management of gastrointestinal lymphomas

Gastrointestinal Lymphomas

Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER

IntroductionIntroduction

• Gastrointestinal lymphomas are the most common form of primary extra nodal lymphomas.

• Primary lymphoma accounts for 1-4% of all gastrointestinal tumors

• Most commonly these are Non Hodgkin’s lymphomas.

• Hodgkin's disease usually involve the GIT secondarily.

• Gastric lymphomas are the most common form of gastrointestinal lymphomas with very interesting etiology and natural history.


EpidemiologyEpidemiology

• Typically account for 15% of all NHL patients.• In our institution GI lymphomas have accounted for

approximately 10% of all NHL patients.• In large retrospective series gastric lymphomas occupy

the lion’s share of the primary GI lymphomas.

80%

15%5%

Gastric

Small Intestinal

Colo rectal


EpidemiologyEpidemiology

• NE Italy has a very high incidence of primary gastric lymphomas e.g. Feltre region1 where population incidence was 66 /100,000 (13* times more common than UK /USA incidence).


StagingStaging

• Most commonly staged by the Ann arbor staging criteria.

• Disadvantages include:– Inadequate information

regarding spread.– Prognostic information is

diluted.– Pattern of spread of GI ENL

is different.• Musshoff1 proposed a

modification for the scheme. (1977) which was adopted at the Lugano workshop for GI ENLs in 1993

IE Limited to the intestine or stomach with focal / multifocal spread.

IIE Involvement of organ & regional nodes

IIE1 Involvement of local nodes

IIE2 Non-contiguous nodes involved.

III E Involvement of organ and lymph-nodes on both sides of diaphragm

IV E Involvement of distant organs & extralymphatic organs.

Blackledge modification of Ann Arbor staging


Pathology Pathology

• Some pathological classification schemes available include:– The Working formulation.

(1972)– The REAL classification

(1993)• Now a days the REAL

classification based upon the cell of origin and immunophenotyping is considered most authentic but for practical purposes the working formulation suffices.

Low grade

► Small lymphocytic

► Follicular small cell

► Follicular mixed

Intermediate grade

► Follicular large cell

► Diffuse small

► Diffuse mixed

► Diffuse large

High grade

► Diffuse large cell lymphoblastic

► Immunoblastic

► Burkitt’s (small, non cleaved cells)


Pathology (contd.)Pathology (contd.)

• In 1973 Issacson and Wright1 gave the concept of MALT lymphomas based upon their findings in 3 patients with FCC type ENLs.

• They found that some low grade lymphomas will recapitulate the features of a Peyers patch rather than a node.

• This was subsequently incorporated into the REAL classification but failed to find a place in the working classification.


MALT lymphomasMALT lymphomas

• The main features identified by Issacson included:– Long history with evidence of

ongoing chronic inflammation in the mucosa.

– Propensity to invade and destroy the epithelium characteristic lesions called lymphoepitheliomas.

– B-cell phenotype with MONOCLONAL plasma cell differentiation.

– Cells retained the homing pattern of the MALT lymphocytes with typical multi focal spread.


MALT lymphoma (contd.)MALT lymphoma (contd.)

• Now MALT lymphomas are categorized as Extranodal marginal zone B-cell lymphomas.

• The term “marginal” refers to the distribution of the lymphoma cells around the germinal centers in Peyers patches


MALT lymphomasMALT lymphomas

• MALT lymphomas don’t have a specific immunological marker but they are positive for:– CD 19 – CD 20– CD 22– CD 79a

• Absence of CD 10 and CD 5 help to differentiate them from Follicle center cell and Mantle cell lymphomas.

PAN B cell Antigens


EtiologyEtiology

• MALT lymphomas have a well understood etiopathogical pathway.

• Predominant association of Gastric MALT with H. Pylori infection exists.

