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.
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
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 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 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
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)
Surgery has a diminishing role in the management of gastric lymphomas as whole.
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 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)
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: 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 *
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)
6 cycles are required in most instances but in limited stage disease 3-4 cycles combined with IFRT has shown better result.
Raderer et al 1 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 series 2 by the same author 36 /37 patients attained CR after CHOP. Out of these 34 had attained CR after only 3 cycles.
Aviles et al 1 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.
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
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.
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