Emily Tanzler , MD Waseet Vance, MD

1. Stereotactic Ablative Radiation Therapy (SABR) for Early Stage Non-Small Cell Lung Cancer Emily Tanzler, MD Waseet Vance, MD

2. Treatment Options for Early Stage Lung Cancer Surgical • Sub-Lobar Resection • Lobectomy • Non-Surgical • Conventional RT • SBRT • RFA

3. Clinical stage I NSCLC patients can be considered falling into three treatment groups: • Average-risk patients: typically treated with lobectomy • High-risk patients: typically treated with sublobar (segmental or wedge) resection • Medically inoperable patients: traditionally treated with external beam radiation therapy.

4. Surgical resection is the gold standard for treatment of patients with stage I and II operable lung cancer • 5-year Overall Survival for stage I NSCLC • Clinical stage IA-61% • Pathologic stage IA-67% • Clinical stage IB-38% • Pathologic stage IB-57% (Mountain CF. Semin. Surg. Oncol. 18:106–115, 2000)

5. Criteria for Resection • FEV1 • ACCP threshold for lobectomy: 1-1.5L • Recent series demonstrated increased complications for FEV1 <47% predicted • DLCO • > 60% Preoperative recommended • < 40% Predicted Post-Op Associated with high morbidity/mortality • Exercise Tolerance

6. High Risk or “Marginally” Operable Patients • Substantial number (15-40%) of NSCLC patients present with impaired cardiopulmonary reserve • Increased risk of peri-operative complications and long-term disability with standard anatomic resections

7. High Risk or “Marginally” Operable Patients • Will have difficulty during and after a lobectomy or pneumonectomy • Getting off ventilator • Getting out of hospital • Readmissions • Decreased vitality/quality of life post-resection

8. Surgical Options – Lobectomy vs. Sublobar Resection T1N0 (Negative mediastinoscopy)

9. Lobectomy vs. Sublobar Resection Sem Thor and CT Surg 2003 • LR ~10% with Lobectomy vs ~20-30% with sublobar resection

10. Medically Inoperable • Observation alone in these patients is not a good option • In a study of 75 Stage I medically inoperable patients treated with observation alone • Lung cancer cause of death in 53% • Death from other comorbidities was 30% (McGarry, Chest 2002)

11. Radiofrequency Ablation Placed percutaneously Electrode heated to 50 - 100° Coagulation Necrosis Treat tumor + margin Indications: Small (<3 cm) NSCLC or mets Complications: Pneumothorax (30%) Fever/Pleurisy/Effusions Radiology 2007

12. Conventional Radiation Therapy IJROBP 1998 Local Control: 50 – 60%

13. Stereotactic Ablative Radiation Therapy (SABR) is the emerging standard in the management of non-small cell lung cancer for the medically inoperable patient.

14. Stereotactic Ablative Radiation Therapy (SABR) • Outpatient • Noninvasive/painless • No sedation or anesthesia required • Completed in 1-5 treatments • Entire course completed in 1-2 weeks • Each treatment only 20-60 minutes • No limitation in activities or recovery downtime • Spares significant lung tissue

15. SABR vs Conventional RT • Local Control • Historic comparisons • SABR 54 Gy in 3 fx, 98% (local), 91% (lobe) (RTOG 0236) • EBRT 60-66 Gy / 30-33 fx, ~50% (Qiao, Lung Cancer 2003) • Beaumont experience comparing SABR vs EBRT (Lanni, Am J ClinOncol 2011) • SABR (48-60 Gy in 4-5 fx, n=45) vs. EBRT (70 Gy/35 fx, n=41) • 3y LC: 88% vs. 66% • Meta-analysis (Grutters, RadiotherOncol 2010) • SABR (n=895) vs. EBRT (n=1326) • 2y OS, 70% vs. 53% • 2y DFS, 83.4% vs. 67.4%

16. Medically Inoperable: Peripheral Tumors- RTOG 0236 • Timmerman et al. JAMA. 2010 Mar 17;303(11):1070-6. • 55 patients with a median follow-up of 34.4 months • T1 tumors (44 patients) • T2 tumors (11 patients) • 3-year primary tumor control rate was 97.6% • 3-year rate of disseminated failure was 22.1%

17. Medically Inoperable: Peripheral Tumors- RTOG 0236 • Disease-free survival at 3 years 48.3% • Overall survival at 3 years 55.8% • Median survival was 48.1 months • Toxicity • Grade 3 toxicity in 7 pts (12.7%); grade 4 in 2 pts (3.6%). No grade 5. • Rare rib fractures and dermatitis have been observed for chest wall tumors

18. MEDICALLY OPERABLE PATIENTS • SABR data from Japan in operable patients who declined surgery • 87 patients with T1 (n=65) or T2 (n=22) tumors treated at 14 Japanese institutions • 5 year survivals for stage IA and IB comparable to surgery • Stage IA=77% • Stage IB=68% (Onishi, IJROBP 2010)

19. MEDICALLY OPERABLE PATIENTS • 50 ptswwith T1 (n=24) or T2 (n=26) tumors treated with SABR from1994 to 1999. • 29 pts were medically operable but refused surgery • Entire cohort of 50 patients: • 3 year LC 94% • 3 year CSS 88% • 3 year OS 66% • Cohort of 29 operable patients • 3 year OS 86% (Uematsu, IJROBP 2001)

20. MEDICALLY OPERABLE PATIENTS • 177 medically operable patients with T1 (60%) or T2 (40%) tumors treated with SABR from2003 to 2010 in the Netherlands • SABR dose of 60 Gy delivered in 3, 5, or 8 fractions using a risk adapted scheme • 3 year LC 93% • 3 year OS 84.7% (Lagerwaard, IJROBP 2012)

21. Treatment Toxicities • Rates are generally low • > grade 3 pneumonitis, hypoxia: < 5% • Related to tumor location & fractionation schedule • Newer fractionation schemes and advanced treatment techniques have further improved toxicity profile

22. SABR Case

23. Treatment Response Timeline Initial Treatment 4 months Complete Radiographic Response 18 months No Evidence of Disease

24. Conclusions • Surgery is the gold standard for operable patients • For inoperable or marginally operable high risk patients with Stage I lung cancer SABR offers excellent local control and similar survival to surgical approaches • Randomized trials have failed to accrue for various reasons- patients and physicians

25. Thank You