By Dr. Moumita Paul

1. RADIOTHERAPY IN CA STOMACH
- CURRENT SCENaRIO
Dr.Moumita Paul
PGT 3rd Year
Moderator : Dr. M. Bhattacharyya
Professor
Radiation Oncology

2. .
ANATOMY
• Stomach is a muscular organ-begins at
gastroesophageal junction and ends at
pylorus
• Divided into four anatomic regions:
- gastric cardia
- fundus
- body and
- Pylorus -- pyloric canal and pyloric
antrum.
• The anterior part of stomach is
covered with peritoneal coverings but
there is no or variable peritoneal
covering over most proximal portion
of GE junction.

3. VASCULAR SUPPLY

4. LYMPHATIC SUPPLY

5. EPIDEMIOLOGY
• Globocan 2018 data—
No. of new cases = 10,33,701
No. of deaths = 7,82,685
• Carcinoma stomach is the 2nd leading cause of
cancer related death after lung cancer.
• The highest incidence are found in East
Asia(Japan and China)>South America
>Eastern Europe.

6. RISK FACTORS
• Non-Modifiable :
• Race or ethnicity: East
Asian/Pacific Islanders
• Age > 45 years
• Family history: 1st degree
relative(2-4 fold)
• Sex : M>F(2-5 fold)
• Genetic factors : E-
cadherin(CDH1) mutation,
Lynch syndrome, FAP, Peutz-
Jegher’s syndrome, Juvenile
polyposis syndrome, hereditary
breast and ovarian cancer
syndrome and Li-Fraumeni
syndrome
• Modifiable :
• H.pylori infection (3-6times)-
distal gastric cancer and
intestinal type
• EBV virus(found in 5-16% of
gastric cancers)
• High intake of smoked and
salted foods
• Diet low in fruits and
vegetables
• Smoking
• Barret‘s esophagus/GERD
• Prior subtotal
gastrectomy(25%)

7. PATHOLOGICAL CLASSIFICATION OF
GASTRIC CANCER
Adenocarcinoma (90 -95%)
Lymphoma(3-5%)
Leiomyosarcoma (2%)
GIST(1%)
Adenocanthoma(1%)
Squamous cell carcinoma. (1%)

9. PATTERNS OF SPREAD
Direct: omenta , pancreas, diaphragm , transverse colon ,
mesocolon ,duodenum ,jejunum , spleen , liver, adrenals,
kidney
Lymphatics: submucosal and subserosal layer of gastric
wall is abundant in lymphatics.
Initial drainage is to lymph nodes along lesser and greater
curvatures(i.e. gastric and gastro-epiploic nodes)but also
includes celiac axis, porta hepatis, splenic, suprapancreatic
, pancreatoduodenal, adjacent para aortic, distal
paraesophageal system.
Hematogenous – liver(MC,30%),lung
Peritoneal involvement

10. CLINICAL PRESENTATION
• Loss of appetite—most common presentation
• Early satiety
• Abdominal discomfort
• Unintentional weight loss
• Nausea and vomiting
• Tarry stool(Melaena)
• Haematemesis
• Duration of symptoms is <3 months in almost 40% of
patients ,>1 year in 20%

11. CLINICAL PRESENTATION
• Advanced disease may present with--
•Abdominal mass -- Epigastric or liver mass
•Periumbilical node(Sister Mary Joseph node)
•Palpable left supraclavicular node (Virchow' s node)
•Enlarged left axillary lymph node (Irish node)
•Rectal nodes (Blummer' s shelf)

12. TNM Staging

13. Diagnostic work up
• History and physical examination
• Lab Investigations : CBC, LFT, RFT, CEA (elevated in
1/3rd ), H.pylori (blood antibody test,urea breath test,
etc.)
• UGI Endoscopy – for direct visualisation and biopsy
• EUS – to assess depth of penetration and lymph node
involvement
• CT chest, abdomen , pelvis with contrast to detect
lymphadenopathy and metastasis
• PET CT - Lower detection rate , since low FDG
accumulates in mucinous and diffuse gastric cancer 40%
of gastric cancer are not FDG avid PET should be used
only in conjunction with CT

14. Diagnostic work up
• Her-2-neu testing – if metastatic
adenocarcinoma
• Laparoscopy with cytology : considered to
assess the extent of disease, peritoneal
implants, and resectability in cT1b or higher
stage , especially if cT3 and/or cN+. May also
consider if planning pre-op CTRT.
• Pre-radiation quantitative renal perfusion
study to evaluate relative bilateral renal
function, which may affect radiation planning
and dose constraints.

