Role of epidural disease in local control of spinal metastases treated with stereotactic body radiation therapy.

Spinal metastases can be contained in the bone or have epidural spread. Whether the extent of epidural involvement changes tumor response to therapy is unknown. The decision of when to treat disease progression with focal radiation therapy with or without surgery vs.

Stereotactic body radiotherapy for treatment of spinal metastasis: A systematic review of the literature.

Background: Advances in local and systemic therapies continue to improve overall survival for patients with cancer, increasing the incidence of spine metastases. Up to 15% of patients with solid tumors develop spinal metastases. Spinal metastases can be particularly devastating for quality of life given the potential pain, neurological deficits from spinal cord compression or cauda equina syndrome, spinal instability, and pathological fractures that may result.

SLC4A11 mediates ammonia import and promotes cancer stemness in hepatocellular carcinoma.

End-stage liver disease is marked by portal hypertension, systemic elevations in ammonia, and development of hepatocellular carcinoma (HCC). While these clinical consequences of cirrhosis are well described, it remains poorly understood whether hepatic insufficiency and the accompanying elevations in ammonia contribute to HCC carcinogenesis. Using preclinical models, we discovered that ammonia entered the cell through the transporter SLC4A11 and served as a nitrogen source for amino acid and nucleotide biosynthesis.

PET/CT-Based Absorbed Dose Maps in Y Selective Internal Radiation Therapy Correlate with Spatial Changes in Liver Function Derived from Dynamic MRI.

Functional liver parenchyma can be damaged from treatment of liver malignancies with Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT.

Follow-up for human papillomavirus-related oropharynx cancer concentrated on unequal symptom change (FOCUS): Prospective patient-reported outcome collection.

Background: Post-treatment surveillance recommendations for oropharyngeal cancer do not vary with p16 status despite the differences in outcomes. The optimal algorithm personalizing follow-up for these patients remains undefined. Here, we evaluate the feasibility and utility of incorporating electronic patient-reported outcomes (ePROs) and circulating tumor DNA (ctDNA) into routine surveillance for patients treated for p16+ oropharynx cancer.

Predictors of Acute and Late Toxicity in Patients Receiving Chemoradiation for Unresectable Pancreatic Cancer.

Purpose: Patients with pancreatic cancer undergoing chemoradiation therapy may experience acute and chronic side effects. We conducted an exploratory analysis of patients with locally advanced pancreatic cancer (LAPC) undergoing definitive chemoradiation to identify factors influencing the occurrence of gastrointestinal (GI) bleeding, short-term radiation side effects, patterns of failure, and survival.

Methods And Materials: Under an institutional review board-approved protocol, we retrospectively studied patients with LAPC treated with chemoradiation.

Patients with progression of spinal metastases who present to the clinic have better outcomes compared to those who present to the emergency department.

Background: As cancer therapies have improved, spinal metastases are increasingly common. Resulting complications have a significant impact on patient's quality of life. Optimal methods of surveillance and avoidance of neurologic deficits are understudied.

A Phase II Study of Optimized Individualized Adaptive Radiotherapy for Hepatocellular Carcinoma.

Purpose: We hypothesized that optimizing the utility of stereotactic body radiotherapy (SBRT) based on the individual patient's probability for tumor control and risk of liver injury would decrease toxicity without sacrificing local control in patients with impaired liver function or tumors not amenable to thermal ablation.

Patients And Methods: Patients with Child-Pugh (CP) A to B7 liver function with aggregate tumor size >3.5 cm, or CP ≥ B8 with any size tumor were prospectively enrolled on an Institutional Review Board-approved phase II clinical trial to undergo SBRT with baseline and midtreatment dose optimization using a quantitative, individualized utility-based analysis.

Does Vascular Collapse Occur After Treatment of Hepatocellular Cancer With Stereotactic Body Radiation Therapy?

There is debate about why stereotactic body radiation therapy (SBRT) produces superior control of hepatocellular cancer (HCC) compared to fractionated treatment. Both preclinical and clinical evidence has been presented to support a "classic" biological explanation: the greater BED of SBRT produces more DNA damage and tumor cell kill. More recently, preclinical evidence has supported the concept of a "new biology", particularly radiation-induced vascular collapse, which increases hypoxia and free radical activation.

Stereotactic body radiation therapy (SBRT) following Yttrium-90 (Y) selective internal radiation therapy (SIRT): a feasibility planning study usingY delivered dose.

.Y selective internal radiation therapy (SIRT) treatment of hepatocellular carcinoma (HCC) can potentially underdose lesions, as identified on post-therapy PET/CT imaging. This study introduces a methodology and explores the feasibility for selectively treating SIRT-underdosed HCC lesions, or lesion subvolumes, with stereotactic body radiation therapy (SBRT) following post-SIRT dosimetry.

Age, race, insurance type, and digital divide index are associated with video visit completion for patients seen for oncologic care in a large hospital system during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic drove rapid adoption of telehealth across oncologic specialties. This revealed barriers to telehealth access and telehealth-related disparities. We explored disparities in telehealth access in patients with cancer accessing oncologic care.

DNA-Dependent Protein Kinase Drives Prostate Cancer Progression through Transcriptional Regulation of the Wnt Signaling Pathway.

Purpose: Protein kinases are known to play a prominent role in oncogenic progression across multiple cancer subtypes, yet their role in prostate cancer progression remains underexplored. The purpose of this study was to identify kinases that drive prostate cancer progression. To discover kinases that drive prostate cancer progression, we investigated the association between gene expression of all known kinases and long-term clinical outcomes in tumor samples from 545 patients with high-risk disease.

