Connecting
Evolution of Immunotherapy for Cancer Treatments
Over the last several decades, there have been numerous marked advances in cancer treatment. Initially, the only options were surgery, radiation or broad-based chemotherapy. These treatment methods have been shown to be effective and are still included in today’s cancer treatment plans. However, the newest addition to cancer treatment regimens is immunotherapy; which target specific aspects of a patient’s immune system and therefore boosts the response to treatment or targets the cancer itself. As genetic sequencing continues to advance, more targets are identified, leading to the creation of new immunotherapies which could potentially prolong the lives of cancer patients. Each patient’s genetic code is different and therefore their targets for immunotherapy vary, individualizing their treatment regimen.
Points of View
LOOKING BEYOND THE TEXTBOOK
During my years in medical school, I had the firm but naïve belief that all I needed to do to be an excellent doctor was to study hard, master all the facts related to various diseases, and learn the finer points about detecting abnormal physical signs. My classmates and I spent many hours reading multiple texts and being detectives on the “wards,” picking up the subtle signs of disease. We frequently suffered the ignominy from failing to accurately diagnose a patient’s problem(s) and not knowing the appropriate tests and management steps.
Immunotherapies come in many shapes and sizes. Many increase the effectiveness of your body’s own immune system by blocking its checkpoints typically used to keep your immune system from overreacting. These medications are referred to as immune checkpoint inhibitors and keep immune cells activated to fight cancer cells. Similar drugs, referred to as immune system modulators, alter the immune system response to be more potent. There are also immunotherapies which directly bind to and kill cancer cells, usually through the utilization of antibodies which bind to one specific target. A prime example of this type of therapy is rituximab, which binds to a specific receptor on the surface of B cells (cells which create antibodies once activated) to help treat many types of lymphoma.
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If only medical practice were so simple! As I’ve gained more experience, the mind-boggling reality of medical practice has been ingrained into my consciousness to a greater and greater extent. Medical practice involves more than my interaction and decisionmaking for my patients. For example, the insurance industry has firmly wedged itself into this exchange. The patient’s investigation or treatment depends on what is “sanctioned” by their insurance. I have also realized that healthcare is among the most regulated industries. My practice is governed not only by my employer but also by licensing boards, drug enforcement agencies, and the Food and Drug Administration. My compensation may partly depend on meeting some quality measures set by government regulations that change annually. Furthermore, I must remain vigilant to legal perils and avoid the ever-present threat of being involved in a lawsuit.
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Rajiv Dhand, MD, Chair
Dr. Kelly McCaul
Dr. Renju Raj
Neuroimmunology
Dr. Ghaida Zaid completed her neurology residency at UTHSC in Memphis in June of 2022. After receiving the prestigious National Multiple Sclerosis Fellowship Award, she was able to pursue specialty fellowship training at the University of Alabama in Birmingham. In September of 2023, Dr. Zaid joined The UT Medical Center in Knoxville, TN as a neuroimmunologist. In this field, she frequently encounters primary CNS immunological disorders such as multiple sclerosis, neuromyelitis optica, and autoimmune encephalitis as well as secondary conditions including neuro-rheumatological and neuro-infectious disorders.
A common misconception she encounters is the belief that MS and related disorders are a “death sentence.” This stigma, often shared within the medical community, can have a negative impact on patient experiences. She is committed to shifting this mindset and empowering patients with knowledge and resources to lead fulfilling lives despite their diagnoses.
Dr. Zaid comments, “What excites me most about neuroimmunology is its intersection with basic science and biology as well as how we apply this knowledge to the nervous system. It’s like solving a puzzle—gathering the details, refining the diagnosis, and then discovering the right treatment options to improve patients’ lives. This process is deeply rewarding and keeps us constantly engaged in the journey of our patients. However, it’s also a field that requires continual learning, as new challenges and discoveries arise regularly.”
The University of Tennessee Medical Center is proudly designated as a Multiple Sclerosis Comprehensive Center which allows Dr. Zaid to provide patients with necessary care and help them explore the complexities of their condition. She is eager to continue expanding the center through research and clinical trials with the goal of making UTMC the premier institution for neuroimmunological diseases in East Tennessee.
