JCT  Vol.4 No.1 , February 2013
Current Treatment and Controversy of Primary Gastric Lymphoma
Abstract: Primary gastric lymphoma (PGL) is not a common cancer and account for 10% of malignant lymphoma and 5% of gastric cancer. The correlation with Helicobacter pylori (H. pylori) infection with mucosa associated lymphoepithelial tumor (MALT) is now well documented and some of the low grade MALT can be cured sorely by triple agent eradication therapy. The most common type of PGL is diffuse large B cell lymphoma which now can be successfully treated with chemotherapy alone. There is still no consensus on the optimal treatment for PGL. In the recent 10 years chemotherapy combined with anti-CD 20 monoclonal antibody such as rituximab, achieved higher complete response rate and more than 80% are long-term survival. The so-called R-CHOP (rituximab, cyclophosphamide, vincristin, prednisolone) now become the new gold standard therapy. The role of surgical resection prior to chemotherapy is controversial and not commonly applied in recent publications. Yet some cases of suboptimal response to R-CHOP or patient is too fragile to tolerate the immuno-chemotherapy will be feasible to surgical resection as a salvage or alternative therapy. The radiotherapy as an adjuvant therapy is less commonly considered. Patients with advanced PGL with high international prognostic index risk and along with co-morbidity diseases are prone to get treatment related complications from above-mentioned modality of treatment, such as GI perforation, neutropenic septicemia, pulmonary infection, fulminate heaptitis B reactivation, respiratory and cardiac impairment can be seen.
Cite this paper: M. Chang, "Current Treatment and Controversy of Primary Gastric Lymphoma," Journal of Cancer Therapy, Vol. 4 No. 1, 2013, pp. 145-152. doi: 10.4236/jct.2013.41020.

[1]   T. Tanaka, K. Shimada, K. Yamamoto, Y. Hirooka, et al. “Retrospective Analysis of Primary Gastric Diffuse Large B Cell Lymphoma in the Rituximab Era: A Multicenter Study of 95 Patients in Japan,” Annals of Hematology, Vol. 91, No. 3, 2012, pp. 383-390. doi:10.1007/s00277-011-1306-0

[2]   A. Aviles, C. Castaneda, S. Cleto, N. Neri, et al., “Rituximab and Chemotherapy in Primary Gastric Lymphoma,” Cancer Biotherapy & Radiopharmaceuticals, Vol. 24, No. 1, 2009, pp. 25-28. doi:10.1089/cbr.2008.0507

[3]   S. Wohrer, A. Puspok, J. Drach, M. Hejna, et al., “Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) for Treatment of Early-Stage Gastric Diffuse Large B-Cell Lymphoma,” Annals of Oncology, Vol. 15, No. 7, 2004, pp. 1086-1090. doi:10.1093/annonc/mdh261

[4]   M. C. Chang, M. J. Huang, Y. W. Su, et al., “Clinical Outcome of Primary Gastric Lymphoma Treated with Chemotherapy Alone or Surgery Followed by Chemotherapy,”Journal of the Formosan Medical Association, Vol. 105, No. 3, 2006, pp. 194-202. doi:10.1016/S0929-6646(09)60305-3

[5]   P. G. Isaacson, “Gastrointestinal Lymphoma,” Human Pathology, Vol. 25, 1994, pp. 1020-1029. doi:10.1016/0046-8177(94)90060-4

[6]   T. Yoshino, K. Omonishi, K. Kobayashi, T. Mannami, et al., “Clinicopathological Fearture of Mucosa Associated Lymphoid Tissue (MALT) Lymphoma: High Grade Transformation and Comparison with Diffuse Large B Cell Lymphoma without MALT Lymphoma Features,” Journal of Clinical Pathology, Vol. 53, 2000, pp. 187-190. doi:10.1136/jcp.53.3.187

[7]   E. S. Jaffe, N. L. Harris, H. Stein and J. W. Vardiman, “World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues,” IARC Press, Lyon, Vol. 2001.

[8]   F. d’Amore, H. Brinker, J. Gronbak, et al., “Non-Hodgkin’s Lymphoma of the Gastrointestinal Tract: A Population-Based Analysis of Incidence, Geographic Distribution, Clinicopathological Presentation, Features, and Prognosis,” Journal of Clinical Oncology, Vol. 12, No. 8, 1994, pp. 1673-1684.

[9]   J. Huang, W. Jiang, R. Xu, H. Huang, et al., “Primary Gastric Non-Hodgkin’s Lymphoma in Chinese Patients: Clinical Characteristics and Prognostic Factors,” BMC Cancer, Vol. 10, 2012, p. 358. doi:10.1186/1471-2407-10-358

[10]   K. Mushoff, “Klinische Stadieneineteilung der Nicht-Hodgkin’s Lymphoma,” Strahlentherapie und Onkologie, Vol. 153, 1977, pp. 218-221.

