[Text on screen: Rhonda Ball
Cancer Survivor and James Ambassador
Sameek Roychowdhury, MD, PhD
Associate Professor, Medical Oncologist
OSUCCC - The James
The Ohio State University - Wexner Medical Center]

[Applause]

Sameek Roychowdhury, MD, PhD: Thank you, Peter, for the kind introduction. Thank you all for being here this evening. What Rhonda and I want to do is share with you a three year journey about how we've been working together to beat cancer through research. 

[Slide titled "Classifying Cancer" is shown alongside two images of microscopes, an old microscope from 1673 and a cartoon of a modern microscope]

And to start, I want to tell you a little bit about how we have classified and understood cancer for the past couple hundred years and what we're doing today. So these are objects that are microscopes, early microscopes, a cartoon of a more recent microscope. And the point I'm trying to make is that we look at cancer based on where in your body it comes from. Did it come from the lung? Did it come from the breast? And then next, we look at it through a microscope. What does it look like? What do those cells look like? 

Those cells are your own cells, and they have two bad properties. First, cancer cells have learned to grow and grow and grow. Second, those cancer cells have learned to travel and invade. So these cells are your own, and they're going places where they don't belong, and that causes organ dysfunction. And that's the problem with cancer. 

[Slide is titled "Cell based view of cancer" and shows an image of a man labeled "1850s" and a pie chart labeled "1998." The pie chart has half taken up by "Adenocarcinoma," a third by "Squamous," and a sixth by "Large-cell."

And so this is what I learned in 1998, my first year of medical school. I had to go back to Ohio State a couple times to get a couple degrees—I didn't get it right the first time. And that first year, I learned what I just described to you, what pathologists have been learning from autopsies since the 1800s, is that cancer, under a microscope, what it looks like. 

And this is a diagram of lung cancer, just an example, three types of lung cancer under a microscope, describing the shapes. But what this didn't tell me was how to take care of those patients. I took lots of tests to memorize this, but it didn't tell me how to take care of my patients. 

[Previous modern cartoon of a microscope is shown and labeled "2012"]

And so I finished medical school. I did my PhD in immunology to study the immune system. After five more years of clinical training, something changed. An unprecedented moment for science, where the day before, we could not go to the moon, and that next day we were going to the moon. And what I'm talking about is technology that had changed the way we look at DNA, technology that allows us to characterize the genes that could be affecting cancer, and we were doing it a million times cheaper and a million times faster. So that's a lot. A million times a million. To put that in perspective, what used to take three and a half billion dollars was now costing a couple of thousand dollars. And what used to take 15 years, we could do in days. 

[Image of a DNA helix being identified from the modern microscope cartoon image]

So we were now studying cancer and characterizing the genetic changes that could be driving those two bad properties, growth and invasion. 

[Video clip of a DNA sequence being identified on a double-stranded DNA helix with the title "Precision Molecular-based Taxonomy"]

So I changed fields, I started to study genetics, I studied with colleagues in computer science. And what I wanted to do is not only study cancer in a research lab with these new, exciting technologies going to the moon, I wanted to bring this to my patients. I was a doctor, and I was a scientist, and I wanted to bring those worlds together. And so how do we ask a question? What is the genetic needle in a haystack in my patients cancer that will help me find the right treatment for them? And for me, it was like a movie. I felt like I was a kid in a candy store with science and bringing this to my patients.

[Text on screen: "Your whole life can change in a second and you never even know it's coming."]

Rhonda Ball: I imagine I am the only person here who remembers that back in the day, Meryl Streep and Liam Neeson made a movie together. They did. The name of the movie was Before and After. What I really remember is the very first sentence spoken, "Your whole life can change in a second and you never even know it's coming." And think about it, we've all had those moments. Something happens, everything changes, and your life is not the same. That is what happened for me on a beautiful September day in 2014. 

[Image of an OSU tailgate]

My husband and I had been tailgating at the Buckeye game the day before. But that Sunday afternoon, I went out to my SUV, which we had not bothered to unpack. I opened up the back hatch and out tumbled a portable cast iron grill, about like that, and it landed right here on my right ankle. Well of course, I got a bump and a bruise, just what you would expect, but I also had another injury. Somehow I did something to my leg, nothing was visible, but it hurt and it really didn't work like it should have been working. This went on for several months. Eventually, I landed with an orthopedic doc, and he gave me the answer to why my leg was hurting. Cancer was eating away at this little bone at the top of my leg.

[Medical image scan of a skeleton with a red arrow pointing near the right proximal head of the femur and pelvic girdle]

Now, that is bad enough, isn't it? But that wasn't all. 

