CARCINOMA STOMACH AND ITS MANAGEMENT DR DEEPTI.pptx

PPT on Ca stomach with anatomy, epidemiology, risk and prognostic factors, classification (including morphological, microscopic and molecular), management with surgery, chemo, radiation, immunotherapy and evidence related to treatment. Contouring guidelines in neoadjuvant and adjuvant setting and current guidelines for treatment

1. CARCINOMA STOMACH DR DEEPTI SIKHA MISHRA MODERATOR: DR ANURITA SRIVASTAVA

2. 2 Ca Stomach 2024 Anatomy Muscular bag, widest, most distensible part of GI tract Begins at GE junction Ends at pylorus J-shaped when empty; pyriform-shaped when partially distended Adult stomach capacity: 1.5-2L Divided into 4 regions: Cardia Fundus Body Pylorus Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

3. 3 Ca stomach 2024 Anatomy (Contd.) Peritoneal Relations Visceral Relations Anterior Visceral Relations Posterior Visceral Relations Liver Diaphragm Anterior abdominal wall BD Chourasia’s Human Anatomy; 9 th Edition

4. 4 Ca stomach 2024 Anatomy (Contd.) Arterial supply BD Chourasia’s Human Anatomy; 9 th Edition Venous Drainage

5. 5 Ca stomach 2024 Anatomy (Contd.) Lymphatic Drainage I II III IV All these nodes finally drain into celiac group of lymph nodes BD Chourasia’s Human Anatomy; 9 th Edition

6. 6 Ca stomach 2024 Anatomy (Contd.) Lymphatic Stations ( Old Classification from Japanese Society) Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

7. 7 Ca stomach 2024 Anatomy (Contd.) Lymphatic Stations ( New Classification from Japanese Society Tiers of LN LN Stations First ( Perigastric ) 1-6 Second 7,8,9,11 Third (metastatic) 10-20, 110-112 Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

8. 8 Ca stomach 2024 Anatomy (Contd.) Nerve Supply Sympathetic: T6 to T10 segments Motor to pyloric sphincter Inhibitory to gastric muscles Chief pathway for pain Parasympathetic: Via vagus nerve Divides into ant & post segments Fans out as nerve of Latarjet Motor & secretory to entire stomach Inhibitory to pyloric sphincter BD Chourasia’s Human Anatomy; 9 th Edition

9. 9 Ca stomach 2024 Anatomy (Contd.) Internal Features Mucosa: Simple columnar epithelium with small tubular glands Turned into folds called gastric rugae In between them, are gastric pits Lamina Propria and muscularis mucosae Submucosa: Connective tissue plus Meissner’s plexus Muscle layer: Outer longitudinal plus inner circular Additional oblique layer in fundus & body Also has Auerbach’s plexus Serosa: single layer of squamous cells BD Chourasia’s Human Anatomy; 9 th Edition

10. 10 Ca stomach 2024 Epidemiology In India it ranks 7 th incidence wise and 6 th mortality wise More common in males with 4.5:1 ratio Global Data Indian Data

11. 11 Ca stomach 2024 Gunderson Tepper et al, 2020; 5 th Edition Classification Lauren Classification Intestinal type Differentiated cancer with tendency to form glands. Occurs in distal stomach Arise from precursor lesions More common in males HER 2 positive Hematogenous spread Diffuse type Less differentiated- signet ring cell, mucin-producing No precursor lesion Tend to be proximal More common in women and younger people EBV positive Lymphatic & transmural spread

12. 12 Ca stomach 2024 Gunderson Tepper et al, 2020; 5 th Edition Classification (Contd.) Lauren Classification (Contd.)

