Objectives: In this study, we analyzed the prognostic value of different MRI progression patterns for survival in patients with recurrent malignant glioma treated with the vascular endothelial growth factor antibody bevacizumab. Patients and Methods: Twenty-six adult patients with recurrent malignant glioma treated with bevacizumab or bevacizumab/irinotecan were retrospectively analyzed for the development of contrast-enhanced (T1-weighted MRI) and T2/FLAIR lesions. According to the progression pattern, patients were divided into 3 subgroups: (1) patients with primarily progressive contrast-enhanced lesions in the first MRI after initiation of therapy (‘primary PD group'); (2) patients with stable or regressive enhanced lesions but progressive FLAIR lesions (‘FLAIR-only PD group'), and (3) patients with stable or regressive contrast-enhanced T1 and FLAIR lesions (‘no PD group'). Results: Overall survival (OS) in the 6 patients in the FLAIR-only PD group was not significantly different from the 11 patients in the no PD group (median 311 vs. 254 days, respectively). In contrast, survival in the FLAIR-only PD group was significantly better (p = 0.025) than in the primary PD group. Conclusion: FLAIR-only progression is not an independent prognostic factor negatively influencing OS in recurrent glioblastoma treated with bevacizumab and should not lead to discontinuation of bevacizumab therapy.

Brain metastasis is one of the most common and devastating complications of melanoma with a median survival (mOS) of four months [1]. Patients with leptomeningeal metastasis, i.e. leptomeningeal melanomatosis (LM), survive with an even shorter median of 10 weeks [2]. Treatment of LM remains palliative with no standard of care to date. In LM, the use of radiation therapy is common, in part but not exclusively due to the fact that parenchymal brain metastases are present in about 50% of patients. The urgent need for systemic treatment is supported by the fact that the majority of patients also have visceral and other systemic metastases [2]. Intrathecal therapy (IT) may be moderately effective since IT is a positive prognostic factor in a large retrospective series including patients mainly treated with methotrexate and interleukin-2 [2]. There are so far no data on the intrathecal use of liposomal cytarabine in LM. In comparison to MTX, liposomal cytarabine has the advantages to be applicable with a longer interval of 14 days and to be as effective upon lumbar injection as upon instillation through an intraventricular reservoir [3]. Thus, intrathecal liposomal cytarabine appears interesting to be explored in conjunction with radiotherapy and systemic chemotherapy. We describe the case of a 50-year-old male, Karnofsky Performance Status 80% who was diagnosed with melanoma of the trunk at level of lumbar vertebral body 2 in November 2003. The patient received multiple therapies for systemic manifestations (local excision, radiotherapy, interferon 2b, cisplatin, carmustin, DTIC, peptide vaccination) of thoracic soft tissue, lung, and the adrenal gland. Retrosternal lymphonodal metastasis was treated with seed-implantation. In January 2008, he presented to our department with headache, vertigo and lumbar radicular pain. Magnetic resonance imaging (MRI) of the whole neuroaxis revealed cerebral metastases of the occipital lobe and next to third ventricle and widespread intraventricular lesions (Figure 1a and c) and affection of the conus medullaris (at level of lumbar vertebral body 3) and lumbar nerve roots. Initial cytological analysis revealed normal cell count, but elevated protein (727 mg/l) and lactate (2.63 mmol/l) levels in the cranial spinal fl uid (CSF). Neuropathologic analysis identifi ed melanoma cells. The patient received radiation therapy of the lumbar vertebrae and spinal cord (lumbar vertebral bodies 2 – 4 with 10 3 Gy), whole brain radiation with (20  2 Gy) combined with temozolomide (TMZ, 75 mg/m 2 ) and an additional stereotactic boost of the occipital metastasis up to a local dose of 50 Gy. The radiochemotherapy was followed by eight cycles of adjuvant TMZ (200 mg/m 2 on 5 of 28 days) and 22 cycles of intrathecal treatment with DepoCyte (50 mg biweekly). The Acta Oncologica, 2011; 50: 1260–1262

