Publications by authors named "Jan C Buckner"

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B.

View Article and Find Full Text PDF

Importance: Long-term outcomes of radiotherapy are important in understanding the risks and benefits of therapies for patients with brain metastases.

Objective: To determine how the use of postoperative whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) is associated with quality of life (QOL), cognitive function, and intracranial tumor control in long-term survivors with 1 to 4 brain metastases.

Design, Setting, And Participants: This secondary analysis of a randomized phase 3 clinical trial included 48 institutions in the US and Canada.

View Article and Find Full Text PDF

Background: Glioblastoma (GBM) has poor prognosis despite aggressive treatment. Dendritic cell (DC) vaccines are promising, but widespread clinical use has not been achieved, possibly reflecting manufacturing issues of antigen choice and DC potency. We previously optimized vaccine manufacture utilizing allogeneic human GBM tumor cell lysate and potent, mature autologous DCs.

View Article and Find Full Text PDF

Background: Patients with glioblastoma (GBM) have a poor prognosis and limited effective treatment options. Bevacizumab has been approved for treatment of recurrent GBM, but there is questionable survival benefit. Based on preclinical and early clinical data indicating that CD105 upregulation may represent a mechanism of resistance to bevacizumab, we hypothesized that combining bevacizumab with the anti-CD105 antibody TRC105 may improve efficacy in recurrent GBM.

View Article and Find Full Text PDF

Background: Decision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within-visit and previsit DAs for localized prostate cancer, and minority men were oversampled.

View Article and Find Full Text PDF
Article Synopsis
  • The NRG Oncology/RTOG 9802 study demonstrated that patients with WHO low-grade glioma benefit from adjuvant chemoradiotherapy, showing improved survival compared to radiotherapy alone.
  • A post hoc analysis evaluated the impact of molecular subgroups on patient outcomes, finding significant differences in progression-free survival (PFS) and overall survival (OS) based on molecular mutations.
  • Specifically, treatment with postradiation chemotherapy (PCV) significantly improved PFS and OS for mutant groups, while showing no benefit for patients in the wild-type subgroup, highlighting the importance of molecular profiling in treatment decisions.
View Article and Find Full Text PDF

Background: The optimal radiation dose for adult supratentorial low-grade glioma is unknown. The aim of this study was to provide a final update on oncologic and cognitive outcomes of high-dose versus low-dose radiation for low-grade glioma.

Methods: Between 1986 and 1994, 203 patients with supratentorial low-grade glioma were randomized (1:1) to 50.

View Article and Find Full Text PDF

Purpose: Whole brain radiation therapy (WBRT) remains a commonly used cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits.

Methods And Materials: NCCTG N107C [Alliance]/CEC.3 randomized 194 patients with brain metastases to either stereotactic radiosurgery alone or WBRT after surgical resection.

View Article and Find Full Text PDF

Background: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The core of standard of care for newly diagnosed GBM was established in 2005 and includes maximum feasible surgical resection followed by radiation and temozolomide, with subsequent temozolomide with or without tumor-treating fields. Unfortunately, nearly all patients experience a recurrence.

View Article and Find Full Text PDF

Background: Optimum management of low-grade gliomas remains controversial, and widespread practice variation exists. This evidence-based meta-analysis evaluates the association of extent of resection, radiation, and chemotherapy with mortality and progression-free survival at 2, 5, and 10 years in patients with low-grade glioma.

Methods: A quantitative systematic review was performed.

View Article and Find Full Text PDF

The treatment of newly diagnosed oligodendroglioma has been revolutionized in the past decade by multiple studies demonstrating that the addition of chemotherapy to radiation therapy results in a significant survival benefit. While the most direct evidence comes from clinical trials that utilized PCV, a chemotherapy regimen consisting of procarbazine, CCNU (lomustine), and vincristine, there is circumstantial evidence suggesting that the oral agent temozolomide (TMZ), which is both better tolerated and logistically simpler than PCV, may also be effective. The lack of currently available direct comparative data for PCV vs TMZ results in a diversity of practice.

View Article and Find Full Text PDF

Background: Src signaling is markedly upregulated in patients with invasive glioblastoma (GBM) after the administration of bevacizumab. The Src family kinase inhibitor dasatinib has been found to effectively block bevacizumab-induced glioma invasion in preclinical models, which led to the hypothesis that combining bevacizumab with dasatinib could increase bevacizumab efficacy in patients with recurrent GBM.

Methods: After the completion of the phase 1 component, the phase 2 trial (ClinicalTrials.

