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Stereotactic Body Radiation Therapy For T1N0M0 Non-small Cell Lung Cancer: First Report for Inoperable Population of a Phase II Trial by Japan Clinical Oncology Group (JCOG 0403)
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International Journal of Radiation Oncology Biology Physics
after CRT was 12 years (range: 1.3-24.1 years). Chemotherapy or race did not affect hazard of first stroke. NF1 was present in three patients. A total of 12 patients received treatment for their stroke (aspirin: n Z 10; anticoagulation: n Z 2). There were 6 recurrent strokes (5 by interview and 1 by chart review) of which 5 had imaging findings consistent with stroke. Median time to develop stroke after first stroke was 15 month (range 5.6 month-8.9 years). Median age at time of recurrent stroke was 27.3 years (range 25.6 - 34.5 years). One patient with recurrent stroke had evidence of NF1. The cumulative incidence of recurrent stroke was 26% (95% CI 951%) at 5 years post first-stroke and 32% (95% CI 13-57%) at 10 years. Conclusions: Survivors of childhood cancer who received CRT are at high risk for first and recurrent stroke. Author Disclosure: S. Mueller: None. K. Sear: None. N. Hills: None. N. Chettout: None. S. Afghani: None. L. Keiko: None. E. Tolentino: None. D. Haas-Kogan: None. H. Fullerton: None.
CI: 42.6% -62.1%), 46.8% (95% CI: 36.7% - 56.2%), respectively. Grade 3 adverse event (AE) was observed in dyspnea 9 (9%), hypoxia 8 (8%), pneumonitis 7 (7%), chest pain 2 (2%), and cough 1(1%). Grade 4 AE was observed in dyspnea 1 (1%) and hypoxia 1 (1%). No grade 5 AE was observed. Conclusions: SBRT for inoperable stage I NSCLC is highly effective with mild toxicity. This treatment should be the new standard treatment replacing conventional radiation therapy. Author Disclosure: Y. Nagata: None. M. Hiraoka: None. T. Shibata: None. H. Onishi: None. M. Kokubo: None. K. Karasawa: None. Y. Shioyama: None. R. Onimaru: None. T. Kozuka: None. S. Ishikura: None.
115 Stereotactic Body Radiation Therapy For T1N0M0 Non-small Cell Lung Cancer: First Report for Inoperable Population of a Phase II Trial by Japan Clinical Oncology Group (JCOG 0403) Y. Nagata,1 M. Hiraoka,2 T. Shibata,3 H. Onishi,4 M. Kokubo,5 K. Karasawa,6 Y. Shioyama,7 R. Onimaru,8 T. Kozuka,9 and S. Ishikura10; 1 Radiation Oncology, Hiroshima University, Hiroshima, Japan, 2 Therapeutic Radiology and Image-applied therapy, Kyoto University, Kyoto, Japan, 3JCOG Data Center, National Cancer Center, Tokyo, Japan, 4 Radiation Oncology, University of Yamanashi, Yamanashi, Japan, 5 Image-based Medicine, Institute of Biomedical research and innovation, Kobe, Japan, 6Radiation Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan, 7Clinical Radiology, Kyushu University, Fukuoka, Japan, 8Radiology, Hokkaido University, Sapporo, Japan, 9Radiation Oncology, The Cancer Institute Hospital, Tokyo, Japan, 10Radiology, Nagoya City University, Nagoya, Japan Purpose/Objective(s): The purpose of JCOG0403 was to evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with both operable and medically inoperable T1N0M0 non-small cell lung cancer (NSCLC) (UICC 6th ed., 2002). The first report for operable population was reported in 2010, and this is the report analyzed for inoperable population. Materials/Methods: The eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0, inoperable patients assessed by thoracic surgeons, PS 0-2, 20 years old, PaO2 60 torr, FEV1.0 700 mL, and written informed consent. The prescription was 48 Gy at the isocenter in 4 fractions over 4-8 days. Four to 10 MV X-rays were allowed. Heterogeneity corrected doses by pencil beam algorithms were used. The GTV included the primary tumor only, CTV margin was not considered, and ITV margin and 5 mm setup margin were added. As a quality assurance program, credentialing of institutions and an individual case review using the Image-guided Therapy Center (ITC) remote review tool were performed. The primary endpoint was the three-year overall survival (OS). The secondary endpoints included OS, progression-free survival (PFS), local-progression free survival (LPFS), event-free survival (EFS), and toxicity. The required sample size was 91 to provide at least 90% power under the hypothesis of the expected value of the primary endpoint of 50% and the threshold value of 35% with a one-sided alpha of 0.05. Taking into account ineligible patients and a precision of estimate, sample size was determined as 100. Results: Between July 2004 and November 2008, 104 inoperable patients were registered in this study from 15 institutions. The patients characteristics were: male 77, female 27; median age 78 (range 59-90); median tumor size 21 mm (range 9-30 mm); adenocarcinomas 50, squamous cell carcinomas 40, others 14; and PS 0/1/2, 49/46/9. All patients completed the protocol treatment. At the last follow-up in December 2011, median follow-up of censored cases was 46.8 months. Of the eligible 100 patients, the 3-year overall survival was 59.9% (the lower limit of 95% CI, 51.4%, exceeded a threshold of 35%, 95% CI: 49.6% - 68.8%), and the 3-year PFS, LPFS, and EFS were 49.8% (95% CI: 39.7% - 59.2%), 52.8% (95%
