- In potentially operable patients -

Size: px

Start display at page:

Download "- In potentially operable patients -"

Pierce Carroll
5 years ago
Views:

Lung Stereotactic Ablative Radiotherapy (SABR) -

Lagerwaard VUMC Amsterdam Stereotactic Ablative

definition Non-gated SBRT delivery Pencil beam

Non-gated SBRT delivery AAA planning Risk adapted

1 Lung Stereotactic Ablative Radiotherapy (SABR) - In potentially operable patients - Frank Lagerwaard VUMC Amsterdam Stereotactic Ablative Radiotherapy (SABR) DCT-based target definition Non-gated SBRT delivery Pencil beam Risk adapted d schemes (3f, 5f, 8f) 20Gy*3; 12Gy*5; Novalis ExacTrac patient setup 8-12 non-coplanar beams Delivery approx. 45 minutes DCT-based target definition Non-gated SBRT delivery AAA planning Risk adapted d schemes (3f, 5f, 8f) 18Gy*3; 11Gy*5; Novalis TX CBCT tumor setup Volumetric arcs (RapidArc) Delivery approx. 10 minutes 1

2 Lung SABR referrals Jan-03 Jan-04 Jan-05 Jan-06 Jan-07 Jan-08 Jan-09 Jan-10 Jan-11 Number of Dutch centers performing lung SABR T1 tumors ( 3 cm), without extensive contact with chest wall or mediastinum 3 x 18 3 fx/week (BED 134 Gy) T1 tumors in broad contact with chest wall or mediastinum, and T2 tumors 5 x 11 3 fx/week (BED 116 Gy) Tumors adjacent to pericardium, brachial plexus or hilus 8 x fx/week (BED 105 Gy) Patient characteristics (N=801) Male:Female 487 (61%):314 (39%) Median age 73 years (range 41-93) Stage 1a Stage 1b Stage 2a Stage 2b No COPD GOLD 1 GOLD 2 GOLD 3 GOLD (29%) 242 (30%) 276 (35%) 50 (6%) Stage 2b 50 (6%) 199 (25%) 106 (13%) 251 (31%) 178 (22%) 61 (8%) Charlson Comorbidity Score Median 2 (range 0-11) Pathological verification No pathological verification 274 (34%) 527 (66%) Inoperable 590 (74%) Refusal/preference 211 (26%) SABR 3 x 18 Gy (3 x 20 Gy with PB) SABR 5 x 11 Gy (5 x 12 Gy with PB) SABR 8 x 7.5 Gy Patient setup & static fields Tumor setup & RapidArc 284 (35%) 341 (43%) 176 (22%) 458 (57%) 343 (42%) * Only pts with a single lesion included 2

3 Lung SABR at VUMC (N=801) Overall years years 34.3% Local years years 8.3% Regional years years 14.7% Distant years years 21.1% 3

Local control after SABR Local recurrences: N=33 Any suspected lesion coded as LR (even without PET/histology) Median time to LR 15 months (range 6-63 months) 93.1% 91.

4 Local control after SABR Local recurrences: N=33 Any suspected lesion coded as LR (even without PET/histology) Median time to LR 15 months (range 6-63 months) 93.1% 91.7% Mature SABR data on long-term local control available Although median time to LR is 15 months; late LR do occur Why do we obtain such high LC rates with SABR >100 Gy 10..?? Critisism on SABR LC results Data are not as mature as for surgery Long-term Japanese data, VUmc 200+ pts >3 years at risk Fibrosis masks the diagnosis of LR True, but any suspicious lesion has been coded as LR Of 33 LR, only 13 had pathology SABR results are based on treating small lesions SABR results are (partly) based on treating benign lesions 4

5 Artificially high LC due to small tumor size? Artificially high LC: SABR for benign lesions? (N=274) 5

LC after SABR (BED >100 Gy 10 ) 90% Can we improve LC even more? Analysis of factors related to LR? Local control = for all BED schemes >100 Gy 10 (i.e. for all 3 SABR schemes) Analysis of factors related to LR?

