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Das Mantelzell-Lymphom − Aktuelle Standards in Diagnostik und Therapie (S.10–15)
Andrea Mayer, Martin Dreyling

  1.  Hoster E, Rosenwald A, Berger F, et al. Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2016; 34(12): 1386–94 
  2. Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016; 388(10044): 565–75
  3. Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, et al. Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma. N Engl J Med. 2017; 377(13): 1250–60
  4. Robak T, Huang H, Jin J, Zhu J, Liu T, Samoilova O, et al. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med. 2015; 372(10): 944–53
  5. Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, Geisler CH, et al. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. 2012; 367(6): 520–31
  6. Dreyling M, Campo E, Hermine O, Jerkeman M, Le Gouill S, Rule S, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; 28(suppl_4): iv62-iv71
  7. Forstpointner R, Unterhalt M, Dreyling M, Bock HP, Repp R, Wandt H, et al. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006; 108(13): 4003–8
  8. Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016; 387(10020): 770–8
  9. Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013; 369(6): 507–16
  10. Wang ML, Lee H, Chuang H, Wagner-Bartak N, Hagemeister F, Westin J, et al. Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. Lancet Oncol. 2016; 17(1): 48–56
  11. Trneny M, Lamy T, Walewski J, Belada D, Mayer J, Radford J, et al. Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial. Lancet Oncol. 2016; 17(3): 319–31
  12. Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, et al. Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009; 27(23): 3822–9
  13. Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006; 24(30): 4867–74

Aktuelle Therapiestrategien beim follikulären Lymphom (S.16–20)
Wolfgang Hiddemann

  1.   HiddemannW, Cheson BC. How we manage follicular lymphoma. Leukemia. 2014; 28: 1388–95
  2. Ghielmini M, Vitolo U, Kimby E, Montoto S, Walewski J, Pfreundschuh M, et al. ESMO guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Ann Oncol 2013; 24: 561–76
  3. Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Byrd JC, Czuczman MS et al. NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin's lymphomas. J Natl Compr Canc Netw. 2010; 8: 288–334
  4. Friedberg JW, Byrtek M, Link BK, Flowers C, Taylor M, Hainsworth J et al. Effectiveness of first-line management strategies for stage I follicular lymphoma: analysis of the National LymphoCare Study. J Clin Oncol  2012; 30: 3368–75
  5. Wennekes L, Ottevanger PB, Raemaekers JM, Schouten HC, de Kok MW, Punt CJ et al. Development and measurement of guideline-based indicators for patients with non-Hodgkin's lymphoma. J Clin Oncol 2011; 29: 1436–44
  6. Herfarth K, Engelhard M,  Borchmann P, Hohloch K, Budach V, Viardot A et al. Treatment of early stage nodal follicular lymphoma using involved-field radiotherapy and rituximab: Preliminary results of the MIR trial (phase II study of the German Low Grade Lymphoma Study Group (GLSG)). Blood 2012; 120: 1634
  7. Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA et al. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet 2003; 362: 516–22
  8. Brice P, Bastion Y, Lepage E, Brousse N, Haïoun C, Moreau P et al. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 1997; 15: 1110–17
  9. Ardeshna K, Qian W, Smith P, Braganca N, Lowry L et al. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014; 15: 424–35
  10. Solal-Céligny P, Bellei M, Marcheselli L, Pesce EA, Pileri S, McLaughlin P, Luminari S et al. Watchful waiting in low-tumor burden follicular lymphoma in the rituximab era: results of an F2-study database. J Clin Oncol 2012; 30: 848–53
  11. Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 2007; 25: 1986–92
  12. Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005; 106: 3725–32
  13. Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008; 26: 4579–86
  14. Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood 2008; 112: 4824–31
  15. Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011; 377: 42–51
  16. Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, et al. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017;377:1331–44
  17. Launonen A, Hiddemann W, Duenzinger U, Fingerle-Rowson G, Nielsen T, Marcus R. Early disease progression predicts poorer survival in patients with follicular lymphoma in the GALLIUM study. Blood 2017, im Druck 
  18. Casulo C, Byrtek M, Dawson KL, Zhou X, Farber CM, Flowers CR et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: An analysis from the National LymphoCare Study. J Clin Oncol. 2015;33: 2516–20
  19. Karlin L, Coiffier B. Ofatumumab in the treatment of non-Hodgkin's lymphomas. Expert Opin Biol Ther. 2015 ;15: 1085–91
  20. Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD et al. Randomized phase II trial comparing Obinutuzumab (GA101) with Rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: Final analysis of the GAUSS Study. J Clin Oncol. 2015; 33: 3467–74
  21. Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 2013; 31: 88–94
  22. Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014; 370: 1008–18
  23. Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB et al. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014; 15: 1311–18
  24. Pastore A, Jurinovic V, Kridel R, Hoster E, Staiger AM et al. Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol. 2015; 16: 1111–22
  25. Ladetto M, Lobetti-Bodoni C, Mantoan B, Ceccarelli M, Boccomini C et al. Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program. Blood. 2013; 122: 3759–66
  26. Dupuis J, Berriolo-Riedinger A, Julian A, Brice P, Tychyj-Pinel C, Tilly H et al. Impact of [(18)F]fluorodeoxyglucose positron emission tomography response evaluation in patients with high-tumor burden follicular lymphoma treated with immunochemotherapy: a prospective study from the Groupe d'Etudes des Lymphomes de l'Adulte and GOELAMS. J Clin Oncol 2012; 30: 4317–22

