Summary
Failure after first-line treatment was reported in 35–60% of immunocompetent patients with primary central nervous system lymphoma (PCNSL). There are currently no reports focusing on salvage therapy. This review analyses prognostic factors and the efficacy of salvage therapy by focusing on data from papers reporting results of first-line treatment in 355 cases. The study group consisted of 173 patients presenting treatment failure. The interval between failure and death (TTD) was compared for age at relapse (≤60 vs >60 years), type of failure (relapse vs progression), time to relapse (≤12 vs >12 months) and salvage treatment (yes vs no). Median TTD was similar in younger and older patients (P = 0.09). Relapsed patients had a longer TTD than patients with progressive disease (P = 0.002). Early relapse led to a shorter TTD than late relapse (P = 0.005). Median TTD was 14 months for patients who underwent salvage therapy and 2 months for untreated cases (P < 0.00001). A multivariate analysis showed an independent prognostic role for salvage therapy and time to relapse. Age and type of failure had no predictive value. Salvage therapy significantly improves outcome and, possibly, quality of life. As many different treatments were used conclusions cannot be made regarding an optimal treatment schedule.
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References
Bessell, E. M., Graus, F., Punt, J. A. G., Firth, J. L., Hope, T., Moloney, A. J., Lopez-Guillermo, A. & Villa, S. (1996). Primary non-Hodgkin’s lymphoma of the CNS treated with BVAM or CHOD/BVAM chemotherapy before radiotherapy. J Clin Oncol 14: 945–954.
Boiardi, A., Silvani, A., Valentini, S., Salmaggi, A., Allegranza, A. & Broggi, G. (1993). Chemotherapy as first treatment for primary malignant non-Hodgkin’s lymphoma of the central nervous system preliminary data. J Neurol 241: 96–100.
Chamberlain, M. C. & Levin, V. A. (1990). Adjuvant chemotherapy for primary lymphoma of the central nervous system. Arch Neurol 47: 1113–1116.
Cox, D. R. (1972). Regression models and life-tables. J R Stat Soc 34: 187–220.
De Angelis, L., Yahalom, J., Thaler, H. T. & Kher, U. (1992). Combined modality therapy for primary CNS lymphoma. J Clin Oncol 10: 635–643.
Di Marco, A., Rosta, L., Campostrini, F., Bonetti, A., Palazzi, M. & Garusi, G. (1986). The role of radiation therapy in the management of primary non-Hodgkin’s lymphomas of the central nervous system: clinical study of 10 cases. Tumori 72: 565–573.
Ferreri, A. J. M., Reni, M. & Villa, E. (1995a). Primary central nervous system lymphoma in immunocompetent patients. Cancer Treat Rev 21: 415–446.
Ferreri, A. J. M., Reni, M., Bolognesi, A., Verusio, C. & Villa, E. (1995b). Combined therapy for primary central nervous system lymphoma in immunocompetent patients. Eur J Cancer 31A: 2008–2012.
Fine, H. A. & Mayer, R. J. (1993). Primary central nervous system lymphoma. Ann Intern Med 119: 1093–1104.
Freilich, R. J., Delattre, J. Y., Monjour, A. & De Angelis, L. M. (1996). Chemotherapy without radiation therapy as initial treatment for primary CNS lymphoma in older patients. Neurology 46: 435–439.
Glass, J., Gruber, M. L., Cher, L. & Hochberg, F. H. (1994). Pre-irradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome. J Neurosurg 81: 188–195.
Glass, J., Shustik, C., Hochberg, F. H., Cher, L. & Gruber, M. L. (1996). Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine and dexamethasone (MCHOD). J Neurooncol 30: 257–265.
Gonzalez, D. & Schuster-Uitterhoeve, L. J. (1983). Primary non-Hodgkin’s lymphoma of the central nervous system. Results of radiotherapy in 15 cases. Cancer 51: 2048–2052.
Jellinger, K. A. & Paulus, W. (1992). Primary central nervous system lymphoma – an update. J Cancer Res Clin Oncol 119: 7–27.
