Appendix 2. List of the thirty-two studies included in qualitative synthesis, (Online only)

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1 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 Sep 15;89(6): DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ, Radiation Therapy Oncology Group Study Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study J Clin Oncol Dec 15;20(24): 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 Oct 20;25(30): 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 Feb;91(3): 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): Abstract 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 Jan;93(1):147 8.

2 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): 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 Aug 20;24(24): 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 Sep;38(6): 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 Oct 31;374(9700): Chamberlain MC, Johnston SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neurooncology Jul;12(7): 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 Feb;20(2): 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

3 (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol Nov;11(11): 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 Nov 20;33(33): 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 Apr;31(8): 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 (Alliance 50202). J Clin Oncol Sep 1;31(25): 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 May 20;26(15): 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 Apr;21(4):

4 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 Jan;54(1): 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 Int J Radiat Oncol Biol Phys. 1992;23(1): 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 Jan 15;121(2): 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 Feb;18(3): 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 Jun;61(3): 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 J Clin Oncol Feb;14(2): 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-

5 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 Apr;18(4): 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 Feb 1;19(3): 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 Mar 1;23(7): 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 Nov 1;31(31): 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 Feb 26;125(9): 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 Apr;100(4):

6 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 J Clin Oncol Mar 15;21(6): 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 Sep;98(3):