• Other bacteria know to be associated include:– Campylobacter jejuni– Borrelia burgdorferi– Chlamydia psittaci

• Several DNA translocations known:– t (11:18)– Trisomy 3


H. PyloriH. Pylori

• A gram –ve spiral bacillus that is know to colonize the gastric mucosa of > 50% of the human population.

• The bacillus elaborates an enzyme urease which allows it to survive in the acidic environment in the stomach.

19911 > 90% prevalence of H pylori infection in patients with gastric MALT.

19932 First evidence of low-grade gastric MALT lymphoma regression after eradication of H. pylori.

19953 First clinical trial confirming that anti-Helicobacter therapy leads to regression of gastric MALT lymphomas.

19984 Molecular detection of clonal B cells in H. pylori gastritis patients that can give rise to further MALT lymphomas.


PathogenesisPathogenesis

H pylori Infection

Chronic gastritis due to bacterial products like NH3

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 criteriaDawsons criteria11

• Originally used to define a primary intestinal lymphoma now modified to define gastric lymphomas also.

• Inclusion criteria: The organ is predominantly involved, and the intra-abdominal lymphadenopathy, if present, corresponds to the expected lymphatic drainage of the organ.

• Exclusion criteria:– Palpable subcutaneous nodule.– Mediastinal lymphadenopathy.– Abnormal leucocytes on PBS / BM aspirate.– Splenic / Hepatic involvement

• Danish criteria2: Patients with primary gastric lymphoma have more than 75% of their disease volume in the stomach, based on clinical and radiological staging


Gastric lymphomasGastric lymphomas

• Usually common in the age group of 50 – 60 yrs.

• Most series report a slight female preponderance.

• Most patients have a history of long standing gastritis.

• 50% are MALT lymphomas and the rest are usually DLBCLs.


Presenting symptomsPresenting symptoms

• Fever & Night sweats are uncommon.

• Almost all patients are symptomatic at presentation.

• Mean duration of symptoms vary from 4 to 10 months prior to diagnosis.

• Approx 20% may present with bleeding and 2% with perforation.

0% 20% 40% 60% 80% 100%

Pain

Wt loss

Nausea

Bleeding

Vomiting

Brooks et al Rackner et al


WorkupWorkup

• Routine hematological workup:– Hemogram – Biochemistry

• Staging workup– UGIE– Barium meal & follow through– CT scan abdomen – Endoscopic USG– Chest X ray– Bone marrow

• Optional– Immunophenotyping

– LDH & ß2 microglobulin

CT scan features :

1. Clefts & tracks in the mucosa.

2. Diffuse wall thickening

3. Rugal prominence

4. Intraluminal mass

5. Lymphadenopathy

Endoscopic USG:

1. Has sensitivity & specificity of 89% and 97% for assessing transmural spread.

2. Specific echogenic patterns reported.


UGIE findingsUGIE findings

• Typical findings are:– Rugal thickening– Diffuse infiltrative process making the

stomach indistensible– Confluent mucosal ulceration– Polypoidal mass.

• Differences between primary gastric and secondary gastric lymphomas:– Fundic and duodenal involvement

uncommon in primary lymphomas– Multifocal growth more common in

SECONDARY lymphomas. – BULKY disease commoner in HGPGL

while diffuse infiltrative pattern seen in LGPGL.

– In contrast polypoidal and ulcerative leisons more common in secondary lymphomas.


Treatment Treatment

• The treatment strategy for MALT lymphoma and DLBCL are different because of the different natural history, response to treatment and prognosis.

• MALT lymphomas are unlike other nodal indolent lymphomas as they are amenable to CURE.

• This is because:– The tumors are very radiosensitive.– They usually have less distant spread.– Often respond to H pylori eradication alone.


H pylori eradicationH pylori eradication

• A triple drug therapy is recommended by the Maastricht 2 -2000 workshop on eradication of H pylori.

• First line regimen is:– PPI B.D.– Clarithromycin 500 mg BD – Amoxicillin 1000 mg BD – In the Indian population the wide spread amoxicillin

resistance makes metronidazole 500mg TD the DOC.

