Phase I study of hyperfractionated whole brain irradiation (HWBI) in the treatment of primary cerebral lymphoma

The poor prognosis for primary cerebral lymphoma following conventional radiation therapy has generally been attributed to high local relapse rates despite initial local control. Hyperfractionated radiation therapy may improve the therapeutic ratio by allowing higher total radiation doses to be prescribed without exceeding the radiation tolerance of the central nervous system (CNS). Eight patients entered a study of hyperfractionated whole brain irradiation (HWBI) between October 1988 and May 1991. The prescribed dose was 64.8 Gy in 54 fractions over 5.5 weeks. All patients were followed clinically and with computed tomographic scanning. Additional investigations to discriminate between lymphoma recurrence and radionecrosis included magnetic resonance imaging (MRI), thallium-201 single photon emission computed tomography (SPECT), and immunocytological examination of the cerebrospinal fluid (CSF). A complete remission as seen on CT scan was achieved in all cases. The overall median survival was 102 weeks. Six patients initially deteriorated neurologically without evidence of tumour recurrence. Three patients have died without evidence of recurrence at 18, 62 and 128 weeks. As of 31 May 1992, three patients remain alive, two with radiation brain injury at 147 and 184 weeks. Treatment toxicity prompted study closure in September 1991. The hyperfractionation regimen used is reported by others to be free from significant morbidity. The pathogenesis of cerebral lymphomas (diffuse disease, angiotropism, subependymal involvement) may adversely affect CNS radiation tolerance.