This document provides information on gastric cancer including: 1. Symptoms, signs, diagnosis and staging using endoscopy, CT scans, laparoscopy and more. 2. Treatment options depending on stage including surgery (D1, D2 lymphadenectomy), chemotherapy, and chemoradiation. 3. Adjuvant therapy recommendations after surgery including S-1 chemotherapy or chemoradiation based on clinical trials. 4. Guidelines for radiation therapy planning and target volumes. 5. Systemic therapy options for advanced or metastatic disease including single agent versus multi-agent chemotherapy.

2. Symptoms
and signs
diagnosis
Treatment
proper

3. Weight loss
(21-60%)
Pain
(62-91%)
Early satiety
Nausea and
vomiting
(5-40%)
asymptomatic
commonest
Metastatic setting
GE JUNCTION
PYLORUS
Ascites, jaundice, or a palpable mass indicates incurable disease
Krukenberg’ s tumor/Blumer’s shelf/ Sister Mary Joseph’s node/ Virchow’s
node

4. TEST
ENDOSCOPY Direct visualization /cytology. Biopsy usual in 90% cases
But linitis plastica & small<3 cm & cardia lesion is difficult to diagnose
DOUBLE
CONTRAST
STUDY
: small lesion limited to inner layer of stomach wall.
CECT SCAN: For both extent of spread & radiation portal (abdomen)
Mediastinal LN ( in case of distal esophageal junction and thoracic
mets.)
HELICAL
CT:
More useful In detection of smaller LN
LAPAROSC
OPIC
STUDY:
Helps in detection in metastatic disease in case of operable lesion in
preoperative imaging. Peritoneal fluid should be sampled in case of
+ve is considered as M1 disease.
• T staging is accurate enough in 86 % case by EUS. Whereas 43% by CT.
• EUS is 1st line imaging modality in T category
• Diffuse /mucinous tumors – pet has lower detection rate. As FDG accumulation is
lower in this cases

6. Esopahgeal cancers and growth within 5 cm from GEJ are staged as
Esophageal ca.
All other ca having midpoint in stomach 5 cm distal to GEJ & within GEJ not
involving the GEJ is termed as gastric ca.

7. Borrmann’s classification:
Type 1: exophytic
Type 2: ulcerative lesion with elevated borders good prognosis
Type 3: ulcerstive lesion infiltrating stomach wall
Type 4: diffusely infiltrating
Type 5: unclassifiable.
PROGNOSTIC FACTORS:
• Tumor Extent Surrounding Tissue Involvement poor prognosis
• Pfs
• Alk Phos Increase
• Ethnicicty
• Aneuploidy
 Minimal node involvement does not alter prognosis.

9. SURGERY
POTENTIALLY CURATIVE.
D1
D1+
D1
D2EMR
PERIGASTRIC
LN
1-6 LN
station.
COELIC
LN
1-11
LN
station

10. EMR Created by Japanese research society for gastric ca
Since only mucosal involvement, nodal mets chance is 1%
• Diameter <3 cm
• Easily manipulated area
• Not done in
submucosal invasion as
chances of nodal mets
is high.
No RCT

11. Target –R0 resection
GASTRECTOMY
Partial total
• 5 cm margin on both side to have a R0 resection
• recent concept about CRM(more incidence due to locally
advanced disease.)
• Role of Frozen section
indicated for
resectable
stage IB–III
Disease.

12. Mid and distal gastric cancer:
• question is partial or total
• On the basis of morbidity , mortality and oncologic out come partial is
prefered than total gastrectomy.
• Three small RCT outcome is comparable in both approaches.
Proximal gastric cancer:
• Esophagogastric Junction(siewart Type II/III)
• Proximal Gastric Cancer
Options:
• Transhiatal Esophagogatsrectomy (Cervical /Thoracic Anastomosis)
• Total Gastrectomy
 Transthoracic is better than transhiatal on basis of perioperative morbidity
 5 year survival better in TTEG(not statistically significant)
 No concensus in siewart type II/III
 Individualized on the basis of surgeon, age ,comorbidity, PFS,T status,
Nstatus

13. Lymphadenectomy:
1. Adequate staging 2.Adequate therapy
At least 15 LN need to be retrieved.
Total gastrectomy
D0: Lymphadenectomy less than D1
D1: Nos. 1–7
D1+:D1, Nos. 8a, 9, 11p
D2: D1+Nos. 8a, 9, 10, 11p, 11d, 12a.
Distal gastrectomy
D0: Lymphadenectomy less than D1
D1: Nos. 1, 3, 4sb, 4d, 5, 6, 7
D1+:D1,Nos. 8a, 9
D2: D1+Nos. 8a, 9, 11p, 12a.
Japanese gastric cancer treatment guidelines 2010 (ver. 3)