13. 13 Ca stomach 2024 Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition Classification (Contd.) Borrmann’s Classification Linitis Plastica Type 5: Unclassifiable

14. 14 Ca stomach 2024 Classification (Contd.) WHO Classification Tubular Papillary Mucinous Poorly cohesive Rare Lauren Intestinal Lauren Diffuse

15. 15 Ca stomach 2024 Classification (Contd.) Molecular Classification ESMO Guidelines for Gastric Cancer 2022 The Cancer Genome Atlas Asian Cancer Research Group MSI Hypermutation MLH-1 gene silencing MSI (Best prognosis) Lauren intestinal Antral location Early detection EBV PIK3CA mutation PD L1 & PD L2 overexpression MSS/TP53 + (Intermediate prognosis) EBV associated TP53 function intact CIN Lauren intestinal T53 mutation MSS/T53 Negative (Intermediate prognosis) Tp53 loss of function mutation GS Lauren diffuse E cadherin mutation MSS EMT (Worst prognosis) Lauren diffuse Younger age Late detection MSI: Miscrosatellite instable CIN: Chromosome instable GS: Genomic stable MSS: Microsatellite stable EBV: Epstein Barr Virus EMT:Epithelial to mesenchymal transition

16. 16 Ca stomach 2024 Classification (Contd.) Molecular Classification ESMO Guidelines for Gastric Cancer 2022

17. 17 Ca stomach 2024 Classification (Contd.) Cancer involving GEJ: Siewert type I – tumor center is located from > 1cm up to 5 cm above GEJ Siewert type II – tumor center is located 1 cm above GEJ and 2 cm below GEJ Siewert type III – tumor center is located 2-5 cm below GEJ

18. 18 Ca stomach 2024 Risk Factors EBV infection associated with 5-16% of gastric cancers Subtotal gastrectomy (25%) & prior radiation exposure Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

19. 19 Ca stomach 2024 . Risk Factors (Contd.): Genetic syndromes Hereditary diffuse gastric cancer (HDGC)- Autosomal dominant, in younger age E-cadherin (CDH1) & PALB2 mutations No precancerous lesion Poorly differentiated Mucin secreting signet ring cell Resistant to treatment & poor prognosis Lynch syndrome Familial adenosis polyposis Peutz-Jeghers syndrome Hereditary breast and ovarian cancer syndrome Li-Fraumeni syndrome Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

20. 20 Ca stomach 2024 Risk Factors (Contd.): Genetic syndromes ESMO Guidelines for Gastric Cancer 2022

21. 21 Ca stomach 2024 Prognostic Factors Tumour extent Poor performance status Elevated alkaline phosphatase levels Poor differentiation Diffuse type Infiltrative growth pattern Caucasians Extensive nodal involvement Transperitoneal seeding & Hematogenous spread Genetic alterations- CD44 expression, p53 mutation, EGFR & ER mutations, hMSH3 & hMLH1 mutations Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

22. 22 Ca stomach 2024 Pathology Adenocarcinomas (90-95%) Lymphomas (2 nd most common) GISTs (1%) Carcinoids (1%) Adenoacanthoma (1%) Leiomyosarcoma (1%) Squamous cell carcinoma (1%) Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition Site wise frequency: Antrum/Distal – 40% Proximal/GEJ – 35% Body – 25%

23. 23 Ca stomach 2024 Pattern of Spread Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

24. 24 Ca stomach 2024 Staging (AJCC 8 th Edition)

25. 25 Ca stomach 2024 Staging (AJCC 8 th Edition)

26. 26 Ca stomach 2024 Staging (AJCC 8 th Edition)

27. 27 Ca stomach 2024 Clinical Presentation Anorexia Early satiety Abdominal discomfort Unintentional weight loss Dysphagia (GE junction or proximal stomach involvement) Anemia-related weakness Nausea and vomiting Tarry stools Duration of symptoms is <3 months in almost 40% of patients and >1 year in 20%. Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

28. 28 Ca stomach 2024 Physical Examination Pallor Lesser Trelat sign Tripe palms Abdominal mass Periumbilical node (Sister Mary Joseph Nodule) Left axillary node (Irish node) Left supraclavicular node (Virchow’s node) Rectal shelf representing peritoneal seeding (Blummer shelf nodule) Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition Clinical Presentation (Contd.)

