Article

Effect of imaging and catheter characteristics on clinical outcome for patients in the PRECISE study

Department of Neurology, University of San Francisco, 350 Parnassus Ave, Suite 609, San Francisco, CA 94117, USA.
Journal of Neuro-Oncology (Impact Factor: 3.07). 01/2011; 101(2):267-77. DOI: 10.1007/s11060-010-0255-0
Source: PubMed

ABSTRACT

The PRECISE study used convection enhanced delivery (CED) to infuse IL13-PE38QQR in patients with recurrent glioblastoma multiforme (GBM) and compared survival to Gliadel Wafers (GW). The objectives of this retrospective evaluation were to assess: (1) catheter positioning in relation to imaging features and (2) to examine the potential impact of catheter positioning, overall catheter placement and imaging features on long term clinical outcome in the PRECISE study. Catheter positioning and overall catheter placement were scored and used as a surrogate of adequate placement. Imaging studies obtained on day 43 and day 71 after resection were each retrospectively reviewed. Catheter positioning scores, catheter overall placement scores, local tumor control and imaging change scores were reviewed and correlated using Generalized Linear Mixed Models. Cox PH regression analysis was used to examine whether these imaging based variables predicted overall survival (OS) and progression free survival (PFS) after adjusting for age and KPS. Of 180 patients in the CED group, 20 patients did not undergo gross total resection. Of the remaining 160 patients only 53% of patients had fully conforming catheters in respect to overall placement and 51% had adequate catheter positioning scores. Better catheter positioning scores were not correlated with local tumor control (P = 0.61) or imaging change score (P = 0.86). OS and PFS were not correlated with catheter positioning score (OS: P = 0.53; PFS: P = 0.72 respectively), overall placement score (OS: P = 0.55; PFS: P = 0.35) or imaging changes on day 43 MRI (P = 0.88). Catheter positioning scores and overall catheter placement scores were not associated with clinical outcome in this large prospective trial.

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    • "Neuro-oncological clinical trials with CED have evaluated a wide range of potential therapeutic agents, including conventional chemotherapies such as paclitaxel (Lidar et al., 2004), topotecan (Bruce et al., 2011); (Anderson et al., 2013), and nimustine (Saito et al., 2011), targeted toxins including IL13- PE38QRR (Kunwar et al., 2010;Mueller et al., 2011;Sampson et al., 2010) and IL4-PE38 (Rand et al., 2000;Shimamura et al., 2006), TP-38 (Rainov and Heidecke, 2004;Sampson et al., 2005), oligonucleotides (Carpentier et al., 2010), and TGF-2 inhibitors (Bogdahn et al., 2011). Unfortunately, the results of all these trials were rather disappointing, which is largely attributed to poor drug distribution to more peripheral areas of diffuse gliomas and drug reflux, resulting in side effects and subtherapeutic drug concentrations within the tumor target cells (Mueller et al., 2011;Kunwar et al., 2010;Sampson et al., 2010). Another major problem in many of these early clinical studies is the lack of visualization of the distribution of the infused drug and unacceptable device-related adverse events. "
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