TRATTAMENTO COMBINATO RADIO- CHEMIOTERAPICO NEL III STADIO NSCLC

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1 TRATTAMENTO COMBINATO RADIO- CHEMIOTERAPICO NEL III STADIO NSCLC Dr.ssa Sara Ramella Radioterapia Oncologica Campus Bio-Medico

2 Trimodality therapy offers a promising chance of long-term survival Evidenze di letteratura Problematiche da affrontare Difficoltà del restaging post terapia di induzione La tossicità del trattamento neoadiuvante

3 Betticher DC et al. Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pn2 non-small-cell lung cancer: a multicenter phase II trial. Nodal clearance rate 31% ( 25% if the entire population of 90 patients) Recent update analysis, a post- surgery local recurrence rate of 60% has been reported. On the basis of this dismal evidence, the Authors themselves affirm that additional efforts should also be focused.. a combined approach J Clin Oncol May 1;21(9):

4 524 pts CT+RT-CT + surgery CT + Surgery Mediastinal Downstaging Pathological Response 45/98 [46%] 59/98[60%] p= /84 [29%] 17/84 [20%] p< Lancet Oncol 2008; 9:

5 The aim of this approach is, via a radical surgery, to obtain a pathological downstaging by essentially clearing the disease at the nodal level: this is directly correlated with an improved survival Percent Survival pstage II-III pstage 0-I Time Trodella L, Annals Oncol 2004 Choi 97 Uy 07- Toronto University D Angelillo RM, Trodella L, JTO 2009

6 Lung Intergroup Trial 0139 Study Design R A N D O M Radical RT-CT RT: 61 Gy Standard frx CT: CDDP 50 mg/m 2 d1,8,29,36 VP16 50 mg/m 2 d1-5,29-33 Neoadj RT-CT Surgery RT: 45 Gy Standard frx CT: CDDP 50 mg/m 2 d1,8,29,36 VP16 50 mg/m 2 d1-5,29-33 N of patients: Radical RTCT 201; Neoadjuvant RTCT: 191

7 PFS OS

8 Overall Survival Lobectomy Pneumonectomy

9 pn0 pn1-3 No Surgery

10 20 years experience: Intensifying chemotherapy improves results in neoadiuvant concurrent chemoradiation for lung cancer 306 pts Lymphonodal clereance % percentage (%) % 39.1% CBCDA-PLAFUR GEM P-GEM Trodella L, Ramella S, D Angelillo RM

11 CT Neoadiuvante Downstaging RT-CT Neoadiuvante Author pcr pn0 Van Zandwijk % 19.1% Betticher % 25.6% Migliorino % 10% De Marinis % 34.7% Cappuzzo % NR Leon % NR Burkes % 18.5% Ramnath % 3% Mean 6.2% 18.4% Author pcr pn0 SWOG 95 15% 38.1% Milstein % NR ESSEN % 27.8% Machtay 04 16% 28.3% Park % 38% Trodella 06 17% 39% Mean 14.5% 32.1%

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13 Trimodality therapy offers a promising chance of long-term survival Evidenze di letteratura Problematiche da affrontare Difficoltà del restaging post terapia di induzione La tossicità del trattamento neoadiuvante

14 Tumor Volume as a Potential Imaging-Based Risk Stratification Factor in Trimodality Therapy for Locally Advanced Non-small Cell-Lung Cancer Tumor Volume (GTV) pre and post Radiation correlates with PFS Kozak M. JTO vol. 6 num. 5 May 2011

15 Comparison of CT Alone, PET Alone, and PET-CT for Detection of Residual Mediastinal Nodal Disease After Induction Chemotherapy P De Leyn et al., J Clin Oncol 24 (21) JULY 2006

16 Trimodality therapy offers a promising chance of long-term survival Evidenze di letteratura Problematiche da affrontare Difficoltà del restaging post terapia di induzione La tossicità del trattamento neoadiuvante

17 Safety

18 Safety Conoscenze gestione dei farmaci e prevenzione dei disturbi Conoscenze radiobiologiche e sviluppo della tecnologia radioterapica

19 Safety D Angelillo RM, Trodella L, JTO 2009

20 Radioterapia: Volumes, Doses and Constraints

21 Radioterapia: Volumes, Doses and Constraints Letteratura con chirurgia dopo dosi 60Gy: New Technologies Krasna et al., Ann Thorac Surg 2010;89:200 6 Certfolio et al, European Journal of Cardio-thoracic Surgery 35 (2009)

22 1372 pts; cn2; Coate,.. Shepherd, JTO March 2011

23 PROGETTO R.E.S.P.I.RO Ricerca E Survey Polmonare In Radioterapia Oncologica IN ITALIA 143 CENTRI DI RADIOTERAPIA CENSITI NEL SITO AIRO (Aprile 2009) 65 PARTECIPANTI ALLA SURVEY Totale dei pazienti NSCLC: Ramella S., Maranzano E, Tumori 2012

24 PROGETTO R.E.S.P.I.RO Ricerca E Survey Polmonare In Radioterapia Oncologica 70% dei centri si dichiara disponibile al trattamento neoadiuvante Ramella S., Maranzano E, Tumori 2012