29. 29 Ca stomach 2024 Diagnostic Workup CBC LFT KFT & SE Tumor markers (CEA/ CA19.9/ CA 72-4) NCCN guidelines version 2.2024

30. 30 Ca stomach 2024 Diagnostic Workup (Contd.) ESMO Guidelines for Gastric Cancer 2022 Pathological analysis Upper GI Endoscopy- preferred diagnostic method allows direct tumor visualization, cytology, and histologic biopsy multiple (5-8) endoscopic biopsies for ulcerated cancers & linitis plastica, deeper biopsies

31. 31 Ca stomach 2024 Diagnostic Workup (Contd.) Pathological analysis (Contd.)

32. 32 Ca stomach 20XX Diagnostic Workup (Contd.) Imaging modalities Endoscopic ultrasonography- identifies extent of invasion sensitivity for T staging 82%, for N staging 91% low specificity of 49% CT scan- for extent of disease for N & M lesser sensitive than EUS for both T & N (77%) low specificity (63%) to r/o mediastinal LN, if extent is till oesophagus

33. 33 Ca stomach 2024 Diagnostic Workup (Contd.) ESMO Guidelines for Gastric Cancer 2022 for detecting peritoneal mets Imaging modalities (Contd.) Laparoscopy & peritoneal washings- sensitivity of 84.6% specificity of 100% pts with low PCI, candidate for HIPEC/PIPAC PETCT- to identify occult mets not useful in mucinous or diffuse tumors not used routinely HIPEC: Hyperthermic Intraperitoneal Chemotherapy PIPAC: Pressurized Intraperitoneal Aerosolised Chemotherapy

34. 34 Presentation title 20XX MANAGEMENT

35. 35 Presentation title 20XX Smoking cessation Nutritional counselling Screening for family history Assess for H pylori status General management

36. 36 Ca stomach 2024 Surgical Management Endoscopic Resection (For Tis/T1a) confined to the mucosa well-differentiated G1-2 ≤ 2 cm non-ulcerated pedunculated LVI & PNI (–ve) Expanded criteria for Endoscopic resection ( if <2 points present) G1/G2-no ulceration, any diameter G1/G2-ulceration, diameter <3cm G3-no ulceration, diameter <2cm ESMO Guidelines for Gastric Cancer 2022

37. 37 Ca stomach 2024 Surgical Management (Contd.) Total/ subtotal gastrectomy for stage IB-III. Distal tumors / expansive tumor growth- distal/ subtotal gastrectomy 80% stomach + 1st portion of duodenum, gastrohepatic & gastrocolic omenta & nodes near to celiac axis branches Distal margin> 2cm Proximal/mid stomach tumors/ infiltrative tumor growth- total gastrectomy Distal margin > 4-6cm Extension beyond the gastric wall- en bloc extended resection Routine splenectomy and bursectomy not done Roux-en-Y reconstruction done Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

38. 38 Ca stomach 2024 Surgical Management (Contd.)

39. 39 Presentation title 20XX Surgical Management (Contd.) LN Dissection D1 dissection- LN along R & L cardia, lesser & greater curvature, suprapyloric and infrapyloric area. D2 dissection- LN along common hepatic, left gastric, celiac, and splenic arteries D3 dissection- LN with any of the porta hepatis and adjacent to the aorta D4: Extended D2 dissection D0 dissection- incomplete removal of the lymph nodes along the greater and lesser curvature Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

40. 40 Presentation title 20XX Evidence for Extent of LN Dissection Dutch Gastric Cancer Trial, Bonenkamp et al 1999 Prospective randomized trial 711 gastric cancer patients curative LRR rates 25% D2 & D1 (41%) dissection Post op complications D2 (43%) & D1 (25%) Post op deaths D2 (10%) & D1 (4%) 5-YR OS D2 (47%) & D1 (45%) JCOG Trial, Sano et al 2004 523 patients Randomized to D2 vs. D2 + PA node dissection 5-year OS (69.2% D2 vs. 70.3% D2 + PALND) . Overall morbidity was higher in the extended Recommended- D2 dissection with ≥ 16 LNs Handbook of Evidence-Based Radiation Oncology; 3 rd Edition