In 18/32 (56%) of LR, tumor immediately adjacent to chest wall, but target contouring was judged to be (too) tight in only 5 pts Only 6 patients (19%) had tumor motion

6 LC after SABR (BED >100 Gy 10 ) 90% Can we improve LC even more? Analysis of factors related to LR? Local control = for all BED schemes >100 Gy 10 (i.e. for all 3 SABR schemes) Analysis of factors related to LR? Retrospective review of steps from target definition to delivery in 32 LR pts. - 4DCT-quality, contouring errors, PTV mobility and planning errors? In 18/32 (56%) of LR, tumor immediately adjacent to chest wall, but target contouring was judged to be (too) tight in only 5 pts Only 6 patients (19%) had tumor motion 1cm on 4DCT In a single patient, unnoticed artifacts in the planning 4DCT-scan (PTV error) In 53% of patients, no apparent explanation for LR 6

Stereotactic Ablative Radiotherapy (SABR) 2003-2008

Pencil beam Risk adapted schemes (3f, 5f, 8f) 20Gy*3;

5Gy*8 @80% Novalis ExacTrac patient setup 8-12

45 minutes 2008-2010 AAA planning Risk adapted

5Gy*8 @80% Novalis TX CBCT tumor setup Volumetric arcs

10 minutes Do newer techniques improve local control?

Patient setup & static fields Tumor setup & RapidArc

7 Stereotactic Ablative Radiotherapy (SABR) DCT-based target definition Non-gated SBRT delivery Pencil beam Risk adapted schemes (3f, 5f, 8f) 20Gy*3; 12Gy*5; Novalis ExacTrac patient setup 8-12 noncoplanar beams Delivery approx. 45 minutes DCT-based target definition Non-gated SBRT delivery AAA planning Risk adapted schemes (3f, 5f, 8f) 18Gy*3; 11Gy*5; Novalis TX CBCT tumor setup Volumetric arcs (RapidArc) Delivery approx. 10 minutes Do newer techniques improve local control? Local control by SABR technique T1a-b tumors only Patient setup & static fields Tumor setup & RapidArc Conclusion: Novel techniques do not (further) improve local control Conclusion: Faster novel techniques do not compromise local control 7

$Incidence Rib fracture 3% Chest wall pain 3% Radiation pneumonitis 2% Pleural effusion 1% Early toxicity CTCAE grade None 52% Grade 1 35%$ Grade 2 12% Grade 3 1% Late toxicity CTC-AE grade None 77% Grade 1 12% Grade 2 6% Grade 3 5% Grade 4 1% Analysis of factors related to LR?

Grade 2 12% Grade 3 1% Late toxicity CTC-AE grade None 77% Grade 1 12% Grade 2 6% Grade 3 5% Grade 4 1% Analysis of factors related to LR?

033) Local control correlates with clinical i l factors; unrelated to SABR delivery Technical improvements unlikely to improve local control

8 Toxicity of SABR Early toxicity Incidence Fatigue 25% Cough 14% Chest wall pain 11% Dyspnea 10% Nausea 3% Skin erythema 3% Late toxicity Incidence Rib fracture 3% Chest wall pain 3% Radiation pneumonitis 2% Pleural effusion 1% Early toxicity CTCAE grade None 52% Grade 1 35% Grade 2 12% Grade 3 1% Late toxicity CTC-AE grade None 77% Grade 1 12% Grade 2 6% Grade 3 5% Grade 4 1% Analysis of factors related to LR? Not correlated with LC Fractionation (BED 10 ) SABR technique Correlated with LC T-stage (p=0.012) Age (p=0.033) Local control correlates with clinical i l factors; unrelated to SABR delivery Technical improvements unlikely to improve local control further Too much statistics. or can we tailor? Age & T-stage Age 75 and T 3 cm LC@3 years 99.2% Age <75 and T >3 cm LC@3 years 85.0% Pts with highest surgical risk, have the best LC.. 8

9 Who is referred for lung SABR? Survival, or the quality of survival? Nationwide Inpatient Sample, 1994 to 2003 (Finlayson E, 2006) 9

data [Surapaneni R, 2012] Risk of second lung cancer highest in 1 st year with the O/E at 6.78 (CI: 6.

