22. Gastric Cancer powerpoint presentation

Gastric Cancer powerpoint presentation

1. GASTRIC CANCER PRESENTER- D r . ABHISHEK MEWARA MODERATOR- D r . MANISH CHATURVEDI J.L.N. MEDICAL COLLEGE AND ASSOSIATED HOSPITALS, AJMER 8.5.2025 1

2. OVERVIEW INTRODUCTION ANATOMY CLASSIFICATION RISK FACTORS CLINICAL PRESENTATION STAGING DIAGNOSTIC WORKUP TREATMENT FOLLOW UP 2

3. INTRODUCTION 3

4. Adenocarcinoma stomach has been one of the leading causes of cancer death lately. Ranks 4th according to recent GLOBOCAN data, with estimated 9,68,784 new cases diagnosed annually and estimated 6,60,175 deaths worldwide. It ranks 6th according to GLOBOCAN, wrt total cases in India. More common in males, and have genetic predisposition. Stomach cancer incidence rates are highly variable by region, being highest in Eastern and Central Asia and in western parts of Latin America. Notably, the global incidence of gastric cancer has declined rapidly over the past few decades, partly due to recognition of certain risk factors such as H. pylori and other dietary and environmental risk factors. 4

5. In Asia (mainly China), the decline has been less dramatic with increase in incidence of early-onset gastric cancer. Gastric adenocarcinomas are primarily classified topographically as cardia (proximal) or non—cardia (distal). Despite the overall decline, there has been increase in in incidence of cancer of the cardia. The shift from distal to proximal may be in part due to decline in distal gastric cancer, however it has also been proposed that cardia cancer is different entity from rest of gastric carcinoma. 5

6. The proximal tumors share demographic and pathologic features with Barrett’s-associated esophageal adenocarcinoma & are more likely to occur in males, which parallels the male predominance in the increasing incidence of the carcinoma of the lower third of the esophagus. The proximal tumors are not associated with severe gastritis characterized by atrophic and/or intestinal metaplasia. These tend to be more aggressive. Environmental risk factors such as cigarette and alcohol are more strongly associated with cardia carcinomas. Also there has been rise in incidence (of both, cardia and non-cardia gastric cancers) among young adults. 6

7. 7

8. 8

9. ANATOMY 9

10. 10

11. 11

12. REGIONAL LYMPH NODES Perigastric along the greater curvature (including greater curvature, greater omental) Perigastric along the lesser curvature (including lesser curvature, lesser omental) Right and left paracardial ( cardioesophageal ) Suprapyloric (including gastroduodenal) Infrapyloric (including gastroepiploic) Along Left gastric artery Along Celiac artery Along Common hepatic artery Hepatoduodenal (along the proper hepatic artery, including portal) Along Splenic artery Along Splenic hilum 12

13. CLASSIFICATION 13

14. Borrman Lauren Seiwert 14

15. BORRMAN CLASSIFICATION 15

16. LAUREN CLASSIFICATION 16

17. SIEWERT CLASSIFICATION Done in all patients with adenocarcinomas involving the EGJ. Siewert Type I: adenocarcinoma of the lower esophagus (often associated with Barrett esophagus) with the epicenter located within 1 cm to 5 cm above the anatomic EGJ. Siewert Type II: true carcinoma of the cardia at the EGJ, with the tumor epicenter within 1 cm above and 2 cm below the EGJ. Siewert Type III: subcardial carcinoma with the tumor epicenter between 2 cm and 5 cm below the EGJ, which infiltrates the EGJ and lower esophagus from below. The treatment of Siewert types I and II is as described in the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers. Siewert type III lesions are considered gastric cancers, and thus should be treated as described in the NCCN Guidelines for Gastric Cancer. 17

18. 18

19. RISK FACTORS 19

20. NUTRITIONAL- Low protein, low fat diet, low fiber , low fruits & vegetables High complex carbs Intake of nitrates Increase intake of salts Smoked foods, canned foods Processed meats Alcohol, smoking Obesity SOCIAL FACTORS- Low socio-economic status MEDICAL- H. Pylori infection EBV infection H/o Gastrectomy Gastritis Syndromes such as FAP, HNPCC, Li Fraumeni, etc. Menetrier’s disease OCCUPATIONAL Coal workers Rubber industry workers 20

