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Predicting Survival following Stereotactic Ablative Radiotherapy in Early-Stage Lung Cancer: A Recursive Partitioning Analysis to Define Risk Groups
Volume 90 Number 1S Supplement 2014
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proximal bronchial tree, heart, great vessels, trachea, or other mediastinal structures. Toxicity was graded by the NIH CTCAE v4.1 and defined as acute if occurring within 3 months and as late if occurring afterward. The association of tumor location with overall survival, progression-free survival, and local control was assessed with Kaplan-Meier analysis and Cox regression modeling. For evaluation of toxicity, chi-square analysis, and logistic regression modeling were used. Results: There were 253 patients included in this analysis (70 central and 183 peripheral). Median follow-up was 24.9 months. Patients with central tumors were more likely to have larger tumors (median 2.6 cm vs. 1.9 cm, p < 0.001) and be treated with a lower BED (median 112.5 Gy vs. 151.2 Gy, p < 0.001) compared to those with peripheral tumors. Univariate analysis revealed that tumor location was not associated with overall survival (52% vs. 56% at 2 years, p Z 0.56), progression-free survival (57% vs. 62% at 2 years, p Z 0.22), local control (83% vs. 90% at 2 years, p Z 0.33), acute grade 2 toxicity (23% vs. 26%, p Z 0.75), acute grade 3 toxicity (1% vs. 7%, p Z 0.12), late grade 2 toxicity (17% vs. 15%, p Z 0.70), or late grade 3 toxicity (7% vs. 3%, p Z 0.15). After adjustment for demographic and clinical covariates in multivariate analysis, tumor location did not predict for any of these outcomes. BED also did not predict for any of these outcomes overall or when stratified by tumor location. Conclusions: Despite presenting with larger tumors and being treated with a lower BED, patients with centrally located NSCLC who received SBRT had similar survival, local control, and toxicity outcomes compared to those with peripheral tumors. One potential reason for the lack of increased toxicity may be the lower median BED used for centrally located tumors. Greater numbers of patients and longer follow-up are needed to further characterize the long-term outcomes following SBRT for these patients. Author Disclosure: H.S. Park: None. E. Harder: None. B.R. Mancini: None. R.H. Decker: None.
LF at 20 months with 2 and 3-year LC rates of 85.7%. Increase tumor volume (median 22 cc) did not predict for LF. There were no grade 3 - 5 cardiac or esophageal toxicities. There was one grade 3 chest-wall toxicity, and one fatal hemoptysis (thoracic toxicity) possibly related to injury to the TBT at 7 months (14 Gy x 3, max bronchus dose Z 34.3 Gy, V30Gy Z 0.11 cc, V20Gy Z 0.22 cc). This patient met the protocol specified dose limits for trachea/ipsilateral bronchus (Max 37.5 Gy, V21 Gy < 1 cc). Cumulative rates of grade 3 - 5 thoracic toxicities were 8.3%. Neither increase TBT dose nor lung V20Gy correlated with higher rates of thoracic toxicity (p > 0.05). Conclusions: SBRT/RFA treatment appears effective for centrally located lung tumors. Early results suggest an acceptable safety profile. However, due to potential untoward and poorly understood interactions between the two modalities, further investigation is required. Caution is advised when SBRT/RFA is offered outside of a clinical trial. Author Disclosure: P. Lee: None. C. Felix: None. F. Abtin: None. J. Wu: None. R. Suh: None. S. Tenn: None. C. Lee: None. P. Wang: None. J.M. Lee: None. E.B. Garon: None. V. Basehart: None. N. Agazaryan: None. M. Steinberg: None.
