2010 欧洲肿瘤医学会：胃粘膜相关淋巴瘤

Annals of Oncology 21 (Supplement 5): v175–v176, 2010 doi:10.1093/annonc/mdq182clinical practice guidelines Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up E. Zucca1 & M. Dreyling2 On behalf of the ESMO Guidelines Working Group* 1Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; 2Department of Medicine III, University Hospital Grosshadern, LMU Munich, Germany incidence Mucosa-associated lymphoid tissue (MALT) lymphomas represent �7% of all non-Hodgkin’s lymphomas and can arise at any extranodal site; however, at least one-third of them present as a primary gastric lymphoma. diagnosis The most common presenting symptoms of gastric MALT lymphoma are non-specific upper gastrointestinal complaints that often lead to an endoscopy usually revealing non-specific gastritis or peptic ulcer with mass lesions being unusual. Diagnosis is based on the histopathologic evaluation of the gastric biopsies [III, A]. If the presence of active Helicobacter pylori infection is not demonstrated by histochemistry, it must be ruled out by urea breath test and/or faecal antigen test. In addition to routine histology and immunohistochemistry, FISH analysis (or PCR) for detection of t(11;18) may be useful for identifying patients that are unlikely to respond to antibiotic therapy [III, B]. staging and risk assessment The initial staging procedures should include a gastroduodenal endoscopy with multiple biopsies taken from each region of the stomach, duodenum, gastro-esophageal junction and from any abnormal-appearing site. Endoscopic ultrasound is recommended to evaluate the regional lymph nodes and gastric wall infiltration [III, A]. Work-up studies should include complete blood counts, basic biochemical studies, including lactate dehydrogenase (LDH) and b2-microglobulin, CT of the chest, abdomen and pelvis, and a bone marrow aspirate and biopsy [IV, C]. The value of positron emission tomography (PET) scan is controversial and has little clinical utility [IV, D]. treatment plan Eradication of H. pylori with antibiotics should be employed as the sole initial treatment of localized (i.e. confined to the stomach) H. pylori-positive gastric MALT lymphoma [II, A]. Any of the highly effective anti-helicobacter antibiotic regimens proposed can be used. In case of unsuccessful H. pylori eradication, a second-line therapy should be attempted with alternative triple- or quadruple-therapy regimens of proton- pump inhibitor plus antibiotics. Helicobacter pylori eradication can induce lymphoma regression and long-term clinical disease control in most patients. The length of time necessary to obtain a remission can span from very few months to >12 months. It is reasonable to attend for at least 12 months before starting another treatment in patients who achieve a clinical and endoscopic remission together with eradication of H. pylori, albeit having persistent (residual) lymphoma at the histological level [III, B]. Several studies of post-antibiotic molecular follow-up have shown the persistence of monoclonal B cells after histological regression of the lymphoma. In these cases, watchful waiting is recommended, while active anticancer treatment (see below) should be reserved for persistently symptomatic or progressive disease. In H. pylori-negative cases or patients who fail antibiotic therapy, irradiation and systemic therapies should be applied depending on the stage of disease; surgery has been not shown to achieve superior results in comparison with more conservative approaches in various trials. Excellent disease control using radiation therapy alone has been reported by several institutions supporting the use of modest-dose involved-field radiotherapy (30–40 Gy radiation to the stomach and perigastric nodes given in 4 weeks) for patients with stage I–II MALT lymphoma of the stomach without evidence of H. pylori infection or persistent lymphoma after antibiotic eradication [III, B]. Patients with systemic disease should be considered for systemic chemotherapy [III] and/or immunotherapy with *Correspondence to: ESMO Guidelines Working Group, ESMO Head Office, Via L. Taddei 4, CH-6962 Viganello-Lugano, Switzerland; E-mail: clinicalrecommendations@esmo.org Approved by the ESMO Guidelines Working Group: December 2006, last update January 2010. This publication supercedes the previously published version—Ann Oncol 2009; 20 (Suppl 4): iv113–iv114. Conflict of interest: Dr Zucca has reported no conflicts of interest; Professor Dreyling has reported that he has received support for research from Roche and that he is a member of its advisory board. ª The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org at St Jude Childrens Research Hospital on Septem ber 4, 2010 a n n o n c.o xfordjournals.org D ow nloaded from anti-CD20 monoclonal antibodies [III]. Only a few compounds and regimens have been tested specifically in MALT lymphomas. Oral alkylating agents (either cyclophosphamide