Management of gastric cancer

Management of Carcinoma
Stomach
Dr. Varshu Goel
Second Year Post-Graduate Resident
Moderators :
Dr. Savita Arora
Dr. Narayan Adhikari
Department of Radiation Oncology
Maulana Azad Medical College, New Delhi

• Stomach begins at the
GE junction and ends at
the pylorus
• Subsites :
• Cardia
• Fundus
• Body
• Pylorus
• Pyloric Antrum
• Pyloric Canal
• Wall has five layers:
mucosa, submucosa,
muscularis, subserosa,
and serosa.
2
Anatomy
AJCC, 8th edition

3
ArterialSupply
• Celiac Artery has three branches:
• Left gastric artery
• Common hepatic artery  right gastric artery and the right
gastroepiploic branch
• Splenic artery  the left gastroepiploic and the short gastric arteries
Perez 7th ed and Devita 11th ed

LymphaticSpread
4
Perez 7th ed and Devita 11th ed

• Third leading cause of cancer-related death
• Median age: 69 years
• Male to female ratio = 2: 1
• Stage at Presentation : Localized 24%, Regional 30%, Distant 35%
• Risk factors for gastric cancer can be classified as modifiable or
nonmodifiable
5
Epidemiologyand RiskFactors
Perez & Brady's Principles and Practice of Radiation Oncology, 7th ed.

Pathology
• Adenocarcinoma 90-95%
• Lymphoma
• Rare :
• GISTs
• Carcinoid (neuroendocrine) tumors
• Adenoacanthomas (1%)
• Squamous cell carcinomas (1%)
• Frequency : Site wise
• Antrum/Distal – 40%
• Proximal/GEJ – 35%
• Body – 25%
6

Pathology
• Borrmann’s histological types, 1926 :
• Type I : polypoid or fungating
• Type II : ulcerating lesions surrounded by elevated
borders
• Type III : ulceration with invasion of the gastric wall
• Type IV : diffusely infiltrating (linitis plastica)
• Type V : unclassifiable
• Lauren classification system, 1965 :
• Intestinal type : improved prognosis (predominates in regions with high
prevalence of gastric cancer)
• Diffuse histologic type : poor prognosis; affects younger patients, more
aggressive
7

8
Pathology
• WHO Classification is based predominantly on histologic cancer patterns
• Tubular = Intestinal Lauren type
• Papillary = Intestinal Lauren type
• Mucinous
• Poorly cohesive = Diffuse Lauren type
• Rare variants
• Cancer Genome Atlas Research Network in 2016 published results of
genomic profiling of 295 primary gastric adenocarcinomas, and four tumor
subtypes were identified:
(a) Epstein-Barr virus (9%)
(b) Microsatellite-unstable tumors (22%)
(c) Genomically stable tumors (20%)
(d) Chromosomally unstable tumors (50%)

9
Clinical Presentation
Perez, 7th ed.
• Abdominal pain and epigastric discomfort : 60-90%
• Anorexia, post prandial fullness and early satiety : 6-40%
• Unintentional weight loss : 20-60%
• Dysphagia (notably if GE junction or proximal stomach involvement)
• Anemia-related weakness and fatigue
• Nausea and vomiting
• Tarry stools
• Advanced disease :
• Liver mass : 30%
• Sister Mary Joseph node = periumbilical node
• Virchow node = left SCLN
• Irish node = left axillary LN
• Blumer shelf = rectal shelf/ peritoneal seeding
• Krukenberg tumor

DiagnosticWorkup
10
• History and physical examination
• Complete blood count (CBC) and comprehensive metabolic panel
• Upper gastrointestinal endoscopy and biopsy
• yields the diagnosis in ≥90% of exophytic lesions
• infiltrative (linitis plastica), small (<3 cm), or cardia lesions may be more
difficult to diagnose
• Endoscopic ultrasonography
• most accurate method of determining depth of tumor invasion
(intramural vs. extramural extension)
• needle biopsies of suspicious nodes
• understages N category