Immunotherapy
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Other newer immunotherapies work in novel ways to create a heightened immune response aimed at cancer cells with one being chimeric antigen receptor T-cell therapy (CAR-T). This treatment involves depleting the patient’s T-cells in the bone marrow and replacing them with genetically engineered T-cells which have been altered to bind to specific targets on the cancer cells. Fortunately, there have been great success stories with this therapy, leading to longer survival in many cancer patients. Our stem cell transplant/cellular therapy team here at UTMC just started utilizing this treatment over the past few years, providing more treatment options for patients all around East Tennessee and the surrounding areas.
The field of immunotherapy remains hyper-focused on developing even more advanced therapies with one of the more recent treatments being tumor infiltrating lymphocytes (TIL). In this therapy, T-cells derived from immune cells at the center of the patient’s tumor origin site are cloned at high numbers and introduced back into the bone marrow. The difference from CAR-T lies in that these treatments are used for solid tumor cancers such as melanoma, providing a brand-new plan of treatment for these types of cancer. According to Dr. Kelly McCaul, one of our in-house Transplant and Cellular Therapy physicians, similar treatments are currently in the works for glioblastoma multiforme (a type of brain cancer with very limited therapeutic options) with new studies recently being published in the New England Journal of Medicine.
Dr. McCaul believes that, “the future of immunotherapy lies in cell-based therapies and a strong reliance on genetic engineering/editing”. Editing of the genome would allow for treatment of genetically linked conditions such as sickle cell anemia and thalassemia, opening a completely new avenue of opportunity for treatment. With well over 1000 groundbreaking treatments underway as evidenced by the clinical trials being conducted through ClinicalTrials.org, there are sure to be even more advancements on the horizon to allow patients the chance to survive their malignancy longer and with a better quality of life.
Points of View
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As a physician, I have access to better treatments and improved devices, but the cost of these advancements sometimes creates moral and ethical dilemmas. Technological advancements and the introduction of artificial intelligence (AI) have brought fresh challenges. Navigating electronic medical records and protecting patients’ health information is essential and the need for cybersecurity has been emphasized. Scientific advancements have been successful at prolonging life for patients with illnesses that were previously incurable, but this has resulted in an aging population with more complex diseases that require advanced levels of specialized care.
Physicians are competitive by training. Competition between physicians for limited positions and resources often produces disappointment and disillusionment. Periodic epidemics and pandemics can further aggravate a stressful work environment; the COVID-19 pandemic being the most recent example. Thus, multiple factors, along with a chronic shortage of physicians in the workforce, often lead to a loss of job satisfaction and burnout. This problem is becoming increasingly evident among current and rising physicians today.
I wish we could bring back the “fantasy” I had as a medical student. We are told that the “all-knowing” AI will take over the role of physicians in providing care to patients. If only we could reduce the complexity of medical practice so that even a computer could do it!
DEI / Resident Highlight: Drs. Tinsley Roberson & Abdul Wasay
UT Graduate School of Medicine welcomed two new PGY-2 Residents this year –Tinsley Roberson, MD and Abdul Wasay, MBBS. Dr. Roberson completed medical school at the University of Alabama in Birmingham and her internship at Medical College of Georgia. She plans to pursue a career as a hospitalist after residency. Dr. Wasay completed medical school at Shalamar Medical College in Pakistan. Following this, he moved to the United States where he began working as a clinic researcher at the University of Louisville in Kentucky prior to completing his internship in Hattiesburg, Mississippi. He is planning to pursue a GI fellowship after residency. Both Tinsley and Abdul recognize the importance of diversity in medicine and the crucial role it plays in providing high quality care. They note that their diverse backgrounds have allowed them to establish connections with patients and develop trust that otherwise may not have been easily obtained. We are very excited to have them as part of our team and to see their careers flourish.