[Medical image scan of the head with a red arrow pointing to a mass near the occipital lobe]

[Microscopic image of the cancer]

It was also back here, and this mystery spot that was right here, I could actually see it and touch it. It was cancer. So I thought, cancer again, this is the third time in six years. What is it? I decided then, cancer is just going to be my lifelong nemesis. When I met Sameek in February, this was my reality. I had a cancer nobody could identify, it was stage four metastatic, and how to treat it, wasn't anyone's guess. I view myself as an optimist, but even I did not think this was something I was going to be able to beat.

[Slide is titled "Looking at Rhonda's tumor for answers" and includes the previous image of precision molecular-based toxonomy and another image of a DNA double helix]

Roychowdhury, MD, PhD: So when we met Rhonda, we enrolled her in a new study for genetic testing of her cancer using these new technologies that I was so excited about. And we looked at her tumor with a panel of 25 genes, as opposed to looking at one gene at a time in the previous decade, and we did find a mutation in a gene called KRAS, K-R-A-S. This was one of the first genes described in cancer in the 1970s. 

Ironically, it's been one of the hardest for us to figure out. So today, we still don't have effective therapies for KRAS, and it's ongoing research at the National Cancer Institute, everywhere. We didn't have a therapy I could offer her, that was the goal of our study, to find novel therapies. So we offered Rhonda radiation treatments to the bone as well as systemic intravenous chemotherapy.

[Image of a CAT scan with a red arrow pointing to a specific area in the abdomen. Text on screen: Treatment and Struggle with chemotherapy
Oct 2015 - April 2016]

Ball: I did begin the traditional chemo in October with very high hopes. And at first, it worked, and then it wasn't working, so we stopped. And it was at about that time period that I became incredibly sick. I could eat nothing, I couldn't keep anything down, I lost 50 pounds. It turns out the culprit was a brand new tumor that was causing a bowel blockage. I ended up getting sicker and skinnier and weaker by the day. And my very dear husband, who's sitting right over there, was a wonderful supporter, but he was worried sick. 

[Image of Rhonda Ball standing with two men]

And of course, he couldn't tell me, he couldn't share that with me, but he literally cried on the shoulder of our two very dear friends, Bill and Gail. I didn't know until much later that he was certain I would not live through the summer because of the cancer.

[Image of a CAT scan with a red arrow pointing to a tumor in a specific area of the abdomen. Text on screen: Recovering from surgery, and Cancer was still growing
July 2016]

Roychowdhury, MD, PhD: So Rhonda recovered from the surgery, lost a lot of weight. You were not in great shape. The CAT scans, like the one shown here, showed that the cancer was growing, so we needed to do something. The window was tight, so we returned to her genetics. 

[Slide is titled "Research findings: Hypermutation" and includes the previous image of precision molecular-based taxonomy]

Every year, as we do testing, things are evolving. We're getting better and better, and so we did new testing of her tumor, and we saw something different. We saw the original KRAS gene that we talked about earlier, that I still had no therapies for, but what we also saw was more mutations, more mutations than we typically see in most patients. And so this pattern we call hypermutation, lots of mutations.

The reason this pattern is important is that that means Rhonda's cancer looks very different from the rest of her body. Remember, cancer is our own cells, so if it looks more foreign, it's a possibility that we can use your immune 
system to fight your cancer. So that leads to the next question, why is your immune system not doing its job? For that matter, in all patients, why do our immune systems not respond reject our cancer? And there's a reason for that. 

[Slide is titled "Checks and Balances of the Immune System" and includes an image of a stoplight with the green light illuminated and an image of a stoplight with the red light illuminated. These images accompany the text "Rhonda's Immune System?"]

There's a system of checks and balances, so there are green lights that are switches on, and there are red lights that are switches off, and we need these, these are necessary. So all of us in this room, we're fortunate to not be having fevers, sweats, chills, body aches, your immune system is off, you don't need it on right now. But if you get cold virus, the flu virus, a pneumonia, cellulitis, your immune system kicks in gear, does its job, takes care of you, and then shuts back down.

And so this complex system to manage the immune system, that's what cancer is manipulating. So what it has done is to subvert your immune system and hide from it. It turns it off so that the cancer can grow, and it's immune to the immune system in a way. And so our goal with therapies that we call immunotherapies to boost the immune system is to find the right trigger point to turn your immune system on. And so based on the fact that Rhonda had hypermutation, we qualified her for a new clinical trial. It took two weeks to screen her and get you qualified, and then we got you started with the immune therapy.

[Slide is titled "After starting immunotherapy" and includes two CAT scans of the cancer, one from 7/25/2016 and the other from 9/12/2016. Each image includes measurements of the tumor with the 7/25/26 tumor measuring 3.4 cm by 2.7cm and the 9/12/2016 tumor measuring 15mm in width]

Ball: I did, I began the treatment on August the 8th. Within hours of having that treatment, this little spot here that I mentioned earlier was on fire. It was like there was an inferno burning inside me, but only right here. And to be honest, it was a little scary, but at the same time, it was exciting, because I thought maybe, maybe for the first time, something is working.

