Hi I'm not entirely in agreement with Lyn's explanation of the effects of radiotherapy. I would definitely agree that radiation is not cumulative but the effects of radiation are. I should point out I did not even study biology to O level, but did study physics to degree level, so I am not frightened of science and since getting PCa I have started reading up on biology.
The following is a brief explanation, if you want to know more you would be advised to Google some of the key phrases below.
As I understand it cells go through "the cell cycle" this is basically sitting around doing there job whatever it be, and then dividing perhaps every three or four years. The cell cycle has phases called G1, S, G2 and M (Google if required). After G1 and G2 are checkpoints. Many cancers are caused by an error at the G2 checkpoint. Quite simply most cancers are a failure of cells to stop at this checkpoint. They reproduce and the daughter cells will also fail to stop at the checkpoint.
So a normal cell at the checkpoint says "do I need to divide? Are there enough cells here already? is my own DNA in good condition?"
If all the condition are right for dividing then it will start to divide. If the DNA is bad, it will be (DNA suffers a lot of damage every day from free oxygen), then it fixes the DNA at this point.
When the DNA is fixed it "unzips", it then joins each strand with DNA bases to make two new copies.
In a cancer cell, it does not stop at this checkpoint. So it does not check if there are already enough cells around. However it has an achillies heel, because it does not check its own DNA either. Radiotherapy is intended to cause a lot of DNA damage, from what I have read "double strand breaks" are really difficult to repair. Normal cells can repair them, but cancer cells can't. Think of a single strand break as a dodgy zip on your trousers you can still zip and unzip but it may be a bit stiff in one place. A double strand break means someone took the scissors to your trousers and cut right through the fabric on both sides of the zip at right angles to the zip, you ain't ever getting that working again.
Radiotherapy does most damage by ionising water in the cells, thus releasing oxygen which breaks DNA. It needs to do so much damage that every cell has got double strand breaks. This damage is cumulative whilst exposed to radiation. Every fraction breaks more DNA. DNA is damaged but hardly any cells are killed. Over the next few years cells will think about dividing, a lot of normal cells will manage to repair their DNA (some won't): cancer cells will just go ahead and attempt to divide, but the zip is broken, so the daughter cells will not get a full compliment of DNA and they will not survive.
So psa nadir will occur when the majority of cancer cells have attempted to divide post radiotherapy. Prostate cells only think about dividing every couple of years.
If your lucky normal prostate cells will carry on dividing so slowly normal psa will recover.
Apparently the theory above came about in the 1970s, scientists realised, that cancer is not rapid cell division, it is just a failure to stop dividing when there are already enough cells.
Hope the above makes sense, start googling if you want to know more.
Sorry John none of this explains your pain.
Edited by member 02 Mar 2020 at 22:35
| Reason: Not specified
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User
The impact of the radiotherapy is cumulative, not the radiation itself. So let's assume that the RT hits 1 million cells and damages their DNA. Those cells divide and multiply × 2 but with the damaged DNA so the cancer does not progress - that is now 2 million damaged cells; they divide and we have 8 million cancer cells that have damaged DNA and do not progress. Generally, that process continues for about 18 months after treatment, which is why your PSA at 18 months post treatment is expected to be your nadir.
The RT damages healthy cells as well, and these replicate with damaged DNA. However, healthy cells are also regenerating so you may find the side effects get worse for a short time after RT but then begin to improve.
"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard
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User
Whatto Birchwood,
I had 63 Iodine 125 Radio active seeds implanted 10 years ago come 20th April 2020 at the then age of 65 years
and apart from the first couple of days have never experienced pain nor nocturia since that time. No two people
are exact duplicates of others treatment. Please look at my profile for fuller details. At the time of procedure my
PSA was 5.4, 10 years later it is 2.5 and slowly stumbling upwards. I bring my circumstances to your attention to
give another insight,together with John the Print, as to what could be a possible outcome of L.D.R. Perhaps you
should consider a scrum down in the very near future with your Urologist/Oncologist.
Following closely behind Lyn Eyre(The Matron) I can inform you with exactness that my Nadir of 1.0 was
reached 2years 6months and 25days post treatment and remained hovering around 1.0 for 3 years.
I suggest you seek an early appointment and have the pain investigated.
Michael.
User
Dave, your explanation is correct, as far as I understand the mechanism.
I will just add that DNA repair inside cells happens much more frequently than just at cell division, indeed for prostate cells, usually well within 24h for healthy cells (it varies for different cell types - lung cells repair DNA much faster). This is why daily radiotherapy cycles work quite well - they give the healthy cells time to repair before being hit again, but the cancer cells which by definition have a faulty DNA repair mechanism don't get to repair in 24h, and the DNA corruptions accumulate day on day. The object is not necessarily to kill the cell or even stop it from working, but you only have to stop it from being able to perform cell division, in order to stop it being malignant. In many cases, the formerly malignant cell will continue to live (and produce PSA into the blood) until it dies of old age (rather than by apoptosis - programmed death before a cell wears out, the mechanism which fails in cancer cells), hence the slow drop in PSA over the next 18 months as the formerly malignant cells die of old age.