14. Pylorus-preserving gastrectomy
D0: Lymphadenectomy less than D1
D1: Nos. 1, 3, 4sb, 4d, 6, 7
D1+:D1,Nos. 8a, 9.
Proximal gastrectomy
D0: Lymphadenectomy less than D1
D1: Nos. 1, 2, 3a, 4sa, 4sb, 7
D1+:D1,Nos. 8a, 9, 11p
Japanese gastric cancer treatment guidelines 2010 (ver. 3)

15. Type Descriptions
D1 lymphadenectomy  T1a tumors that do not meet the criteria for EMR
 cT1bN0 tumors that are differentiated type and <1.5
cm
D1+lymphadenectomy  cT1N0 tumors other than the above
D2 lymphadenectomy  potentially curable T2-T4 tumors, & cT1N+tumors.
 complete clearance of No. 10 nodes by splenectomy
should be considered for potentially curable T2-T4
tumors invading the greater curvature of the upper
stomach.
D2+lymphadenectomy  Non standard
 prophylactic para-aortic lymphadenectomy
 Denied by jcog 9501
 prognosis of this population is poor.
Japanese gastric cancer treatment guidelines 2010 (ver. 3)
A recent meta-analysisof 12 randomised, controlled trials (RCTs) confirmed no overall
survival (OS) benefit for D2 lymphadenectomy, although a benefit was seen among patients
who had resection without a splenectomy and/or pancreatectomy

16. Adjuvant therapy:
chemotherapy
1007
patients
Stage
II/III
tumor
R0 D2
dissection
S-1
S-1 an oral
fluoropyrimidine
(tegafur and
oxonic acid)
Overall survival 80%
vs. 70%
(improved)
Not sure about extrapolation to western population.

17. Meta analysis of 17 trials
Resectable
gastric ca
post sx
Adjuvant
CT
• Significant DFS, OS
improvement with
hazard ratio 0.82
• 5% improvement in
5 year survival.
• Conclusion: 5FU
based CT is
warranted.
Not sure about extrapolation to western population.

19. Closed early due to higher mortality rate in CTRT arm, but
reaching to a plateau stage. Ultimately CTRT arm has superior
survival. Also that is more prominent in resected patients.

20. Adjuvant therapy:
Radiothaerapy+/- chemotherapy
INT 0116
Stage Ib –IV ca
N= 556
45GY/25#
+
5FU leucovorin
Relapse free
survival=48%
vs.31%(p<.001)
3 yr OS= 50%
vs.41%
(p<.005)
OBS.
Local recurrence
19% vs.29%
 Clear survival advantage of chemoradiation
 strongly support its integration into the routine
care of patients with curatively resected high-risk carcinoma of
the stomach and GE junction.

21. CALGB 80101 : POST OP CHEMO f/b CTRT f/b CT does not improve over all
survival in comparison of ECF to CF
ARTIST study
Korean phase III study
458 patients
D2 resection
f/b chemoradiation (XRT+cepacitabine/cisplatin)
vs.
Chemotherapy(capecitabine/cisaplatin)
• Not significant DFS
• In subgroup analysis pathologic lymph node
superior DFS is found
Conclusion: RT+CT does not significantly reduce
recurrence

22. ARTIST
STUDY II
IS UNDER
PROCESS
CRITICS trial
Study design:
Induction therapy (ECF) followed by D1+
resection followed by another 3 cycle +/-RT

23. PREOP CT/CTRT
Success of CTRT neoadjuvant setting in esophagus and rectum has raised
enthusiasm in ca stomach which seems to be a logical approach.
Only phase II study are there regarding CTRT.
Md Anderson cancer centre:
 preop protocol of CDDP+leucovorin and 5FUf/b 45 GY /25# +5FU f/b D2
resection.
 64 months longer median saurvival in pathological responding tumor than
non responding(13%).
 Another study showed FU+ paclitaxel+CDDP f/b 45 GY/25# +5 FU
&leucovorin f/b D2 resection.
 78% R0 resection, pathological complete response 25%, partial response
15%

24. PREOP CT/CTRT
POET
study Induction therapy CDDP +5FU vs.
similar induction f/b concurrent
etoposide /CDDP +RT
 Preop CTRT arm- higher N0 rate.(64% vs.37%)
 pCR rate is high(16% vs. 2%)
 Improved local control (76% vs. 59%)
 and overall survival.(47% vs. 28%)
Closed early due to
slow accrual
Another TOPGEAR study is under process.