Kaplan, E. L. & Meier, P. (1958). Non-parametric estimations from incomplete observations. J Am Stat Assoc 53: 457–481.
Kawakami, Y., Tabuchi, K., Ohnishi, K., Asari, S. & Nishimoto, A. (1985). Primary central nervous system lymphoma. J Neurosurg 62: 522–527.
Krogh-Jensen, M., d’Amore, F., Jensen, M. K., Christensen, B. E., Thorling, K., Pedersen, M., Johansen, P., Boesen, A. M. & Andersen, E. (1994). Incidence, clinicopathological features and outcome of primary central nervous system lymphomas. Ann Oncol 5: 349–354.
Lachance, D. H., Brizel, D. M., Gockerman, J. P., Halperin, E. C., Burger, P. C., Boyko, O. B., Brown, M. T. & Schold, S. C. (1994). Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma: short duration response and multifocal intracerebral recurrence preceding radiotherapy. Neurology 44: 1721–1727.
Letendre, L., Banks, P. M., Reese, D. F., Miller, R. H., Scanlon, P. W. & Kiely, J. M. (1982). Primary lymphoma of the central nervous system. Cancer 49: 939–943.
Ling, S. M., Roach, M., Larson, D. A. & Wara, W. M. (1994). Radiotherapy of primary central nervous system lymphoma in patients with and without human immunodeficiency virus. Ten years of treatment experience at the university of California san Francisco. Cancer 73: 2570–2582.
Loeffler, J. S., Ervin, T. J., Mauch, P., Skarin, A., Weinstein, H. J., Canellos, G. & Cassady, J. R. (1985). Primary lymphomas of the central nervous system: patterns of failure and factors that influence survival. J Clin Oncol 3: 490–494.
McLaughlin Velasquez, W. S., Redman, J. R., Yung, W. K. A., Hagermeister, F. B., Rodriguez, M. A. & Cabanillas, F. (1988). Chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin for parenchymal brain lymphoma. J Natl Cancer Inst 80: 1408–1412.
Mendenhall, N. P., Thar, T. L., Agee, O. F., Harty-Golder, B., Ballinger, W. E. & Million, R. R. (1983). Primary lymphoma of the central nervous system: computerized tomography scan characteristics and treatment results for 12 cases. Cancer 52: 1993–2000.
Murray, K., Kun, L. & Cox, J. (1986). Primary malignant lymphoma of the central nervous system. J Neurosurg 65: 600–607.
Nelson, D. F., Martz, K. L., Bonner, H., Nelson, J. S., Newall, J., Kerman, H. D., Thomson, J. W. & Murray, K. J. (1992). Non-Hodgkin’s lymphomas 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 23: 9–17.
Neuwelt, E. A., Goldman, D. L., Dahlborg, S. A., Crossen, J., Ramsey, F., Roman-Goldstein, S., Braziel, R. & Dana, B. (1991). Primary CNS lymphoma treated with osmotic blood–brain barrier disruption: prolonged survival and preservation of cognitive function. J Clin Oncol 9: 1580–1590.
O’Neill, B. P., O’Fallon, J. R., Earle, J. D., Colgan, J. P., Brown, L. D. & Krigel, R. L. (1995). Primary central nervous system non-Hodgkin’s lymphoma: survival advantages with combined initial therapy?. Int J Radiat Oncol Biol Phys 33: 663–673.
Peto, R. & Pike, M. C. (1973). Conservatism of the approximation (O–E)/E in the LogRank test for survival data or tumor incidence data. Biometrics 29: 579–583.
Pollack, I. F., Dade Lunsford, L., Flickinger, J. C. & Dameshek, H. L. (1989). Prognostic factors in the diagnosis and treatment of primary central nervous system lymphoma. Cancer 63: 939–947.
Rampen, F. H. J., van Andel, J. G., Sizoo, W. & van Unnik, J. A. M. (1980). Radiation therapy in primary non-Hodgkin’s lymphomas of the CNS. Eur J Cancer 16: 177–184.
