Sublobar Resection and Brachytherapy for Small Peripheral Lung Tumors

1. Sublobar Resection and Brachytherapy for Small Peripheral Lung Tumors Hiran C Fernando FRCS, FACS Chief Thoracic Surgery Boston Medical Center, Boston University

2. Presenter DisclosureHiran C Fernando FRCSThe following relationships exist related to this presentation: CSA Medical ( Role Consultant; Not relevant to presentation Galil (Role Consultant; Not relevant to presentation

3. Comparison of Rx Modalities for Stage I NSCLC

4. Can we reduce the higher local recurrence that occurs with sublobar resection using radiation?

5. Adjuvant Radiation for Local ControlMiller and Hatcher Ann Thorac Surg 44:340-343, 1987 • Non-Randomized study • FEV-1 < 1 L or FEV 25-75 < 0.6L • Stage I = 31 , Stage II = 1 • Segmentectomy=10 , Wedge=22 • Radiation to resected area and hilum – 4500 cGy Results: • Local Recurrence in 20 patients with no radiation was 40% • Local Recurrence in 32 patients with radiation was 6.25%

6. Adjuvant Radiation • Post-operative external beam radiation; • time consuming • Can result in additional loss of pulmonary function • Not all patients are compliant with therapy • Difficulties in identifying staple line

7. Adjuvant Brachytherapy • Intra-operative brachytherapy • All patients receive uniform doses of radiotherapy • 100% patient compliance • “One-time” treatment • Minimizes radiation injury to remaining lung

8. Adjunctive Intra-operative 125I Brachytherapy • Two techniques; • “Sutures strands” containing 125I seeds • Lee at al.Ann Thorac Surg 2003;75:237-43 • Mesh Brachytherapy • D’Amato TA et al. Chest 1998;114:1112-5

9. ~$546 per ring. Each strand has 10 I-125 seeds. Oncura, Arlington Heights, IL.

10. “Suture Strand” Placement

13. Absorbable mesh preloaded with I-125 seeds Order 4-5 strands with 1-1.5 cm spacing for total of 20-25 mCi Patient-specific seed distribution Simple double lead pouch packaging/shielding Autoradiograph and 10 seed assay Each strand woven through mesh 20 times for anchored geometry Pre-Fabricated Device

16. CxR after SRB

17. Studies of Adjuvant Brachytherapy

18. Impact of Brachytherapy (Bx) after sublobar resection (SR)Fernando et al; JTCVS 2005;129:261-7

19. Z4032; Randomized Phase III Study of Sublobar Resection (SR) vs Sublobar Resection plus Brachytherapy (SRB) in High-risk patients with NSCLC , 3cm or smaller

20. Z4032; Study Aims • Primary Objective • Compare time to local recurrence between SR and SRB • Secondary Objectives • Compare morbidity and mortality • Compare overall survival and failure-free survival • Determine effect on quality of life (SF36 and UC San Diego Shortness of Breath Questionnaire) • Determine effect on pulmonary function

22. Early PFT results • PFT’s; FEV1%, DLCO% • Baseline, 3m, • 12m and 24m to be assessed • UC San Diego Shortness of Breath Questionnaire • 24 items, 0 – 5 [not at all-maximally breathless] scale • Scale reversed, scored to form total score (0-120) • Score transformed 0-100 [worse-best QOL] scale

23. PFT outcomes • PFT’s/Dyspnea Score; • change in median scores from baseline-M3 compared within each arm • 10% or 10-point change deemed “clinically meaningful” and compared between arms • Examined factors associated with “clinically meaningful” change; • approach [VATS/open] • tumor location [UL vs LL] • 30-day respiratory AE

24. Change in PFT and Dyspnea Score No significant differences

25. “Clinically Meaningful” Change

26. Clinically Meaningful Decrease in PFT/Dyspnea • Multivariate analysis to determine the impact of; • Tumor location [upper vs. lower lobe] • Approach [VATS vs. Thoracotomy] • 30 day grade 3-4 respiratory AE • Resection location associated with decrease in FEV1% • 22% of lower lobe vs 9% upper lobe resections • OR 2.84; p= 0.03

28. Z4032 AE; Statistical analysis • Treatment arms compared for G3+ AE • Risk factors for AE studied-multivariable logistic model • age , • baseline DLCO% and FEV1% (continuous variable) • Upper vs lower lobe resection • Performance status • Optimal cutpoints also explored using the median values of baseline DLCO% / FEV1%

29. 30 and 90 day mortality (G5 AE) • No difference between SR and SRB • 30 days- 3 (1.4%) • Cardiopulmonary arrest (SR) =1 • CVA (SRB) =1 • PE (SRB) =1 • 90 days 6 (2.7%) • Cancer progression (SR) =2 • Cardiac arrest (SRB) =1 • 4/6 deaths attributable to surgery

30. G3+ AE; SR versus SRB (no difference in G4+AE as well)

31. G3+ AE all patients • Groups combined for further analysis • Age, baseline PFT, PS, tumor location • Days 0-30 • FEV1% associated with “any” G3+ AE (p=0.05) • DLCO% associated with “respiratory” G3+ AE (p=0.03) • Days 0-90 • DLCO% associated with “respiratory” AE (0.05) (FEV1% / DLCO% as continuous variables)

32. Median DLCO% (<46 vs. ≥46) as Predictor of G3+AE

33. Median FEV1% (<50 vs. ≥50) as Predictor of 3+AE

34. Z4032;Technique analysisM Kent at al; STSA Nov 2012 • 214 eligible patients • 137 (64%) VATS and 77 (36%) thoracotomy • Segmentectomy in only 57 (27%) • VATS similar to thoracotomy wrt to; • Use of segmentectomy • Ly node count, stations sampled and margin

35. Wedge vs SegmentectomyNodal Evaluation

36. Wedge vs SegmentectomyMargin Status

37. Current Conclusions Z4032 • SR (+/-br) does not negatively impact PFT at early follow-up • Brachytherapy does not lead to additional morbidity / mortality • Lower lobe SR associated with greater decrease in FEV1% at 3 months • 30 and 90 day mortality of 1.4% and 2.7% (all patients) • 30 and 90 day any G3+ AE of 27.9% and 33.3% (all patients)

38. Current conclusions Z4032 (2) • DLCO (<46%) associated with increased G3+ AE at 30 and 90 days • Segmentectomy only performed in 27% cases by credentialed surgeons • Segmentectomy -better pathological effectiveness • better margin (size and M:T ratio) • Lymph node count and stations sampled

39. Thankyou!