DiagnosticWorkup
11
• Abdominal CECT determine abdominal extent of disease and extension to
surgically unresectable structures
• overstages T and understages N category
• CECT of the chest will help to rule out involvement of mediastinal nodes
or the lung parenchyma
• MRI for characterization of indeterminate liver lesions
• Diagnostic laparoscopy for patients with locally advanced-stage disease
• peritoneal fluid can be sampled for cytology : M1 if positive
• HER2 and PD-L1 testing if metastatic adenocarcinoma is
documented/suspected
• H. pylori testing performed and treatment delivered where clinically
indicated

DiagnosticWorkup
12
• PET-CT Scan:
• detect occult metastases in operable patients in 10% and changing
patient management in 15%
• low FDG accumulation in patients with diffuse or mucinous/signet-ring
tumors
• Approximately 40% of gastric carcinomas may not be detected with PET
scan
• response to neoadjuvant therapy, including treatment modification in
poor responders and potential indicator of prognosis in these patients :
ongoing Alliance A021302 study
• Consider pre-radiation quantitative renal perfusion study to evaluate
relative bilateral renal function, which may affect radiation planning and
dose constraints

AJCCTNM Staging
13
AJCC Cancer Staging Manual, 8th ed.
T
category
T criteria
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ: intraepithelial tumor without invasion of the
lamina propria, high grade dysplasia
T1
T1a
T1b
Tumor invades the lamina propria or muscularis mucosae
Tumor invades submucosa
T2 Tumor invades the muscularis propria
T3 Tumor penetrates the subserosal connective tissue without
invasion of the visceral peritoneum or adjacent structures
T4
T4a
T4b
Tumor invades the serosa (visceral peritoneum)
Tumor invades the adjacent structures/organs

14
PrimarySite
Perez 7th edition and AJCC, 8th edition
There is either no or variable visceral peritoneal covering at the most proximal
portion of the GE junction
Positive radial margins at this site are often “true” positive margins

15
N category N criteria
Nx Regional lymph node(s) cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in 1 or 2 regional lymph nodes
N2 Metastasis in 3 to 6 regional lymph nodes
N3
N3a
N3b
Metastasis in 7 to 15 regional lymph nodes
Metastasis in 16 or more regional lymph nodes
M
category
M criteria
M0 No distant metastasis
M1 Distant Metastasis

AJCCPrognosticStageGrouping
16
AJCC Cancer Staging Manual, 8th ed., Page 211

17

18
• Tumor Extent : hematogenous/transperitoneal spread = poor
• LN involvement : number and location
• Performance Status = Poor
• ALP levels : elevated = poor
• Ethnicity : East Asians/Pacific Islanders
• MSI : high MSI (MSI-H) is better for surgery alone, MSS/MSI-L
respond with better DFS in R0 with 5FU based regimens
• Her2 status (ToGA trial – better median OS 13.8/11.1 months)
• CEA and CA19-9 : surveillance
PrognosticFactor
Perez 7th ed. and AJCC, 8th ed.

20
Surgery:
• For proximal (cardia): total or proximal gastrectomy
• Aim for ≥5 cm proximal and distal margins whenever possible
• Remove minimum 16 LNs (D2 nodal dissection preferred)
• Vit B supplementation due to lack of intrinsic factor production
• For distal (body and antrum): subtotal gastrectomy
• Unresectable:
• Consider placing feeding jejunostomy tube
• For gastric outlet obstruction, gastrojejunostomy is preferable over
endoluminal stenting
• Palliation : gastrectomy without LN dissection or palliative radiation if
symptomatic (i.e., bleeding, obstruction)
Perez, 7th ed

• Post op RT indication : Intergroup 0116 results
• CTRT in disease extension through the gastric wall and/or with lymph
nodes positive for tumor
• CTRT and maintenance fluoropyrimidine-based chemotherapy for
patients with stage IB-IV and M0 gastric cancer
• Definitive CTRT with 5-FU based chemotherapy : locally confined
gastric cancer that either is not technically resectable or occurs in
medically inoperable patients
21
Radiotherapy
Perez 7th ed.