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Purpose/Objective(s): Stereotactic Ablative Radiotherapy (SABR) is now a guideline-specified curative treatment modality for patients with early stage non-small cell lung cancer (NSCLC). This analysis was undertaken to develop a prognostic model for overall survival (OS) in these patients using recursive partitioning analysis (RPA). Materials/Methods: Our institution maintains a database on lung tumor patients treated with both SABR and hypofractionated radiotherapy. Details on baseline characteristics, treatment, and follow-up information are prospectively entered. SABR was delivered using a risk-adapted scheme of 54 Gy in 3 fractions, 55 Gy in 5 fractions, 60 Gy in 8 fractions, and the hypofractionated scheme used with stereotactic on-line setup was 60 Gy in 12 fractions, all based on tumor size and location. The following categories of patients were excluded: previous lung cancer, other synchronous malignancies, multiple lung tumors, and those without 18-FDG PET staging. Six hundred seventy-six stage I NSCLC patients treated between 2003 and 2012 remained eligible for analysis, consisting of both medically inoperable and potentially operable patients, with the latter defined by criteria described previously [Lagerwaard 2012]. Patients were randomly dividing into a training set (n Z 451, 67%) and a validation set (n Z 225, 33%). In the training set, 22 unique parameters consisting of various patient, treatment, and tumor factors were entered into a model where recursive partitioning was used to prognosticate for OS. After selection of a clinically appropriate model, classes developed in the training set were applied to stratify patients from the validation set. The log-rank test was used to determine differences in OS among the RPA classes for the validation and training sets. Results: At a median follow-up of 25.5 months (range 0.9-113.9), the median OS for the entire cohort was 51.3 months. RPA identified 6 risk classes: class I - potentially operable and PTV < 45 cc; class II - potentially operable and PTV > 45 cc; class III - medically inoperable and diameter < 2.4 cm and age < 76; class IV - medically inoperable and diameter < 2.4 cm and age > 76; class V - medically inoperable, diameter > 2.4 and BED10 > 100 Gy; and class VI - medically inoperable, diameter > 2.4 and BED10 < 100 Gy. In the training set, median OS was not reached for class I, and for classes II-VI were 58.7, 44.0, 25.8, 20.5, and 10.0 months, respectively. The RPA model could significantly discriminate between risk classes in both the
Early Outcomes from a Prospective Phase II Trial Evaluating Safety and Efficacy of Combining SBRT with RFA for Centrally Located Lung Tumors P. Lee, C. Felix, F. Abtin, J. Wu, R. Suh, S. Tenn, C. Lee, P. Wang, J.M. Lee, E.B. Garon, V. Basehart, N. Agazaryan, and M. Steinberg; University of California Los Angeles, Los Angeles, CA Purpose/Objective(s): Lung tumors near central airways are difficult to treat with SBRT or radiofrequency ablation (RFA) due to safety and technical considerations. Lower control rates or unacceptable toxicity to central organs have been seen when treating central compared to peripheral tumors. We hypothesized a combined approach (SBRT/RFA), at lower intensity for each, can have synergistic effects to improve local control (LC) while reducing treatment-related morbidity. Materials/Methods: An IRB-approved, single-arm Phase II study was designed for medically inoperable patients with primary or recurrent central lung tumors. Tumors 1 - 2 cm from the tracheal-bronchial tree (TBT) received 14 Gy x 3, and those within 1 cm of TBT received 12 Gy x 3 followed by RFA (within 10 days). Patients with tumors that were > 5 cm and those with prior thoracic RT near the target were ineligible. Primary endpoints were to achieve no more than 20% grade 3 thoracic, esophageal, or cardiac toxicity and at least 80% one-year LC rate using a Bayesian sequential monitoring design. Data monitoring was performed by the institutional Data Safety Monitoring Board. Serum was collected for biomarker studies pre, during, and post-treatment. PFTs were obtained pre, and at 3 and 12 months post-treatment to assess impact on lung function. Follow-up included clinical exams, PET-CTs at 6 weeks and one year, as well as CTs at 3, 6, and 9 months post-treatment. A local failure (LF) was defined on follow-up CT by RECIST (v1.0) or serial increase in FDG at 6 weeks and 1 year. Toxicity was defined by CTACE (v3.0). Results: From 2010 - 2013, 13 patients were enrolled, with 12 patients (13 lesions) eligible for analysis (one withdrew consent). Four patients had primary NSCLC with the remaining patients having metastatic lesions. Median follow-up time was 20.1 months (range: 2.7-42.9), and median overall survival was 32 months by Kaplan-Meier method. There was one
