Management of Gastric Cancer

By – Dr. Satyajeet Rath

Moderator – Prof. Kamal Sahni

Date - 31/01/17

Treatment of gastric CA

Treatment of localised disease

(stage I-III)

Stage I diseaseEMRLimited surgical resectionGastrectomy

Stage II & IIISubtotal gastrectomy or

Total gastrectomy With lymphadenectomy

Followed by Post-op ChemoRT

OrPeri-op Chemotherapy

Treatment of metastatic disease

(stage IV)

Stage IVChemotherapy

Palliative surgeryPalliative radiotherapy

Standard Treatment

Management of stage I gastric carcinoma

1) Endoscopic Mucosal ResectionIndications:Well differentiated carcinoma.Tumor 20 mm or less in size for elevated types.Tumor 10 mm or less in size for depressed types.Tumor not associated with peptic ulcersInvasion limited to mucosa. (Japanese gastric cancer association guidelines)

Advantage:Better quality of lifeLess incidence of post-op complication.

• Complication: Bleeding (0 to 20.5%)Perforation (0 to 5.2%)

• RCTs are needed to establish an outcome advantage over open surgery.

2) Limited Surgical Resection• Indication:• Low rate of LN involvement in EGC limited resection may be a

reasonable option.• No well accepted criteria.• Based on available pathological studies-a. Small < 3 cm intramucosal tumorb. Nonulcerated intramucosal tumor of any size• Procedure: Gastrotomy with full thickness local excision• Lymph node dissection not required.

3) Gastrectomy

Indication for EGC• Patient who have intramucosal tumor with poor histologic

differentiation.• Size > 3 cm• Tumor invasion up to submucosa or beyond

Gastrectomy

Subtotal gastrectomy• Removal of-• 80 % stomach, gastrohepaic

and gastrocolic omenta & first part of duodenum. (2 cm distal to pylorus)• Preservation of short gastric

vessels.

Total gastrectomy• Removal of-• Entire stomach, 7-8 cm of

distal esophagus, gastrohepatic, gastrocolic omenta, first part of duodenum (2 cm distal to pylorus)• If tumor adhere to the spleen,

pancreas, liver, diaphragm, colon, or mesocolon then involved organ or organs are removed en bloc.

There appears no advantage to performing total gastrectomy if subtotal gastrectomy produces satisfactory margin 5 cm.

Total and Sub total Gastrectomy

Subtotal GastrectomyRoux-en-Y reconstruction (more commonly)Gastroduodenostomy (less commonly)

Total Gastrectomy

Management of stage II and III Gastric carcinoma

• Resectable disease• Surgery followed by

adjuvant treatment (chemoradiation)

• Perioperative chemotherapy followed by surgery

Unresectable disease chemoradiation

- Loco regionally advanced• Involvement of root of mesenteric node• Hepatoduodenal nodes• Para aortic nodes• Invasion or encasement of major vessels• Distant metastases or peritoneal seeding

Criteria - unresectability

Goal of surgery – To achieve a microscopically complete resection (R0)Need 5-6 cm margin.10% incidence of tumor + margin if only 4-6 cm gross

margin is taken.30% incidence of + margin if 2 cm gross margin is taken.

Extent of resection for Mid & Distal Gastric Ca

• Depends on the gross and microscopic status of surgical margins.• Three small prospective RCT compared total gastrectomy

with subtotal gastrectomy conclude that R0 resection can be achieved by subtotal gastrectomy over total gastrectomy and relevant for distal gastric CA.

Bozzetti F, Marubini E, Bonfanti G, et al. Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group. Ann Surg 1999;230(2):170.

Extent of resection for proximal gastric Ca

Options – Optimal surgical procedure is matter of debate. Transabdominal approach with resection of lower

esophagus and proximal stomach or total gastrectomy. Combined transabdominal and Transthoracic approach -

Esophagogastrectomy with an intrathoracic or cervical anastmosis b/w proximal esophagus and distal stomach.

