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RTOG 0813 Trial of Stereotactic Body Radiation Therapy (SBRT) for Centrally Located Non-Small Cell Lung Cancer (NSCLC)
S8
International Journal of Radiation Oncology Biology Physics
Results: Seventy-five patients (15 per dose cohort) enrolled with median age of 62 years. Median follow-up for cohorts 1, 2, 3, 4, and 5 were 49.9, 38.3, 25.5, 19.5, and 11.4 months, respectively. There were 60 acute grade 1 toxicity events (breast pain, hyperpigmentation, paresthesia, radiation dermatitis, fatigue) and 2 acute grade 2 toxicities (axillary paresthesia, radiation dermatitis). There were 29 late grade 1 toxicity events (breast pain, chest wall pain, radiation dermatitis, telangiectasias, hyperpigmentation, fatigue, fibrosis), 7 late grade 2 toxicity events (breast pain, rib fracture, fibrosis). Only 3 grade 3 toxicities were experienced (1 patient with breast cellulitis and 2 patients with acute dermatitis in the 37.5 Gy dose levels). There was 1 DLT in the overall cohort (Grade 3 dermatitis in the 37.5 Gy dose level). Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 97.3%, 97.1%, 98.1%, and 100% at baseline, 6, 12, and 24 months post S-PBI while patients scored the same period as 86.5%, 97.1%, 96.2%, and 94.9% (P Z 0.127). There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions with the occurrence of only 1 DLT. Patients felt cosmetic results improved within the first year after surgery and SBRT. There have been no recurrences or distant metastases to date. Our results continue to show minimal toxicity with excellent cosmesis, however further follow-up is warranted. Author Disclosure: A.S. Rahimi: Transplant Hepatologist; Baylor Hospital. Faculty Physician; University of Texas Southwestern Medical Center. Research Grant; Accuray. K. Thomas: None. A. Spangler: Oversight of Radiation Oncology Residency Programs; ACGME. M. Leitch: None. R. Rao: None. R. Wooldridge: None. A. Rivers: None. S. Seiler: None. K.V. Albuquerque: None. S. Stevenson: None. S. Goudreau: Physician; Medical Specialists Inc., PA. Faculty Physician; University of Texas Southwestern Medical Center. Board Member; Health Beacons Clinical Advisory Board. D.P. Garwood: None. B. Haley: None. D. Euhus: None. D. Chen: None. J.H. Heinzerling: None. C. Ding: None. A. Gao: None. C. Ahn: None. R.D. Timmerman: None.
delivered over 1.5-2 weeks. Phase I data analysis revealed that maximum tolerated dose was the highest dose level allowed on the study, 12 Gy/fr x 5 fractions. Thirty-three eligible pts were treated with 12 Gy/fx, and another 38 pts were treated on the preceding dose level of 11.5 Gy/fr; this is the report of efficacy based on patients in those two cohorts. Results: Patients were elderly, and the majority had performance status 01. T1 cancers were treated in 58% of pts in the 11.5 Gy/fr cohort and 70% in 12 Gy/fr cohort. Median PTV volumes were 43cc (range 14.85 - 155.05 cc) and 32 cc (7.48 - 117.25) respectively. Organs closest to PTV/most at risk were main bronchus (45% and 39%, respectively) and large vessels (53% and 21%). Median follow-up was 33 months (mo) for the 11.5 Gy/fr cohort and 29.8 mo for the 12 Gy/fr cohort (49 and 31.8 mo for the surviving pts, respectively). Late toxicities grade 3 or greater (G3+) attributed to SBRT were 2 G5 toxicities in the 11.5 Gy/fr cohort, and in the 12 Gy/fr cohort 3 G3 (2 respiratory, 1 cardiac), 1 G4 (esophageal perforation), and 1 G5 (pulmonary hemorrhage) toxicities. The Table details the incidence of attributed G3+ toxicity, observed failure patterns, and outcomes.
Abstract 16; Table 1 Dose level Number (n) of eligible patients Pts w Toxicity G3+ (at any time) Pts w Early Toxicity G3+ (within 1st yr) Pts with Late Toxicity G3+ (beyond 1st yr) Pts with primary tumor failure Pts with involved lobe failure Pts with regional (lymph node) failure Pts with distant failure 2-year local control 2-yr progression free survival 2-year overall survival (OS)
11.5 Gy x 5fr 38 6 5 2 4 2 2 6 89.4% (81.6-97.4%)* 52.2% (35.3-66.6%)* 70.2% (52.6-82.3%)*
12 Gy x 5fr 33 7 4 5 6 2 4 5 87.7% (78.3-97%)* 54.5% (36.3-69.6%)* 72.7% (54.1-84.8%)*
*90% confidence interval.
16 Efficacy and Toxicity Analysis of NRG Oncology/RTOG 0813 Trial of Stereotactic Body Radiation Therapy (SBRT) for Centrally Located Non-Small Cell Lung Cancer (NSCLC) A. Bezjak,1 R. Paulus,2 L.E. Gaspar,3 R.D. Timmerman,4 W.L. Straube,5 W.F. Ryan,6 Y. Garces,7 A.T. Pu,8 A.K. Singh,9 G.M. Videtic,10 R.C. McGarry,11 P. Iyengar,4 J.R. Pantarotto,12 J.J. Urbanic,13 A. Sun,14 M.E. Daly,15 I.S. Grills,16 D.P. Normolle,17 J.D. Bradley,5 and H. Choy18; 1 Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 2NRG Oncology, Philadelphia, PA, 3Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 4 University of Texas Southwestern Medical Center, Dallas, TX, 5 Washington University, St. Louis, MO, 6Pocono Cancer Center, East Stroudsburg, PA, 7Mayo Clinic, Rochester, MN, 8Sutter Medical Group Radiological Associates of Sacramento, Sacramento, CA, 9Roswell Park Cancer Institute, Buffalo, NY, 10Cleveland Clinic, Cleveland, OH, 11 University of Maryland Medical Systems, Baltimore, MD, 12The Ottawa Hospital, Ottawa, ON, Canada, 13Arizona Oncology Services Foundation, Tucson, AZ, 14Princess Margaret Hospital, Toronto, ON, Canada, 15 University of California Davis Comprehensive Cancer Center, Sacramento, CA, 16Beaumont Health System, Royal Oak, MI, 17University of Pittsburgh Cancer Institute, Pittsburgh, PA, 18Princess Margaret Cancer Centre, Toronto, ON, Canada Purpose/Objective(s): The phase I results of NRG/RTOG 0813 trial were reported at ASTRO 2015. We hereby report the phase II results - efficacy and toxicity beyond year 1. Materials/Methods: Medically inoperable patients (pts) with biopsy proven, PET staged T1-2 (<5 cm) N0M0 centrally located NSCLC (within or touching the zone of the proximal bronchial tree or adjacent to mediastinal or pericardial pleura) were successively accrued onto a doseescalating 5 fraction SBRT schedule ranging from 10-12 Gy/fraction (fr)
Conclusion: Observed local control at 2 yrs in 71 pts treated with the two highest doses levels (11.5-12 Gy/fr x 5 fr) in this multicenter trial was high, and G3+ toxicity rates were acceptable. Two-year OS rates of 70% in this medically inoperable group of elderly pts with comorbidities were comparable to pts with peripheral early stage tumors. This project was supported by grants U10CA21661 (RTOG-Ops-Stat), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U10CA37422 (CCOP), and CA81647 (ATC) from the National Cancer Institute (NCI). Author Disclosure: A. Bezjak: Was president 2012-2014; CARO. R. Paulus: None. L.E. Gaspar: None. R.D. Timmerman: Research Grant; Varian Medical Systems, Elekta Oncology. Offer Scientific Advice; D3 Corporation. W.L. Straube: Receive funding; NIH. W.F. Ryan: Employee; Precomo Medical Centre. None; William Ryan MD. Y. Garces: None. A.T. Pu: None. A.K. Singh: None. G.M. Videtic: None. R.C. McGarry: None. P. Iyengar: None. J.R. Pantarotto: Chair of academic group; University of Ottawa. J.J. Urbanic: grant reviewer; Mesothelioma Applied Research Foundation. A. Sun: None. M.E. Daly: None. I.S. Grills: Stock; Greater Michigan-Gamma Knife. N/A; Greater MichiganGamma Knife. D.P. Normolle: None. J.D. Bradley: Research Grant; Mevion Medical Systems, ViewRay Inc. Proton Therapy Advisory Board; Varian Medical. Organize clinical trials in lung cancer; NRG Oncology. H. Choy: None.
