Carcinoma stomach

1. Carcinoma Stomach
Management
Dr. Kiran Kumar BR
Moderator: Dr. Bhaskar

2. OUTLINE
• ANATOMY
• EPIDEMIOLOGY
• RISK FACTORS AND
ETIOLOGY
• PATHOLOGY
• CLINICAL-PRESENTATION
• WORKUPAND STAGING
• PROGNOSTIC FACTORS
MANAGEMENT:
• SURGERY
• RADIATION
• CHEMOTHERAPY
• SUPPORTING EVIDENCE
• FOLLOW UP
• CONCLUSION AND
RECOMMENDATIONS

3. TNM STAGING

7. TREATMENT GROUPS
• Locoregional carcinoma-
Stage I-III or M0
Potentially resectable disease in medically fit pts
who are able to tolerate major abdominal surgery.
Unresectable disease in medically fit pts
Medically unfit pts.
• Metastatic ca- stage IV / M1

8. TREATMENT OPTIONS
• Surgery - Primary treatment
• Radiation – Adjuvant/palliative
• CCT- Perioperative/Adjuvant/palliative
• Chemoradiation- Adjuvant
• Best supportive care.

10. SURGERY
PRINCIPLE
Complete resection of tumor with 5 cm margin
proximally and distally.
• R0 – no macroscopic or microscopic tumor at
resection margins.
• R1 – microscopic margins +ve.
• R2 – macroscopic margins +ve.
• AIM - R0 resection always.

11. SURGERY
• Primary treatment of gastric cancer
• OPTIONS-
 Radical Total Gastrectomy –
 Diffuse involvement
 Proximal involvement.
 Radical Subtotal Gastrectomy –
 Distal cancers,
 Equivalent survival
 Lesser complications
 In proximal cancer, total gastrectomy is
not necessary when subtotal gastrectomy
will provide a 5 cm clearance of the gross
tumour.

12. Endoscopic Mucosal Resection
T1 early lesions that are padunculated
Well differentiated
Small size <3cm
No submucosal involvement- chance of LN involvement- <5%
SPLENECTOMY
Splenectomy is sometimes performed, particularly in cancers of
proximal third of stomach and tumours of the body near the
greater curvature
Cancers in these locations are more likely to metastasize to lymph
nodes in the splenic hilum that can not be excised without
splenectomy.

13. LN DISSECTION

14.  D1 – Perigastric node( Station 1-6)
 D2 –D1+ perarterial nodes(left gastric, hepatic, celiac, splenic)(7-11)
 D3- D2+ hepatoduodenal, peripancreatic, mesenteric root, portocaval, P-A
nodes, middle colic(13-16)
 D2 to D3 – extended or systemic lymphadenectomies (ELND)
 D0-D1- conservative/limited lymphadenectomies(CLND)
 PRINCIPLE- Dissect the echelon of nodes a level higher than the highest
level of known metastasis;
 Controversy-balancing the benefits of a more extensive, complete
lymphadenectomy with the associated higher risk of morbidity/mortality.

15. WILL ROGERS PHENOMENON
Diff. in survival b/w Japan & West-
STAGE MIGRATION.
 Extensive pathologic LN evaluation leads to upstaging & subsequent
statistical improvements in overall survival when compared stage for stage.
 Western patients would be staged inappropriately "low" because of failure
to examine node-bearing areas accurately, affecting the outcome toward a
worse prognosis.
CURRENT STATUS OF LN DISSECTION
 ELND improves the quality of staging, allowing standardization of
prognostic factors and survival data worldwide.
 Routine D2 lymphadenectomy is difficult to justify based on available
evidence.
 Issues- patient selection, surgeon experience, ?survival benefit.
 Minimum, D1 lymphadenectomy should include pathologic examination
of at least 15 nodes.