Transhiatal esophagectomy with resection of esophagus & EGJ with mediastinal dissection through esophageal hiatus of diaphragm.

Lymphadenectomy- Lymph node stations

Extent of lymphadenectomy

• Japanese Research Society for the study of Gastric Cancer• N1 : LN stations 1-6 (perigastric LN)• N2 : LN stations 7-11 (extra perigastric LN)• N3 : LN stations 12-14 (hepatoduodenal LN)• N4 : LN stations 15-16 (para aortic LN)• Data suggest removal and analysis of at least 15 LNs is

required.• Indeed AJCC staging system accounts for analysis of 16 or

more LNs to assign a pathologic N stage.

Lymph Node DissectionD0- incomplete dissection of N1 nodesD1- removal of involved proximal and distal stomach with

margin or total gastrectomy along with removal of lesser and greater omental lymph nodes (Includes right and left cardiac lymph nodes, right gastric artery and supra and infra pyloric nodes)

D2 – D1 plus removal of all nodes along left gastric artery, common hepatic artery, celiac artery, splenic hilum and artery

D3 – D2 plus omentectomy, clearence of porta hepatis lymph nodes and para-aortic lymph nodes, spleenectomy, pancreatectomy.

D1 and D2 resection in proximal third Gastric CA

D1 and D2 resection in middle third Gastric CA

D1 and D2 resection in lower third Gastric CA

Benefit of D2 dissection over D1

MRC (medical research counsel) trial (follow-up 5 yr)

Dutch Cancer Group Trial (follow-up 15 yr)

D1 D2 P D1 D2 P

Overall survival (%) 35 33 NS 21 29 NS

Operative mortality rates

6 13 .004 4 10 .004

Post-operative complication rates

28 46 .001 25 43 <.001

Locoregional recurrences

- - - 22 12

Songun I, Putter H, Kranenbarg EM, et al. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 2010;11(5):439.

Partial pancreatectomy & splenectomy – resect or preserve?

• Multiple trial have demonstrated that routine spleenectomy and pancreatectomy for gastric cancer does not increase survival and is associated with increased morbidity and mortality except in cases where direct extension of tumor. (Bozzetti et al 1997, Csendes et al 2002, Wu et al 2006, Dutch trial, MRC trial)

Patterns of failure in 82 evaluable patients in the University of Minnesota Reoperation series

Failure rates after surgery

Radiotherapy

• RT alone• Chemoradiation

Indications

• Post op RT with concurrent and maintenance 5 FU based chemotherapy is recommended for patient with stage IB-IV and M0 gastric cancer.

• For T2N0, Chemoradiation if it has • Poorly differeniated• LVSI+ve• PNI +ve• High grade disease

• RT with concomitant 5FU based chemotherapy for locally confined gastric cancer that either is not technically resectable or occurs in medically inoperable patients.

• Incomplete gastric resection.• Positive surgical margins.

Resected Stage IB-IV (M0)Gastric AdenoCa

5-FU/LV

5-FU/LV 5-FU/LV

5-FU/LV x2 (D1-5/q30days)RADIATION4500 cGy/25# 425/20mg/m2

400/20mg/m2 400/20mg/m2

425/20mg/m2

1 mo

Patient selection 556 patients with completely resected gastric cancer IB to IV M0Nearly 70% had T3 , T4 disease85% had Lymph nodal metsOnly 10% underwent D2 dissection

INT-0116

MacDonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725–730.

Sx f/b Post op Chemo-Rt

Sx alone P value

RFS 48% 31% 0.001

3 yr OS 50% 41% 0.005

Median OS

36 mnths 27 mnths 0.005

Local Failure

19% 29% Significant

Gr ¾ GI Toxicity

54% 33% Significant

Initial results – 5 yrs FULong term results - 10 yrs FU• Postoperative chemoradiation

significantly improved OS and RFS.• With more than 10 years of median

follow-up, survival remains improved in patients with stage IB-IV (M0)

• No increases in late toxic effects were noted

• Only 64% of patients completed treatment and 17% discontinued treatment due to toxicity

The results of the INT-0116 trial have established postoperative chemoradiation therapy as a standard of care in patients with completely resected gastric cancer who have not received preoperative therapy

• Median overall survival was 37 months versus 38 months (p = .8), 3-year overall survival 50% versus 52%, and 3-year disease-free survival 46% versus 47%.