The long noncoding RNA HORAS5 mediates castration-resistant prostate cancer survival by activating the androgen receptor transcriptional program.

Prostate cancer (PCa) is driven by the androgen receptor (AR)-signaling axis. Hormonal therapy often mitigates PCa progression, but a notable number of cases progress to castration-resistant PCa (CRPC). CRPC retains AR activity and is incurable.

Development of a RNA-Seq Based Prognostic Signature in Lung Adenocarcinoma.

Background: Precision therapy for lung cancer will require comprehensive genomic testing to identify actionable targets as well as ascertain disease prognosis. RNA-seq is a robust platform that meets these requirements, but microarray-derived prognostic signatures are not optimal for RNA-seq data. Thus, we undertook the first prognostic analysis of lung adenocarcinoma RNA-seq data and generated a prognostic signature.

The bright side of dark matter: lncRNAs in cancer.

The traditional view of genome organization has been upended in the last decade with the discovery of vast amounts of non-protein-coding transcription. After initial concerns that this "dark matter" of the genome was transcriptional noise, it is apparent that a subset of these noncoding RNAs are functional. Long noncoding RNA (lncRNA) genes resemble protein-coding genes in several key aspects, and they have myriad molecular functions across many cellular pathways and processes, including oncogenic signaling.

MDM2 Inhibition Sensitizes Prostate Cancer Cells to Androgen Ablation and Radiotherapy in a p53-Dependent Manner.

Purpose: Increased murine double minute 2 (MDM2) expression, independent of p53 status, is associated with increased cancer-specific mortality for men with prostate cancer treated with radiotherapy. We assessed MI-219, a small molecule inhibitor of MDM2 with improved pharmacokinetics over nutlin-3, for sensitization of prostate cancer cells to radiotherapy and androgen deprivation therapy, a standard treatment option for men with high-risk prostate cancer.

Experimental Design: The effect of MDM2 inhibition by MI-219 was assessed in vitro and in vivo with mouse xenograft models across multiple prostate cancer cell lines containing varying p53 functional status.

Patient-Level DNA Damage and Repair Pathway Profiles and Prognosis After Prostatectomy for High-Risk Prostate Cancer.

Importance: A substantial number of patients diagnosed with high-risk prostate cancer are at risk for metastatic progression after primary treatment. Better biomarkers are needed to identify patients at the highest risk to guide therapy intensification.

Objective: To create a DNA damage and repair (DDR) pathway profiling method for use as a prognostic signature biomarker in high-risk prostate cancer.

The Landscape of Prognostic Outlier Genes in High-Risk Prostate Cancer.

Purpose: There is a clear need to improve risk stratification and to identify novel therapeutic targets in aggressive prostate cancer. The goal of this study was to investigate genes with outlier expression with prognostic association in high-risk prostate cancer patients as potential biomarkers and drug targets.

Experimental Design: We interrogated microarray gene expression data from prostatectomy samples from 545 high-risk prostate cancer patients with long-term follow-up (mean 13.

Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy.

Background And Purpose: Stereotactic body radiotherapy (SBRT) is being used for prostate cancer, but concerns persist about toxicity compared to other radiotherapy options.

Materials And Methods: We conducted a multi-institutional pooled cohort analysis of patient-reported quality of life (QOL) [EPIC-26] before and after intensity-modulated radiotherapy (IMRT), brachytherapy, or SBRT for localized prostate cancer. Data were analyzed by mean domain score, minimal clinically detectable difference (MCD) in domain score, and multivariate analyses to determine factors associated with domain scores at 2-years.

The landscape of long noncoding RNAs in the human transcriptome.

Long noncoding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes including cancer. To delineate genome-wide lncRNA expression, we curated 7,256 RNA sequencing (RNA-seq) libraries from tumors, normal tissues and cell lines comprising over 43 Tb of sequence from 25 independent studies. We applied ab initio assembly methodology to this data set, yielding a consensus human transcriptome of 91,013 expressed genes.

The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc.

Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology, contributing to tumor proliferation, invasion, and metastasis. Here, we describe a role for the oncogenic lncRNA PCAT-1 in prostate cancer proliferation through cMyc. We find that PCAT-1-mediated proliferation is dependent on cMyc protein stabilization, and using expression profiling, we observed that cMyc is required for a subset of PCAT-1-induced expression changes.

Induction of the small heat shock protein alphaB-crystallin by genotoxic stress is mediated by p53 and p73.

The small heat shock protein alphaB-crystallin is a molecular chaperone that is induced by stress and protects cells by inhibiting protein aggregation and apoptosis. To identify novel transcriptional regulators of the alphaB-crystallin gene, we examined the alphaB-crystallin promoter for conserved transcription factor DNA-binding elements and identified a putative response element for the p53 tumor suppressor protein. Ectopic expression of wild-type p53 induced alphaB-crystallin mRNA and protein with delayed kinetics compared to p21.

Regulation of alphaB-crystallin gene expression by the transcription factor Ets1 in breast cancer.

Recent studies indicate that the small heat shock protein alphaB-crystallin is expressed in poor prognosis basal-like breast tumors and likely contributes to their aggressive phenotype. However, the mechanisms underlying the deregulated expression of alphaB-crystallin in basal-like tumors are poorly understood. Using a bioinformatics approach, we identified a putative DNA binding motif in the human alphaB-crystallin promoter for the proto-oncogene Ets1, a member of the ETS transcription factor family that bind to DNA at palindromic ETS-binding sites (EBS).