Head and Neck Cancer Clinical Research on ClinicalTrials.gov: An Opportunity for Radiation Oncologists.

Purpose: Many improvements in head and neck cancer (HNC) outcomes are related to optimization of radiation therapy (RT) dose, fractionation, normal-tissue sparing, and technology. However, prior work has shown that the literature of randomized controlled trials is dominated by industry-sponsored trials that have lower rates of incorporating RT. We characterized HNC clinical trials, hypothesizing that RT-specific research questions may be relatively underrepresented among HNC randomized controlled trials.

A low percentage of metastases in deep brain and temporal lobe structures.

Background: Whole-brain radiotherapy (WBRT) in patients with brain metastases (BM) is associated with neurocognitive decline. Given its crucial role in learning and memory, efforts to mitigate this toxicity have mostly focused on sparing radiation to the hippocampus. We hypothesized that BM are not evenly distributed across the brain and that several additional areas may be avoided in WBRT based on a low risk of developing BM.

Funding Support and Principal Investigator Leadership of Oncology Clinical Trials Using Radiation Therapy.

Purpose: Sources of funding and principal investigator (PI) leadership for clinical trials using radiation therapy (RT) are not well characterized but are important mediators of innovation, particularly because funding for trials from the National Institutes of Health (NIH) has decreased and industry funding has increased. We sought to determine characteristics of trials using RT that are associated with industry funding, NIH funding, and radiation oncologist (RO) PI leadership.

Methods And Materials: www.

Adjuvant chemoradiation does not improve survival in elderly patients with high-risk resected head and neck cancer.

Objectives/hypothesis: Randomized trials have demonstrated that adjuvant chemoradiotherapy (CRT) confers an overall survival (OS) benefit over adjuvant radiation therapy (RT) alone in patients with resected head and neck squamous cell carcinoma (HNSCC) with adverse pathologic features (positive surgical margins [SM+] and/or extracapsular extension [ECE]). Whether this OS benefit exists in an elderly population remains unknown.

Study Design: Retrospective database study.

Impact of total radiotherapy dose on survival for head and neck Merkel cell carcinoma after resection.

Background: Head and neck Merkel cell carcinoma (MCC) is commonly treated with surgery and adjuvant radiotherapy (RT) for high-risk features. The optimal radiation dose is unknown.

Methods: One thousand six hundred twenty-five eligible patients with head and neck MCC were identified in the National Cancer Data Base (NCDB).

Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience.

Background: Tri-modality therapy (TMT) is a recognized treatment strategy for selected patients with muscle-invasive bladder cancer (MIBC).

Objective: Report long-term outcomes of patients with MIBC treated by TMT.

Design, Setting, And Participants: Four hundred and seventy-five patients with cT2-T4a MIBC were enrolled on protocols or treated as per protocol at the Massachusetts General Hospital between 1986 and 2013.

Prostate-Specific Antigen Failure and Risk of Death Within Comorbidity Subgroups Among Men With Unfavorable-Risk Prostate Cancer Treated in a Randomized Trial.

Purpose Physicians sometimes make management recommendations on the basis of early results from randomized controlled trials (RCTs) relating to reduced prostate-specific antigen (PSA) failure, yet whether this early end point is associated with all-cause mortality (ACM), particularly in men with competing risks, is unknown. Using a validated metric in men treated within the context of an RCT, we aimed to determine whether PSA failure is associated with the risk of ACM stratified by comorbidity score. Patients and Methods Between 1995 and 2001, 206 men with localized (T1b to 2b) intermediate- and high-risk prostate cancer (PC) were randomly assigned to receive radiation therapy or radiation therapy and 6 months of ADT.

Assessment of M867, a selective caspase-3 inhibitor, in an orthotopic mouse model for non-small cell lung carcinoma.

Radiation-induced lung injury (RILI) is a significant dose limiting complication of thoracic radiation for lung, breast, and esophageal cancer. Strategies for increasing the therapeutic index of radiation involve the use of radiosensitizing agents. We investigated the potential of M867 to sensitize non-small cell lung cancer (NSCLC) to radiation in vivo, while assessing its protective effects in normal lung parenchyma.

ALDH7A1 expression is associated with recurrence in patients with surgically resected non-small-cell lung carcinoma.

