Increasing Radiation Effectivness

radiationI intend to have this post evolving over time as I have a large collection of research indicating various approaches to enhance the effectiveness of radiotherapy. Therefore, I am not going to debate on whether radiotherapy is good or bad. Instead, I will focus on how to make the best of it once we decided to use this anti-cancer tool. So here are some relevant aspects on this line:

Increasing the chance for a radiation induced abscopal effect: A neutrophil perspective

The so-called “abscopal effect” is the effect in which radiation therapy delivered to a primary site of cancer also results in shrinkage or elimination of cancer cells in other metastatic sites that were not exposed to radiation. This effect has been observed for decades in some lucky patients. However, this “abscopal effect” is not controllable and it happens randomly as it is not well understood by scientists. What is clear is that somehow, in some special conditions, killing cancer cells at a specific location in the body triggers a T cell-mediated anti-tumor immune response.

Interestingly, an article published in Science Daily on 21st September 2016, sumerizes a recent publsihed paper that brings more clarity extactly on this very interesting subject:  Neutrophils are key to harnessing anti-tumor immune response from radiation therapy, study finds

This recent study indicates that the reason for the radiation induced “abscopal effects” seems to be the following:  radiation destroys tumor-associated neutrophils (TANs), recruiting new neutrophils into the tumor; these new radiation-induced neutrophils (RT-Ns) attack the tumor cells by producing molecules that damage them, generating a downstream tumor-specific, T cell-mediated anti-tumor immune response.

Moreover, the researchers were able to enhance the tumor killing capacity of the RT-Ns by administering G-CSF (Granulocyte-colony stimulating factor), a naturally occurring protein (cytokine) in the body that stimulates bone marrow to produce more white blood cells including neutrophils. Note that G-CSF (commercially available) is routinely used to treat neutropenia. Granulocyte-colony stimulating factor is indicated for neutropenia caused by cancer chemotherapy, osteomyelodysplasia symptom-complex and aplastic anemia, congenital and idopathic neutropenia, etc, and also promoting increase of neutrophil count after bone marrow transplant. (Ref.)

Interestingly, G-CSF may be stimulated by corticosteroids (Ref.). Thus, glucocorticoids dose-dependently increase plasma levels of granulocyte colony stimulating factor (G-CSF) (Ref.). As a result, I assume that if G-CSF is not available, administrating corticosteroids before radiation may also help to increase neutrophils  in the blood. Having the radiation in the morning may also help as cortisol (a corticosteroid) is at the highest levels early in the morning with its peek at around 8-9 am (Ref.). Indeed, here is a study indicating the correlation between cortisol circadian variation and neutrophils variation (Ref.).

In conclusion, administration of G-CSF or corticosteroids prior to radiation may increase the chance for a whole body anti cancer response. Administrating radiation early in the morning may further help on the same line.

Increasing the chance for a radiation induced abscopal effect: A T-cell perspective

In order to induce an abscopal anti-tumor immune response following radiation, besides the role of neutrophiles discussed above, T cells’s capability to act against cancer cells is essential.

Recently, it has been shown that a patient with a cancer type known not to respond to T-cell “release” focused therapy based on ipilimumab (a human monoclonal anti-CTLA-4 antibody) experienced an immune response when ipilimumab was administrated just next day after radiation session. Here is the very nice case report: An Abscopal Response to Radiation and Ipilimumab in a Patient with Metastatic Non-Small Cell Lung Cancer http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930458/ As it can be seen from this report, the patient had a very nice and sharp results that led to the immune system cleaning up his entire body of metastasis.

What I can learn from this, is that administration of immunotheraphy just after radiation session (e.g. next day) will increase the chance for an abscopal effect. anti-CTLA-4 or anti-PDL1/PD1 immuno therapies can be used for this as they should be available to anyone (at list in Germany that is the case). Personally, I would consider lowering the typical dose of immuno therapies from 3mg/kg typically suggested to about 1mg/kg and administer both of them (e.g. ipilimumab and nivolumab) at the same time to eliminate more mechanisms that regulate the action of T-cells. (I would lower the doses of the two therapies to both reduce the toxicity and the cost, while it is known (from private clinics in Germany) that response to these therapies can also be obtained at lower doses, as low as 1mg/kg/month/patient.)