Scholarly Activity 2024
Pulmonary Critical Care Publications:
• Josan E, Wadi G. Fellows Reading List. AABIP. ePub 26 Aug 2024
• Dhand R, Wadi G. Evaluation of Respiratory Acidosis. BMJ. ePub 26 Aug 2024
• Singh S, Josan E, Kovacs C. Clinical impact of community-acquired respiratory viruses in patients with solid organ transplants. Transplantation Proceedings. 08/23/2024; 000: 1-3. PMID: 39181762
• Li J, Liu K, Lyu S, Jing G, Dai B, Dhand R, Lin HL, Pelosi P, Berlinski A, Rello J, Torres A, Luyt CE, Michotte JB, Lu Q, Reychler G, Vecellio L, de Andrade AD, Rouby JJ, Fink JB, Ehrmann S. Aerosol therapy in adult critically ill patients: a consensus statement regarding aerosol administration strategies during various modes of respiratory support. Ann Intensive Care. 2023 Jul 12;13(1):63.
• Terry P, Dhand, R. The 2023 GOLD Report: Updated Guidelines for Inhaled Pharmacological Therapy in Patients with Stable COPD. Pulm Ther. 2023 Jul 20. doi: 10.1007/s41030-023-00233-z. Online ahead of print.
• Dhand R, Treat S, Ferris J, Terry P, Walker T, Elder S, Church D, Dennis D, Faircloth B, Onar G, Heidel E, Biney I, Valdes M, Bhagat M, Fuerst N, Cusick S. Safety, Efficacy, and Feasibility of Nebulized Long-Acting Bronchodilators vs Short-Acting Bronchodilators in Hospitalized Patients With Acute Exacerbations of COPD. CHEST. 12/01/2024; 2 (4) : 1-10
Cardiology Publications:
• Sachs V, Scoma C, Shaikh K, Budoff M, Almeida S. Regional and socioeconomic disparities in calcium scans. Journal of Cardiovascular Computed Tomography. 08/16/2024; 00: 1-4. PMID: 39153865
• Tran PM, Fogelson B, Heidel RE, Baljepally R. A Comparison of Rural and Urban Differences in Geographic Proximity to Outpatient Stroke Rehabilitation Services in Tennessee. J Cardiopulm Rehabil Prev. 2024 Sep 18. doi: 10.1097/HCR.0000000000000898. Epub ahead of print. PMID: 39298543
CME OPPORTUNITIES
Hybrid attendance: half joining via Zoom or Microsoft Teams!
• 11th Annual Primary Care CME Conference, approved for AMA PRA Category 1 Credit™ hours this year. The conference will be held in-person at the Bridgewater Place in Knoxville, TN on March 1st, 2025. We hope you can join us for this informative event.
• View course information, agenda, and fees at: Primary Care CME Details
• Cardiology Conferences, held weekly on Wednesdays in the Medicine Conference Room for 0.75 hour CME credit.
• Medicine Grand Rounds, held on the 2nd and 4th Tuesdays of each month in the Medicine Conference Room for 1.00 hour CME credit.
• Ethics Case Rounds, held on the 4th Thursday of the month at noon in Wood Auditorium and are available for 1.00 hour CME credit.
• Pulm/HTN Conferences, held on the 2nd Monday of the month at noon in different locations and are available for 1.00 hour CME credit.
Tinsley Roberson Abdul Wasay
Ethics Case Rounds: Ethics and Incarcerated Patients
Ethics Case Rounds are monthly, hospital-wide discussions of morally distressing cases. Cases are de-identified to protect patient confidentiality.
“Wayne” is a 56 y/o gentleman who was admitted from prison after he suffered a cardiac arrest that resulted in a fall, hitting his head. He was found to be in septic shock due to pneumonia. He required intubation and vasopressors, then was admitted to the ICU.
His Advance Care Plan (ACP), which was provided by the prison, indicated he would not want to live in a permanently unconscious, confused, or dependent state. It identified his sister as his health care power of attorney (POA). However, guards at bedside stated hospital personnel could not contact family, and that the Warden would make any necessary decisions.
Ethical Issues
Et hically and legally, incarcerated patients have the same rights to informed consent and refusal as found in the community, including use of a POA or surrogate if they are incapacitated. Owing to the conflict of interest it would pose; correctional facility personnel must not make medical decisions for incarcerated patients. At the same time, incarcerated patients raise a safety concern. Outside visitors of incarcerated patients may pose a danger or may compromise officers’ ability to maintain the patient in custody while they are away from the corrections facility. Additionally, a person’s incarceration status may indicate likelihood of threatening behavior to hospital staff (though usually it does not). Thus, health care and corrections personnel must collaborate to ensure a safe and respectful environment for all.