41. 41 Presentation title 20XX Surgical Management (Contd.) LN Dissection cT1aN0/cT1bN0 (<1.5cm, well differentiated) : D1 cT1bN0 (other than above) : D1+ cT2-4, N+ (Potentially curable) : D2 Japanese Gastric Cancer Treatment Guidelines, 2018; 5 th Edition

42. 42 Ca stomach 2024 Surgical Management (Contd.) Patterns of Failure Common mechanisms of failure after “curative” resection in clinical, reoperative , and autopsy serie s Progressive extension of the operative procedure didn’t help either Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

43. 43 Presentation title 20XX EVOLUTION OF ADDITIONAL TREATMENT

44. 44 Presentation title 20XX

45. 45 Ca stomach 2024 Adjuvant CT Trials ACTS-GC Trial Sakuramoto et al 2007 CLASSIC Trial Yung J Bang et al 2012 Prospective Randomised Trial of 1059 pts Phase3 RCT Stage II-III gastric ca patients Stage II-IIIB gastric cancer Surgery alone vs surgery with adjuvant S-1 (oral tegafur, gimeracil , and oteracil ) Surgery alone vs surgery with adjuvant Capeox , 8 3-week cycles for 6 months OS at 3 years was significantly higher with adjuvant CHT compared to observation (80.1% vs. 70.1%; p = .002) 3-yr DFS 74% in adjuvant CT group & 60% in surgery alone group Handbook of Evidence-Based Radiation Oncology; 3 rd Edition

46. 46 Presentation title 20XX Adjuvant CTRT Trials MacDonald, INT0116 2012 Trial ARTIST Trial Lee et al 2015 CRITICS Trial Verheji et al 2016 Prospective Randomised Trial Prospective Randomised Trial Prospective Randomised Trial Stage IB-IV (M0) gastric cancer or GEJ adenocarcinoma 458 pts with R0 resection and D2 LND Stage IB-IV (M0) gastric cancer with neoadjuvant CT & D2 dissection Surgery alone versus surgery followed by CHT 5-FU &LCV with RT of 45 Gy/25 fx Adjuvant XP or RT (45 Gy/25 fx) with capecitabine and cisplatin (XP) Adjuvant ECX/EOX or chemoRT (45 Gy/25 fx with weekly XP) Improved 3 yr OS (50/41) and RFS (48/31),decrease LRR (19/29) Adjuvant CTRT did not improve DFS and OS compared to adjuvant CHT alone No OS benefit, more Gr3 toxicity in adjuvant CTRT group Handbook of Evidence-Based Radiation Oncology; 3 rd Edition

47. 47 Presentation title 20XX Adjuvant CTRT Trials (Contd.) ARTIST 2 Trial S Park et al 2021 Phase 3 RCT Compared 3 adjuvant regimens Oral S-1 for 1 year vs oral S-1 plus Oxali for 6 months vs oral S-1 plus Oxali plus CTRT Primary end point: disease free survival at 3 years Pts with D2 dissection node positive cases, adjuvant SOX (72.8%) /SOXRT (74.3%) improved DFS No difference in DFS between SOX & SOXRT

48. 48 Presentation title 20XX Handbook of Evidence-Based Radiation Oncology; 3 rd Edition Periop CT Trials MAGIC Trial Cunningham et al 2006 FLOT4/ MAGIC –B Trial Al Batran et al 2017 Prospective Randomised Trial Phase III trial Stage II-IV (M0) potentially resectable adenocarcinoma of stomach (74%), GEJ (11%), or lower third of esophagus (14%) ≥cT2 or node-positive resectable gastric or GEJ adenocarcinoma Surgery alone or preoperative ECF, surgery, and postoperative ECF 3 pre-op and 3 post-op cycles of ECF/ECX or 4 pre-op and 4 post-op cycles of FLOT Improved PFS(HR 0.66) and OS (HR 0.75) and 5 yr Survival (36/23) Improved median OS (35 vs 50 months) and PFS (18 vs 30 months)

