It started with a chat over coffee about their work, which focuses on different aspects of the cancer continuum. One researcher looks at the rate of cancer diagnoses and deaths in the population; the other looks at survivorship and ways to improve care.
Together, these MUSC Hollings Cancer Center investigators are now launching a new multidisciplinary study that will use computer simulation modeling and patient inputs to create a more nuanced picture for predicting personalized treatment outcomes for the growing population of older adults with human papillomavirus (HPV)-related oropharyngeal cancer.
Ashish Deshmukh, Ph.D., co-leader of the Cancer Prevention and Control research program at Hollings, whose research focuses on HPV-related cancers, and surgical oncologist Evan Graboyes, M.D., who serves as director of the Survivorship and Cancer Outcomes Research (SCOR) program at Hollings, received a $3.2 million five-year grant from the National Cancer Institute that will optimize treatment for this specific patient population.
"Patients with HPV-related oropharynx cancer have excellent outcomes," Graboyes said. "And there are many ongoing clinical trials that are looking at how to maintain good outcomes but make treatment less toxic."
But most of what's currently known and being studied about outcomes is based on middle-aged patients. HPV-related oropharyngeal cancer is already on the rise by about 3% each year, and the largest increase to come is in older adults. Within the next couple of decades, more than 60% of cases are expected to be in people over the age of 65.
Treating older adults with cancer is different and challenging. They may have multiple medical conditions and may be less resilient than younger adults. Older adults may also have different preferences and priorities in terms of survival, cure, treatment toxicity and quality of life.
In order to understand the likely outcomes of different treatment options in different patients, Deshmukh and Graboyes will run an in-silico trial – a computer simulation that maps out all possible outcomes.
"We use simulation modeling for questions that are impractical to solve in the real world. They may be unethical or just very challenging," Deshmukh explained. "It's just impossible to conduct one real-world study that could perform comprehensive comparative effectiveness analysis of all possible treatment strategies and help older adults understand the expected benefits and harms over their lifetime."
They're using de-identified information on more than 200,000 patients, their pre-existing health conditions, the treatments they underwent, the side effects they dealt with and how long they lived after treatment. That information will be programmed into the computer model along with information that the researchers will be gathering about how oropharyngeal cancer survivors value different quality-of-life questions.
The model will then run all possible scenarios for each patient and show how the outcomes differ.
"This project will allow us to consider both quality of life and oncological outcomes to identify patient-centered treatment options that optimize health outcomes," Deshmukh said.
Deshmukh and Graboyes hope that this will offer future patients a better idea of the outcomes they are likely to face, given their individual health statuses and quality of life preferences.
"Let's suppose we have three or four different choices of treatment, and we will know what the expected harms and benefits, as well as long-term outcomes, would be – the in-silico trial will provide the answers. The findings from this study could be used to develop a decision aid or decision tool that clinicians can use with their patients that integrate the patient's values and preferences," Deshmukh said.
"I think this will really fill a critical clinical need," Graboyes added.
"The best source of knowledge, and the perspective we are most interested in representing, are the people who have actually lived through these toxicities, which I think are sometimes hard to imagine."Evan Graboyes, M.D.
Real-world clinical trials are critical, he noted, but the information that comes out of them is for an "average" patient. They generally don't account for variations in age or health and certainly not for all possible variables.
To get at the quality-of-life questions, the study will work with oropharyngeal cancer survivors to understand what they value and why.
All cancers and cancer treatments carry the possibility of serious side effects. Head and neck cancers, like oropharyngeal cancer, are a little different in that unpleasant or uncomfortable outcomes can't be hidden, like problems with talking, eating or facial expressions.
"The best source of knowledge, and the perspective we are most interested in representing, are the people who have actually lived through these toxicities, which I think are sometimes hard to imagine," Graboyes said. "They've done the process of adapting to them, so they can weigh not being able to eat or having a feeding tube or having radiation scar tissue."
The survivors will participate in a research setup known as "the standard gamble." They'll watch videos that illustrate life with different toxicity outcomes and think about how much they would be willing to trade "quantity" of life for the different lifestyle outcomes.
"The standard gamble is a challenging experiment but is considered a gold-standard method to understand patient values," Deshmukh said. "Because what we're trying to do is understand how patients value treatment; whether for them it's important to gain health benefits, in terms of life expectancy, or if they would rather preserve their quality of life over potential gains in life expectancy. So there's a trade-off. Some treatments may improve your life expectancy but can be associated with consequences. Are you willing to gain those benefits with some consequences that you may suffer?"
Deshmukh and Graboyes are benefiting from multidisciplinary expertise across MUSC as they embark on the study. They're working with Leslie Lenert, M.D., who works in data science and informatics and researches cognitive support for decision-making; Betsy Hill, Ph.D., director of the Biostatistics Shared Resource at Hollings, who will provide statistical support; Gerard Silvestri, M.D., a lung cancer researcher who is providing assistance with the standard gamble and decision science; radiation oncologist Bhisham Chera, M.D., who has expertise in radiation therapy for HPV-related cancers; Kalyani Sonawane, Ph.D., who is a data expert and health outcomes researcher; and Haluk Damgacioglu, Ph.D., who is providing bioinformatics and machine learning expertise.
To help to ensure that the research is patient-centered and that survivors of HPV-related oropharyngeal cancer have a voice in the science, the team is working closely with its external patient advisory board.