[11]   A. Rohatiner, F. d’Amore, B. Coiffier, et al., “Report on a Workshop Convened to Discuss the Pathological and Staging Classifications of Gastrointestinal Tract Lymphoma,” Annals of Oncology, Vol. 5, No. 5, 1994, pp. 397-400.

[12]   G. Salles, R. Herbrecht, H. Tilly, et al., “Aggressive Primary Gastrointestinal Lymphomas: Review of 91 Patients Treated with the LNH-84 Regimen. A Study of the Group d’Etude des Lymphomes Agressifs,” American Journal of Medicine, Vol. 90, No. 1, 1991, pp. 77-84. doi:10.1016/0002-9343(91)90509-V

[13]   M. Raderer, J. Valencak, C. ?sterreicher, et al., “Chemotherapy for the Treatment of Patients with Primary High Grade Gastric B-cell Lymphoma of Modified Ann Arbor Stages IE and IIE,” Cancer, Vol. 88, No. 9, 2000, pp. 1979-1985. doi:10.1002/(SICI)1097-0142(20000501)88:9<1979::AID-CNCR1>3.0.CO;2-L

[14]   M. H. Maor, W. S. Valesquez, L. M. Fuller, et al., “Stomach Conservation in Stage IE and IIE Gastric Non-Hodgkin’s Lymphoma,” Journal of Clinical Oncology, Vol. 8, No. 2, 1990, pp. 266-271.

[15]   M. H. Shiu, L. Z. Nisce, A. Pinna, et al., “Recent Results of Multimodal Therapy of Gastric Lymphoma,” Cancer, Vol. 58, No. 7, 1986, pp. 1389-1399. doi:10.1002/1097-0142(19861001)58:7<1389::AID-CNCR2820580702>3.0.CO;2-Y

[16]   F. A. Sheperd, W. K. Evans, G. Kutas, et al., “Chemotherapy Following Surgery for Stage IE and IIE Non-Hodgkin’s Lymphoma of the Gastrointestinal Tract,” Journal of Clinical Oncology, Vol. 6, No. 2, 1988, pp. 253-260.

[17]   M. K. Gospodarowicz, S. B. Sutcliffe, R. M. Clark, et al., “Outcome Analysis of Localized Gastrointestinal Lymphoma Treated with Surgery and Postoperative Irradiation,” International Journal of Radiation Oncology, Biology and Physics, Vol. 19, No. 6, 1990, pp. 1351-1355. doi:10.1016/0360-3016(90)90343-I

[18]   C. Rosen, J. A. Heerden, L. K. Martin, et al., “Is an Aggressive Surgical Approach to the Patient with Gastric Lymphoma Warranted?” Annals of Surgery, Vol. 205, No. 6, 1987, pp. 634-640. doi:10.1097/00000658-198706000-00004

[19]   M. S. Hockey, J. Powel, J. Crocker, et al., “Primary Gastric Lymphoma,” British Journal of Surgery, Vol. 74, No. 6, 1987, pp. 483-487. doi:10.1002/bjs.1800740620

[20]   R. J. Schwarz, J. M. Conners, N. Schmidt, et al., “Diagnosis and Management of Stage IE and Stage IIE Gastric Lymphomas,” The American Journal of Surgery, Vol. 165, No. 5, 1993, pp. 561-565. doi:10.1016/S0002-9610(05)80435-0

[21]   E. D. Durr, J. A. Bonner, J. G. Strickler, et al., “Management of Stage IE Primary Gastric Lymphoma,” Acta Haematologica, Vol. 94, No. 2, 1995, pp. 59-68. doi:10.1159/000203975

[22]   S. S. Yoon, D. G. Coit, C. S. Portlock, et al., “The Diminishing Role of Surgery in the Treatment of Gastric Lymphoma,” Annals of Surgery, Vol. 240, No. 2004, pp. 28-37. doi:10.1097/01.sla.0000129356.81281.0c

[23]   A. Avilés, M. J. Nambo, N. Neri, et al., “The Role of Surgery in Primary Gastric Lymphoma: Results of a Controlled Clinical Trial,” Annals of Surgery, Vol. 240, No. 1, 2004, pp. 44-50. doi:10.1097/01.sla.0000129354.31318.f1

[24]   D. de Jong, B. M. P. Aleman, B. G. Taal, et al., “Controversies and Consensus in the Diagnosis, Work-Up and Treatment of Gastric Lymphoma: An International Survey,” Annals of Oncology, Vol. 10, No. 3, 1999, pp. 275-280. doi:10.1023/A:1008392022152

[25]   T. P. Miller, S. Dahlberg, J. R. Cassady, et al., “Chemotherapy Alone Compared Chemotherapy Plus Radiotherapy for Localized Intermediate- and High-Grade Non-Hodgkin’s Lymphoma,” The New England Journal of Medicine, Vol. 339, 1998, pp. 21-26. doi:10.1056/NEJM199807023390104

[26]   W. P. Sheridan, G. Medley, G. N. Brodie, “Non-Hodgkin’s Lymphoma of the Stomach: A Prospective Pilot Study of Surgery plus Chemotherapy in Early and Advanced Disease,” Journal of Clinical Oncology, Vol. 3, No. 4, 1985, pp. 495-500.

