Dr. Hedvig Hricak: Horizons in Innovation and Health

We’re going to turn it now and look a little bit ahead, and I’ll invite our colleague and friend, Dr. Hedvig Hricak, the professor and chair of radiology at Memorial Sloan-Kettering, to give us her thoughts about horizons in innovation and health, and what the future holds. Hedvig, it’s great to have you. Thank you, Steve, and good afternoon, everybody. I don’t have to tell you that it is a tremendous privilege and a great honor to be asked to join this great celebration of 10 years of NIBIB. It is not only a celebration of the wonderful new institute; it is also a celebration of its director, Rod – 10 years for you as well, so congratulations. And it isn’t only that the scientific community congratulates you.
Obviously, the Senate, for once, unanimously vote for something to stand behind and celebrate science as well. (Laughter.) So Rod gave me this topic of horizons in innovation and what the future holds. I really think that we are only at the very beginning of celebrating NIBIB and seeing how important the institute is. The next decade is going to bring many more innovations.
There will be a convergence of the life science, physical science and engineering. And I would like to quote Shirley Tilghman, who said that as much as new ideas are fundamental to the advancement of science, technologic innovations are the engine of scientific process. And we have seen many of those examples today. I’ll concentrate on cancer and oncology, since it is a field that I’m very passionate about.
There’s no question that our ultimate goal is preemptive medicine. For the next 10 years, it is going to be importance of prevention, early detection and then precision – what we used to call a personalized medicine. In all three, technology and imaging play extremely important role. It has been said that in the last 25 years, imaging, more than any other single tool of chemotherapy, have actually advanced cancer care. Is it going to be an improved survival for breast or lung cancer?
In treatment, decision making, treatment planning, where not only that imaging has eliminated many exploratory laparotomies, probably all of them in the – almost all of them in this country.
But extremely important, imaging allows more effective surgical management. In treatment follow-up, I don’t think that we should no longer really discuss and have controversies in treatment – in treatment follow-up, should it be a single measurement of volumetric display? Every biology model of cancer is showing you volumes and not single measurement. Obviously, volume is much more sensitive, and allows us much better prediction of treatment. But the problem is where we do need to concentrate.
Volumetric measurements on imaging have to be robust, have to be automated and widely disseminated. It is not single versus volume; it is how we can make volumetric measurements user-friendly. And this is where we do need technologies. So what the future holds: it’s health IT. Health IT, in our opinion, is much more than electronic medical records. Today, in daily use of health care, we use computers largely as file cabinets. To model, we will use them as intelligent system that thinks with us – not always for us, but with us.
And one of the big developments that is on the horizon – and it’s already here – it’s analytical computing. Computer system capable of answering questions posed in natural language will, more than anything else, allow dissemination of evidence-based standard of care. We have a contract with Watson and the IBM, and I can tell you that what’s wonderful about Watson: he doesn’t forget, he does as taught.
The number of informations – and we’re doing it in lung cancer – it is spectacular. And we are not afraid that once the product is commercial, to have it widespread throughout the country and around the world so we can offer the same standard of care globally. Is it going to be big data in Google? It’s a different system, realized only on genomics. Is it going to be healthier life from Technion University in Israel?
We don’t know, but with so much hope that one day they’ll join, and we will have open-source software so we can really use the best of the best. Another one that is tremendously already changing the health care is mobile technology. Those are monitoring devices, implantable chips. We are changing the health and treatment monitoring from what we call a social contract.
If you don’t feel well, call me. If you have fever, call me. Well, that’s really not a precision medicine. Now we’re going to have a real-time data collection, and going to be convergence of technology and health. We going to do it; it’s already done on the whole monitoring, portable monitoring patient with ovarian cancer – CA-125 goes up, serum biomarkers.
You don’t have to wait for six months to come in. We can have a real-time monitoring. And this is what’s going to give us precision medicine – treatment tailored to individual patient, treatment that we’re going to give at the right time, at the right place and with the right modality. But there is another aspect in health care, not just in oncology.
For the last 300 years, we relied on gross anatomy. But if Rembrandt were to paint his famous anatomy lecture today, it would be molecular. There’s no question. We have moved – medicine in the 21st century is molecular. We have new biosignature tools that are enabling a paradigm shift from one size fits all to medicine that’s predictive, prognostic and personalized. As issued earlier this year by the IOM, precision medicine in the 21st century is individual, precisely tailored, evidence-based medicine.
At present, that evidence-based, tailored medicine heavily relies on biopsy. Example of breast cancer – she on initial study; she’s HER2 positive. Unfortunately, she developed metastatic disease. The biopsy shows dedifferentiation, and she is now HER2 negative. Dedifferentiation of metastatic disease occurs in more than one-third of patients.