Chemotherapy
• Tumour downsizing prior to
surgery
• Increase rate of curative (R0)
resection*
• Eliminating micro-metastatic
disease and achieving systemic
control
• Demonstrates sensitivity to
chemotherapy
• Better tolerated than post-
operative therapy
*Boige et al., ASCO 2007
Advantages
• Potential risk of peri-operative
morbidity
• Definitive surgery may be
delayed if significant toxicity
occurs
• Risk of disease progression
during preoperative treatment
Disadvantages
Gunderson, 4th ed

Neo-adjuvant Adjuvant
Chemo Chemo-RT Chemo Chemo-RT
CLASSIC
ACTS-GC
INT 0116
CRITICS
CRITICS-II
ARTIST
ARTIST-II
MAGIC
MAGIC B
CROSS
TOPGEAR
Evolution of Rx Strategies

Chemo Chemo-RT
vsChemo Chemo-RTvs

Chemo Chemo-RT
vs
INT 0116
2001
observation
5-FU/LVx1c 
45Gy/25# CCRT
with 5FU/LV 
5-FU/LVx2c
Improved 3 yr
OS (50/41) and
RFS (48/31);
decrease local
failure (19/29)
Chemo Chemo-RTvs

Chemo Chemo-RT
vs
INT 0116
2001
MAGIC
2006
observation Sx alone
5-FU/LVx1c 
45Gy/25# CCRT
with 5FU/LV 
5-FU/LVx2c
ECFSxECF
(50 D1/ 60 D1/
200 D1-21)
Improved 3 yr
OS (50/41) and
RFS (48/31);
decrease local
failure (19/29)
Improved
PFS(HR 0.66)
and OS (HR
0.75) and 5 yr
Survival (36/23)
Chemo Chemo-RTvs

Chemo Chemo-RT
vs
INT 0116
2001
MAGIC
2006
ACTS-GC/S-1
2007
observation Sx alone observation
5-FU/LVx1c 
45Gy/25# CCRT
with 5FU/LV 
5-FU/LVx2c
ECFSxECF
(50 D1/ 60 D1/
200 D1-21)
S-1 for 1 year
(tegafur +
oxonic acid)
Improved 3 yr
OS (50/41) and
RFS (48/31);
decrease local
failure (19/29)
Improved
PFS(HR 0.66)
and OS (HR
0.75) and 5 yr
Survival (36/23)
improved 3 yr
OS (80/70)
Chemo Chemo-RTvs

Chemo Chemo-RT
vs
INT 0116
2001
MAGIC
2006
ACTS-GC/S-1
2007
ARTIST
2011
observation Sx alone observation 6c XP
5-FU/LVx1c 
45Gy/25# CCRT
with 5FU/LV 
5-FU/LVx2c
ECFSxECF
(50 D1/ 60 D1/
200 D1-21)
S-1 for 1 year
(tegafur +
oxonic acid)
2c XP  45 Gy
CCRT with X 
2c XP
Improved 3 yr
OS (50/41) and
RFS (48/31);
decrease local
failure (19/29)
Improved
PFS(HR 0.66)
and OS (HR
0.75) and 5 yr
Survival (36/23)
improved 3 yr
OS (80/70)
Improved DFS in
N+ and
intestinal GC
Chemo Chemo-RTvs

Chemo Chemo-RT
vs
INT 0116
2001
MAGIC
2006
ACTS-GC/S-1
2007
ARTIST
2011
CLASSIC
2012
observation Sx alone observation 6c XP observation
5-FU/LVx1c 
45Gy/25# CCRT
with 5FU/LV 
5-FU/LVx2c
ECFSxECF
(50 D1/ 60 D1/
200 D1-21)
S-1 for 1 year
(tegafur +
oxonic acid)
2c XP  45 Gy
CCRT with X 
2c XP
Cape-Ox x 8c
(1000 D1-14 / 130
D1)
Improved 3 yr
OS (50/41) and
RFS (48/31);
decrease local
failure (19/29)
Improved
PFS(HR 0.66)
and OS (HR
0.75) and 5 yr
Survival (36/23)
improved 3 yr
OS (80/70)
Improved DFS in
N+ and
intestinal GC
Improved DFS
(74/59)
Chemo Chemo-RTvs