View Article and Find Full Text PDF

Purpose: To evaluate the pharmacokinetics and efficacy of imatinib in patients with recurrent oligodendroglial tumors.

Methods: Patients with progressive WHO grade II-III recurrent tumors after prior RT and chemotherapy were eligible. A phase I dose-escalation study was conducted for patients on enzyme-inducing anticonvulsants (EIAC).

View Article and Find Full Text PDF

Following the identification of key molecular alterations that provided superior prognostication and led to the updated 2016 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification, the understanding of glioma behavior has rapidly evolved. Mutations in isocitrate dehydrogenase 1 and 2 are present in the majority of adult grade 2 and 3 gliomas, and when used in conjunction with codeletion for classification, the prognostic distinction between grade 2 versus grade 3 is diminished. As such, the previously often used term of "low-grade glioma," which referred to grade 2 gliomas, has now been replaced by the phrase "lower-grade glioma" to encompass both grade 2 and 3 tumors.

View Article and Find Full Text PDF

In the context of the new WHO classification system, all low-grade gliomas must have an IDH mutation, with or without 1p/19q codeletion. Upon discovery of the tumor, maximal safe surgical resection is the most appropriate first step due to the current inability to differentiate between IDH mutant and IDH wild-type tumors by imaging alone. In the postoperative setting, based on the synthesis and interpretation of the available data, we recommend utilizing conventional radiation therapy and PCV in all high-risk-low-grade gliomas.

View Article and Find Full Text PDF

Aims: Rhabdomyosarcomas of bone are extremely rare, with fewer than 10 reported cases. A very rare subtype of spindle cell/sclerosing rhabdomyosarcoma harbouring a FUS-TFCP2 fusion and involving both soft tissue and bone locations has been reported very recently. We report only the fourth case of this unusual, clinically aggressive rhabdomyosarcoma.

View Article and Find Full Text PDF

Background: Mitogen-activated protein kinase (MAPK) activation and mammalian target of rapamycin (mTOR)-dependent signaling are hallmarks of glioblastoma. In the current study, the authors conducted a phase 1/2 study of sorafenib (an inhibitor of Raf kinase and vascular endothelial growth factor receptor 2 [VEGFR-2]) and the mTOR inhibitor temsirolimus in patients with recurrent glioblastoma.

Methods: Patients with recurrent glioblastoma who developed disease progression after surgery or radiotherapy plus temozolomide and with ≤2 prior chemotherapy regimens were eligible.

View Article and Find Full Text PDF

The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast material in essentially all GBM has popularized a belief that the BBB is uniformly disrupted in all GBM patients so that consideration of drug distribution across the BBB is not relevant in designing therapies for GBM.

View Article and Find Full Text PDF

Background: Vorinostat, a histone deacetylase (HDAC) inhibitor, has shown radiosensitizing properties in preclinical studies. This open-label, single-arm trial evaluated the maximum tolerated dose (MTD; phase I) and efficacy (phase II) of vorinostat combined with standard chemoradiation in newly diagnosed glioblastoma.

Methods: Patients received oral vorinostat (300 or 400 mg/day) on days 1-5 weekly during temozolomide chemoradiation.

View Article and Find Full Text PDF

Purpose: To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis.

Methods And Materials: In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.

View Article and Find Full Text PDF

Despite recent randomized, prospective evidence supporting use of RT and chemotherapy (CRT) for high-risk low-grade gliomas (LGG), many patients have historically received RT alone, chemotherapy alone or observation postoperatively. The purpose of this study is to evaluate outcomes for historical treatments in comparison to CRT for high-risk diffuse WHO grade II glioma patients. Records from 309 adults with WHO grade II glioma (1997-2008) eligible for RTOG 9802 (incomplete resection/biopsy or age ≥40 years) were retrospectively reviewed.

View Article and Find Full Text PDF

Predicting methylation of the O6-methylguanine methyltransferase (MGMT) gene status utilizing MRI imaging is of high importance since it is a predictor of response and prognosis in brain tumors. In this study, we compare three different residual deep neural network (ResNet) architectures to evaluate their ability in predicting MGMT methylation status without the need for a distinct tumor segmentation step. We found that the ResNet50 (50 layers) architecture was the best performing model, achieving an accuracy of 94.

View Article and Find Full Text PDF

Purpose: To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs).

Materials And Methods: We retrospectively reviewed records of 34 patients diagnosed with primary intracranial NGGCT between 1988 and 2014.

Results: Thirty-four patients received induction chemotherapy followed by radiation with or without surgery.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: