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1.
Clin Cancer Res ; 30(2): 323-333, 2024 01 17.
Article in English | MEDLINE | ID: mdl-38047868

ABSTRACT

PURPOSE: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma. PATIENTS AND METHODS: Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers. RESULTS: Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4-31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months-undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms. CONCLUSIONS: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.


Subject(s)
Chordoma , Lung Neoplasms , Adult , Humans , Pemetrexed/adverse effects , Chordoma/pathology , Pilot Projects , Glutamates/adverse effects , Guanine/therapeutic use , Neoplasm Staging , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Treatment Outcome , Lung Neoplasms/drug therapy
2.
J Neurooncol ; 76(1): 23-30, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16155724

ABSTRACT

The type III variant of the epidermal growth factor receptor (EGFRvIII) mutation is present in 20-25% of patients with glioblastoma multiforme (GBM). EGFRvIII is not expressed in normal tissue and is therefore a suitable candidate antigen for dendritic cell (DC) based immunotherapy of GBM. To identify the antigenic epitope(s) that may serve as targets for EGFRvIII-specific cytotoxic T lymphocytes (CTLs), the peptide sequence of EGFRvIII was screened with two software programs to predict candidate epitopes restricted by the major histocompatibility complex class I subtype HLA-A0201, which is the predominant subtype in most ethnic groups. Three predicted peptides were constructed and loaded to mature human DCs generated from peripheral blood monocytes. Autologous CD8+ T cells were stimulated in vitro with the EGFRvIII peptide-pulsed DCs. One of the three peptides was found to induce EGFRvIII-specific CTLs as demonstrated by IFN-gamma production and cytotoxicity against HLA-A0201+ EGFRvIII transfected U87 glioma cells. These results suggest that vaccination with EGFRvIII peptide-pulsed DCs or adoptive transfer of in vitro elicited EGFRvIII-specific CTLs by EGFRvIII peptide-pulsed DCs are potential approaches to the treatment of glioma patients.


Subject(s)
Brain Neoplasms/immunology , Dendritic Cells/immunology , ErbB Receptors/genetics , Glioma/immunology , Immunotherapy , T-Lymphocytes, Cytotoxic/immunology , Brain Neoplasms/pathology , CD8-Positive T-Lymphocytes , Epitopes , Glioma/pathology , HLA-A Antigens/immunology , HLA-A2 Antigen , Humans , Immunotherapy, Adoptive , Monocytes , Restriction Mapping , Software , Vaccination
3.
Radiographics ; 24(3): 637-55, 2004.
Article in English | MEDLINE | ID: mdl-15143219

ABSTRACT

Computed tomographic (CT) angiography is a well-known tool for detection of intracranial aneurysms and the planning of therapeutic intervention. Despite a wealth of existing studies and an increase in image quality due to use of multisection CT and increasingly sophisticated postprocessing tools such as direct volume rendering, CT angiography has still not replaced digital subtraction angiography as the standard of reference for detection of intracranial aneurysms. One reason may be that CT angiography is still not a uniformly standardized method, particularly with regard to image postprocessing. Several methods for two- and three-dimensional visualization can be used: multiplanar reformation, maximum intensity projection, shaded surface display, and direct volume rendering. Pitfalls of CT angiography include lack of visibility of small arteries, difficulty differentiating the infundibular dilatation at the origin of an artery from an aneurysm, the kissing vessel artifact, demonstration of venous structures that can simulate aneurysms, inability to identify thrombosis and calcification on three-dimensional images, and beam hardening artifacts produced by aneurysm clips. Finally, an algorithm for the safe and useful application of CT angiography in patients with subarachnoid hemorrhage has been developed, which takes into account the varying quality of equipment and software at different imaging centers.


Subject(s)
Aneurysm, Ruptured/diagnostic imaging , Angiography/methods , Image Processing, Computer-Assisted/methods , Intracranial Aneurysm/diagnostic imaging , Tomography, Spiral Computed/methods , Algorithms , Angiography/instrumentation , Angiography/standards , Angiography, Digital Subtraction , Artifacts , Color , Humans , Imaging, Three-Dimensional , Rupture, Spontaneous , Sensitivity and Specificity , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/etiology , Tomography, Spiral Computed/instrumentation , Tomography, Spiral Computed/standards
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