Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma

Department of Radiation Oncology, New York University Langone Medical Center, 566 First Avenue, New York, NY 10014, USA.
Journal of Neuro-Oncology (Impact Factor: 3.07). 03/2011; 102(1):121-7. DOI: 10.1007/s11060-010-0301-y
Source: PubMed


Prognosis of diffuse intrinsic pontine gliomas (DIPGs) remains poor. Failure has been predominantly local, with leptomeningeal dissemination (LD) occurring in 4-33% of patients in pre-MRI era series. Routine craniospinal imaging after initial treatment may reveal other relapse patterns relapse. Sixteen consecutive pediatric patients with DIPG treated between 2006 and 2009 were retrospectively reviewed. Treatment regimens, recurrence patterns, survival, and pathologic diagnosis were recorded. Fourteen patients received involved-field radiotherapy to 54 Gy, and two patients received craniospinal irradiation for LD at presentation. Neuraxis MRI was performed at diagnosis and at 4 month intervals following radiotherapy. Fifteen patients have had progression of disease (median progression-free survival 5.0 ± 1.2 months), and 13 patients have died (median survival 9.0 ± 1.4 months). Local failure occurred in 12 patients (75%). LD occurred in nine patients (56%). LD was present at diagnosis in three patients, after initial staging and treatment in six patients, and during autopsy in two patients. Median overall survival was 12.0 ± 3.3 months without LD and 8.0 ± 2.1 months with LD (P = 0.059, log rank test). Median progression-free survival was 9.5 ± 3.9 months without LD and 3.0 ± 2.1 months with LD (P = 0.012, log rank test). The high incidence of LD probably reflects liberal use of spine MRI surveillance. All patients should undergo routine craniospinal imaging at diagnosis and follow-up. Central nervous system prophylaxis should be considered in future clinical trials.

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Available from: Matthias Karajannis, May 19, 2015
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    • "Children <3 years old at diagnosis can have a prolonged survival, living years after their diagnosis, often with temporary disease stabilization (Broniscer et al., 2008; Jackson et al., 2013; Thompson & Kosnik, 2005). While primary dissemination of DIPGs is rare (Benesch, Wagner, Berthold, & Wolff, 2005), dissemination of DIPGs at recurrence is common (Gururangan et al., 2006; Sethi et al., 2011). The pattern of disease spread at progression is not prognostic (Wagner et al., 2006). "
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    ABSTRACT: Diffuse intrinsic pontine gliomas (DIPGs) are a fairly common pediatric brain tumor, and children with these tumors have a dismal prognosis. They generally are diagnosed within the first decade of life, and due to their location within the pons, these tumors are not surgically resectable. The median survival for children with DIPGs is less than 1 year, in spite of decades of clinical trial development of unique approaches to radiation therapy and chemotherapy. Novel therapies are under investigation for these deadly tumors. As clinicians and researchers make a concerted effort to obtain tumor tissue, the molecular signals of these tumors are being investigated in an attempt to uncover targetable therapies for DIPGs. In addition, direct application of chemotherapies into the tumor (convection-enhanced delivery) is being investigated as a novel delivery system for treatment of DIPGs. Overall, DIPGs require creative thinking and a disciplined approach for development of a therapy that can improve the prognosis for these unfortunate children.
    Advances in Cancer Research 06/2014; 121:235-59. DOI:10.1016/B978-0-12-800249-0.00006-8 · 5.32 Impact Factor
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    • "Local relapse has been extensively documented in many series as the primary mode of failure in DIPG (21–23), that is why we did not undergo in our study routine neuraxis imaging after initial therapy and spinal imaging were reserved for symptomatic patients. However; study done by Sethi et al. (24) recommended that all DIPG patients undergo spine and brain MRI scans at the time of initial presentation and at regular intervals during follow up as high incidence of leptomeningeal disease was observed at diagnosis and recurrence . In their study, patients with leptomeningeal involvement had shorter overall survival compared to patients with localized disease. "
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    ABSTRACT: Background Pediatric diffuse intrinsic pontine glioma (DIPG) remains dismal regardless the new therapeutic and technical advances. Objective To investigate the value of magnetic resonance imaging (MRI) in predicting DIPG prognosis. Patients and methods Twenty-five DIPG patients with 95 (initial and post radiotherapy) MR examinations were studied. Hydrocephalus was detected in 6 cases (24%), basilar artery encasement in 20 (80%), ill defined border in 16 (64%), perilesional edema in 2 cases (8%) and none showed leptomeningeal spread. Conformal 3-dimensional radiotherapy (39 Gy/13 fractions or 54 Gy/30 fractions) was applied. Results The median overall survival (MOS) was 9.3 months (95% CI: 7.9–10.8) and the one year overall survival was 18 ± 8.9%. Post radiation MRI performed 3–6 months after treatment showed regression in 8 cases (32%), stationary course in 5 (20%) and progression in 12 cases (48%). The MOS was higher in children whose MRI showed regression (10.0, CI: 6.3–13.7) than those with radiological progression (8.0, CI: 5.9–10.1 months) or stationary course (7.0, CI: 4.9–9.1). However; these differences did not rank to the level of significance. There was no statistical association of tumor size (p = 0.907), presence of hemorrhage (p = 0.314), or surrounding edema (p = 0.263); entrapment of the basilar artery (p = 0.782); pattern of enhancement (p = 0.851); and hydrocephalus (p = 0.354) with the length of the overall survival. Conclusions Though MRI is the mainstay for the diagnosis of DIPG, yet its prognostic value is limited. New MR techniques as MR spectroscopy and diffusion tensor imaging should be evaluated as additional tools for prognostic evaluation of DIPG.
    Egyptian Journal of Radiology and Nuclear Medicine 12/2013; 44(4):871–878. DOI:10.1016/j.ejrnm.2013.09.007
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    • "This may be an underestimate, as spinal disease is not always investigated in asymptomatic patients. Significantly higher numbers of patients (up to 56%) have evidence of spinal metastases or leptomeningeal dissemination at the time of recurrence or autopsy (Donahue et al., 1998; Gururangan et al., 2006; Sethi et al., 2011). "
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    ABSTRACT: Diffuse intrinsic pontine gliomas (DIPGs) are amongst the most challenging tumors to treat. Surgery is not an option, the effects of radiation therapy are temporary, and no chemotherapeutic agent has demonstrated significant efficacy. Numerous clinical trials of new agents and novel therapeutic approaches have been performed over the course of several decades in efforts to improve the outcome of children with DIPG, yet without success. The diagnosis of DIPG is based on radiographic findings in the setting of a typical clinical presentation, and tissue is not routinely obtained as the standard of care. The paradigm for treating children with these tumors has been based on that for supratentorial high-grade gliomas in adults as the biology of these lesions were presumed to be similar. However, recent pivotal studies demonstrate that DIPGs appear to be their own entity. Simply identifying this fact releases a number of constraints and opens opportunities for biologic investigation of these lesions, setting the stage to move forward in identifying DIPG-specific treatments. This review will summarize the current state of knowledge of DIPG, discuss obstacles to therapy, and summarize results of recent biologic studies.
    Frontiers in Oncology 12/2012; 2:205. DOI:10.3389/fonc.2012.00205
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