Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma

Abstract

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease which is often associated with Helicobacter pylori (H. pylori) infection. First-line treatment of stage IE and IIE localized gastric MALT lymphoma is based on the eradication of H. pylori. The presence of H. pylori resistance factors such as translocation t (11;18), peri-gastric lymph node involvement and the degree of tumor infiltration of the gastric wall; or lack of response to antibiotic therapy are two main indications to treat with definitive radiotherapy (RT). RT is an effective treatment in localized gastric MALT lymphoma. A moderate dose of 30 Gy allows a high cure rate while being well tolerated. After treatment, regular gastric endoscopic follow-up is necessary to detect a potential occurrence of gastric adenocarcinoma.

Key Words: Radiotherapy, Mucosa-associated lymphoid tissue, MALT, Helicobacter pylori, Lymphoma, Review

Core Tip: In this review, after Helicobacter pylori eradication failure, radiotherapy is an effective and well tolerated treatment in localized gastric mucosa-associated lymphoid tissue lymphoma. A moderate dose of 30 Gy allows a high cure rate while being well tolerated. Long-term gastric endoscopy follow-up is necessary to detect a possible occurrence of a stomach carcinoma.

INTRODUCTION

Extranodal marginal zone lymphoma (EMZL) is an indolent non-Hodgkin's B-cell lymphoma. It belongs to the heterogeneous group of MZLs, beside splenic MZL and nodal MZL. It has an extra-nodal origin. EMZL can develop from mucosal, called also mucosa-associated lymphoid tissue (MALT) lymphoma, and non-mucosal sites, in various organs such as the stomach, small intestine, bronchi, thyroid gland, liver, kidney, breast, salivary glands, orbit/orbital adnexa, or skin. It can be associated with autoimmune diseases such as Hashimoto's thyroiditis or Sjögren's syndrome. The most common sites of EMZL are the stomach, the orbit/orbital adnexa and the skin, and gastric MALT-lymphoma accounts for 30%–50% of all MALT-lymphoma locations[1,2].

The incidence of non-Hodgkin lymphoma (NHL) has increased by 70% between 1975 and 2017[3]. MALT gastric lymphoma is rare: It represents 4% of all NHL and approximately 5% of primary gastric neoplasms[4]. According of the SEER United States database, new cases of NHL and gastric cancer were respectively 77240 and 27600 in 2020 in the United Stade of America[3], which corresponds to between 1380 and 3090 new cases of gastric MALT lymphoma.

The MALT-IPI index was developed to identify patients with a poor prognosis and thus to allow for appropriate treatment of patients with EMZL. This index classified patients into three prognostic groups (low, intermediate, and high) that are predictive for event-free, progression-free and overall survival (OS), whatever the extranodal site of the lymphoma, gastric or non-gastric. The 5-year event-free survival (EFS) rates in the low-, intermediate-, and high-risk groups were 70%, 56%, and 29%, respectively. This index was based on: Age ≥ 70 years, Ann Arbor stage III or IV and elevated lactate dehydrogenase (LDH). The MALT-IPI has been developed from 401 patients treated with chlorambucil, rituximab, or both in the international randomized trial IELSG-19. The index was subsequently validated by merging three independent cohorts of MALT lymphoma patients (n = 633 patients)[5].

In 90% of cases, gastric MALT lymphoma is associated with a Helicobacter pylori (H. pylori) infection. H. pylori prevalence in developed countries decreased after 2000: In Europe from 48.8% to 39.8%, in Northern America from 42.7% to 26.6%, and in Oceania from 26.6% to 18.7% whereas it remained stable elsewhere: In Asia (53.6% before 2000 vs 54.3% after 2000) and South America and the Caribbean (62.8% before 2000 vs 60.2% after 2000)[6]. In Europe, the prevalence of H. pylori infection decreased from 92% in the 80’s to 61% between 1995-2004 and then to 32% between 2005 -2013 for the United Kingdom, from 82% between 1999-2003 to 69% between 2004-2014 in Austria and from 61% between 1997-2002 to 17% between 2004-2014 for Italy[7-10] (Figure 1).

Figure 1 Prevalence of Helicobacter pylori infection in gastric marginal zone lymphoma. MALT: Mucosa-associated lymphoid tissue.

