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Società Triveneta di ChirurgiaAviano, 25 Febbraio 2012
Carcinoma Gastrico
Localmente Avanzato:Terapie
Integrate
Progetto NEOX-RT
Antonino De Paoli
UO Oncologia Radioterapica, CRO Aviano
Gastric Cancer - Current Issues
Changing epidemiology(diagnosis and treatment implications)
Curative surgery (mainstay of treatment)
Adjuvant chemotherapy(still controversial)
Adjuvant chemoradiation(possible benefit)
Perioperative chemotherapy(possible benefit)
Neo-adjuvant and adjuvant therapy for gastric cancer: different strategies
Post-operative
Chemoradiotherapy
(trend to preoperative CT-RT
in academic centers)
Peri-operative
Chemotherapy
(ECF- 5FU/cisplatin)
Post-operative
Chemotherapy
(S-1 or combination)
Postoperative CT
Ongoing Trials
US (Intergroup Trial)
Post-op 5FU/LV + RT/5FU vs ECF + RT/5FU(Does ECF improve efficacy of post-op CRT?)
EUPeriop ECX vs Periop ECX-BEV (MAGIC-B)
(Is there a role of biologics?)
Preop ECX-Surg-postop ECX vs RT/X-DDP (CRITICS)(What is the role of postop CT-RT?)
Preop ECX x3 vs ECX x2-RT/X+postop ECX (EORTC)(What is the role of preop CT-RT?)
JapanAdjuvant S1 vs Surgery alone
Cosa fare nella pratica clinica
• T3 N0 no terapia
• T2/3/4 N+ terapia con 5FU, o ECF o CDDP, de Gramont MitC.
• Se chirurgia inadeguata (Lfn <15 LN, R1) RT-CT
• Se chirurgia adeguata, ma elevato N-ratio (>25%) RT-CT
Cascinu S - IRST Meldola, 2010
Japanese Research Society for
Gastric Cancer
1 right paracardium
2 left paracardium
3 lesser curvature
4 greater curvature
5 suprapylorum
6 infrapylorum
7 left gastric artery
8 common hepatic artery
9 celiac artery
10 splenic hilum
11 proximal splenic artery
12 hepatoduodenal ligament (a,b,p)
13 posterior surface of the pancreatic head
14 superior mesenteric vessels
15 middle colic vessels
16 abdominal aorta
41
58
613
17
1011
14
12b+p
16b1
20
110
20
4
1011
14
6
111
12b+p5
4
3
1
5
812b+p
6
Macdonald
281 pts%
RT-CT compliance
Korean
544 pts%
64.0 75.0G3 Acute Tox
G4 Acute Tox
41.0
32.0
23.5
6.0
PostOp RT-CT Toxicity
Macdonald JS et al – NEJM -2001
Kim S et al – IJROBP – 2005
Mattiucci GCet al – ESTRO- 2010
Italian pool
348 pts%
96.0
14.2
CENTRI PARTECIPANTI
Trieste
Aviano
Padova
Firenze S.M. Annunziata
Firenze
Chieti
Ancona
Viterbo
Varese
Arezzo
Roma UCSC
Siena
Rionero in
Vulture
Barletta
S.G.Rotondo
Taranto
Perugia
MeldolaIvrea
AIRO-GI Working Group
Ongoing Trials
Italy
ITACAS-2 Phase III Study
Periop vs post-op EOX and assessment of
benefit of post-op RT/Cape
DOX Phase II randomised Study
Periop DOX vs Preop DOX
NEOX-RT Phase II Study
Preop EOX + RT/OX
Sponsor: Istituto di Ricerche Farmacologiche “Mario Negri”
Supported by: AIFA
Medical Oncology: Francesco Di Costanzo (P.Investigator)
Radiation Oncology: Vincenzo Valentini
Surgery: Donato Nitti
ITACA-S 2 (Intergroup Trial in Adjuvant Chemotherapy for Adenocarcinoma
of the Stomach 2):
Comparison of the efficacy of a peri-operative versus a post-operative
chemotherapy treatment in patients with operable gastric cancer and
assessment of the benefit of a post-operative
chemo-radiotherapy
STUDIO ITACA-S 2
MAGIC
ITACA-S1
CRITICS
INT-0116
Disegno dello Studio
Preoperative
Chemoradiotherapy
in Castric Cancer-
The MD Anderson
. experience
pCR: 23% - R0 Rate: 95%
Post Op Compl: 38%
Post Op Death: 2.8% Fujitani K et al Ann Surg Oncol 2007
Reed VK et al IJROBP 2008
Post-op mortality: 5.6% vs 5.9%
Post-op morbility: 46% vs 45%
Post-op hosp stay (med): 13 d vs 13 d
MAGIC data, NEJM 2006
Ajani JA et Al – JCO – 2005
Cunningham et Al - NEJM – 2006Sthal M et al- JCO-2009
The risk of tumour progression
Neoadjuv ChemoRT in Gastric Cancer
MDACC
9/41 (22%) not resected for PD at surgery
Magic trial
37/209 (18%) not resected for PD at surgery