• 2nd line regimen in case of failure:– PPI BD– Bismuth subsalicylate 120 mg QDS– Metronidazole 500 mg TD– Tetracycline 500 mg QDS

X 7 days

X 7 days


H pylori eradicationH pylori eradication

• Guide lines for FU in patients on H pylori eradication therapy are as below.

• Further FU should be done for a prolonged period of time ( 2 - 4 years).

• In some situations where the initial infection has not been cured a 2nd course of antibiotics is appropriate before any other measures

Fresh Biopsy at 3 months

Lymphoma positive

Lymphoma negative

Local RT

Observation

Fresh Biopsy at 6 months


ResultsResults

• H pylori eradication is proven to result in CR in many patients who have Stage IE gastric MALT lymphomas.

• Indicators of response2:– Stage IE disease– Negative for t (11:18)

• However Neubauer et al3 have shown the presence of monoclonal B cells during follow-up in 22 of 31 (70%) assessable patients in complete remission by PCR.

Study Total CR %Roggero et al1 26 15 57%

Liu et al 2 64 47 73%

Neubauer et al3 35 50 70%

Takeshita et al 4 41 21 71%


RadiotherapyRadiotherapy

• Radiotherapy forms the most commonly used modality for definitive treatment of gastric MALT lymphomas.

• Localized and are highly radiosensitive.• RT offers the benefits of:

– Organ preservation– Acceptable local toxicity – Absence of systemic toxicity– Reliable and durable cure – Maintenance of quality of life– Less stringent FU requirements.– Lower treatment cost in 3rd world countries.



• Doses: 30 -35 Gy delivered over 4 – 5 weeks is the usual standard.

• Both Co60 and LINACs can be used with equal efficacy and toxicity profiles.

• These lymphomas are know to respond to lower doses of radiation than other indolent lymphomas.

• No comparative trials between whole abdomen and IFRT but toxicity of the former significantly more.


Target volumesTarget volumes

• CTV definition:– Entire stomach.– Perigastric lymph nodes.– Added 5 mm margins.

• The organs at risk include:– Left Kidney– Pancreas– Liver– Heart– Lower portions of lung

Paracardiac

PyloricGastro- epiploic

Hepatic

Splenic


Applied anatomyApplied anatomy

• Surface markings: (in supine patient)– Fundus: At the 5th

interspace or the 6th costal cartilage, a little below the apex of the heart

– Cardia: Opposite the 7th left costal cartilage about 2.5 cm from the side of the sternum;

• Corresponds to the level of the D-10 vertebra.

– Pylorus: On the transpyloric line about 1 cm. to the right of the middle line.

• Corresponds to the level of the L-1 vertebra


PlanningPlanning

• The planning process is preceded by delineation of the organs at risk and the site of interest using appropriate oral / IV contrast.

• Usually a 2 field technique is used with the field borders as demonstrated.

• In order to spare the left kidney separate field arrangements may be used. MC a 3 field technique is used.

• However alternate field arrangements lead to unnecessary liver radiation dose.


RT ResultsRT Results

Series N Stage

Dose (Gy) FU Technique

Koch et al1 (2005)144 I / II 30 Gy + 10 Gy boost 42 mo EFRT*

Tsang et al2 (2003)13 I / II 25 Gy ( 20–30) 59 mo IFRT

Koch et al3 (2001)52 I /II 30 Gy + 10 Gy boost 52 mo EFRT**

Schechter et al4 (1998)17 I / II 30 Gy (28.5-43.5) 27 mo IFRT

** 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.


RT resultsRT results

93.1%

90.7%

87.9% 87.6%

100.0%100.0% 100.0%100.0%

80%82%

84%86%

88%90%

92%94%

96%98%

100%102%

Koch 2005 Tsang Koch 2001 Schetcher

5 yr EFS 5 Yr OS


RT FailureRT Failure

Series In field failure Out field failure Total

Koch et al (2005) Not specified Not specified 6 (4.1%)

Tsang et al (2003) 0 0 0

Koch et al (2001) Not specified Not specified 7 ( 13.4%)*

Schechter et al (1998) 0 0 0

* 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.