OBJECTIVE:The NOA-05 multicenter trial was performed to analyze the efficacy of primary chemotherapy with procarbazine and lomustine (PC) in patients with gliomatosis cerebri (GC) and to define clinical, imaging, and molecular factors influencing outcome.METHODS:Thirty-five patients with previously untreated GC were treated with up to six 56-day courses of 110mg/m(2) lomustine on day 1 and 60mg/m(2) procarbazine on days 8 to 21. The primary endpoint was the rate of patients without therapy failure (defined as progressive disease, death from any cause, or termination of PC therapy before the end of course 4) at 8 months after the beginning of PC chemotherapy.RESULTS:The failure-free survival rate at 8 months was 50.3%. Median progression-free survival was 14 months. At progression, 12 patients received salvage radiotherapy. Median overall survival was 30 months. Multivariate analysis revealed isocitrate dehydrogenase 1 (IDH1) gene mutation (hazard ratio [HR], 0.11; 95% confidence interval [CI], 0.02-0.58) and initial presentation without a bilateral symmetrical infiltration pattern on magnetic resonance imaging (HR 0.07, 95%CI 0.01-0.54) as independent prognostic factors associated with prolonged survival. IDH1 mutation was significantly associated with MGMT promoter methylation and an oligodendroglial tumor component.INTERPRETATION:PC chemotherapy is effective in GC. With the NOA-05 trial being the first prospective multicenter trial in GC, PC chemotherapy can be regarded as a promising option for the primary therapy of these tumors.

Background: In a previous trial (NOA-01), the combination of nimustine and teniposide showed efficacy in previously untreated glioblastoma (GBM). After establishing temozolomide as standard first-line therapy in GBM patients, the nimustine (ACNU)/teniposide (VM-26) combination has been employed as salvage chemotherapy for recurrent GBM. However, data on the toxicity and efficacy of this regimen in recurrent GBM are lacking. Patients and Methods: In two neurooncological centers, all patients with recurrent GBM treated with nimustine (90 mg/m2, day 1/42) and teniposide (45–70 mg/m2, days 1–3/42) were analyzed retrospectively for progression-free survival (PFS), overall survival (OS) and toxicity. Results: Thirty-five patients (median age 51 years, range 25–71 years) were identified. Six months after chemotherapy initiation, PFS was 29% and the median OS 6 months; 23% of patients were alive ≥1 year after initiation of nimustine-teniposide chemotherapy. Grade 4 hematotoxicity was observed in 12 of 35 patients (34%) and in 14 of 83 evaluable chemotherapy courses (17%). Conclusions: The benefit of the nimustine-teniposide combination is moderate in patients with recurrent GBM. The data support the efficacy of the nimustine-teniposide chemotherapy, but the rate of high-grade hematotoxicity is increased.

Objective: This series explores temozolomide monotherapy in elderly patients with primary CNS lymphoma (PCNSL) and severe comorbidities.

X. Cheng, Houston, USA A. Chicca, Pisa, Italy C. Chiesa, Rome, Italy K. Chikamatsu, Chuo, Japan C.H. Cho, Pokfulam, China E.C. Echegi, Belize, UK C. Chung, Nashville, USA J. Ciccolini, Marseille, France E.C. Citak, Besevler, Ankara, Turkey P. Comella, Naples, Italy D. Czock, Ulm, Germany M.E. da Silva Barros, Minas Gerais, Brazil A. Dalhoff, Wuppertal, Germany G. D‘Amico, Monza, Italy P.M. De Angelis, Oslo, Norway U. De Giorgi, Lecce, Italy M.P. Decatris, Nicosia, Cyprus P. Demoly, Montpellier, France Y. Diao, Quanzhou, China C. Díaz, San José, Costa Rica L. Dijkshoorn, Leiden, The Netherlands R. Dollner, Oslo, Norway P.M. Dougherty, Houston, USA H.F. Duang, Beijing, China J. Dufer, Reims, France B. Dvorchik, Tampa, USA G. Dy, Buffalo, USA T.H. Ecke, Bad Saarow, Germany F. Eckel, Munich, Germany P.H. Edelstein, Philadelphia, USA U. Edet, Kuwait, Kuwait H. Egusa, Suita-city, Japan L.S. Einbond, New York, USA F. El Karak, Lyon, France Z. El-Sayed, Mansoura, Egypt R.J. Epstein, Pokfulam, China H. Erdogan, Tokat, Turkey J.E. Sollid, Tromso, Norway M. Erman, Ankara, Turkey A. Falcone, Livorno, Italy J. Fang, Kumamoto, Japan D. Farge, Paris, France J. Feliu, Madrid, Spain Z. Fishelson, Tel Aviv, Greece U. Flückiger, Basel, Switzerland N. Frimodt-Moller, Copenhagen, Denmark S.M. Gadgeel, Detroit, USA J. Abraham, Baltimore, USA D. Adam, Munich, Germany M.U. Adikwu, Abuja, Nigeria R. Agarwal, Denver, USA J.A. Ainsa, Zaragoza, Spain S. Aksoy, Ankara, Turkey C. Andreadis, Thessaloniki, Greece N. Androulakis, Heraklion, Greece G. Angarano, Foggia, Italy I. Aquerreta, Pamplona, Spain M. Auerbach, Baltimore, USA A. Avilés, Mexico City, Mexico F. Aykan, Capa, Turkey E. Bajetta, Milan, Italy A. Bamias, Athens, Greece G. Baracco, Miami, USA R.R. Baral, Kolkata, India C. Barone, Rome, Italy R. Bartoletti, Florence, Italy R. Bauer, Graz, Austria R. Bayston, Nottingham, UK C.M. Bebear, Bordeaux, France M. Benvenuto, Lexington, USA J.R. Berenson, Los Angeles, USA R. Bianco, Naples, Italy S. Bilaceroglu, Izmir, Turkey S. Boeck, Munich, Germany N. Boku, Kashiwa, Japan C. Bolenz, Mannheim, Germany W. Bonnez, Rochester, USA S. Bonora, Turin, Italy R. Borrás, Valencia, Spain G. Boz, Aviano, Italy C. Braconi, Ancona, Italy G.G. Brandi, Bologna, Italy R.A. Brodsky, Baltimore, USA D.R. Budhi, Chandigarh, India J. Bulitta, Nuremberg-Heroldsberg, Germany J.P. Burgués, Palma de Mallorca, Spain M. Caira, Rondebosch, South Africa N. Callizot, Illkirch, France M. Caraglia, Naples, Italy C. Carlo-Stella, Milan, Italy V. Catalano, Pesaro, Italy S. Cavalcanti, Aracaju, Brazil A. Chao, Tao-Yuan, Taiwan S.F. Chen, Hong Kong, China

