Radiation is being used more frequently to treat gastric lymphoma (rather than surgery), the study from Willich is noted below

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A breif review of the recent literature is noted below:

Operative and conservative management of primary gastric lymphoma: interim results of a German multicenter study.

Willich NA, Reinartz G, Horst EJ, Delker G, Reers B, Hiddemann W, Tiemann M, Parwaresch R, Grothaus-Pinke B, Kocik J, Koch P.   Int J Radiat Oncol Biol Phys 2000 Mar 1;46(4):895-901

Department of Radiotherapy, University of Munster, Munster, Germany. willich@uni-muenster.de

A total of 381 evaluable patients had been accrued then.Treatment decision concerning operative or conservative management was due to the initially acting physician. Patients with resection of low grade lymphoma received total abdominal irradiation 30 Gy + 10 Gy boost to incompletely resected areas. After resection of high grade lymphoma CHOP chemotherapy (4 cycles for stage IE, 6 cycles for higher stages) after McKelvy was followed by total abdominal irradiation 30 Gy for stage IE respectively involved field irradiation 30 Gy for higher stages with 10 Gy boost to incompletely resected areas. Primary conservative- treatment consisted of six cycles COP chemotherapy after Bagley for low grade lymphomas stage > IE and total abdominal irradiation 30 Gy + 10 Gy boost to involved areas for all stages. Patients with high grade lymphomas received 4 x CHOP followed by total abdominal irradiation 30 Gy + 10 Gy boost to involved areas or 6 x CHOP plus involved field radiation therapy with 40 Gy. 257 patients are considered for analysis due to exclusion criteria of the study, 190 of them were suffered from gastric lymphoma. Their median observation time is 29 months, maximum observation time is 68 months. RESULTS: Sites of involvement were stomach in 73.4%, small bowel 9.6%, ileocoecal region 6.9%, and other sites 3.2% More than one GI site was involved in 6.9%. Gastric lymphomas achieved a survival probability of 89% after 3 years. Though surgical and conservative treatment was not randomized, outcome was analyzed in gastric NHL stages I and II (histologic subtype not considered showing no significant influence). At 3 and 5 years survival is 88% in resected cases vs. 94% and 86% in conservatively treated patients (p = 0.350). Analyzing only stages I + II(1) surgery also seems of no advantage even considering only RO-resections. There was one acute gastrointestinal bleeding under primary chemotherapy for a high grade lymphoma. Toxicities of grade III and IV WHO were rarely seen during treatment. All other acute toxicities were not more than grade II WHO. CONCLUSION: Conservative treatment in this setting is feasible. The operative approach seems not to be advantageous compared to conservative treatment and should be critically reconsidered.

Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone.

Schechter NR, Portlock CS, Yahalom J.  J Clin Oncol 1998 May;16(5):1916-21
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach (MLS) has recently been defined as a distinct clinicopathologic entity, often associated with Helicobacter pylori infection. Many regard antibiotic therapy as the primary treatment of MLS, but in the absence of H pylori infection, or when salvage of antibiotic failures is required, gastrectomy and/or chemotherapy have frequently been used. This study evaluates the efficacy of low-dose radiotherapy alone as an alternative to surgery. PATIENTS AND METHODS: Seventeen patients with stage I to II(2) low-grade MLS without evidence of H pylori infection or with persistent lymphoma after antibiotic therapy of associated H pylori infection were included in this series. Median age was 69 years (range, 39 to 84). Median total radiation dose was 30 Gy (range, 28.5 to 43.5 Gy) delivered in 1.5-Gy fractions within 4 weeks to the stomach and adjacent lymph nodes. Following treatment, all patients underwent endoscopic evaluation and biopsy at a median of 4 months, at 6-month intervals to 2 years, and annually thereafter. RESULTS: All obtained a biopsy-confirmed complete response. At a median follow-up time of 27 months (range, 11 to 68) from completion of radiotherapy, event-free survival was 100%. Treatment was well tolerated, with no significant acute side effects. All remained asymptomatic at last follow-up. CONCLUSION: These results suggest that effective treatment of MLS with low-dose radiation therapy alone is feasible and safe, and allows stomach preservation. Longer follow-up evaluation is required to determine the long-term efficacy of this treatment approach and its side effects. Further studies should clarify the indications for radiotherapy in H pylori-negative or antibiotic-resistant cases of MLS.