• Conclusions from these preliminary results were that following curative resection of gastric or GE junction adenocarcinoma, postoperative chemoradiotherapy using ECF before and after 5-FU–based radiation does not improve survival compared to bolus 5-FU/leucovorin given in the same manner.

Intergroup trial CALGB 80101, 2011

One cycle of 5-FU/leucovorin, followed by 45 Gy with concurrent continuous infusion 5-FU, followed by two additional cycles of 5-FU/leucovorin

One cycle of ECF (epirubicin, cisplatin, 5-FU), followed by 45 Gy with concurrent, continuous infusional 5-FU, followed by two additional cycles of reduced dose ECF.

vs

Fuchs C, Tepper J, Niedzwiecki D, et al. Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FU/LV before and all CRT: intergroup trial CALGB80101. J Clin Oncol 2011;29:4003.

• Adenoca of esophagus or gastric cardia• Pre op arm : 2 cycles Cis/5FU (wk 1 & 6) + RT 40Gy/15#,starting with chemo• Preoperative chemoradiation with fluorouracil and cisplatin followed by surgery.

(trimodality arm)• Experimental arm was superior to surgery alone in patients with resectable

adenocarcinoma of the esophagus (74 patients) and gastric cardia (39 patients) in terms of survival.

• The median survival was 16 months and 11 months (p-0.01) • 3-yr survival of 32% in experimental arm vs. 6% in control arm. (p-0.01)• Multimodal treatment is superior to surgery alone for patients with resectable

adenocarcinoma

Preoperative Chemoradiation Therapy Walsh et al 1996

Walsh TN, Noonan N, Hollywood D, et al. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996;335:462–467.

• Zhang and colleagues randomized 370 patients to preoperative RT or surgery alone.

• 143 Resection rates were also higher in the preoperative RT arm (89.5%) compared to surgery alone (79%)

• preoperative RT improves local control and 5 yr survival• 5 yr OS rates were 30% and 20% in preop RT+ SX and SX alone arm

respectively. (p= .009)• Further local and regional nodal control was 61% & 61% in preoperative

irradiation and surgery and 48% & 45% in surgery alone arm.

Pre op RT

Zhang ZX, Gu XZ, Yin WB, et al. Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC)—report on 370 patients. Int J Radiat Oncol Biol Phys 1998;42:929–934.

Zhang et al 1998

Post-op Radiotherapy alone

432 patients with Resectable Gastric Cancer

Surgery

Surgery Surgery

Chemotherapy (FAM)

Radiotherapy

British Stomach Cancer Group

Hallissey MT, Dunn JA, Ward LC, et al. The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up. Lancet 1994;343:1309–1312.

Post op radiation therapy dose was 45 to 50 Gy in 25 to 28 fraction

The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up

• 5 yr survival for-• Surgery alone 20%• Surgery followed by RT 12%• Surgery followed by chemotherapy 19%

• There was a significant reduction in loco regional recurrence with the addition of RT to surgery (27% with surgery vs. 10% for surgery plus RT and 19% for surgery plus chemotherapy)• No survival benefit at 5yr Follow up for patient who received

PORT• Drawbacks – • inclusion of 171 pts. underwent resection with gross or

microscopic residual carcinoma• Only 68% pts in PORT arm received a dose 40.5 Gy or more

and 24% received none.

• The theoretical advantage of this approach ability to deliver a more intensive dose of radiation to the tumor bed

• Randomized patients based on the day of hospital admission to surgery plus IORT (28-35 Gy) versus surgery alone.