RT toxicityRT toxicity

• In the series reported by Tsang et al toxicity reported included transient anorexia and malaise and occasional nausea or dyspepsia, and were treated conservatively. Late ulceration or hemorrhage was not observed.

• Separate toxicity data has not been reported by the German NHL study group but a total of – 11 treatment related deaths were observed in

the 2005 study (total 759 patients) – 11 patients died in the 2002 series (total 185). – In this study whole abdomen radiation was used.


Renal toxicityRenal toxicity

• Reported by Maor et al in 1998, who analysed 27 patients who had received > 24 Gy to at least 1/3rd of the left kidney. ( Mean prescribed dose = 37.9 Gy at 1.5 Gy/ #)

• 3 patients had persistent, mild elevations of urea and creatinine levels but all had received Cisplatin

• Only 2 patients developed hypertension, both at a low level of 150/90; one patient had had 40 Gy to the whole kidney, the other 40 Gy to half the kidney.

• Ipsilateral kidney shrinkage was evident in most patients. The degree of atrophy was related to the volume of kidney irradiated.


SurgerySurgery

• Surgery has a diminishing role in the management of gastric lymphomas as whole.

• Reasons:– A total gastric resection is required as the entire stomach

is at risk.– Morbidity of gastrectomy series ranges 8% -16%– Multifocal nature of the disease results in inability to obtain

clear resection margins– Survival benefit over conservative management is absent– Risks of RT / CCT feared in past now greatly diminished.– 50 – 70% of all tumors are resectable.– Subtotal resection has resulted in poorer control rates in

many series (German NHL studies found both EFS and OS significantly poorer in patients with subtotal resections).


Results Results

Series Surgery RT

Aviles et al (2005)1

N 80 78

10 yr EFS 52% 52%

OS 80% 75%

Series Surgery RT

Koch et al (2001)

N 52 32

5 yr EFS 87.6% 82.2%

5 yr OS 90.6% 87.2%

Series Surgery RT

Sonnen et al (1994)

N 34 23

5 yr EFS 83% 88%

5 yr OS 90% 92%

Series Surgery RT

Norman et al (2000)

N 27 56

5 yr OS 88% 87%


Indications Indications

• Modern day indications for surgery in gastric MALT lymphomas include:– Perforation– Bleeding– Obstruction– Salvage after RT / CCT failure

• Institutional practice plays an important role in defining the optimal practice in the absence of prospective randomized trials comparing stomach preservation vs resection.


ChemotherapyChemotherapy

• Primary chemotherapy has not been successful in limited stage MALT lymphomas owing to the indolent nature of the disease.

• CCT is usually reserved for a symptomatic patient with bulky abdominal disease who is not suited for RT.

• The regimen of choice is CHOP in the doses administered in DLBCL.

• In the patient with poorer GC COP or single agent may be used.

• H pylori eradication is usually recommended concurrently.• Fisher et al comment that from the SWOG experience it

is seen that the pattern of relapse in MZL is similar to that observed in follicular lymphomas implying CCT alone may not be curative.



• Main concern for patients undergoing CCT is the risk of gastric perforation as it carries a 100% mortality rate in the immunosuppressed.

• The incidence of chemotherapy-induced complications is variable and has been reported to be as high as 13% to 25%

• In a review of the literature involving 188 patients, Gobbi et al reported an incidence of 3.2% and 2.7% for perforation and bleeding, respectively.

• Now a days it appears that risk is inherent and is not increased by medical treatment


Gastric MALT: ApproachGastric MALT: Approach11

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*

* NCCN advocates observation in patients who have advanced stage IV but asymptomatic disease.


