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Gastrointestinal Lymphomas
Introduction ,[object Object],[object Object],[object Object],[object Object],[object Object]
Epidemiology ,[object Object],[object Object],[object Object]
Epidemiology ,[object Object]
Staging ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Blackledge modification of Ann Arbor staging Involvement of distant organs & extralymphatic organs. IV E Involvement of organ and lymph-nodes on both sides of diaphragm III E ,[object Object],[object Object],Involvement of organ & regional nodes  IIE Limited to the intestine or stomach with focal / multifocal spread. IE
Pathology  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],High grade ,[object Object],[object Object],[object Object],[object Object],Intermediate grade ,[object Object],[object Object],[object Object],Low grade
Pathology (contd.) ,[object Object],[object Object],[object Object]
MALT lymphomas ,[object Object],[object Object],[object Object],[object Object],[object Object]
MALT lymphoma (contd.) ,[object Object],[object Object]
MALT lymphomas ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],PAN B cell Antigens
Etiology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
H. Pylori ,[object Object],[object Object],Molecular detection of  clonal B cells  in H. pylori gastritis patients that can give rise to further MALT lymphomas. 1998 4 First  clinical trial  confirming that anti-Helicobacter therapy leads to regression of gastric MALT lymphomas. 1995 3 First evidence of low-grade gastric MALT lymphoma  regression  after eradication of H. pylori. 1993 2 > 90%  prevalence of H pylori infection in patients with gastric MALT. 1991 1
Pathogenesis H pylori  Infection Chronic gastritis due to bacterial products like  NH 3 Polyclonal  multiplication of B cells in face of antigenic stimulation. Acquisition of  EARLY  t(11:18  ) Monoclonal proliferation in face of continuous antigenic stimulation   Independence from continued  H. pylori  infection and low risk of other abnormalities. Lymphomatous transformation
Dawsons criteria 1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Gastric lymphomas ,[object Object],[object Object],[object Object],[object Object]
Presenting symptoms ,[object Object],[object Object],[object Object],[object Object]
Workup ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
UGIE findings ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Treatment  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
H pylori eradication ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],X 7 days X 7 days
H pylori eradication ,[object Object],[object Object],[object Object],Fresh Biopsy at 3 months Lymphoma positive Lymphoma negative Local RT  Observation Fresh Biopsy at 6 months
Results ,[object Object],[object Object],[object Object],[object Object],[object Object],71% 21 41 Takeshita et al  4 70% 50 35 Neubauer et al 3 47 15 CR 73% 64 Liu et al  2 57% 26 Roggero et al 1 % Total Study
Radiotherapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Radiotherapy ,[object Object],[object Object],[object Object],[object Object]
Target volumes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Paracardiac Pyloric Gastro- epiploic Hepatic Splenic
Applied anatomy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Planning ,[object Object],[object Object],[object Object],[object Object]
RT Results **  In 2001 Koch et al treated all patients by WAR. (+ 6 cycles CHOP in stage IIE patients) *  In 2005 field borders were shrunk to lower border of L5 in stage I N.B. Little clinical data exists for treatment of stage III /IV gastric MALT lymphoma perhaps owing to the relative rarity of the disease. EFRT ** 52 mo 30 Gy + 10 Gy boost I /II 52 Koch et al 3  (2001) IFRT 27 mo 30 Gy (28.5-43.5) I / II 17 Schechter et al 4  (1998) IFRT 59 mo 25 Gy ( 20–30) I / II 13 Tsang et al 2  (2003) 42 mo FU I / II Stage EFRT * Technique 30 Gy + 10 Gy boost 144 Koch et al 1  (2005) Dose (Gy) N Series
RT results
RT Failure *  Combined figures for DLBCL & low grade lymphoma Noteworthy point is that  5 out of 6  relapses in the German 02/96 study were seen in stage IIE (Blackledge stage) patient perhaps indicating a need for a combined modality approach in these patients. 0 0 0 Schechter et al (1998) 7 ( 13.4%) * Not specified Not specified Koch et al (2001) 0 0 0 Tsang et al (2003) 6 (4.1%) Not specified Not specified Koch et al (2005) Total Out field failure In field failure Series
RT toxicity ,[object Object],[object Object],[object Object],[object Object],[object Object]
Renal toxicity ,[object Object],[object Object],[object Object],[object Object]
Surgery ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Results  75% 80% OS 52% 52% 10 yr EFS 78 80 N  Aviles et al (2005) 1 RT Surgery Series 87.2% 90.6% 5 yr OS 82.2% 87.6% 5 yr EFS 32 52 N RT Koch et al (2001) Surgery Series RT Surgery Series 92% 90% 5 yr OS 88% 83% 5 yr EFS 23 34 N Sonnen et al (1994) RT Surgery Series 87% 88% 5 yr OS 56 27 N Norman et al (2000)