Chemo Chemo-RT
vs
CROSS
2012
Sx alone
CTRT 41.4Gy/
23# with Pacli/
Carbo Sx
Improved OS
(median OS
49.4/24 months,
HR 0.65)
Chemo Chemo-RTvs

Chemo Chemo-RT
vs
CROSS
2012
CRITICS
2018
Sx alone ECXSxECX
CTRT 41.4Gy/
23# with Pacli/
Carbo Sx
ECXSx45
Gy/25# CTRT
Improved OS
(median OS
49.4/24 months,
HR 0.65)
No improved OS
Chemo Chemo-RTvs

Chemo Chemo-RT
vs
CROSS
2012
CRITICS
2018
TOPGEAR
(ongoing)
ARTIST-II
(ongoing)
D2 with N+
CRITICS-II
(ongoing)
Sx alone ECXSxECX 3c ECF  Sx
3c ECF
S1 x 8c 4 c X DOC  Sx
CTRT 41.4Gy/
23# with Pacli/
Carbo Sx
ECXSx45
Gy/25# CTRT
2c ECF 
CTRT Sx  3c
ECF
S1+ oxaliplatin x
8c
2 c X DOC 
CTRT
(Pacli/Carbo) 
Sx
Improved OS
(median OS
49.4/24 months,
HR 0.65)
No improved OS 2c SOX  45 Gy
with S-1  4c
SOX
CTRT(Pacli/Carb
o)  Sx
Chemo Chemo-RTvs

TreatmentAlgorithm
Biopsy confirmed Gastric Ca
M1M0
PalliationcTis or
cT1a
EMR
Locoregional
cT1b = Sx
cT2-4, any N = peri-op
CT
Unresectable or
non-surgical
candidate
CTRT
R0 R1/R2 CTRT
Re-stage
pT2N0
Surveillance
if no high risk
pT3/4,N+,
high risk
CT/CTRT NCCN 2019
Potentially resectable

RT techniques
Conventional
Conformal

Anteroposterior-posteroanterior (AP-PA) field
Superior Bottom of T8 or T9 to cover celiac
axis, GEJ, fundus and dome of
diaphragm
Inferior Bottom of L3 to cover
gastroduodenal nodes
Left Include 2/3rd to 3/4th of left
hemidiaphragm to cover fundus,
supradiaphragmatic and splenic
nodes
Right 3-4 cm lateral to vertebral bodies
to cover antrum, porta hepatic
and gastroduodenal nodes
Conventional technique
Field Design
Step by Step Radiation Therapy: Treatment and Planning

….Continued Conventional technique
Lateral field
Superior Same as AP-PA
Inferior Same as AP-PA
Anterior Anterior abdominal wall
Posterior One-half to 2/3rd of vertebral
bodies
Step by Step Radiation Therapy: Treatment and Planning
Field Design

ConformalTechniques
3D-CRT
IMRT

ConformalTechnique: CT Simulation
38
• Patient fasting for >2 hours before simulation as well as at treatment
• Arms are generally placed overhead and knees supported
• Oral Contrast administered to delineate the stomach (if surgically
naïve)
• IV contrast is generally used to delineate mediastinal and abdominal
vascular nodal basins, including the celiac axis
• Respiratory gating or breath hold techniques may help to reduce target
motion with respiration
• If patients lose >10% of their body weight during therapy,
consideration should be given to repeat CT planning

Gross tumor volumes (GTV) : GTV_T + GTV_N.
• GTV_T : Primary tumor (including the perigastric tumor extension)
Clinical target volume (CTV_T): depends on site of the stomach.
• Proximal 1/3rd : contour of the stomach with exclusion of pylorus
and antrum , 5 cm margin from GTV.
• Middle 1/3rd : contour of the stomach from cardia to pylorus.
• Distal 1/3rd : contour of the stomach with exclusion of cardia and
fundus.
• 3 cm margin In case of infiltration of the pylorus or the
duodenum
TargetVolumesin UnresectedCases

Proximal stomach CA Mid & Distal stomach CA
ITV CTV+1cm radial margin, 1.5 cm
distal and 1 cm proximal
CTV+1.5 cm in all direction.
PTV ITV+ 5 mm ITV+ 5 mm
ITV and PTV