Therapie der aggressiven B-Zell-Lymphome (S.21–26)
Niels Murawski und Michael Pfreundschuh 

  1. Shiels MS, Engels EA, Linet MS, Clarke CA, Li J, Hall HI, et al. The epidemic of non-Hodgkin lymphoma in the United States: disentangling the effect of HIV, 1992-2009. Cancer Epidemiol Biomarkers Prev 2013; 22: 1069–78
  2. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 1993; 329: 987–94
  3. Held G, Murawski N, Ziepert M, Fleckenstein J, Poschel V, Zwick C, et al. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol 2014; 32: 1112–8
  4. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32: 3059–68
  5. Horn H, Ziepert M, Wartenberg M, Staiger AM, Barth TF, Bernd HW, et al. Different biological risk factors in young poor-prognosis and elderly patients with diffuse large B-cell lymphoma. Leukemia 2015; 29: 1564–70
  6. Staiger AM, Ziepert M, Horn H, Scott DW, Barth TFE, Bernd HW, et al. Clinical Impact of the Cell-of-Origin Classification and the MYC/ BCL2 Dual Expresser Status in Diffuse Large B-Cell Lymphoma Treated Within Prospective Clinical Trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group. J Clin Oncol 2017; 35: 2515–26
  7. Scott DW, Mottok A, Ennishi D, Wright GW, Farinha P, Ben-Neriah S, et al. Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin Determined by Digital Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Biopsies. J Clin Oncol 2015; 33: 2848–56
  8. Pfreundschuh M, Kuhnt E, Trumper L, Osterborg A, Trneny M, Shepherd L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 2011; 12: 1013–22
  9. Stephens DM, LeBlanc ML, Li H, Miller TP, Puvvada SD, Friedberg JWSSM. Continued risk of relapse independent of teatment modality in limited stage diffuse large B-cell lymphoma: Final and long-term analysis of SWOG study S8736. Hematol Oncol 2015; 33: 170
  10. Sehn LH, Savage KJ, Hoskins P, Klasa R, Shenkier T, Voss N, et al. Limited-stage diffuse large B-cell lymphoma patients with a negative PET scan following three cycles of R-CHOP can be effectively treated with abbreviated chemoimmunotherapy alone. Blood 2007; 110[11]:242a
  11. Tilly H, Gomes da SM, Vitolo U, Jack A, Meignan M, Lopez-Guillermo A, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 Suppl 5: v116–v125
  12. Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, et al. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol 2012; 13: 1250–9
  13. Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, et al. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol 2017; 18: 1076–88
  14. Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med 2013; 369: 1681–90
  15. Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 2008; 9:105–16
  16. Pfreundschuh M, Poeschel V, Zeynalova S, Haenel M, Held G, Schmitz N, et al. Optimization of rituximab for the treatment of DLBCL (II): Extendet rituximab exposure time in the SMARTE-R-CHOP-14 trial of the DSHNHL. J Clin Oncol 2014; 32: 4127–33
  17. Pfreundschuh M., Murawski N, Christofyllakis K, Altmann B, Ziepert M, Haenel M, et al. Excellent outcome of elderly patients with favourable-prognosis DLBCL treated with 4 cycles CHOP/CHLIP-14 plus 8 applications of rituximab and a PET-based intensification strategy that includes involved-site radiotherapy (IS-RT): Results of the first 120 patients of the OPTIMAL>60 trial of the DSHNHL.  Blood 2017 (in press) 
  18. Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, et al. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol 2013; 14: 525–33
  19. Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, et al. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet 2013; 381: 1817–26
  20. Pfreundschuh M, Christofyllakis K, Altmann B, Ziepert M, Hänel M, Viardot A, et al. Radiotherapy (RT) to bulky disease PET-negative after immunochemotherapy can be spared in elderly DLBCL patients: Results of a planned interim analysis of the first 187 patients with bulky disease treated in the OPTIMAL>60 study of the DSHNHL. J Clin Oncol 2017; 35[15S]: 393s
  21. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373–83
  22. 22. Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol 2011; 12: 460–8
  23. Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Ferme C, et al. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol 2017; 4: e46–e55
  24. Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, et al. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial. J Clin Oncol 2014; 32: 282–7
  25. Mounier N, El Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, et al. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial. Haematologica 2013; 98: 1726–31
  26. Pfreundschuh M, Muller C, Zeynalova S, Kuhnt E, Wiesen MH, Held G, et al. Suboptimal dosing of rituximab in male and female patients with DLBCL. Blood 2014; 123: 640–6
  27. Bittenbring JT, Neumann F, Altmann B, Achenbach M, Reichrath J, Ziepert M, et al. Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab. J Clin Oncol 2014; 32: 3242–8
  28. Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med 2015; 21: 922–6
  29. Roberts AW, Advani RH, Kahl BS, Persky D, Sweetenham JW, Carney DA, et al. Phase 1 study of the safety, pharmacokinetics, and antitumour activity of the BCL2 inhibitor navitoclax in combination with rituximab in patients with relapsed or refractory CD20+ lymphoid malignancies. Br J Haematol 2015; 170: 669–78
  30. Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, et al. Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. J Clin Oncol 2016; 34: 2698–704

