I am a radiation oncologist who specializes in the treatment of prostate cancer. I am interested in identifying competing causes of death among cancer patients and reducing these risks while improving quality of life at the lowest possible cost. My mother and I immigrated to the United States from Estonia in 1990. It was difficult for us to learn English, at first, and adjust to American culture. We also struggled to obtain adequate healthcare because we were not eligible for Medicaid, and we had difficulty understanding advice from pharmacists when purchasing medications. I know that my story is not a unique one, as there are many immigrants to the United States. My early experiences taught me that most patients do not need complex and expensive medical therapies. The most effective therapy is often relatively inexpensive and involves lifestyle interventions, such as diet and exercise.  However, patients need to be trained in its rationale and delivery.

After completing my Bachelors of Science in Neuroscience and Bachelors of Arts in Hispanic Languages and Literatures (both summa cum laude, 2003-2007), I matriculated at Temple University School of Medicine (2007-2011), where I helped a diverse population of underserved patients who had limited resources and could not afford costly therapies. I subsequently pursued an internship and research fellowship at Thomas Jefferson University Hospital (2011-2013), and then trained in radiation oncology at Fox Chase Cancer Center (2013-2017). After residency, I joined the Department of Radiation Oncology at Penn State Cancer Institute. In 2021 I was appointed the Vice Chair, Ed and Associate Professor in the Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, in Cleveland, OH. My research has several objectives, culminating in my clinical trial.

 

Aim 1. To optimize the treatment of prostate cancer patients. My work has centered on optimizing care for men with prostate cancer, including staging,1,2 “short-course” radiotherapy (i.e., 5 weeks of treatment),3 “very-short course” radiotherapy (i.e., over 1 week),4,5 biologically equivalent dose escalation,6-8 brachytherapy,6,9-12 treatment devices and technologies,13-15 treatment of high risk disease,16,17 treatment of radio-recurrent disease,18 post-treatment monitoring,19 quality of care,20 and patient-reported outcomes.21 Based on these works, my team helps to create treatment guidelines, including the American College of Radiology / American Radium Society guidelines for planning of radiation therapy, 22,23 multidisciplinary management of prostate cancer, 24 treatment during COVID-19,25 and post-prostatectomy evaluation and management. Further, my research helps to identify men who are at the highest risk of death from prostate cancer vs competing causes of death, and toxicities from therapy.

 

Aim 2. To identify patients at risk for competing causes of death. My research reveals that cancer patients, particularly men with prostate cancer, are more likely to die of competing causes of death rather than their cancer.26,27 My team has led several investigations to identify patients at highest risk of death from particular causes, including cardiovascular diseases27 (including heart disease28 and stroke29) and suicide.30 The risk factors for death from particular causes depend on primary tumor site, age, time to follow up, and comorbidities. For example, elderly, white, unmarried males are at an increased risk to die of suicide.30 Patients with cancer of the prostate, breast, and colorectum contribute to the plurality of those dying of stroke.29 Comorbidities increase risk of death from competing causes, and they increase risk of death from cancer and toxicity from treatment.31-33 Patients who do die of cancer typically die of metastatic disease, leading me to my next objective.

 

Aim 3. To characterize clinical phenotypic signatures of metastatic cancer. In current staging systems, once cancer metastasizes, patients are grouped into isolated Stage IV cohorts. Treatment usually involves indefinite and toxic systemic therapy and quality of life is poor. However, current staging systems are outdated — they do not incorporate unique clinical and genomic factors, which are important prognosticators.34,35

Thus, I am characterizing metastatic disease36-38 and redefining staging of metastatic cancer by using an inverse approach. My team is analyzing data from over 100,000 cancer patients to evaluate common clinical and genomic patterns to create phenotypes. Clinically, these phenotypes may be used to identify patients at risk for harboring occult metastases; improve ability to predict survival; identify patients at low risk of cancer-specific mortality and therefore at higher risk of competing mortality; and identify patients who will have greatest benefit from early palliative care for rapidly progressing disease39 or treatment intensification with stereotactic radiotherapy for oligometastases.40-44 Biologically, the results may be used to identify the underlying pathways responsible for metastasis to particular subsites of the body and develop treatments to target these pathways. 

Most patients die of metastatic disease and most of the cost associated with cancer care focuses on these patients. The cost to bring a single cancer drug to market is currently about $650 million dollars,45 and most studies that include metastatic cancer patients show an overall survival benefit in the intervention-arm of only a few months,46,47 at >$100,000 per quality-adjusted life-year.48 Thus, finding quality, low-cost interventions that improve outcomes and quality of life is crucial. 

 

Aim 4. To use comparative effectiveness research to identify high-quality and low-cost cancer treatments. As a clinician with a focus on genitourinary cancers, I am particularly interested in prostate cancer therapy.3,4,6,9,11-13,24,49 Across many cancers, my research supports the use of short-course radiation therapy because it has equal efficacy and limited toxicity.50-54 Historically, certain cancers (e.g., kidney), were never treated with radiation therapy, and I am evaluating bringing this treatment to the forefront.55,56 I have particular interest in stereotactic body radiation therapy because it appears to kill cancer cells by necroptosis, creating a pseudo-infection, and triggering an immune response against the cancer.57-60 Finally, my research reveals that the best treatment for cancer patients is on a clinical trial.61 Based on the data gathered from these objectives, I have identified exercise therapy as an ideal intervention for cancer patients, and my goal is to evaluate this treatment modality.

 Why is exercise therapy ideal for cancer patients?  First, exercise therapy can decrease the risk of both cancer and non-cancer related deaths, and it can improve quality of life. Few existing therapies are able to accomplish two of these endpoints, much less all three.  Second, exercise therapy is ideal for patients with metastatic disease, that is, patients who are at high risk to die from their cancer because few treatments work in this setting46,47 and generally cost >$100,000 per year.48  Third, exercise therapy is an archetype of cost-effective quality care, and I estimate it will cost <$1,000 per patient per year. Most patients will be eligible to be on a clinical trial evaluating its effectiveness. Exercise therapy is also available to minorities, underserved, and those without insurance, all of whom do not receive the same care as privately-insured patients. My work is supported by funding from the National Institutes of Health (NIH) and the American Cancer Society (ACS) to investigate the use of exercise therapy for metastatic prostate cancer patients receiving radiation therapy (titled EXERT for prostate cancer). As the lead author on the American College of Radiology / American Radium Society radiotherapy planning guidelines,22,23 I aim to integrate exercise therapy in future prostate cancer guidelines.

 

 

REFERENCES

 

  1. Zaorsky NG, Li T, Devarajan K, Horwitz EM, Buyyounouski MK. Assessment of the American Joint Committee on Cancer staging (sixth and seventh editions) for clinically localized prostate cancer treated with external beam radiotherapy and comparison with the National Comprehensive Cancer Network risk-stratification method. Cancer. 2012;118(22):5535-5543.
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  3. Zaorsky NG, Ohri N, Showalter TN, Dicker AP, Den RB. Systematic review of hypofractionated radiation therapy for prostate cancer. Cancer Treat Rev. 2013;39(7):728-736.
  4. Zaorsky NG, Hurwitz MD, Dicker AP, Showalter TN, Den RB. Is robotic arm stereotactic body radiation therapy “virtual high dose ratebrachytherapy” for prostate cancer? An analysis of comparative effectiveness using published data [corrected]. Expert Rev Med Devices. 2015;12(3):317-327.
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