Mucosa-associated lymphoid tissue lymphoma of the stomach: long term outcome after local treatment.   Cancer 1999 Jan 1;85(1):9-17

Fung CY, Grossbard ML, Linggood RM, Younger J, Flieder A, Harris NL, Graeme-Cook F.
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.

BACKGROUND: Although antibiotic therapy is emerging as effective initial treatment for patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT), there is a subset of patients for whom antibiotics are ineffective or inappropriate. Surgical resection can be curative, but total gastrectomy may be required for the eradication of all disease. To identify the optimal nonantibiotic therapy for early stage gastric MALT lymphoma, the authors retrospectively evaluated the Massachusetts General Hospital experience with gastric MALT lymphoma. METHODS: Disease patterns and treatment outcomes were retrospectively analyzed in data from 21 consecutive patients with gastric MALT lymphoma who were treated between 1978 and 1995 at the Massachusetts General Hospital. RESULTS: Sixteen patients were Stage IE, and 5 were in higher stages. Treatment consisted of resection with or without radiation or chemotherapy (14 patients), radiation alone (4 patients), or radiation plus chemotherapy (2 patients). Thirteen Stage IE patients received local therapy only. The 10-year actuarial relapse free survival rate for Stage IE patients was 93%, with 1 relapse among 15 treated patients. Because the patient who relapsed was treated successfully with chemotherapy, the 10-year cancer free survival was 100%. Overall survival for Stage IE patients was 93% at 5 years and 58% at 10 years, with no deaths from lymphoma. CONCLUSIONS: These data indicate that a high probability of long term remission can be achieved with only local treatment of patients with Stage I gastric MALT lymphoma. Preliminary results suggest that radiation therapy is well tolerated and effective and may well be the optimal nonantibiotic treatment for patients with localized gastric MALT lymphoma.Moderate radiation doses (mean, 3400 cGy) have led to 100% local control for MALT lymphoma of the orbit in our experience.Therefore, doses in the range of 3000-3600 cGy likely are sufficient for the eradication of gastric MALT lymphoma.

Radiotherapy of MALT-lymphoma of the stomach

Szekely J, Petranyi A, Glavak C, Schneider T, Rosta A, Esik O.   Orv Hetil 2002 Jul 14;143(28):1683-9

Orszagos Onkologiai intezet, Sugarterapias Osztaly, Budapest. szekely@oncol.hu

INTRODUCTION: The stomach is the most common extranodal site of the low-grade MALT lymphoma. This lymphoma usually appears in elderly patients, with typically indolent signs. At the time of the diagnosis, the lymphoma is usually localized in the stomach and/or the adjacent lymph nodes. The choice in these cases is local treatment, which in the past involved only a surgical approach (total/partial gastrectomy), whereas more recently radiotherapy is preferred. PURPOSE: The radiation fields cover the whole stomach and the paragastric lymph nodes. The radiation doses range from 30 to 40 Gy, given in 1.5 Gy fractions 5 days a week. An adequate dose distribution to the target volume can be achieved by 3D treatment planning and conformal irradiation. METHODS: At our institute, 5 patients were treated with this method, the intention was curative in 3 cases, and palliative in 2 cases. The median dose in the 4 cases completed as initially planned was 33.6 Gy, delivered at 1.5 Gy per fraction. The adjacent critical organs do not exceed the tolerance doses by this method. RESULTS: In these 4 cases, complete regression was achieved, as determined by endoscopy and biopsy. In the fifth, locally advanced case, irradiation had to be terminated because of gastric bleeding. During irradiation, no other severe acute side-effects were detected. CONCLUSION: The literature and our preliminary results confirm that radiation therapy for early, localized MALT lymphoma of the stomach, or in disseminated cases, can be not only effective and safe, but offers the significant advantages of low treatment-related morbidity and preservation of the gastric function.

Primary gastric lymphoma: brief overview of the recent Princess Margaret Hospital experience.