116 Sublobar Resection With Intraoperative 125I Brachytherapy Versus Stereotactic Body Radiation Therapy for Treatment of Clinical Early-Stage Non-small Cell Lung Cancer in Patients not Eligible for Lobectomy C.S. Platta,1 T.J. Kruser,1 T.L. Weigel,1 W.A. Tome,1 R.K. Das,1 H.M. Geye,1 D. Khuntia,2 M.P. Mehta,3 and G.M. Cannon1; 1University of Wisconsin Hospital and Clinics Madison, Madison, WI, 2Western Radiation Oncology, San Mateo, CA, 3Northwestern University, Chicago, IL Purpose/Objective(s): The standard of care for early stage non-small cell lung cancer (NSCLC) is lobectomy with lymph node dissection. In this analysis, two alternative therapies for early stage NSCLC in patients not candidates for anatomic lobectomy are compared: thoracoscopic sublobar resection (SLR) with intraoperative 125I brachytherapy implant along the staple line versus stereotactic body radiation therapy (SBRT). Materials/Methods: A total of 95 patients with early stage NSCLC treated with either SLR resection or 125I brachytherapy (n Z 45) or SBRT (n Z 50) between January 2004 and June 2011 were retrospectively identified. Prescription dose for SLR with brachytherapy was either 100 Gy at 0.5 cm (n Z 32) or 120 Gy at 0.5 cm (n Z 13). SBRT median dose and fractionation scheme was 60 Gy in 5 fractions, corresponding to a median BED of 132 Gy. Charlson Comorbidity Index (CCI) scores were calculated for all patients. Local control (LC), regional control (RC), disease free survival (DFS), overall survival (OS) and toxicity between the two cohorts were compared. Results: The median age was 68 years (range 49-87) in the SLR group, and 76.5 years (range 52-89) in the SBRT group. Median follow-up was 15.8 months. The median CCI score for the brachytherapy group was 4 (range 2-8), and 6 (range 3-12) (p < 0.01) for the SBRT group. The median hospital stay was 3 days (range 1-18 days) in the SLR cohort, with 1 perioperative death (2.2% perioperative mortality). There were no treatment related deaths in the SBRT group. Five patients (11.1%) experienced grade 3 or higher toxicities in the brachytherapy group versus 9 (18.0%) in the SBRT cohort. At 24 months, there was no significant difference in actuarial LC (95.8 vs. 97.1%, p Z 0.51), RC (88.2 vs. 92.7%, p Z 0.64), and DFS (78.7 vs. 87.7%, p Z 0.82) between brachytherapy and SBRT. There was a trend towards improved 1 and 2 year actuarial OS for the brachytherapy over the SBRT group, 97.8 versus 76.0% and 77.2 versus 51.2% (p Z 0.09), respectively. Conclusions: No randomized trials have compared these two modalities. In this analysis, both SLR with 125I brachytherapy and SBRT showed equivalent outcomes in terms of LC, RC, DFS and OS. There is a trend towards improved OS in the brachytherapy group, likely reflective of the worse CCI score within the SBRT group and an anticipated increased risk of death from intercurrent disease. The higher CCI score within the SBRT group is consistent with our institutional practice of preferentially pursuing SLR with brachytherapy in surgical candidates. Both SLR with 125I brachytherapy and SBRT are viable alternatives for clinical early stage NSCLC patients who cannot tolerate lobectomy. Author Disclosure: C.S. Platta: None. T.J. Kruser: None. T.L. Weigel: None. W.A. Tome: E. Research Grant; Philips Radiation Oncology Systems. N. Royalty; Sole author of a monograph in mathematical physics entitled: Path Integrals on Group Manifolds. O. Patent/License Fee/
International Journal of Radiation Oncology Biology Physics
after CRT was 12 years (range: 1.3-24.1 years). Chemotherapy or race did not affect hazard of first stroke. NF1 was present in three patients. A total of 12 patients received treatment for their stroke (aspirin: n Z 10; anticoagulation: n Z 2). There were 6 recurrent strokes (5 by interview and 1 by chart review) of which 5 had imaging findings consistent with stroke. Median time to develop stroke after first stroke was 15 month (range 5.6 month-8.9 years). Median age at time of recurrent stroke was 27.3 years (range 25.6 - 34.5 years). One patient with recurrent stroke had evidence of NF1. The cumulative incidence of recurrent stroke was 26% (95% CI 951%) at 5 years post first-stroke and 32% (95% CI 13-57%) at 10 years. Conclusions: Survivors of childhood cancer who received CRT are at high risk for first and recurrent stroke. Author Disclosure: S. Mueller: None. K. Sear: None. N. Hills: None. N. Chettout: None. S. Afghani: None. L. Keiko: None. E. Tolentino: None. D. Haas-Kogan: None. H. Fullerton: None.
