Gastric cancer, investigations and management
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Gastric Cancer
Dr. Amina Abdul RahmanJunior ResidentDept. of Radiotherapy
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Investigations Management Surgery Radiotherapy CCRT Chemotherapy Supportive care Treatment algorithm
Gastric Cancer
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Investigations
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Investigation tools
• Endoscopy• CT• EUS• PET/CT• MRI• Laparoscopic staging
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Endoscopy
• Flexible Fibreoptic endoscopy with biopsy is more than 90% accurate in diagnosis
• Higher +ve yield in exophytic growths• Less accurate in infiltrative lesions• Difficult sites are cardia and antrum.
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Endoscopic image of Gastric Ca
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CT Scan and PET
• For pre-op T Staging, accuracy 80%• Nodal staging 78%• Wall thickening/ polypoidal mass/ focal
infiltration of gastric wall• PET low detection rate• Combined PET/CT higher accuracy
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EUS
• Assess depth of invasion and regional lymph nodes more accurately than CT
• Depicts individual layers of the gastric wall• Limited to an area 5cm from the probe
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EUS Images of Stomach layers
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Laparoscopic Staging
• Detecting radiographically occult metastases in T3 and/or N+ disease
• Peritoneal fluid cytology for detecting occult carcinomatosis
• If positive, considered as metastatic disease• All T3 and/or N+ disease should undergo
laparoscopic staging and peritoneal washings.
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Management
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Management
• Surgery• Radiotherapy• Chemotherapy• Supportive Care
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Surgery
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Surgery
• Endoscopic mucosal resection• Limited Gastric resection• Subtotal/total gastrectomy
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Principles of Surgery
• Requires adequate pre-op staging• R0 resection• Subtotal> total gastrectomy• Margin 0f 4 cm• Atleast 15 lymph nodes should be resected
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Surgery
• T1a : EMR• T1b -T3 : Gastrectomy• T4 : Gastrectomy with enbloc resection
of involved structures
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Endoscopic Mucosal Resection
Gastric sparing R0 resection without LN dissection for EGC who are expected to have low metastatic potential
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Endoscopic mucosal resection
• Indication: • EGC limited to the mucosa• Size of ≤2 cm in elevated type• Size of ≤1 cm in depressed type• No ulceration• Favorable histology• No lymphovascular invasion
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Limited Surgical Resection
• Candidates for EMR• Gastrotomy with full thickness local excision• Lymph node dissection not required
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Total and Sub total Gastrectomy
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Subtotal Gastrectomy
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Total Gastrectomy
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Lymph Node Dissection
• 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)
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D2 dissection
• Dutch Cancer Group Trial compared D1 with D2 dissection
• Higher morbidity, mortality with no diff in OS• But long term follow up showed fewer loco-
regional recurrences (12% vs 22%) and fewer cancer related deaths.(37% vs. 48%)
• No benefit for D3 dissection
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• D2 dissection is now recommended
- Remove at least 15 LN- Avoid splenectomy and pancreatectomy- Perform in high volume centers
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Features of inoperability
• Peritoneal involvement visible omental deposits positive peritoneal cytology• N3/N4 node• Involvement or encasement of vascular
structures• Distant metastases
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Palliative Surgery
• Limited gastric resections• For palliation of symptoms like obstruction,
and bleeding• GJ > stenting
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Radiotherapy
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Radiotherapy
• Preoperative• Postoperative Adjuvant for R0 resection RT to residual or gross disease• Palliative
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Preoperative RT
Zhang et al from Beijing 370 potentially resectable gastric cardia cancers
Pre-OP RT (40 Gy in 20#)
Surgery
Surgery alone
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Preoperative RT
• Increases rate of R0 resection• Incidence of local and regional lymph node
failure was reduced• But no difference in rate of distant failure
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Adjuvant Radiotherapy
British Stomach Cancer Group 432 patients with Resectable Gastric Cancer
No survival benefit at 5yr Follow up
Surgery 27%
Surgery Surgery
Chemotherapy 19%
Radiotherapy 10%
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Adjuvant RT
• No survival benefit when RT alone was given• Reduction in locoregional recurrence
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Palliative RT
• Bleeding• Obstruction• Pain• Median of 50 Gy is recommended
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Concurrent Chemoradiotherapy
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INT- 0116 Trial
Patient selection • 556 patients with completely resected gastric
cancer IB to IV M0• Nearly 70% had T3 , T4 disease• 85% had Lymph nodal mets• Only 10% underwent D2 dissection
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Postoperative CCRT
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INT 0116
• Median OS 36 months vs. 27months• Local recurrence rate 19% vs. 29%• 3 yr relapse free survival rates 48% vs. 32%• Post op CCRT as standard of care in patients
with IB to IV M0 disease who have undergone R0 resection
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Was concurrent chemoradiotherapy compensating for the inferior surgery in the INT 0116 trial?