Gospodarowicz MK, Pintilie M, Tsang R, Patterson B, Bezjak A, Wells W.   Recent Results Cancer Res 2000;156:108-15
Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Canada.

Primary gastric lymphoma is the commonest form of presentation for gastrointestinal lymphomas and the stomach is one of the most frequent sites of extranodal lymphoma. We present a review of the Princess Margaret Hospital (PMH) experience to illustrate the favorable prognosis and examine the long-term outcomes in this disease. Between 1967 and 1996, 149 consecutive patients with gastric lymphoma were treated at the PMH. The majority (122 patients) presented with diffuse large-cell lymphoma and 78 had stage I disease. In the past, the standard treatment was surgery (partial gastrectomy) followed by post-operative radiation therapy (RT; 78 patients). The overall 10-year survival was 62%. For patients who were treated with surgery and post-operative RT (operable disease) between 1967 and 1985, the 10-year rates of overall survival and cause-specific survival were 66.2% and 88%, respectively. In the past decade, combined-modality therapy with chemotherapy followed by RT was introduced for large-cell lymphoma, while RT alone was used for mucosa-associated lymphoid tissue (MALT) lymphoma. In 45 patients treated in the past decade, the overall 5-year survival was 86%, the cause-specific survival was 95.5%, and the relapse-free rate was 87.3%. These results support the view that primary gastric lymphoma is a highly curable disease. Future efforts should focus on reducing treatment morbidity, while preserving excellent results.

Stage I and II MALT lymphoma: results of treatment with radiotherapy.

Tsang RW, Gospodarowicz MK, Pintilie M, Bezjak A, Wells W, Hodgson DC, Crump M.   Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1258-64
Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada. richard.tsang@rmp.uhn.on.ca

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following involved field radiation therapy (RT). PATIENTS AND METHODS: Seventy patients with Stage IE (62) and IIE (8) disease were treated between 1989 and 1998. Patients with transformed MALT were excluded. The median age was 62 years (range, 24--83 years), M:F ratio 1:2.2. Presenting sites included stomach, 15; orbital adnexa, 19; salivary glands, 15; thyroid, 8; lung, 5; upper airways, 3 (nasopharynx, 2; larynx, 1); urinary bladder, 3; breast, 1; and rectum, 1. Staging included site-specific imaging, CT abdomen in 66 patients (94%) and bone marrow biopsy in 54 (77%). Sixty-two patients received radiation therapy: 52 received RT alone, 7 received chemotherapy and RT, and 3 received antibiotics followed by RT. Median RT dose was 30 Gy (range, 17.5--35 Gy). Most frequently used RT prescriptions were 25 Gy (26 patients-18 orbit, 6 stomach, and 2 salivary glands), 30 Gy (23 patients), and 35 Gy (8 patients). Five patients had complete surgical excision of lymphoma and no other treatment (stomach 1, salivary 2, lung 2), whereas 2 patients with gastric lymphoma received antibiotics only. One patient refused treatment and was excluded from the analysis of treatment outcome, leaving 69 patients with a median follow-up of 4.2 years (range, 0.3-11.4 years). RESULTS: A complete response was achieved in 66/69 patients, and 3 patients had partial response (2 lung, 1 orbit). The 5-year disease-free survival (DFS) was 76%, and the overall survival was 96%. No relapses were observed in patients with stomach and thyroid lymphoma. The 5-year DFS for these patients was 93%, in contrast to 69% for patients presenting in other sites (p = 0.006). Among the 5 patients treated with surgery only, 2 relapsed locally (lung, and minor salivary gland). Among 62 patients who received RT, 8 relapsed (2 salivary, 3 orbit, 1 nasopharynx, 1 larynx, 1 breast). Three patients relapsed in the nonirradiated contralateral paired organ, 4 in distant sites, and 1 in both local and distant sites. The overall local control rate with radiation was 97% (60/62 patients). CONCLUSION: Localized MALT lymphomas have excellent prognosis following moderate-dose RT. Gastric and thyroid MALT lymphomas have better early outcome, as compared to the other sites where distant failure is more common. Relapses were observed in nonirradiated paired organs or distant sites. Further follow-up is required to assess the impact of failure on survival.

Low-grade MALT lymphoma of the stomach: a review of treatment options.