21. CLINICAL PRESENTATION 21

22. Anorexia Early satiety Abdominal pain & discomfort (usually epigastric, vague, mild in early disease but more severe and constant in advanced disease) Unintentional weight loss Dysphagia (notably if GE junction or proximal stomach involvement) Anemia-related weakness (occult GI bleed with or without IDA) Nausea and vomiting Tarry stools Duration of symptoms is <3 months in almost 40% of patients and >1 year in 20%. 22

23. M/C sites of metastasis are liver, peritoneal surfaces, and the non regional or distant lymph nodes; less commonly in ovary ( Krukenberg Tumor ), CNS, bone. Physical examination can reveal advanced disease, for which the presentation may include- an abdominal mass (epigastric or liver mass as well as a periumbilical node [i.e., Sister Mary Joseph node ]) palpable left supraclavicular nodes (i.e., Virchow node ) an enlarged left axillary lymph node ( Irish node ) rectal shelf (representing peritoneal seeding [i.e., Blumer shelf ]). 23

24. Paraneoplastic manifestations include- Dermatologic findings may include sudden appearance of diffuse seborrheic keratoses ( sign of Leser- Trélat ) or Acanthosis nigrans . MAHA ( microangipathic hemolytic anemia ) Membranous nephropathy Hypercoagulable state ( Trousseau’s syndrome ) Polyarteritis nodosa 24

25. GENETIC SYNDROMES ASSOCIATED WITH GASTRIC CARCINOMA 25

26. Approximately 10% of gastric cancers are linked to genetic syndromes. The most common being hereditary diffuse gastric cancer (HDGC), which is characterized by an AD inheritance, pertaining a 60% to 80% increased risk of gastric cancer. Some of these cases are believed to be due to mutations in E-cadherin (CDH1). The presence of CDH1 mutations portends a lifetime risk of gastric cancer development of 70% to 80%. Prophylactic gastrectomy is often recommended once patients are >20 years of age in these patients. Other syndromes associated with increased risk include Lynch syndrome (DNA mismatch repair gene mutation), Familial adenomatous polyposis (APC mutation), Peutz-Jeghers syndrome (STK11 mutation), Juvenile polyposis syndrome (SMAD4 mutation), Hereditary breast and ovarian cancer syndrome, and Li-Fraumeni syndrome (TP53 mutation) 26

27. STAGING 27

28. 28

29. 29

30. 30

31. DIAGNOSTIC WORKUP 31

32. 32

33. TREATMENT 33

34. 34

35. SURGERY 35

36. Tis or T1a tumors may be candidates for EMR or ESD. T1b–T3: Adequate gastric resection to achieve negative microscopic margins along with lymphadenectomy. Distal gastrectomy Subtotal gastrectomy Total gastrectomy T4b tumors require en bloc resection of involved structures. Gastric resection should include the regional lymphatics— perigastric lymph nodes (D1) and those along the named vessels of the celiac axis (D2), with a goal of examining at least 16 or greater lymph nodes. 36

37. EMR (ENDOSCOPIC MUCOSAL RESECTION), ESD (ENDOSCOPIC SUBMUCOSAL DISSECTION) EMR or ESD of early-stage gastric cancer can be considered adequate therapy when the lesion is ≤2 cm in diameter is shown on histopathology to be well or moderately well differentiated does not penetrate beyond the superficial submucosa does not exhibit LVI, and has clear lateral and deep margins. 37

38. R0 resection: no tumor microscopically at the surgical margin. R1 resection: tumor microscopically at the surgical margin. R2 resection: tumor macroscopically at the surgical margin. D0 dissection: dissection of some of the perigastric lymph nodes. D1 dissection: dissection of all perigastric lymph nodes. D2 dissection: dissection of perigastric + celiac axis lymph nodes. (Celiac axis lymph nodes: The celiac trunk, left gastric artery, common hepatic artery, and lymph nodes around the splenic artery.) D3 dissection: D2 + hepatoduodenal, peripancreatic, and mesentery root lymph nodes dissection. D4 dissection: D3 + para-aortic lymph nodes dissection. 38