• The limited data suggest that IORT may be beneficial in selected patients with gastric cancer.

• There was an improvement in OS with IORT (Takahashi & Abe)• It was limited to patients with stage III and IV disease• The use of IORT in gastric cancer, although encouraging, remains

investigational.• IORT

• For locally advanced disease – improves LC rates• As a boost to boost to EBRT to improve LRC in celiac area

Intraoperative Radiation Therapy

Abe M, Takahashi M, Ono K, et al. Japan gastric trials in intraoperative radiation therapy. Int J Radiat Oncol Biol Phys 1988;15:1431–1433.

Chemotherapy

• Peri-operative chemotherapy• Post-operative chemotherapy

Pre-operative Chemotherapy: Advantages• 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

Pre-operative Chemotherapy: Potential Disadvantages

• Potential risk of peri-operative morbidity• Definitive surgery may be delayed if significant toxicity occurs• Risk of disease progression during preoperative treatment

503 T2 or higher non metastatic Gastric & GEJ tumor, R0 resection but no D2 dissection

ECF Surgery ECF Surgery alone

• Primary end point – OS• Median FU – 48 mnths• Rates of postoperative complications were similar in both arms (46% and 45%

respectively), as was the postop 1 month mortality. • Adjusted HR for death, 0.74 (95% CI 0.59 to 0.93; p = 0.008)• HR for progression 0.66; 95% CI 0.53 to 0.81; p<0.001)

MAGIC Trial - MRC Adjuvant Gastric Infusional Chemotherapy

Cunningham et al. N Engl J Med. 2005;355(1):877–89.

• 5-year survival 36% vs. 23% (p-0.009)• Limitations:

• Only 42% of patients in the test group completed all protocol treatment.• 5 year survival data with a median survival of 4 years is questionable.

• Conclusion: Perioperative chemotherapy with a regimen of ECF improves OS and PFS among patients with resectable adenocarcinoma of the stomach, lower esophagus, or GE junction, as compared with surgery alone.

Cunningham et al. N Engl J Med. 2005;355(1):877–89.

• ACCORD 07/ FNCLCC/FFCD trial, 2011• N = 224; 75% of patients had adenocarcinoma of the lower esophagus or

EGJ and 25% had gastric cancer)• Use of CDDP + 5FU as perioperative CT and compare it with surgery alone.• 2-3 Pre-op cycles of FU 800 mg/m2/d as continuous intravenous (IV)

infusion for 5 consecutive days (days 1 to 5) and cisplatin 100 mg/m2 as a 1-hour infusion, every 28 days, and 3-4 postoperative cycles

• Sx was done 4 to 6 weeks after completion of the last cycle of chemotherapy • Primary end point - OS

Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011;29:1715–1721.

• Perioperative chemotherapy significantly increased the curative resection rate, DFS, and OS in patients with resectable cancer.

• The 5-year OS rate was 38% for patients in the surgery plus perioperative chemotherapy group and 24% in the surgery only group (P = .02)

• The results of these two studies established perioperative chemotherapy as another alternative option for patients with resectable gastric cancer who have undergone curative surgery with limited lymph node dissection (D0 or D1).

• These studies were not powered to evaluate its role when D2 lymph node dissection is performed

CLASSIC - Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer

• 1035 pts• Median FU – 34.2 mnths• Stage II-IIIB gastric cancer with curative D2 resection• Randomised to Sx alone vs Sx + 8 cycles Cap/Ox• Cap - 1000 mg/m2 twice daily on days 1 to 14; Ox - 130 mg/m2 on day 1• Primary end point DFS (74% vs 59%; p<0·0001) • Grd ¾ GI Tox. – 56% vs 6%• Adjuvant therapy with capecitabine and oxaliplatin improves 3 year disease-free

survival after D2 gastrectomy compared with D2 gastrectomy only

ACTS GC /S-1 trial• Novel oral fluoropyrimidine S-1 (combination of tegafur [prodrug of fluorouracil; 5-

chloro-2,4-dihydropyridine] and oxonic acid)• 1059 patients - randomized to Sx alone or Sx f/b Post-op Chemo with S-1 for 1 yr• Stage II (excluding T1) or III gastric cancer who underwent R0 resection with D2 LN

dissection • Median FU – 2.9 yrs• The 3-year OS rate was 80.1% and 70.1%, respectively, for S-1 group & Sx alone

Postoperative Chemotherapy

Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 2007;357:1810–1820.

