Gastric Cancer

Ahmed ZeeneldinAssociate professor of Medical

OncologyNCI, CU

TNM Staging• T1

– T1A: mucosa– T1B: Submucosa

• T2: Muscle• T3: subserosa• T4

– T4A: serosa (visceral peritoneum) only– T4B: adjacent organs

• N1: 1-2 regional LN+• N2: 3-6• N3: =>7

– N3A: 7-15– N3B: >15

• M1: Mets

Stage• IA,B• IIA,B• III A,B,C• IV: M1

Treatment Stage TNM Neoadj

TTTGastrectomy

AdjTTT

Palliative

Early IA T1a mucosa No May/EMR

No No

T1b Sub-mucosa

No Yes No No

Late IV M1 Mets No No MainCT

M0 IB-IIIC* Irresctunfit 4 S

T4 or others

CT or CCRT

May inCR or mPR

may after S CT or CRT

May in <mPR

Resectable

May**CT (1st) or CCRT (2nd)

May (3rd) Contin ECFx 3if not given b4 SCT or CRT

MayCT or CCRT

* Laparscopic staging b4 surgery** preop CT > CRT are prefered to surgery (CT>CRT>S)Patients unfit 4 S can receive CRT or CT

Post surgical treatment

Surgery

• Gastrectomytypes:– Distal– Subtotal– Total

• Lymphadenctomy:– D1– D2

Principles of Surgery• Aim: complete resection with negative margins (=>4 cm)• Residaul (R)

– R0: no residaul– R1: microscopic (+SM)– R2: microscopic

• Gastrectomy: Distal is better than total in tolerance and nutrition with similar outcomes

• D1 vs D2: is debatabele– Japanese recommend D2– Westerns do not– NCCN: recommends D2 as a retrospective SEER trial showed advantage

• If post-operative CRT will be given, jejenostomy feeding tube may be put

Chemotherapy

Pre and postoperative• Operable cases• GE junction and AC included• Category 1 Regimens

– ECF (Epirubicin, cisplatin and 5-FU)

– ECF modifications

Palliative• In metastatic or locally Advanced

where chemoradiation is not recommended:

• Category 1 regimens:– DCF (Docetaxel, cisplatin and 5-FU)– ECF – ECF modifications

• Category 2 regimens:– Irinotecan plus cisplatin– Oxaliplatin plus fluoropyrimidine (5-

FU or capecitabine) – DCF modifications– Irinotecan plus fluoropyrimidine (5-

FU or capecitabine) – Paclitaxel-based regimen – Trastuzumab

Chemoradiotherapy

Preoperative Chemoradiation: • Docetaxel or paclitaxel plus

fluoropyrimidine (5-FU or capecitabine) (category 2B)

• Cisplatin plus fluoropyrimidine (category 2B)

Postoperative ChemoradiationADJUVANT

• GE junction denocarcinomaincluded

• Fluoropyrimidine (5-FU or capecitabine) (category 1)

Site shift in GC

• USA and some Europe• More:

– Proximal Lesser curve– Cardia– GE junction

• Other parts of the world (Japan, China)– Non-proximal

• Why: ? Reflux, food health

Incidence

• 4th woldwide• Commonest in Japan, China• In Egypt:

Risk factors

• Infection: H pylori• Smoking• High salt intake• Other dietary factors• Hereditary (1-3%)

Prognostic factors

• Stage: TNM– T: increasing T– N: higher numbers of positive LNS– M: presence of mets

• Grade: undifferentiated tumors• Poor PS• High LDH

Perioperative chemotyherapy

14

MAGIC trial

S ECF-S-ECF P

253 250

Median OS 20 26 0.008

5- Year OS 23% 36%

Median PFS 13 20 <0.001

HR of death 1 0.75 0.008

HR of progression 1 0.66 <0.001

16

• MRC (MAGIC trial)• Resectable gastric (74%) , lower esophagus (14%),

EGJ (11%)• S vs ECFx3àSàECFx3• # 253 250• 5y OS 23 36%• PFS HR 0.66• Down-staging Cunningham N Engl J M 355(1). 2006

Adjuvant CRT in gastric and GE AC

Design

inclusion: =>T2 or LN+

Before RT: one cycle5FU: 425 mg PSM D1-5LV: 20 mg PSM D1-5

Concomitant CRT: two cyclesRT: 4500 CGy (25 F in 5 weeks)5FU: 400 mg PSM 1st 4 & last 3 daysLV: 20 mg PSM 1st 4 & last 3 days

One month Post RT: two cycle q 4w5FU: 425 mg PSM D1-5LV: 20 mg PSM D1-5

Dose reduced for G3/4 toxicities

Results

S S+CRT P

275 281

Median OS 27 m 36 m 0.005

Median RFS 19 m 30 m <0.001

HR of death 1.35 1 0.005

HR of relapse 1.52 1 <0.001

Toxic death 0 3 pts (1%)

G3/4 toxicities 41/32 %

Chemotherapy for advanced or metastatic disease

Capecitabine and oxaliplatin in G,E, EG caREAL-2 trial

CocclusionsECF ECX EOF EOX P

N 249 241 241 239

Median OS (m) 9.9m* 9.9m 9.3m 11.2m* * Sig

1-year S 38%* 41% 40% 47%* *Sig

ORR 41% 46% 42% 48% NS

CRR 4% 4% 2.6% 4% NS

PFS 6.2 m 6.7m 6.5m 7m NS

Capetiabine is similar to FUOxaliplatin is similar to cisplatinEOX is better than ECX

ML studyCapecitabine cisplatin (XP) vs 5FU cisplatin (FP)

XP FP

RR 41% 29%

Median OS 10.5 m 9.3 m

PFS similar similar

Metaanalysis of capetcitabine in GC

Capecitabine 5FU P

Median OS 10.7 m 9.5 m 0.027

Median PFS 6.6 m 6 m NS

RR 46% 38% 0.006

independent predictors of poor survival •Poor performance status, •age <60 and•metastatic disease.

Benefit of capecitabine

S1 in gastric carcinoma

OS PFS

S1P S1 P

Median OS 13 m 11 m S

Median PFS 6 m 4 m S

RR 54% 32% 0.002

CS FS

521 508

Median OS 8.6 m 7.9 m 0.2

Safety and tolerance

Better Worse

Anti-HER2 in gastric cancer

ToGa trial

FP/XP FPT/XPT

300 300

Median OS 11.1 m 13.5 m S

Safety comparable

CHF No No

Omitting cisplatin

Irinotecan, however, is best suited after front- line therapy

Adding Docetaxel

TTP OS