39. 39 TOTAL GASTRECTOMY SUBTOTAL GASTRECTOMY

40. SYSTEMIC THERAPY 40

41. 41

42. Regimens should be chosen in the context of performance status (PS), medical comorbidities, and toxicity profile. Trastuzumab should be added to first-line chemotherapy for advanced HER2 overexpression positive adenocarcinoma. Two-drug regimens are preferred for patients with advanced disease because of lower toxicity. The use of three cytotoxic drugs in a regimen should be reserved for patients who are medically fit with excellent PS and easy access to frequent toxicity evaluations. PERIOPERATIVE CT (4 cycles preoperative and 4 cycles postoperative) FLOT (Fluorouracil, leucovorin, oxaliplatin, and docetaxel) Fluoropyrimidine + Oxaliplatin 42

43. CAPECITABINE Antimetabolite. Inactive as a prodrug, converted to 5-FU. Converted to 5-FU in liver and tumor tissues by thymidine phosphorylase. Good oral bioavailability, hence given orally. 1250 mg/m 2 , PO, BD, for 2 weeks with 1 week rest, or 1500mg/m2, P/O, BD, for 1 week with 1 week off- when used as monotherapy. 850-1000 mg/m 2 , PO, BD, for 2 weeks when used with other chemotherapeutic agents. Taken with a glass of water within 30 min of meal. Main S/E- Hand foot syndrome/ palmo -plantar erythrodysaesthesia is a characteristic S/E. T/t- Vitamin B6 50 mg PO, BD, or celecoxib 200 mg PO, BD, or nicotine patch, and adequate hydration, urea-based moisturizers and lotions, etc. 43

44. OXALIPLATIN Platinum analogue. Cell cycle non specific. Binds N7 position of adenine and guanine and disrupts cell division. IV only. Usual dosage- 100-130 mg/m 2 IV over 2 hrs in a 3-weekly schedule. Main S/E- Neurotoxicity. Ca +2 /Mg +2 infusions for treating neurotoxicity. Nephrotoxicity Anaphylaxis 44

45. 5 FLORO URACIL Antimetabolite. S phase specific. IV only. Usual dose- 450 mg/m 2 IV day 1-5 every 28 days. Antitumor activity enhanced by leucovorin and methotrexate. Main S/E- Hand foot syndrome Myelosuppression. T/t- Vistonuridine 10 gm PO, QID for 5 days. 45

46. FOLINIC ACID/ LEUCOVORIN It is a Folic acid analogue. Given along with 5 FU to potentiate its action. It acts as a ligand, gets attached to the receptor of tumor cells and aids the binding of 5FU to the cells. Administered before giving 5 FU. It is also given along with Methotrexate. When given with Methotrexate, it replenishes the Folic Acid reserves which have been decreased due to Methotrexate toxicity. 46

47. PACLITAXEL Taxane . Antimicrotubule agent. Cell cycle specific agent (M phase), enhaces microtubule polymerization. Only IV. Usual dosage- 135-175 mg/m 2 IV 3 hr infusion q3w, 80-100 mg/m 2 IV 1 hr infusion q1w . Potent radiosensitizer. Main S/E- Hypersensitivity reaction Neurotoxicity Cardiotoxic (mild) Myelosuppression 47

48. DOCETAXEL Taxane , semisynthetic agent. Antimicrotubule agent. Cell cycle specific agent (M phase), enhances microtubule polymerization. Only IV. Usual dosage- 75 mg/m 2 IV q3w. Radiosensitizer. Main S/E- Hypersensitivity Myelosuppression Fluid retention syndrome Maculopapular rash Vesicant 48

49. CISPLATIN Platinum analog. AKA CDDP. Binds to DNA at N7 position of adenine and guanine, produces cross links. Cell cycle non specific agent. IV or Intraperitoneal. Used mostly in squamous cell neoplasms. Radiosensitizer. Usual dosage- 50-100 mg/m 2 IV as either q1w or q3w. Also 20 mg/m 2 IV if used on day 1-5 q3w. If used with paclitaxel, administered after it. Main S/E- Most emetogenic Nephrotoxic Peripheral neuropathy Ototoxicity SIADH 49

50. CARBOPLATIN Platinum analog. Binds to DNA at N7 position of adenine and guanine, produces cross links. Cell cycle non specific agent. Only IV. Dose calculated by AUC, based on GFR. Calvert formula- Dose (mg) = Target AUC x (GFR+25). If used with paclitaxel, administered after it. Main S/E- Myelosuppression Nausea and vomiting Nephrotoxic Peripheral neuropathy 50