User
Thanks Andy,
I knew my explanation didn't fit well with daily fractionation, and I must be missing something. Anyway we'd better keep quiet otherwise Matron will tell us off for talking after lights out :-)
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User
Whatto Birchwood,
You gotta kick arse. Mister Nice Guy will continue to suffer while you remain in pain
Start being a little forceful with your appointed nurse. You should not be experiencing pain after
such a long time since the treatment.
Good luck and start flexing your muscels and not just the pelvic ones.
Michael.
Edited by member 03 Mar 2020 at 09:02
| Reason: Not specified
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User
Hi I had Brachytherapy in September 2016 and had no real problems and a lot less problems than i expected.I had some pain killers and Tamsulosin to relax my bladder but had no increase in pain yes a lot of bruising and still getting up two or three times a night to pee.
Overall i am very pleased with my operation three years on and wish you well in the future.
John.
User
The impact of the radiotherapy is cumulative, not the radiation itself. So let's assume that the RT hits 1 million cells and damages their DNA. Those cells divide and multiply × 2 but with the damaged DNA so the cancer does not progress - that is now 2 million damaged cells; they divide and we have 8 million cancer cells that have damaged DNA and do not progress. Generally, that process continues for about 18 months after treatment, which is why your PSA at 18 months post treatment is expected to be your nadir.
The RT damages healthy cells as well, and these replicate with damaged DNA. However, healthy cells are also regenerating so you may find the side effects get worse for a short time after RT but then begin to improve.
"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard
|
User
Hi John,
Thanks for your reply, I am on Tamsulosin and considering taking Panadol On the basis of stopping the pain to stop the trigger??
User
Thanks Lyn, that explains it much better. My understanding was that good and bad cells were damaged but only the good cells could replicate ... just have to hang in there until Christmas then
User
Thanks Lyn,
You always come along to help us and i learn a little bit more,I need a glass of wine to digest that.😂
Regards John.
User
Whatto Birchwood,
I had 63 Iodine 125 Radio active seeds implanted 10 years ago come 20th April 2020 at the then age of 65 years
and apart from the first couple of days have never experienced pain nor nocturia since that time. No two people
are exact duplicates of others treatment. Please look at my profile for fuller details. At the time of procedure my
PSA was 5.4, 10 years later it is 2.5 and slowly stumbling upwards. I bring my circumstances to your attention to
give another insight,together with John the Print, as to what could be a possible outcome of L.D.R. Perhaps you
should consider a scrum down in the very near future with your Urologist/Oncologist.
Following closely behind Lyn Eyre(The Matron) I can inform you with exactness that my Nadir of 1.0 was
reached 2years 6months and 25days post treatment and remained hovering around 1.0 for 3 years.
I suggest you seek an early appointment and have the pain investigated.
Michael.
User
Hi Micheal,
My PSA was 8 on the doctors letter but 10 was mentioned by the oncologist before Brachytherapy.
I have been signed off by the Oncologist with PSA 0.6, now monitored by the cancer nurse, last checkup two weeks ago, a couple of week prior I presented myself to Urology because the pain had increased and I had a loss control, I.e. couldn’t get to the loo in time. Urology diagnosed a UTI and prescribed antibiotics. The nurse thought that I may not have had a UTI, it was more likely to be a related to the Brachytherapy ... unfortunately they didn’t follow through by sending my sample to the lab for testing.
It’s a bit annoying because they are all in the same department at Guys.
User
Whatto Birchwood,
You gotta kick arse. Mister Nice Guy will continue to suffer while you remain in pain
Start being a little forceful with your appointed nurse. You should not be experiencing pain after
such a long time since the treatment.
Good luck and start flexing your muscels and not just the pelvic ones.
Michael.
Edited by member 03 Mar 2020 at 09:02
| Reason: Not specified
User
Hi I'm not entirely in agreement with Lyn's explanation of the effects of radiotherapy. I would definitely agree that radiation is not cumulative but the effects of radiation are. I should point out I did not even study biology to O level, but did study physics to degree level, so I am not frightened of science and since getting PCa I have started reading up on biology.
The following is a brief explanation, if you want to know more you would be advised to Google some of the key phrases below.
As I understand it cells go through "the cell cycle" this is basically sitting around doing there job whatever it be, and then dividing perhaps every three or four years. The cell cycle has phases called G1, S, G2 and M (Google if required). After G1 and G2 are checkpoints. Many cancers are caused by an error at the G2 checkpoint. Quite simply most cancers are a failure of cells to stop at this checkpoint. They reproduce and the daughter cells will also fail to stop at the checkpoint.
