Applicazione Clinica: Polmone Andrea Riccardo Filippi Dipar5mento di Oncologia Università di Torino
A technique for delivering external beam radiotherapy i. with a high degree of accuracy to an extra-cranial target, ii. using high doses of irradiation, iii. in 1-8 treatment fractions. 4-D imaging Sophisticated plans CT scan on treatment couch Delivery in <4 mins (FFF) S. Senan, M. Guckemberger, U. Ricardi Stage I NSCLC and oligometasta5c disease The IASLC Mul5disciplinary approach to Thoracic Oncology, 2014
SABR for peripheral lung tumors ESMO Clinical Prac5ce Guidelines 2013: SABR is the non surgical treatment of choice (dose to a biologically equivalent tumor dose > 100 Gy) NCCN guidelines (version 3.2014): non surgical treatment of choice
SABR for Stage I NSCLC: phase II studies Loo et al, Discovery Medicine 2011 UNIVERSITA DEGLI STUDI DI TORINO
Mono- ins5tu5onal largest study, with/without histological diagnosis 676 pa5ents Median follow- up 5me: 32.9 months Senthi et al, Lancet Oncol 2012 UNIVERSITA DEGLI STUDI DI TORINO
German Society for Radia5on Oncology (DEGRO) Observa5onal Mul5centric Study OS @3 years 47.1% [Guckenberger et al, JTO 2013]
SABR in stage I histologically proven NSCLC: an Italian mul5center observa5onal study 2B OVERALL SURVIVAL 1,0 0,8 0,6 0,4 0,2 OVERALL SURVIVAL % 1 year: 94.0 % 2 years: 81.6 % 3 years: 68.0 0,0,00 12,00 24,00 36,00 48,00 60,00 72,00 84,00 96,00 Time since enrollement (months) Ricardi et al, Lung Cancer 2014 Number at risk 196 165 107 63 37 15 7 4 1
SABR 2014: surgical viewpoints Await results of randomized clinical trials Late local recurrences may be a problem Upstaging occult nodal disease is beneficial SABR is equivalent to a wedge excision
Trials of surgery versus SABR Morganaki D, unpublished
SPACE - A - A randomized study of of SABR vs vs modern convenuonal RT RT (3D- CRT) in in medically inoperable stage I I NSCLC From 2007 to 2011 102 pa5ents Results ARM A MST 41.3 months OS @ 2 years 65% @ 3 years 34% Pneumoni5s (any G) 16% Esophagi5s 9% R ARM A: SABR (66 Gy/ 3 fr) ARM B: 3D- CRT (70 Gy/ 35 fr) ARM B MST 42.1 months OS @ 2 years 62% @ 3 years 34% Pneumoni5s (any G) 34% Esophagi5s 32% SABR is much more convenient for the pa5ent and more cost effec5ve standard treatment for inoperable pa5ents with stage I NSCLC Nyman J et al, ESTRO 2014 (abstract)
SABR - some surgical viewpoints Await results of randomized clinical trials Late local recurrences may be a problem Upstaging occult nodal disease is beneficial SABR is equivalent to a wedge excision
Recurrences following surgery (n= 1294 pts) Lou F, JTCVS 2012
Time to distant failure Senthi et al, Lancet Oncol 2012
Murthy SC et al, Ann Thorac Surg 2010 N = 285 pa5ents from Cleveland Clinic
SABR - some surgical viewpoints Await results of randomized clinical trials Late local recurrences may be a problem Upstaging occult nodal disease is beneficial SABR is equivalent to a wedge excision
Stage I NSCLC: Recurrence paherns Propensity score- matched analysis of stage I- II NSCLC treated using either SABR or VATS- lobectomy 86 VATS- lobectomy and 527 SABR pa5ents eligible Nodal staging in VATS group in accordance with ESTS guidelines Matching covariates: Gender - Age ctnm - Tumor diameter Histology - Tumor loca8on FEV 1% - WHO score Charlson comorbidity Verstegen et al, Annals of Oncology 2013
Common terminology for recurrences Propensity- score matched analysis [Verstegen NE, 2013]: Locoregional control was defined as the absence of a recurrence adjacent to the surgical margin or planning target volume, and/or in the ipsilateral hilum/ medias5num ACCP- STS, Chest 2012
Propensity score- matched analysis Verstegen et al, Annals of Oncology 2013
Propensity score- matched analysis Verstegen et al, Annals of Oncology 2013
SABR - some surgical viewpoints Await results of randomized clinical trials Late local recurrences may be a problem Upstaging occult nodal disease is beneficial SABR is equivalent to a wedge excision
SABR is not comparable to wedge excision Grills I, JCO 2010: Outcomes of SABR or wedge excision at single- ins5tu5on Freedom from local failure Freedom from regional failure
T1, GOLD I- IV T2, GOLD I- II R&O, 2011
Stage I- II NSCLC and severe COPD? Systema5c Review: Eligible pa5ents had to have GOLD III- IV or a predicted postopera5ve FEV 1 of 40% Palma D et al, IJROBP 2012
Palma et al, JCO 2010
Prognos5c factors?
