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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 disease
EMR
Limited surgical resection
Gastre...
Management of stage I gastric carcinoma
1) Endoscopic Mucosal Resection
Indications:
Well differentiated carcinoma.
Tumor 20 mm or less in size for elevated typ...
2) Limited Surgical Resection
• Indication:
• Low rate of LN involvement in EGC limited resection may be a
reasonable opti...
3) Gastrectomy
Indication for EGC
• Patient who have intramucosal tumor with poor histologic
differentiation.
• Size > 3 ...
Gastrectomy
Subtotal gastrectomy
• Removal of-
• 80 % stomach, gastrohepaic
and gastrocolic omenta &
first part of duodenu...
Total and Sub total Gastrectomy
Subtotal Gastrectomy
Roux-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
(chemoradia...
- Loco regionally advanced
• Involvement of root of mesenteric node
• Hepatoduodenal nodes
• Para aortic nodes
• Invasion ...
Extent of resection for Mid & Distal Gastric Ca
• Depends on the gross and microscopic status of surgical
margins.
• Three...
Extent of resection for proximal gastric Ca
Options –
 Optimal surgical procedure is matter of debate.
 Transabdominal ...
Lymphadenectomy- Lymph node stations
Extent of lymphadenectomy
• Japanese Research Society for the study of Gastric Cancer
• N1 : LN stations 1-6 (perigastric ...
Lymph Node Dissection
D0- incomplete dissection of N1 nodes
D1- removal of involved proximal and distal stomach with
mar...
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...
Partial pancreatectomy & splenectomy –
resect or preserve?
• Multiple trial have demonstrated that routine spleenectomy
an...
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...
Resected
Stage IB-IV (M0)
Gastric AdenoCa
5-FU/LV
5-FU/LV 5-FU/LV
5-FU/LV x2 (D1-5/q30days)RADIATION
4500 cGy/25# 425/20mg...
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
...
The results of the INT-0116 trial have established postoperative chemoradiation
therapy as a standard of care in patients ...
• Median overall survival was 37 months versus 38 months (p = .8), 3-year overall
survival 50% versus 52%, and 3-year dise...
• Adenoca of esophagus or gastric cardia
• Pre op arm : 2 cycles Cis/5FU (wk 1 & 6) + RT 40Gy/15#,starting with chemo
• Pr...
• Zhang and colleagues randomized 370 patients to preoperative RT or surgery
alone.
• 143 Resection rates were also higher...
Post-op Radiotherapy alone
 432 patients with Resectable Gastric Cancer
Surgery Surgery Surgery
Chemotherapy
(FAM)
Radiot...
• 5 yr survival for-
• Surgery alone 20%
• Surgery followed by RT 12%
• Surgery followed by chemotherapy 19%
• There was a...
• The theoretical advantage of this approach ability to deliver a more
intensive dose of radiation to the tumor bed
• Rand...
Chemotherapy
• Peri-operative chemotherapy
• Post-operative chemotherapy
Pre-operative Chemotherapy: Advantages
• Tumour downsizing prior to surgery
• Increase rate of curative (R0) resection*
• ...
503 T2 or higher non metastatic Gastric & GEJ tumor, R0 resection but no D2
dissection
ECF Surgery ECF Surgery alone
• Pri...
• 5-year survival 36% vs. 23% (p-0.009)
• Limitations:
• Only 42% of patients in the test group completed all protocol tre...
• ACCORD 07/ FNCLCC/FFCD trial, 2011
• N = 224; 75% of patients had adenocarcinoma of the lower esophagus or EGJ
and 25% h...
• Perioperative chemotherapy significantly increased the curative resection rate,
DFS, and OS in patients with resectable ...
CLASSIC - Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer
• 1035 pts
• Median FU – 34.2 mnths
• Stage II-III...
 ACTS GC /S-1 trial
• Novel oral fluoropyrimidine S-1 (combination of tegafur [prodrug of fluorouracil;
5-chloro-2,4-dihy...
• 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 regi...
Post-op CTRT vs Post-op CT
• ARTIST – Adjuvant Chemo-radiation in Stomach Cancer Trial
• 459 R0 resected gastric cancer pa...
• In the subgroup of patients with pathologic LN metastasis at the time of Sx (n =
396), patients randomly assigned to the...
GASTRIC Meta-analysis
• IPD Meta-analysis – 17 trials (3838 pts)
• Adjuvant chemotherapy was associated with a statistical...
Targated therapies
Outcome Chemotherapy +
Trastuzumab
(n = 294)
Chemotherapy
Alone
(n = 290)
HR (95% CI) P Value
Median OS, mos 13.8 11.1 0.7...
Evidence from meta-analysis favoring Adjuvant treatment
RT techniques
conventional
Conformal
• Supine position.
• Immobilization: Legs with knee support, thermoplastic
device or vacuum cushion is recommended
• Posit...
Field design
Anteroposterior-posteroanterior (AP-
PA) field
Superior Bottom of T8 or T9
Inferior Bottom of L3
Left Include...
….Continued Conventional technique
Lateral field
Superior Same as AP-PA
Inferior Same as AP-PA
Anterior Anterior abdominal...
Simulation film for T3 antral tumor with two of five peritumoral
lymph nodes metastatically involved
Conformal technique
3D-CRT
IMRT
• Supine position.
• Immobilization: Legs with knee support, thermoplastic
device or vacuum cushion is recommended
• Posit...
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 per...
Clinical target volume (CTV_T): depends on site of the
stomach.
• proximal 1/3rd : contour of the stomach with exclusion ...
Lymph node stations
Stations of LN to be taken:
CTV_Nodal: Proximal stomach / GEJ Type I, II, III
Type 1 Type II Type III
1,2,7,9,19,20,110,1...
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)/T3
N0
Variable for
prox/distal
Include i...
T4bN0
Prox: variable Prox/Mid/Dis: As
for T4aN0 + site of
adherence with 3-5
cm margin
Nodes related to site of
adherenceM...
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 a...
• Doses in the range of 45 to 50.4 Gy should be
delivered at 1.8 Gy per fraction
• For treatment of inoperable disease, th...
• Although parallel-opposed AP/PA fields are a practical
arrangement for tumor bed and nodal irradiation.
• Multifield tec...
Stage wise treatment :
• T1N0 :
• Surgery alone (partial or total gastrectomy with at leaast D1 LN
dissection)
• Selected ...
Futurestrategies
Thank You
Satyajeet Carcinoma Stomach management
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Satyajeet Carcinoma Stomach management