First-line treatment of stage IE and IIE localized gastric MALT lymphoma is based on the eradication of H. pylori. Recommended anti-H. pylori therapy includes a proton pump inhibitor (or ranitidine bismuth citrate), clarithromycin and amoxicillin (or metronidazole).

Because MALT lymphoma is rare, treatment recommendations are based on studies with low levels of evidence (Figure 2). The aim of this review is to assess the effectiveness and tolerance of radiotherapy (RT) and the alternative treatments.

Figure 2 Gastric mucosa-associated lymphoid tissue lymphoma therapeutic algorithm. HP: Helicobacter pylori.

STAGING OF GASTRIC MALT LYMPHOMA

Previously, staging of MALT gastric lymphoma was based on Lugano staging system[11] which is a modification of the Ann Arbor staging system. More recently, Paris staging system[12] which corresponds to the tumor, node, metastasis system for gastric cancer, has been proposed. The Paris system has the advantage, over the Lugano staging system, of better describing the depth of invasion into the gastric wall (Tables 1 and 2).

Table 1 Paris staging system.

	Tumour extension
T1m N0 M0	Mucosa
T1sm N0 M0	Submucosa
T2 N0 M0	Muscularis propria
T3 N0 M0	Serosa
T1–3 N1 M0	Perigastric lymph nodes
T1–3 N2 M0	More distant regional nodes
T4 N0–2 M0	Invasion of adjacent structures with or without abdominal lymph nodes
T1–4 N3 M0	Extra-abdominal lymph nodes
T1–4 N0–3 M1	Distant (non-contiguous) GI sites involvement
T1–4 N0–3 M2	Non-GI sites involvement

T: Tumor; N: Nodes; M: Metastasis; GI: Gastrointestinal

Table 2 Lugano staging system.

Stage
Stage I	Confined to the GI tract (single primary or multiple, non-contiguous)
Stage II	Extension into abdomen
II1	Local nodal involvement
II2	Distant nodal involvement
Stage IIE	Penetration of serosa to involve adjacent organs or tissues
Stage IV	Disseminated extranodal involvement or concomitant supra-diaphragmatic nodal involvement

GI: Gastrointestinal.

According to ESMO guidelines, initial staging should include history and physical examination, full blood and differential counts, biochemistry including renal and liver function tests, protein electrophoresis, LDH and beta2-microglobulin, serum and urine immunofixation, serology for hepatitis B virus, hepatitis C virus (HCV) and human immunodeficiency virus and cryoglobulins and cryocrit if HCV-positive.

Staging should include

Gastroduodenal endoscopy of any abnormal lesion associated with systematic multiple biopsies. The following tumor analyses from biopsies, performed by an expert pathologist in hematology, are mandatory: (1) Immunohistochemistry panel analysis: CD20, CD3, CD5, CD10, BCL2, kappa/Lambda, CD21 or CD23, BCL6, cyclin D1 and immunoglobulin D; and (2) H. pylori testing: The detection of the t (11;18) (q21;q21) translocation by Fluorescence in situ hybridization is only recommended in case of failure of anti-H. pylori antibiotic treatment.

Endoscopic ultrasound is recommended to evaluate gastric wall infiltration and perigastric lymph node involvement.

Imaging includes chest and abdominal computed tomography (CT): Positron emission tomography (PET)/CT is not recommended before the treatment.

H. PYLORI ERADICATION

In a study of 103 patients with stage IE and IIE gastric MALT lymphoma, Moleiro et al[13] reported 83% complete response (CR) (78/103) with a mean follow-up of 7 mo (2–63 mo) after H. pylori eradication treatment and 86% (67/103) with a mean follow-up time of 105 mo. H. pylori infection (P = 0.004) and lymphoma location to the antrum/body (P = 0.016) were significantly associated with higher and lower CR rates, respectively. Relapse occurred in 11/78 (14%) patients after a mean time-lapse of 21 mo. The absence of H. pylori re-infection (P = 0.038), the need for only one eradication regimen (P = 0.009) and antrum lymphomas (P = 0.031) correlated with lower relapse rates. At stage IIE, H. pylori eradication was performed in 17/24 patients but only five experienced CR (30%)[13].

A systematic review of 32 publications revealed that CR was achieved in 78% of 1408 patients with low-grade stage I/II1 gastric MALT lymphoma in treated with H. pylori eradication[14].

