Comprehensive overview of gastric Cancer: staging, diagnosis, and treatment

1. Gastric Cancer
Ahmed Zeeneldin
Associate professor of Medical
Oncology
NCI, CU

2. 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 Stage
• N3: =>7 • IA,B
– N3A: 7-15
– N3B: >15 • IIA,B
• M1: Mets • III A,B,C
• IV: M1

3. Treatment
Stage TNM Neoadj Gastr Adj Palliative
TTT ectomy TTT
Early IA T1a mucosa No May/ No No
EMR
T1b Sub- No Yes No No
mucosa
Late IV M1 Mets No No Main
CT
M0 IB-IIIC* Irresct T4 or CT or May in may after S May in
unfit 4 S others CCRT CR or mPR CT or CRT <mPR
Resec May** May (3rd) Contin ECFx 3 May
table CT (1st) or if not given b4 S CT or
CCRT (2nd) CT or CRT CCRT
* Laparscopic staging b4 surgery
** preop CT > CRT are prefered to surgery (CT>CRT>S)
Patients unfit 4 S can receive CRT or CT

4. Post surgical treatment

5. Surgery
• Gastrectomy
types:
– Distal
– Subtotal
– Total
• Lymphadenc
tomy:
– D1
– D2

6. 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

7. Chemotherapy
Pre and postoperative Palliative
• Operable cases • In metastatic or locally Advanced
where chemoradiation is not
• GE junction and AC included recommended:
• Category 1 Regimens • Category 1 regimens:
– DCF (Docetaxel, cisplatin and 5-FU)
– ECF (Epirubicin, cisplatin and 5-FU) – ECF
– ECF modifications – 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

8. Chemoradiotherapy
Postoperative Chemoradiation
Preoperative Chemoradiation: ADJUVANT
• Docetaxel or paclitaxel plus • GE junction denocarcinoma
fluoropyrimidine (5-FU or included
capecitabine) (category 2B) • Fluoropyrimidine (5-FU or
• Cisplatin plus capecitabine) (category 1)
fluoropyrimidine (category
2B)

9. 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

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

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

12. Prognostic factors
• Stage: TNM
– T: increasing T
– N: higher numbers of positive LNS
– M: presence of mets
• Grade: undifferentiated tumors
• Poor PS
• High LDH

13. Perioperative chemotyherapy

14. MAGIC trial
14

15. 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
16

17. Adjuvant CRT in gastric and GE AC

18. Design
inclusion: =>T2 or LN+
Before RT: one cycle
5FU: 425 mg PSM D1-5
LV: 20 mg PSM D1-5
Concomitant CRT: two cycles
RT: 4500 CGy (25 F in 5 weeks)
5FU: 400 mg PSM 1st 4 & last 3 days
LV: 20 mg PSM 1st 4 & last 3 days
One month Post RT: two cycle q 4w
5FU: 425 mg PSM D1-5
LV: 20 mg PSM D1-5
Dose reduced for G3/4 toxicities

19. Results

20. 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 %

21. Chemotherapy for advanced or
metastatic disease

22. Capecitabine and oxaliplatin in G,E, EG ca
REAL-2 trial

28. Cocclusions
ECF 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 FU
Oxaliplatin is similar to cisplatin
EOX is better than ECX

29. ML study
Capecitabine cisplatin (XP) vs 5FU cisplatin (FP)
XP FP
RR 41% 29%
Median OS 10.5 m 9.3 m
PFS similar similar

30. Metaanalysis of capetcitabine in GC

32. Capecitabine 5FU P
Median OS 10.7 m 9.5 m 0.027
Median PFS 6.6 m 6m NS
RR 46% 38% 0.006
independent predictors of poor survival
•Poor performance status,
•age <60 and
•metastatic disease.

33. Benefit of capecitabine

34. S1 in gastric carcinoma

36. OS PFS
S1P S1 P
Median OS 13 m 11 m S
Median PFS 6m 4m S
RR 54% 32% 0.002

37. CS FS
521 508
Median OS 8.6 m 7.9 m 0.2
Safety and Better Worse
tolerance

38. Anti-HER2 in gastric cancer
ToGa trial

39. FP/XP FPT/XPT
300 300
Median OS 11.1 m 13.5 m S
Safety comparable
CHF No No

40. Omitting cisplatin

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

43. Adding Docetaxel

45. TTP OS