55 Predicting Survival following Stereotactic Ablative Radiotherapy in Early-Stage Lung Cancer: A Recursive Partitioning Analysis to Define Risk Groups A.V. Louie,1 G. Rodrigues,2 C. Haasbeek,3 A. Warner,2 F.J. Lagerwaard,1 D.A. Palma,2 B.J. Slotman,4 and S. Senan1; 1VU University Medical Center, Amsterdam, Netherlands, 2London Regional Cancer Program, London, ON, Canada, 3VU University Medical Center, Amsterdam 1081HV, Netherlands, 4VU University Medical Center, Amsterdam 1081 HV, Netherlands
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training and validation sets (p < 0.0001). Overall survival in the validation set correlated closely with survival in the training set. Conclusions: This validated model demonstrates that operability, tumor diameter, PTV size, BED10 and age form the basis of a new risk stratification for OS in stage I NSCLC patients treated with SABR that may help define subgroups for future clinical trials. Author Disclosure: A.V. Louie: L. Funding Other; CARO-Elekta Research Fellowship, Royal College of Physicians and Surgeons of Canada Detweiler Travelling Fellowship, Resident Research Career Development Award - University of Western Ontario. G. Rodrigues: None. C. Haasbeek: None. A. Warner: None. F.J. Lagerwaard: F. Honoraria; Varian Medical Systems. D.A. Palma: None. B.J. Slotman: E. Research Grant; Varian Medical Systems. F. Honoraria; Varian Medical Systems. G. Consultant; Varian Medical Systems. I. Travel Expenses; Varian Medical Systems. S. Senan: E. Research Grant; Varian Medical Systems. F. Honoraria; Varian Medical Systems. G. Consultant; Varian Medical Systems. I. Travel Expenses; Varian Medical Systems.
Conclusions: Patients with inoperable non-small cell lung cancer treated with SBRT had a survival rate of 40% at 5 years. While tumor control rates remain high compared to conventional fractionation results, late failures were observed particularly in the involved (untreated) residual lobe. However, an excess of late-appearing toxicity was not observed. Author Disclosure: R.D. Timmerman: E. Research Grant; Varian Medical Systems. C. Hu: None. J. Michalski: None. W. Straube: None. J. Galvin: None. D. Johnstone: None. J. Bradley: None. R. Barriger: None. A. Bezjak: None. G.M. Videtic: None. L. Nedzi: None. M. Werner-Wasik: None. Y. Chen: None. R.U. Komaki: None. H. Choy: None.
56 Long-term Results of RTOG 0236: A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients with Medically Inoperable Stage I Non-Small Cell Lung Cancer R.D. Timmerman,1 C. Hu,2 J. Michalski,3 W. Straube,3 J. Galvin,4 D. Johnstone,5 J. Bradley,3 R. Barriger,6 A. Bezjak,7 G.M. Videtic,8 L. Nedzi,1 M. Werner-Wasik,4 Y. Chen,9 R.U. Komaki,10 and H. Choy1; 1 University of Texas Southwestern Medical School, Dallas, TX, 2American College of Radiology, Philadelphia, PA, 3Washington University Medical Center, St. Louis, MO, 4Thomas Jefferson Hospital, Philadelphia, PA, 5 Medical College of Wisconsin, Milwaukee, WI, 6Indiana University Medical Center, Indianapolis, IN, 7Princess Margaret Hospital, Toronto, ON, 8Cleveland Clinic, Cleveland, OH, 9University of Rochester Medical Center, Rochester, NY, 10M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): Patients with early stage but medically inoperable lung cancer historically had poor primary tumor control and high mortality with conventional radiotherapy. SBRT appeared to improve outcomes, as suggested by the initial published results of RTOG 0236. Herein, we update those results with longer follow-up. Materials/Methods: The study was a Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1T2N0M0 non-small cell tumors (measuring 5 cm in diameter) and medical conditions precluding surgical treatment. The prescription dose was 18 Gy per fraction X 3 fractions (54 Gy total) with entire treatment lasting between 1½ and 2 weeks. The study opened May 26, 2004, and closed October 13, 2006; data were analyzed through October 15, 2013. The primary end point was 2-year actuarial primary tumor control; secondary end points were disease-free survival (i.e., primary tumor, involved lobe, regional, and disseminated recurrence), treatment-related toxicity, and overall survival. Results: A total of 59 patients accrued, of which 55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) with a median follow-up of 4.0 years (7.2 years for surviving patients). Four patients had an in-field/marginal (primary) tumor failure (range, 1.8-4.8 years after SBRT); the estimated 5-year primary tumor failure rate was 7%. Nine additional patients had recurrence within the involved lobe (range 0.1-5.9 years after SBRT); the 5-year primary tumor and involved lobe (local) failure rate was 20%. Seven patients experienced regional failure (range, 2.8-5.2 years after SBRT); the 5-year local-regional failure rate was 38%. Fifteen patients experienced disseminated recurrence; the 5-year disseminated failure rate was 31%. The rates for disease free and overall survival at 5 years were 26% and 40%, respectively. The median overall survival was 4 years. Protocol treatment-related grade 3 and 4 adverse events were reported in 15 patients and in 2 patients, respectively, modestly more than was described in the previous 3-year report. No grade 5 adverse events were reported.