But we have a problem with biopsy. The first study, which was in Nature last year, the report on the Cancer Genome Atlas research, shows genetic intratumoral heterogeneity, and they said probably contributes to treatment failures and drug resistance. In the New England of Medicine (sic) earlier this year, there was an excellent study on renal cancer saying that intratumoral heterogeneity can lead to underestimation on tumor genomics landscape portrayed from a single tumor-biopsy.
They go on to say, maybe we should have multiple biopsies of the same tumor in the same patient; otherwise we’re going to have great challenges to personal medicine and biomarker development. And this is why predictive biomarkers and the precision medicine relies on imaging. Here’s an example: It’s a targeted imaging for breast cancer metastasis.
On the FDG scan, which is purely glucose metabolism, the lesion is very well seen, but the lesion is homogeneous. However, when you do specific receptor imaging – and this is trustuzumab, which is a form of HER2 receptors – you see the heterogeneity of the lesion, and you understand why, as radiologists, so often we see mixed or incomplete tumor response.
At present, we do do more than one biopsy, because we need to learn; we are in the validation phase. But those biopsies are really more and more done with the help of technology, with robotics, because that what gives us precision and standardization. A single, outstanding radiology – radiologist in any place doesn’t really help globally cancer care, but technology, being what’s on computer or robotics, will help us. And then, through technology, we are actually in vivo learning about biology.
And we are confirming what genetic studies have shown us: patient with metastatic prostate cancer, soft tissue and bony metastasis. On FDG, which is a glycolysis, soft tissue lesions have very high, avid uptake, so they are – they would be sensitive, glycolysis – (inaudible) – drug. However, in the bone, there is no uptake. When you do specific androgen receptor imaging, the bone lesion now shows uptake, has androgen receptors; soft tissue does not. A single therapy very often will not give us an answer.
We now understand that we need cocktail therapies, and it’s one of our biggest challenge. Different patient: metastasis in both hips. On glycolysis, the lesion on the left side has high uptake, but on PSMA antibody – this is an extracellular PSMA antibody – both right and left hip have lesions. So we can tailor the treatment according to the targeted imaging.
But the question is, so many of those patients have multiple lesion. Knowing inter- and intratumoral heterogeneity, heterogeneity within the same tumor, heterogeneity between metastatic disease, and also heterogeneity that happens over time – can we really biopsy every lesion? If yes, patient is going to look like this one, full with needle.
This is a sculpture from the Grace Cathedral in San Francisco. We cannot afford that. We need integrated diagnostics that’s going to have multiple components. In pathology, it’s going to be multiplexing. In radiology, it’s going to be multiparametric and go through different modalities. It’s going to be our ability, through technology, to see tumor volumetrically and assess tumor aggressiveness. When we look at all the information of integrated technology that we have, look how low is the cognitive ability.
In even in a cancer patient, how much more do we have to go in the information that is present? So information overload is not going to be solved by any specialty, by any single physician. It is going to be solved only through technology. So integrated diagnostics, which are essential to the precision medicine, will require some form of analytical computing.
But we have a different program. Now we have integrated diagnostics. We need customized therapy and we need theranostics. Will the future be Print me a Stradivarius? Will 3-D printers move from material science to print the drugs; and even, going further, print me a drug and the contrast media at the same time? I know it sounds very futuristic, but every great achievement started with an idea, and only idea. How already today, theranostics and targeted imaging and targeted therapy affect clinical trials?
You cannot solve new problems using old tools. In this patient, prostate cancer metastasis, if you would use CT as the endpoint, the drug would fail. But if you use a targeted imaging of androgen receptor to look at the androgen drug, not only that the drug is excellent, but we closed clinical trials ahead of its schedule (inaudible.) So theranostics and future clinical trials on targeted imaging, on targeted therapy, no question will require a form of targeted imaging, such as this one, patient androgen receptor imaging, multiple metastasis and then the follow-up showing excellent response.
This is what we need to aim towards. The reason is that when you look at the expenditure – and a lot of economy was brought up earlier – the GDP – health care rises higher than GDP. Cancer care is higher than the total health care, and the most troubling thing are cancer drugs. So predictive biomarker for tumor response are absolutely essential.
This is a great study; it’s an economical study on cetuximab, which is a miracle drug for colon cancer metastasis, but 36 percent of patients in population science conventional clinical trial did not respond. This study shows that we can save as much as $600 million in drug costs alone. This does not take into account the patient that’s taking a drug that doesn’t help.
