Biomedical subjects

Tracy T Batchelor

Publications and source records attributed to Tracy T Batchelor.

26 records · Page 2Linked to original sources

PubMed2004

Age-dependent prognostic effects of genetic alterations in glioblastoma.

PURPOSE: Although the genetic alterations in glioblastoma have been well characterized, reports regarding their prognostic effects have been inconsistent. EXPERIMENTAL DESIGN: In this series of 140 consecutive cases of glioblastoma treated at a single center, we analyzed the frequency, age dependency and prognostic effects of TP53 mutation, CDKN2A/p16 deletion, EGFR amplification, as well as loss of chromosome 1p, chromosome 10q, and chromosome 19q. The complete set of genetic alterations was available on 60 of 140 patients. RESULTS: In this cohort of glioblastoma cases, TP53 mutation was significantly associated with patient age. The prognostic effects of TP53 mutation, EGFR amplification, CDKN2A/p16 alterations, and loss of chromosome 1p were dependent on the age of the patient. CONCLUSIONS: This is the first observation that the prognostic effects of TP53, 1p, and CDKN2A/p16 alterations are dependent on patient age. These observations concerning the interactions of age and genetic changes in glioblastoma suggest that tumorigenic pathways to glioblastoma vary with the age of the patient and that future molecular marker studies should carefully evaluate the potential age-dependent prognostic effects of these biological variables. The inconsistent or negative prognostic effects of molecular markers reported in prior studies of glioblastoma may be because different effects at different ages may have resulted in a cancellation of an overall effect in the entire cohort.

Adolescent↗

PubMed2004

Phase 2 study of weekly irinotecan in adults with recurrent malignant glioma: final report of NABTT 97-11.

The primary objective of this study was to determine the proportion of patients exhibiting a radiographic response in a cohort of patients with recurrent malignant glioma who were treated with irinotecan. Secondary objectives were to determine progression-free survival, overall survival, and toxicity. The trial was terminated after the first 18 patients were enrolled in this multicenter, 2-stage, phase 2 study. Twelve patients received concurrent enzyme-inducing antiepileptic drugs, and 6 did not. Each cycle consisted of a 90-min i.v. infusion of irinotecan every week for 4 consecutive weeks, followed by 2 weeks off. One patient had a complete response, 5 patients had stable disease, 5 patients had radiographic progression, 6 patients were removed from the study because of toxicity, and 1 patient refused further therapy and was removed from the study. The response rate in this study was 6% (1/18), and 28% (5/18) of these patients progressed while receiving irinotecan. Dose-limiting toxicities consisted of diarrhea in 5 patients, neutropenia in 1 patient, infection in 1 patient, and respiratory failure in 1 patient. Irinotecan had minimal efficacy in this cohort of 18 patients with recurrent malignant glioma. Toxicity was significant but similar to that reported in other patient populations.

Adult↗

PubMed2003

Malignant peripheral nerve sheath tumor: the clinical spectrum and outcome of treatment.

Malignant peripheral nerve sheath tumors (MPNST) are derived from Schwann cells or pluripotent cells of the neural crest. Delay of diagnosis is common, especially in lesions affecting proximal parts of the peripheral nervous system. Presented is a series of 54 patients with MPNST seen at a single institution over a 10-year period. In this series, tumor diameter of <5 cm, gross total resection of the tumor, and younger age were favorable prognostic variables.

Humans↗

PubMed2003

Gene expression-based classification of malignant gliomas correlates better with survival than histological classification.

In modern clinical neuro-oncology, histopathological diagnosis affects therapeutic decisions and prognostic estimation more than any other variable. Among high-grade gliomas, histologically classic glioblastomas and anaplastic oligodendrogliomas follow markedly different clinical courses. Unfortunately, many malignant gliomas are diagnostically challenging; these nonclassic lesions are difficult to classify by histological features, generating considerable interobserver variability and limited diagnostic reproducibility. The resulting tentative pathological diagnoses create significant clinical confusion. We investigated whether gene expression profiling, coupled with class prediction methodology, could be used to classify high-grade gliomas in a manner more objective, explicit, and consistent than standard pathology. Microarray analysis was used to determine the expression of approximately 12000 genes in a set of 50 gliomas, 28 glioblastomas and 22 anaplastic oligodendrogliomas. Supervised learning approaches were used to build a two-class prediction model based on a subset of 14 glioblastomas and 7 anaplastic oligodendrogliomas with classic histology. A 20-feature k-nearest neighbor model correctly classified 18 of the 21 classic cases in leave-one-out cross-validation when compared with pathological diagnoses. This model was then used to predict the classification of clinically common, histologically nonclassic samples. When tumors were classified according to pathology, the survival of patients with nonclassic glioblastoma and nonclassic anaplastic oligodendroglioma was not significantly different (P = 0.19). However, class distinctions according to the model were significantly associated with survival outcome (P = 0.05). This class prediction model was capable of classifying high-grade, nonclassic glial tumors objectively and reproducibly. Moreover, the model provided a more accurate predictor of prognosis in these nonclassic lesions than did pathological classification. These data suggest that class prediction models, based on defined molecular profiles, classify diagnostically challenging malignant gliomas in a manner that better correlates with clinical outcome than does standard pathology.

Brain Neoplasms↗

PubMed2003

Leptomeningeal metastases.