57 Comparing Patterns of Recurrence and Survival in Conventionally Fractionated Radiation with Stereotactic Body Radiation Therapy for Early-Stage NSCLC F. Shaikh,1 A. Foster,2 Z. Zhang,2 K. Woo,2 S.U. Din,2 D. Gelblum,3 E.D. Yorke,2 K. Rosenzweig,4 A.J. Wu,2 and A. Rimner5; 1Columbia University Medical Center, New York, NY, 2Memorial Sloan-Kettering Cancer Center, New York, NY, 3Memorial Sloan-Kettering Cancer Center, Commack, NY, 4Mount Sinai Medical Center, New York, NY, 5MSKCC, New York, NY Purpose/Objective(s): Stereotactic Body Radiation Therapy (SBRT) has quickly been adopted as the standard of care for inoperable early-stage NSCLC, with consistently reported local control rates > 90%, improving upon historical means. However, data directly comparing the outcomes of SBRT with those of conventionally fractionated radiotherapy (CONV) is lacking. A randomized trial addressing this question is ongoing in Australia. Here we report our institutional experience in treating earlystage NSCLC with CONV and SBRT. Materials/Methods: Between 1990 and 2013, 525 patients with earlystage NSCLC (T1-T2N0M0) were treated with definitive radiotherapy using CONV (n Z 127) or SBRT (n Z 398). No patients received chemotherapy, surgery or radiofrequency ablation as a part of their treatment for this primary. Competing risks analysis was performed for incidence of local, nodal and distant failures. Overall survival (OS) was analyzed by the Kaplan-Meier method. Patient factors in univariate analysis (UVA) were incorporated in a multivariate analysis (MVA) for each endpoint. Results: Patient characteristics of both treatment groups are as follows: median age: 77 years (range: 46-95), 92% former/current smokers, median KPS: 80 (range: 40-100), T-stage: 52% T1, 48% T2, histology: 69% adenocarcinoma, 25% squamous, and 6% NSCLC, not otherwise specified (NOS). The median dose delivered for CONV is 75.6 Gy in 1.8-2 Gy fractions (range 60-90 Gy; median biologically equivalent dose (BED) Z 89.2 Gy) and 48 Gy in 4 fractions (range 45- 60 Gy; median BED Z 105.6 Gy) for SBRT. The SBRT group contains more T1 tumors (p < 0.001), more former than current smokers (p Z 0.005), more adenocarcinomas (p < 0.001), and a higher mean BED (p < 0.001) than CONV. No difference in gender, KPS or age is noted between the groups. With a median follow-up of 19.3 months (23.5 months in surviving patients), the 3-year local failure rate is 34.1% in the CONV group and 13.6% in the SBRT group (p < 0.001). The 3-year OS rates are 38.9% and 52.9%, respectively (p Z 0.024). Treatment group is not correlated with nodal and distant metastases. On MVA, female gender, T1 stage, adenocarcinoma subtype, and SBRT use are significantly associated with higher local control. However, only age, KPS, T1-stage, and adenocarcinoma subtype are identified as significant variables in MVA for OS. T-stage is the only variable correlated with all four endpoints in MVA. Conclusions: On UVA, SBRT demonstrates a significant advantage in local control and OS, with no significant effect on nodal failure or distant metastases rates. On MVA, SBRT is associated with improved local control, but not OS. T1-stage and adenocarcinoma subtype correlate most significantly with OS on MVA. Our data supports continued use of SBRT as treatment for early-stage NSCLC for its strong impact on local control and possible impact on survival.