Reni, M., Ferreri, A. J. M., Garancini, M. P. & Villa, E. (1997). Therapeutic management of primary central nervous system lymphoma in immunocompetent patients: results of a critical review of the literature. Ann Oncol 8: 227–234.
Rodriguez, M. A., Cabanillas, F. C., Hagemeister, F. B., McLaughlin, P., Romaguera, J., Swan, F. & Velasquez, W. S. (1995). A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory lymphomas. Ann Oncol 6: 609–611.
Sagerman, R. H., Cassady, J. R. & Chang, C. H. (1967). Radiation therapy for intracranial lymphoma. Radiology 88: 552–554.
Sarazin, M., Ameri, A., Monjour, A., Nibio, A., Poisson, M. & Delattre, J. Y. (1995). Primary central nervous system lymphoma: treatment with chemotherapy and radiotherapy. Eur J Cancer 31A: 2003–2007.
Schultz, C., Scott, C., Sherman, W., Donahue, B., Fields, J., Murray, K., Fisher, B., Abrams, R. & Meis-Kindblom, J. (1996). 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 14: 556–564.
Selch, M. T., Shimizu, K. T., De Salles, A. F., Sutton, C. & Parker, R. G. (1994). Primary central nervous system lymphoma. Am J Clin Oncol 17: 286–293.
Shibamoto, Y., Tsutsui, K., Dodo, Y., Yamabe, H., Shima, N. & Abe, M. (1990). Improved survival rate in primary intracranial lymphoma treated by high-dose radiation and systemic Vincristine–Doxorubicin–Cyclophosphamide–Prednisolone chemotherapy. Cancer 65: 1907–1912.
Soclé, G., Piprot-Chauffat, C., Schlienger, M., Legars, D., Thurel, C., Mikol, J., Ifran, N., Briere, J., Pene, F., Gindrey-Vie, B., Marin, J. L., Desablens, B. & Laugier, A. (1990). Primary lymphoma of the central nervous system: an unresolved therapeutic problem. Cancer 65: 322–326.
Uematsu, M., Kondo, M., Dokiya, T., Oguchi, Y., Toya, S., Torikata, C., Kuribayashi, T. & Hashimoto, S. (1992). Primary non-AIDS related brain lymphoma. Patterns of failure following radiotherapy. Acta Oncol 31: 551–554.
Vakili, S. T., Muller, J., Shidnia, H. & Campbell, R. L. (1986). Primary lymphoma of the central nervous system: a clinicopathologic analysis of 206 cases. J Surg Oncol 33: 95–102.
Velasquez, W. S., McLaughlin, P., Tucker, S., Hagemeister, F. B., Swan, F., Rodriguez, M. A., Romaguera, J., Rubenstein, E. & Cabanillas, F. (1994). ESHAP – an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol 12: 1169–1176.
Watne, K., Scott, H., Hager, B., Lindegaard, M. W., Nome, O., Abrahamsen, A. F. & Hirschberg, H. (1992). Primary malignant lymphoma of the brain. A report of 24 cases from the Norwegian Radium Hospital. Acta Oncol 31: 545–550.
Woodman, R., Shin, K. & Pineo, G. (1985). Primary non-Hodgkin lymphoma of the brain: a review. Medicine 64: 425–430.
Yasunaga, T., Takahashi, M., Uozumi, H., Takada, C., Kawano, S., Baba, Y., Nakamura, I., Sonoda, H. & Matsukado, Y. (1986). Radiation therapy of primary malignant lymphoma of the brain. Acta Radiol Oncol 25: 23–28.
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Reni, M., Ferreri, A. & Villa, E. Second-line treatment for primary central nervous system lymphoma. Br J Cancer 79, 530–534 (1999). https://doi.org/10.1038/sj.bjc.6690083
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DOI: https://doi.org/10.1038/sj.bjc.6690083
Keywords
- primary central nervous system lymphoma
- salvage treatment
- brain neoplasms
- extranodal lymphomas
- non-Hodgkin’s lymphoma
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