Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. Medicine, http://dx.doi.org/10.1056/NEJMoa1308345 New England Journal ofAccess to the published version may require subscription. N.B. When citing this work, cite the original published paper. Permanent link to this version:http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-89503T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med 370;8 nejm

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Background. We conducted a nonrandomized international study for intracranial germinoma that compared chemotherapy followed by local radiotherapy with reduced-dose craniospinal irradiation (CSI) alone, to determine whether the combined treatment regimen produced equivalent outcome and avoided irradiation beyond the primary tumor site(s). Methods. Patients with localized germinoma received either CSI or 2 courses of carboplatin and etoposide alternating with etoposide and ifosfamide, followed by local radiotherapy. Metastatic patients received CSI with focal boosts to primary tumor and metastatic sites, with the option to be preceded with chemotherapy. Results. Patients with localized germinoma (n ¼ 190) received either CSI alone (n ¼ 125) or combined therapy (n ¼ 65), demonstrating no differences in 5-year event-free or overall survival, but a difference in progression-free survival (0.97 + 0.02 vs 0.88 + 0.04; P ¼ .04). Seven of 65 patients receiving combined treatment experienced relapse (6 with ventricular recurrence outside the primary radiotherapy field), and only 4 of 125 patients treated with CSI alone experienced relapse (all at the primary tumor site). Metastatic patients (n ¼ 45) had 0.98 + 0.023 event-free and overall survival. Conclusions. Localized germinoma can be treated with reduced dose CSI alone or with chemotherapy and reduced-field radiotherapy. The pattern of relapse suggests inclusion of ventricles in the radiation field. G erminomas contribute to about 60% of all intracranial germ cell tumors located in the pineal gland, suprasellar region, basal ganglia, and hypothalamus.1 Intracranial germinomas are highly radiosensitive, with a tendency to spread via cerebrospinal fluid (CSF), and systemic craniospinal radiation therapy has been the standard treatment for many decades.2,3 With this treatment approach, the majority of patients have been cured. 4 Concerns have long been raised about the potential adverse effects of radiotherapy.4 -6 Therefore, other treatment approaches were introduced to evaluate craniospinal irradiation alone, but with reduced doses, compared with previous practice, or chemotherapy either in combination with radiotherapy or alone. 7,8 In the German MAKEI 89 trial, 30 Gy were applied to the craniospinal axis (CSI) with an additional tumor boost of 15 Gy. 9 With this regimen, 88% of the patients remained relapse-free at 5 years. In 1990, the French Society of Paediatric Oncology initiated a trial using chemotherapy and local field radiotherapy in localized germinomas with favorable results. 10 In 1998, Matsutani et al 11,12 reported excellent survival for germinomas treated with surgery, followed by extended field or whole brain radiotherapy. Patients who received chemotherapy before reduced radiotherapy (30 Gy) were all alive at a median follow-up of 4.3 years. Aoyama et al 13 presented promising excellent results in a second Japanese series including 16 germinomas treated with surgery, followed by chemotherapy and low-dose involved-field radiotherapy. Approaches using c...