Background: Gliomatosis cerebri (GC) is a diffuse infiltrating glial tumor with involvement of at least 3 cerebral lobes. There are only few data on the efficacy of initial chemotherapy in patients with GC. Patients and Methods: In 3 neurooncological centers, patients with newly diagnosed GC who had received procarbazine (60 mg/m2, days 8–21/56) and CCNU (110 mg/m2, day 1/56) chemotherapy (PC) as initial treatment were analyzed for progression-free survival, overall survival and toxicity. Results: Twelve patients (median age 46 years, range 27–72) were analyzed. The median progression-free survival and the median overall survival were 16 and 37 months. Grade 3 or 4 hematotoxicity was observed in 3 of 12 patients (25%). Conclusions: These data support the efficacy of PC chemotherapy in newly diagnosed GC. Initial PC chemotherapy should be considered as a treatment option and evaluated in larger clinical trials.

13018 Background: There is no established standard chemotherapy for recurrent glioblastoma (GBM). In a previous trial (NOA-01), the combination of nimustine and teniposide showed efficacy in previously untreated GBM. After temozolomide has been established as the standard for primary therapy of GBM, nimustin and teniposide is now been used as a second or third line chemotherapy for recurrent GBM. However, there are no data on toxicity and efficacy of this regimen in recurrent GBM. Methods: In two neurooncological centers, all patients with recurrent glioblastoma who had received nimustine (90 mg/m2, day 1/42) and tenoposide (45–60 mg/m2, days 1–3/42) chemotherapy were analyzed retrospectively for progression-free survival, overall survival and toxicity. Results: Thirty-five patients, median age 51 years (range 25–71), all of them pretreated with temozolomide were identified. The rate of progression-free patients at 6 months after initiation of therapy was 29%. The median overall survival after initiation of nimustine/teniposide was 7 months and 14% of patients survived 1 year or longer after diagnosis of recurrent disease. Grade 4 hematotoxicity according to the common terminology criteria for adverse events (CTCAE v 3.0) was observed in 12/35 patients (34%) and in 12/83 chemotherapy cycles (14%). No high-grade non-hematological toxicity was observed. Conclusions: These data support the efficacy of nimustine and teniposide combination chemotherapy in recurrent GBM. Nimustine and teniposide combination therapy is associated with a comparably high rate of high-grade hematotoxicity. No significant financial relationships to disclose.

A.B. Benson, Chicago, Ill. A. Chang, Singapore A.L. Cheng, Taipei J.F. Cleary, Madison, Wisc. M.S. Ernstoff , Lebanon, N.H. J.-J. Grau, Barcelona D.F. Hayes, Ann Arbor, Mich. C.S. Johnson, Buff alo, N.Y. M.J. Kelley, Durham, N.C. P.J. Loehrer, Indianapolis, Ind. J.R. Marshall, Buff alo, N.Y. S. Monfardini, Padua R. Nagler, Haifa R. Ohno, Nagoya B. Pestalozzi, Zurich H.M. Pinedo, Amsterdam D. Raghavan, Cleveland, Ohio E. Repasky, Buff alo, N.Y. C.N. Sternberg, Rome R. Stupp, Lausanne M.S. Tallman, Chicago, Ill. S. Tanaka, Hiroshima M. Tian, Houston, Tex. D.L. Trump, Buff alo, N.Y. T. Wiegel, Ulm W. Yasui, Hiroshima H. Zhang, Hangzhou City Editor-in-Chief