Gastrointestinal tract lymphoma

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Information about Gastrointestinal tract lymphoma

Published on December 16, 2016

Author: DrShadSalimAkhterAkh

Source: slideshare.net

1. Gastrointestinal Tract Lymphoma Dr. Shad Salim Akhtar MBBS, MD, MRCP(UK), FRCP(Edin), FACP(USA), Member AUICC Fellows Consultant Medical Oncologist Medical Director Prince Faisal Oncology Center & KFSH Prof. of Clinical Medicine, Qassim Medical University Buraidah, Al-Qassim, KSA

2. Non Hodgkin's Lymphoma  Heterogeneous collection of lympho-proliferative diseases  Is it the same disease at all sites???  Major divisions  Nodal  Extra nodal  Around 33-40% are extra nodal  GIT is the commonest extra- nodal site  Around 50% Henessey BT et al. Lancet Oncol 2004;5:341

3. Extra nodal NHL  Clinically dominant (>75%) extra nodal component with  No or Minor nodal involvement (25%)  Tonsils / Waldeyer’s ring?? Zucca E et al: Ann Oncol 1997; 8:727

4. GI NHL-Definition  Localized disease to the GIT  Stage IE, IIE disease  Lymphoma patients exhibiting GI symptoms or have a predominant lesion in GI Dawson IMP et al: Br. J Surg 1961; 49:80 Lewin KJ et al: Cancer 1978; 42:693 Haber DA et al: Semin Oncol 1988; 15:154

5. All patients who present with NHL that apparently originated at an extra nodal site even in the presence of disseminated disease, as long as the extra nodal component is dominant” GI NHL-Definition Krol ADG et al: Ann Oncol 2003; 14:131

6. NHL-Increasing incidence  1970 10.2/100,000  1990 18.5/100,000  81% increase or 3.6% per year  Extra nodal NHL 3-6.9%/year  Nodal NHL 1.7-2.5%/year Vose JM et al: Hematology 2002; 242 Ries LAG et al: National Cancer Institute 2002`

7. GI NHL-Sites of involvement Author Total Gastric Intest Koch P 371 277 70 Liang R 442 238 184 Radaszkiewicz T 307 264 59 Morton JE 175 78 95 Azab MB 106 55 43 Amer MH 185 94 91 El Foudeh M 215 185 66 Nakamura S 455 342 96 Ducreux M 78 42 13

8. GI NHL-Major symptoms Pain Nausea vomiting Bleeding Weight loss Diarrhea Acute abdomen

9. GI NHL-Symptoms versus site Stomach Small intestine Colorectal Pain Pain Pain Nausea & Vomiting Obstruction Bleeding Weight loss Weight loss Diarrhea Bleeding Malabsorption Crump M et al: Semin Oncol 1999; 26:324

10. GI NHL-Staging system TNM I Single nodal region Localized single extra lymphatic organ/site IE II 2 or more node regions same side of diaphragm Localized single extra lymphatic organ/site with its regional nodes+/- other nodes on the same side of diaphragm IIE III Node regions both sides of diaphragm+/- localized single extra lymphatic organ/site Spleen / Both IIIE IIIS IIIES IV Diffuse or multi focal involvement of extra lymphatic organs+/- regional nodes; isolated extra lymphatic organ and non regional lymph nodes Sobin LH et al: TNM Manual 6th Edition 2002; 238

11. GI NHL-Staging system Stage I  Tumor confined to the GI tract  Single primary site or multiple non contiguous lesions Stage II  Tumor extending into abdomen from a primary GI site  Nodal involvement  II1 local (paragastric / paraintestinal)  II2 distant (mesenteric, para-aortic, paracaval, pelvic, inguinal) Rohatiner A et al: Ann Oncol 1994; 5:397

12. Stage IIE  Penetration of serosa to involve adjacent organs or tissues Stage IV  Disseminated extra nodal involvement or  GIT lesion with supradiaphragmatic nodal involvement GI NHL-Staging system Rohatiner A et al: Ann Oncol 1994; 5:397

13.  ? X to denote the organ of origin  X [stomach] II (gastric NHL with local nodes involved)  X [stomach, colon] II  Addition of IP index as in AJCC Cancer Staging Manual 6th Edition? GI NHL- Staging Suggested modifications Armitage JO; N Engl J Med 2005; 352:1250 Grothus-Pinke B et al: Ann Oncol 1996; 7:S126

14. GI NHL-Work up  History & physical examination  Weight loss not recorded as a B symptom  Waldeyer’s ring assessment especially with limited GI involvement  Routine bloods  Endoscopic examination  CT  Barium studies  Bone marrow examination!!!  Endoscopic USG

15. GI NHL-Do they need laparotomy for diagnosis? In 30-50% of intestinal NHL who may present as an emergency Endoscopic biopsy from accessible lesions  Diagnostic accuracy 62% to 98.5%  First attempt diagnosis 80% of above  May miss areas of transformation Al Akwaa AM et al: Worl J Gastroenterol 2004; 10:5