CI: 42.6% -62.1%), 46.8% (95% CI: 36.7% - 56.2%), respectively. Grade 3 adverse event (AE) was observed in dyspnea 9 (9%), hypoxia 8 (8%), pneumonitis 7 (7%), chest pain 2 (2%), and cough 1(1%). Grade 4 AE was observed in dyspnea 1 (1%) and hypoxia 1 (1%). No grade 5 AE was observed. Conclusions: SBRT for inoperable stage I NSCLC is highly effective with mild toxicity. This treatment should be the new standard treatment replacing conventional radiation therapy. Author Disclosure: Y. Nagata: None. M. Hiraoka: None. T. Shibata: None. H. Onishi: None. M. Kokubo: None. K. Karasawa: None. Y. Shioyama: None. R. Onimaru: None. T. Kozuka: None. S. Ishikura: None.
115 Stereotactic Body Radiation Therapy For T1N0M0 Non-small Cell Lung Cancer: First Report for Inoperable Population of a Phase II Trial by Japan Clinical Oncology Group (JCOG 0403) Y. Nagata,1 M. Hiraoka,2 T. Shibata,3 H. Onishi,4 M. Kokubo,5 K. Karasawa,6 Y. Shioyama,7 R. Onimaru,8 T. Kozuka,9 and S. Ishikura10; 1 Radiation Oncology, Hiroshima University, Hiroshima, Japan, 2 Therapeutic Radiology and Image-applied therapy, Kyoto University, Kyoto, Japan, 3JCOG Data Center, National Cancer Center, Tokyo, Japan, 4 Radiation Oncology, University of Yamanashi, Yamanashi, Japan, 5 Image-based Medicine, Institute of Biomedical research and innovation, Kobe, Japan, 6Radiation Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan, 7Clinical Radiology, Kyushu University, Fukuoka, Japan, 8Radiology, Hokkaido University, Sapporo, Japan, 9Radiation Oncology, The Cancer Institute Hospital, Tokyo, Japan, 10Radiology, Nagoya City University, Nagoya, Japan Purpose/Objective(s): The purpose of JCOG0403 was to evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with both operable and medically inoperable T1N0M0 non-small cell lung cancer (NSCLC) (UICC 6th ed., 2002). The first report for operable population was reported in 2010, and this is the report analyzed for inoperable population. Materials/Methods: The eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0, inoperable patients assessed by thoracic surgeons, PS 0-2, 20 years old, PaO2 60 torr, FEV1.0 700 mL, and written informed consent. The prescription was 48 Gy at the isocenter in 4 fractions over 4-8 days. Four to 10 MV X-rays were allowed. Heterogeneity corrected doses by pencil beam algorithms were used. The GTV included the primary tumor only, CTV margin was not considered, and ITV margin and 5 mm setup margin were added. As a quality assurance program, credentialing of institutions and an individual case review using the Image-guided Therapy Center (ITC) remote review tool were performed. The primary endpoint was the three-year overall survival (OS). The secondary endpoints included OS, progression-free survival (PFS), local-progression free survival (LPFS), event-free survival (EFS), and toxicity. The required sample size was 91 to provide at least 90% power under the hypothesis of the expected value of the primary endpoint of 50% and the threshold value of 35% with a one-sided alpha of 0.05. Taking into account ineligible patients and a precision of estimate, sample size was determined as 100. Results: Between July 2004 and November 2008, 104 inoperable patients were registered in this study from 15 institutions. The patients characteristics were: male 77, female 27; median age 78 (range 59-90); median tumor size 21 mm (range 9-30 mm); adenocarcinomas 50, squamous cell carcinomas 40, others 14; and PS 0/1/2, 49/46/9. All patients completed the protocol treatment. At the last follow-up in December 2011, median follow-up of censored cases was 46.8 months. Of the eligible 100 patients, the 3-year overall survival was 59.9% (the lower limit of 95% CI, 51.4%, exceeded a threshold of 35%, 95% CI: 49.6% - 68.8%), and the 3-year PFS, LPFS, and EFS were 49.8% (95% CI: 39.7% - 59.2%), 52.8% (95%
