This module covers the 8 ways to treat cancer:
1) Surgery
2) Chemotherapy
3) Radiation Therapy
4) Targeted Therapies
5) Immunotherapy
6) Hormone Therapies
7) Hyperthermia Therapy
8) Metabolic Therapies

How cancer treatments work
Preventing and managing side-effects

Video Transcript:

This is the third module of the cancer course, and this is all about cancer treatments and side effects. I’m going to go into the 8 main ways to treat cancer. There is quite a lot of overlap between some of them. The lines are a bit blurred, and there are some relatively common treatments that don’t exactly fit into any of the main character categories. So I will try to tackle that as they come up.

Traditionally up until really just a few years ago, the 3 pillars of cancer treatment were surgery, chemotherapy and radiotherapy, and that was really it.  Things have changed a lot, even just in the past 10 years, but unfortunately a lot of the thinking in Oncology hasn’t changed. That’s really quite understandable if you think about it, because people fall back to their fundamental education. If you have an oncologist who’s an experienced oncologist in their 40s or 50s, they went to medical school quite a while ago. Although it’s very likely they’ve kept up with the changes in chemotherapy for example, because that’s the main thing an oncologist will deal with, their knowledge of radiotherapy, oncological surgery, and these newer treatments, may be just things that they were taught at medical school.

For example, when they heard about the new treatments we have now, when they were at medical school 20 something years ago, those were just all experimental or theoretical treatments.

An example of that would be the particle treatments. It’s a type of radiotherapy using particles. When they were invented, which was actually a long time ago, (proton beam therapy was invented maybe in the 1950s or 60s), they were invented before CT scanning. So they weren’t really practical treatments, because you didn’t have good targeting, and you didn’t have CT scans to see what was going on.

You’ve got to be a bit careful when you’re talking to non-specialist clinical staff about treatments. Your oncologist should have some grasp of radiotherapy, but they might not know a lot of the nuances, and they may be given false information by various agencies, and they have to really take that at face value.

I’m specifically thinking about proton beam therapy, where the National Health Service in the UK was strongly against proton beam therapy, at least on paper, until very recently. All the oncologists were saying “it’s an unproven treatment that they’re using abroad, that they shouldn’t be using”. There was a very high profile case in fact, of a couple who took their child somewhere in Europe, for proton beam therapy and this was seen as a terrible thing in the NHS. Now, the UK finally has some proton beam therapy, and they are changing some of their content on the NHS websites about proton beam therapy.

But just bear in mind, we’re always dealing with old thinking when we talk about cancer treatments, and that’s to a large extent unavoidable, because you compare cancer treatments by 5 year survival mainly.  The 5 years of stats are the previous five years, or the 5 years before that treatment became approved. Those stats update very slowly over time, so it’s very natural that we’re talking about history, we’re seeing the past, and we’re talking about it as if it’s current, when it really isn’t.

So the 3 pillars of cancer care have always been surgery, chemo and radiotherapy. But the big change really, I guess in the past 15 years, is the widespread use of molecular targeted drugs or targeted therapies. Then much more recently, immunotherapies and particularly since 2017, the big change of the immunotherapies with checkpoint inhibitors.

Checkpoint Inhibitors, the way the media explain it, is they take the brakes off the immune system. That’s partially accurate and is to some extent a useful idea, that your immune system wants to attack the cancer – that’s what the immune system is evolved to do. But it can’t, because the cancer cells are not presenting the right labels. The cancer cells are ignoring signals from your immune system that they ought to be dying. So it’s about checkpoint Inhibitors and PD1 targeted drugs and PDL1.

PD1 is “Programmed Death 1”.  This is a molecule on the surface of a cell that tells it to die. PDL1 is Programed Death Ligand 1, and that’s the receiving bit on the cell.

So the idea with checkpoint Inhibitors, is that you can take the brakes off the immune system, and the immune system will then recognize the cancer and kill it. This doesn’t really work in practice the way that the media and the pharmaceutical companies tell us, because many patients have a lot of immune suppression, so there just isn’t much of an immune system to do the attacking.

