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

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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/

Volume 84  Number 3S  Supplement 2012 Copyright; WI Alumni Research Foundation. R.K. Das: None. H.M. Geye: None. D. Khuntia: F. Honoraria; Varian Medical Systems, Procertus. G. Consultant; Radion Global Advisor. J. Funding Other; Tomotherapy, Inc.. L. Stock Options; Radion Global. M.P. Mehta: G. Consultant; Bristol Meyers Squibb (Knowledgepoint), Merck, Novartis (Articulate Science), Abbott, BioStrategies, Elekta, Frankel Group, Gerson, MAPI values, NCI, Novellos, Quark, SS Bala, Tomotherapy, US Oncology, Vertex. J. Funding Other; Apogenix, Adnexus, Elsevier, CME Products, MCM, Medscape, GRACE Foundation, Prime Oncology, WebMD, Strategic Edge, Vindico, ASCO, Cleveland Clinic, IL Radiological Society, Institute for Medical Education, MDACC, Resurrection Hospital, UT San Antonio. L. Stock Options; Accuray, Colby, Pharmacyclics, Procertus, Stemina. N. Royalty; DEMOS. O. Patent/License Fee/Copyright; WARF. Q. Leadership; Parmacyclics, Colby, Stemina, Procertus, Apogenix. G.M. Cannon: None.

117 Patterns of Disease Recurrence Following Either Stereotactic Ablative Radiation Therapy (SABR) or Lobectomy by Video-assisted Thoracoscopic Surgery (VATS) in Stage I-II Non-small Cell Lung Cancer: Outcomes of a Propensity Score-matched Analysis S. Senan,1 N. Verstegen,1 D.A. Palma,2 G. Rodrigues,2 F.J. Lagerwaard,1 A. van der Elst,3 R. Mollema,4 A. Warner,2 B.J. Slotman,1 and J.W. Oosterhuis1; 1VU University Medical Center, Amsterdam, Netherlands, 2London Regional Cancer Program, London, ON, Canada, 3 Department of Surgery, Spaarne Hospital, Hoofddorp, Netherlands, 4 Department of Surgery, Medical Center Alkmaar, Alkmaar, Netherlands Purpose/Objective(s): VATS-lobectomy is increasingly seen as a preferred procedure in early-stage NSCLC. High local control rates are also seen after stereotactic ablative radiation therapy (SABR) in these patients. We performed a propensity score-matched analysis to compare loco-regional control after both procedures. Materials/Methods: Patients with stage I-II NSCLC treated at 6 hospitals with VATS lobectomy were eligible. Details of SABR patients were obtained from a single-institutional database. Patients were matched using propensity scores based on cTNM, age, gender, Charlson comorbidity score, lung function and performance score. Matching was performed blinded to all outcomes. Excluded were: synchronous/prior lung tumors or COPD GOLD IV. In total 86 VATS- and 527 SABR patients were eligible for matching (1:1 ratio, caliper distance 0.025). Loco-regional failure was defined as recurrence in/adjacent to the planning target volume or surgical margins, ipsilateral hilum or mediastinum. Recurrences were biopsyconfirmed or PET-positive and reviewed by a multidisciplinary tumor board. Patients upstaged during VATS or developing recurrence were treated according to Dutch guidelines. Results: The matched cohort consisted of patients with cT1-3N0 NSCLC following SABR (n Z 64) or VATS-lobectomy (n Z 64). Mean age of SABR and VATS patients were 71 and 68 years, and median follow-up was 30 and 16 months, respectively. Pre-treatment histological confirmation of stage I NSCLC was available in 53% of SABR patients and 50% of VATS patients. Three planned VATS resections (4.7%) were converted into an open lobectomy, all due to hemorrhage that was difficult to control. The median number of dissected lymph node stations was 4 (range 1-6). Median number of dissected lymph nodes was 8.5 (range 1-24), and 71.9% of patients had 6 or more individual nodes dissected. Unsuspected nodal disease was detected during surgery in 12 (18.8%) patients. Of these, 4 patients (6.3%) had N1disease and 8 patients (12.5%) had unsuspected N2 disease. Upstaging during surgery was not scored as a recurrence. SABR patients had a better loco-regional control rates at 1- and 3-years (96.8% and 93.3% vs. 86.9% and 82.6%, respectively, p Z 0.03). Three-year progression-free survival did not significantly differ between groups (79.3% vs. 63.2%, p Z 0.09). The rates of distant recurrence and overall survival did not differ significantly. Conclusions: The 3-year progression-free survival and overall survival were similar after SABR and VATS-lobectomy. However, loco-regional control was superior after SABR. These findings support accrual in randomized controlled trials evaluating both treatments.