51. TRASTUZUMAB AKA Herceptin. Anti HER 2 antibody. Recombinant humanized monoclonal antibody. Usual dose- 8 mg/kg IV over 90 min loading dose, f/b 6 mg/kg IV over 90 min maintenance dose, q3w. Main S/E- Cardiotoxic Infusion reaction 51

52. RADIATION THERAPY 52

53. Radiation therapy, usually administered with concomitant fluoropyrimidine based chemotherapy, is indicated for locally confined gastric cancer that either is not technically resectable or occurs in medically inoperable patients. Historically, 2D based radiation planning has been carried out primarily using anatomic landmarks as well as fluoroscopic barium swallow to determine field borders. Those who undergo gastric resection with incomplete tumor resection or have truly positive margins of resection are also appropriately managed by combined-modality therapy. For unresectable lesions with moderate periesophageal extension, it may not be possible to exclude an adequate amount of the heart with AP/PA fields, and the use of lateral or oblique fields for a portion of treatment, as well as adopting IMRT techniques, is likely indicated. 53

54. Patients with locally advanced disease that is unresectable with negative margins would be identified preoperatively with endoscopic ultrasonography and CT staging. Preoperative chemoradiation then could precede an attempt at gross total resection, alone or in combination with IORT, and maintenance chemotherapy. In patients with high-risk features- poorly differentiated or higher-grade cancers lymph vascular invasion perineural invasion age <50 years suboptimal resection including lymph node resection, postoperative chemoradiotherapy may be indicated. 54

55. RT Dosing : 45-50.4 Gy (1.8 Gy/day), total 25-28 fractions Higher doses may be used for positive surgical margins in selected cases as a boost to that area- 55-60 Gy. Meticulous treatment planning is required to reduce unnecessary dose to OARs. 55

56. POSITION: Supine FIELD: AP/PA parallel opposed fields BORDERS:- SUPERIOR BORDER: at T10/T11 INFERIOR BORDER: at L3/L4 ,for proximal 1/3 or GE junction: at L1/L2 LEFT LATERAL: include all remaining peri-gastric nodes, antral/distal 1/3 lesions, splenic hilum RIGHT LATERAL: preop location of primary tumour or porta hepatis (whichever is further) 56

57. 57

58. PRINCIPLES OF CHEMORADIATION THERAPY 58

59. INDICATION OF POST-OP CT-RT- If no pre-op CT/ CT-RT All pT3 and pT4 less than D2 dissection High nodal burden All R1 and R2 resection if no pre-op RT or CT-RT. If Pre-op RT/ CT-RT given- Not indicated 59

60. POSTOPERATIVE CT-RT- for patients who received less than a D2 lymph node dissection The INTERGROUP 0116 TRIAL formed the basis for postoperative adjuvant CT-RT strategy REGIMEN 1 (FU + Leucovorin) : 2 cycles before and 4 cycles after CT-RT. For cycles after CT-RT, begin CT 1 month after CT-RT. Leucovorin 400 mg/m 2 IV on day 1, Fluorouracil 400 mg/m 2 IV push on day 1 ,Fluorouracil 1200 mg/m 2 IV continuous infusion over 24 hours daily on days 1 and 2 cycled every 14 days. With radiation: Fluorouracil 200–250 mg/m 2 IV continuous infusion over 24 hours daily on days 1–5 weekly for 5 weeks. 60

61. REGIMEN 2 (Capecitabine) : 1 cycle before and 2 cycles after CT-RT. For cycles after CT-RT, begin CT 1 month after CT-RT. Capecitabine 750–1000 mg/m 2 PO BID on Days 1–14 cycled every 21 days, for pre and post CT-RT. With RT: Capecitabine 625–825 mg/m 2 PO BID on days 1–5 weekly for 5 weeks. 61

62. FOLLOW UP 62

63. 63

64. 64

65. REFERENCES Perez Dobb Springer Devita AJCC NCCN Grays Anatomy Google 65

66. NEXT SEMINAR CA ESOPHAGUS Dr. ARTI KUMAWAT 9.5.2025 66

67. THANK YOU, AND HAVE A NICE DAY. 67