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proximal bronchial tree, heart, great vessels, trachea, or other mediastinal structures. Toxicity was graded by the NIH CTCAE v4.1 and defined as acute if occurring within 3 months and as late if occurring afterward. The association of tumor location with overall survival, progression-free survival, and local control was assessed with Kaplan-Meier analysis and Cox regression modeling. For evaluation of toxicity, chi-square analysis, and logistic regression modeling were used. Results: There were 253 patients included in this analysis (70 central and 183 peripheral). Median follow-up was 24.9 months. Patients with central tumors were more likely to have larger tumors (median 2.6 cm vs. 1.9 cm, p < 0.001) and be treated with a lower BED (median 112.5 Gy vs. 151.2 Gy, p < 0.001) compared to those with peripheral tumors. Univariate analysis revealed that tumor location was not associated with overall survival (52% vs. 56% at 2 years, p Z 0.56), progression-free survival (57% vs. 62% at 2 years, p Z 0.22), local control (83% vs. 90% at 2 years, p Z 0.33), acute grade 2 toxicity (23% vs. 26%, p Z 0.75), acute grade 3 toxicity (1% vs. 7%, p Z 0.12), late grade 2 toxicity (17% vs. 15%, p Z 0.70), or late grade 3 toxicity (7% vs. 3%, p Z 0.15). After adjustment for demographic and clinical covariates in multivariate analysis, tumor location did not predict for any of these outcomes. BED also did not predict for any of these outcomes overall or when stratified by tumor location. Conclusions: Despite presenting with larger tumors and being treated with a lower BED, patients with centrally located NSCLC who received SBRT had similar survival, local control, and toxicity outcomes compared to those with peripheral tumors. One potential reason for the lack of increased toxicity may be the lower median BED used for centrally located tumors. Greater numbers of patients and longer follow-up are needed to further characterize the long-term outcomes following SBRT for these patients. Author Disclosure: H.S. Park: None. E. Harder: None. B.R. Mancini: None. R.H. Decker: None.
LF at 20 months with 2 and 3-year LC rates of 85.7%. Increase tumor volume (median 22 cc) did not predict for LF. There were no grade 3 - 5 cardiac or esophageal toxicities. There was one grade 3 chest-wall toxicity, and one fatal hemoptysis (thoracic toxicity) possibly related to injury to the TBT at 7 months (14 Gy x 3, max bronchus dose Z 34.3 Gy, V30Gy Z 0.11 cc, V20Gy Z 0.22 cc). This patient met the protocol specified dose limits for trachea/ipsilateral bronchus (Max 37.5 Gy, V21 Gy < 1 cc). Cumulative rates of grade 3 - 5 thoracic toxicities were 8.3%. Neither increase TBT dose nor lung V20Gy correlated with higher rates of thoracic toxicity (p > 0.05). Conclusions: SBRT/RFA treatment appears effective for centrally located lung tumors. Early results suggest an acceptable safety profile. However, due to potential untoward and poorly understood interactions between the two modalities, further investigation is required. Caution is advised when SBRT/RFA is offered outside of a clinical trial. Author Disclosure: P. Lee: None. C. Felix: None. F. Abtin: None. J. Wu: None. R. Suh: None. S. Tenn: None. C. Lee: None. P. Wang: None. J.M. Lee: None. E.B. Garon: None. V. Basehart: None. N. Agazaryan: None. M. Steinberg: None.