Note that, preclinical models support use of hypofractionated RT in daily doses of 6 to 8 Gy given 5 or 3 times, over a single high dose treatment of 20 Gy, in order to maximize likelihood of generating an effective anti-tumor immune response with anti-CTLA-4. Consistent with this finding, the most dramatic cases of abscopal effect reported with ipilimumab and RT have utilized RT doses and fractionation [26, 27, 29, 30] similar to the RT regimens effective in preclinical studies. However, abscopal effects were also reported in patients treated with a wider range of RT doses [26, 29, 31]. (Ref.)

Here is a clinical trial Phase 2 showing important abscopal effects in NSCLC patients including complete resolution after combining Radiotherapy with Ipilimumab: http://www.redjournal.org/article/S0360-3016(15)00890-1/fulltext The treatment approach included Ipilimumab (3mg/kg i.v.) within 24 hrs of starting RT (6 Gy x5 daily fractions) to one lesion. Ipi was repeated every 21 days x3.

Fractionation better than single-fraction treatment

The negative influence of hypoxic cells against local tumor control is apparently greater in hypofractionated SRT and the greatest in single-fraction treatment. During fractionation, however, surviving hypoxic tumor cells reoxygenate and become more sensitive to subsequent irradiation. (Ref.)

More content will be added asap on other approaches to increase radio therapy effectiveness.

References:

Current clinical trials testing the combination of immunotherapy with radiotherapy http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028964/

Increasing evidence demonstrates that radiation acts as an immune stimulus, recruiting immune mediators that enable anti-tumor responses within and outside the radiation field. There has been a rapid expansion in the number of clinical trials harnessing radiation to enhance antitumor immunity. If positive, results of these trials will lead to a paradigm shift in the use of radiotherapy. In this review, we discuss the rationale for trials combining radiation with various immunotherapies, provide an update of recent clinical trial results and highlight trials currently in progress. We also address issues pertaining to the optimal incorporation of immunotherapy with radiation, including sequencing of treatment, radiation dosing and evaluation of clinical trial endpoints.

Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. http://www.ncbi.nlm.nih.gov/pubmed/15701862/

The combination of local RT with CTLA-4 blockade is a promising new immunotherapeutic strategy against poorly immunogenic metastatic cancers.

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

Please read an extended version of the Disclaimer here: https://www.cancertreatmentsresearch.com/?page_id=1794

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59 thoughts on “Increasing Radiation Effectivness

  1. I’ve been a bit busy lately but really wanted to key in on researching the abscopal effect. Dr. Williams tries to induce this effect (and based on certain things he showed me, has succeeded) by applying immunotherapy drugs intra-tumorally prior to inducing local tumour destruction through cryoablation.

    In a simplistic sense, all new immunotherapy drugs tend to try to induce the abscopal effect with some frequency. The problem is that they’re being applied systemically, and cause a huge deal of potentially fatal and dangerous side effects. I think immunotherapy might be one piece to the abscopal effect puzzle, but there has to be more. Maybe combination of immunotherapy drugs with radiation or local treament would be more effective. But even still, I feel like there’s something of an X-Factor missing in the puzzle and maybe neutrophils might be part of it.

    Thanks for the post.

    1. Thanks Meech for your comment. Indeed, abscopal effect is challenging to achieve but possible. Besides the need for neutrophils, T-cells should be able to act. On that line, I would think that a treatment with intravenous Natrium Bicarbonate prior to radiotheraphy and after that should help. And/or the proton pump inhibition strategy discussed in an earlier post.

        1. I guess you meant NaBic not NaCl? Long term administration might help but on short term I would not expect much from the oral administration. And as you know, when fighting cancer we always have to use the most effective route (assuming it is accessible). NaBic IV is cheap and I would expect is accessible to nearly anyone as it is probably available at any clinic.

  2. Hi, Daniel!

    Thank You for Your posts! You do great job!!!!

    I have secondary hormonal breast cancer in bones and currently on anastrazole, zoledronic acid and metformin, simvastatin, doxycycline (COC protocol).

    As new bone spots appeared I will perform radiation therapy for few bone spots.
    I read Your post and found very interesting idea about granulocyte colony-stimulating factor prior to radiotherapy.

    http://www.pnas.org/content/113/40/11300.full

    How do You think – should I stop to take metformin, doxycycline and statin during granulocyte colony-stimulating factor action and during radiotherapy? Could they work synergeticaly or they are antagonists?

    Which granulocyte colony-stimulating factor do You sugest? Filgrastim could be ok?