Oral Scientific Sessions

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Author Disclosure: S. Senan: E. Research Grant; Varian Medical Systems. F. Honoraria; Varian Medical Systems. N. Verstegen: None. D.A. Palma: None. G. Rodrigues: E. Research Grant; Tomotherapy. F.J. Lagerwaard: E. Research Grant; Varian Medical Systems. F. Honoraria; Varian Medical Systems. A. van der Elst: None. R. Mollema: None. A. Warner: None. B.J. Slotman: E. Research Grant; Varian Medical Systems. F. Honoraria; Varian Medical Systems. J.W. Oosterhuis: None.

118 A Phase II Study of Accelerated Hypofractionated 3-dimensional Conformal Radiation Therapy for Inoperable T1-3 N0 M0 Non-small Cell Lung Cancer: NCIC CTG BR.25 P. Cheung,1,2 S. Faria,3 S. Ahmed,4 P. Chabot,5 J. Greenland,6 E. Kurien,7 I. Mohamed,8 J. Wright,9 K. Ding,10 and C. O’Callaghan11; 1Sunnybrook Odette Cancer Centre, Toronto, ON, Canada, 2Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 3McGill University, Montreal, QC, Canada, 4Cancer Care Manitoba, Winnipeg, MB, Canada, 5Hopital Maisonneuve-Rosemont, Montreal, QC, Canada, 6 Memorial University of Newfoundland, St. John’s, NL, Canada, 7Tom Baker Cancer Centre, Calgary, AB, Canada, 8Cancer Centre for the Southern Interior, BC Cancer Agency, Kelowna, BC, Canada, 9Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada, 10National Cancer Institute of Canada Clinical Trials Group, Queen’s University, Kingston, ON, Canada, 11National Institute of Canada Clinical Trials Group, Queen’s University, Kingston, ON, Canada Purpose/Objective(s): Radiation therapy is a curative treatment option for early stage non-small cell lung cancer (NSCLC). Based on promising retrospective data using accelerated hypofractionated schedules, a prospective multi-institutional phase II trial was performed. This was done in an era when the majority of centers did not have stereotactic body radiation therapy capability. Materials/Methods: From 2006-2008, 80 patients with peripherally located T1-3 N0 M0 NSCLC were enrolled from 17 institutions across Canada. All patients had biopsy confirmation of NSCLC. Maximum allowable tumor size was 5 cm. Eligible patients received a dose of 60 Gy in 15 fractions using a 3-dimensional conformal technique without inhomogeneity correction. The gross tumor volume (GTV) was the primary tumor only, with no expansion for the clinical target volume (CTV). The planning target volume (PTV) margin was 1.5 cm in all directions. The PTV margin could be decreased to 1.0 cm in the transverse plane to spare critical structures. An assessment for breathing induced tumor motion (fluoroscopy or 4D CT) was required to ensure that the tumor was adequately covered by the PTV. Daily image guidance was not mandated during treatment. All radiation therapy plans were centrally reviewed. Patients were evaluated weekly during treatment and every 4 months afterwards until 2 years. From years 2 to 5, the follow-up decreased to every 6 months. The primary endpoint was the 2 year local control rate of the primary tumor using a modified RECIST criteria. Toxicities were measured using the CTCAE v3.0. Results: Five patients were found to be ineligible and 2 had major protocol violations. Median follow-up of the patients was 49 months (range 21-63 months). Median age of the patients was 75.9 years. 80% of patients were ECOG 0-1 at baseline. The actuarial rate of local control at 2 years was 88%. Overall survival was 69% at 2 years. The actuarial rates of developing regional and distant relapse at 2 years were 9% and 24%, respectively. Distant relapse included the development of a solitary tumor anywhere in the lung separate from the treated primary tumor. Tumor size >3 cm was associated with a statistically significant increase in distant relapse (p Z 0.03). The most common grade > Z 3 toxicities were fatigue (6.3%), cough (7.5%), dyspnea (13.8%), and pneumonitis (10%). One patient died of massive hemoptysis over 2 years after radiation therapy that was scored as possibly related to the protocol treatment. Conclusions: Conformal radiation therapy to a dose of 60 Gy in 15 fractions resulted in favorable local control and overall survival rates in patients with medically inoperable T1-3 N0 M0 NSCLC. Severe toxicities