What happens to cancer cells after radiation

Some papers say the effect of radiation is different depending on the phase the cells. That the cells must be in the dividing phase, otherwise they just live on without the ability to divide. That's scary. I thought that eventually all the cancer cells would die and be carried out of the body by the natural waste removal process.

As I understand it is variable.   Some cells may die quickly from the radiation effect.   This is more so with the stronger focal radiation like HDR brachytherapy, SBRT, etc.   Most, hopefully, all the radiated cells suffer DNA damage that they are unable to repair (healthy cells are also damaged, but are better able to repair the damage).   This will stop their reproduction and thus tumor growth and spread.   Eventually most will die (apoptosis) and be swept out of the body.   Their death and removal from the body is evidenced by the falling PSA.

The prostate cell is one of the longest living cell in the body.   This is one of the reasons that the cancer is generally slow to divide and spread and not so vulnerable to chemotherapy (which works better on short lived cells that are more active).   Thus many of the cells can remain alive in the body for a very long time.    Hence the reason why it may take 18-36 months for the radiation patient ro reach the PSA nadir where the surgery patient reaches it very quickly (killing the cancer versus removing it).

One of the mutations that occur in the cancer cell is that the normal cell life span doesn't work and the cell can live as long as the host is alive.   But, so long as they are not reproducing or spreading they may not cause any problems.   It is known that some PCa cells can go dormant for a very long time and then awaken.   This is especially true when they find their way into the bones.   A client of mine went PSA undetectable for 16 years after surgery only to find his PSA rising.   He was then treated with ADT. 

As I understand it the electrons (or protons) pass through the body at extremely high speed and strike cells delivering damage. When the electrons (protons) strike the cell nucleus they damage the DNA helix and the cell struggles to repair such damage. In succeeding cell divisions the damage is more difficult for the cell to maintain cohesion, and mitosis (cell multiplication or "dividing phase") is affected. Duplication of damaged chromosomes during mitosis aggravates this damage and cell malfunction accumulates. Over time, some days, weeks, months, or maybe longer, these cells eventually have such DNA breakdown that they lose the ability to divide and replicate and thus lose their constituent parts to the corpus as a whole. This is cell "death". All death is a reconstitution, of course.
This occurs during radiation with healthy cells also, but with precise targeting and dose adjustment the hope is that tumor cells are affected more so than healthy cells. The cost/benefit calculation comes into play at this point.

Steve n Dallas said...
Sixty Minutes had a great show last night.. They talked about cancer had more to do with Healthy cells not being able to die naturally then bad cells dieing...

Did you mean this?

www.cbsnews.com/news/billionaire-doctor-fights-cancer-in-unconventional-way/

Before SRT I was debating whether or not to have adjuvant hormone therapy. I thought I'd want the cells to be as weak os possible during radiation. My doctor said he could go either way, but argued that it might be better if the cells were trying to divide during radiation. That convinced me, and I didn't do hormone therapy. So far so good, undetectable 18 months out.

FoxRun said...

Steve n Dallas said...
Sixty Minutes had a great show last night.. They talked about cancer had more to do with Healthy cells not being able to die naturally then bad cells dieing...

Did you mean this?

www.cbsnews.com/news/billionaire-doctor-fights-cancer-in-unconventional-way/

That's the one. Pretty interesting story.

HDR brachytherapy can be used for salvage after other radiation.   Perhaps other focal radiation like SBRT might also be available.   External beam IMRT/IGRT might also be used depending on the amount of radiation you already had and the passage of a certain amount of time.   When asked about repeat radiation, most rad oncs simply say no, but some will more appropriately say, it all depends.   The reason we rarely see a second round of radiation is that it is extremely rare to suffer a local recurrence after radiation.   If there is a recurrence, it is because cancer was already outside the radiation area.

My wife had breast cancer in 1996 with a lumpectomy, radiation, and chemotherapy.   She was told she could never again have radiation.   In 2010 she had another breast cancer.   This time double mastectomy.   The surgeon wasn't pleased with a margin and sent us to a very skilled rad onc.   He labored over the records of the past radiation with his physicist and dosemetrist and designed a highly focal method to just the one suspicious spot and delivered 30 fractions.   My wife is doing just fine. 

I had the oligo-metastatic RT that Myers has made several recent vlogs about. Mine was at Dattoli in summer 2012. The bed, lymph nodes and two bone mets were treated. I declined the Samarium injections offered. When Myers started testing me a year ago for immune factors I was below standard and declining. He started me on some over the counter assistance with mushroom extract and N-Acetylcystein (sp?) but there was little change. I have recently started Leukine injections. Myers suggests the the radiation to the nodes was the contributing factor and not the bone and marrow. The other RT side effects were quite predictable and dealt with easily.
My psa was undetectable for 10 months after T recovery and has been rising now and I anticipate restarting therapy in the coming year. All in all I believe it was worth it to reset my clock, as it were.

tarhoosier said...
As I understand it the electrons (or protons) pass through the body at extremely high speed and strike cells delivering damage.