16. RELAPSE PATTERN AFTER CURATIVE RESECTION
• Cure Rates with surgery alone not adequate.
• High rates of both LRR & distant metastasis.
• T1-T2/N0 only had adequate cure with surgery alone- 90%.
• Radical surg + ELND, does not prevent relapses.
• Subsequent relapse within the site of a prior ELND was
frequent,=>incomplete LN and lymphatic excision.
• Progressive extension of surgery => min. increase in cure rates, offset by a
corresponding increase in operative mortality.
Incidence and patterns of Local relapse predictable based on anatomical
factors, pathways of tumour spread, initial extent of disease, and anatomic
limitations for surgery.
 Distant failures also common.
 Combinations of chemotherapy and irradiation are necessary to alter both
short- and long-term survival.

17. PATTERN OF RELAPSE

18. RADIOTHERAPY
• Post op XRT
• Pre op XRT
• Intraoperative RT
• Palliative RT
Indications-
 T3-4 resectable disease
 Margins positive
 Residual disease
 LN +ve disease
 Inoperable

19. RADIOTHERAPY TARGET
• Idealized portals from patterns of failure data need modification
individually for patient's initial extent of disease.
• Gastric/tumor bed, anastomosis and gastric remnant, and regional
lymphatics should be included in most patients.
• Major nodal chains at risk include
lesser and greater curvature;
celiac axis;
pancreaticoduodenal,
splenic,
suprapancreatic,
porta hepatis groups;
para-aortics to the level of L3.
Any tumor originating in the stomach has a high propensity of spread to nodes along
the greater and lesser curvature, although they are most likely to spread to those sites
in close anatomic proximity to the primary tumor mass.

20. BORDERS
SUPERIOR BORDER- Bottom of T8 or T9 to
cover celiac axis, GE junction, fundus, and the
dome of left hemidiaphragm
INFERIOR BORDER- Bottom of L3 to cover
gastroduodenal nodes and antrum
LEFT BORDER- Include two third to three
Fourth of left hemidiaphragm to cover fundus,
suprapancreatic nodes and splenic nodes
RT LATERAL- 3 to 4 cm lateral to vertebral
Bodies to cover the antrum , porta hepatis,
and gastroduodenal nodes
Dose of RT- 45-50Gy/25#/5weeks, 1.8-2Gy/#

21. IVP 1 MIN IVP 3 MIN

22.  Position supine
 AP/PA parallel opposed fields
 Weighted equally or anteriorly more to
decrease spinal cord dose
 Blocks whenever possible should be
used to decrease dose to –
 Liver (70% <30Gy)
 Kidney (2/3 <20Gy)
 Heart (1/3 <45Gy)
IVP 10 MINS

24. CONTOURING OF CTV

27. LN INVOLVEMENT IN PROXIMAL THIRD STOMACH

29. LN INVOLVEMENT IN MIDDLE THIRD

31. LN INVOLVEMENT IN DISTAL THIRD

32. GASTRIC REMNANT
SPLENIC HILUM
PERIPANCREATIC
PORTA-HEPATIS

35. PRE OP RT
Series groups No of pts Survival
5 yr
LRR
Beijing Sx
Pre
RT(40)
199
171
20
30
52
39
Three other studies from Russia also evaluated role of adjuvant pre op
RT in potentially resectable patients.
All showed improved 3 yr and 5 yr survivals.
All trials used different doses of RT
Role for unresectable LAD evaluated in different studies show survival
benefit of 9-10 months

36. POST OP RT
Post op RT improves local control but does not improve survival unless combined
With chemotherapy

37. IORT
• Advantage
Deliver a single, large fraction (10-35Gy) to tumour &
tumour bed
Exclusion or protection of surrounding normal tissue
from the high-dose field.
Disadvantages
Intense fibrosis.
Neurological complications.
Still a investigational tool.
Yet to be proved better than conventional RT.
Need special equipment and expertise.
Options- IORT+/-XRT

38. Linear accelerator with electron lucite
applicator

39. IDEAL INTEGRATION OF IORT AND EBRT

43. CHEMOTHERAPY
• Single agent therapy
• Combination therapy-
Resectable d/s-
Perioperative,
Post operative.
Locally advanced/metastatic d/s

44. SINGLE AGENT CCT
• The results - disappointing.
• CR in metastatic disease rare.
• PR – limited.
• Objective responses – limited & brief
duration
• Most widely used agents-
• 5-fluorouracil
• Cisplatin
• Taxanes
• Single-agent therapy may be a reasonable
approach in patients who would not
tolerate, combination therapy.