    Thank You!

    1. Dear Sirsna,

      Thank you for your words of appreciation! COC protocol includes drugs that I also find very useful. I do not see a reason to stop the drugs with the exception of one that is doxycycline. I would probably stop doxycycline for a week or two prior to the radiotherapy. That is because of the negative effect of doxy on the gut bacteria and as a result on immune system https://www.cancertreatmentsresearch.com/gut-bacteria-amplifies-immunotherapy/
      However, you need to decide with your doctor if it is a good idea to stop.
      Also note that I do very much like Doxycycline and its anti cancer effects just that in this case it would not fit well with the goal of achieving an abscopal effect. The point is that if we want to have chances for an abscopal effect we need to have an immune system in a good shape.
      On this line, two weeks prior to radiotherapy I would also take probiotics – and the best probiotic is sauerkraut juice.

      If I would go for radiotherapy, I would also strongly consider a pH strategy such as discussed here https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ The idea is that radiotheraphy seems to reduce the pH inside the cancer cells. And using the above pH strategy will help to further reduce that and as a result increase the anticancer effects. That is expected. You are already using Statins and Statins are known as MCT1/MCT4 inhibitors which means that you are already addressing one on the points the pH strategy is addressing https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ The best would be if your doctor could also use Amiloride to address the other major proton exchange mechanism. Omeprazole (which you already may take to protect your gut from Doxycycline) and Acetozolamide may further help to address other proton channels and further increase the chance for a successful immunotheraphy but also for an active immune system during and after radiotheraphy. But you would need to do this with the help with your doctor since Amiloride is on prescription and you need a doctor to follow the K level every two weeks.

      The above should all be easy to implement with the help of a kind medical doctor or a family doctors.

      I do not have a G-CFS in mind that would be best.

      If you have other questions please let me know, and I apologize for the delay of my response.

      Kind regards,
      Daniel

    2. Here are more ideas to improve the immune system in preparation for radiotherapy: https://www.cancertreatmentsresearch.com/dendritic-cell-therapy-supporting-strategies/

      Cimetidine will also help not only against metastasis but also inhibiting Tregs and thus maintaining an active immune system around radiotherapy.

      Here is a nice article to read in case I didn’t added above as a reference:

      Radiation therapy and the abscopal effect: a concept comes of age https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828732/

  3. Thank You, Daniel for answer !

    I highly appreciate Your knowledge.

    After 2 week course of doxycycline 100mg/day I feel tired and my tongue is dark brown (I am surprised by this reaction because we used to take it for months as antimalaria`s drug 10 years ago without serious side effects). As I take COC medications on my own I do not have doctor to whom discuss about on or off doxycycline.

    According to doxycycline COC have mixed schedule – 1 month doxy, 1 month Mebendazole. I am in the middle of 1 month doxy.

    Naturally brewed sauerkraut is my favorite food, thank You for reminder. I like to eat bowl of in a day it if I remember. I am proud that my little 4 years old is loving sauerkraut as much as I, but 5 years old agrees to take sauerkraut juice, but with condicion that kefir will follow after s.juice :).

    I must confess that I have lost understanding about neutrophils – which one are pro-tumor neutrophils and which are anti-tumor neutrophils, regulatory T (tregs)…

    I also take :
    Melatonin at night 10mg
    Aspirin 75mg
    vitamin D, omega 3, VitaminK2 (MK-7)
    ECGC and green tea
    Metformin 500-750mg /3x /day
    doxycycline 100mg/day
    Simvastatin 40mg / day
    Anastrazole
    Indole-3-carbinol
    beta glucans
    zoledronic acid i/v

    I can restart curcuma (turmeric) with black pepper & olive oil (could not find place in my drug schedule)

    I am not taking Omeprazole, but I will start it. Thanks for advise. This I can get without prescription.

    I can not find what is Acedozolamide and Amiloride (I affraid they are not in my country).

    What do You think about Dipyridamole? And Propranolol? Just get them from Romania (thanks, Carl, for contact :)).

    And ine more question – I have heard about good words about hyperthermia, but what do you think about Hipothermia (aka. winter swimming, criosaunas, cold shower)? It is huge short adrenaline boost, but is it good or not?

    2 years ago I had oligometastasis in vertebrae T6 (with fracture). Got radiation un 3 month later PET scans showed all silent.
    Now Pet scan shows 1 new spot in vertebrae T7, 1 spot in intestinal bone, and my right femur is full with spots, few of them lytic with holes in bone.

    best whises,
    i.