In my case, I’ve had this type of immunotherapy called Adoptive Cell Transfer, where you are actually given far more immune cells. In my case, it was autologous – meaning grown from my own white blood cells, so that hopefully you don’t get such a high % of those transferred cells being destroyed by your immune system, and also you don’t get those dangerous allergic reactions that we hear about with, for example, CAR T-Cell or the checkpoint inhibitors.

Having these targeted therapies available has really changed a lot in cancer treatment.  Unfortunately, the thinking hasn’t changed with it, and there are subtleties with that. Often patients are told they can’t have surgery or they’re not eligible for surgery, or surgery wouldn’t help in that case. That’s because historically, the outcome for the surgery was maybe not so great and the risk was too high. But now with good molecular targeted therapies after surgery, it could often tip the balance towards surgery. So you do have to be a bit careful about that.

So we’ve got surgery, chemotherapy, radiotherapy, targeted therapies, immunotherapy and hormone therapies. These are the ones I know least about and I really need to study a bit. Hormone therapies are used for example in prostate cancer and gynecological cancers, e.g. breast cancer, ovarian cancer, those kinds of things. There’ll be hormone treatment there. Some people would put them in together with targeted therapies. The mechanism is a bit different.

Then there’s hyperthermia therapy. This is one that is often dismissed by oncologists as maybe an unproven treatment or something like that, which isn’t it. It can’t really be the case because hyperthermia therapy is a whole branch of Oncology. Some types of hyperthermia therapy are very standard for all cancers. Ablation (where using heat to destroy cancer cells) is used a lot for lots of types of cancer.

The most well-known of that would be RFA (radio frequency ablation). That’s often used when cancer spreads to the liver, or when cancer spreads to the lungs. That’s when a special needle is inserted into the tumor, in a non-surgical procedure. You get a local anesthetic – (hopefully a load of sedation), but you’re not under general anesthetic, so you’re not unconscious and you don’t have the kind of risks/danger associated with general anesthetic. The needle is then heated using radio waves, to ablate the tumors. You could consider that a type of hyperthermia therapy. There’s a similar one, using microwaves ( for some reason that’s called MFA – microwave frequency ablation) even though of course microwaves are a type of radio wave. Silly naming but I didn’t come up with it. That’s when you bring a tumor to ablation temperature – the heat literally destroys it.

There are things like HIPEC (heated intra peritoneal chemotherapy). That’s where chemotherapy is pumped into the abdomen. I guess many of us have or have had chemo ports or something called PICC lines- basically a plastic tube that goes into your body,  and it’s got a block of plastic on the surface end, so that it’s easy to inject chemo into.

With HIPEC, you have 2 of those placed on your abdomen and heated chemotherapy is pumped in, it circulates it in your abdomen, and is pumped out. This is done in some procedures for up to 24 hours – pumping heated chemo around you, and you’re conscious. That could be before or after surgery to remove all the visible cancer that can safely be removed.

So that’s also a form of hyperthermia therapy, even though they’re using chemotherapy drugs, there does seem to be a hyperthermic effect. Hyperthermia is where you’re bringing up the tissue to maybe what’s called a fever temperature. I’m afraid I don’t know the imperial system, but for metric it’s 41 degrees Celsius, to bring the tumor or cancer cells up to that kind of temperature. That damages the cells. It causes protective proteins to form on the cells, which your immune system can then target. Those are called Heat Shock Proteins, and there are many different kinds, but conveniently, the different kinds are different sizes.  So they’re just referred to by the diameter of the protein in nanometers. The key one for fever temperature hyperthermia is HSP 70. It forms on the surface of the cancer cells, and gets damaged by your immune system afterwards.

Finally metabolic therapy. That’s trying to inhibit the cancer metabolism or starve it of energy, to damage it, to force it into a less efficient metabolic pathway. Also, cancer tumors metabolize with anaerobic respiration. As we remember from school, when you’re just walking around or jogging along, you’re in aerobic respiration. That’s when you’ve got enough oxygen. When you do really intense exercise, your muscles work anaerobically, so they’re not in the presence of atmospheric oxygen. We’re using oxygen inside the cells and blood, but not free molecular oxygen. The side effect of that, which we all know, is lactic acid. That’s what causes muscle burning and stuff in your muscles, when you do intense exercise. ,

There is this idea that when cancer cells are metabolizing, because they’re producing this lactic acid that is surrounding the tumors, building up around the tumors. It seems that that environment (called the tumor microenvironment) is very important for modulating the immune system. On a very crude level, when the white blood cells are trying to get in, they die in the lactic acid.

