La Radioterapia nel Trattamento IntegratoQuali vantaggi dalla valutazioneQuali vantaggi dalla valutazione 

biologico/molecolare?

S. ArcangeliU O C RadioterapiaU.O.C. Radioterapia

Azienda Ospedaliera San Camillo – ForlaniniRoma

Is Definitive Therapy Justified2013

pyin Lung Cancer Patients

ith Oligometastatic Disease ?with Oligometastatic Disease ?

Site 1976 1982 1994 2008

6 8 90Breast 75 76 85 90

Colon 50 55 63 65viva

l

Prostate 67 73 93 100

-y S

urv

Rectum 48 52 61 68

Lung 12 13 14 17

5-

CA CANCER J CLIN 2013

20132013

2014

Surgery for Lung Metastasesg y g

2013

• From 1999-2012, 61 NSCLC patients with 1-3 oligomets

received definitive treatment to all sites of disease, pooled

from 2 large cancer centers in Netherlands and Canadafrom 2 large cancer centers in Netherlands and Canada

• 82% solitary met, 15% 2 mets, 3% 3 mets

• Location: 59% brain; 18% bone; 7% each for

contralateral lung, adrenal, and distant LN.

2013

2013

A l i f RCTA meta-analysis of 5 RCTs of Chemotherapy: 2-year OS = 20%

Laporte S, BMJ Open 2013p , p

2-year OS: 38%

2013

5 year OS: 23.3% (8.3–86%)

2013

• 60% of studies included patients withp

brain metastases only

• neither intervention is supported by level

1 evidence from RCTs

long-term survival reflective of patient

selection, or a treatment effect ?

2012

Median OS: 13,5 mos Median PFS: 12,1 mos

15% patients were progression free after 2 years

2014

Median OS 26 months, 5-year OS 29.4 %

Average 5-year OS = 2% for stage IV NSCLCAverage 5 year OS = 2% for stage IV NSCLCRami Porta R, Ann Thorac Cardiovasc Surg 2009

2012

50%

65%

Non Small Cell Lung Cancer: F Hi t l T G iFrom Histology To Genomics

Adk (70%)“Druggable” genomic alterations

Ad i EGFREGFR

Druggable genomic alterations

Kinases Adenocarcinoma EGFRUnknown EGFRUnknownKinases

Critical to growth & survival of

KRAS

MET

KRAS

MET

& survival of NSCLC

EML4-ALKPIK3CAERBB2

MET Amplification

EML4-ALKPIK3CAERBB2

MET Amplification

BRAFPIK3CA

ERBB2MEK1ERBB2

Amplification BRAFPIK3CA

ERBB2MEK1ERBB2

Amplification

The “Darwinian” oncology

Targeted therapies: molecular vs spatialg p p

2012

2014

SABR Definition

Future Directions

Changing MindsetPERSONALIZED MEDICINE: A PARADIGM SHIFT IN HEALTHCARE

The right treatment

At the right dose

F th i ht ti tFor the right patient

At the right time

For the best outcome

NSCLC ALK + CRIZOTINIB RT+CRIZOTINIB