15. TREATMENT OPTIONS
• Surgery –primary treatment
• Radiation
• Chemoradiation
• Best supportive care

16. APPROACH TO MANAGEMENT

22. ROLE OF RADIOTHERAPY
 Post op EBRT
 Pre op EBRT
 Intraoperative RT
 Palliative RT
Indications-
o T3-4 resectable disease
o Margin positive
o LN +ve disease
o Inoperable disease

23. RADIOTHERAPY TARGET
• Gastric /tumor bed, anastomostic site, gastric remnants
and regional lymphatics should be included in most cases.
• Major nodal chain at risk include
Lesser and greater curvature
Celiac axis
Pancreaticoduodenal
Splenic
Suprapancreatic
Porta hepatic groups
Para-aortics to the level of L3

24. • 2D Planning technique
• Position : Supine
• AP/PA parallel opposed fields used in 2D techniques
• Blocks should be used ,to reduce the dose to
liver(70%<3Gy) Kidney(2/3<20Gy), Heart (1/3<45Gy)
• The radiation field must include gastric/tumor bed,
anastomosis and gastric remnants along with regional
lymphatics.
• Major nodal chain at risk includes the lesser and greater
curvature, celiac axis, pancreaticoduodenal, supra
pancreatic , porta hepatis , spenic and in some para
aortic to the level of L3.

25. Borders for 2D Conventional technique
Superior border: bottom of T8 or T9 to cover celiac axis,
GE junction , fundus and dome of left hemi diaphragm
Inferior border: bottom of L3 to cover gastro duodenal
nodes and antrum
Left lateral border : include 2/3 to 3/4th of left
hemidiaphragm to cover fundus ,suprapancreatic nodes
and splenic nodes.
Right lateral border : 3 to 4 cm lateral to vertebral bodies
to cover the antrum , porta hepatis ,and gastro duodenal
nodes
Dose of RT: 45-50.4Gy/25-28#/5 weeks

26. Fig: Simulation in post operative T3 antral tumor with left & right kidney block

27. RADIATION THERAPY TECHNIQUES
• SIMULATION
• Ensure adequate nutrition prior to radiation
• Patient may require feeding tube (preferable if placed at
the time of surgery)
• Patient should fast 3 hours before simulation and all
treatments.
• During CT simulation patient is properly positioned ,
straightened , immobilized & hands are placed above head.
• Oral & IV contrasts are used for proper delineation of
stomach & mediastinal lymphnodes.
• Respiratory gating or breath hold technique can be used to
restrict tumor motion & avoid normal tissue irradiation
• 4D CT scan may be appropriate to assess tumour motion

28. TREATMENT PLANNING
Target design:
GTV: based on diagnostic CT images ,
esophagogastroduodenoscopy or endoscopic
ultrasound. It includes the recreation of
tumor volume in case of adjuvant settings.
CTV: For accounting subclinical spread of
disease CTV is drawn based on some
anatomical landmarks.
• The stomach is divided into 3 equal
lengths(upper/proximal, middle and distal)
classified by location of bulk of their masses
in these sites.

29.  Japanese Gastric Cancer
Association recommended--
• CTV for proximal 3rd stomach -- contour of stomach
with exclusion of pylorus and antrum(keeping a
minimum margin of 5cm from GTV)
• CTV for middle 3rd tumour – contour of stomach
from cardia to the pylorus
• CTV for distal 3rd tumour—contour of stomach
excluding cardiac or fundus .If pyloric or duodenal
invasion is present , the CTV would be expanded
along the duodenum with a margin of 3cm from the
tumor.