116 Sublobar Resection With Intraoperative 125I Brachytherapy Versus Stereotactic Body Radiation Therapy for Treatment of Clinical Early-Stage Non-small Cell Lung Cancer in Patients not Eligible for Lobectomy C.S. Platta,1 T.J. Kruser,1 T.L. Weigel,1 W.A. Tome,1 R.K. Das,1 H.M. Geye,1 D. Khuntia,2 M.P. Mehta,3 and G.M. Cannon1; 1University of Wisconsin Hospital and Clinics Madison, Madison, WI, 2Western Radiation Oncology, San Mateo, CA, 3Northwestern University, Chicago, IL Purpose/Objective(s): The standard of care for early stage non-small cell lung cancer (NSCLC) is lobectomy with lymph node dissection. In this analysis, two alternative therapies for early stage NSCLC in patients not candidates for anatomic lobectomy are compared: thoracoscopic sublobar resection (SLR) with intraoperative 125I brachytherapy implant along the staple line versus stereotactic body radiation therapy (SBRT). Materials/Methods: A total of 95 patients with early stage NSCLC treated with either SLR resection or 125I brachytherapy (n Z 45) or SBRT (n Z 50) between January 2004 and June 2011 were retrospectively identified. Prescription dose for SLR with brachytherapy was either 100 Gy at 0.5 cm (n Z 32) or 120 Gy at 0.5 cm (n Z 13). SBRT median dose and fractionation scheme was 60 Gy in 5 fractions, corresponding to a median BED of 132 Gy. Charlson Comorbidity Index (CCI) scores were calculated for all patients. Local control (LC), regional control (RC), disease free survival (DFS), overall survival (OS) and toxicity between the two cohorts were compared. Results: The median age was 68 years (range 49-87) in the SLR group, and 76.5 years (range 52-89) in the SBRT group. Median follow-up was 15.8 months. The median CCI score for the brachytherapy group was 4 (range 2-8), and 6 (range 3-12) (p < 0.01) for the SBRT group. The median hospital stay was 3 days (range 1-18 days) in the SLR cohort, with 1 perioperative death (2.2% perioperative mortality). There were no treatment related deaths in the SBRT group. Five patients (11.1%) experienced grade 3 or higher toxicities in the brachytherapy group versus 9 (18.0%) in the SBRT cohort. At 24 months, there was no significant difference in actuarial LC (95.8 vs. 97.1%, p Z 0.51), RC (88.2 vs. 92.7%, p Z 0.64), and DFS (78.7 vs. 87.7%, p Z 0.82) between brachytherapy and SBRT. There was a trend towards improved 1 and 2 year actuarial OS for the brachytherapy over the SBRT group, 97.8 versus 76.0% and 77.2 versus 51.2% (p Z 0.09), respectively. Conclusions: No randomized trials have compared these two modalities. In this analysis, both SLR with 125I brachytherapy and SBRT showed equivalent outcomes in terms of LC, RC, DFS and OS. There is a trend towards improved OS in the brachytherapy group, likely reflective of the worse CCI score within the SBRT group and an anticipated increased risk of death from intercurrent disease. The higher CCI score within the SBRT group is consistent with our institutional practice of preferentially pursuing SLR with brachytherapy in surgical candidates. Both SLR with 125I brachytherapy and SBRT are viable alternatives for clinical early stage NSCLC patients who cannot tolerate lobectomy. Author Disclosure: C.S. Platta: None. T.J. Kruser: None. T.L. Weigel: None. W.A. Tome: E. Research Grant; Philips Radiation Oncology Systems. N. Royalty; Sole author of a monograph in mathematical physics entitled: Path Integrals on Group Manifolds. O. Patent/License Fee/