    1. Dear I,

      Thank you.

      Acetazolamide and Amiloride role are shortly explained here https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ but even more in the included references. Both are diuretics, each working in a different way. I’ve got my Amiloride from here http://www.buypharma1.com/ but anyone using it has to have its K blood levels checked every one to two weeks since blood K may incraese.

      Dipyridamole: I like it, I intend to write about is and I know a lady with breast cancer using it for long time (next to others) – she is fighting triple negative and she is alive way beyond statistics. Given the way it works I would expect it will help radiotherapy as well.

      Propranolol: it was of great help to us and I wrote about its anti cancer mechanisms here https://www.cancertreatmentsresearch.com/propranolol-hexokinase-2-inhibiton-a-similar-anticancer-mechanism-as-that-of-3-bromopyruvate-3bp/ but I would be careful with it since it will lower the heart rate. If the heart rate is already low for the one intending to use it, it may be dangerous. In that case, I would avoid it.

      Btw, how that you’ve got them from Romania? I do know that it is easier to get drugs from Romania 🙂

      I do not have yet a view on hipothermia and cancer, so I can not answer that question. But maybe someone else reading this comment could help on this.

      Btw, I was once speaking with a prof from an important cancer center in US about Baicalein. They wanted to start up a clinical trial using Baicalein against breast cancer. Indeed, I have seen in a statistics based on chemosensitivity studies showing that cancer cells from breast cancer patients were almost always responding to Baicalein. Baicalein can be bought from China in pure form or as a part of whole plant in supplements such as this one https://www.iherb.com/pr/dragon-herbs-standardized-scute-500-mg-each-100-veggie-caps/55598

      Kind regards,
      Daniel

  4. Radiotherapy: Changing the Game in Immunotherapy.
    http://www.cell.com/trends/cancer/fulltext/S2405-8033(16)30036-X

    Prospects for combining targeted and conventional cancer therapy with immunotherapy.
    (The treatment of tumours with, for example, anthracycline-based chemotherapy can elicit an adaptive stress response that is accompanied by immune-stimulating pathways)
    http://www.nature.com/nrc/journal/vaop/ncurrent/fig_tab/nrc.2017.17_F4.html

  5. Hi, everyone !
    I decided to post some updates according my radiotherapy.

    2 weeks (11.04.2017.) prior radiotherapy my blood test showed:
    WBC leukocyte count, [email protected]/L 6.8
    Neutrophil count, [email protected]/L 5.0
    Lymphocyte count, [email protected]/L 1.3

    In the time of this blood test I took folowing medications:
    Metformin, simvastatin, doxycycline, omeprazole, aspirin, probiotics, anastrazole, vit D, K2, omega 3, melatonin
    On 13.04.2017. started to take dipyridamole, slowly raising the dose from 25mg till 200mg/day.
    On 19.04.2017. stopped doxycycline, started antihistamine Loratadine.
    On 21.04.2017. started subcutaneous g-csf stimulant Tevagrastim 30IU – I had 1 dose 3 following days (21.-23).
    On 25.04.2017. first injection of Dexamethasone (corticosteroide)

    Few ours before radiotherapy (25.04.2017.) my blood test showed:
    WBC leukocyte count, [email protected]/L 14.5 (previously 6.8)
    Neutrophil count, [email protected]/L 11.7 (previously 5.0)
    Lymphocyte count, [email protected]/L 1.8 (previously 1.3)

    I got 1 single dose radiation 8Gy to spine (repeated irradiation(previous was 2 years ago 20Gy))

    26.04.2017 second injection of dexamethasone

    1 day after radiation (26.04.2017) my blood test showed:
    WBC leukocyte count, [email protected]/L 8.8 (previously 14.5)
    Neutrophils count, [email protected]/L 6.9 (previously 11.7)
    Lymphocyte count, [email protected]/L 1.3 (previously 1.8)

    I got 1 more dose of tevagrastim late evening yesterday.

    And I must start today oral dexamethasone for 1 week.

    As we can see – very sharp changes prior and post single 8Gy radiation dose.
    Of course, I would like to see some immune response also outside radiation field.

    In the end of May I will have another course or radiotherapy to my Femur. This time 3Gy x 10x = 30Gy.
    I think I will repeat with g-csf stimulant Tevagrastim.
    Dear Daniel and all others here, How do You think – should I change something in the pattern of medication schedule now and prior to second session of radiation in the end of May?

