Hello, everyone, welcome back. On this section, we'll be talking about Imaging and Clinical Oncology, why it's important. In the earlier lectures that we've had that were a part of this series, we had a introduction to the common cancers and an introduction to cancer biology. Here, we're going to apply that knowledge to see how we manage cancer clinically. Generally, there's six different techniques that one uses to manage cancer. The first one is we try to keep it away which is cancer prevention. Next, we know that we can't prevent it all the time so we watch out for it and we do that by cancer screening. Next, if we think that cancer is present then we have to determine for certain if it is, that's a cancer diagnosis. Once we know for certain, that cancer is present, then we need to determine how advanced it is and that's cancer staging. Once we treat a cancer, we check to see if a treatment worked and that's assessment of treatment response. And then finally, after we've treated someone we need to always keep watch, to make sure it doesn't return, and that's monitoring. So I've just gone through six techniques of how to manage cancer, based on the earlier lectures that we've had. And the thing that I want to point out is five of those techniques involve imaging. So that's why imaging is important in oncology. And we'll just go through the five management techniques. The first one that we'll talk about is cancer screening. The screening tests are done to find cancer at an early stage before one has symptoms when it may be easier to treat and possible to cure. Screening tests should always be inexpensive and safe as possible with what we would call a low risk to high benefit ratio because we're not certain if it's present. We're just checking. The common cancers that we've been discussing so far that were discussed in lecture one, the incidents in etiology of cancer. Dr. talked about screening a bit in his lecture, in what we saw that was the six common cancers, four of them use imaging and screening. We screen for lung cancer with CT scans, we screen for colon cancer using plain films. It's not our first choice, but we do use plain films to screen. Of course, we use mammography to screen for breast cancer and ultrasound to screen for liver cancer. Next, we'll show you some examples of each. Here is an example of a CT scan that was done to screen for lung cancer. Did you remember the CT scan is produced with x-ray's as an axial view, no contrast was used on the image on the right. You'll see the cancer, which is an adenocarcinoma, which Dr. discussed in lecture one, the different types of cancers. It's in the right lung. Here we have an example of imaging that was done for colon cancer screening. The test of choice to screen for colon cancer in the United States is colonoscopy. But sometimes barium enema tests are done. In this case that's what this is an example of. We use a plain film, there's contrasts used here is barium and air. So barium is outline in the colon and air is just standing it. The patient is actually lying on their left side which is what’s called the left lateral decubitus. You'll see that the barium has pull to the left side of the colon all away through that helps outline it, and also you can see that there's a mass in the hepatic flexure of the colon. The arrow is pointing to it. And then also there's a few small polyps noted throughout the hip of two of them indicated here. Here we have an example of breast cancer screening. We usually use mammograms to screen for breast cancer, sometimes MRIs or ultrasounds are used. On the left is an example of a mammogram. There's a very small cancer that's shown in the top left with the arrow. So you'll remember that mammograms are done with x-rays. The particular view is cranial to caudal. That just means that the view is from the top to the bottom. No contrast is needed in these images, because you can appreciate the very fine detail. On the top right, there's an example of a breast ultrasound. A cancer is shown there, the dark area. It has a different density that's why, because the tissue is different from the tissue around it, that's why it's showing darker on the image, and on the bottom right is a breast MRI sagittal view or side view. This particular MRI is color enhanced to help appreciate the lesion probably a little bit better which is outlined in yellow there. The last screening test we'll talk about is for liver cancer, which is done with ultrasound. We can see here on the right as the example of a liver cancer, which is taking up most of the right lobe of the liver. You can appreciate that it's a little bit harder to see which structures are what when you look at an ultrasound image, however, the advantage of ultrasound is that it's much less expensive than other imaging. We've talked about how imaging helps with cancer screening, now we're going to talk about how imaging is used in cancer diagnosis. In our previous lecture, we discussed how pathology is considered what we call the gold standard in cancer diagnosis. You always want to have tissue to be certain when you make your diagnosis, so therefore imaging is generally a part of the work-up as we say. It supplements the pathology but it's generally not used alone to diagnose a cancer. However, for biopsies, which is a way to obtain tissue of the lung and breast and liver. They're sometimes what we call image guided. So an example is the image on the right, is a what we call a CT guided lung biopsy for a lung cancer or lung lesion, which was later diagnosed as cancer. And you'll see on the top right, there's sort of like a long straight white line that's actually the needle. And their using the CT scan to help direct the needle directly into the mass so they can obtain tissue. Then next, cancer management technique staging. I'm going to talk a little bit about how imaging is used in staging. The purpose of cancer staging is to determine how advance the cancer is because that will predict the disease course or what we call the prognosis. And it also determines the treatment options that are available. How do we identify the invasiveness of the cancer? First, we look at the primary tumor and we see is it confined within the tumor? Is it coming slightly out of the tumor, is it completely out? Next, we look at the nearby lymph nodes and see if they have been invaded, and then we look at distant tissue. And this is also known as the TNM system, tumor, nodes, and metastasis and that was discussed in a previous lecture. So how is imaging used in cancer staging? We use imaging to look in places where we know the cancer likes to go. Tropism which was discussed in an earlier lecture, means that when cancer cells extravasate, they go to certain organ sites where they tend to thrive. This is also part of Paget's seed in soil