Aim: The purpose of this study was to describe the prognostic significance of ALDH7A1 in surgically treated non-small-cell lung carcinoma. (NSCLC).

Materials & Methods: We immunohistochemically analyzed ALDH7A1 expression in surgically resected NSCLC from 89 patients using a tissue microarray.

ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK.

Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC). While in clinical trials, PF02341066 has shown a significant therapeutic benefit as a single agent; the effectiveness of combining it with other therapeutic modalities including ionizing radiation remains unknown. To further elucidate the role of PF02341066 in tumor inhibition, we examined its effects alone and in combination with radiation on downstream signaling, apoptosis, and radiosensitivity in two NSCLC cell lines in vitro: H3122, which harbors the EML4-ALK fusion, and H460, which does not.

Role of insulin-like growth factor-1 signaling pathway in cisplatin-resistant lung cancer cells.

Purpose: The development of drug-resistant phenotypes has been a major obstacle to cisplatin use in non-small-cell lung cancer. We aimed to identify some of the molecular mechanisms that underlie cisplatin resistance using microarray expression analysis.

Methods And Materials: H460 cells were treated with cisplatin.

BV6, an IAP antagonist, activates apoptosis and enhances radiosensitization of non-small cell lung carcinoma in vitro.

Introduction: Defects in the apoptosis pathway limit the effectiveness of radiation in non-small cell lung cancer (NSCLC) therapy. BV6 is an antagonist of cIAP1 and XIAP, members of the inhibitors of apoptosis (IAP) family. We investigated the potential of BV6 to sensitize NSCLC cell lines to radiation.

A novel bioluminescence orthotopic mouse model for advanced lung cancer.

Lung cancer is the leading cause of cancer-related death in the United States despite recent advances in our understanding of this challenging disease. An animal model for high-throughput screening of therapeutic agents for advanced lung cancer could help promote the development of more successful treatment interventions. To develop our orthotopic lung cancer model, luciferase-expressing A549 cancer cells were injected into the mediastinum of athymic nude mice.

MLN8054, a small molecule inhibitor of aurora kinase a, sensitizes androgen-resistant prostate cancer to radiation.

Purpose: To determine whether MLN8054, an Aurora kinase A (Aurora-A) inhibitor causes radiosensitization in androgen-insensitive prostate cancer cells in vitro and in vivo.

Methods And Materials: In vitro studies consisted of culturing PC3 and DU145 prostate cancer cells and then immunoblotting Aurora A and phospho-Aurora A after radiation and/or nocodazole with MLN8054. Phases of the cell cycle were measured with flow cytometry.

Inhibition of JAK2 signaling by TG101209 enhances radiotherapy in lung cancer models.

Introduction: Persistent STAT3 activation contributes to lung carcinogenesis. Survivin, one of STAT3-regulated genes, is antiapoptotic and confers cancer radioresistance.

Methods: We tested whether TG101209, a small-molecule inhibitor of JAK2 (a STAT3-activating tyrosine kinase), affected survivin expression and sensitized lung cancer to radiation.

Enhanced radiosensitivity of androgen-resistant prostate cancer: AZD1152-mediated Aurora kinase B inhibition.

Aurora kinase B (AURKB) is critical to the process of mitosis, aiding in chromosome condensation by phosphorylating histone H3. We investigated the effects of AZD1152, an AURKB inhibitor, on radiosensitivity of androgen-insensitive prostate cancer cells. The goal of this study was to test whether AZD1152 increases the susceptibility of hormone-refractory prostate cancer cells to radiation-induced DNA damage and to determine the conditions of AZD1152 treatment that maximize radiosensitization.

Terameprocol (tetra-O-methyl nordihydroguaiaretic acid), an inhibitor of Sp1-mediated survivin transcription, induces radiosensitization in non-small cell lung carcinoma.

Introduction: Survivin, an inhibitor of apoptosis protein and key regulator of mitosis, is up-regulated in a variety of cancers and is often associated with a worse prognosis. Terameprocol down-regulates the Sp1-mediated transcription of survivin and Cdk1, which is important for cell cycle progression and many other proteins. Survivin inhibition has previously been shown to result in the induction of apoptosis and radiosensitization.