17 A Phase 2 Randomized Study of 2 Stereotactic Body Radiation Therapy (SBRT) Regimens for Medically Inoperable Patients With Node-Negative, Peripheral Non-Small Cell Lung Cancer G.M. Videtic,1 J.A. Gomez Suescun,2 K.L. Stephans,1 J.A. Bogart,3 L. Tian,4 A. Groman,5 and A.K. Singh4; 1Cleveland Clinic, Cleveland,
International Journal of Radiation Oncology Biology Physics
Results: Seventy-five patients (15 per dose cohort) enrolled with median age of 62 years. Median follow-up for cohorts 1, 2, 3, 4, and 5 were 49.9, 38.3, 25.5, 19.5, and 11.4 months, respectively. There were 60 acute grade 1 toxicity events (breast pain, hyperpigmentation, paresthesia, radiation dermatitis, fatigue) and 2 acute grade 2 toxicities (axillary paresthesia, radiation dermatitis). There were 29 late grade 1 toxicity events (breast pain, chest wall pain, radiation dermatitis, telangiectasias, hyperpigmentation, fatigue, fibrosis), 7 late grade 2 toxicity events (breast pain, rib fracture, fibrosis). Only 3 grade 3 toxicities were experienced (1 patient with breast cellulitis and 2 patients with acute dermatitis in the 37.5 Gy dose levels). There was 1 DLT in the overall cohort (Grade 3 dermatitis in the 37.5 Gy dose level). Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 97.3%, 97.1%, 98.1%, and 100% at baseline, 6, 12, and 24 months post S-PBI while patients scored the same period as 86.5%, 97.1%, 96.2%, and 94.9% (P Z 0.127). There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions with the occurrence of only 1 DLT. Patients felt cosmetic results improved within the first year after surgery and SBRT. There have been no recurrences or distant metastases to date. Our results continue to show minimal toxicity with excellent cosmesis, however further follow-up is warranted. Author Disclosure: A.S. Rahimi: Transplant Hepatologist; Baylor Hospital. Faculty Physician; University of Texas Southwestern Medical Center. Research Grant; Accuray. K. Thomas: None. A. Spangler: Oversight of Radiation Oncology Residency Programs; ACGME. M. Leitch: None. R. Rao: None. R. Wooldridge: None. A. Rivers: None. S. Seiler: None. K.V. Albuquerque: None. S. Stevenson: None. S. Goudreau: Physician; Medical Specialists Inc., PA. Faculty Physician; University of Texas Southwestern Medical Center. Board Member; Health Beacons Clinical Advisory Board. D.P. Garwood: None. B. Haley: None. D. Euhus: None. D. Chen: None. J.H. Heinzerling: None. C. Ding: None. A. Gao: None. C. Ahn: None. R.D. Timmerman: None.
delivered over 1.5-2 weeks. Phase I data analysis revealed that maximum tolerated dose was the highest dose level allowed on the study, 12 Gy/fr x 5 fractions. Thirty-three eligible pts were treated with 12 Gy/fx, and another 38 pts were treated on the preceding dose level of 11.5 Gy/fr; this is the report of efficacy based on patients in those two cohorts. Results: Patients were elderly, and the majority had performance status 01. T1 cancers were treated in 58% of pts in the 11.5 Gy/fr cohort and 70% in 12 Gy/fr cohort. Median PTV volumes were 43cc (range 14.85 - 155.05 cc) and 32 cc (7.48 - 117.25) respectively. Organs closest to PTV/most at risk were main bronchus (45% and 39%, respectively) and large vessels (53% and 21%). Median follow-up was 33 months (mo) for the 11.5 Gy/fr cohort and 29.8 mo for the 12 Gy/fr cohort (49 and 31.8 mo for the surviving pts, respectively). Late toxicities grade 3 or greater (G3+) attributed to SBRT were 2 G5 toxicities in the 11.5 Gy/fr cohort, and in the 12 Gy/fr cohort 3 G3 (2 respiratory, 1 cardiac), 1 G4 (esophageal perforation), and 1 G5 (pulmonary hemorrhage) toxicities. The Table details the incidence of attributed G3+ toxicity, observed failure patterns, and outcomes.
Abstract 16; Table 1 Dose level Number (n) of eligible patients Pts w Toxicity G3+ (at any time) Pts w Early Toxicity G3+ (within 1st yr) Pts with Late Toxicity G3+ (beyond 1st yr) Pts with primary tumor failure Pts with involved lobe failure Pts with regional (lymph node) failure Pts with distant failure 2-year local control 2-yr progression free survival 2-year overall survival (OS)
11.5 Gy x 5fr 38 6 5 2 4 2 2 6 89.4% (81.6-97.4%)* 52.2% (35.3-66.6%)* 70.2% (52.6-82.3%)*
12 Gy x 5fr 33 7 4 5 6 2 4 5 87.7% (78.3-97%)* 54.5% (36.3-69.6%)* 72.7% (54.1-84.8%)*
*90% confidence interval.
