Biomedical subjects

Matthew A Spear

Publications and source records attributed to Matthew A Spear.

3 recordsLinked to original sources

PubMed2006

Focal radiation therapy of brain metastases after complete surgical resection.

Brain metastases are a frequent occurrence in cancer patients and result in significant morbidity and mortality. The three main treatments for brain metastases include surgery, radiation, and/or chemotherapy, alone or in combination. After resection alone, local recurrence rates are high. Whole brain radiation therapy can decrease the probability of recurrence; however, this has some disadvantages. Focal radiation therapy (FRT) may provide many of the same benefits without some of these disadvantages. In this study, we retrospectively analyzed patients with single brain metastases treated with FRT after surgery. Doses ranged from 14 Gy as single dose stereotactic radiosurgery (SRS) to 54 Gy in 27 2-Gy fractions as conformal fractionated radiotherapy. Four of the seven patients had a same-site recurrence, with an average time to recurrence of 115.5 d. Median dose in the patients that had same-site recurrence was 42 Gy. One of these patients is currently living. Two patients did not have recurrence, and one patient had a recurrence at a different site within the brain. The low rate of out-of-field recurrences during the patients life indicates focal radiation may be a reasonable therapeutic alternative. Given the number of patients with same-site recurrences, wide field margins around the tumor volume or higher radiation doses than those typically used in palliative regimens may be useful in post-excisional FRT. Additionally, we found that a longer delay in the initiation of FRT after initial diagnosis may result in a decreased time to same-site recurrence. However, further studies are warranted given the small number of patients in this study.

Adult↗

PubMed2005

Temozolomide and radiation for aggressive pediatric central nervous system malignancies.

This study describes the outcomes of children treated with combinations of temozolomide and radiation therapy for various aggressive central nervous system malignancies. Their age at diagnosis ranged from 1 to 15 years. Patients with focal disease were treated with concomitant temozolomide (daily 75 mg/m) and three-dimensional conformal radiotherapy in a dose that ranged from 50 to 54 Gy, followed by temozolomide (200 mg/m/d x 5 days/month in three patients, 150 mg/m x 5 days/ month in one patient). Patients with disseminated disease were treated with craniospinal radiation (39.6 Gy) before conformal boost. One patient received temozolomide (200 mg/m x 5 days/month) before craniospinal radiation, and one patient received temozolomide (daily 95 mg/m) concomitant with craniospinal radiation and a radiosurgical boost, followed by temozolomide (200 mg/m x 5 days/month). Three patients achieved a partial response during treatment, with two of these patients dying of progressive disease after treatment. One patient has no evidence of disease. Three patients achieved stable disease, with one of these patients dying of progressive disease after treatment. Toxicities observed included low-grade neutropenia, thrombocytopenia, and lymphopenia. The combination of temozolomide and radiotherapy appears to be well tolerated in a variety of treatment schemas for aggressive pediatric central nervous system malignancies. This information is of particular use in designing future studies, given the recent positive results in a randomized study examining the use of temozolomide concomitant with radiation in the treatment of adult glioblastoma.

Adolescent↗

PubMed2003

HSV-1 amplicon peptide display vector.

There are significant uses for expressing foreign peptide epitopes in viral surface attachment proteins in terms of investigating viral targeting, biology, and immunology. HSV-1 attachment, followed by fusion and entry, is mediated in large part by the binding of viral surface glycoproteins to cell surface receptors, primarily through heparan sulfate (HS) glycosaminoglycan residues. We constructed a HSV-1 amplicon plasmid (pCONGA) carrying the gC primary attachment protein gene with unique restriction sites flanking the HS binding domain (HSBD) (residues 33-176) to allow rapid, high efficiency substitution with foreign peptide domains. To test this system, a His tag with an additional unique restriction site (for selection and assay digests) was recombined into the pCONGA HSBD site to create pCONGAH. Infection of pCONGAH transfected Vero cells with HSV-1 helper virus (gCdelta2-3 or hrR3) produced His-modified gC as demonstrated by western blot analysis with co-localization of anti-gC and anti-His tag antibodies to a protein of appropriate molecular weight (50 kd). As CONGA and CONGAH amplicons carry a GFP transgene and the gCdelta2-3 and hrR3 viruses carry a lacZ transgene, vector stocks produced from 1 x 10(5) Vero cells could be titered for competent vector on cell monolayers and were demonstrated to contain 2 x 10(5) amplicon vector transducing units (t.u.)/ml and 1 x 10(7) virus t.u./ml. As the amplicon plasmids also contain the neomycin resistance gene (neo(r)), long term vector producer cell lines were created using G418 selection. This amplicon system provides means to rapidly and efficiently generate HSV-1 amplicon and viral vector expressing surface attachment proteins modified with different peptide epitopes for investigational and therapeutic uses, with the advantages of an amplicon plasmid that can be used with interchangeable helper virus vectors, is designed specifically for easy manipulation, and carries GFP and neo(r) transgenes for marker and selection functions.

Animals↗