Chemotherapy Dosing in Patients with Obesity: Are Oncologists Optimally Balancing Risks and Benefits to Avoid Overtreatment and Undertreatment?
Abstract
Almost 300,000 new cases of invasive breast cancer will be diagnosed this year, and military active-duty females have up to 40% higher risk of breast cancer than the general population. The vast majority of these are considered curable with a combination of surgery, radiation, chemotherapy, and/or targeted therapy. However, balancing the benefit and harms of chemotherapy has always been challenging. There is currently no perfect way to predict which patients will benefit from chemotherapy, and the toxicities associated with the treatment can be severe, permanent, and even life-threatening. Unfortunately, maximally tolerated chemotherapy doses are required for optimal survival. In real-world practice, 13% to 20% of patients are hospitalized, 23% to 55% require dose reductions, and up to 67% report experiencing moderate-to-severe toxicity, all as a result of their chemotherapy treatment. These negative outcomes are even more pronounced for patients with obesity, who are more likely to experience treatment-induced toxicity as well as breast cancer recurrence and death. The optimal chemotherapy dose that balances better survival with tolerable toxicity is not clear for patients with obesity, as guidelines are based on randomized clinical trials that enrolled younger healthier patients and lack head-to-head comparisons of the chemotherapy regimen recommended and used in clinical practice today. This uncertainty in the efficacy and safety of chemotherapy for patients with obesity may result in overtreatment and/or unnecessary toxicity. Over 42% of adults are now obese, defined by body mass index (BMI) >30, and almost 10% have BMI >40. There is an urgent need to evaluate the use of chemotherapy and its outcomes in current practice for patients with and without obesity. We propose a population-based, observational study of chemotherapy use in a large sample of real-world breast cancer patients (minimum estimated study cohort of 18,000), using a centralized multimodal database of interoperable electronic health records (EHRs) from 13 large health care systems with a catchment population of over 34 million. Our research team is uniquely positioned and qualified to address the overarching challenges of overtreatment and toxicity with chemotherapy. In our first Aim, we will identify the study cohort and characterize the various combinations and doses of chemotherapy (regimen), resulting in the most up-to-date estimates of the use of chemotherapy in current, real-world practice for a large, population-based sample of breast cancer patients. We will also estimate the extent of non-guideline chemotherapy use for patients with and without obesity. In Aim 2, we will assess the clinical appropriateness of the chemotherapy treatment choice and identify whether deviations from guidelines are explained by obesity itself, treatment-induced toxicity, comorbidity, or lack of supportive care medications. Finally in Aim 3, we will assess the results of these chemotherapy choices and the impact of obesity, toxicity, and dose reductions on survival. We will also develop a framework for overtreatment and undertreatment in chemotherapy to assess the full balance of treatment benefits and harms experienced by patients with and without obesity in current practice. Upon successful completion of our aims, we will have identified which combinations of chemotherapy (and what doses) result in excess toxicity or worse outcomes in patients with and without obesity. We will also identify any unmet needs with regards to the use of supportive care medications that help manage symptoms of nausea and vomiting, as well as protect against damage to blood cells. These and other findings will be immediately applicable and help inform treatment decision-making in real-world clinical practice and achieve outcomes important to patients. This proposed project could also lead to a major breakthrough in the use of chemotherapy to cure breast canc
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310654
Entities
People
- Joan Neuner
Organizations
- Medical College of Wisconsin
- United States Army