    Thank You,
    ieva

    1. Dear ivea, thank you for your clear post. I am traveling now and need more time to carefully read and add my opinion. Please send me a reminder on Saturday and will allocate time. I hope others will give you feedback in the mean time. Thank you.

      1. Dear Daniel,
        can I ask, please, did You find any new ideas about my previous post?
        I can add that I feel good, I am now in deep country and can not perform blood test for current situation. I just continue to take medications. It seems that Medrol (corticosteroide) gives me energy boost (maybe because it uppers blood glucose?).

        1. Dear ieva,

          Yes, corticosteroide may do that so you may want to stop if you do not need that unless the medical doctor recommended you to maintain.

          As promised here are a few ideas that you could look into:

          What we would need for a systemic response following e.g. radiation is:
          1. Radiation should be effective in killing at least some cancer cells to trigger the immuneresponse
          2. Immune system should be in the right shape
          3. Immune system should be able to act

          One of the major issue against 1.and 3. is Hypoxia. This is because
          • oxygen is a critical determinant of the response of cells to irradiation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752413/
          • Hypoxia means the glycolysis will be high and so the acidity around the tumor which in turn deactivates immune system, even if we have a well-shaped immune system

          Therefore, to address Hypoxia, I would
          • make sure will increase the oxygen at the tumor site and
          • reduce acidity around the tumor

          Increasing oxygen can be done for example with one or a combination of the following, prior to radiation:
          • hyperbaric chamber https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510426/
          • vasodilators (e.g. Naicin/Vitamin B3 or Nitroglycerin, but also Quercetin) http://www.news-medical.net/news/20150827/Nitroglycerin-can-be-repurposed-to-treat-cancer-researchers-find.aspx dipyridamole may be enough but adding Vitamin B3 may help
          • Myo-inositol TrisPyroPhosphate to increase red blood cells’ ability to release oxygen https://www.ncbi.nlm.nih.gov/pubmed/23045284

          These are just a few ideas, you may think of more

          Reducing acidity around the tumor can be done by one or a combination of the following, prior to radiation:
          • Using proton pump inhibitors discussed here https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ the tumor will become more sensitive to heat and radiotheraphy.
          • Using Sodium Bicarbonate IV prior to radiation
          • Using glycolsis inhibitors such as 2DG, etc. (I discussed many on this website) http://www.nature.com/onc/journal/v25/n34/abs/1209597a.html

          Note: proton pump inhibitors will not only help by creating a better environment for the immune “learn and act” process around the tumors (once there is a break down on cancer cells by radiation) but will also work in synergy with radiation to kill tumors cells since radiation also lowers intracellular Ph, same as proton pump inhibitors. There is a lot of research on this and here is an example of a research group working on this line https://www.radiationoncology.umn.edu/research/division-radiation-biology-and-molecular-cancer-therapeutics

          To address the issue nr. 2 (from top), i.e. immune system has to be in the right shape, you may want to consider:
          • The two ideas discussed in the post above – you are already using one but you may also want to consider very low dose immunotheraphy after radiation if you could find a medical doctor to support. You may also consider other immune activating solutions such as immunomax (discussed on this website – since you are close to Russia you may have access to it), mistletoe injections, etc.
          • There are many supplements that can help activate the immune system and I am sure you are aware of many but I would ad Coriolus to that if possible
          • Probiotics is very important specifically when using Antibiotics – bets Probiotics is sauerkraut juice https://www.cancertreatmentsresearch.com/gut-bacteria-amplifies-immunotherapy/ Due to this I would stop the use of Doxycicline while trying to build up the immune response

          To further address the issue nr. 3 (from the top), I would use ways to inhibit Tregs and MDSC cells prior to radiation, using H1 and H2 blockade with e.g. Cimetidine and Cetirizine https://www.cancertreatmentsresearch.com/antihistamine/ Indeed you already used an antihistamine but you may want to map it with the short article I wrote and the related references.
          Low dose cyclophosphamide is often suggested by very good medical doctors to be used around immunotheraphy to enhance immune reaction due to Treg inhibition https://www.cancertreatmentsresearch.com/dendritic-cell-therapy-supporting-strategies/

          I think, this may represent a good strategy around the radiotherapy.

          I hope this helps.

