Gastric cancer, investigations and management

Gastric Cancer

Dr. Amina Abdul RahmanJunior ResidentDept. of Radiotherapy

Investigations Management Surgery Radiotherapy CCRT Chemotherapy Supportive care Treatment algorithm

Gastric Cancer

Investigations

Investigation tools

• Endoscopy• CT• EUS• PET/CT• MRI• Laparoscopic staging

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.

Endoscopic image of Gastric Ca

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

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

EUS Images of Stomach layers

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.

Management

Management

• Surgery• Radiotherapy• Chemotherapy• Supportive Care

Surgery

Surgery

• Endoscopic mucosal resection• Limited Gastric resection• Subtotal/total gastrectomy

Principles of Surgery

• Requires adequate pre-op staging• R0 resection• Subtotal> total gastrectomy• Margin 0f 4 cm• Atleast 15 lymph nodes should be resected

Surgery

• T1a : EMR• T1b -T3 : Gastrectomy• T4 : Gastrectomy with enbloc resection

of involved structures

Endoscopic Mucosal Resection

Gastric sparing R0 resection without LN dissection for EGC who are expected to have low metastatic potential

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

Limited Surgical Resection

• Candidates for EMR• Gastrotomy with full thickness local excision• Lymph node dissection not required

Total and Sub total Gastrectomy

Subtotal Gastrectomy

Total Gastrectomy

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)

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

• D2 dissection is now recommended

- Remove at least 15 LN- Avoid splenectomy and pancreatectomy- Perform in high volume centers

Features of inoperability

• Peritoneal involvement visible omental deposits positive peritoneal cytology• N3/N4 node• Involvement or encasement of vascular

structures• Distant metastases

Palliative Surgery

• Limited gastric resections• For palliation of symptoms like obstruction,

and bleeding• GJ > stenting

Radiotherapy

Radiotherapy

• Preoperative• Postoperative Adjuvant for R0 resection RT to residual or gross disease• Palliative

Preoperative RT

Zhang et al from Beijing 370 potentially resectable gastric cardia cancers

Pre-OP RT (40 Gy in 20#)

Surgery

Surgery alone

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

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%

Adjuvant RT

• No survival benefit when RT alone was given• Reduction in locoregional recurrence

Palliative RT

• Bleeding• Obstruction• Pain• Median of 50 Gy is recommended

Concurrent Chemoradiotherapy

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

Postoperative CCRT

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

Was concurrent chemoradiotherapy compensating for the inferior surgery in the INT 0116 trial?

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

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

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

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%

Clinicopathological factors for local recurrence

• Positive serosal margin (circumferential)

• Narrow longitudinal margins

• Lymph nodal recurrence

Lymph nodes to include for subsite specific RT Planning

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

24sa

10

Upper one third of GEJ

• Subpyloric LN mets are rare• Increased risk of paraesophageal LN involvement

Lower one third / Antrum

• Increased risk of subpyloric LN mets • But splenic LN mets are rare• Sparing splenic LN may spare the left kidney

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.

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

Superior border

• Bottom of T8 or T9 to cover coeliac axis, GEJ, fundus

• Treat the dome of left diaphragm

• Locate the site of anastomoses

Inferior border

• Usually fixed at L3 for infrapyloric and GastroDuodenal LN

• L1 or L2 for prox tumors

Left border

• Include the silhouette of the residual stomach to include perigastric LN

• May avoid splenic hilum on antral lesions

Right Border

• Include pre op location of tumor• Porta hepatis , that is 3-4 cm lateral to the

vertebral bodies

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

Ancillary Care

• Nutrition and Hydration

• Watch for myelosupression

• Manage nausea and vomiting

• Vit B12, Fe, Ca supplementation

• Prophylactic H2 blockers

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

Chemotherapy

Chemotherapy

• Neoadjuvant chemotherapy• Adjuvant for R0 resection• For residual or locally advanced disease• For metastatic disease

Perioperative Chemotherapy

• MAGIC Trial503 T2 or higher non metastatic Gastric & GEJ tumor, R0 resection but no D2 dissection

ECF Surgery ECF Surgery alone

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%

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

ACTS-GC Trial

• 3 yr over all survival was 80% in the S1 gp vs 70% in the surgery alone group

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%

• 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

What is the ideal preoperative Rx- preop chemo or preop chemoRT?

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

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

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)

SPIRITS Trial

Locally adv/ metastatic disease

Cisplatin with S1 S1 alone

• Found to have superior response in Diffuse Histology

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

Treatment Algorithm

The End