Therefore, today, nobody around the world would give cetuximab without having a KRAS testing. So the success of the drug – and the failure went from 36 to only 9 percent. There is still host drug mechanism that we don’t understand. So how do we do theranostics, targeted imaging, and how can we already today save cost on drugs and tremendously help a patient?
It wasn’t long time ago, if you have thyroid cancer, you develop metastasis. There are multiple metastases in the lung. We give you iodine because that’s how we treat. But a number of patients have refractory thyroid cancer. So now we do iodine-124 PET/CT imaging. We see that in this patient, the lung cancer has no iodine optic. The number of drugs, of MEK inhibitors that are coming on the market, this is just one of them. Five weeks after, signal turned (ph) action has been interrupted, and the metastasis now have that optic of iodine, and the patient now can be treated.
So you help the patient, and you certainly help a health care economy. And this is another example, probably one of those how we wish the future is going to look. This is a heat shock protein. It’s a great drug for metastasis. What we did, we simply exchanged the iodine molecule on the drug for iodine-124. So now we have theranostics, we have targeted imaging, and we have targeted treatment.
Why is it important? This is a heat shock protein – patient, another patient with breast cancer metastasis. On the FDG scan, we see – on CT and a PET FDG, we see that she has lesion in the lung, and she has a lesion in the bone. When we looked at this on the FDG 19 days later, when she was on treatment, lesion in the lung has tremendously responded; lesion in the bone is the same, or perhaps even worse.
Now, let’s do targeted imaging. On targeted imaging, lesion in the lung picks up heat shock protein. So therefore the drug is going to act. Lesion in the bone has no heat shock protein. You can give her all the drugs you want. There are no receptors to look at the drug. And then when you look 21 hours later, that heat shock protein receptor was in the lung lesion are even higher.
So we can use imaging not only to select patients, but we can actually do phamarcokinetics. And there is where technology and imaging should, and we do believe will, change the way we practice oncology. There are 23 different radiopharmaceutical produced in house. They’re all in clinical use. And all those highlighted in yellow are first time in humans. But we have a large team.
We are really privileged, and we are lucky. But this is not how you can disseminate modern care throughout the United States. So just show you a brief history. We all know C11, but did you know that in 1975 – for some of you, it may be seem that far back, but it is not – C1 glucose was done prepared by photosynthesis. It was extracted from mashed-up Swiss chard – (inaudible) – Swiss chards leaves and green solution was injected into the patients.
They were brave. They didn’t have FDA problems or regulatory issues. And only in few places it was done, but that’s how we did C11 glucose. Today we have a black box. It is done very well through the automated versatile synthesis. But again, it requires a large team and a large infrastructure. Will tomorrow bring 3-D printing and solve the problem of radioactive material being brought from someplace else?
We have to believe that it will. And the change is imminent. So when we look at the horizons in innovations, opportunities are unprecedented. We live in revolutionary times of molecular medicine and technologic innovations. And many of those innovations are coming outside the conventional field of health care, and we really have to embrace them. Technologic innovations are outpacing regulatory processes and legislation. But we are not the only one. Every industry that has – (inaudible) – that has innovations is having similar problem.
The progress – especially in FDA, there has been a progress – but it will be made even faster as the society really gets together with science and pushes forward. Another one that so often we get upset, and that is this downturn of the economy. But history from the McKenzie (ph) report suggests that even in the deepest economical downturns can create huge opportunities for innovation.
Hewlett-Packard was starting during the big depression, and probably one of the best innovations for DuPont happened at the same time. But this is why with all the innovations, with money being tight, we today need NIBIB more than ever before. We need their support. We need their guidance. And we need them to help us look at the egg (ph) and paint a wonderful world.
And for that, to NIBIB and all the staff, congratulations. (Applause.) Time for a question? Of course. A question or comment for Dr. Hricak? So nobody challenging 3-D printing. I thought they were going to throw tomatoes. (Chuckles.) No one’s challenging 3-D printing. That – (chuckles) – I guess not. Oh, yes, maybe one. OK. So some of the images are also giving a lot of – (inaudible) – to the patients, especially for the – (inaudible) – for lung cancer. So how do you think we could deal with – (inaudible) – make it acceptable?
So the – I think the question was that many diagnostic imaging tests deliver modest doses of iodinizing radiation. And is this problematic for us going forward? Excessive radiation and excessive use of imaging is problematic for – no matter what you do. And this is why we actually believe that analytical computing such as Watson will probably be even stronger than the clinical decision-making tools because it incorporates not only when to order CT but what other studies to do.
And I actually firmly believe that the one way to standardize our care, to decrease use of imaging when we don’t need imaging is going to come from technology and analytical computing. Thank you very much for the glimpse into the future.