Metabolic treatments are often done using “off-label” drugs. That means using a drug that is developed for one purpose, that’s been repurposed. This is called repurposed drugs or off-label drug use. The one I took was metformin, which is a diabetes drug.  But there are a whole bunch of other ones. Based on talking to researchers about this, it does seem the effect of metabolic treatment is very small. In my case, the reason I did metformin for quite a few years, is because it’s very cheap and safe, and I was having immunotherapy at the time. So if the reduction in lactic acid around the tumors helps the immunotherapy a bit, it’s an incredibly cheap way of getting more for my money.

If I’m paying for this quite expensive immunotherapy, and a certain % of those white blood cells are just dying in this acidic tumor microenvironment, it seems sensible that if I can take this old cheap diabetes drug and make it a few % more effective, then obviously I chose to do that.

So those are the 8 main ways of treating cancer. There is some overlap, for example, there is some radiotherapy done during surgery. There’s a whole kind of blurring between immunotherapies and molecular targeted therapies. There are kind of odd things, like cryotherapy, where you’re freezing the tumors to death. That’s included in hyperthermia therapy for some reason. There are other odd things. Lots of hospitals will do RFA in their radiology department, because it’s scanner guided or ultrasound guided.

So that is a run through of the treatments. The treatments available to you depend on the origin of the cancer, the location, particularly where it’s spread to, the size of the tumors matters quite a bit, the number of tumors.

That’s changing for some things, but for example with radio frequency ablation, a rule of thumb in the past was that it was only worth doing if there were <3 tumors in the liver, and the  diameter of the largest tumor was 30 mm. That’s changed a lot recently. In countries that are doing a lot of RFA, they found benefit from doing RFA even when there’s 10s of tumors in the liver. They found a benefit of doing even if there were really quite big tumors, because you could get to a point where surgery became safe.

If you imagine a tumor –  say someone’s got a liver tumor pushing against the portal vein-  the surgeon looks at the scan and says “Sorry, can’t touch this”. You may be able to get it shrunk with RFA and maybe chemo as well. One of the really good points of radio frequency ablation for the liver is that it doesn’t reduce your liver function, so you can continue chemo just as normal. As I said, they do overlap.

Your health makes a big difference to what treatments you can have. Obviously with surgery, surgeons will talk about this thing called PS or “Performance Status”. Performance status is really, are you fit for surgery? Part of that is, are you going to do okay during the surgery and part of it is also the recovery. With surgery, you talk about ideas like the chance of not surviving the surgery, but then also the chance of serious problems afterwards, particularly in that first 30 days – that’s called morbidity. Of course mortality is the chance of making it through the surgery. Performance status is often in the questionnaire. It will be assessed to some extent by the surgeon, but mainly by the anesthesiologist. It’s things like, are you OK to go up and downstairs, can you take care of your daily life, are you bedridden. That influences a lot what surgery is safe to do, and also what is worth doing. But one thing I found from looking at patients who are long-term stage 4 survivors of colon cancer, because those are the patients I mainly talk with, is that things do change.

There are plenty of cases, for example like me, where I had an inoperable liver and it became operable later on. Now that’s not because my performance status has changed, but it’s because the cancer and the other parts of my body were dealt with through immunotherapy, molecular targeted therapy, hyperthermia therapy, radiotherapy, and a bunch of other stuff.

So it’s really important when you’re told “no” for a treatment, that you realize the chances are they’re saying no at that point in time, based on your current situation. In the case of surgery, it also really reflects the surgeon’s situation. If you’re told no for surgery, if you’re told you’re ineligible for surgery or you have inoperable lymph nodes, say para-aortic lymph nodes, (back near spine, close to the aorta coming from your heart ) – a tricky place to to be removed by surgery.  But another surgeon at a different hospital with a different team, maybe who specializes in that, may be able to do it safely. So you do have to be a bit careful when people are saying “no” for treatments.