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Satyajeet Carcinoma Stomach management

  1. 1. Management of Gastric Cancer By – Dr. Satyajeet Rath Moderator – Prof. Kamal Sahni Date - 31/01/17
  2. 2. Treatment of gastric CA Treatment of localised disease (stage I-III) Stage I disease EMR Limited surgical resection Gastrectomy Stage II & III Subtotal gastrectomy or Total gastrectomy With lymphadenectomy Followed by Post-op ChemoRT Or Peri-op Chemotherapy Treatment of metastatic disease (stage IV) Stage IV Chemotherapy Palliative surgery Palliative radiotherapy Standard Treatment
  3. 3. Management of stage I gastric carcinoma
  4. 4. 1) Endoscopic Mucosal Resection Indications: 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 ulcers Invasion limited to mucosa. (Japanese gastric cancer association guidelines) Advantage: Better quality of life Less 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.
  5. 5. 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 tumor b. Nonulcerated intramucosal tumor of any size • Procedure: Gastrotomy with full thickness local excision • Lymph node dissection not required.
  6. 6. 3) Gastrectomy Indication for EGC • Patient who have intramucosal tumor with poor histologic differentiation. • Size > 3 cm • Tumor invasion up to submucosa or beyond
  7. 7. 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.
  8. 8. Total and Sub total Gastrectomy
  9. 9. Subtotal Gastrectomy Roux-en-Y reconstruction (more commonly) Gastroduodenostomy (less commonly)
  10. 10. Total Gastrectomy
  11. 11. Management of stage II and III Gastric carcinoma • Resectable disease • Surgery followed by adjuvant treatment (chemoradiation) • Perioperative chemotherapy followed by surgery Unresectable disease chemoradiation
  12. 12. - 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.
  13. 13. 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.
  14. 14. 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.
  15. 15. Lymphadenectomy- Lymph node stations
  16. 16. 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.
  17. 17. Lymph Node Dissection D0- incomplete dissection of N1 nodes D1- 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.
  18. 18. D1 and D2 resection in proximal third Gastric CA
  19. 19. D1 and D2 resection in middle third Gastric CA
  20. 20. D1 and D2 resection in lower third Gastric CA
  21. 21. 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.
  22. 22. 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)
  23. 23. Patterns of failure in 82 evaluable patients in the University of Minnesota Reoperation series Failure rates after surgery
  24. 24. Radiotherapy • RT alone • Chemoradiation
  25. 25. 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.
  26. 26. Resected Stage IB-IV (M0) Gastric AdenoCa 5-FU/LV 5-FU/LV 5-FU/LV 5-FU/LV x2 (D1-5/q30days)RADIATION 4500 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 M0 Nearly 70% had T3 , T4 disease 85% had Lymph nodal mets Only 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.
  27. 27. 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 FU Long 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
  28. 28. 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
  29. 29. • 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.
  30. 30. • 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.
  31. 31. • 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
  32. 32. 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
  33. 33. • 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.
  34. 34. • 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.
  35. 35. Chemotherapy • Peri-operative chemotherapy • Post-operative chemotherapy
  36. 36. 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
  37. 37. 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.
  38. 38. • 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.
  39. 39. • 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.
  40. 40. • 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
  41. 41. 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
  42. 42.  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.
  43. 43. • 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
  44. 44. 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.
  45. 45. • 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).
  46. 46. 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
  47. 47. Targated therapies
  48. 48. 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 benefit Safety profile were similar
  49. 49. Evidence from meta-analysis favoring Adjuvant treatment
  50. 50. RT techniques conventional Conformal
  51. 51. • 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
  52. 52. Field design Anteroposterior-posteroanterior (AP- PA) field Superior 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
  53. 53. ….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
  54. 54. Simulation film for T3 antral tumor with two of five peritumoral lymph nodes metastatically involved
  55. 55. Conformal technique 3D-CRT IMRT
  56. 56. • 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
  57. 57. Target volumes – • GTV in pre-op/unresectable cases • CTV • PTV Target volume definition
  58. 58. 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.
  59. 59. 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
  60. 60. Lymph node stations
  61. 61. Stations of LN to be taken: CTV_Nodal: Proximal stomach / GEJ Type I, II, III Type 1 Type II Type III 1,2,7,9,19,20,110,111,112. 1,2,3,4sa,7,9,11p,19,20,110,1 11 1,2,3,4sa,4sb,7,9,10,11p,1 1d,19
  62. 62. 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
  63. 63. Target Volumes in post-op cases
  64. 64. RT: Post op- cases
  65. 65. Stage Remaining stomach Tumor bed volume Nodal volume T2N0 (invasion upto serosa)/T3 N0 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
  66. 66. T4bN0 Prox: 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 T1-2 For 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: preferable As for T4a/b N0 for all sites As for T3N+ and T4bN0Mid: include Distal: preferable
  67. 67. 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
  68. 68. • 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
  69. 69. • 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
  70. 70. 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
  71. 71. Futurestrategies
  72. 72. Thank You

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