16. FNAC Laparoscopic biopsy  Frozen section facility  Bone marrow in the same sitting All tissues must be sent for  Histological  Immunohistochemistry  Cytogenetic studies GI NHL-Diagnosis? Kaleem Z et al: Am J Clin Pathol 2001; 115:136 Koniaris LG et al: J Am Coll Surg 2003; 197:127

17. GI NHL-Histological types  Diffuse B cell large cell  Secondary DLBCL  Extra nodal marginal zone lymphoma (MALT)  Follicular lymphoma  Mantle cell lymphoma  Burkitt’s lymphoma  Enteropathy type T cell lymphoma  Peripheral T cell lymphoma NOS  Majority of cases seen in KSA are DLBCL type

18. Risk of relapse from complete response according to the primary site of the lymphoma. GI, gastrointestinal. J Clin Oncol 23. © 2005Lo´ pez-Guillermo et al DOI: 10.1200/JCO.2005.07.155

19. Overall survival of 382 patients with diffuse large B-cell lymphoma according to the primary site of the lymphoma. GI, gastrointestinal. J Clin Oncol 23. © 2005 in pressLo´ pez-Guillermo et al DOI: 10.1200/JCO.2005.07.155

20. OS and EFS of nodal vs extra nodal lymphoma in 1168 patients including 216 GI lymphomas defined as per Krol ADG et al. Krol ADG et al: Ann Oncol 2003; 14:131

21. Extra nodal lymphomas-Why do these do better  Gene expression of typical germinal center type B cell rather than activated circulating B cell. Former better prognosis  Additionally  bcl2 protein expression in the absence of t(14:18) translocation are susceptible to rituximab. ?? Significance in GI lymphomas Armitage JO: N Engl J Med 2004; 325:1250 J Clin Oncol 23. © 2005 in pressLo´ pez-Guillermo et al

22. Is surgical resection important for? Definitive diagnosis Improving survival (stage I & II) Preventing complications Gastric DBCLC NHL-Therapy questions?

23. Role of radiotherapy Role of chemotherapy Which chemotherapy Gastric DBCLC NHL-Therapy questions?

24. Gastrectomy – Points in favor  Multiple studies  Stage I surgical resection may be curative  ? The number of MALT lymphomas in these series  Patients undergoing radical excision have a superior outcome  ? Inidicator of low burden disease  Multimodality treatment better survival  Small non randomized retrospective studies  Data collected is of many years Crump M et al: Semin Oncol 1999; 26:324

25. Role of radiotherapy Multiple retrospective studies positive for multimodality therapy Has been used as the sole modality of therapy especially in MALT Post operative adjuvant 88% OS rate Problems of late toxicity Reserve for residual disease, elderly or inoperable patients Koniaris LG et al: J Am Coll Surg 2003; 197:127

26. Adjuvant RT in Early Stage NHL Miller TP et al NEJM 1998;339:21 Comp surg excision Complete response 5 yrs surv RFS 5 yrs surv OS Life threat toxic 58 104/243(73%) 64% 72% 40% 58 106/142(75%) 77% 82% 30% 0.03 0.02 0.06 CHOP 8 CHOP3+RT Stage I/II lymphoblastic NHL excluded

27. What therapy? Stage IPI Rx 5yr MSur Limited stage Proposed description I, IE 0 CHOP(3) + RT >90% Yes Very limited I, IE, II, IIE (non bulky) >=1 CHOP(3) + RT 70% Yes Limited Bulky II, IIE >=1 CHOP(8) 50% No Advanced Fisher RI et al: Hematology 2004; 221

28. German multi-center study  Prospective non randomized  Surgery left to the treating physician  Post operative therapy standardized

29.  277 patients accrued and 185 analyzed  IE 96; II1E 58; II2 E 31  High grade 101 pts (54.6%)  70% without low grade component Type Stage CT RT HG IE CHOP 4 EFRT (30G) + boost IIE COP 6 IFRT (40G) Gastric Lymphoma Therapy- German MC Study Koch P et al: J Clin Oncol 2001; 19:3874

30. Gastric Lymphoma Therapy- German MC Study Type Stage CT RT LG resected IE X EFRT IIE COP 6 EFRT LG unresec IE EFRT+boost IIE COP 6 EFRT+boost Koch P et al: J Clin Oncol 2001; 19:3874

31. Gastric Lymphoma Therapy- German MC Study High grade No surgery Surgery+CRT Number 54 47 EFS 69.6% 76.6% NS OS 77.9% 78.9% NS Low grade Number 52 32 EFS 87.6% 82.2% NS OS 90.2 87.2 NS Koch P et al: J Clin Oncol 2001; 19:3874

32. No Surgery Surgery Event free survival surgical intervention & conservative therapy only Koch Petal:JClinOncol 2001;19:3874

33. nonrandomized comparison; all histologic subtypes Koch P et al: J Clin Oncol 2001; 19:3874

34. EFS EFS of gastric lymphoma resected completely vs partial or incomplete resection Koch P et al: J Clin Oncol 2001; 19:3874