Indications  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Chemotherapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Chemotherapy ,[object Object],[object Object],[object Object],[object Object]
Gastric MALT: Approach 1 *  NCCN advocates observation in patients who have advanced stage IV but asymptomatic disease. Gastric MALT Stage IE  Others H pylori positive H pylori (-)ve or t (11:18) +ve  H pylori eradication Recurrence / Failure Local Radiotherapy  Complications  e.g. Bleeding/ perforation/ Bulky disease Uncomplicated  * Surgery ? Radiation + CCT *
High Grade Lymphomas 1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Approach Stage I & II Non Bulky Disease Bulky Disease CCT with CHOP x 6 cycles  ± Rituximab (CD 20 +ve) IFRT 30 – 35 Gy  in 4 – 5 weeks ≥  2 risk factors No risk factors CCT with CHOP x 3-4 cycles  ± Rituximab (CD 20 +ve)
Chemotherapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Chemotherapy ,[object Object],[object Object],[object Object],[object Object]
Chemotherapy ,[object Object],[object Object],96% 91% 53% 54% 10 yr OS 92% 150 CCT alone 82% 153 Surgery + CT 23% 138 Surgery + RT 28% 148 Surgery 10 yr EFS N ARM
Results: CMT Early stage NA 94% 2 yr OS NA 88% 2 yr EFS NA 52 N Satoshi et al (2005) 77.9%  86.0%  5 yr EFS 77.8%  21 91.6% 91.1% 44 CCT + Sx 72.6%  5 yr OS 38 N Liu et al (2000) 85.9% 5 yr EFS 90.5% 5 yr OS 40 N Binn et al (2003) CCT ± RT Series 76.6% 69.6% 2 yr EFS 78.9% 77.9% 2 yr OS 47 54 N Koch et al (2001) 85.4%  88.4%  5 yr EFS 87.5%  49 62% 67% 13 CCT + Sx 88.5%  5 yr OS 188 N Koch et al (2005) 85% 5 yr EFS 60% 5 yr OS 24 N Popescu et al (2003) CCT ± RT Series
Advanced Stage ,[object Object],[object Object],[object Object]
Intestinal NHL ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],33.8% 34.2% 8.4% 9% Multiple sites 12.6%
Histology Intestinal Lymphomas B Cell Lymphoma (60% - 70%) T cell lymphoma (  20% - 30%) High Grade B cell (70% -80%) Low – intermediate grade (20% - 30%) MALT Others (mainly MCL) Mediterranean lymphoma Or Immunoproliferative small intestinal disease
Presentation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Management : B cell  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Radiotherapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Radiotherapy ,[object Object],[object Object],[object Object],[object Object]
Chemotherapy ,[object Object],[object Object],[object Object],[object Object]
Results Survival Relapse 65% (5 yr)  35 (87) 71.3% Sx + CCT ± RT  All Cortelazzo et al   5 45% (4 yr)  NA NA Sx + CCT All Otter et al   4   (population based registry study) 47% (10 yr)  13 (52) 85.2% Sx + CCT ± RT (WAR)  All 94% (2yr)  8 (19) Chul et al  3 95% Sx + CCT (CHOP) I & II 59% (5yr)  1 (2) Duam et al  2 4 (22) 20% 100%  CR CCT (MACOP - B) only III & IV SX + CCT (CHOP / MACOP B) I & II Zinzani et al  1   Modality Stage
T cell lymphomas ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
T cell lymphomas ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Treatment ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Prognostic factors ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Rare presentations ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Rare presentations ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
HIV associated lymphoma ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Conclusions ,[object Object],[object Object],[object Object],[object Object],[object Object]

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Management of Gastrointestinal Lymphomas

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  • 13. Pathogenesis H pylori Infection Chronic gastritis due to bacterial products like NH 3 Polyclonal multiplication of B cells in face of antigenic stimulation. Acquisition of EARLY t(11:18 ) Monoclonal proliferation in face of continuous antigenic stimulation Independence from continued H. pylori infection and low risk of other abnormalities. Lymphomatous transformation
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  • 28. RT Results ** In 2001 Koch et al treated all patients by WAR. (+ 6 cycles CHOP in stage IIE patients) * In 2005 field borders were shrunk to lower border of L5 in stage I N.B. Little clinical data exists for treatment of stage III /IV gastric MALT lymphoma perhaps owing to the relative rarity of the disease. EFRT ** 52 mo 30 Gy + 10 Gy boost I /II 52 Koch et al 3 (2001) IFRT 27 mo 30 Gy (28.5-43.5) I / II 17 Schechter et al 4 (1998) IFRT 59 mo 25 Gy ( 20–30) I / II 13 Tsang et al 2 (2003) 42 mo FU I / II Stage EFRT * Technique 30 Gy + 10 Gy boost 144 Koch et al 1 (2005) Dose (Gy) N Series
  • 30. RT Failure * Combined figures for DLBCL & low grade lymphoma Noteworthy point is that 5 out of 6 relapses in the German 02/96 study were seen in stage IIE (Blackledge stage) patient perhaps indicating a need for a combined modality approach in these patients. 0 0 0 Schechter et al (1998) 7 ( 13.4%) * Not specified Not specified Koch et al (2001) 0 0 0 Tsang et al (2003) 6 (4.1%) Not specified Not specified Koch et al (2005) Total Out field failure In field failure Series
  • 31.
