Appendix 2. List of the thirty-two studies included in qualitative synthesis, (Online only) 1. Mead GM, Bleehen NM, Gregor A, Bullimore J, Shirley D, Rampling RP, et al. A medical research council randomized trial in patients with primary cerebral non- Hodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Cancer. 2000 Sep 15;89(6):1359 70. 2. DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ, Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol. 2002 Dec 15;20(24):4643 8. 3. Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007 Oct 20;25(30):4730 5. 4. Pels H, Juergens A, Glasmacher A, Schulz H, Engert A, Linnebank M, et al. Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study. J Neurooncol. 2009 Feb;91(3):299 305. 5. Ferreri AJ, Cwynarski K, Pulczynski E, et al. Addition of thiotepa and rituximab to antimetabolites significantly improves outcome in primary CNS lymphoma: the first randomization of the IELSG32 trial [abstract]. Hematol Oncol. 2015;33(suppl 1):103-104. Abstract 009. 6. Illerhaus G, Müller F, Feuerhake F, Schäfer A-O, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147 8.
7. Schorb E, Finke J, Ferreri AJM, Ihorst G, Mikesch K, Kasenda B, et al. High-dose chemotherapy and autologous stem cell transplant compared with conventional chemotherapy for consolidation in newly diagnosed primary CNS lymphoma-a randomized phase III trial (MATRix). BMC Cancer. 2016;16(1):282. 8. Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, et al. Highdose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865 70. 9. Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, et al. Highdose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417 20. 10. Ferreri AJM, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, et al. High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009 Oct 31;374(9700):1512 20. 11. Chamberlain MC, Johnston SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neurooncology. 2010 Jul;12(7):736 44. 12. Illerhaus G, Marks R, Müller F, Ihorst G, Feuerhake F, Deckert M, et al. Highdose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study. Ann Oncol. 2009 Feb;20(2):319 25. 13. Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma
(G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036 47. 14. Ferreri AJM, Donadoni G, Cabras MG, Patti C, Mian M, Zambello R, et al. High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial. J Clin Oncol. 2015 Nov 20;33(33):3903 10. 15. Cheng T, Forsyth P, Chaudhry A, Morris D, Glück S, Russell JA, et al. High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant. 2003 Apr;31(8):679 85. 16. Rubenstein JL, Hsi ED, Johnson JL, Jung S-H, Nakashima MO, Grant B, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol. 2013 Sep 1;31(25):3061 8. 17. Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, et al. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512 8. 18. Ghesquières H, Ferlay C, Sebban C, Perol D, Bosly A, Casasnovas O, et al. Longterm follow-up of an age-adapted C5R protocol followed by radiotherapy in 99 newly diagnosed primary CNS lymphomas: a prospective multicentric phase II study of the Groupe d Etude des Lymphomes de l Adulte (GELA). Ann Oncol. 2010 Apr;21(4):842 50.
19. Nayak L, Abrey LE, Drappatz J, Gilbert MR, Reardon DA, Wen PY, et al. Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma. Leuk Lymphoma. 2013 Jan;54(1):58 61. 20. Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD, et al. Non- Hodgkin s lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys. 1992;23(1):9 17. 21. Chen Y-B, Batchelor T, Li S, Hochberg E, Brezina M, Jones S, et al. Phase 2 trial of high-dose rituximab with high-dose cytarabine mobilization therapy and high-dose thiotepa, busulfan, and cyclophosphamide autologous stem cell transplantation in patients with central nervous system involvement by non-hodgkin lymphoma. Cancer. 2015 Jan 15;121(2):226 33. 22. O Brien P, Roos D, Pratt G, Liew K, Barton M, Poulsen M, et al. Phase II multicenter study of brief single-agent methotrexate followed by irradiation in primary CNS lymphoma. J Clin Oncol. 2000 Feb;18(3):519 26. 23. Wang Y, Liu B, Xu D, Zhao H, Zhu Y, Xu J, et al. Phase II trial of temozolomide plus concurrent whole-brain radiation followed by TNV regimen as adjuvant therapy for patients with newly diagnosed primary CNS lymphoma. Neurol India. 2013 Jun;61(3):260 4. 24. Schultz C, Scott C, Sherman W, Donahue B, Fields J, Murray K, et al. Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88-06. J Clin Oncol. 1996 Feb;14(2):556 64. 25. Montemurro M, Kiefer T, Schüler F, Al-Ali HK, Wolf H-H, Herbst R, et al. Primary central nervous system lymphoma treated with high-dose methotrexate, high-
dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007 Apr;18(4):665 71. 26. Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N, et al. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol. 2001 Feb 1;19(3):742 9. 27. Nguyen PL, Chakravarti A, Finkelstein DM, Hochberg FH, Batchelor TT, Loeffler JS. Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma. J Clin Oncol. 2005 Mar 1;23(7):1507 13. 28. Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, et al. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013 Nov 1;31(31):3971 9. 29. Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, et al. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403 10. 30. Pulczynski EJ, Kuittinen O, Erlanson M, Hagberg H, Fosså A, Eriksson M, et al. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group. Haematologica. 2015 Apr;100(4):534 40.
31. Batchelor T, Carson K, O Neill A, Grossman SA, Alavi J, New P, et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol. 2003 Mar 15;21(6):1044 9. 32. Choi MK, Kang ES, Kim DW, Ko YH, Seok H, Park JH, et al. Treatment outcome of relapsed/refractory primary central nervous system diffuse large B-cell lymphoma: a single-center experience of autologous stem cell transplantation. Int J Hematol. 2013 Sep;98(3):346 54.