16 Efficacy and Toxicity Analysis of NRG Oncology/RTOG 0813 Trial of Stereotactic Body Radiation Therapy (SBRT) for Centrally Located Non-Small Cell Lung Cancer (NSCLC) A. Bezjak,1 R. Paulus,2 L.E. Gaspar,3 R.D. Timmerman,4 W.L. Straube,5 W.F. Ryan,6 Y. Garces,7 A.T. Pu,8 A.K. Singh,9 G.M. Videtic,10 R.C. McGarry,11 P. Iyengar,4 J.R. Pantarotto,12 J.J. Urbanic,13 A. Sun,14 M.E. Daly,15 I.S. Grills,16 D.P. Normolle,17 J.D. Bradley,5 and H. Choy18; 1 Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 2NRG Oncology, Philadelphia, PA, 3Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 4 University of Texas Southwestern Medical Center, Dallas, TX, 5 Washington University, St. Louis, MO, 6Pocono Cancer Center, East Stroudsburg, PA, 7Mayo Clinic, Rochester, MN, 8Sutter Medical Group Radiological Associates of Sacramento, Sacramento, CA, 9Roswell Park Cancer Institute, Buffalo, NY, 10Cleveland Clinic, Cleveland, OH, 11 University of Maryland Medical Systems, Baltimore, MD, 12The Ottawa Hospital, Ottawa, ON, Canada, 13Arizona Oncology Services Foundation, Tucson, AZ, 14Princess Margaret Hospital, Toronto, ON, Canada, 15 University of California Davis Comprehensive Cancer Center, Sacramento, CA, 16Beaumont Health System, Royal Oak, MI, 17University of Pittsburgh Cancer Institute, Pittsburgh, PA, 18Princess Margaret Cancer Centre, Toronto, ON, Canada Purpose/Objective(s): The phase I results of NRG/RTOG 0813 trial were reported at ASTRO 2015. We hereby report the phase II results - efficacy and toxicity beyond year 1. Materials/Methods: Medically inoperable patients (pts) with biopsy proven, PET staged T1-2 (<5 cm) N0M0 centrally located NSCLC (within or touching the zone of the proximal bronchial tree or adjacent to mediastinal or pericardial pleura) were successively accrued onto a doseescalating 5 fraction SBRT schedule ranging from 10-12 Gy/fraction (fr)
Conclusion: Observed local control at 2 yrs in 71 pts treated with the two highest doses levels (11.5-12 Gy/fr x 5 fr) in this multicenter trial was high, and G3+ toxicity rates were acceptable. Two-year OS rates of 70% in this medically inoperable group of elderly pts with comorbidities were comparable to pts with peripheral early stage tumors. This project was supported by grants U10CA21661 (RTOG-Ops-Stat), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U10CA37422 (CCOP), and CA81647 (ATC) from the National Cancer Institute (NCI). Author Disclosure: A. Bezjak: Was president 2012-2014; CARO. R. Paulus: None. L.E. Gaspar: None. R.D. Timmerman: Research Grant; Varian Medical Systems, Elekta Oncology. Offer Scientific Advice; D3 Corporation. W.L. Straube: Receive funding; NIH. W.F. Ryan: Employee; Precomo Medical Centre. None; William Ryan MD. Y. Garces: None. A.T. Pu: None. A.K. Singh: None. G.M. Videtic: None. R.C. McGarry: None. P. Iyengar: None. J.R. Pantarotto: Chair of academic group; University of Ottawa. J.J. Urbanic: grant reviewer; Mesothelioma Applied Research Foundation. A. Sun: None. M.E. Daly: None. I.S. Grills: Stock; Greater Michigan-Gamma Knife. N/A; Greater MichiganGamma Knife. D.P. Normolle: None. J.D. Bradley: Research Grant; Mevion Medical Systems, ViewRay Inc. Proton Therapy Advisory Board; Varian Medical. Organize clinical trials in lung cancer; NRG Oncology. H. Choy: None.
17 A Phase 2 Randomized Study of 2 Stereotactic Body Radiation Therapy (SBRT) Regimens for Medically Inoperable Patients With Node-Negative, Peripheral Non-Small Cell Lung Cancer G.M. Videtic,1 J.A. Gomez Suescun,2 K.L. Stephans,1 J.A. Bogart,3 L. Tian,4 A. Groman,5 and A.K. Singh4; 1Cleveland Clinic, Cleveland,