Be extra careful if it’s the oncologist saying it, not the specialist, because let’s say your oncologist may have gone to talk to a radiotherapist, maybe at a team meeting if you’re in the UK, where the team system is used at every NHS Hospital. There could be a lot of information and reasoning why you’re not eligible for that certain treatment. But if you had the details, you might be able to find a different option. For example, for radiotherapy, there might be a different form of radiotherapy you could do. If you’ve had radiotherapy before, and then you’re rejected on the grounds that you’ve already had radiotherapy, and had too much radiation, you may be able to find a different mode of radiotherapy which is safe to do.

So we do have to be skeptical, we do need to push a little bit. We have to be very careful when thinking about viable treatments, because we’re usually being told answers based on economics and big statistics. That’s to do with what treatment tends to work over time, for the average cancer patient. Also, what’s worth the money for the government. Let’s say you’re in the US, then it’s what the insurance company will pay for, and they have exactly the same kind of thinking and reasoning.

But we’re concerned with our situation, and it could be that a treatment that’s not viable to do for the general population, could mean having that treatment may give us a good result that opens up other treatments.

I’m speaking very much from experience there, because that’s exactly what’s happened in my situation – that treatments opened up the possibility of other treatments.

The next thing to talk about really is the intent of the treatment, and we need to find out if it is curative. For some reason in radiotherapy, that’s called radical intent. I don’t know why, maybe they just think it sounds better. Or, is it palliative – trying to extend life or make you more comfortable if you have tumors pushing against nerves, that kind of thing. But if you’re accessing very advanced treatments, this line between curative and palliative is very blurred.

I had treatments that in most countries would be considered palliative, but because it was a combination of treatments, it has potentially been curative. I’ve had palliative treatments that opened up options for other treatments that have been radical intent. So the lines blur, particularly when you’re getting really good new treatments. It’s kind of old thinking of “palliative /curative”. Understandable but old.

Obviously we’re balancing the risks and the benefits. But you need to think about the risks and benefits to you, not the risks and benefits to a typical block of 10,000 cancer patients in your position, where someone’s deciding what drug to be funded, or someone at an insurance company is deciding what’s worth paying for and what’s not. We’re concerned with our personal situation. We have to base it on our situation-  our tumors, our spread of cancer, not the statistics for making difficult economic positions.

I’m not having to make these difficult decisions about what drugs to fund and what drugs not to fund, but when it’s my health, my life ,then I have to guide the specialists to not turn away from treatments that they read in a medical journal as being not economically viable, because I’m just thinking about me. It’s just one person.

When we compare treatments, we’re generally looking at the MOS, the median overall survival. You’ll hear some people saying, “Well the median overall survival for this treatment was 9 months, and the best current treatment median overall survival was four months, and therefore you should do this treatment”. Be very skeptical of these stats. If you know about stats and you’re interested, it’s eye-opening to dig into them a bit. You can ask how many people in that study; are there any other studies that support that or contradict that; are there any reasons why that study may not apply to me?

I had a liver surgeon tell me it was too dangerous to do liver surgery for me, because I had had radiotherapy to my liver. He produced a graph from the paper and I said okay, this graph was about  people doing liver surgery and after radiotherapy, and then tumors coming back (not just tumors in the liver but throughout the body). But it was a study of 300 patients, from 12 years ago. It was a couple of years ago when he was showing it to me. It was also not patients where the colorectal cancer had spread to the liver, which is my situation, it was primary liver cancer. I politely told the surgeon that this was of no relevance to me at all, and went to see some surgeons who were able to do the admittedly dangerous difficult surgery. In my case, they did a fantastic job and I lived to tell the tale.

So we do have to be careful with these stats, because medical professionals do tend to pick stats that support their way of thinking, which again is understandable. If you’re a radiologist, you think radiotherapy is really good, and of course you’re naturally going to remember the studies that support the treatment that you think works best.

There’s confirmation bias and there’s availability bias.  Availability bias is the idea that we believe what we can remember, and of course that’s deadly. But if you’re a specialist in say CyberKnife, and you read journals every month on radiotherapy, the articles on CyberKnife are naturally going to pop out for you. You’re naturally going to remember them more, because CyberKnife is what you deal with every day, so you’re going to have an unconscious bias towards that.