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Purpose/Objective(s): Stereotactic Ablative Radiotherapy (SABR) is now a guideline-specified curative treatment modality for patients with early stage non-small cell lung cancer (NSCLC). This analysis was undertaken to develop a prognostic model for overall survival (OS) in these patients using recursive partitioning analysis (RPA). Materials/Methods: Our institution maintains a database on lung tumor patients treated with both SABR and hypofractionated radiotherapy. Details on baseline characteristics, treatment, and follow-up information are prospectively entered. SABR was delivered using a risk-adapted scheme of 54 Gy in 3 fractions, 55 Gy in 5 fractions, 60 Gy in 8 fractions, and the hypofractionated scheme used with stereotactic on-line setup was 60 Gy in 12 fractions, all based on tumor size and location. The following categories of patients were excluded: previous lung cancer, other synchronous malignancies, multiple lung tumors, and those without 18-FDG PET staging. Six hundred seventy-six stage I NSCLC patients treated between 2003 and 2012 remained eligible for analysis, consisting of both medically inoperable and potentially operable patients, with the latter defined by criteria described previously [Lagerwaard 2012]. Patients were randomly dividing into a training set (n Z 451, 67%) and a validation set (n Z 225, 33%). In the training set, 22 unique parameters consisting of various patient, treatment, and tumor factors were entered into a model where recursive partitioning was used to prognosticate for OS. After selection of a clinically appropriate model, classes developed in the training set were applied to stratify patients from the validation set. The log-rank test was used to determine differences in OS among the RPA classes for the validation and training sets. Results: At a median follow-up of 25.5 months (range 0.9-113.9), the median OS for the entire cohort was 51.3 months. RPA identified 6 risk classes: class I - potentially operable and PTV < 45 cc; class II - potentially operable and PTV > 45 cc; class III - medically inoperable and diameter < 2.4 cm and age < 76; class IV - medically inoperable and diameter < 2.4 cm and age > 76; class V - medically inoperable, diameter > 2.4 and BED10 > 100 Gy; and class VI - medically inoperable, diameter > 2.4 and BED10 < 100 Gy. In the training set, median OS was not reached for class I, and for classes II-VI were 58.7, 44.0, 25.8, 20.5, and 10.0 months, respectively. The RPA model could significantly discriminate between risk classes in both the
Early Outcomes from a Prospective Phase II Trial Evaluating Safety and Efficacy of Combining SBRT with RFA for Centrally Located Lung Tumors P. Lee, C. Felix, F. Abtin, J. Wu, R. Suh, S. Tenn, C. Lee, P. Wang, J.M. Lee, E.B. Garon, V. Basehart, N. Agazaryan, and M. Steinberg; University of California Los Angeles, Los Angeles, CA Purpose/Objective(s): Lung tumors near central airways are difficult to treat with SBRT or radiofrequency ablation (RFA) due to safety and technical considerations. Lower control rates or unacceptable toxicity to central organs have been seen when treating central compared to peripheral tumors. We hypothesized a combined approach (SBRT/RFA), at lower intensity for each, can have synergistic effects to improve local control (LC) while reducing treatment-related morbidity. Materials/Methods: An IRB-approved, single-arm Phase II study was designed for medically inoperable patients with primary or recurrent central lung tumors. Tumors 1 - 2 cm from the tracheal-bronchial tree (TBT) received 14 Gy x 3, and those within 1 cm of TBT received 12 Gy x 3 followed by RFA (within 10 days). Patients with tumors that were > 5 cm and those with prior thoracic RT near the target were ineligible. Primary endpoints were to achieve no more than 20% grade 3 thoracic, esophageal, or cardiac toxicity and at least 80% one-year LC rate using a Bayesian sequential monitoring design. Data monitoring was performed by the institutional Data Safety Monitoring Board. Serum was collected for biomarker studies pre, during, and post-treatment. PFTs were obtained pre, and at 3 and 12 months post-treatment to assess impact on lung function. Follow-up included clinical exams, PET-CTs at 6 weeks and one year, as well as CTs at 3, 6, and 9 months post-treatment. A local failure (LF) was defined on follow-up CT by RECIST (v1.0) or serial increase in FDG at 6 weeks and 1 year. Toxicity was defined by CTACE (v3.0). Results: From 2010 - 2013, 13 patients were enrolled, with 12 patients (13 lesions) eligible for analysis (one withdrew consent). Four patients had primary NSCLC with the remaining patients having metastatic lesions. Median follow-up time was 20.1 months (range: 2.7-42.9), and median overall survival was 32 months by Kaplan-Meier method. There was one