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ARTIST 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• No reduction of recurrence in pts with R0 and D2
dissection
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Preoperative chemoRT
• Pilot study of preop chemoRT with concurrent 5FU infusion and IORT by Lowy et al for potentially resectable disease
• Significant PR in 63%• Complete PR in 11%• NCCN Category 2B recommendation
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Rationale for Adjuvant Radiotherapy
• Pattern of failure data 60% relapse in Tumor Bed Regional nodes Stump / anastomosis 20% will recur in these sites alone• Unpredictable pattern of lymph node involvement
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Rationale for Radiotherapy
• Sterilizes known local residual disease Mayo Trial Residual/ recurrent gastric cancer
Radiotherapy aloneMean survival 6 months5 yr survival 0%
CCRT 45 Gy with 5FU bolusMean survival 13 months5 yr survival 12%
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Clinicopathological factors for local recurrence
• Positive serosal margin (circumferential)
• Narrow longitudinal margins
• Lymph nodal recurrence
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Lymph nodes to include for subsite specific RT Planning
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Middle 1/3rd or multiple gastric subsite primaries
• Perigastric LN of cardia, lesser curvature, greater curvature (LN station 1 – 6)
• LN stations 10, 11 ( splenic hilus, splenic A.)• LN station 12 (hepatoduodenal), treat porta
hepatis
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24sa
10
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Upper one third of GEJ
• Subpyloric LN mets are rare• Increased risk of paraesophageal LN involvement
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Lower one third / Antrum
• Increased risk of subpyloric LN mets • But splenic LN mets are rare• Sparing splenic LN may spare the left kidney
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RT planning
• Patient should be simulated and treated in the supine position
• intra venous and/or oral contrast should be given to aid target localization
• Use of an immobilization device is strongly recommended.
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Target Volume
• Tumor Bed• Primary Lymph nodes• With an adequate margin of 1.5 – 2 cm• Dose is 45 – 50.4 Gy, 1.8Gy/fraction
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Superior border
• Bottom of T8 or T9 to cover coeliac axis, GEJ, fundus
• Treat the dome of left diaphragm
• Locate the site of anastomoses
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Inferior border
• Usually fixed at L3 for infrapyloric and GastroDuodenal LN
• L1 or L2 for prox tumors
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Left border
• Include the silhouette of the residual stomach to include perigastric LN
• May avoid splenic hilum on antral lesions
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Right Border
• Include pre op location of tumor• Porta hepatis , that is 3-4 cm lateral to the
vertebral bodies
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Organs at Risk
• Kidney atleast 3/4th of one kidney should be exclude to receive more than 20Gy• Heart no more than 30% of the heart should receive > 40Gy• Liver no more than 60% of the liver should receive >30 Gy
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Ancillary Care
• Nutrition and Hydration
• Watch for myelosupression
• Manage nausea and vomiting
• Vit B12, Fe, Ca supplementation
• Prophylactic H2 blockers
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Methods to decrease toxicity
• Treat both fields daily• Use high energy linac• AP-PA field better than 4 fields to spare kidney• Use wedges or shaped blocks• 3D planning to generate DVH for liver, kidney
and SI
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Chemotherapy
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Chemotherapy
• Neoadjuvant chemotherapy• Adjuvant for R0 resection• For residual or locally advanced disease• For metastatic disease
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Perioperative Chemotherapy
• MAGIC Trial503 T2 or higher non metastatic Gastric & GEJ tumor, R0 resection but no D2 dissection
ECF Surgery ECF Surgery alone
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MAGIC Trial
• Resected tumor size was smaller, less advanced• No increase in post operative complications• Better overall survival • Longer progression free survival• 5 yr survival 36% vs 23%
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ACTS- GC TRIAL
• S1 (Tegafur+oxonic acid) as adj treatment in T2 and higher, R0 resection with D2 dissection
Surgery Surgery alone
S1 for one year
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ACTS-GC Trial
• 3 yr over all survival was 80% in the S1 gp vs 70% in the surgery alone group
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CLASSIC Trial
• China, Taiwan, S. Korea Stage II- IIIB R0 resection with D2 dissection
Surgery Surgery alone
Capecitabine+oxaliplatin for 8 cycles 3 yr DFS was 74% vs 59%
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• The ACTS-GC Trial and the CLASSIC Trial studied role of adj chemo in pts with D2 dissection
Post op concurrent chemo RT is preferred in patients who have undergone D0/D1 resection
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What is the ideal preoperative Rx- preop chemo or preop chemoRT?
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Preop Chemo or Preop Chemo RT? TOPGEAR
Patients with resectable T2 or higher, any N
Preop ECF x 3 Preop CCRT with 5FU Surgery Surgery
Postop ECF x 3 Postop ECF x 3
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Chemotherapy for locally advanced and metastatic disease
• Chemo with DCF was evaluated in V325 Trial locally adv/metastatic disease
DCF CF• TTP was 5 m vs 3m fav DCF• ORR was 37% vs 25% fav DCF
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Chemotherapy for locally advanced and metastatic disease
• REAL-2 and ML 17032• ECF, ECX, EOX, EOF• Capecitabine was similar to 5FU • Oxaliplatin was similar to Cisplatin
• Irinotecan in second line setting (FOLFIRI)
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SPIRITS Trial
Locally adv/ metastatic disease
Cisplatin with S1 S1 alone
• Found to have superior response in Diffuse Histology
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Targeted therapy
ToGA Trial locally adv/ metastatic disease with Her2neu 3+
Trastuzumab+ F/X +P F/X +PImproved OS in the Trastuzumab gp 13m vs. 11 m
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Treatment Algorithm
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The End