Gastrointestinal Lymphomas
Oct 19, 2014
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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).
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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)
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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%
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
RadiotherapyRadiotherapy
• 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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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).
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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%
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
ChemotherapyChemotherapy
• 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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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)
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
ChemotherapyChemotherapy
• 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)
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
ChemotherapyChemotherapy
• 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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
ChemotherapyChemotherapy
• 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%
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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%
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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%
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
RadiotherapyRadiotherapy
• 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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
RadiotherapyRadiotherapy
• 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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
ChemotherapyChemotherapy
• 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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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)
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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%
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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)
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.
Moderator: Dr. S C Sharma, HOD, Departmet of Radiotherapy, PGIMER
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.