          Kind regards,
          Daniel

          1. Hi all!

            Now I can say that my Immunomax is driving to me from Russia :). I had to call to several pharmacies and only in few I found it. It was not possible also to order to Russian pharmacies as it was out of stock also from suppliers. Hope to get it tomorrow.

            Daniel, can I ask, please, about Cimetidine and estrogen boosting?
            As my cancer has estrogen receptors 100%, I am confused about estrogen stimulating…. (My cancer also has 80% Progesteron receptors, 100% Androgen receptors and I am now on Aromthaze Inhibitor)…?

            Thanks,
            ieva

  6. Hi!
    A Little update from me

    Today I started my next radiation session. This time to femur where both lytic and blastic lesions appeared.
    Today before scans my blood count was :

    Leukocytes 12.6 (ten days ago 3.6)
    neutrophils 9.5 (ten days ago 1.2)
    Lymphocytes 1.98 (ten days ago 1.1)

    I used all the same medications plus two g-csf 30 iu (week ago and 5 days ago)
    zoledronic acid (bisphosphonates i/v) 2 days ago
    light immune stimulant Maitake (just it was at home already)
    I did not start “Immunomax” because when i got it I did not have enough time for full course so I leave it for after radiation time.

    I will have 10 radiations sessions.
    IN the middle of summer I will have 3th radiation session to another two spots.

    Best regards,
    ieva

    1. Thanks a lot of the update ieva! Very large immune response to the two medications. Mushrooms are also well known to enhance the immune system. Including Maitake, Coriolus, Agaricus, etc.
      All the best!

      1. Hi all!

        Two month after last g-csf strategy and radiotherapy course to bone my newest blood markers still rise (CA15-3 has doubled).

        I thinking how I can change some treatment strategy and do something went wrong?

        BR-MA (CA 15-3)
        59.7 IU/mL aug-2017
        26.4 IU/mL may-2017
        22.8 IU/mL may-2017
        17.4 IU/mL apr-2017
        10.8 IU/mL feb-2017
        8.0 IU/mL sep-2016

        7.9 IU/mL feb-2016
        9.1 IU/mL apr-2015

        Best regards,
        ieva

        1. Hi Ieva,

          I am sorry to hear that the CA is advancing. Although is difficult to say, if I look at the data you shared, it seems like the change in evolution started sometime between Feb. and April. So I was wondering if there was any special treatment change you did (stop or start) in March? Was that the time when the bone spots emerged?

          What is the proposal of your oncologist for the next steps?

          Also, what is the treatment you are doing now? Conventional and complementary. Maybe we can give you some ideas.

          Kind regards,
          Daniel

          1. Thank You, Daniel, for Your response and support !!!

            It seems that my tumor changed aggressiveness while I had a 1.5-2 month pause jan-feb-2017 in medications, that affect tumor`s metabolism prior to Pet/ct scan. I had Pet/ct scan on 1th of March 2017 where new bone spots appeared (before that I supposed to be NED as my oncologist wanted to take of Zoledronic acid). I will see my new oncologist next week when we will discuss next steps. (I changed supervising oncologist in june as my previous oncologist believed that there is no reason to change complementary treatment (anti hormonal) despite the fact that Pet scan showed few new spots).

            We should also take in mind that g-csf treatment can make false positive Ca15-3 elevating (but somehow I feel it`s not my case). In past 3 month I totally received 7-8 injections of G-CSF Tevagrastim 30IU, with last injection ~1.5-2 month ago (which is not so high dose, although it contributed to a strong fluctuation in white blood and neutrophil cell counts).

            “…CONCLUSIONS: These data provide strong evidence that G-CSF administration can induce elevation of CA 15-3 and indicate that false-positive results should be considered when evaluating CA 15-3 in patients who are receiving G-CSF. It is speculated that this phenomenon occurs through the induction of MUC1 antigen of unknown origin by G-CSF. Experimental investigation of this clinical observation is warranted.”
            http://www.thedoctorsdoctor.com/labtests/ca15-3.htm

            “The neutrophil, not the tumor: serum CA 15-3 elevation as a result of granulocyte–colony-stimulating factor-induced neutrophil MU1C overexpression and neutrophilia in patients with breast carcinoma receiving adjuvant chemotherapy.”
            https://www.ncbi.nlm.nih.gov/pubmed/15386335