49. 49 Presentation title 20XX Handbook of Evidence-Based Radiation Oncology; 3 rd Edition Preop CTRT Trials RTOG 9904 Ajani et al 2006 CROSS Trial Van Hagen et al 2012 POET Trial Stahl et al 2017 Phase II RCT Phase III RCT Phase III RCT Potentially resectable T2-3 NxM0 gastric adenocarcinoma T1N1 or T2-3 N0-1 esophagus or GEJ T3-4 Adenocarcinoma of the GE junction Induction CT, followed by concurrent CTRT (45 Gy/25 fx) and then surgery Surgery alone vs surgery with NACTRT ((41.4 Gy/23 fx, Pacli / Carbo) Preop CTRT f/b surgery vs preop CT alone f/b surgery NACTRT had 26% pCR rate, which may be associated with higher OS Improved 5-yr OS (47% vs 33%), PFS (44% vs 27%), and reduced locoregional progression (22% vs 38%) and distant progression (39% vs 48%) Benefit in both 3-yr OS (16.7%) &5-yr OS (14%) & RFS (17.5%)

50. 50 Presentation title 20XX Ongoing Trials TOPGEAR Trial 2017 CRITICS 2 Trial 2018 Phase 3 RCT Phase 2 RCT Periop ECF 3c f/b Sx f/b 3 c ECF Preop 2c ECF  CTRT  Sx  3c ECF 4 cycles of DOC 2 cycles of DOC followed by chemoradiotherapy (45Gy in combination with weekly pacli & carbo) chemoradiotherapy primary endpoint is overall survival Primary endpoint is event-free survival

51. 51 Presentation title 20XX Chemotherapy Periop setting FLOT regimen 5FU 2.6gm infusion over 24 hrs D1 Leucovorin 200 mg/m2 IV on Day 1 Oxaliplatin 85 mg/m2 IV on Day 1 Docetaxel 50 mg/m2 IV on Day 1 mFOLFOX6 regimen Oxaliplatin 85 mg/m2 IV on D 1 Leucovorin 400 mg/m2 IV on D 1 Fluorouracil 400 mg/m2 IV Push on D 1 Fluorouracil 1200 mg/m2 IV continuous infusion over 24hrs D1 & 2 Every 14 days, 4 cycles preop & 4 cycles postop NCCN guidelines version 2.2024

52. 52 Ca stomach 2024 Chemotherapy (Contd.) Periop setting (Contd.) CAPEOX regimen Capecitabine 1000 mg/m2 PO BID on Days 1–14 Oxaliplatin 130 mg/m2 IV on Day 1 Every 21 days, 4 cycles preop and 4 cycles post op Preop setting Paclitaxel 50 mg/m2 IV on Day 1 Carboplatin AUC 2 IV on Day 1 Weekly for 5 weeks NCCN guidelines version 2.2024

53. 53 Presentation title 20XX Chemotherapy (Contd.) Preop setting with CTRT Oxaliplatin 85 mg/m2 IV on D 1 Leucovorin 400 mg/m2 IV on D1 Fluorouracil 400 mg/m2 IV Push on D1 Fluorouracil 400 mg/m2 IV Push on D1 Fluorouracil 800 mg/m2 IV continuous infusion over 24 hours daily on D 1 and 2 Oxaliplatin 85 mg/m2 IV on Days 1, 15, and 29 for 3 doses Capecitabine 625 mg/m2 PO BID on Days 1–5 weekly for 5 weeks Every 14 days for 3 cycles with RT NCCN guidelines version 2.2024