High Grade LymphomasHigh Grade Lymphomas11

• Higher frequency of weight loss at presentation• Palpable abdominal mass• Hepatomegaly• Peripheral lymphadenopathy• Elevated serum LDH • Higher incidence of stage III-IV disease• Significantly larger primary tumors• Deeper invasion of the gastric wall, • Infiltration of the abdominal lymph nodes • Visceral extension


ApproachApproach

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)



• CCT forms the mainstay of treatment of high grade localized lymphomas of stomach.

• Multiple centers report survival rates between 70 – 80%

• Therapy should be initiated with CHOP in the following doses:– Cyclophosphamide (750 mg /m2)– Adriamycin (50 mg /m2)– Vincristine (1.5 mg / m2)

– Prednisone (100 mg D1 – D5)



• Number of cycles required? – 6 cycles are required in most instances but in

limited stage disease 3-4 cycles combined with IFRT has shown better result.

• Raderer et al1 found that 24 / 25 patients had CR after CHOP and 22 were alive after 2 yrs. They concluded that primary CCT with CHOP was a effective treatment modality in patients with stage I / II gastric DLBCL.

• In another series2 by the same author 36 /37 patients attained CR after CHOP. Out of these 34 had attained CR after only 3 cycles.



• Aviles et al1 reported the following results in PRT comparing 4 different therapeutic strategies in stage I / II gastric DLBCL.

• CHOP was used in standard doses and RT was given to a tune of 40 Gy.

ARM N 10 yr EFS 10 yr OS

Surgery 148 28% 54%

Surgery + RT 138 23% 53%

Surgery + CT 153 82% 91%

CCT alone 150 92% 96%


Results: CMT Early stageResults: CMT Early stage

Series CCT ± RT CCT + Sx

Binn et al (2003)

N 40 44

5 yr OS 90.5% 91.1%

5 yr EFS 85.9% 91.6%

Liu et al (2000)

N 38 21

5 yr OS 72.6% 77.8%

5 yr EFS 86.0% 77.9%

Satoshi et al (2005)

N 52 NA

2 yr EFS 88% NA

2 yr OS 94% NA

Series CCT ± RT CCT + Sx

Popescu et al (2003)

N 24 13

5 yr OS 60% 67%

5 yr EFS 85% 62%

Koch et al (2005)

N 188 49

5 yr OS 88.5% 87.5%

5 yr EFS 88.4% 85.4%

Koch et al (2001)

N 54 47

2 yr OS 77.9% 78.9%

2 yr EFS 69.6% 76.6%

compaq

Look at another study in the notes section

compaq

Surgery in Gastric Lymphoma?[Standard intervention in primary lymphoma of the stomach--initial results of a prospective multicenter study] Verreet PR, Fischbach W, Muller-Hermelink HK, Roher HD.An R0 resection seems to be a rather aggressive treatment, but can be achieved in 80% of localized gastric lymphomas and should be seen in contrast to other effective treatment modalities. For curative treatment at stage EI1-EII1, total gastrectomy with systematic lymphadenectomy (D2) seems to be necessary. Basic information about the clear diagnosis, tumor dissemination and the individual prognosis only becomes available by a standardized operation as part of multimodal therapeutic concepts.Langenbecks Arch Chir Suppl Kongressbd. 1996;113:237-40.To assess the efficacy of primary chemotherapy for treatment of early stage patients with gastric lymphoma, multiple agent chemotherapy was given to patients prior to surgery. Five patients with stages IE and IIE of primary gastric lymphoma (54-65 years of age; three men, two women) were treated with multiple agent chemotherapy prior to gastric resection. In all patients the diagnosis was established by endoscopic biopsy. Two patients had stage IE disease, and three had stage IIE. Histopathologically, there was one diffuse large cell lesion and four diffuse medium cell lesions. All patients received two cycles of VEPA every 4 weeks. On the 16th to 44th day after completion of chemotherapy, total gastrectomy, systematic dissection of regional lymph nodes with resection of the caudal pancreas, and splenectomy were performed. Swelling of the regional lymph nodes was noted in four cases. In all five cases, histologic findings revealed no residual cells of malignant lymphoma in the resected specimen.Early stage gastric lymphoma: is operation essential? Tanaka Y, Takao T, Watanabe H, Kido T, Ogawa N, Iwase K, Sunada S, Sando K, Kawamoto S, Koto K, et al. World J Surg. 1994 Nov-Dec;18(6):896-9.