LM is an increasingly common neurologic complication of cancer with variable clinical manifestations. Although there are no curative treatments, currently available therapies can preserve neurologic function and potentially improve quality of life. Further research into the mechanisms of leptomeningeal metastasis will elucidate molecular and cellular pathways that may allow identification of potential targets to interrupt this process early or to prevent this complication. Animal models are needed to further define the pathophysiology of LM and to provide an experimental system to test novel treatments [242-245]. There is an urgent need to develop new drug-based or radiation-based treatments for patients with LM. Randomized clinical trials are the appropriate study design to determine the efficacy of new treatments for LM. However, surrogate markers for response must be developed to facilitate the identification of effective regimens. Survival is not the optimal end point for such studies as most patients who develop this complication already have advanced, incurable cancer. Prevention of or delay in neurologic progression is one objective that has been utilized in recent randomized trials in patients with LM, and this end point deserves further attention. Although the development of LM represents a poor prognostic marker in patients with cancer it is important for physicians to recognize the symptoms and signs of the disease and establish the diagnosis as early in the disease course as possible. This may provide an opportunity for effective intervention that can improve quality of life, prevent further neurologic deterioration and, for a subset of patients, improve survival.

Humans↗

PubMed2003

High-dose methotrexate for intraocular lymphoma.

PURPOSE: Intraocular lymphoma (IOL) frequently coexists with primary central nervous system lymphoma(PCNSL). We sought to determine the efficacy of high-dose methotrexate (MTX) alone in patients with IOL. We also sought to determine whether micromolar levels of MTX could be achieved in the aqueous and vitreous humor of the eye after i.v. administration of the drug. EXPERIMENTAL DESIGN: Nine patients with concurrent PCNSL and IOL or isolated IOL were treated with MTX alone. All patients were treated with i.v. 8 g/m(2) MTX. MTX concentrations in serum, aqueous humor, and vitreous humor were obtained in seven of nine patients with IOL and in one additional patient with PCNSL but no evidence of IOL. RESULTS: Micromolar concentrations of MTX were present in both ocular chambers 4 h after completion of the infusion in eight of eight patients. Levels of MTX were lower in the vitreous humor compared with the aqueous humor in five of six patients in whom both chambers were assayed. Initial response of IOL to MTX was demonstrated by seven of nine patients (six complete responses and one partial response), whereas two patients had persistent IOL despite achievement of micromolar concentrations of MTX. In the patients with concurrent PCNSL and IOL, seven of seven had complete responses in the brain after treatment with MTX. Three of seven patients with initial response of IOL experienced relapse in the eye requiring orbital radiation, and four of nine patients had sustained response of IOL to MTX. CONCLUSIONS: A subset of patients with IOL may experience sustained remission when treated with high-dose i.v. MTX alone. Although micromolar MTX concentrations are present in the eye 4 h after infusion, the lower concentration achieved in vitreous humor may contribute to persistence of IOL.

Adult↗

PubMed2003

BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma.

PURPOSE: The purpose of this study was to investigate the histogenetic origin of primary central nervous system lymphoma (PCNSL) with respect to stage of B-cell differentiation and to identify prognostic markers in a cohort of patients with PCNSL treated with i.v. high-dose methotrexate therapy. EXPERIMENTAL DESIGN: This study included 33 patients with PCNSL treated with high-dose i.v. methotrexate at the Massachusetts General Hospital for whom archival tumor tissue was available. All 33 patients tested negative for HIV. The lymphomas were morphologically subclassified according to the Kiel system, as modified in the WHO classification. Immunohistochemistry for the following antigens was performed: BCL-6; BCL-2; MUM1; CD10; vs38c; CD138; CD44; p16; and p53. Fluorescence in situ hybridization and multiplex PCR for CDKN2A/p16 were also performed. RESULTS: There were 17 women and 16 men enrolled, with a median age of 60 years. All tumors were diffuse large B-cell lymphomas. Of the 23 cases that could be subclassified, 22 were centroblastic, and 1 was immunoblastic. Twenty-six of 33 tumors were BCL-6+, 6 of 32 tumors were CD10+, 27 of 29 tumors were BCL-2+, 31 of 32 tumors were MUM1+, 11 of 31 tumors were CD44+, 4 of 33 tumors were vs38c+, and 0 of 32 tumors were CD138+. There were 18 of 32 (56%) complete responses and 8 of 32 (25%) partial responses to methotrexate, whereas 6 of 33 (18%) progressed during treatment. Ten patients died of disease. Expression of BCL-6 was significantly associated with longer overall survival (P = 0.002; median survival, 101 versus 14.7 months, with approximately 95% lower confidence limits of 41.7 and 8.8 months, respectively). CONCLUSIONS: In this group of 33 patients with PCNSL, expression of BCL-6 was significantly associated with longer overall survival. BCL-6 warrants further investigation as a potentially important prognostic marker in this disease.

Adult↗

PubMed2002

Primary nervous system lymphoma.

Primary nervous system lymphoma (PNSL) is a rare type of non-Hodgkin's lymphoma confined to the nervous system. Although significant progress has been made in the treatment of PNSL over the past decade, patients with this disease are rarely cured. Until recently, whole brain radiation therapy has been the standard treatment for PNSL. However, whole brain radiation therapy is associated with a high relapse rate and late neurotoxicity after chemotherapy, especially in patients older than 60 years of age. Methotrexate-based chemotherapy has become the standard approach to treat patients with newly diagnosed PNSL. Ongoing research efforts are focused on identifying chemotherapeutic agents with good antilymphoma activity that penetrate the blood-brain barrier. The roles of intrathecal chemotherapy and blood-brain barrier disruption are not fully defined. Given the rarity of this tumor, patients with PNSL should be referred to tertiary cancer centers where ongoing clinical trials are underway to identify the optimal treatment of PNSL.

Antineoplastic Agents↗