: Thirty-five Gy delivered in one fraction is a tolerable dose in selected patients with liver metastases with early indication of treatment activity. Enrollment in the study has continued at dose level 2. Author Disclosure: J.J. Meyer: None. W. Rule: None. R. Schwarz: F. Honoraria; Novartis. G. Consultant; Novartis. R.D. Sims: None. R. Timmerman: None.
1064 Individualized High Precision Radiation Therapy for Liver Tumors Based on 4D List Mode PET/CT I. Ernst,1 C. Moustakis,1 F. Buether,2 J. Dullat,1 S. Scobioala,1 N. Willich,1 U. Haverkamp,1 and H.T. Eich1; 1Westfaelic Wilhelm University, Muenster, Germany, 2European Institute of Molecular Imaging, Muenster, Germany Purpose/Objective(s): Individual target motion is a major problem in high precision radiation therapy techniques. Four-dimensional list mode PET/CT can solve this problem for PET visible lesions by valid detection of movements. This study evaluates our clinical experience using 4D list mode- based target delineation in free breathing stereotactic body radiation therapy (SBRT) of liver tumors. Materials/Methods: Eighty-five patients were enrolled. They suffered from metastases (n Z 76; one to four lesions), Klatskin tumor (n Z 7) or