Schechter NR, Yahalom J.    Int J Radiat Oncol Biol Phys 2000 Mar 15;46(5):1093-103
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

PURPOSE: Low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach (MLS) is often associated with the presence of Helicobacter pylori (H. pylori) bacteria. Eradication of the infection with antibiotic therapy may result in regression of the lymphoma. But when antibiotic treatment fails to reverse the malignant process or if H. pylori is absent, other treatment options should be considered. Because MLS is often confined to the stomach and regional lymph nodes, it is potentially curable with local therapy. Endoscopy and improved imaging, with endoscopic ultrasound (EUS) and computerized tomography (CT), have reduced the prior dependence on surgery for diagnosis and staging of gastric lymphomas. METHODS AND RESULTS: This review details the advances in the diagnosis, classification, and imaging of MLS. We also describe the experience that supports the use of radiation therapy as the preferred treatment of MLS in patients who have not responded to antibiotic therapy or have not had evidence for H. pylori infection. CONCLUSIONS: Radiation therapy for MLS is not only effective and safe, but offers the significant advantage of low morbidity and gastric function preservation.

Review: While the sensitivity of gastric lymphoma to radiation therapy has long been known, it was the move towards noninvasive staging procedures that has led to renewed interest in noninvasive treatment modalities such as radiotherapy. In the past, the primary treatment for primary gastric lymphoma was resection. When radiation therapy and/or chemotherapy was used, the approach tended to vary from patient to patient, leading to difficulties in data interpretation Nevertheless, in some studies, a survival advantage has been demonstrated for postoperative radiation therapy  In 1988, Burgers and colleagues  reported results of the Netherlands Cancer Institute where, since 1978, 24 clinical Stage I gastric NHL patients were treated with radiation therapy alone in an attempt to avoid, whenever possible, partial or complete gastrectomy. The radiation therapy consisted of WART (whole abdominal radiation therapy) of 20 Gy in 3 weeks, five fractions per week, followed by a boost to the whole stomach and para-aortic lymph nodes to L2–L3 with an additional 20 Gy in 2 weeks, for a total dose of 40 Gy. The 4-year actuarial disease-free survival rate was 83% with a median follow-up of 48 months. Unfortunately, one cannot determine from this report the specific histologies of the patients who received radiation therapy alone.

At Memorial Sloan Kettering Cancer Center we have reported our experience in treating 17 patients with specifically low-grade B-cell gastric MALT lymphoma with primary radiation therapy to the stomach and perigastric lymph nodes. Seventeen patients with Stage I to II2 low-grade MALT lymphoma of the stomach without evidence of H. pylori infection or with persistent lymphoma after antibiotic therapy of associated H. pylori infection were included in this series. The median age was 69 years (range 39–84 years). The median total radiation dose was 30 Gy (range 28.5–43.5 Gy) delivered in 1.5-Gy fractions within 4 weeks to the stomach and adjacent lymph nodes. Following treatment, all patients underwent endoscopic evaluation and biopsy at a median of 4 months, at 6-month intervals to 2 years, and annually thereafter. All obtained a biopsy-confirmed complete response. At a median follow-up time of 27 months (range 11–68 months) from completion of radiotherapy, event-free survival was 100%. Treatment was well tolerated, with no significant acute side effects. All remained asymptomatic at last follow-up. These results suggest that effective treatment of MALT lymphoma of the stomach with low-dose radiation therapy alone is feasible and safe, and allows gastric preservation. Longer follow-up evaluation will be required to determine the long-term efficacy of this treatment approach and its side effects. Further studies should clarify the indications for radiotherapy in H. pylori-negative or antibiotic-resistant cases of MALT lymphoma of the stomach.

The main argument against irradiation of the stomach has been the risk of perforation and bleeding; other concerns include renal toxicity and the induction of second malignancies. On review of the literature, these risks appear minimal. The incidence of radiation-induced perforation or bleeding is < 4%. In Mittal and colleagues' literature review, published in 1983, only 4% (3/75) developed gastric perforation; and only 1% (1/75) developed gastric perforation directly attributable to radiation therapy treatment.