45. COMBINATION CCT REGIMENS
• FAM
 5-FU 600 mg/M2 IV D- 1,8, 29,36
 Doxorubicin 30 mg/M2 IV D- 1,29
 Mitomycin C 10 mg/M2 IV D-1
(REF: MacDonald et al. Ann Intern Med 1980; 93:533-536)
 Repeat every 56 days
• FAMTx
 Methotrexate 1500 mg/M2 IV D 1 give MTX first and then wait 1 hour
and give 5-FU
 5-FU 1500 mg/M2 IV D- 1
 Leucovorin 15 mg/M2 PO Q6H D 2-4 X total 12 doses starting 24 hrs
after MTx
 Doxorubicin 30 mg/M2 IV D- 15
REF: Kelsen et al. J Clin Oncol 1992; 10:541-548
 Repeat cycle on day 29

46.  ECF
 Epirubicin 50 mg/M2 IV D 1
 Cisplatin 60 mg/M2 IV D 1
 5-FU 200 mg/M2/d CIV(X21 days) daily
 REF: Webb et al. J Clin Oncol 1997; 15:261-267
Irinotecan/ cisplatin
 Irinotecan 70 mg/M2 IV days 1, 15
 Cisplatin 80 mg/M2 IV day 1
 REF: Boku et al. J Clin Oncol 1999; 17:319-323
 Repeat every 28 days

47.  PF paclitaxel/fluorouracil
 Paclitaxel 175 mg/M2 IV (over 3 h) day 1
 5-FU 1500 mg/M2 IV (over 3 h) day 2
 REF: Murad et al. Am J Clin Oncol 1999; 22:580-586
 Repeat every 21 days for a maximum of 7 cycles
 CF
 Cisplatin: 100 mg/m2 IV over 1–3 hrs D-1
 5-FU: 1,000 mg/m2/day IV cont infus D1–5
 Repeat cycle every 28 days
Docetaxel + Cisplatin
 Docetaxel: 85 mg/m2 IV D 1
 Cisplatin: 75 mg/m2 IV D 1
3 wkly repeated.
TPF
 Docetaxel: 75 mg/m2 IV D 1
 Cisplatin: 75 mg/m2 IV over 1–3 hrs D 1
 5-FU: 750 mg/m2/day IV cont infusion D 1–5
 Repeat cycle every 21 days.

49. ADJUVANT CCT
• 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.

50. PERIOPERATIVE CT
MAGIC TRIAL
• Surgery alone or Surgery plus three cycles of
preoperative epirubicin, cisplatin, and infusional
5-FU (ECF regimen) and three cycles of
postoperative ECF therapy.
• The use of perioperative chemotherapy was
associated with significant improvement in
survival compared with surgery alone.

52. MAGIC TRIAL
NO. OF
PATIENTS
MEDIAN
SURVIVAL(
MONTH)
3 YEAR
SURVIVAL(
%)
5 YEAR
SURVIVAL(
%)
RFS (%)
ONLY
SURGERY
253 20 31 23 26
PERIOPERA
TIVE CCT
250 24 45 36 39

54. FLOT 4
• FLOT4 (NCT01216644) is a multicenter,
randomized, investigator-initiated, phase 3 trial.
• It compares the docetaxel-based triplet FLOT
with the anthracycline-based triplet ECF/ECX as
a periop treatment for pts with resectable gastric
or GEJ adenocarcinoma.
• (docetaxel 50 mg/m2, oxaliplatin 85 mg/m²,
leucovorin 200 mg/m², and 5-FU 2600 mg/m²)

