Publications

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  • Survival of patients with head and neck cancer treated with definitive radiotherapy and concurrent cisplatin or concurrent cetuximab: A Surveillance, Epidemiology, and End Results-Medicare analysis. Cancer Xiang, M., Holsinger, F. C., Colevas, A. D., Chen, M. M., Le, Q., Beadle, B. M. 2018

    Abstract

    BACKGROUND: Cisplatin and cetuximab are both systemic therapies commonly used in combination with radiation (RT) for the definitive treatment of head and neck cancers, but their comparative efficacy is unclear.METHODS: Patients with locoregionally advanced (American Joint Committee on Cancer stage III-IVB) squamous cell carcinomas of the oropharynx, larynx, or hypopharynx were identified in the Surveillance, Epidemiology, and End Results-Medicare database. Patients received either cisplatin or cetuximab concurrent with RT, as determined by Medicare claims. The primary study outcome was head and neck cancer-specific mortality (CSM) analyzed with competing risks. Filtering, propensity score matching, and multivariable Fine-Gray regression were used to adjust for differences between the cisplatin and cetuximab cohorts, including age, comorbidity, and cycles of systemic therapy received.RESULTS: The total cohort consisted of 1395 patients, of whom 786 (56%) received cisplatin and 609 (44%) received cetuximab; the median follow-up was 3.5 years in the patients who remained alive. In the cetuximab cohort, CSM was significantly higher than in the cisplatin cohort (39% vs 25% at 3 years; P < .0001). In the matched cohorts (n = 414), the adjusted hazard ratio of CSM for cetuximab was 1.65 (95% confidence interval, 1.30-2.09; P < .0001) relative to cisplatin, corresponding to an absolute difference of approximately 10% in both CSM and overall survival at 3 years. Cetuximab was associated with less dysphagia, more dermatitis, and a similar incidence of mucositis.CONCLUSIONS: In this sizeable, national patient population, treatment with cetuximab was associated with significantly higher CSM than cisplatin. These results suggest that cisplatin may be the preferred chemotherapeutic agent in this setting. Cancer 2018;124:000-000.

    View details for PubMedID 30332498

  • Comparative Effectiveness and Toxicity of Cetuximab or Cisplatin With Concurrent Radiation for Locoregionally Advanced Squamous Cell Carcinoma of The Head And Neck: A Population-Based Analysis Xiang, M., Holsinger, F., Chen, M., Colevas, A., Beadle, B. ELSEVIER SCIENCE INC. 2018: E16
  • Gene expression-based discovery of atovaquone as a STAT3 inhibitor and anticancer agent BLOOD Xiang, M., Kim, H., Ho, V. T., Walker, S. R., Bar-Natan, M., Anahtar, M., Liu, S., Toniolo, P. A., Kroll, Y., Jones, N., Giaccone, Z. T., Heppler, L. N., Ye, D. Q., Marineau, J. J., Shaw, D., Bradner, J. E., Blonquist, T., Neuberg, D., Hetz, C., Stone, R. M., Soiffer, R. J., Frank, D. A. 2016; 128 (14): 1845-1853

    Abstract

    The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is frequently activated inappropriately in a wide range of hematological and solid cancers, but clinically-available therapies targeting STAT3 are lacking. Using a computational strategy to identify compounds opposing the gene expression signature of STAT3, we discovered atovaquone (Mepron™), an FDA-approved anti-microbial, to be a potent STAT3 inhibitor. We show that, at drug concentrations routinely achieved clinically in human plasma, atovaquone inhibits STAT3 phosphorylation, the expression of STAT3 target genes, and the viability of STAT3-dependent hematological cancer cells. These effects were also observed with atovaquone treatment of primary blasts isolated from patients with acute myelogenous leukemia or acute lymphocytic leukemia. Atovaquone is not a kinase inhibitor, but instead rapidly and specifically downregulates cell-surface expression of glycoprotein 130 (gp130), which is required for STAT3 activation in multiple contexts. The administration of oral atovaquone to mice inhibited tumor growth and prolonged survival in a murine model of multiple myeloma. Finally, in patients with acute myelogenous leukemia treated with hematopoietic stem cell transplantation, extended use of atovaquone for Pneumocystis prophylaxis was associated with improved relapse-free survival. These findings establish atovaquone as a novel, clinically-accessible STAT3 inhibitor with evidence of anti-cancer efficacy in both animal models and humans.

    View details for DOI 10.1182/blood-2015-07-660506

    View details for Web of Science ID 000385737900012

    View details for PubMedID 27531676

    View details for PubMedCentralID PMC5054697

  • Brachytherapy boost and cancer-specific mortality in favorable high-risk and other high-risk prostate cancer. Muralidhar, V., Xiang, M. I., Orio, P. F., Martin, N. E., Beard, C., Feng, F., Hoffman, K. E., Nguyen, P. L. AMER SOC CLINICAL ONCOLOGY. 2016
  • Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer JOURNAL OF CONTEMPORARY BRACHYTHERAPY Muralidhar, V., Xiang, M., Orio, P. F., Martin, N. E., Beard, C. J., Feng, F. Y., Hoffman, K. E., Nguyen, P. L. 2016; 8 (1): 1-6

    Abstract

    Recent retrospective data suggest that brachytherapy (BT) boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA < 10 ng/ml or T1c, Gleason 6, PSA > 20 ng/ml).We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT) only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM) after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors.EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258), and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270). Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022).Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined "favorable high-risk" category may be used to personalize therapy for men with high-risk disease.

    View details for DOI 10.5114/jcb.2016.58080

    View details for Web of Science ID 000372138300001

    View details for PubMedID 26985191

    View details for PubMedCentralID PMC4793071