[27]   F. A. Shepherd, W. K. Evans, G. Kutas, et al., “Chemotherapy Following Surgery for Stages IE and IIE Non-Hodgkin’s Lymphoma of the Gastrointestinal Tract,” Journal of Clinical Oncology, Vol. 6, No. 2, 1988, pp. 253-260.

[28]   D. C. Cooper, R. Doria, E. Salloum, et al., “Primary Gastrointestinal Lymphomas,” Gastroenterologist, Vol. 4, 1996, pp. 54-64.

[29]   A. Ruskoné-Fourmestraux, P. Aegerter, A. Delmer, et al., “Primary Digestive Tract Lymphoma: A Prospective Multicentric Study of 91 Patients-Group d’Etude des Lymphoma Digestifs,” Gastroenterology, Vol. 105, No. 6, 1993, pp. 1662-1671.

[30]   P. G. Gobbi, P. Dionigi, F. Barbieri, et al., “The Role of Surgery in the Multimodal Treatment of Primary Gastric Non-Hodgkin’s Lymphoma: A Report of 76 Cases and Review of the Literature,” Cancer, Vol. 65, No. 11, 1990, pp. 2528-2536. doi:10.1002/1097-0142(19900601)65:11<2528::AID-CNCR2820651123>3.0.CO;2-W

[31]   G. Bellesi, A. Alterini, A. Messori, et al., “Combined Surgery and Chemotherapy for the Treatment of Primary Gastrointestinal Intermediate- or High-Grade Non-Hodgkin’s Lymphomas,” British Journal of Cancer, Vol. 60, 1989, pp. 244-248. doi:10.1038/bjc.1989.262

[32]   C. Tondini, F. Giardini, P. Bezztti, et al., “Combined Modality Treatment for Primary Gastrointestinal Non-Hodgkin’s Lymphoma: The Milan Cancer Institute Experience,” Annals of Oncology, Vol. 4, No. 10, 1993, pp. 831-837.

[33]   V. L. Rackner, J. A. Thirlby, “Ryan Role of Surgery in Multimodality Therapy for Gastrointestinal Lymphoma,” The American Journal of Surgery, Vol. 161, No. 5, 1991, pp. 570-575. doi:10.1016/0002-9610(91)90902-P

[34]   A. Ruskoné-Fourmestraux, P. Aegerter, A. Delmer, et al., “Primary Digestive Tract Lymphoma: A Prospective Multicentric Study of 91 Patients-Group d’Etude des Lymphoma Digestifs,” Gastroenterology, Vol. 105, No. 6, 1993, pp. 1662-1671.

[35]   H. T. Liu, C. Hsu, C. L. Chen, et al., “Chemotherapy Alone versus Surgery Followed by Chemotherapy for Stage I/IIE Large-Cell Lymphoma of the Stomach,” American Journal of Hematology, Vol. 64, No. 3, 2000, pp. 175-179. doi:10.1002/1096-8652(200007)64:3<175::AID-AJH6>3.0.CO;2-7

[36]   B. Coiffier, C. Gisselbrecht, R. Herbrecht, et al., “LNH-84 Regimen: A Multicentric Study of Intensive Chemotherapy in 737 Patients with Aggressive Malignant Lymphoma,” Journal of Clinical Oncology, Vol. 7, 1989, pp. 1018-1026.

[37]   S. Nakamura, T. Matsumoto, M. Iida, et al., “Primary Gastric Lymphoma in Japan: A Clinicopathologic Analysis of 455 Patients with Special Reference to Its Time Trends,” Cancer, Vol. 97, No. 10, 2003, pp. 2462-2473. doi:10.1002/cncr.11415

[38]   C. L. Ho, A. T. Hsieh, M. S. Dai, et al., “Non-Hodgkin’s Lymphoma of the Stomach: Treatment Outcomes for 57 Patients over a 20-Year Period,” Journal of the Chinese Medical Association, Vol. 68, No. 1, 2005, pp. 11-15. doi:10.1016/S1726-4901(09)70125-X

[39]   M. Binn, A. Rouskoné-Fourmestraux, E. Lepage, et al., “Surgical Resection plus Chemotherapy versus Chemotherapy Alone: Comparison of Two Strategies to Treat Diffuses Large B-Cell Lymphoma,” Annals of Oncology, Vol. 14, No. 12, 2003, pp. 1751-1757. doi:10.1093/annonc/mdg495