In a Japanese multicenter cohort study, 420 patients with gastric MALT had undergone successful H. pylori eradication. Seventy-seven percent (323 patients) responded to H. pylori eradication. Absence of H. pylori, submucosal invasion and t (11;18)/API2-MALT1 were independent predictors of resistance to H. pylori eradication. Among responders, MALT relapsed in 3% of patients while progressive disease occurred in 27% of non-responders (27/97). After a median follow-up of 6 years, freedom from treatment failure (FFTF), OS and EFS at 10 years were 90%, 95% and 86%, respectively. Peri-gastric lymph node involvement and the depth of tumor infiltration in the gastric wall are factors also associated with a poor tumor response after H. pylori eradication[15].

H. pylori disappears usually 6 wk after the start of H. pylori eradication, soon after the completion of drug therapy, whereas MALT lymphoma usually takes several months to disappear (median 6 mo; extremes 3-24 mo).

However, if there is no H. pylori infection, the remission rate after antibiotic therapy is low (between 15% and 30%).

The translocation t (11;18) (q21;q21)/(API2-MALT1) is observed in 20 to 30% of gastric MALT lymphomas. It is associated with a higher rate of recurrence after eradication. This translocation is also associated with a lower response rate after alkylating-agent-based chemotherapy (90% vs 40% approximately), but not with rituximab.

According to ESMO clinical practice guidelines, the presence of H. pylori resistance factors, or lack of response to antibiotic therapy are the two main indications to treat with definitive RT. Given the possibility of a delayed response, RT should not be recommended for asymptomatic patients with non-progressive residual disease within the 9–12 mo following successful H. pylori eradication therapy. Patients with asymptomatic minimal residual disease may have an indolent course and may not require further treatment.

Some expert groups recommend RT in the case of localized disease and chemotherapy with or without immunotherapy in the case of advanced disease.

RT FOR GASTRIC MALT LYMPHOMA

Results of RT

Indolent NHLs are sensitive to moderate doses of RT. In this literature review, the median delivered dose was 30 Gy (Table 3). For localized gastric lymphomas, exclusive RT in the case of failure of H. pylori eradication gives very good results with a complete remission rate of 96% to 100% for a median follow-up of between 1.3 and 4.1 years without long-term side effects. The local tumor control is excellent after exclusive RT with fewer than 5% of patients experiencing local relapse after treatment. Gastric RT is well tolerated with hardly any severe (G3+) acute or late toxicities. Some studies have reported only mild (G1-2) and transient acute gastro-intestinal toxicities.

Table 3 Studies of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma.