hypothesis, where he made the analogy that cancer cells are like seeds and they like to go to certain organs where they know they'll thrive, which is now I guess the seed going to a good soil. On the table that I have here, I have listed the common cancers and for each one the common sites of metastases for each cancer. And this was from an earlier lecture, but what I've added to the right is the imaging that would be done for staging for that particular cancer. For example, if a patient was diagnosed with breast cancer, and the imaging work up began to look for staging, for breast cancer we see that it likes to go to the bone. So we would need to obtain a bone scan. It likes to go to the chest, so we would get a CT of the chest. It likes to go to the liver, so we would have to include the abdomen in the CT, and finally, it likes to go to the brain, so we finally have to make sure that we would obtain a CT of the brain to look there as well. Now on this slide we're going to talk a little bit about how imaging is used to assess the response to treatment. And basically, what imaging does is it tells us when there's been a change in tumor burden, what we hope there to be actually tumor shrinkage in response to treatment. An example of a common imaging response assessment tool, is the RECIST guidelines. RECIST is the response evaluation criteria in solid tumors, in this particular set of guidelines there's four categories of response. The first is a complete response where you would take a scan after a patient's been treated and note that all the targets lesions, what they call target lesions or lesions that have been treated, have completely disappeared. A partial response is a 30% decrease in size of the sum of all the target lesions. A progressive disease is a 20% increase in the sum of the target lesions. And in a stable disease, is smaller changes that don't quite meet any of the above criteria. But here we have an example of how imaging assessment of response was used to guide therapy. This is a series of MRI scans with contrast of the brain of a patient with brain cancer. So in A, there's a baseline scam before treatment. And the tumor is the white area in the center, toward the top. It's actually in the right and left frontal lobes. And it extends downward into the another part of the brain, the thalamus. It's not quite as white there, but I have a orange dotted line there which represents a measurement that we'll be taking of the longest diameter of the lesion. And that's our baseline measurement. And B, this is after the patient has been treated. They've had surgery, they've had radiation and they have had chemotherapy. And then they've had a image taken and you can see just at a quick look that there's actually been a good response. There's just a small area remaining that's still enhancing. It's actually a little bit covered up by the orange dotted line, but it's quite small. It hasn't disappeared so it's not a complete response, but it's at least 30% so that's a partial response. In C, the patient at that point had been on what is called maintenance chemotherapy. And while they were on maintenance, a scan was taken, which shows that the cancer has recurred a little bit in the thalamus area. It's less than a 20% increase so it's still what's considered stable disease, not progressive. However, in response to that, the patient received radiation in that area. And then another scan was taken, this is in D, and you'll see that there was actually progression. The area's actually larger. The tumor's enhancing more after radiation. So that it may not be exactly a 20% increase, but it's close. So it's sort of in the middle what we would call stable disease to progressive disease. The patient wasn't treated again in panel E. They were given a new chemotherapy, this have chemotherapy number two there. And you'll see that the image has gotten actually larger, clearly more than 20%. That's a progressive disease. And then finally in panel F, the patient was given an immunotherapy and then a third type of chemotherapy and you'll see that the lesion actually is regressing now. It might not quite be 30% but it's close so that's a partial response. So this is an example of how imaging has guided therapy all the way through. So essentially at the completion of treatment you would follow the patient with whatever type of the imaging best characterized the cancer when it was active in order to monitor for recurrent cancer. So for example, if a patient had colon cancer which showed up well on a CT scan after treatment was completed, then we would follow them with CT scans at regular intervals. Then why does this work? In an earlier lecture, Dr. Zarif had talked to you about the hallmarks of cancer. For imaging monitoring where actually exploiting some of this hallmarks. Cancer hallmark number six is alter metabolism and that means that cancer cells take up more glucose than other cells. So for example of a patient had a cancer that especially liked glucose then that cancer would show up well on a scan that utilizes glucose. Here we have an example on the left of a nuclear medicine scan where the radionucleotide was attached to glucose and injected into the patient. In circulation, it went to where the glucose is being most actively metabolized which would be the tumor. So for the scan sort of does what we call it lights up. And then after therapy when the tumor's eradicated, it would no longer be taking up glucose, so it would show up cold on this scan. What we call cold, it just doesn't light up anymore. So then this scan would be good for this particular patient to monitor them afterward for return of the tumor. And then another cancer hallmark that we use or exploit to monitor patients after therapy is number nine, which was angiogenesis. And angiogenesis cancer cells survive by inducing the formation of new blood vessels. That's how they feed their growth. That means that cancers tend to have many blood vessels, or to be what we call hypervascular. This bodes well with our IV-contrast and hand studies, because iodinated contrast is injected into a blood vessel and then will preferentially go to tumors because there are hypervascular. So that's why they light up on the images. Here you see a CT scan of the brain with contrast. So there are three brain lesions that have taken up the contrast which is allowing us to visualize them. After therapy, when the tumors are killed and then there are no longer extra blood vessels present, they will no longer light up. So the cut skin in this particular patient could be used to monitor them over time to watch for tumor occurrence. So this concludes the section on why imaging is important in oncology. So in our final section of this lecture, we'll talk about the theory of oligometastases and how treatment is supported by imaging.
