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SBRT for Early Stage Lung Cancer Ali Mirmiran, MD Nebraska Methodist Hospital March 4, 2014 Objective To discuss the role of stereotactic body radiotherapy (SBRT) in early stage lung cancer Epidemiology Lung cancer is the most frequent cause of cancer death in men & women (28% of all cancer deaths) There are more deaths from lung cancer in the United States than from cancers of the breast & prostate combined 1 85% of lung cancer is NSCLC 25% have stage 1 or stage 2 disease at diagnosis Optimal mgmt for these stages is surgery 60-80% 5 yr survival for stage I, as compared to 15-30% for conventional RT In the treatment of early-stage NSCLC, radiotherapy has played only a minor role, because surgery delivers superior results, as compared with conventional RT In patients with comorbidities, especially of cardiovascular origin, radiotherapy is often the only therapeutic alternative Conventional RT 5 year survival rate ranges from 10-30% 5 yr LC about 50% Avg dose 60-70 Gy in 1.8-2.0 Gy fractions 2 What is SBRT? An ablative therapy where potent doses of radiation are directed at tumors with known boundaries Prescriptions of few fractions & large doses are used Initially, applied to intracranial tumors Lax & Blomgren (Sweden) were the first to apply it to extracranial tumors Requirements for SBRT Medically inoperable? Baseline FEV1 < 40% predicted post-op FEV1 <30% predicted DLCO < 40% predicted PO2 < 70 mm Hg PCO2 > 50 mm Hg Other conditions Likely Continued stability in body frame for longer than 30 minutes SBRT Set-up & Planning Standard immobilization device is a firm frame (e.g. Elekta Body Frame) & vacuum pillow system Restricting respiratory movement throughout treatment is helpful for accuracy Three different techniques which may be used to restrict respiratory movements include dampening/inhibition, gating, & tracking Dampening/inhibitory technique is the most common method which uses an abdominal compression device 3 Tumor Tracking 4 Respiratory Gating Playback Indicator Breathing Signal Upper Threshold Lower Threshold Beam On / Off Indicator Treatment and Dosing SBRT mimics the radiosurgery concept of using many beams which converge on the target The beams can be non-coplanar Imaging can be done with 4D CT Treatment doses are in the range of 50-60 Gy in three to five fractions, however no uniform standard yet Normal tissue- must limit dose Spinal cord, esophagus, brachial plexus, heart, trachea, bronchus, etc … limit to about 6-10 Gy / fx 5 6 7 8 9 Overall survival rate according to the biologic effective dose in medically operable patients 10 Onishi et al 2004: Results Local recurrence: 33 patients (15%) 26.4% for BED < 100 Gy, 8.1% for BED ≥ 100 Gy (p < 0.05) No difference in local recurrence between stage IA & Stage IB when treated with BED ≥ 100 Gy BED ≥ 100 Gy necessary for optimal control BED = nd [(1+d)/ α/β] (α/β) = 10 Gy Onishi et al, 2004 Onishi et al, 2004 Take home point: Survival rates in selected patients (medically operable, BED >100 Gy) were excellent, & potentially comparable to those of surgery 11 12 13 Evaluating SBRT: Challenges Problems with interpreting local control Local normal tissue effects Pt death before follow-up cloud interpretation Differences in definition of local control Differences in dosing & fractionation schedule Confounding factors: prior XRT treatment, chemo Separating out medically inoperable grp from refused surgery grp 14 Kimura et al, 2006: CT Appearance of Radiation Injury of the Lung and Clinical Symptoms After SBRT for Lung Cancers; are Patients with Pulmonary Emphysema also Candidates for SBRT for Lung Cancers? Purpose: analyze CT appearance of radiation injury to the lung & evaluate appearance in patients with emphysema 45 patients with 52 primary or metastatic lesions Median age 75 Dose 54-60 Gy total, 8-14 fx Follow-up CTs done at 1,3,6, then every 6 months Kimura et al, 2006: Results Acute radiation pneumonitis (< 6 months after SBRT) had 5 patterns: Diffuse consolidation: 38.5% Patchy consolidation & ground glass opacities (GGO): 15.4% Diffuse GGO: 11.5% Patchy GGO: 2.0% No evidence of increasing density:32.6% Classification of Radiation Fibrosis (> 6 months after SBRT) Modified Conventional Pattern: 61.5% Mass-like Pattern: 17.3% Scar-like Pattern: 21.2% 15 Kimura et al, 2006 Most patients with no evidence of increased density pattern & the scar like pattern also had emphysema (p <.00038, 0.00044, respectively) Diffuse consolidation pattern; a 78-year-old woman with Stage IB lung cancer (adenocarcinoma), 60 Gy/8 fractions (a) before SBRT, (b) 2 months after SBRT A 74-year-old man with metastatic lung cancer from lung cancer (squamous cell carcinoma), 56 Gy/14 fractions. This case was diagnosed as pulmonary emphysema Grade 2, no evidence of increasing density pattern as acute radiation pneumonitis, & scar-like pattern as radiation fibrosis. (a) Before SBRT, (b) 3 months after SBRT, (c) 20 months after SBRT 16 Typical Appearance of Radiation Injury After SBRT ~ 1 month after SBRT: no radiologic change 3-6 months: diffuse or patchy consolidation in the high-dose region & diffuse or patchy GGO in the low-dose region – radiation pneumonitis 6-9 months: solid or dense consolidation, which usually move toward the mediastinum or hilum with shrinkage 1-2 yrs: stable opacities 17 Clinical Trials 18 Subjects for Further Investigation SBRT as a boost after conventional RT SBRT vs Surgery in medically operable Optimal dosing 19 Conclusions Overall, SBRT studies showed better LC & OS than conventional RT with minimal toxicity. SBRT is becoming/has become the standard for medically inoperable stage I NSCLC It could potentially become first-line treatment in operable patients It is hoped the stereotactic treatments not only will give medically frail patients with early stage lung cancer a choice but perhaps someday be another option for a larger spectrum of lung cancer patients. -Robert Timmerman, MD Special thanks to Dr. Hauke 20