  • 32.
  • 33.
  • 34. Results 75% 80% OS 52% 52% 10 yr EFS 78 80 N Aviles et al (2005) 1 RT Surgery Series 87.2% 90.6% 5 yr OS 82.2% 87.6% 5 yr EFS 32 52 N RT Koch et al (2001) Surgery Series RT Surgery Series 92% 90% 5 yr OS 88% 83% 5 yr EFS 23 34 N Sonnen et al (1994) RT Surgery Series 87% 88% 5 yr OS 56 27 N Norman et al (2000)
  • 35.
  • 36.
  • 37.
  • 38. Gastric MALT: Approach 1 * NCCN advocates observation in patients who have advanced stage IV but asymptomatic disease. Gastric MALT Stage IE Others H pylori positive H pylori (-)ve or t (11:18) +ve H pylori eradication Recurrence / Failure Local Radiotherapy Complications e.g. Bleeding/ perforation/ Bulky disease Uncomplicated * Surgery ? Radiation + CCT *
  • 39.
  • 40. Approach Stage I & II Non Bulky Disease Bulky Disease CCT with CHOP x 6 cycles ± Rituximab (CD 20 +ve) IFRT 30 – 35 Gy in 4 – 5 weeks ≥ 2 risk factors No risk factors CCT with CHOP x 3-4 cycles ± Rituximab (CD 20 +ve)
  • 41.
  • 42.
  • 43.
  • 44. Results: CMT Early stage NA 94% 2 yr OS NA 88% 2 yr EFS NA 52 N Satoshi et al (2005) 77.9% 86.0% 5 yr EFS 77.8% 21 91.6% 91.1% 44 CCT + Sx 72.6% 5 yr OS 38 N Liu et al (2000) 85.9% 5 yr EFS 90.5% 5 yr OS 40 N Binn et al (2003) CCT ± RT Series 76.6% 69.6% 2 yr EFS 78.9% 77.9% 2 yr OS 47 54 N Koch et al (2001) 85.4% 88.4% 5 yr EFS 87.5% 49 62% 67% 13 CCT + Sx 88.5% 5 yr OS 188 N Koch et al (2005) 85% 5 yr EFS 60% 5 yr OS 24 N Popescu et al (2003) CCT ± RT Series
  • 45.
  • 46.
  • 47. Histology Intestinal Lymphomas B Cell Lymphoma (60% - 70%) T cell lymphoma ( 20% - 30%) High Grade B cell (70% -80%) Low – intermediate grade (20% - 30%) MALT Others (mainly MCL) Mediterranean lymphoma Or Immunoproliferative small intestinal disease
  • 48.
  • 49.
  • 50.
  • 51.
  • 52.
  • 53. Results Survival Relapse 65% (5 yr) 35 (87) 71.3% Sx + CCT ± RT All Cortelazzo et al 5 45% (4 yr) NA NA Sx + CCT All Otter et al 4 (population based registry study) 47% (10 yr) 13 (52) 85.2% Sx + CCT ± RT (WAR) All 94% (2yr) 8 (19) Chul et al 3 95% Sx + CCT (CHOP) I & II 59% (5yr) 1 (2) Duam et al 2 4 (22) 20% 100% CR CCT (MACOP - B) only III & IV SX + CCT (CHOP / MACOP B) I & II Zinzani et al 1 Modality Stage
  • 54.
  • 55.
  • 56.
  • 57.
  • 58.
  • 59.
  • 60.
  • 61.