Cox Regression Mul5variable Analysis on Histologically Proven NSCLC in Italian observa5onal cohort study Table 3 Multivariate analysis. Parameter LR DFS OS CSS HR (95% CI) p HR (95% CI) p HR (95% CI) p HR (95% CI) p Stage IB vs IA 0.55 (0.03 10.3) 0.69 3.06 (1.62 5.77) 0.001 * 2.46 (1.28 4.74) 0.007 * 3.47 (1.50 7.98) 0.003 * GTV volume >13 cc vs 13 cc 4.4 (0.73 26.7) 0.1 1.04 (0.57 1.88) 0.89 1.04 (0.59 1.82) 0.89 1.37 (0.59 3.16) 0.45 Sex Male vs Female 0.5 (0.08 3.2) 0.47 1.05 (0.57 1.92) 0.87 0.94 (0.51 1.74) 0.86 0.79 (0.31 1.98) 0.61 Age >75 years vs 75 years 0.6 (0.15 2.57) 0.52 1.39 (0.83 2.36) 0.21 1.39 (0.83 2.32) 0.2 1.28 (0.63 2.61) 0.49 Histology Adenocarcinoma vs others 2.42 (0.39 14.84) 0.34 1.12 (0.64 1.97) 0.68 1.21 (0.68 2.16) 0.8 1.17 (0.52 2.61) 0.69 Abbreviations: LR, local recurrence; DFS, disease-free survival; OS, overall survival; CSS, cancer-specific survival; HR, hazard ratio; CI, confidence interval. 3A CANCER SPECIFIC SURVIVAL 3B OVERALL SURVIVAL 1,0 - Stage IA - Stage IB 1,0 - Stage IA - Stage IB 0,8 0,8 0,6 0,6 0,4 0,4 0,2 0,2 Log rank p < 0.001 Log rank p < 0.001 0,0 0,0,00 12,00 24,00 36,00 48,00 60,00 72,00 84,00 96,00 Time since enrollement (months) Number at risk Stage IA 155 137 98 58 34 14 7 4 1 Stage IB 41 28 9 6 3 0 0 0 0,00 12,00 24,00 36,00 48,00 60,00 72,00 84,00 96,00 Time since enrollement (months) Number at risk Stage IA 155 137 98 58 34 14 7 4 1 Stage IB 41 28 9 6 3 0 0 0 0
Mul5variate analysis form the DEGRO Observa5onal Mul5centric Study Guckenberger et al, JTO 2013
Toxicity and Quality of Life
Poor baseline PFT did not predict decreased OS FEV1 mean decline 5.8%; DLCO mean decline 6.3% (SS at 6 weeks and 3 months) Minimal changes of arterial blood gases and no decline in oxygen saturation Stanic S et al, IJROBP 2014
SABR and Quality of Life No declines in QoL reported after SABR van der Voort van Zyp NC, IJROBP 2010 Widder J, IJROBP 2011 Lagerwaard F, JTO 2012 Videtic GM, Support Care Cancer 2013
Quality of Life self assessed Lagerwaard et al, JTO 2012
SABR in Lung Mets
Before tumors metastasize When combined with adjuvant therapies for the treatment of micrometasta5c disease To eradicate oligometastases To poten5ally eradicate residual disease aver effec5ve systemic treatments SABR is one of the best treatment opuons, with increasing potenual Nature Clin Pract Oncol, 2005
Clinical Trials on SABR for Lung Oligometastases Schulz, Filippi et al, J Thor Oncol 2014
Consecu5ve pa5ents treated between 2007 and 2010 (68 PME and 42 SABR) PME: first choice S A B R : s e c o n d b e s t alterna8ve 3- ys OS years acer SABR: 60% 3- ys OS acer PME: 62% Widder et al, R&O, 2013
Aknowledgements Thoracic Oncology Unit University of Torino Radia5on Oncology: Cris5na Mantovani, Alessia Guarneri, Serena Badellino, Umberto Ricardi Medical Oncology: Lucio Buffoni, Silvia Novello, Giorgio V. Scagliow Thoracic Surgery: Enrico Ruffini Pneumology: Paolo Solidoro