54. 54 Ca stomach 2024 NCCN guidelines version 2.2024 Chemotherapy (Contd.) Post-op chemoradiation (D2 dissection not done) Post-op chemotherapy (D2 dissection done)

55. 55 Ca stomach 2024 Radiotherapy Neoadjuvant setting Adjuvant setting Definitive setting Palliative setting Ensure adequate nutrition before radiation. Fasting for 3 hours before simulation and treatment Supine position with arms above head Immobilisation using thermoplastic cast/ alpha cradle/ wing board/ vaclok. Use preop imaging, operative notes, surgical clips, and pathological report for delineation. Handbook of Evidence-Based Radiation Oncology; 3 rd Edition

56. 56 Ca stomach 2024 Radiotherapy (Contd.) Convention 2D Planning Parallel opposed AP/PA FIELDS Lateral field: Anteriorly from anterior abdominal wall & posteriorly upto 1/2 -2/3 rd vertebral body Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

57. 57 Ca stomach 2024 Radiotherapy (Contd.) 3D Planning Immobilization and patient position Oral contrast to delineate the small bowel IV contrast to delineate the tumor and LN Slice thickness of 3-5mm 10-15 cm above the diaphragm to 2-3 cm below the iliac crest.

58. 58 Ca stomach 2024 Radiotherapy (Contd.) Neoadjuvant & Definitive setting GTV primary- Gross visible lesion on imaging CTV primary- depending upon location Proximal: stomach without pylorus/ antrum 5 cm margin, including distal esophagus Body: entire stomach including cardia & pylorus Distal: stomach without cardia & fundus 5cm margin to be given if pylorus involved then 3cm of duodenum taken GTV node- Gross visible node on imaging CTV node- depending upon location 5mm margin to involved nodes Respiratory gating/ deep breath holding techniques to overcome normal respiratory motion changes 1.5cm margin from CTV to get ITV 5mm margin from ITV to get PTV Delineation of Primary Delineation of Node Dose: 45 Gy at1.8 Gy per fraction, five days a week in NA setting 54-59.4 Gy at 1.8Gy per fraction for 5 days a week in definitive setting

59. 59 Ca stomach 2024 Radiotherapy (Contd.) Neoadjuvant & Definitive setting If tumor involving GE junction then levels 20 & 110-111 also included

60. 60 Ca stomach 2024 Radiotherapy (Contd.) Neoadjuvant & Definitive setting

61. 61 Ca stomach 2024 Radiotherapy (Contd.) Neoadjuvant & Definitive setting

62. 62 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

63. 63 Ca stomach 2024 Radiotherapy (Contd.) Neoadjuvant & Definitive setting

64. 64 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

65. 65 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

66. 66 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

67. 67 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

68. 68 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

69. 69 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

70. 70 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

71. 71 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

72. 72 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

73. 73 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

74. 74 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

75. 75 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

76. 76 Presentation title 20XX Radiotherapy (Contd.) Neoadjuvant & Definitive setting

77. 77 Ca stomach 2024 Radiotherapy (Contd.) Adjuvant setting

78. 78 Ca stomach 2024 Radiotherapy (Contd.) Adjuvant setting

79. 79 Ca stomach 2024 Radiotherapy (Contd.) Adjuvant setting

80. 80 Ca stomach 2024 Radiotherapy (Contd.) Adjuvant Dose: 45 Gy/1.8 Gy/fx. May consider 5.4 to 9 Gy boost for positive margins/gross residual disease

81. 81 Presentation title 20XX Radiotherapy (Contd.) Adjuvant

82. 82 Presentation title 20XX Radiotherapy (Contd.) Adjuvant

83. 83 Ca stomach 2024 Radiotherapy (Contd.) Newer Techniques IMRT Volumetric Arc therapy Helical tomotherapy Proton therapy

84. 84 Presentation title 20XX Radiotherapy (Contd.) Newer Techniques 2D Planning 3DCRT Planning IMRT Planning