As patients, we do have to be really careful of this kind of thing. To some extent, we can prepare ourselves for some of these treatments. I’ve had 3 big surgeries and I will be talking about surgery in the surgery module. The 3 classic things for preparing for surgery are to get the weight down, stop smoking if you smoke, and stop drinking if you drink. I know they’re all easier said than done.

I only found out just around the time of my last big surgery, that if you want to lose fat from the inside of your body, then that fat responds much better to exercise than to reduce calorie intake. I had been reducing my calorie intake quite a bit. This was because my surgery was going to be very deep in the pelvis, and men tend to have a deep narrow pelvis, so there’s not a lot of room for this in this situation (this was reconnecting intestines) for the surgeon to be poking around. All your organs in the abdomen that protect have got protective fat on them.

If you need to make more room for a surgeon to have an easier job, then you want to concentrate on exercise for that.

The other big thing we can do for surgery, is prepare the heart and lungs as much as possible. This is one where unfortunately things are a bit easier for men than women. The male body responds a lot better to hard exercise for heart and lungs than the female body, although obviously the female body responds too. But unfortunately the female body has to work a bit more for the same gains which is unfair, but that’s what evolution gave us. So getting a strong heart and lungs makes a big difference, and any heavy exercise will help a lot.

I did running up and down steps with ankle weights. When I say running, to be honest it was fast walking, but it seemed to make a big difference.

Physical strength is also something that is worth building up. I don’t see any reason why that would help during the surgery, but often after surgery you are in bed a lot and you lose strength really quickly, it is scary. Just by being in bed a lot, especially in hospital, but even when you go home and you’re feeling pretty frail. So you want a lot of strength before you go into the surgery.

I found particularly getting the leg strength up, because you’re going to be a bit unstable on your feet, and getting grip strength up especially if you’ve had a lot of chemotherapy which tends to cause peripheral nerve damage.

Just a weird one but for radiotherapy, it’s really worth asking what position you’re going to be in for radiotherapy. You’ll usually be shown this in the preparation days for radiotherapy. Often for radiotherapy, you need something that keeps your body in a certain position. You’ll go and they’ll make that for you, or they’ll scan you or measure you and then make some kind of thing for you. In my case for proton beam therapy, it was kind of a mattress. They scanned me and then they made this unique mattress. Interestingly, on my last day of proton beam therapy when I was looking around, taking a tour of the machine, they showed me a room where they keep all the mattresses. They have to keep them for a certain number of years before they can be disposed of, because they’re radioactive.

With Tomotherapy, which is another type of radiotherapy, for the preparation day, I had to lie down again on a kind of mattress, but this was full of sand and they had a way of locking it in shape. I was pushed around to get me in the right position, and then they pumped out the air from this sand-filled mattress. They call it the “back lock”. The reason I mention it is that often for radiotherapy, you might have your arms above your head, and if you’re in a radiotherapy where it’s scanner guided, (you have to be in exactly the right position, it takes a while to get into that position, you have to lie there for a while during the radiotherapy, and then you have to stay in position while they check that the targeting was OK), it can be quite a strain.

So if you’ve got tight shoulders it’s really worth doing some exercise to loosen them up. The way you do that is you go to a sports physiotherapist and explain you’re having radiotherapy and show them how you’re going to have to lie, and they will give you some exercises that you can do every day. You generally get pretty good results in 3 weeks. So if you can find out 2-3 weeks before, and do those exercises just to make sure that you’re comfortable lying in an awkward position for extended periods of time. That’s true regardless of the targeting (you might have to have your legs in a weird position or whatever).

I struggled a lot in Japan because the beds tend to be a bit short for me. I’m not particularly tall, but I’m definitely taller than the average Japanese citizen.  So sometimes I was in weird positions with foam blocks under my feet and stuff, and not very comfortable. So that’s a very small thing you can do. Preparation makes a big difference.

Another big way to prepare for certain cancer treatments is going to the dentist. It’s really worth doing. Some hospitals, that will be part of what they do for your surgery for example, or radiotherapy. When you have radiotherapy anywhere near your mouth, it increases the chance of cavities forming, which is why it’s really important to go to the dentist.