• The 3-year OS rate was 80.1% and 70.1%, respectively, for S-1 group & Sx alone

Results of our trial is not valid in regions where D2 surgery is not considered the standard operation

Post-op CTRT vs Post-op CT

• ARTIST – Adjuvant Chemo-radiation in Stomach Cancer Trial• 459 R0 resected gastric cancer patients who have undergone D2 dissection• Arm A : 6 cycles of XP• Arm B: 2 cycles XP CCRT with X 2 cycles XP• XP - capecitabine 2,000 mg/m2 per day from D 1 - 14 and cisplatin 60 mg/m2

on day 1 • CCRT - 45-Gy XRT (capecitabine 1,650 mg/m2 per day for 5 weeks )• Median FU – 53 mnths

Lee J, Lim DH, Kim S, et al. Radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol 2011 December 19.

• In the subgroup of patients with pathologic LN metastasis at the time of Sx (n = 396), patients randomly assigned to the XP/RT/XP arm experienced superior disease-free survival when compared with those who received XP alone (p = .0365).

• Updated analysis 2015, With 7 years of follow-up• DFS remained similar between treatment arms• OS also was similar • There was a similar trend for DFS and OS by stage of disease.• Subgroup analyses also showed that chemoradiotherapy significantly improved

DFS (p=.04)in patients with node +ve disease and with intestinal-type GC (p=.03)

• No reduction of recurrence in pts with R0 and D2 dissection

• Treatment was completed as planned by 75.4% of patients (172 of 228) in the XP arm and 81.7% (188 of 230) in the XP/RT/XP arm.

• The addition of radiation to XP chemotherapy did not significantly prolong disease-free survival (p = .086).

GASTRIC Meta-analysis

• IPD Meta-analysis – 17 trials (3838 pts)• Adjuvant chemotherapy was associated with a statistically significant

benefit in terms of • OS (HR, 0.82; 95% CI, 0.76-0.90; P .001) • DFS (HR, 0.82; 95% CI, 0.75-0.90; P .001)

• 5-yr OS increased from 49.6% to 55.3% with chemotherapy • Postop adjuvant 5-FU based chemo was associated with reduced risk of

death in gastric cancer (HR-0.82) compared with surgery alone.

Paoletti et al., JAMA 2010

Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, Rougier P, Sakamoto J, Sargent D, Sasako M, Van Cutsem E, Buyse M. Bene t of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA 2010; 303: 1729-1737

Targated therapies

Outcome Chemotherapy + Trastuzumab

(n = 294)

Chemotherapy Alone

(n = 290)

HR (95% CI) P Value

Median OS, mos 13.8 11.1 0.74 (0.60-0.91) .0046

Median PFS, mos 6.7 5.5 0.71 (0.59-0.85) .0002

Established transtuzumab and chemotherapy is a new standard of care for Her-2 neu expressing advanced gastric and EGJ adenocarcinoma.

Significant OS benefitSafety profile were similar

Evidence from meta-analysis favoring Adjuvant treatment

RT techniquesconventionalConformal

• Supine position. • Immobilization: Legs with knee support, thermoplastic

device or vacuum cushion is recommended• Position of hands: arms lifted above the head• Oral contrast• Intravenous contrast

Conventional technique: simulation

Field design

Anteroposterior-posteroanterior (AP-PA) fieldSuperior Bottom of T8 or T9

Inferior Bottom of L3

Left Include 2/3rd to 3/4th of left hemidiaphragm

right 3-4 cm lateral to vertebral bodies

….Continued Conventional technique

….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

Simulation film for T3 antral tumor with two of five peritumoral lymph nodes metastatically involved