85. 85 Ca stomach 2024 Radiotherapy (Contd.) IORT

86. 86 Ca stomach 2024 Radiotherapy (Contd.) Normal Tissue Dose Constraints NCCN guidelines version 2.2024

87. 87 Ca stomach 2024 Radiotherapy (Contd.) Sequalae Acute complications- nausea, anorexia, fatigue, & myelosuppression with chemo H2-blocker or PPI for ulcer prophylaxis For severe nausea, ondansetron 8 mg 1 h before RT daily and every 8 h Late complications- dyspepsia, radiation gastritis, and gastric ulcers. late effects are rare with 40–52 Gy Handbook of Evidence-Based Radiation Oncology; 3 rd Edition

88. 88 Ca stomach 2024 Treatment Paradigm (Radical Approach) NCCN guidelines version 2.2024

89. 89 Ca stomach 2024 Treatment Paradigm (Radical Approach) With Upfront Surgery NCCN guidelines version 2.2024 *High risk features include higher grade cancer, LVSI, PNI or <50yr pt without D2 dissection

90. 90 Ca stomach 2024 Treatment Paradigm (Radical Approach- After Preop treatment) NCCN guidelines version 2.2024

91. 91 Presentation title 20XX Treatment Paradigm (Radical Approach- After Preop treatment) NCCN guidelines version 2.2024

92. 92 Presentation title 20XX Treatment Paradigm (Radical Approach) Following Surgery after NA Treatment NCCN guidelines version 2.2024

93. 93 Presentation title 20XX Surveillence History & physical examination – 3-6 monthly for first 2 years 6-12 monthly till 5 years Routine blood investigations Imaging Endoscopy for surgically resected cases As clinically indicated Nutritional assessment in surgically resected cases

94. 94 Presentation title 20XX Treatment Paradigm (Recurrent Cases) NCCN guidelines version 2.2024

95. 95 Ca stomach 2024 NCCN guidelines version 2.2024 Treatment in Unresectable/ Metastatic disease (Evidence for Immunotherapy) ToGA trial KEYNOTE-811 trial REGARD Trial RAINBOW Trial Checkmate-649 trial KEYNOTE-158 trial HER2 overexpression-positive advanced gastric or EGJ adenocarcinoma HER2 overexpression-positive adenocarcinoma of GE junction Previously treated advanced or metastatic GE junction cancer Metastatic gastric or EGJ adenocarcinoma progressing on first-line chemotherapy Previously untreated, HER2-negative, unresectable gastric, EGJ, or esophageal adenocarcinoma Previously treated metastatic TMB-H solid tumors Significant improvement in median OS with the addition of trastuzumab Improved ORR (74% vs. 52%; P = .0001) on adding Pembrolizumab with Trastuzumab Median OS improved in 2 nd line Ramicirumab Improved median OS & PFS with Ramucirumab significant improvements in OS and PFS in patients with a PD-L1 CPS of ≥5 with pembrolizumab Improved ORR on addition of pembrolizumab

96. 96 Ca stomach 2024 NCCN guidelines version 2.2024 Treatment in Unresectable/ Metastatic disease(Chemotherapy)

97. 97 Presentation title 20XX NCCN guidelines version 2.2024 Treatment Paradigm (Palliative Intent) Metastatic (cM1/ pM1) Progressive disease Poor performance Unresectable, non-surgical candidate Persistent local disease

98. 98 Ca stomach 2024 NCCN guidelines version 2.2024 Surgical Management for Palliation Unresectable- peritoneal involvement encasement of major vessels distant mets Indication- bleeding gastric outlet obstruction Palliative resection Gastrojejenostomy Venting gastrostomy Lymph node dissection not required Perez & Brady’s Principles & Practice of Radiation Oncology; 7 th Edition

99. 99 Presentation title 20XX Gastric MALToma

100. 100 Presentation title 20XX Gastric GIST

101. 2024 Ca stomach 101 THANK YOU