30. General CTV recommendations
• For proximal gastric cancers undergoing
esophagectomy with intrathoracic anastomosis,
CTV includes—
• 3-4 cm of the mucosa of the esophagus and distal
stomach
• Tumour bed(including medial 2/3rd of the left
hemidiaphragm
• Lymph node stations 1 to 4, 7, and 9 to 11 (11,12;
if GEJ involved then stations 20, 110, 111)

31. General CTV recommendations
• For midlle third patients undergoing total
gasrectomy with Roux-en-Y EJ anastomosis,
the CTV typically includes-
• 3-4 cm of the mucosa of the esophagus and
jejunum
• Tumour bed
• Lymph node stations 3-11(12,13) and 1,2 in
case of prox.third involvement

32. General CTV recommendations
• For distal third tumours undergoing distal
gastrectomy with gastrojejunal anastomosis,
CTV include—
• 3-4 cm of the mucosa of the proximal stomach
and jejunum
• 3-4 cm of duodenal stump
• Tumour bed
• Lymph node stations 3-9, and 11-13

34. ITV and PTV
• CTV should consist of atleast 5 mm margin
around the vessels to include the lymph
nodes.
• ITV should be taken atleast 1.5 cm in all
direction over CTV if target motion is not
accounted .
• PTV –made 5mm margin over ITV.

35. • For unresectable lesion with periesophageal
extension heart is not possible to spare, hence
use of oblique or lateral fields is indicated.
• For node positive cases ,there should be wide
coverage of remaining stomach ,anastomosis ,
tumor bed & nodal drainage regions.
• For node negative cases with wide surgical
margin & 15 LN evaluation , treatment to nodal
bed is optional

39. INTRAOPERATIVE RADIATION THERAPY
•Single large dose 10 to 35 Gy of RT can be delivered to tumor
&tumor bed in single fraction during operation.
•5 yr survival rate was found to be better by Abe et al with IORT
compared to surgery alone(28 to 35 Gy with electron beams were
delivered during the surgical procedure to tumour beds, high risk
lymphnodes and/or remaining cancer nests after gastrectomy).

40. Fig:showing CTV contouring of post op T3N0 antral primary along with OARs.

42. Sequelae of RT
Acute :
• Anorexia
• Nausea, Vomiting
• Fatigue
• Esophagitis
• Epidermitis
• Dehydration
• Weight loss
Late :
• Dyspepsia
• Radiation Gastritis
• Uncomplicated gastric
ulcer
• Complicated gastric ulcer
(with perforation or
obstruction)
• Nephrotoxicity
• Cardiotoxicity(pericarditis
, effusion)

43. PREOPERATIVE CHEMORADIATION VS PREOPERATIVE
CHEMOTHERAPY ALONE
•Patients with locally advanced adenocarcinomas of the oesophagogastric
junction (Siewert types I–III) were eligible.
• Randomisation was done to chemotherapy (group A) or induction
chemotherapy and chemoradiotherapy (CRT; group B) followed by surgery.
•The primary end-point of the study was overall survival at 3 years.
•Although the primary end-point overall survival of the study was not met, our
long-term follow-up data suggest a benefit in local progression-free survival
when radiotherapy was added to preoperative chemotherapy in patients with
locally advanced adenocarcinoma of the oesophagogastric junction.

44. •Results : The median overall survival in the surgery only group was 27
months, as compared with 36 months in the chemoradiotherapy group; the
hazard ratio for death was 1.35 (95 percent confidence interval, 1.09 to
1.66; P=0.005).
Three patients (1 percent) died from toxic effects of the chemoradiotherapy;
grade 3 toxic effects occurred in 41 percent of the patients in the
chemoradiotherapy group, and grade 4 toxic effects occurred in 32 percent.
•Conclusions : Postoperative chemoradiotherapy should be considered for
all patients at high risk for recurrence of adenocarcinoma of the stomach or
gastroesophageal junction who have undergone curative resection.

46. •Open-label, randomised phase 3 trial, we enrolled patients aged 18 years or older who
had stage IB– IVA resectable gastric or gastro-oesophageal adenocarcinoma.
•Randomisation into either perioperative chemotherapy (chemotherapy group) or
preoperative chemotherapy with postoperative chemoradiotherapy (chemoradiotherapy
group).
•Postoperative treatment started within 4–12 weeks after surgery. Chemotherapy
consisted of three preoperative 21-day cycles and three postoperative cycles of
intravenous epirubicin (50 mg/m 2 on day 1), cisplatin (60 mg/m 2 on day 1) or oxaliplatin
(130 mg/m 2 on day 1), and capecitabine (1000 mg/m 2 orally as tablets twice daily for 14
days in combination with epirubicin and cisplatin, or 625 mg/m 2 orally as tablets twice
daily for 21 days in combination with epirubicin and oxaliplatin), received once every
three weeks.