Conformal technique3D-CRT

IMRT

• Supine position. • Immobilization: Legs with knee support, thermoplastic

device or vacuum cushion is recommended• Position of hands: arms lifted above the head• 3- to 5-mm slice thickness• Oral contrast• Intravenous contrast

Conformal technique: simulation

Target volumes –• GTV in pre-op/unresectable cases• CTV• PTV

Target volume definition

Target Volumes in Unresected cases

• Gross tumor volumes (GTV) : GTV_T + GTV_N.

• GTV_T : Primary tumor (including the perigastric tumor extension)

• In case of induction/neoadjuvant CT, GTV prior to this.

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,

Contd…Target Volumes in Unresected cases

Lymph node stations

Stations of LN to be taken:

CTV_Nodal: Proximal stomach / GEJ Type I, II, III

Type 1 Type II Type III1,2,7,9,19,20,110,111,112. 1,2,3,4sa,7,9,11p,19,20,110,1

111,2,3,4sa,4sb,7,9,10,11p,11d,19

CTV_Nodal contd…

Middle 1/3rd Lower 1/3rd

LN st. 1 – 6,10,11,12 3,5,7,8,9,11p,12a,12b,12p,13,17,18

Target Volumes in post-op cases

RT: Post op- cases

Stage Remaining stomach

Tumor bed volume Nodal volume

T2N0 (invasion upto serosa)/T3N0

Variable for prox/distal

Include in mid1/3rd

Prox: medial lt hemidiaphragm, adjacent body of pancreas(with or without tail)

Prox: none or optional

Mid: body of pancreas (with or without tail)

Mid: none or optional

Dis: head of pancreas (with or without body), 1st & 2nd part of duodenum

Dis: none or optional

T4aN0

Variable for prox/distal

Include in mid1/3rd

Prox: medial lt hemidiaphragm, adjacent body of pancreas(with or without tail)

Prox: none or optional

Mid: body of pancreas (with or without tail)

Mid: none or optional

Dis: head of pancreas (with or without body), 1st & 2nd part of duodenum

Dis: none or optional

Guidelines: site specific

T4bN0Prox: variable Prox/Mid/Dis: As

for T4aN0 + site of adherence with 3-5 cm margin

Nodes related to site of adherenceMid: include

Distal: preferable

T1-3N+

Prox: preferable

Not indicated for T1-2For T3N+ same as for T3N0

Prox: PG,CN,SpLN,SpLNs with or without PEN, HNpd, PHN

Mid: include Mid: PG,CN,SpLN,SpLNs, HNpd, PHN

Distal: preferable Distal : PG,CN,HNpd,SpLNs (SpLN opt)

T4N+

Prox: preferableAs for T4a/b N0 for all sites

As for T3N+ and T4bN0Mid: include

Distal: preferable

PTV

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

•  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

• Although parallel-opposed AP/PA fields are a practical arrangement for tumor bed and nodal irradiation.• Multifield techniques should be used if they can improve

long-term tolerance of normal tissues

Field design

Stage wise treatment :• T1N0 :

• Surgery alone (partial or total gastrectomy with at leaast D1 LN dissection)• Selected T1a pts for EMR

• T2-4 and/or LN+ resectable/operable :• Sx postop 1c x 5FU/Lv 2c Conc. 5FU/Lv + 45Gy RT 1c x

5FU/Lv (INT0116)• Preop ECF x 3c Sx postop ECF x 3c (MAGIC)• Sx alone may be considered for T2N0 without high risk features (like pd, hg, LVI+, PNI+, Age <50yrs)

• T2-4 and/or LN+ unresectable/inoperable :• Conc. ChemoRT (45-50.4 Gy)• Chemo alone (ECF, EOX, DCF, FOLFOX/XELOX, Pacli/Carbo)• Based supportive care• RT alone in palliative doses

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