Paola Gaviani

CXCL12, CXCR4 and CXCR7 expression in brain metastases.

Brain metastases occur in about 25% of patients who die of cancer. The most common sources of brain metastases in adults are lung, breast, kidney, colorectal cancer and melanoma. The chemokine/receptor system CXCL12/CXCR4 plays a key role in multiple biological functions; among these, homing of neoplastic cells from the primary site to the target and metastasis progression. Recently, an alternative CXCL12 receptor, CXCR7, has been discovered. The aim of our study was to investigate the expression of CXCL12 and its receptors CXCR4 and CXCR7 by immunohistochemistry in 56 patients with metastatic brain disease from different non-CNS primary tumors and evaluate their prognostic relevance as well as that of other patient/treatment-related features on patient survival. CXCL12 showed an expression in tumor cells and in tumor vessels; CXCR7 was expressed by tumor and endothelial cells (both within the tumor and in the adjacent brain tissue), while CXCR4 showed a positivity in all samples with a nuclear pattern. Among the investigated immunohistochemical parameters, only CXCL12 expression in tumor endothelial cells showed a statistically significant correlation with shorter survival (p=0.04 log-rank), perhaps identifying more aggressive tumors. Thus, this is the first study evaluating at the same time the expression of CXCL12 and its two receptors in a cohort of brain metastases.

Intrathecal synthesis of tumor markers is a highly sensitive test in the diagnosis of leptomeningeal metastasis from solid cancers

Abstract Background: Identification of neoplastic cells in cerebrospinal fluid (CSF) by cytological analysis is the key diagnostic feature of leptomeningeal metastasis (LM). Because of the lack of sensitivity of this test, considerable efforts have been made to identify alternative diagnostic markers. Data from the literature suggest that measurement of tumor markers (TM) in CSF may be helpful for improving the diagnosis. Methods: We analyzed the concentrations of the TM carcinoembryonic antigen (CEA), CA15.3, CA125 and CA19.9 in both CSF and serum from 18 patients with neoplastic meningitis diagnosed by CSF cytology. We also performed these same measurements in 50 patients affected by other neurological diseases (OND) in order to evaluate putative intrathecal synthesis. In addition, CSF and serum concentrations of the proangiogenic factor VEGF (vascular endothelial growth factor) were evaluated. Results: All LM patients showed intrathecal synthesis for at least one TM. In one patient, a negative CSF cytology after treatment paralleled normalization of tumor marker synthesis. None of the OND patients displayed intrathecal TM synthesis. The VEGF Index (CSF/serum VEGF relative to CSF/serum albumin ratios) was significantly higher in LM patients compared with the control group. However, significant overlap between LM patients and values seen in those with OND was observed. Conclusions: Evaluation of intrathecal TM synthesis is a specific, sensitive, reliable, and reproducible diagnostic tool, and is useful to support diagnosis of carcinomatous meningitis. Clin Chem Lab Med 2009;47:874–9.

Combined chemotherapy with temozolomide and fotemustine in recurrent glioblastoma patients

Both temozolomide (TMZ) and fotemustine (FTM) are considered to be active agents in recurrent glioblastoma. The objective of this study is to assess the efficacy and toxicity profile of a sequential combination of TMZ and FTM in recurrent glioblastoma after standard treatment with TMZ and radiotherapy. The rationale for evaluating this regimen was, in part, the single-agent activity of both agents against recurrent glioblastoma. Furthermore, temozolomide seems to reduce O6-alkylguanine DNA alkyltransferase (AGAT) activity in vitro, suggesting that temozolomide might enhance the antitumor activity of fotemustine by reducing AGAT activity [1].

Acute late-onset encephalopathy after radiotherapy: an unusual life-threatening complication.

Unusual late-onset complications of brain irradiation, characterized by reversible neurologic focal signs, seizures, and MRI alterations, have recently been reported and classified as stroke-like migraine attacks after radiation therapy (SMART)1 and peri-ictal pseudoprogression (PIPG).2

Erratum: Salvage chemotherapy with procarbazine and fotemustine combination in the treatment of temozolomide treated recurrent glioblastoma patients (J Neurooncol (2008) vol. 87 (143-151) (10.1007/ s11060-007-9427-y))

Whole group of 54 recurrent glioblastoma patients 19.3 (13.7–24.4) 26.7 (10.6–42.8) II line chemotherapy: 31 patients treated at first recurrence-progression 19.7 (13.7–25.2) 17.1 (0–34.3) Reoperated 19.7 (13.6–26.1) ne Non-reoperated 16.7 (6.8–26.5) 42.8 (8.8–77) III line chemotherapy: 23 patients treated at second recurrence-progression 19.3 (6.8–32.1) 45.8 (16.6–75) Reoperated 25.7 (13.3–38.6) 50.9 (19.1–82.7) Non-reoperated ne ne