Clinical and genomic predictors of toxicity

Identification of clinical and genomic predictors of toxicity.

Toxicity associated with treatment also impacts the patient. For example, Temozolomide, the most common agent used in the treatment of brain tumors, has a low overall incidence of myelotoxicity (impact on blood counts that help to fight infection or clot the blood). However, in the select patients who develop toxicity, there are significant clinical implications (treatment holds or cessation, and even death). I work with an interdisciplinary group that began to explore the clinical predictors of this toxicity and then explored associated genomic changes associated with risk (Armstrong et al., 2009). Currently, I am also working with a research team exploring risk factors and pathogenesis of radiation-induced fatigue and sleepiness, which is a major symptom in a large percentage of patients undergoing cranial radiotherapy for their brain tumor (Armstrong, Shade, et al., 2016). The ultimate goal of this part of my research is to begin to uncover phenotypes associated with symptoms and to uncover the underlying biologic processes, so that we can initiate measures prior to the occurrence of symptoms, rather than waiting for them to occur and then trying to mitigate them.

In addition to conducting focused outcomes research as outlined previously, I have over 25 years’ dedication to the clinical care of persons with tumors of the CNS. This work is the best part of my job and is a critical linkage and inspiration in my research, with the goal of improving the daily life of patients and improving our understanding of the underlying biology of symptoms and experience that our patients have.

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References 1. Armstrong T. S. Symptoms experience a concept analysis. Oncology Nursing Society

2003;30(4):601-606. 2. Armstrong T. S, Cohen M. Z, Eriksen L., Cleeland C. Content validity of self-report

measurement instruments an illustration from the development of the Brain Tumor Module of the M. D. Anderson Symptom Inventory. Oncology Nursing Society 2005;32(3):669-676.

3. Armstrong T. S, Mendoza T., Gning I., et al. Validation of the M. D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT). Journal of Neuro-Oncology 2006;80(1):27-35.

4. Armstrong T. S, Cao Y., Scheurer M. E, et al. Risk analysis of severe myelotoxicity with temozolomide The effects of clinical and genetic factors. Neuro-Oncology 2009;11(6):825-832.

5. Armstrong T. S, Gning I., Mendoza T. R, et al. Reliability and validity of the M. D. Anderson Symptom Inventory-Spine Tumor Module. Journal of Neurosurgery Spine 2010;12(4):421-430.

6. Armstrong T. S, Vera-Bolanos E., Bekele B. N, et al. Adult ependymal tumors prognosis and the M. D. Anderson Cancer Center experience. Neuro-Oncology 2010;12(8):862-870.

7. Armstrong T. S, Vera-Bolanos E., Gilbert M. R. Clinical course of adult patients with ependymoma results of the Adult Ependymoma Outcomes Project. Cancer 2011;117(22):5133- 5141.

8. Armstrong T. S, Vera-Bolanos E., Gning I., et al. The impact of symptom interference using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) on prediction of recurrence in primary brain tumor patients. Cancer 2011;117(14):3222-3228.

9. Armstrong T. S, Wefel J. S, Gning I., et al. Congruence of primary brain tumor patient and caregiver symptom report. Cancer 2012;118(20):5026-5037.

10. Armstrong T. S, Wefel J. S, Wang M., et al. Net clinical benefit analysis of radiation therapy oncology group 0525 a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma. Journal of Clinical Oncology 2013;31(32):4076-4084.

11. Armstrong T. S, Vera-Bolanos E., Acquaye A. A, et al. The symptom burden of primary brain tumors evidence for a core set of tumor and treatment-related symptoms. Neuro-Oncology 2015;18(2):252-260 Epub August 19, 2015.

12. Armstrong T. S, Bishof A. M, Brown P. D, et al. Determining priority signs and symptoms for use as clinical outcomes assessments in trials including patients with malignant gliomas panel 1 report. Neuro-Oncology 2016;18(Suppl. 2):ii1-ii12.

13. Armstrong T. S, Shade M. Y, Breton G., et al. Sleep-wake disturbance in patients with brain tumors.;: Neuro-Oncology, in press2016;

14. Gilbert M. R, Dignam J. J, Armstrong T. S, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. New England Journal of Medicine 2014;370(8):699-708.

15. Helfer J. L, Wen P. Y, Blakeley J., et al. Report of the Jumpstarting Brain Tumor Drug Development Coalition and FDA clinical trials clinical outcome assessment endpoints workshop (October 15, 2014, Bethesda, MD). Neuro-Oncology 2016;18(Suppl. 2):ii26-ii36.

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