In t his spirit of collaboration, the University of Tennessee Medical Center (UTMC) has developed a policy in partnership with Tennessee Department of Corrections (TDOC) and the Knox County Sheriff’s Office to foster safe and ethically sound decision-making processes for incarcerated patients.
Key points include:
• Correctional facilities and UTMC staff will communicate throughout the patient’s hospitalization, both to share health information and to determine how to safely contact decision makers for patients who lack decisionmaking capacity.
• Incarcerated patients will be designated as “No Information” patients. Only the attending physician, APP, or fellow will speak with decision makers for incarcerated patients, and calls made to decision makers of incarcerated patients will be made through the hospital operator so the patient’s location will remain confidential.
• UT MC team members will not attempt to learn the nature of the patient’s charges or convictions but will rely on personnel from the patient’s correctional facility for information needed to ensure everyone’s safety.
The matter was referred up the chain of command. Ultimately, the Assistant Medical Director of TDOC clarified that Wayne’s sister was indeed the appropriate decision maker as she was his power of attorney (POA). At that point, Wayne had been in the ICU for a week, and his condition had been deteriorating. At best, he would require a lengthy convalescence and ultimately live in a permanently dependent state.
Wayne’s sister requested that she and other family members be allowed to visit, and the Warden approved this. After extensive conversations with the attending, they decided to proceed with transition to comfort measures only. However, the guards at bedside maintained that their Warden is responsible for his decisions while he is in prison. Extubation was held in order to clarify the process. Unfortunately, family was unable to remain in town. The attending was able to clarify that Wayne’s sister had decision-making authority. He spoke with her by phone, and she confirmed the decision for comfort measures. Wayne was transitioned to comfort measures and extubated. He died later that day.
Comments on this case may be sent to amendola@utmck.edu
References
• Batbold S, Duke JD, Riggan KA, DeMartino ES. Decision-Making for Hospitalized Incarcerated Patients Lacking Decisional Capacity. JAMA Intern Med. 2024 Jan 1;184(1):28-35. doi: 10.1001/jamainternmed.2023.5794. PMID: 38048093; PMCID: PMC10696514.
• Tennessee Department of Corrections 2022 113.51 Consent/Refusal of Treatment
Presentations, Publications, Awards
Department of Medicine faculty, residents, and fellows share their knowledge and experience by publishing and presenting across the world. For a list of our most recent accomplishments, visit http://gsm.utmck.edu/internalmed/scholars.cfm.
Thank You For Your Support
For information about philanthropic giving to the UT Graduate School of Medicine, Department of Medicine, please contact the Development Office at 865-305-6611 or development@utmck.edu.
If you would like more information about any of the topics in this issue of In Touch, please contact the Department of Medicine at 865-305-9340 or visit http://gsm.utmck.edu/internalmed/main.cfm. We look forward to your input. Thank you.
Stay In Touch!
Alumni, please update your contact information by completing the simple form at http://gsm.utmck.edu/internalmed/alumni.cfm or by calling the Department of Medicine at 865-305-9340. Thank you!
In Touch
Vol. 13 Issue 4: October 2024
Publisher
Rajiv Dhand, MD, Chair, Department of Medicine and Associate Dean of Clinical Affairs
Editor
Annette Mendola, PhD
Administrative Director
Jenny Roark
Contributors
Jenny Roark
Rajiv Dhand, MD
Annette Mendola, PhD
Cassandra Mosley
Erin Hamric, DO
Logan Shaver, DO
Katelyn Rimmer
Alex Ayres
Mary Ellen Johnson
Ty Gaylor, DO
Design
J Squared Graphics
In Touch is produced by the University of Tennessee Graduate School of Medicine, Department of Medicine. The mission of the newsletter is to build pride in the Department of Medicine by communicating the accessible, collaborative and human aspects of the department while highlighting pertinent achievements and activities. Contact Us In Touch
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Disclaimer: quotes/ interviews are edited for length and clarity