35. Gastrectomy present status  Organ preservation is an important quality of life issue  Resectabilty rates range from 60-80%  Operative mortality and morbidity rates range from 3-25%  Patient preference, tumor size, stage and resectability should be considered

36. Gastrectomy ideal approach “in between the extremes of never and always”

37. Which chemotherapy CHOP Variations Additional immunotherapy Gastric NHL-Chemotherapy

38. Binds CD20, which is present on normal and malignant pre- B and mature B cells; >90% of B-cell NHL express CD20 May induce antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity, based on in vitro data Also triggers apoptosis (programmed cell death) in vitro No apparent dependence on cell cycle for activity Rituximab

39. DLBCL Gastric origin Algorithm for therapy Localized (stage I, II) Advanced disease Complications Complete resectionPossible Not possible CHOP X 6-8 +Ritux CHOPX3+Ritux IFRT (avoid in young) Residual disease EFRT (avoid in young) Resection CR

40. GI NHL-Site of disease- Geographical Variation Site USA Ger Fra KSA NGui Nigeria Jord Gast 77 277 43 185 24 19 23 Small Intest 36 35 39 66* 55 62 59 Ileo- cecal 26 13 Colon 17 3 10 21 19 15 Rect 6 6 Panc 10 5 0 0 Diffu 5 24 16 10 0 2 Kniaris LG :J Am Coll Surg2003;197:127 Koch P :JCO 2001;19:3861

41. Intestinal DLBCL  Surgical intervention is less controversial  Acute presentation more common  Completely resected patients do better  Generally poorer prognosis as compared to gastric  Survival  Early stage disease better  Surgery+CT+RT 50-70%  Single modality 30-50% Koniaris LG et al: J Am Coll Surg 2003; 197:127 Daum S et al: J Clin Oncol 2003; 21:2740

42. Marginal Zone Mantle Zone Germinal Centre (Contains post germinal centre B cells, monocytoid B cells, plasma cells and centrocyte like cells) Normal MALT Rooney N et al: Curr Diag Pathol 2004; 10:69

43. Calam J etal. BMJ 2001;323:980 Relation of H pylori infection to UGI conditions

44. H pylori and Malt lymphoma  ~90% have H pylori in gastric mucosa~90% have H pylori in gastric mucosa  Case control studies confirm relationshipCase control studies confirm relationship between previous infection and lymphomabetween previous infection and lymphoma  Clonal B cell detection in chronic gastritisClonal B cell detection in chronic gastritis which precedes lymphomawhich precedes lymphoma  H pylori strain specific T cells promoteH pylori strain specific T cells promote lymphoma growth in culturelymphoma growth in culture  Eradication of H pylori causes regression inEradication of H pylori causes regression in 75% of caces75% of caces

45. Gastric MALT lymphoma  MALT reacts with the antigen present within the lumen  An Pr Cells +H pyhlori antigen+CD4+ T cells stimulate peoliferation of B cells  B cells synthesize immunoglobulins  Immunoglobulins react with autoantigens Parsonnet J et al: N Engl J Med 2004; 350:213

46. Rooney N et al: Curr Diag Pathol 2004; 10:69

47. Rooney N et al: Curr Diag Pathol 2004; 10:69

48. Gastric MALT types A low grade classical  <5% blasts and clusters of <10 cells B  10-20% transformed cells  Clusters of >20 cells C high grade transformation with sheets of transformed cells D no MALT component is recognizable Isaacson PG: Hematology 2001; 241

49. MALT lymphoma management  Careful imaging  CT scan  Endoscopic ultrasonography  Sufficient tissue to  Differentiate from  Mantle cell lymphoma  Follicular lymphoma  Confirm presence of more transformed clone  Immunohistochemical studies (bcl2 expression)

50. Gastric MALT management  Antibiotic therapy  Regression in approximately 75% cases  Time to regression may be as long as 18 months  Predictors of failure of antibiotic therapy  t(14:18) do not respond to antibiotics  Node positive disease  Depth of invasion muscularis mucosa  Lymphoma clone persists  Therefore it becomes dormant rather than disappear Isaacson PG; Best Prac & Res 2005; 18:57 Cavalli F et al: Hematology 2001; 241

51.  Surgical resection  Antrectomy usually adequate  Radiotherapy  Chemotherapy  Alone or in combinations  5 yr DFS  >95% in IE  75% in IIE Gastric MALT management antibiotic failure or advanced Koniaris LG: J Am Coll Surg 2003; 197:127

52. IPSID  MALT type B cell lymphoma  Proximal small intestine involved  Geographical distribution  Mediterranean Middle East  Africa  Far East  Children & young adults  Monotypic truncated immunoglobulin α heavy chain Lecuit M et al: N Engl J Med 2004; 350:239

53. IPSID  Campylobacter jejuni  Small group of patients (4/6)  FISH, PCR, DNA sequencing and immunohistochemistry  Early stages respond to antibiotics  Non responsive pts progress to lymphoma  Lymphoplasmacytic & immunoblastic  Locally invasive and metastatic  Poor prognosis

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