Ref.	Country	Patients, n (%)	Stage	Failure of H. pylori eradication or H. pylori	H. pylori	Median [Total RT dose]	Median F/U (mo)	Survival	Relapse (Local/distant)	Toxicity G3+
Schechter et al[31], 1998	NY, United States	17	IE = 71%; II1 = 24%, II2 = 5%	17/17	12/17	30 Gy [28.5–43.5]	27 [11–68]	NR	0/0	0
Park et al[32], 2002	Korea	6	IE = 100%	4/6	1/6	30.6 Gy [30–39]	12	100%	0/0	0
Tsang et al[33], 2003	Canada	13/93 (gastric and RT subgroup)	IA = 88%; IIA = 10%, IIB = 2%	13/13	7/15	26.2 [20–35]	61	98% at 5 yr for the entire cohort	0/0	0
Koch et al[24], 2005	Germany	144/332 (indolent subgroup with conservative management)	I = 66%; II1 = 17%; II2 = 17%	NR	NR	40 Gy	42 [0.07–97.4]	93% at 3.5 yr	6	9
Avilés et al[34], 2005	Mexcio	78/241 (RT group)	IE = 73%; IIE = 27%	NR	NR	40 Gy	90 [58–139]	75% at 10 yr	0/30	0
Sugimoto et al[35], 2006	Japan	3	I = 3	3/3	0	39 Gy [36–40]	42 [24–72]	100%	0/0	0
Tsai et al[36], 2007	MA, United Sttaes	18/77 gastric and RT subgroup	IE = 100%	6/18	NR	30 Gy [18–40]	61 [2–177]	91% at 5 yr for the entire cohort	0 over 11 patients treated by RT	NR
Yamashita et al[37], 2008	Japan	11/41 gastric subgroup	IE = 90%; IIE = 10% (whole cohort)	6/11	5/11	30 Gy	32 [2–162]	100%	0/0	0
Vrieling et al[38], 2008	The Netherlands	68/115 (RT subgroup)	I = 79%; II1 = 12%, II2 = 9%	85/115	13/115	40 Gy [31–44]	150 [7–301] (radiotherapy only cohort)	78% at 5 yr (entire cohort)	3/4	NR
Gobbi et al[39], 2009	Italia	5	IE = 4; IIE = 1	5/5	0/5	30 Gy	48 [21–70]	80%	0	0
Tomita et al[40], 2009	Japan	20/50 (gastric subgroup)	IE = 96%; IIE = 4% (entire cohort)	20/20	7/20	32 Gy [25.6–50]	92	97% at 5 yr (entire cohort)	0	2% for all cohort
Goda et al[41], 2010	Canada	25/167 (gastric subgroup)	IA = 90%; IIA = 9%; IIB = 1%	19/19	5/19	30 Gy [20-35]	89 [8–194]	95% at 5-yr (entire cohort)	0	NR
Okada et al[42], 2012	Japan	22	IE = 19; IIE = 3	22/22	14/22	30 Gy	74 [27–159]	91% at 5-yr	0/3	0
Kim et al[43]; 2013	Korea	64	IE = 53 (83%); IIE = 11 (17%)	56/60	33/64	36 Gy	39 [9–131]	94% at 5-yr	5	0
Wirth et al[16], 2013	International (IELSG)	102	IE = 84%; IIE = 16%	80/102	45/90	40 Gy [26–46]	95 [4–528]	70% at 10 yr	7/5	NR
Nam et al[44], 2014	Korea	41 (MALT subgroup)	IE = 77%; IIE = 23%	29/41	29.6%(whole cohort)	30.6 Gy [30.6-43.2]	48 [6– 158]	90% at 5-yr (entire cohort)	1/0	0
Abe et al[45], 2013	Japan	34	IE = 34 (100%)	34/34	17/34	30 Gy	90 (14–156)	100% at 5-yr	1 (emergency gastrectomy during RT at 15 Gy for acute bleeding)/0	1
Ruskoné-Fourmestraux et al[18], 2015	France	53	IE = 45 (85%); IIE = 8 (15%)	53/53	15/53	30 Gy	59 (4–199)	94% at 5-yr	0/0	0
Lim et al[46], 2016	Korea	33	IE = 30 (91%); IIE = 3 (9%)	33/33	17/33	30.6 Gy	50 (12–145)	97% at 5-yr	0	0
Ohkubo et al[47], 2017	Japan	27	IE = 27 (100%)	24/27	15/27	30 Gy [30–39.5]	121 (8–176)	92% at 5-yr; 87% at 10-yr	0/2	2/27 (White blood cell count decreases)
Teckie et al[48], 2017	NY, United States	122/225 (gastric and RT subgroup)	IE = 225 (92%); IIE = 19 (8%)	115/122	78/122	30 Gy	62 [2–256]	92% at 5-yr; 79% at 10-yr for all the subgroups	7 (gastric subgroup)	NR
Pinnix et al[17], 2019	TX, United States	32	IE = 25(78%); IIE = 5 (16%); IV = 2 (6%)	32/32	25/32	36 Gy (2; 6%); 30 Gy (n = 19; 59%); 24 Gy (n = 11; 34%)	55 [32–78]	97% at 2-yr	1/1	NR
Schmelz et al[49], 2019	Germany	22	IE = 20; IIE = 2	22/22	0/22	25.2 Gy/36 Gy	79 [36.4 –143.8]	100% at 56.6 yr	0	NR
Watanabe et al[50], 2020	Japan	30/34 (gastric subgroup)	IE = 100%	26/30	16/30	30 Gy [30–40]	61 [9–136]	94.7% at 5 yr	0/2	0

RT: Radiotherapy; NR: Not reported; H. pylori: Helicobacter pylori.

In the IELSG retrospective multicentric international study, Wirth et al[16] reported in 102 patients treated by extended field or whole abdomen RT for gastric MZL and persistent H. pylori infection after eradication or H. pylori, 88% of FFTF at 10-years. RT median dose delivered to the stomach was 40 Gy (26–46). In this study, RT field size, RT dose, and failure of prior therapy (H. pylori eradication, chemotherapy or surgery) were not associated with inferior RT efficacy[16]. Second malignancies were reported in 5 of 41 patients who had gastric/nodal irradiation only, of which two were likely in-field (2 colon), one was likely out of field (bladder) and two had uncertain relationship to field (1 breast, 1 lung).