47. • Chemoradiotherapy consisted of 45 Gy in 25
fractions of 1·8 Gy, for 5 weeks, five daily
fractions per week, combined with capecitabine
(575 mg/m 2 orally twice daily on radiotherapy
days) and cisplatin (20 mg/m 2 intravenously on
day 1 of each 5 weeks of radiation treatment).
• Interpretation: Postoperative chemoradiotherapy
did not improve overall survival compared with
postoperative chemotherapy in patients with
resectable gastric cancer treated with adequate
preoperative chemotherapy and surgery.

48. •Comparison of the efficacy of different chemotherapy regimens and chemoradiotherapy in
patients with D2-resected, stage II/III, node-positive GC.
•Patients with pathologically-staged II or III, node-positive, D2-resected GC, to receive
adjuvant S-1 (40-60 mg twice daily 4-weeks-on/2-weeks-off) for one year, S-1 (2-weeks-
on/1-week-off) plus oxaliplatin 130 mg/m2 (SOX) for six months, or SOX plus
chemoradiotherapy 45 Gy (SOXRT).
•Randomization was stratified according to the type of surgery (total or subtotal
gastrectomy), stage (II or III), and Lauren histologic classification (diffuse or intestinal).
•The primary endpoint was disease-free survival (DFS). A total of 900 patients had to be
enrolled to demonstrate superiority of SOX or SOXRT to S-1 (hazard ratio [HR] 0.667), with
90% power at a two-sided significance level of 5%.

49. • DFS in the control arm (S-1) were significantly
shorter than in SOX and SOXRT arms (stratified
HR for recurrence): S-1 vs SOX, 0.617 (P =
0.016) and S-1 vs. SOXRT, 0.686 (P = 0.057).
The DFS at 3-years was found to be 65%, 78%
and 73% in S-1, SOX and SOXRT arms,
respectively. No difference in DFS between
SOX and SOXRT was found (HR 0.910, P =
0.667).

50. •Patients with adenocarcinoma of the stomach were randomized to perioperative ECF
alone or with preoperative chemoradiation.
•The ECF-alone group received three preoperative cycles of ECF, while the chemoradiation
group received two cycles of preoperative ECF followed by chemoradiation. Both groups
received three postoperative cycles of ECF.
•The proportion of patients proceeding to surgery was 90% (ECF group) and 85%
(chemoradiation group).
•Grade 3 or higher surgical complications occurred in 22% of patients in both groups.
Furthermore, grade 3 or higher gastrointestinal toxicity occurred in 32% (ECF group) and
30% (chemoradiation group) of patients, while hematologic toxicity occurred in 50 and
52% of patients.
•Conclusions :These results demonstrate that preoperative chemoradiation can be safely
delivered to the vast majority of patients without a significant increase in treatment
toxicity or surgical morbidity.

52. •Retrospective data were collected from January 2009 to December 2014.
The 5- and 7-year OS and disease-free survival (DFS) were compared
between the two groups using the Chi-square test.
•A total of 415 eligible patients were identified (135 adjuvant
chemoradiotherapy, 280 adjuvant chemotherapy).
•Significant 5- and 7-year OS and DFS benefits were found in the adjuvant
chemoradiotherapy group versus chemotherapy group.
Conclusion: Patients in the adjuvant chemoradiotherapy group had a lower
locoregional relapse. Subset analysis also identified significant OS benefits
of adjuvant chemoradiotherapy in patients with LN ratio <50%, pIIIA, and
pIIIB stage disease, while OS benefits were not observed in patients with
tumor deposits, pN3b classification, or pIIIC stage disease.

53. Conclusion
• RT with concomitant fluoropyrimidine-based CT –
indicated for locally confined gastric
cancer(unresectable or medically inoperable).
• Patients with R1/R2 gastric resection and positive
nodes should be appropriately managed by
combined modality therapy.
• Pre-op chemoradiation is preferred in patients
with locally advanced disease that is unresectable
with negative margins so that gross total
resection can be attempted alone or in
combination with IORT, and maintenance CT.

54. • Post-op irradiation and concurrent and
maintenance fluoropyrimidine based
treatment are generally recommended for
Stage IB to IV and M0 gastric cancer.
• Role of post-op chemoradiation in T2N0
tumours remains controversial.
• In patients with high risk features(poorly diff
or high grade cancers, LVI, PNI, age<50 yrs, or
suboptimal resection including LN resection),
post-op chemoradiotherapy may also be
indicated.

55. Thank
You