55. • FLOT improved OS (mOS, 35 mon with ECX/ECF
vs. 50 mon with FLOT p = 0.012). 3y OS rate was
48% with ECF/ECX and 57% with FLOT.
• FLOT also improved PFS (mPFS, 18 mon with
ECX/ECF vs. 30 mon with FLOT p = 0.004).
• Conclusion: Periop FLOT improved outcome in
patients with resectable gastric and GEJ cancer
compared to periop ECF/ECX.

57. CONCURRENT CRT- PHASE II TRIALS
Study No Surv
median
Long% LRR No LRR %
MGH
Sx
RT+5-FU
110
14
-
24
38/5
43/5
46
2
42
14
TJUH
Sx
RT+CCT
70
20
12
19
13/5
21/5
17
3
45
19
Penn
Sx
SX+RT
Sx+RT+C
CT
40
17
27
16
15
21
31/2
50/2
55/2
31
4
4
75
24
15
Mayo
Rt + 5-
FU+_Le
25 19 31/4 5 20

58. INT-0116
 Agent Dosage
 5-FU 425 mg/M2 IV bolus days 1-5
 Leucovorin 20 mg/M2 IV bolus days 1-5
 1 cycle postop, followed by
 XRT–adjuvant
 5-FU 425 mg/M2 IV bolus days 1-4,38-40
 Leucovorin 20 mg/M2 IV bolus days 1-4,38-40
 concurrently with XRT
 CCT given on first 4 and last 3 days of RT followed by-
 POST RT
 5-FU 425 mg/M2 IV bolus days 1-5
 Leucovorin 20 mg/M2 IV bolus days 1-5
 every 28 days for 2 cycles

60. RESULTS

63. RESULTS

65. CALGB 80101
• Postoperative adjuvant chemoradiation for gastric or
GE junction adenocarcinoma using ECF before and
after 5-FU/radiotherapy compared to bolus 5-FU/LV
before and after 5-FU/radiotherapy:Intergroup trial
CALGB 80101
CS Fuchs, JE Tepper, D Niedzwiecki, D Hollis,
HJ Mamon, RS Swanson, DG Haller,
T Dragovich, SR Alberts, G Bjarnson, CG Willett,
PC Enzinger, RM Goldberg, AP Venook, RJ Mayer

67. CALGB 80101
Overall Survival by Treatment Arm
Arm
Median
OS*
3-year OS 5-year OS
Hazard
Ratio (95%
CI)
5-FU/LV 36.6 mos 50% 41%
ECF 37.8 mos 52% 44%
1.03 (0.80-
1.34)
*P, log rank = 0.80

72. UNRESECTABLE CARCINOMAS
• CRITERIA-
 Peritoneal involvement
 Distant mets
 Invasion/encasement of blood vessels
 Level 3 or 4 LN on imaging
• Palliative surgery- AIM-
 Palliate symptom
 least morbidity
 Least mortality
 INDICATIONS-
 Pyloric obstruction(GOO)
 Bleeding
 Pain
 OPTIONS-
 Distal gastrectomy,
 Total gastrectomy,
 Gastrojejunostomy,
 Intubations,
 Laser recanalization,

74. ROLE OF CRT IN UNRESECTABLE CARCINOMA

76. ROLE OF NEOADJUVANT CCT
• Potentially resectable LAD-
 EFP/EAP/FAMTX/CF- 15-16 m median survival with pCR only in 7-9 % in
FAMTX pts of 60-70% resected.
• Boderline resectable LAD
 EAP/CF- 30/15 m median survival and only EAP regime showing 7%
pCR in 70% resected
• Unresectable LAD
 EAP/FMTX- 18 m survival with 44% resected and 15 % CR.
• So all phase II trials showing some significance and none of 2
phase III trials showed any benefit.
In general, pathological complete response rate is low and the
impact of NACT on survival is even less.