25. General Principles of Planning and Target Delineation for
Adjuvant Radiation for Adenocarcinomas of the Gastro
esophageal Junction and the Stomach:
 Fast for 2–3 h before CT simulation.
 Before treatments to ensure an
empty stomach and enhance daily
treatment reproducibility
 Planning CT scans of 3–5 mm
thickness
 Supine position with arms
overhead, from top of the
diaphragm (for stomach) or carina
(for tumour of GE junction or
cardia) to the bottom of L4.
 Immobilisation with a Vac-Lok is
recommended for treatment with
IMRT
 IV contrast is preferred to demonstrate
blood vessels particularly for lymph nodes;
 preoperative CT scans should be used to
aid identification of preoperative tumour
volume and nodal groups to be treated.
a total dose of 45 Gy in 25
fractions of 1.8 Gy, 5 Fractions/week
by 3D-conformal / intensity-
modulated radiation therapy
techniques

26. Target
volumes
Definition and description
GTV Gross residual disease defined by CT imaging and surgical findings
PTV (residual
disease)
GTV/positive margins + 1.5 cm. Cone down boost after 45 Gy to a total
dose of 50.4 to 54Gy in 1.8Gy/fraction
CTV 45 Coverage of nodal groups according to subsite . Also includes remnant
stomach, anastomosis (gastrojejunal, oesophagojejunal), duodenal stump
PTV 45 CTV 45+ 1 cm margin. A larger margin may be required for organ motion
and setup uncertainties
Three areas must be identified as CTV for adjuvant radiotherapy:
 gastric tumour bed,
 anastomosis/ stumps
 regional lymphatics.
 hepatogastric ligament should preferably be treated in all cases as it is at high risk of
recurrence.
It represents the part of the lesser omentum that runs between the
lesser curvature of the stomach and liver and contains the left and right gastric nodes that
are not always completely removed at surgery

31. Advanced
stage IV
CT
Single
agent
multiagent
Supportive
care
 Wagner et al . In a meta analysis of Cochrane collaboration found that overall survival is
More in CT arm supporting evidence in favour of CT.(hazard ratio of 0.39)
2 year survival is more in CT arm.
QOL is also better in CT arm.
Wagner AD, Unverzagt S, Grothe W, et al . Chemotherapy for advanced cancer. Cochrane
Database Syst Rev 2010; (3):CD004064

32. Single Agent Multiagent
S-1, 5fu, Capecitabine,
Paclitaxel, docetaxel, irinotecan,
Epi-/Doxorubicin.
Wagner et al. in their Cochrane
review showed that multiagent
is better than single agent.
Response rate ranges from 19%-
49%
Highest for S-1 and lowest For
cisplatin & epi/doxorubicin.
 OS is 8.3 moths vs. 6.7
months
 HR is 0.82
 Treatment related mortality
slightly higher in combination
arm, but statistically
significant.

33. CDDP
+5FU
 Established
protocol decade
long
 Mostly used in
control arm in
various study
 Losing its
importance first as
isolated use, with
the advent of other
agents.
 KANG ET AL, REAL -
2, FLAGS TRIAL
showing oral
formulation is non
inferior than
infusion.
DCF
TAX 325
 Median TTP is
3.7 vs. 5.6
months
 2 year survival
is 8.8%vs. 18.4%
 Response is
37%vs.28 %
 Toxicity is also
substantially
increased.
*USFDA approval
FOLFIRI
 Phase 2 trial
proves advantage
over folfiri vs. CF
 PHASE 3 trial
IF vs. CF objective
response same .
Toxicity somewhat
less.

34. REAL -2 TRIAL
EOX
ECF
ECX
EOF
 MEDIAN OS : ECF 9.9 months, EOF 9.3 months, ECX 9.9 months, and EOX
11.2 months
 The 1-year overall survival was also similar and ranged from 37.7% to
46.8%, the best outcome being seen with EOX and the lowest with the
control arm of ECF . The authors concluded the oxal iplatin could be
substituted for cisplatin, and capecitabine could be substituted for fluorouracil
in the palliative setting.

35. TRANSTUZUMAB
 Overexpression or amplification of HER2 (EGFR2) 20 % patients with gastric
cancer.
 TOGA trial: median OS is 13.5 vs. 11.1 months. Response rate is 47 % vs. 35
%.
 Trastuzumab has been approved in Europe for HER2-positive gastric
cancer .
Targated therapy
EGFR TRANSTUZUMAB,CETUXIMAB
EGFR :TKI LAPATINIB,GEFTINIB,ERLOTINIB
VEGF BEVACIZUMAB (AVAGAST trial)
VEGF:TKI SUNITINIB
mTOR
inhibitor
EVEROLIMUS