When you’re doing surgery, particularly those longer surgeries, your mouth is wide open for a long time. It’s got the airway forced in. My surgeries were generally ~ 6-8 hours. There’s a very high chance of infection from your mouth. It’s very easy to pick up pneumonia, because essentially parts of the lung are more exposed to the air than they usually would be in the course of your usual breathing. So that’s really worth doing.

If you’re on chemo or if you’re going to be on chemo,  it’s really worth going to the dentist first to have everything checked and have really good cleaning done. One of the side effects of most chemos is that wound healing is impaired. So you can’t do a tooth extraction. Even having dental work done might cause a lot of bleeding. So going to the dentist before really does help a lot.

Unfortunately with some chemo and molecular targeted therapy, you also get a lot of gum trouble. So again, you really want to go to the dentist first.

Another big bit of preparing for treatment is planning your recovery. This is most relevant for surgery, but planning how you’re going to deal with stuff after surgery, particularly in those first few weeks. Some kind of recovery plan – maybe you want to involve friends and family in that. Surgeons encourage you a lot to walk straight after surgery, particularly abdominal surgery. Early standing, early walking, early eating- it’s very unpleasant but it’s been really proven to make a big difference in reducing complications afterwards. Things like getting that deep breathing going as quickly as possible, helps prevent pneumonia.

On the subject of pneumonia, I got pneumonia after my first two surgeries. Then I thought, “Why am I getting pneumonia, why don’t I go and get a pneumonia vaccine?”. So I paid the money to get the pneumonia vaccine privately. It’s only about 80 % effective and fortunately I didn’t get pneumonia for the third surgery, which is nice because the second time I got pneumonia, I got a collapsed lung as well, which wasn’t so fun.

So there are a bunch of ways you can prepare for surgery.

I will just go over some side effects. I think we’re all very familiar with hair loss from chemotherapy- it’s like a classic one, also to some extent from radiotherapy as well, but that does depend a lot on the chemo drugs.Many common chemo drugs don’t cause hair loss.

In the UK particularly for gynecological cancers, there’s like there’s a lot of emphasis put on preventing hair loss by wearing an iced cap. I’ve read some of the data on that and I’m pretty skeptical. I don’t know why it’s such a big thing in the UK. I haven’t really heard of it much in other countries, but the idea is that you wear an ice cold cap during the chemo, and that reduces the circulation in your head. For chemo for breast cancer, ovarian cancer, less of the chemo is going to go up into your head.

The reason that chemo causes so many side effects including hair loss, is that chemo targets dividing cells. So anywhere in your body where cells are dividing (of course for adults we’re not growing hopefully) but that’s things like the lining of your mouth, the skin cells, hair follicles or the lining of the GI tract –  stomach lining, intestines obviously.  So that’s why chemo tends to cause diarrhea, constipation, and those kinds of problems.

Skin problems – skin care is really important for many cancer treatments. Radiotherapy, because you get burning and stuff. But also even surgery, just because you’re often in an environment like “canned air” for extended periods of time. So taking care of your skin is really important, and nurses are fantastic about that kind of thing.

That is an overview of cancer treatments and the effects. Other side effects of course –  nausea – that’s a really hard thing to deal with. I found that every time I talk to a medical professional, I’ll say that I vomit very easily, please just give me everything to stop the vomiting and nausea, and that was relatively effective after a while. I should say here with surgery as well, if you’re someone who vomits easily like me, if you’ve never had surgery before and are having surgery, it’s really important to tell the anaesthesiologist that, because they will put an anti-vomit drug when you come round. In surgery number two ,I had the anti- vomit drug and of course when surgery number three was happening, they said “Have you vomited before from surgery?” and I said “no”, remembering surgery number two, forgetting I’d had the anti-vomit drug. So of course surgery number three, I vomited a lot after it which is really painful. So don’t do that – have anti-vomit drugs, it’s really helpful.

In future sessions, I’m going to go in detail over types of radiotherapy, types of surgery, different molecular drugs, different chemotherapies and their effects and side effects, some of the hormone therapies, hyperthermia therapy like the HIPEC I mentioned in this module.

So please join me for those too, and I hope you found this one useful.