or chlorambucil) or purine nucleoside analogues (fludarabine, cladribine) can result in a high rate of disease control. The activity of the anti-CD20 monoclonal antibody rituximab has also been shown in phase II studies and its efficacy in combination with chlorambucil is being investigated in a randomized study. There is no clear evidence in the published literature to recommend any specific drug or regimen; it should, however, be mentioned that treatment with purine analogues might be associated with an increased risk of secondary myelodisplasia. Aggressive anthracycline-containing regimens are not usually necessary and should be reserved for the few patients with high tumour burden. Lymphoma with diffuse large cell infiltration should be treated according to the recommendations for diffuse large cell lymphoma. response evaluation and follow-up Histological evaluation of repeat biopsies remains an essential follow-up procedure. Unfortunately, the interpretation of lymphoid infiltrate in post-treatment gastric biopsies can be very difficult and there are no uniform criteria for the definition of histological remission. A preliminary breath test or stool antigen test should be performed at least 4 weeks after the antibiotic treatment to document H. pylori eradication. Then, a strict endoscopic follow-up is recommended, with multiple biopsies taken 2–3 months after treatment, and subsequently, at least twice per year for 2 years, to monitor the histological regression of the lymphoma. Gastric MALT lymphomas have limited tendency to distant spreading and to histological transformation. Transient histological local relapses are possible but tend to be self-limiting especially in the absence of H. pylori reinfection. In the case of persistent but stable residual disease or histological relapse (without distant dissemination and/or gross endoscopic tumour) a watch-and- wait policy appears to be safe [IV, C]. Nevertheless, long-term careful endoscopic and systemic (blood counts and minimal adequate radiological or ultrasound examinations) follow-up once per year is recommended for all patients. Indeed, the risk of gastric adenocarcinoma among patients diagnosed with gastric MALT lymphoma has been reported to be sixfold higher than in the general population. note Levels of Evidence [I–V] and Grades of Recommendation [A–D] as used by the American Society of Clinical Oncology are given in square brackets. Statements without grading are considered justified standard clinical practice by the expert authors and the ESMO faculty. literature 1. Ferrucci PF, Zucca E. Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years? Br J Haematol 2007; 136: 521–538. 2. Ferreri AJ, Zucca E. Marginal-zone lymphoma. Crit Rev Oncol Hematol 2007; 63: 245–256. 3. Bertoni F, Zucca E. State-of-the-art therapeutics: marginal-zone lymphoma. J Clin Oncol 2005; 23: 6415–6420. 4. Copie-Bergman C, Wotherspoon A. MALT lymphoma pathology, initial diagnosis, and posttreatment evaluation. In Cavalli F, Stein H, Zucca E (eds): Extranodal Lymphomas Pathology and Management. London: Informa Health Care 2008; 114–123. 5. Levy M, Copie-Bergman C, Traulle C et al. Conservative treatment of primary gastric low-grade B-cell lymphomaofmucosa-associated lymphoid tissue: predictive factors of response and outcome. Am J Gastroenterol 2002; 97: 292–297. 6. Fuccio L, Laterza L, Zagari RM et al. Treatment of Helicobacter pylori infection. BMJ 2008: 337: a1454. 7. Koch P, Probst A, Berdel WE et al. Treatment results in localized primary gastric lymphoma: data of patients registered within the German multicenter study (GIT NHL 02/96). J Clin Oncol 2005; 23: 7050–7059. 8. Tsang RW, Gospodarowicz MK. Radiation therapy for localized low-grade non- Hodgkin’s lymphomas. Hematol Oncol 2005; 23: 10–17. 9. Martinelli G, Laszlo D, Ferreri AJ et al. Clinical activity of rituximab in gastric marginal zone non-Hodgkin’s lymphoma resistant to or not eligible for anti- Helicobacter pylori therapy. J Clin Oncol 2005; 23: 1979–1983. 10. Fischbach W, Goebeler ME, Ruskone-Fourmestraux A et al. Most patients with minimal histological residuals of gastric MALT lymphoma after successful eradication of Helicobacter pylori can be managed safely by a watch and wait strategy: experience from a large international series. Gut 2007; 56: 1685–1687. 11. Stathis A, Chini C, Bertoni F et al. Long-term outcome following Helicobacter pylori eradication in a retrospective study of 105 patients with localized gastric marginal zone B-cell lymphoma of MALT type. Ann Oncol 2009; 20: 1086–1093. 12. Capelle LG, de Vries AC, Looman CW et al. Gastric MALT lymphoma: epidemiology and high adenocarcinoma risk in a nation-wide study. Eur J Cancer 2008; 44: 2470–2476. clinical practice guidelines Annals of Oncology v176 | Zucca & Dreyling Volume 21 | Supplement 5 | May 2010 at St Jude Childrens Research Hospital on Septem ber 4, 2010 a n n o n c.o xfordjournals.org D ow nloaded from