So a normal cell at the checkpoint says "do I need to divide? Are there enough cells here already? is my own DNA in good condition?"
If all the condition are right for dividing then it will start to divide. If the DNA is bad, it will be (DNA suffers a lot of damage every day from free oxygen), then it fixes the DNA at this point.
When the DNA is fixed it "unzips", it then joins each strand with DNA bases to make two new copies.
In a cancer cell, it does not stop at this checkpoint. So it does not check if there are already enough cells around. However it has an achillies heel, because it does not check its own DNA either. Radiotherapy is intended to cause a lot of DNA damage, from what I have read "double strand breaks" are really difficult to repair. Normal cells can repair them, but cancer cells can't. Think of a single strand break as a dodgy zip on your trousers you can still zip and unzip but it may be a bit stiff in one place. A double strand break means someone took the scissors to your trousers and cut right through the fabric on both sides of the zip at right angles to the zip, you ain't ever getting that working again.
Radiotherapy does most damage by ionising water in the cells, thus releasing oxygen which breaks DNA. It needs to do so much damage that every cell has got double strand breaks. This damage is cumulative whilst exposed to radiation. Every fraction breaks more DNA. DNA is damaged but hardly any cells are killed. Over the next few years cells will think about dividing, a lot of normal cells will manage to repair their DNA (some won't): cancer cells will just go ahead and attempt to divide, but the zip is broken, so the daughter cells will not get a full compliment of DNA and they will not survive.
So psa nadir will occur when the majority of cancer cells have attempted to divide post radiotherapy. Prostate cells only think about dividing every couple of years.
If your lucky normal prostate cells will carry on dividing so slowly normal psa will recover.
Apparently the theory above came about in the 1970s, scientists realised, that cancer is not rapid cell division, it is just a failure to stop dividing when there are already enough cells.
Hope the above makes sense, start googling if you want to know more.
Sorry John none of this explains your pain.
Edited by member 02 Mar 2020 at 22:35
| Reason: Not specified
|
User
Thanks for the detailed explanation Dave,
I am a engineer so never really got into biology, effects of radiation, etc. but it’s funny how being diagnosed focuses you on learning about your body and treatment.
User
Dave, your explanation is correct, as far as I understand the mechanism.
I will just add that DNA repair inside cells happens much more frequently than just at cell division, indeed for prostate cells, usually well within 24h for healthy cells (it varies for different cell types - lung cells repair DNA much faster). This is why daily radiotherapy cycles work quite well - they give the healthy cells time to repair before being hit again, but the cancer cells which by definition have a faulty DNA repair mechanism don't get to repair in 24h, and the DNA corruptions accumulate day on day. The object is not necessarily to kill the cell or even stop it from working, but you only have to stop it from being able to perform cell division, in order to stop it being malignant. In many cases, the formerly malignant cell will continue to live (and produce PSA into the blood) until it dies of old age (rather than by apoptosis - programmed death before a cell wears out, the mechanism which fails in cancer cells), hence the slow drop in PSA over the next 18 months as the formerly malignant cells die of old age.
User
I bet you are a bundle of laughs at a dinner party! Obviously, it was a simplified explanation - a lot of people like to visualise what's happening rather than the technicals.
You probably wouldn't agree with my fruit bowl explanation of staging either (because obviously there isn't really an orange and an apple next to the prostate) but it works for many readers.
"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard
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User
Hi Lyn,
People stopped inviting me to parties ages ago. I think it was when I started telling five year olds that Father Christmas doesn't exist, (but he doesn't, as I had to point out to the annoyed parents).
I like the simple explanations, but if someone wants to go further, they now have a bit more info. I know a lot of people will just skip over though.
Apples and oranges. You can't compare one with the other!!! Can not compute, can not compute, %#@#-£&..
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User
Thanks Andy,
I knew my explanation didn't fit well with daily fractionation, and I must be missing something. Anyway we'd better keep quiet otherwise Matron will tell us off for talking after lights out :-)
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User
Hi Dave, just to prove that some people read to the bottom of the posts.
I have been told I am an orange because I have skin, and oranges have skin, etc. ... maybe I am a prune because my skin is becoming wrinkled.
I am hoping this RT is removing the rotten apples from the barrel 😉
User
Originally Posted by: Online Community MemberHi Lyn,
People stopped inviting me to parties ages ago. I think it was when I started telling five year olds that Father Christmas doesn't exist, (but he doesn't, as I had to point out to the annoyed parents).
I like the simple explanations, but if someone wants to go further, they now have a bit more info. I know a lot of people will just skip over though.
Apples and oranges. You can't compare one with the other!!! Can not compute, can not compute, %#@#-£&..
😂 I caused much offence in our neighbourhood by telling my children where babies came from long before any of the other parents were quite ready for their children to hear it from mine
"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard
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