ASTRO News Brie iefin ing: Refin inin ing Treatment Decis isions - PowerPoint PPT Presentation

ASTRO News Brie iefin ing: Refin inin ing Treatment Decis isions Monday, September 26, 8-9am ET Moderator: George Rodrigues, MD, PhD, London Health Sciences Centre • N107C/CEC.3: A Phase e II III Tria rial of of Pos ost-Operativ ive Stereotactic ic Radio iosurgery Com Compared with ith Whol ole Br Brain in Radio iotherapy for Res esec ected ed Metastatic Br Brain Dis Disease Paul D. Brown, MD, Mayo Clinic • Pos ost-operativ ive Stereotactic Radio iosurgery vs. . Observation for Co Comple letely Res esec ected Br Brain in Metastases es: Res esult lts of of a Prospective Randomized ed Stu tudy Anita Mahajan, MD, MD Anderson Cancer Center • A Phase III III Randomized Stu tudy of of Im Image Guid ided Co Conventional l vs Acce ccelerated, Hy Hypofractionated Radia iati tion for or Poo oor Perf erformance e Statu tus Stage II II and II III NSCLC Patien tients – An In Interim Analy lysis is Puneeth Iyengar, MD, PhD, University of Texas Southwestern • Extreme Hy Hypofractionati tion vs. . Co Conventionall lly Fractionated Radio iotherapy for In Intermedia iate Ris isk Prostate Ca Cancer: Earl rly Toxicity Res esult lts fr from th the e Scandin inavia ian Randomized Phase e II III Tria rial "H "HYP YPO-RT RT-PC PC" Anders Widmark, MD, PhD, Umeå University, Sweden

N107C/CEC.3: A Phase III III Trial of f Post-Operative Stereotactic Radiosurgery ry (S (SRS) Compared wit ith Whole Brain Radiotherapy (W (WBRT) ) for Resected Metastatic Brain Dis isease P. D. Brown 1,2 , K. V. Ballman 3 , J. Cerhan 1 , S. K. Anderson 1 , X. W. Carrero 1 , A. C. Whitton 4 , J. Greenspoon 4 , I. F. Parney 1 , N. N. Laack 1 , J. B. Ashman 5 , J. P. Bahary 6 , C. G. Hadjipanayis 7 , J. J. Urbanic 8 , F. G. Barker II 9 , E. Farace 10 , D. Khuntia 11 , C. Giannini 1 , J. C. Buckner 1 , E. Galanis 1 , and D. Roberge 6 1 Mayo Clinic, Rochester, MN, 2 The University of Texas MD Anderson Cancer Center, Houston, TX, 3 Weill Cornell Medicine, New York, NY, 4 Juravinski Cancer Centre, Hamilton, ON, Canada, 5 Mayo Clinic, Phoenix, AZ, 6 Hopital Notre-Dame du CHUM, Montreal, QC, Canada, 7 Winship Cancer Institute, Emory University, Atlanta, GA, 8 University of California, San Diego, La Jolla, CA, 9 Massachusetts General Hospital, Boston, MA, 10 Penn State University College of Medicine, Hershey, PA, 11 Western Radiation Oncology, Mountain View, CA

Background • WBRT standard of care after resection of brain metastasis to improve local control • However WBRT after resection • No survival benefit • Side effects (hair loss, fatigue, skin redness) • Concerns cognitive impact • Growing practice of SRS to the surgical cavity to reduce risk cognitive toxicity • Despite no level I efficacy data Post-Op SRS • Despite costs of SRS • Need to prospectively evaluate and compare SRS surgical bed to WBRT, the standard of care

Method R  Age (18 to 59 vs. ≥ 60) S a  Extra-Cranial Disease t WBRT +SRS unresect mets Controlled (≤ 3 vs. > 3 mo) n r Resected  Number Pre-Op Brain Mets (1 d a Brain vs. 2-4) o Met* t  Histology (Lung vs. m SRS + SRS unresected mets Radioresistant vs. Other) i i  Resection Cavity Max Diam f ( ≤ 3cm vs. > 3cm) z y  Institution e Eligibility Criteria: Primary Endpoints: Patient Assessments: • • S/P resection 1 lesion I: Cognitive Deterioration Free MRI • • 0-3 unresected mets Survival Quality of Life (QOL) • • No chemo during radiation II: Overall Survival Cognitive Battery *194 patients, 59% Lung Primary Tumor, 77% single metastasis

Results Worse Cognitive Function No Dif ifference in in Surviv ival wit ith WBRT SRS WBRT

Results Su Surgic ical l bed control l sim simil ilar, , alt lthough long-term better lo r with ith WBR BRT However, with WBRT… - Worse quality of life (QOL) - More toxicity - Longer treatment course and delayed systemic therapy WBRT SRS

Conclusions Post-Op SRS for patients with resected brain metastases should also be a standard of care with equiv ivale lent survival, better preservation of cognitive function and QOL, and less toxicity than WBRT.