Oh Boy, Oh Boy! Said Peter, jumping up and down excitedly. Finally something where I can say something about radiation and be fairly sure I am right! X-Rays are photons not electrons. That's it... all I really know. The rest is speculation.

The theory that HT ought to protect cancer cells from radiation damage is respectable. Seems to make sense. If the cells with the damaged DNA die when they try to divide then if you can keep them dividing briskly after you zap them... it sounds right... but it doesn't seem to work that way. Dunno why. The hormones make the cells more likely to die from the radiation.

My best theory is that they die from the depression and ennui which the hormones are well known to cause.

Mitch:
I am tested monthly for CD4, CD8, NK cells and some others as an overall immune blood set, among other tests. Seven vials of blood total monthly. These immune factors have not come into normal range since testing started a year ago. I started Leukine (sagramostim) just a few days before last month's test so no response noted yet and will be another week before the next test. Myers says response by immune cells to Leukine is seen in all men (is that possible? All?). I hope so.
T-cells? Are they the same as I am tested for? I do not know what test will identify T-cells as I only barely understand the tests I undergo now.
When I last saw Myers 6 weeks ago he said he saw my immune response regularly in men with such radiation and specifically said it was not bone and marrow response as that was red blood cell production.

tarhoosier in Charlotte

I read this thread the other day, and thought there was nothing I could add to JNF's (as usual) excellent explanation. But then I saw Peter jumping up and down excitedly, and Andrew sending cancer cells to hell, and realized I was missing all the fun. I just have a few comments re assorted posts.

Radiation and immune function
I think you're all correct, but you are describing different settings. When radiation is used on the prostate and isolated mets, it raises the immune response.(I have seen no studies about immune suppression from extensive lymph node treatment, so I can't comment on that.) Hypofractionation (SBRT & HDR) seems to raise the immune response the best, and ADT seems to help in that situation too. The nasty suckers are blasted apart and tons (ok, not tons) of antigens are presented to T cells, starting a strong immune response. Those activated T-cells seek out and destroy micromets elsewhere. Lupron Jim is maximizing this abscopal effect by taking Provenge before, during and after his SBRT. Eventually the T-cells get bored, perhaps the same ennui that PDA speaks of, and stop working. There are now checkpoint blockers like Yervoy and PD-L1 blockers that keep them awake and alert.

The situation is different, however, when radiation is applied to long sections of bone, the bone marrow, where white blood cells are born, becomes fallow. This is done on purpose, for example, to cure some kinds of leukemia.

Re-irradiation for salvage
Once again, I have little to add to what JNF said. IMRT, at about 80 Gy, does get pretty close to the limit after which healthy tissue can no longer self-repair. They push it as high as 86 Gy at MSK sometimes on high precision linacs. It is not at all clear that it's a lifetime limit, however. One RO I spoke to claims that every 5 years, healthy tissue has repaired enough such that it's like it's only been subjected to half the dose. I haven't seen any research to confirm or refute this and just pass it along FWIW.

Spot re-irradiation is entirely possible (it's called "focal salvage radiation") in the rare cases when a local failure has occurred. In a recent 7-yr f/u SBRT analysis, 4% failed, but only 1% was a local failure. In such cases, SBRT, HDR brachy, and LDR brachy have all been used for salvage with low rates of side effects. The situation is even better when SBRT or brachy have been used as the only original therapy because the original radiation dose is only half as big.

While proton may not yet be used for salvage, a related therapy, carbon ion, is being used in Heidelberg for that purpose.

Mitch in SC - I invite you to re-examine your notions about chemo for PC, which would probably be Taxotere (docetaxel). It does not have the toxicity profile that you probably think of when you think of chemo. And the side effects are lighter, and more tolerable, the younger and healthier you are. Most men who have taken it say it has increased their QOL rather than decreased it. Taking some time to do it while you are still hormone sensitive may give you a median of 17 extra months of higher QOL time. I'm not saying that it will be easy for the couple of months or so that you take it, but most get excellent health recovery afterwards, and that health may last a long time.

- Allen

Both of my parents went through chemo for different cancers, and I am well aware of what it can do. All I can tell you is every cancer is different, and what you think you know about chemo from another cancer is probably not true for PC. You also reinforce what I believe - it is a terrible idea to ask any doctor, or anyone else for that matter, what he would do if he were you. He is not you. He can scarcely imagine what it is like to be you and to be in your shoes. The decision is all yours and what he would do doesn't matter one iota.A good doctor wouldn't tell you, and an empowered patient wouldn't ask.

- Allen