[40]   J. C. Vaillant, A. Ruskoné-Fourmestraux, P. Aegerter, et al., “Management and Long-Term Results of Surgery for Localized Gastric Lymphomas,” The American Journal of Surgery, Vol. 179, No. 3, 2000, pp. 216-222. doi:10.1016/S0002-9610(00)00295-6

[41]   B. P. Koch, F. del Valle, W. E. Berdel, et al., “Primary Gastrointestinal Non-Hodgkin’s Lymphoma: II. Combined Surgical and Conservative or Conservative Management Only in Localized Gastric Lymphoma-Results of the Prospective German Multicenter Study GIT NHL 01/92,” Journal of Clinical Oncology, Vol. 19, No. 18, 2001, pp. 3874-3878.

[42]   Y. Lv, X. N. Wang, H. Liang, “Clinical Analysis of 200 Patients with Primary Gastric Lymphoma,” Zhonghua Wei Chang Wai Ke Za Zhi, Vol. 15, No. 2, 2012, pp. 157-160.

[43]   F. Sel?ukbiricik, D. Tural, O. Elicin, S. Berk, et al., “Primary Gastric Lymphoma: Conservative Treatment Modality is Not Inferior to Surgery for Early-Stage Disease,” ISRN Oncology, Vol. 2012, 2012, p. 951816. doi:10.5402/2012/951816

[44]   B. Coiffier, C. Gisselbrecht, A. Bosly, et al., “Ten Years Follow-Up of the GELA LNH98.5 Study, First Randomized Study Comparing R-CHOP to CHOP Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma,” ASH 2009.

[45]   A. Ruskoné-Fourmestraux, A. Lavergne, P. H. Aegerter, F. Megraud, et al., “Predictive Factors for Regression of Gastric MALT Lymphoma after Anti-Helicobacter Pylori Treatment,” Gut, Vol. 48, No. 3, 2001, pp. 297-303. doi:10.1136/gut.48.3.297

[46]   L. T. Chen, J. T. Lin, J. J. Tai, G. H. Chen, et al., “Long-Term Results of Anti-Helicobacter Pylori Therapy in Early-Stage Gastric High-Grade Transformed MALT Lymphoma,” Journal of the National Cancer Institute, Vol. 97, No. 18, 2005, pp. 1345-1353. doi:10.1093/jnci/dji277

[47]   S. Nakamura, T. Matsumoto, H. Suekane, M. Takeshita, et al., “Predictive Value of Endoscopic Ultrasonography for Regression of Gastric Low Grade and High Grade MALT Lymphomas after Eradication of Helicobacter Pylori,” Gut, Vol. 48, No. 4, 2001, pp. 454-60. doi:10.1136/gut.48.4.454

[48]   W. W. Ng, C. P. Lam, W. K. Chau, A. Fen-Yau Li, et al., “Regression of High-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphoma with Helicobacter Pylori after Triple Antibiotic Therapy,” Gastrointestinal Endoscopy, Vol. 51, No. 1, 2000, pp. 93-96. doi:10.1016/S0016-5107(00)70399-3

[49]   L. Cavanna, R. Pagani, P. Seghini, et al., “High Grade B-Cell Gastric Lymphoma with Complete Pathologic Remission after Eradication of Helicobacter Pylori Infection: Report of a Case and Review of the Literature,” World Journal of Surgical Oncology, Vol. 6, 2008, p. 35

[50]   B. Cheson, M. Rummel Bendamustine, “Rebirth of an Old Drug,” Journal of Clinical Oncology, 2009, pp. 1492-1501.

[51]   M. Rummel, E. Sahah, Al-Batran et al., “Bedamustine plus Rituximab is Effective as Favorable Toxicity Profile in the Treatment of Mantle Cell and Low Grade Non-Hodgkin’s Lymphoma,” Journal of Clinical Oncology, Vol. 23, No. 15, 2005, pp. 3383-3389.

[52]   K. Dunleavy, S. Pittluga, M. S. Czuczman, et al., “Differential Efficacy of Bortezomib plus Chemotherapy within Molecular Subtype of Diffuse Large B Cell Lymphoma,” Blood, Vol. 113, No. 24, 2009, pp. 6069-6076.

[53]   F. J. Hernandez-Ilizaliturri, G. Deeb, P. L. Zinzani, et al., “Higher Response to Lenalidomide in Relapsed/Refractory Diffuse Large B Cell Lymphoma in Non-Germinal Center B-Cell-Like Than in Germinal Center B-Cell-Like Phenotype,” Cancer, Vol. 117, No. 22, 2011, pp. 5058-5066.