Advanced StageAdvanced Stage

• Sparse evidence is available for advanced stage high grade gastric lymphomas but consensus is systemic chemotherapy with or without IFRT.

• It is unclear as to how much surgery is useful in these patients.

• Role of radiotherapy has remained undefined as it has not shown to add to the overall survival. However most studies reveal a better local control.


Intestinal NHLIntestinal NHL

• Account for 50% - 20% all primary GI lymphomas.

• These account for 19-38% of all small intestinal malignancies

• Like gastric lymphomas males are more commonly affected.

• Associations:– C. Jejuni infection– Gluten sensitive

enteropathy ( T cell )

33.8%

34.2%

8.4%

9%

Multiple sites 12.6%


HistologyHistology

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

OrImmunoproliferative

small intestinal disease


PresentationPresentation

• Most common modes of presentation include:– Pain– Anorexia– Weight loss

• Obstruction / perforation more commonly reported than for gastric lymphomas (30% -40%).

• T cell lymphomas are notorious for association with:– Obstruction & perforation (50% -30%)– Protein loosing enteropathy ( hypoalbuminemia)– Anemia and thrombocytosis


Management : B cell Management : B cell

• DLBCL of the intestines are managed similar to DLBCL of the stomach with anthracycline based chemotherapy being the mainstay of treatment.

• However primary surgery is more commonly needed to– Establish the diagnosis– Stage the disease– Relieve obstruction & prevent perforation– Reduce tumor bulk– Treat peritonitis resulting from perforation



• RT results in better local control.• Addition of RT justified when there is:

– Bulky residual disease– Partial resections / debulking

• Techniques : WAR / IFRT. • Dose is limited to 30 Gy due to the intrinsic

radiosensitivity of the tumor as well as the surrounding organs.

• Dose per fraction should be 1.5 -18 Gy• Whole abdomen radiation associated with

greater toxicity and has not been proven better as compared to IFRT.



• Chul et al report that in 31 patients who received WAR ± CCT 3 patients had recurrence in abdomen/ pelvis and 5 patients had recurrence outside.

• CCT reduced recurrences outside the field ( 6.7% vs 33%).

• However rates of infield recurrences did not differ (11% vs 9%).

• Other series report incidence of recurrence outside RT field ranges from 50 - 60% if CCT is not added.



• Guidelines for addiction of CCT for Small intestinal lymphomas are non existent.

• CHOP x 6 cycles delivered 3 weekly is the standard of care.

• Other CCT regimens have been used for aggressive B cell lymphomas but results are equivocal.

• In low grade lymphomas esp. MALT lymphomas addition of CCT remains debatable in view of the indolent nature of the disease and prolonged expected survival.


ResultsResults

Stage Modality CR Relapse Survival

Zinzani et al 1

I & II SX + CCT (CHOP / MACOP B) 100% 4 (22) 59% (5yr)

III & IV CCT (MACOP - B) only 20% 1 (2)

Duam et al 2

I & II Sx + CCT (CHOP) 95% 8 (19) 94% (2yr)

Chul et al 3

All Sx + CCT ± RT (WAR) 85.2% 13 (52) 47% (10 yr)

Otter et al 4 (population based registry study)

All Sx + CCT NA NA 45% (4 yr)

Cortelazzo et al 5

All Sx + CCT ± RT 71.3% 35 (87) 65% (5 yr)


T cell lymphomasT cell lymphomas

• Special features are:– Occurs in 7% -12 % patients with celiac disease

or dermatitis herpetiformis.– Has 3 types (Chott et al)

• Enteropathy associated T cell lymphoma (EATCL)• EATCL like lymphoma without enteropathy• Non EATCL

– A gluten free diet can prevent the occurrence of T cell lymphomas in patients of celiac disease.