10 Marginally operable (high-risk) patients Potential gains to be achieved Reduce mortality of initial treatment Survival with acceptable QoL Fitness to undergo Rx for 2 nd tumors and recurrences SEER data [Surapaneni R, 2012] Risk of second lung cancer highest in 1 st year with the O/E at 6.78 (CI: ) and continues to be high at 10 years (O/E 4.12; CI: ) SABR for operable Stage I NSCLC 10

11 Defining potentially operable patients From a total of 801 pts in the VUmc SABR database, potentially operable pts were retrospectively identified by excluding those with: Prior high-dose (chemo-)rth Prior pneumonectomy GOLD Class 3 WHO performance score 3 Major cardiovascular morbidity Concurrent other malignancy Major comorbidity, e.g. recent CVA 211 potentially operable patients Characteristics of operable patients 11

SABR for fitter, operable patients 211 potentially operable patients (26% of referrals to Vumc

5% operable Operable pts Median survival >5 years (NR) 30-day mortality 0% inoperable 2-year

years 2001-2003 37% 31% 32% 2003 SABR introduced 2004-2006 36% 33% 31% Surgery Radiotherapy

12 SABR for fitter, operable patients 211 potentially operable patients (26% of referrals to Vumc ) Predicted 30-day mortality for lobectomy (Thoracoscore): 2.5% operable Operable pts Median survival >5 years (NR) 30-day mortality 0% inoperable 2-year survival 87% 3 year survival 84% 5 year survival 62% years 95% RC@3 years 90% DC@3 years 90% Lagerwaard et al., IJROBP 2011 [updated] Dutch national analysis ( ) 4605 stage I NSCLC patients aged 75 years % 31% 32% 2003 SABR introduced % 33% 31% Surgery Radiotherapy Neither % 38% * 25% 0% 20% 40% 60% 80% 100% Percentage of patients aged 75 years or older with stage I NSCLC * estimated utilization of SABR in radiotherapy group was >75%, Haasbeek C,

13 Overall survival of patients with stage I NSCLC aged 75years in the Netherlands treated between 2007 and 2009 CJA Haasbeek;WCLC 2011 Combined data of overall survival of patients with stage I NSCLC aged 75 years in the Netherlands, and 177 potentially operable SABR patients (median age 76) treated in the VUmc 13

SABR for Stage I NSCLC Mature local control rates of >90% at long follow-up Provocative personal

.): Unlikely that technical innovation will further improve SABR outcome SABR may be preferred over

Surgical risk is higher AND outcome (LC 99%) of SABR is better in patients aged 75 years In view of

14 SABR for Stage I NSCLC Mature local control rates of >90% at long follow-up Provocative personal statements (don t blame the organizers..): Unlikely that technical innovation will further improve SABR outcome SABR may be preferred over surgery in elderly patients with T1a-b tumors. Surgical risk is higher AND outcome (LC 99%) of SABR is better in patients aged 75 years In view of the favorable long-term results of SABR in borderline operable patients: why not perform mediastinal staging, SABR, follow-up. Reserve surgery for early recurrence? SABR for Stage I NSCLC Thank you for your patience. 14

Stereotactic ablative radiotherapy in early NSCLC and metastases

Stereotactic ablative radiotherapy in early NSCLC and metastases Scheduled: 0810-0830 hrs, 10 March 2012 Professor Suresh Senan Department of Radiation Oncology SABR in stage I NSCLC A major treatment