Roychowdhury, MD, PhD: And it was. 

[Roychowdhury, MD, PhD, embraces Rhonda Ball]

So scans that you can see there, the tumor under her breast bone is shrinking just like she thought, just after six weeks of therapy.

[Slide is titled "6 weeks after starting immunotherapy" and includes an image of Rhonda Ball with a group of people at an OSU tailgate]

Ball: And here I am back to tailgating. This is September, and I am with lifelong friends I made while living in Baker Hall on South Campus, if you guys remember where that is. And we have been friends for 40 years. Now, I know I look a little skinnier here, but I'm feeling really terrific by this time.

Roychowdhury, MD, PhD: So this is the picture that we want. We want to send Rhonda back to tailgating, back to friends and family, and we wanna do that for all of our patients. 

[Slide is titled "Who else has Hypermutation (MSI)?" and includes an image of the outline of Ohio with tons of red dots scattered around the state]

And so we asked a research question, who else has this pattern of hypermutation? So we designed an algorithm to detect it from genetics data, and we looked at 11,000 patients with cancer.

[Image of Ohio outline now includes only ten red dots]

And we found that up to three to four percent of patients could actually have hypermutation, and you could have it irrespective of what kind of cancer. That means every cancer patient could have this hypermutation and could benefit from immunotherapy. 

[Slide is titled "New MSIDx test New immunotherapy trials" and includes an image of a DNA helix and a cartoon image of pills]

With that, we needed to develop a test that we could use for all of those patients, not just for one type of cancer. So we developed a test that we called MSIDx, it's a short acronym for hypermutation. This was funded by a grant from the National Cancer Institute. And with that, that three year experience of our developing expertise, learning from 
Rhonda, understanding hypermutation, developing an algorithm, publishing papers, getting a grant, that puts us in position to develop new immunotherapies and clinical trials with the pharmaceutical industry so we can bring more novel therapies to our patients.

[Slide is titled "Last day of immunotherapy for 2 years" and includes an image of Rhonda Ball in a hospital bed surrounded by a group of people. This image is captioned "July 24, 2018 52/52"]

Ball: This was a red letter day for me, because this is the day, July 24th of this year, that I had my final treatment as part of the clinical trial. I call it number 52 of 52, because that is the number of times I did this over a two year period. As you can see, my husband's there to help me celebrate, Sameek, and members of his research team. Lots of happy faces, as there should be. And I was and am still so thankful, but I alone am not enough. There needs to be more people like me, more patients who get this chance at a second chance at life.

Roychowdhury, MD, PhD: So this is the part where we're working together now, right? And so our goal is to find those other patients, just like Rhonda, and find a way to help benefit them. And so we're using this new network called the ORIEN network—Oncology Research Information Exchange Network. 

[An outline of North America is shown with tons of red dots scattered throughout. The following text is also included: National Impact
The James
The Ohio State University - Comprehensive Cancer Center
network
Oncology
Research
Information
Exchange
Network]

This was founded by the James Cancer Hospital, the Moffitt Cancer Center. And what this network lets us do is to reach patients from over 15 major hospitals across the country and get access to 10,000 patients worth of cancer information and data per year, mine it with our algorithms, find patients who have hypermutation, and carry out Rhonda's wish to help more patients with that same marker.

[Same image of the outline of North America, but now fewer red dots are shown]

And we can do this for hypermutation, but we can also do this for other markers that we've discovered and offering novel therapies for by matching it to that marker in biology. 

[Multiple images of individuals working together in various settings as well as seven headshots of workers. The images are captioned with the following text: Genomics Diagnostics, Cancer Biology, Targets & Therapy, Computational Biology, Biology Students, Collaborators]

Research like this doesn't happen without a multidisciplinary team of talented people working together—going from Rhonda, to genetics, to diagnostics, to computer science, to drug development, and clinical trials. And you need a place that's special, that has a certain culture that allows that type of teamwork and constant training to happen. And we have that culture. The Comprehensive Cancer Center, the James Cancer Hospital, the Wexner Medical Center, my favorite bike ride, Pelotonia, and The Ohio State University.

[Text on screen: The James
The Ohio State University - Comprehensive Cancer Center
IMPACT
Right Patient
Right Treatment
Right Time]

Ball: Three months after my last treatment, I am totally convinced that I am alive today because of research. Docs like Sameek, scientists, and researchers may be doing the work, but big-hearted, generous individuals are making that possible. 

[Roychowdhury, MD, PhD, embraces Rhonda Ball as she speaks]

You don't realize it, but when you support research like this, you're saving lives. I know, because people just like you saved mine. And for that, I am now and forever grateful, so thank you.

[Applause]