55 Predicting Survival following Stereotactic Ablative Radiotherapy in Early-Stage Lung Cancer: A Recursive Partitioning Analysis to Define Risk Groups A.V. Louie,1 G. Rodrigues,2 C. Haasbeek,3 A. Warner,2 F.J. Lagerwaard,1 D.A. Palma,2 B.J. Slotman,4 and S. Senan1; 1VU University Medical Center, Amsterdam, Netherlands, 2London Regional Cancer Program, London, ON, Canada, 3VU University Medical Center, Amsterdam 1081HV, Netherlands, 4VU University Medical Center, Amsterdam 1081 HV, Netherlands
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training and validation sets (p < 0.0001). Overall survival in the validation set correlated closely with survival in the training set. Conclusions: This validated model demonstrates that operability, tumor diameter, PTV size, BED10 and age form the basis of a new risk stratification for OS in stage I NSCLC patients treated with SABR that may help define subgroups for future clinical trials. Author Disclosure: A.V. Louie: L. Funding Other; CARO-Elekta Research Fellowship, Royal College of Physicians and Surgeons of Canada Detweiler Travelling Fellowship, Resident Research Career Development Award - University of Western Ontario. G. Rodrigues: None. C. Haasbeek: None. A. Warner: None. F.J. Lagerwaard: F. Honoraria; Varian Medical Systems. D.A. Palma: None. B.J. Slotman: E. Research Grant; Varian Medical Systems. F. Honoraria; Varian Medical Systems. G. Consultant; Varian Medical Systems. I. Travel Expenses; Varian Medical Systems. S. Senan: E. Research Grant; Varian Medical Systems. F. Honoraria; Varian Medical Systems. G. Consultant; Varian Medical Systems. I. Travel Expenses; Varian Medical Systems.
Conclusions: Patients with inoperable non-small cell lung cancer treated with SBRT had a survival rate of 40% at 5 years. While tumor control rates remain high compared to conventional fractionation results, late failures were observed particularly in the involved (untreated) residual lobe. However, an excess of late-appearing toxicity was not observed. Author Disclosure: R.D. Timmerman: E. Research Grant; Varian Medical Systems. C. Hu: None. J. Michalski: None. W. Straube: None. J. Galvin: None. D. Johnstone: None. J. Bradley: None. R. Barriger: None. A. Bezjak: None. G.M. Videtic: None. L. Nedzi: None. M. Werner-Wasik: None. Y. Chen: None. R.U. Komaki: None. H. Choy: None.
56 Long-term Results of RTOG 0236: A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients with Medically Inoperable Stage I Non-Small Cell Lung Cancer R.D. Timmerman,1 C. Hu,2 J. Michalski,3 W. Straube,3 J. Galvin,4 D. Johnstone,5 J. Bradley,3 R. Barriger,6 A. Bezjak,7 G.M. Videtic,8 L. Nedzi,1 M. Werner-Wasik,4 Y. Chen,9 R.U. Komaki,10 and H. Choy1; 1 University of Texas Southwestern Medical School, Dallas, TX, 2American College of Radiology, Philadelphia, PA, 3Washington University Medical Center, St. Louis, MO, 4Thomas Jefferson Hospital, Philadelphia, PA, 5 Medical College of Wisconsin, Milwaukee, WI, 6Indiana University Medical Center, Indianapolis, IN, 7Princess Margaret Hospital, Toronto, ON, 8Cleveland Clinic, Cleveland, OH, 9University of Rochester Medical Center, Rochester, NY, 10M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): Patients with early stage but medically inoperable lung cancer historically had poor primary tumor control and high mortality with conventional radiotherapy. SBRT appeared to improve outcomes, as suggested by the initial published results of RTOG 0236. Herein, we update those results with longer follow-up. Materials/Methods: The study was a Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1T2N0M0 non-small cell tumors (measuring 5 cm in diameter) and medical conditions precluding surgical treatment. The prescription dose was 18 Gy per fraction X 3 fractions (54 Gy total) with entire treatment lasting between 1½ and 2 weeks. The study opened May 26, 2004, and closed October 13, 2006; data were analyzed through October 15, 2013. The primary end point was 2-year actuarial primary tumor control; secondary end points were disease-free survival (i.e., primary tumor, involved lobe, regional, and disseminated recurrence), treatment-related toxicity, and overall survival. Results: A total of 59 patients accrued, of which 55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) with a median follow-up of 4.0 years (7.2 years for surviving patients). Four patients had an in-field/marginal (primary) tumor failure (range, 1.8-4.8 years after SBRT); the estimated 5-year primary tumor failure rate was 7%. Nine additional patients had recurrence within the involved lobe (range 0.1-5.9 years after SBRT); the 5-year primary tumor and involved lobe (local) failure rate was 20%. Seven patients experienced regional failure (range, 2.8-5.2 years after SBRT); the 5-year local-regional failure rate was 38%. Fifteen patients experienced disseminated recurrence; the 5-year disseminated failure rate was 31%. The rates for disease free and overall survival at 5 years were 26% and 40%, respectively. The median overall survival was 4 years. Protocol treatment-related grade 3 and 4 adverse events were reported in 15 patients and in 2 patients, respectively, modestly more than was described in the previous 3-year report. No grade 5 adverse events were reported.