In 1990, Talamonti and colleagues  reported in the Archives of Surgery, a review of 42 patients with primary gastrointestinal lymphoma. In their report, five of the patients who did not undergo surgical resection before radiation or chemotherapy developed severe life-threatening complications resuting from progression of their primary tumor. However, none of the five patients who developed bleeding or perforation had Stage I or II gastric lymphoma: one was a 65-year-old with Stage III gastric lymphoma; one was a 61-year-old with Stage IV colonic lymphoma; one was a 61-year-old with Stage IV small intestinal lymphoma; one was a 59-year-old with Stage II small intestinal lymphoma; and one was a 64-year-old with Stage IV colonic lymphoma.. In their review of nonsurgical approaches to gastric lymphoma, Varsos and Yahalom distinguished between complications arising in early-stage patients and complications of advanced-stage (nonoperable) cases. The reported incidence of perforation or hemorrhage occurring with nonsurgical treatment of primary gastric lymphoma, including advanced stages was 9.7% (15/158). Yet, the incidence of gastric perforation or hemorrhage in nonsurgically treated cases of primary gastric lymphoma limited to the stomach and first echelon lymph nodes was only 3.5% (3/86).

The risk of clinically significant hypertension or renal dysfunction attributable to primary radiation therapy of gastric lymphoma patients is rare (160). Typically, only the left kidney needs to be in a high-dose region. Should part or the entire right kidney receive a significant dose of radiation, the risk of hypertension may increase..

The possibility exists for development of a second malignancy, such as adenocarcinoma, years after radiation therapy treatment; its incidence, however, is rare. Patients with gastric lymphoma tend to be at increased risk for gastric adenocarcinoma, irrespective of the treatment modality, be it surgery, radiation therapy, chemotherapy, or some combination thereof . This may be due to a common pathogenesis of gastric lymphoma and gastric adenocarcinoma, as recent data have accumulated linking adenocarcinoma of the stomach with H. pylori infection.

Mucosa-associated lymphoid tissue lymphoma with initial supradiaphragmatic presentation: natural history and patterns of disease progression.

Liao Z, Ha CS, McLaughlin P, Manning JT, Hess M, Cabanillas F, Cox JD.   Int J Radiat Oncol Biol Phys 2000 Sep 1;48(2):399-403
Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma commonly presents in the gastrointestinal (GI) tract. Supradiaphragmatic MALT lymphoma is less common and its natural history is not well defined. This study was conducted to understand the natural history, to determine the frequency of synchronous disease in the GI tract, and to understand the patterns of disease progression after treatment for supradiaphragmatic MALT lymphoma. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 39 patients who presented with supradiaphragmatic MALT lymphoma between 1991 and 1997. RESULTS: The median age of patients was 58 years (range, 25-90 years) with 16 male and 23 female patients. The most common primary site was salivary gland followed by ocular adnexa, lung, oral cavity, and others. Sixteen patients underwent esophagogastroduodenoscopy and biopsy (EGD + Bx) and 4 were found to have gastric involvement. Ann Arbor stages were the following: IEA, 17; IIEA, 5, IIEB, 1; and IVA, 16. The initial treatments were: involved field radiation therapy (n = 10), chemotherapy (n = 14), combination of radiation therapy and chemotherapy (n = 9), observation after biopsy (n = 4), antibiotics only (n = 1), and patient refusal of further intervention (n = 1). Seven patients received antibiotics as a part of the initial treatment.Every patient except for 1 was alive at a median follow-up of 39.5 months (range, 3-83 months). Thirty-six patients achieved complete response (CR) to the initial treatment. The actuarial 5-year progression-free survival rate was 83%. Progression of the disease occurred in 4 patients, with 2 in the stomach. Salvage attempts were made to 4 and were successful in 3. Of the 2 patients who relapsed in the stomach, 1 had negative EGD + Bx at the time of initial diagnosis. An EGD + Bx was not done in the second patient. CONCLUSION: Supradiaphragmatic MALT lymphoma appears to have a favorable prognosis. However, routine evaluation of the stomach is recommended for patients who present with supradiaphragmatic MALT lymphoma at the time of initial evaluation and at the time of relapse. Patients who failed initial therapy can be successfully salvaged with further treatment.