– In cases in which large immunoblast-like cells predominate, CD30 expression is characteristic.


T cell lymphomasT cell lymphomas

• Major differences from B cell lymphomas are:– Frequent need for emergency operations.– Poorer survival – Poorer response to CCT– Tumor progression and death commoner during

CCT– Poorer GC at presentation preclude any therapy

in many– More frequent and earlier relapses.

compaq

See note


TreatmentTreatment

• Owing to the rarity the ideal treatment remains controversial.

• Primary surgery followed by CCT is best.• A higher frequency of intestinal perforation and

bleeding noted by some if Sx is omitted. • In the largest series by Daum et al1 (n = 35)

– 2yr OS was 28% only

• In another large series by Gale et al2 (n = 31) – 5-year OS was 19.7%,, – 5-year failure-free survival rate was only 3.2%


Prognostic factorsPrognostic factors

• Stage of disease: – 80.8% of 5yr survival for tumors smaller than 5 cm vs. 44.4% for

larger lesions, (p < 0.05).– 68.6% in stage II 1E to 44.4% in stage II 2E – DFS falls from 57.1% in stage II 1E to 16.7% in stage II 2E

• Depth of invasion and serosal penetration:– 5 yr survival rate decreases for the stages I to III from 82% to

24%.• Grade of disease :

– The five-year survival rate for low-grade and high-grade tumors was 91% and 56%, respectively.

• Other factors:– Older age > 60– Elevated serum LDH– T cell type lymphoma– Higher cell proliferation index– Genetic markers like t (11:18)


Rare presentationsRare presentations

Multiple lymphomatous polyposis• Considered to represent Mantle cell

lymphoma of the intestine but can represent other types too

• Characterized by multiple polyps involving long segments of the gastrointestinal (GI) tract

• Best diagnosed by barium studies.• CCT is the basis for treatment• Poor prognosis


Rare presentationsRare presentations

Immunoproliferative small intestinal disease

• IPSID is associated predominantly with poor socioeconomic conditions

• Affecting young adults with almost equal sex incidence

• Involves predominantly the proximal small intestine

• Associated with multiple pathogens• Patients present with progressive

malabsorption in the 2nd and 3rd decades.• Diagnosis is established by small bowel

biopsy, with or without high serum levels of the alpha heavy chain protein

• Spontaneous remissions in early stages• Tetracycline and metronidazole

recommended in the initial treatment.


HIV associated lymphomaHIV associated lymphoma

• HIV infection leads to a 100 times greater risk of lymphomas.

• MC Large B cell type lymphomas are seen.• Extranodal involvement and advanced stage at

presentation are common.• Anal and rectal lymphomas are seen frequently.• Patients have B symptoms more frequently.• Therapy is complicated by ongoing immunosupression.• HAART + CHOP x 6 cycles forms the current standard of

care.• Rituximab is dangerous – greater chance of fatal

infection due to aggravation of CD4+ cell loss.


ConclusionsConclusions

• Gastrointestinal lymphomas are an important subgroup of extranodal lymphomas.

• Among them MALT lymphomas are unique as they are very much curable by conservative measures.

• Combined modality stomach sparing therapy with CCT and RT is feasible in majority of the localized gastric lymphomas.

• Surgery forms the mainstay of treatment for intestinal lymphomas

• Elucidation of the important role of gut flora in the pathogenesis of these diseases can act as a model for all lymphomas.

management of gastrointestinal lymphomas

Health & Medicine

francisco

regional lymph

extranodal

localized

controlled

german multicenter

stage ii 1e

helicobacter