UPDATE: Aktueller Stand der Therapie des Magenkarzinoms (S.39–42)
Ewald Wöll

  1. Howlader N NA, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). . SEER Cancer Statistics Review, 1975-2013, National Cancer Institute. Bethesda, MD, 2016; seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site, April 2016
  2. Lordick F AD, Borner M, Bruns CJ, Eisterer W, Faber G, Hegewisch-Becker S, Möhler M, Pritzkuleit R, Stahl M, Thuss-Patience P, Wöll E. Onkopedia Leitlinien Magenkarzinom. www.onkopedia.com 2017
  3. Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014; 513: 202–9
  4. Cunningham D, Allum WH, Stenning SP et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006; 355: 11–20
  5. Ychou M, Boige V, Pignon JP et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011; 29: 1715–21
  6. Al-Batran SE, Hofheinz RD, Pauligk C et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 2016; 17: 1697–708
  7. Al-Batran S, N H, H S et al. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): A multicenter, randomized phase 3 trial. J Clin Oncol 2017; 35
  8. Group G, Paoletti X, Oba K et al. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA 2010; 303: 1729–37
  9. Macdonald JS, Smalley SR, Benedetti J et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001; 345: 725–30
  10. Wagner AD, Grothe W, Haerting J et al. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 2006; 24: 2903-2909.
  11. Smyth EC, Verheij M, Allum W et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27: v38–v49
  12. Thuss-Patience PC, Kretzschmar A, Bichev D et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 2011; 47: 2306–14
  13. Kang JH, Lee SI, Lim DH et al. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 2012; 30: 1513–18
  14. Wilke H, Muro K, Van Cutsem E et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014; 15: 1224–35
  15. 15. Fuchs CS, Tomasek J, Yong CJ et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014; 383: 31–9
  16. Bang YJ, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010; 376: 687–97
  17. Kang YK, Boku N, Satoh T et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017