German trial
12/119 (10%) not resected for PD at surgery
INT-0116
Valentini V et al, Tumori 2008
Magic
D2 = 10% D2 = 40%
The “L” shape survival curve of Gastric Cancer
NEOX-RT Study
NEOADJUVANT
EPIRUBICIN-OXALIPLATIN-XELODA AND
OXALIPLATIN-XELODA RADIOTHERAPY
IN LOCALLY ADVANCED, RESECTABLE,
GASTRIC CANCER
A PHASE II COLLABORATIVE STUDY
Actived March 2009
NEOX-RT StudyPatients with locally advanced uT3-4,N0 or any uT,N+M0(LPS)
potentially resectable, EGJ(II-III)-Gastric Cancer
Induction
chemotherapy EOX x 3 cycles (q 3weeks)
for 9 weeks
Patients with early metabolic
disease progression (CT-
PET) will undergo to
immediate surgery
Responding pts CT-PET evaluation after 2
cycles EOX
Objective Response
(Endoscopy/EUS)
after 9 weeks
Chemoradiotherapy
RT 45 Gy
+ Oxaliplatin-Xeloda
for 5 weeks
Restaging CT-PET
CT abdomen and chest
Objective Response
(Endoscopy/EUS)
after 4 weeks from CT-RT
Surgery Week 22
SURGERY +/- IORT
4-6 weeks after chemoradiotherapy
Path Response Rate
R0 Resection Rate
Treat Compliance
NEOX-RT Study
Pre-Op CT
EOX x 3
Pre-Op CT-RT
OX + 45Gy (+/-CB)
Surgery +/-IORT
D2 10 Gy
1 - 9 12 - 16 21 - 22
weeks
CT-PET CT-PET CT-PET
Tissue banking
Nutritional monitoring and support
Quality of Life
Epirubicin 50 mg/m2 d1 3D-CRT 45Gy/25fr +/- 10Gy/10fr, 2 weekly
Oxaliplatin 130mg/m2 d1 Oxaliplatin 30mg/m2, weekly
Xeloda 625mg/m2 bid d1-21 Xeloda 625mg/m2, bid, d1-35
Use the following general planning
guidelines for therapy
Prerequisite Step
N
Procedure
Presumed loco-regional
cancer
1 Clinical staging and Endoscopic Ultrasound,
CT-PET
Non-metastatic cancer 2 Laparoscopy and peritoneal staging
No peritoneal cancer and
eligibility criteria
fulfilled
3 Get consent, register and start preoperative
Chemotherapy
Completed preoperative
chemotherapy (if CT-
PET responsive)
4 Rest 2 weeks then start preoperative
Chemoradiotherapy
Completed preoperative
chemoradiotherapy
5 Rest 4-5 weeks then proceed with
preoperative work-up
Non-metastatic cancer 6 Attempt Surgery +/-IORT
Completed all therapy 7 Follow-up for 5 years or until death
NEOX-RT Study - Investigator
BoardStudy Coordinator
Mario Lise
Centro di Riferimento Oncologico, Aviano
Chair Investigators
Surgeon
Domenico D’Ugo
Università Cattolica S.Cuore, Roma
Donato Nitti
Università di Padova
Francesco De Marchi
Centro di Riferimento Oncologico, Aviano
Alberto Marchet
Università di Padova, Padova
Radiation Oncologist
Antonino De Paoli
Centro di Riferimento Oncologico, Aviano
Vincenzo Valentini
Università Cattolica S.Cuore, Roma
Medical Oncologist
Carlo Barone
Università Cattolica S.Cuore, Roma
Sergio Frustaci
Centro di Riferimento Oncologico, Aviano
Data management
Clinical Trial Office
Centro di Riferimento Oncologico, Aviano
NEOX-RT Centri Partecipanti
CRO-Aviano Onc Chir, OncMed, OncRad
Ospedale Pordenone I°Chir, II°Chir, Onc Med
Ospedale S.Vito Chir, Onc Med
Ospedale Spilimbergo Chir, Onc Med
Ospedale Portogruaro Chir, Onc Med
UniversitàPD-IOV II°Clin Chir, OncMed, RadOnc
UCSC Roma I°Clin Chir, OncMed,RadOnc
SFN Roma Chir, OncMed, RadOnc
Ospedale Trento I°Chir, II°Chir, OncMed, RadOnc
Statistical considerations and
Sample Size
Primary end-point: pCR (all entered patients)
Sample size: 49 patients
pCR difference 15% (p0=5%; p1=20%)
I° Step 21 patients; if >1pCR, II° Step 20 patients.
Overall 41 patients; if 85% path asssessed,
TOTAL 49 patients
Simon’s two stage design
NEOX-RT Accrual 3-09 to 2-012
Patients accrued: 18
Completed Preop Program: 13
Ongoing Preop Program: 3
Underwent to Surgery: 14 (2pCR)
1 patient had emergency operation (bleeding)
1 patient drop-out (refusal)
1 patient had postop complication (re-operation)CRO 2008
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