ASTRO News Brie iefin ing: Refin inin ing Treatment Decis isions Monday, September 26, 8-9am ET Moderator: George Rodrigues, MD, PhD, London Health Sciences Centre • N107C/CEC.3: A Phase III Trial of Post-Operative Stereotactic Radiosurgery Compared with Whole Brain Radiotherapy for Resected Metastatic Brain Disease Paul D. Brown, MD, Mayo Clinic • Pos ost-operativ ive Stereotactic Radio iosurgery vs. . Observation for Co Comple letely Res esec ected Br Brain in Metastases es: Res esult lts of of a Prospective Randomized ed Stu tudy Anit nita Mah ahajan, MD, , MD D And nderson Can Cancer Cen Center • A Phase III Randomized Study of Image Guided Conventional vs Accelerated, Hypofractionated Radiation for Poor Performance Status Stage II and III NSCLC Patients – An Interim Analysis Puneeth Iyengar, MD, PhD, University of Texas Southwestern • Extreme Hypofractionation vs. Conventionally Fractionated Radiotherapy for Intermediate Risk Prostate Cancer: Early Toxicity Results from the Scandinavian Randomized Phase III Trial "HYPO-RT-PC" Anders Widmark, MD, PhD, Umeå University, Sweden

Post-operative Stereotactic Radiosurgery ry vs. Observ rvation for Completely Resected Brain Metastases: Results of f a Prospective Randomized Stu tudy A. Mahajan 1 , S. Ahmed 2 , J. Li 3 , M. F. McAleer 1 , J. Weinberg 4 , P. D. Brown 3 , S. Prabhu 4 , F. F. Lang 4 , S. L. McGovern 1 , I. E. McCutcheon 4 , A. Heimberger 4 , E. P. Sulman 3 , A. J. Ghia 1 , S. Ferguson 4 , K. Hess 5 , and G. Rao 4 1 Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 2 Department of Neuroradiology, UT MD Anderson Cancer Center, Houston, TX, 3 The University of Texas MD Anderson Cancer Center, Houston, TX, 4 Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 5 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX

Background Local Failure after surgery alone vs surgery+WBRT • Surgical resection and whole brain radiotherapy (WBRT) independently have Surgery alone been shown to improve local control for Surgery + WBRT brain metastasis • Whole brain radiation (WBRT) has been used in the post operative setting but has a deleterious impact on cognition • Post operative stereotactic radiosurgery (SRS) may improve local control and allow delay or avoidance of WBRT Patchell et al JAMA 1998;280(17) 1485-89

Background and Rationale • Retrospective studies suggest local control rates of 80 to 90% after post-op SRS • Surgical techniques have evolved suggesting that en bloc resection may be a favorable method to removing metastases in order to decrease resection cavity contamination • Goal: Validate retrospective studies by evaluating SRS to the post- operative cavity in a prospective manner

Study Objectives • Primary Objective: • Determine whether the addition of post-operative SRS to the resection cavity results in improved local tumor control compared to surgical resection alone • Secondary Objectives • Rate of distant brain metastasis, overall survival, WBRT

Method GTR Day 0 Str tratification Register & Stratify Day 14- Register & Randomize 1. Histology 1. 1 vs 2-3 BM 21 2. Size >3cm, <3cm 3. 1 vs 2,3 mets 2. Melanoma vs other 3. Pre-operative tumor size <3cm vs > RANDOMIZE 3cm Day 15- OBS Randomizatio ion SRS 30 • SRS-cav or observation (OBS) of the surgical cavity (or cavities if >1 lesion was MRI 5-7 wks resected) • Remaining 1-2 metastasis were treated FU + MRI q 6-9 wk x 1 y with SRS FU + MRI q 3-4 mo x 1 y

Results: Local Control Local Control ARM RM 6 mo o LC 12 mo o LC 95% CI Ha Hazard Ra Ratio OBS 57% 45% 33-61% 0.46 (0.25- 0.85) SRS 83% 72% 60-87% P=0.01 ARM RM Med ed Tim Time to o Loc oc Rec ec 95% CI OBS 7.6 mo 5.3 - nr SRS Not reached 15.6 - nr

Results: DBM & OS Distant Brain Metastasis Overall Survival v v ARM 12 mo DB 12 DBM Fr Free Haz azard Ra Ratio ARM Med OS OS Haz azard Ra Ratio OBS 33% OBS 17 mo 0.79 (0.50-1.24) 1.22 (0.79-1.87) P=0.29 P=0.37 SRS 43% SRS 17 mo

Variables influencing LC Local Recurrence by Tumor Size 1.0 1.0 Init In itial Tumor N LC LC Dia iameter 0.8 0.8 Freedom from Local Recurrence < 2.5 cm 40 91% Log Rank p = 0.0004 0.6 0.6 p=0.0004 2.6-3.5 cm 55 43% 0.4 0.4 >3.5 cm 33 46% 0 - 2.5: N = 40, 3 ev, 12 mon = 91% 0.2 0.2 2.6 - 3.5: N = 55, 25 ev, 12 mon = 43% > 3.5: N = 33, 17 ev, 12 mon = 46% 0.0 0.0 0 5 10 15 20 Months

Conclusions • Post-operative SRS after complete resection significantly improves local control • There was no difference in distant brain metastases (DBM) or overall survival (OS) between the two groups. • Further analysis will be presented to determine whether specific patients benefit more from post-operative SRS. => Initial Tumor Size may provide guidance on magnitude of benefit => Increasing dose of SRS may allow improved LC on larger tumors