Outline. WBRT field. Brain Metastases. Whole Brain RT Prophylactic WBRT Stereotactic radiosurgery (SRS) 1 fraction Stereotactic frame

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Radiation Therapy for Advanced NSC Lung Ca Alexander Gottschalk, M.D., Ph.D. Associate Professor Director of CyberKnife Radiosurgery Department of Radiation Oncology University of California San Francisco Radiation for Advanced NSC Lung Ca Outline Brain metastasis Whole Brain RT Prophylactic WBRT Stereotactic radiosurgery (SRS) 1 fraction Stereotactic frame Stereotactic body radiotherapy (SBRT = 2-5 fractions) for M1 disease for recurrent disease Brain Metastases Brain Metastases WBRT field Survival is 3-5 mo with WBRT (hasn t changed in decades). 1

Prophylactic whole brain for stage IIIA/B RTOG 0214 ASTRO 2009 356 patients randomized between WBRT (30 Gy/15 fx) or observation XRT 1-yr DFS 56% 51% 1-yr OS 76% 77% Observation CNS mets 8% 18% p=0.004 Decrease immediate and delayed recall Radiosurgery for Brain Mets Limited number of lesions < 3 cm in diameter 18 Gy at 55% IDL PR 6 mo p RS SRS for brain mets from NSCLCa Sheehan J Neurosurg 2002 273 patients and 627 metastases from NSCLCa treated with SRS Median OS 15 months Local control of the treat lesion was 84% Improved survival was associated with: KPS Controlled systemic disease Time for lung ca diagnosis 71 yo M with T1N1M1 squamous cell lung cancer; synchronous brain met. SRS for Brain Mets Limited number of lesions < 3 cm in diameter 2

SRS for Brain Mets Limited number of lesions < 3 cm in diameter Day of RS 11 mo. SRS 17.5 Gy, thoracic chemo/rt; NED at 11 mo.; 2nd GK at 1.5 yr for 1 new asx met; did well for 5 years SRS for synchronous solitary brain mets from NSCLCa Flannery IJROBP 2008 42 NSCLCa patients treated with SRS and 26/42 had treatment of lung primary Median OS 18 months 5-year OS 20% Improved survival was associated with: KPS Treatment of lung primary SBRT to lung primary for M1 disease 73 yo woman 3/07 Solitary brain met -> Resected, path adenoca PET/CT -> RUL mass Received systemic therapy 9/07 and 3/08 GK for additional brain mets 12/08 PET/CT only showed RUL mass SBRT to lung primary for M1 disease 3/09 SBRT (48 Gy in 4 fx) 5/09 PET/CT -> decrease in size RUL mass 7/09 Chest CT band-like atelectasis RUL 3

SBRT to lung primary for M1 disease 3/09 SBRT (48 Gy in 4 fx) 5/09 PET/CT -> decrease in size RUL mass 7/09 Chest CT band-like atelectasis RUL 3/09 7/09 87 yo woman 2005 SOB -> RUL mass CXR CT -> RUL and RLL mass 2/06 BX RUL -> NSCLCa 5/06 wedge resection of both RUL and RLL masses Path -> both showed adeno ca Followed with serial scans 1/07 CT -> new RUL mass 3/08 CT -> RUL mass 1 cm 6/08 CT -> RUL mass 1.9 cm CT -> RUL mass 2.3 cm adjacent to prior wedge site. No other disease 87 yo woman 2005 SOB -> RUL mass CXR CT -> RUL and RLL mass 2/06 BX RUL -> NSCLCa 5/06 wedge resection of both RUL and RLL masses Path -> both showed adeno ca Followed with serial scans 1/07 CT -> new RUL mass 3/08 CT -> RUL mass 1 cm 6/08 CT -> RUL mass 1.9 cm CT -> RUL mass 2.3 cm adjacent to prior wedge site. No other disease 4

4/09 4/09 8/09 4/09 8/09 1st Author Primary Lung Cancer T1&2 - SBRT # of Pts Dose (Gy) McGarry 47 8-24 x 3 fx Onishi 257 BED 108 (57-180) Uematsu 50 50-60/5 60/5-10 fx Median FU (mo) 27 for T1 19 for T2 Local Control 79% 53 86% 36 in living pts 94% Nagata 45 12 x 4 fx 30 m 98% Timmerman 70 T1:20 x 3 T2:22 x 3 17.6 m 95% 20 5

SBRT for lung mets 83 yo woman 2006 Right buttock mass -> leiomyosarcoma Resection and post-operative XRT 2/07 CT -> RUL mass 1 cm 3/07 VATS -> 2 nodules mets LMS 6/07 hemoptysis -> CT showed 2.6 cm RLL nodules SBRT for lung mets 7/07 SBRT 50 Gy in 5 fractions Hemoptysis resolved 10/07 CT -> previous RLL mass resolved, but development of multiple new pulmonary nodules 1st Author SBRT for Lung Metastases Number of Pts Uematsu 22 43 lesions Dose (Gy) 30-75/5 75/5-15 fx Median FU (m) 11 97% Local Control Hara 17 20-30 x1 13 70% (< 30 Gy) 86% (30 Gy) Lee 19 26 lesions 10 x 3-4 fx 18 17/19 = 88% Whyte 8 15 x 1 7 91% for both primary & met SBRT for other mets Spine (Chang J Neurosurg spine 2007) 63 patients and 74 lesions 1-year control rate 84% Adrenal (Chawla IJROBP, 2009) 30 patients 1-year local control 55% Dose lower due bowel concerns Liver (Euro J Cancer, 2009) 2-year local control 71-86% 6

SBRT for oligometastases Milano Cancer 2008 121 patients with 5 or less metastatic sites 1 o sites: 32% breast, 26% colorectal, 19% lung met sites: 54 liver, 50 lung, 28 LN, 15 bone, 5 brain, 2 adrenal OS PFS LC DC 2yr 50% 26% 67% 34% 4yr 28% 20% 60% 25% Favorable predictors of OS breast cancer no adrenal mets Smaller volume of treated mets Conclusions Poor survival with whole brain RT for brain mets - SRS should be considered for select candidates Prophylactic WBRT decreases brain failure but does not improved survival SBRT can be used to control primary lung tumors in patients with limited metastatic disease SBRT can be used to control recurrent/persistent lung tumors after conventional treatment SBRT can be used to control bone, liver, adrenal mets in select patients Aggressive therapy of primary lung tumors and oligometastases may produce some long-term survivors 7