77. METASTATIC DISEASE
SURGERY
 Palliative resection
 Endoluminal stenting
 Endoscopic laser treatment
 Gastrostomy tube placement
RADIATION
Radiation therapy is capable of providing substantial palliation of local gastric
cancer symptoms.
 50% to 75% of patients improve
 Indications-
 gastric outlet obstruction,
 pain from local tumor extension
 benefit may increase with concomitant 5FU administration,
 The median duration of palliation varies from 4 to 18 months in reports addressing
this issue
 Dose- PGI – 30gray/10#/2wks.

78. SINGLE AGENT
 Doxorubicin, mitomycinC, etoposide, cisplatin,5-FU- response rate of 20%
or more
 Docetaxel- 23% response rate
 Irinotacan- 23% response rate
 Paclitaxel- 17-21% response rate
Complete remission is extremely rare and remission duration is 3-5 months.
COMBINATION CCT
 Reliable response in 25-50% of patients
 Median survival of 3-5 months
CCT

79. RESULTS
EORTC
RESPONSE RATE MEDIAN SURVIVAL
FAM 41% 42 weeks
FAMTX 9% 29 weeks
ROYAL MARSADEN HOSPITAL
RESPONSE RATE SURVIVAL
FAMTX 21% 6 month
ECF 45% 9 month
1 year survival Median survival
EOX 46.8% 11.2 month
ECF 37.7% 9.9 month

80. TAXANE REGIMEN
PHASE II TRIAL
-Docetaxel plus cisplatin- response rate of 28-46% and median survival is 10.5 -11.4
month
PHASE III TRIAL
DCF CF
RESPONSE RATE 69% 59%
CCT OR BSC
- All the trials have showed better survival with CCT

81. ROLE OF TARGETED THERAPY(TOGA)
Patients with overexpression of HER2 by IHC or by FISH
Trastuzumab+
cis/5-FU
Cis/5-FU
MEDIAN OS 13.5 month 11.1 month

82. SEQUELAE OF THERAPY
• Anorexia, nausea, and fatigue -very common.
• Nutritional complications and myelo-suppression-especially in CRT
 Need careful nutritional support councelling and antiemetic therapy.
 Blood counts monitoring twice weekly during CRT to avoid sepsis or bleeding.
 Achlorohydria –
 16 to 36 Gy reduce secretion of pepsin and HCL (25% to 40%) persisting 1 to 6 m, with
25% upto 1 to 5 yrs or more.
• Gastric late effects categorized by the Walter Reed Group
 dyspepsia,
 radiation gastritis,
 uncomplicated gastric ulcer,
 gastric ulcer with perforation
 obstruction

83. TREATMENT ALGORITHM

84. TREATMENT ALGORITHM

86. 5 YEAR OS
 Stage IA- 71%
 Stage IB- 57%
 Stage IIA- 46%
 Stage IIB- 33%
 Stage IIIA- 20%
 Stage IIIB- 14%
 Stage IIIc- 9%
 Stage IV- 4%
(SEER 1991-2000)

87. CONCLUSION
 Endoscopy with direct visualisation, cytology and biopsy yields the
diagnosis in > 90% of patients.
 Locally advanced disease is the most common presentation.
 Only curative treatment is surgical resection of all gross and microscopic
disease.
 Even after curative gastrectomy, disease recurs in local or distant site or
both in the majority of patients.
 Efforts to improve these poor results have focused on developing pre and
postoperative systemic and local adjuvant therapies.
 Chemoradiation is the preferred adjuvant modality in patients with stage
IB, II, IIIA, IIIB or IIIc and M0 gastric cancer.
 In case of locally unresectable disease, combined modality therapy is
reasonable approach.

89. • Thank you