57 Comparing Patterns of Recurrence and Survival in Conventionally Fractionated Radiation with Stereotactic Body Radiation Therapy for Early-Stage NSCLC F. Shaikh,1 A. Foster,2 Z. Zhang,2 K. Woo,2 S.U. Din,2 D. Gelblum,3 E.D. Yorke,2 K. Rosenzweig,4 A.J. Wu,2 and A. Rimner5; 1Columbia University Medical Center, New York, NY, 2Memorial Sloan-Kettering Cancer Center, New York, NY, 3Memorial Sloan-Kettering Cancer Center, Commack, NY, 4Mount Sinai Medical Center, New York, NY, 5MSKCC, New York, NY Purpose/Objective(s): Stereotactic Body Radiation Therapy (SBRT) has quickly been adopted as the standard of care for inoperable early-stage NSCLC, with consistently reported local control rates > 90%, improving upon historical means. However, data directly comparing the outcomes of SBRT with those of conventionally fractionated radiotherapy (CONV) is lacking. A randomized trial addressing this question is ongoing in Australia. Here we report our institutional experience in treating earlystage NSCLC with CONV and SBRT. Materials/Methods: Between 1990 and 2013, 525 patients with earlystage NSCLC (T1-T2N0M0) were treated with definitive radiotherapy using CONV (n Z 127) or SBRT (n Z 398). No patients received chemotherapy, surgery or radiofrequency ablation as a part of their treatment for this primary. Competing risks analysis was performed for incidence of local, nodal and distant failures. Overall survival (OS) was analyzed by the Kaplan-Meier method. Patient factors in univariate analysis (UVA) were incorporated in a multivariate analysis (MVA) for each endpoint. Results: Patient characteristics of both treatment groups are as follows: median age: 77 years (range: 46-95), 92% former/current smokers, median KPS: 80 (range: 40-100), T-stage: 52% T1, 48% T2, histology: 69% adenocarcinoma, 25% squamous, and 6% NSCLC, not otherwise specified (NOS). The median dose delivered for CONV is 75.6 Gy in 1.8-2 Gy fractions (range 60-90 Gy; median biologically equivalent dose (BED) Z 89.2 Gy) and 48 Gy in 4 fractions (range 45- 60 Gy; median BED Z 105.6 Gy) for SBRT. The SBRT group contains more T1 tumors (p < 0.001), more former than current smokers (p Z 0.005), more adenocarcinomas (p < 0.001), and a higher mean BED (p < 0.001) than CONV. No difference in gender, KPS or age is noted between the groups. With a median follow-up of 19.3 months (23.5 months in surviving patients), the 3-year local failure rate is 34.1% in the CONV group and 13.6% in the SBRT group (p < 0.001). The 3-year OS rates are 38.9% and 52.9%, respectively (p Z 0.024). Treatment group is not correlated with nodal and distant metastases. On MVA, female gender, T1 stage, adenocarcinoma subtype, and SBRT use are significantly associated with higher local control. However, only age, KPS, T1-stage, and adenocarcinoma subtype are identified as significant variables in MVA for OS. T-stage is the only variable correlated with all four endpoints in MVA. Conclusions: On UVA, SBRT demonstrates a significant advantage in local control and OS, with no significant effect on nodal failure or distant metastases rates. On MVA, SBRT is associated with improved local control, but not OS. T1-stage and adenocarcinoma subtype correlate most significantly with OS on MVA. Our data supports continued use of SBRT as treatment for early-stage NSCLC for its strong impact on local control and possible impact on survival.