• Doses in the range of 45 to 50.4 Gy should be delivered at 1.8 Gy per
fraction for treatment of inoperable disease, this dose is followed by
a 5.4- to 9-Gy cone-down boost to GTV plus 1.5 cm to a total dose of
50.4–54 Gy.
Dose
Perez 7e

Stage Remaining
stomach
Tumor bed volume Nodal volume
T2N0 (with
invasion of
subserosa)/T3N0
Variable for
prox/distal
Include in
mid 1/3rd
Prox: medial lt hemidiaphragm,
adjacent body of pancreas(  tail)
Prox: none or perigastric;
optional : periesophageal,
mediastinal, celiac
Mid: body of pancreas (  tail) Mid: none or perigastric;
optional : Celiac, Splenic,
Suprapancr., Pancr.duod.,
portahepatis
Dis: head of pancreas ( body), 1st
& 2nd part of duodenum
Dis: none or perigastric;
optional : Pancr.duod.,
portahepatis, Celiac,
Suprapancr.
Site Specific Guidelines
Perez 7e

Stage Remaining
stomach
Tumor bed volume Nodal volume
T4N0
Variable for
prox/distal
Include in
mid1/3rd
Prox: medial lt hemidiaphragm,
adjacent body of pancreas(  tail)
plus site(s) of adherence with 3–5
cm margin
Prox: nodes related to site
of adherence  perigastric,
periesophageal,
mediastinal, celiac
Mid: body of pancreas (  tail)
plus site(s) of adherence with 3–5
cm margin
Mid: nodes related to site
of adherence  perigastric,
Celiac, splenic, Suprapancr.,
Pancr.duod., portahepatis
Dis: head of pancreas ( body), 1st
& 2nd part of duodenum plus
site(s) of adherence with 3–5 cm
margin
Dis: nodes related to site of
adherence  perigastric,
Pancr.duod., portahepatis,
Celiac, Suprapancr.
Perez 7e

Stage Remaining stomach Tumor bed volume Nodal volume
T1-2N+
Prox: preferable
Not indicated for T1;
As above for T2 into
subserosa
Prox: Perigastric, Celiac,
Splenic, Suprapancr 
periesophageal, mediast.,
Mid: include Mid: perigastric, Celiac,
splenic, Suprapancr.,
Distal: preferable Distal : perigastric,
Pancr.duod., portahepatis,
Celiac, Suprapancr.;
optional : splenic hilum
T3-4N+
Prox: preferable
As for T3/4 N0 As for T1/2N+ and T4N0
Mid: include
Distal: preferable
Perez 7e

OAR Dose limitation
kidney Ipsilateral : V20 < 70%
contralateral kidney : V20 < 30%
Combined volume : V20< 50%
liver V30 < 30%)
Spinal cord Dmax≤ 45 Gy
Lung combined lung volume V20 < 20%
Heart Whole volume: V40 <30%
V25 <50%
OARand Dose Constraints
Perez 7e

(A) Left paracardial (orange); (B) greater curvature (blue), splenic hilum (brown), right paracardial (forest green); (C) greater
curvature (blue), lesser curvature (dark blue), splenic (sky blue), splenic hilum (brown); (D) greater curvature (blue), lesser
curvature (dark blue), splenic (sky blue), splenic hilum (brown), left gastric (aquamarine, dashed);
Wo et, 2013
LN anatomy: Intact Stomach

Wo et, 2013
Lt paracardial LN 2 Rt paracardial LN 1
Greater
curvature
LN 4
Splenic hilum
LN 10
Splenic hilum
LN 10
Greater
curvature
Lesser
curvature LN 3
Splenic
LN 11
Greater
curvatureLesser
curvature
Splenic
Splenic hilum
Left gastric
LN 7
(A) Left paracardial (orange); (B) greater curvature (blue), splenic hilum (brown), right paracardial (forest green); (C) greater
curvature (blue), lesser curvature (dark blue), splenic (sky blue), splenic hilum (brown); (D) greater curvature (blue), lesser
curvature (dark blue), splenic (sky blue), splenic hilum (brown), left gastric (aquamarine, dashed);