In a retrospective monocentric study that evaluated the outcome of 32 patients treated for gastric MALT lymphoma with involved site radiation therapy using intensity modulated radiation therapy (IMRT), Pinnix et al[17] have reported excellent outcome with 2-year Freedom from local treatment failure, FFTF, and OS of 100%, 100% and 97%, respectively. Moreover, they did not observe any association between the lower 24 Gy dose with FFLTF (P = 0.819), FFTF (P = 0.819) or OS (P = 0.469)[17].

The excellent results and safety of moderate-dose RT, 30 Gy, have been confirmed by the GELD/FFCD prospective study that included 53 patients, all well selected (H. pylori eradication failure, H. pylori negative). The response rate was very high (98%). After 4.9-years median follow-up, the overall lymphoma survival was 94%[18]. Neither local or distant relapses nor severe acute or late G3+ toxicities were observed.

In a large retrospective monocentric study from the Memorial Sloan Kettering Hospital New York, Teckie et al[19] reported very favorable outcome in patients treated for gastric MALT lymphoma by moderate dose of RT (30 Gy). Indeed, gastric location was associated with the best relapse free-survival among patients treated by RT for MZL. After a long follow-up [62 mo (2–256)], local failures occurred in only 7 out of 102 treated patients[19].

The main weaknesses of most of the studies reported in this review are, their retrospective nature, often monocentric, their small sample size, their short follow-up and that some studies have included patients who had not failed to H. pylori eradication.

The median delivered dose in this literature review is in accordance with the ILROG guidelines: 30-30.6 Gy in conventional fractionation (1.8 to 2 Gy/d and 5 d per week) on gastric and peri gastric lymph node volumes (involved site RT)[20]. During RT, proton pump inhibitor and 5-HT3 serotonin receptor antagonist are recommended to prevent acute side effects.

RT treatment planification

CT Simulation: Patients must be simulated and treated with an empty stomach after a fast of at least 4 h or overnight.

Patients should be simulated supine with arms up using customized immobilization device.

A small volume (50 cc) of oral contrast medium should be used.

CT images should be acquired before and after oral contrast medium.

Intravenous contrast medium injection is recommended in case of lymph nodes involvement.

In order to reduce margins, respiratory motion should be assessed with 4D-CT.

Volume definition (ILROG recommendations)

The gross tumor volume corresponds to the gastric tumor and the macroscopically invaded lymph nodes determined on CT or PET-CT.

Because gastric MALT lymphoma is often associated with multifocal involvement of the stomach and may spread to regional lymph nodes, radiation volumes should include the entire stomach as well as the perigastric lymph nodes of the lesser and greater curvatures.

The clinical target volume (CTV) corresponds to the entire stomach from the gastroesophageal junction to the duodenal bulb; the whole gastric wall and the perigastric lymph nodes must be included.

The internal target volume needs to be determined by 4D-CT in order to take into account stomach mobility during breathing.

In the absence of 4D-CT, 2 cm margins should be added to the CTV to take into account the respiratory movement of the stomach.

For the planning target volume (PTV), an additional margin of 0.5 to 1 cm should be added, to take into account setup variation.

In order to reduce the margins due to respiratory movements, modern irradiation techniques such as deep-inspiratory breath-hold (DIBH) and 4D-Cone Beam Computed Tomography (CBCT)-Image Guided Radiation Therapy, should be used. In a retrospective study of 10 patients treated for gastric NHL including 5 MALT and 5 DLBCL, Christopherson et al[21] have reported that DIBH led to reduced dose to the heart and the kidneys, through improved spatial separation between the heart and the stomach, while simultaneously allowing for reduced target volumes, without compromising target coverage or increasing dose to other organs at risk (OAR)[21].

Shimohigashi et al[22] reported that the use of 4D-CBCT reduced the PTV when applying 4D soft-tissue matching, compared to skin and bone matchings. Based on these results, authors recommended daily 4D-CBCT during RT treatment[22].

The following OAR should be delineated: Liver, kidneys, bowels, heart, lungs and spinal cord. 3D conformal RT, IMRT or VMAT (Figure 3), are recommended to reduce the dose delivered to the kidneys and liver.

Figure 3  Example of dose distribution using volumetric modulated arc therapy in gastric mucosa-associated lymphoid tissue lymphoma.

Prescribed dose

The median delivered dose in this literature review is in agreement with the ILROG guidelines: 30-30.6 Gy in conventional fractionation (1.8 to 2 Gy/d and 5 d per week) on gastric and perigastric lymph node volumes (involved site RT)[23].

Prevention of side effects

During RT, proton pump inhibitor and 5-HT3 serotonin receptor antagonist are recommended to prevent acute side effects.

OTHER TREATMENT APPROCHES

Surgery

In the GIT NHL 02/96 multicentric non-randomized German study, Koch et al[24] have reported no survival advantage at 42 mo of surgery ± adjuvant RT in case of R1/R2 resection grade or stage II disease in comparison with exclusive RT without surgery in 144 patients treated for localized primary gastric indolent lymphoma (86% vs 91%)[24].

In clinical practice, surgical treatment is rarely indicated. The only current indications are emergency situations such as perforation or uncontrolled bleeding in endoscopy.

Systemic therapy

In the IELSG-19 randomized trial that included 401 patients with localized or disseminated gastric and non-gastric MALT lymphoma, the combination of rituximab and chlorambucil was significantly superior to chlorambucil monotherapy and rituximab monotherapy in terms of response rate [79% vs 63% vs 56%, respectively (P < 0.001)], EFS (68% vs 51% vs 51%, P = 0.0009) and progression-free survival at 5 years (72% vs 59% vs 57%, P = 0.0119). Five-year OS was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were reported[23].

In the MALT2008-01 phase II Spanish multicentric study that included 57 patients with localized or disseminated gastric and non-gastric MALT lymphoma, the combination of bendamustine and rituximab for first-line systemic treatment resulted in a complete or unconfirmed CR rates of 98% and an EFS at 4 years of 88%. Progression-free survival at 4 years was 93% with no differences between patients with gastric and non-gastric sites[25].

Watchful waiting

Long-term complications after treatment of indolent lymphomas have been reported, including a significant increase in secondary cancers. The risk of recurrence in patients with minimal residual gastric MALT lymphoma after successful eradication of H. pylori without oncological treatment, is low. Watchful waiting with regular endoscopies and biopsies could therefore be considered, particularly in elderly patients or in patients with comorbidity[26]. This decision to treat or not, should be discussed in the setting of a multidisciplinary meeting.

FOLLOW-UP

Follow-up after treatment of localized gastric-MALT is based on upper gastrointestinal endoscopy. The follow-up differs slightly between expert groups.

NCCN recommendations

Endoscopic control 3 mo after RT: In case of CR: Clinical follow-up every 3–6 mo for 5 years and then yearly or as clinically indicated.

The timing of endoscopy and imaging is not determined: They should be decided on according to clinical symptoms.

ESMO recommendations

Following RT treatment, endoscopic controls with gastric biopsies and systemic follow-up (clinical examination, blood counts) every 12-18 mo are recommended.

Follow-up after H. pylori eradication

Following the documentation of H. pylori eradication, strict endoscopic follow-up is recommended, with multiple biopsies taken 2-3 mo after treatment to rule out tumor progression, and subsequently every 6 mo for 2 years to monitor the histological regression of the gastric lymphoma.

Because of its reliability, it is recommended to use the GELA histological scoring system for post-therapy biopsies evaluation[27]. Comparison with previous biopsies is helpful to assess response.

SECONDARY GASTRIC CANCERS

In spite of the excellent cure rate, long-term follow-up by endoscopy is required as cases of gastric adenocarcinomas have been reported during follow-up of cured lymphomas[26,28,29]. Moreover, the Dutch epidemiological study by Capelle et al[30] found a 6-fold increase in the risk of gastric adenocarcinoma compared to the general population in patients with a history of gastric lymphoma regardless of treatment. This risk was 16.6 times higher in patients with gastric MALT lymphoma aged between 45 and 59 years than in the Dutch population (P < 0.001)[30].

CONCLUSION

RT is a highly effective treatment in the management of localized gastric MALT lymphomas resistant to H. pylori eradication with a cure rate close to 100% and no major toxicity. Long follow-up with gastric endoscopy monitoring is necessary to diagnose at an early stage the potential occurrence of gastric adenocarcinoma.

ACKNOWLEDGEMENTS

The authors would like to thank Mr. Abdellah El Mouqaddem, a physicist from our department, for the dosimetry using VMAT technique presented in this article.