(E) greater curvature (blue), lesser curvature (dark blue), splenic (sky blue), left gastric (aquamarine, dashed), paraortic (red),
hepatoduodenal (bright green);(F) greater curvature (blue), lesser curvature (dark blue), splenic (sky blue), paraortic (red),
hepatoduodenal (spring green), commonhepatic (dark purple), celiac (pink); (G) greater curvature (blue), lesser curvature (dark blue),
paraortic (red), hepatoduodenal (bright green), suprapyloric (yellow); (H) greater curvature (blue), paraortic (red), pancreatic (lime green),
superior mesenteric (violet), infrapyloric (green, dashed)
Wo et, 2013

(E) greater curvature (blue), lesser curvature (dark blue), splenic (sky blue), left gastric (aquamarine, dashed), paraortic (red),
hepatoduodenal (bright green);(F) greater curvature (blue), lesser curvature (dark blue), splenic (sky blue), paraortic (red),
hepatoduodenal (spring green), commonhepatic (dark purple), celiac (pink); (G) greater curvature (blue), lesser curvature (dark blue),
paraortic (red), hepatoduodenal (bright green), suprapyloric (yellow); (H) greater curvature (blue), paraortic (red), pancreatic (lime green),
superior mesenteric (violet), infrapyloric (green, dashed)
Greater
curvatureLesser
curvature
Splenic
LG
Paraaortic
LN 16
Hepatoduodenal
LN 12
Greater
curvature
Paraaortic
Lesser
curvature
Hepatoduodenal
Suprapyloric
LN 5
Greater
curvature
ParaaorticPancreatic LN 13
Infrapyloric LN 6
Celiac LN 9
Wo et, 2013

Total gastrectomy with Roux-en-Y esophagojejunostomy. (A) Splenic hilum (brown), splenic (sky blue); (B) splenic hilum
(brown), splenic (sky blue), hepatoduodenal (spring green), common hepatic (dark purple); suprapyloric (yellow); (C) splenic
hilum (brown), paraortic (red), celiac (salmon pink), pancreatic (lime green), infrapyloric (green, dashed); (D) paraortic (red),
pancreatic (lime green), superior mesenteric (violet).
Splenic hilum
LN 10
Splenic LN 11 Hepatoduodenal
LN 12
Suprapyloric LN 5
Common Hepatic LN 8
Celiac LN 9
Pancreatic
LN 13
Infrapyloric LN 6
Pancreatic Superior Mesentric
LN 14
TotalGastrectomywithRoux-en-YEsophagojejunostomy
Wo et, 2013

Subtotal gastrectomy. (A) R paracardial (forest green), L paracardial (orange), splenic hilum (brown); (B) lesser curvature
(dark blue), greater curvature (blue), splenic (sky blue), splenic hilum (brown); (C) greater curvature (blue), splenic (sky
blue); paraortic (red), left gastric (aquamarine, dashed), celiac (salmon pink); (D) greater curvature (blue), splenic (sky blue);
paraortic (red), left gastric (aquamarine, dashed), celiac (salmon pink); common hepatic (dark purple);
Rt paracardial
Lt paracardial
Splenic hilum
Greater
curvature
Lesser
curvature
Splenic
Left gastric
Celiac
PA
Common Hepatic
SubtotalGastrectomy
Wo et, 2013

• Anorexia, nausea, and fatigue are very common complaints during
gastric radiation therapy
• Nutritional complications
• Myelosuppression
Late complications-
• Dyspepsia
• radiation gastritis
• uncomplicated gastric ulcer
• gastric ulcer with perforation or obstruction
Sequelae
Perez 7e

• Neo-adjuvant /adjuvant treatment improves disease free survival
and overall survival
• Post op chemotherapy alone can be considered in pN0 D2 dissected
patients
• Adjuvant chemoRT in less than D2 dissection and node positive
patients
• Periop vs adjuvant chemoRT : peri-op can be preferred as it reduces
toxicity of trimodality treatment and outcomes are similar
Summary

Management of gastric cancer

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