            Here I tried to list my treatments through last years :

            apr-2014 : finished standart treatment of local breast cancer (chemo+surgery+radiation+antihormonal Tamoxifen+curcumin, black peppers, greens, vit D, fish oil, green tea, running)

            may-2015 : first mets to bone (radiation therapy to spine, from Tamoxifen to Anastrazole, introduced myself to ketogenic diet, Zoledronic acid (bisphosponate) every 3 weeks, Melatonin), vit D, fish oil, Magnesium, stable for ~ 1.5-2 years

            jun-2016 : added low dose Metformin XR(slow release) 1000mg, added Aspirin 75mg

            oct-2016 : MRI suspicious activity in previous radiated spine, blood cholesterol levels very high – added Atorvastatin, weaned off keto diet (too many coconut oil fot me), added Berberine

            jan-2017 : stopped Zoledronic, Atorvastatin, Metformin for 1.5-2 month (prior to Pet scan)

            mar-2017 : Pet scan shows spots in bone, back to statins (Simvastatin 40-60mg), full dose Metformin (2000mg), Melatonin (10-20mg), Anastrazole (anti hormonal), back to Zoledronic acid every 3-4 weeks, added Doxycicline 100mg(continued for 2 month), Aspirin 75mg, Beta Glycans, I3P, probiotics, sauercraut.

            apr-2017 : stopped Doxycicline (I took it around 50days), started Loratadine (anti histamine), started Dypiridamole, 3 doses of g-csf 30IU prior to radiotherapy, 2 injections of Dexamethasone prior to the first radiotherapy(one 7Gy dose to previosly radiated spine), oral Dexamethasone for few days after radiotherapy, added Ranitidine, Omeprazole

            may-2017 : added Maitake, PPI Omeprazole(40-80mg), started Mebendazole, blood cholesterol back to normal

            jun-2017: added Baicalen, Omeprazole (40-80mg), changed anti hormonals to Letrozole (changed supervising oncologist), started ECGC, try to add Cimetidine 200mg – 800mg (used for 2 weeks), stopped Ranitidine, 1 injection of g-csf Tevagrastim 30IU prior second radiotherapy course(10doses of total 30Gy), 3 injections of g-csf Tevagrastim 30IUduring this radiotherapy course, Immunomax half of 1 course (3 injections), Diclofenac

            jul-2017 : third course of radiation(2 single doses of 8Gy to 2 spots), stopped Mebendazole, stopped Cimetidine (subcutaneous bleeding), Diclofenac

            aug-2017 : still on following medications:

            Simvastatin 60mg, Dipyridamole 100mg, Metformin 2000mg, Zoledronic acid (bisphosponate) every 3 weeks, antihormonal Letrozole, PPI Omeprazole 40mg, anti histamine Loratadine, Aspirin 75mg, Melatonin, ECGC, I3P, Baicalen, Diclofenac, probiotics, vit D, fish oil

            best regards,
            ieva

            1. Hi all !

              Updates from me:

              With my oncologist we decided to wait for 1-2 month and then repeat blood markers. She offered to me some diagnostic (CT or bone scintigraphy), but agreed to wait.

              Best regards,
              i.

            2. I am sorry to hear that. Please let me know what are the plans of you and your oncologist and will try to think together with you on that line. I will find the time for that shortly. The historical overview above is very helpful.

              I have a specific question: have you seen any specific trends of markers that were different, before, during and after Doxy cycle?

            3. Hi Daniel!

              Thank You for Your fast response ! I was at the down for few days but now I am back :)…

              I can`t reach my oncologist these days, but it seems that she will offer some diagnostic scans to see what`s going on.

              Here I tried to put on paper exact dates and results of CA15-3 markers before, during, after doxy:

              20th of February CA15-3 11 U/mL, CEA 0.5ng/L

              I started doxycycline in the middle of March and stopped few days before first radiotherapy

              1th of March Pet scan shows spots in bones

              ~14th of March I started doxycycline 100mg/day.
              11th of April CA15-3 19 U/mL, CEA 0.85ng/L

              Stopped Doxycycline on ~21th of April.

              On 22th, 23th, 24th of April I had 3-4 injections of G-CSF plus 2 neutrophil stimulating Dexamethasone injections.
              25th of April single dose 7Gy Radiotherapy to spine

              26th of April CA15-3 17 U/mL
              15th of May CA15-3 23 U/mL
              24th of May CA15-3 26 U/mL

              8th of June radiotherapy + G-CSF
              4th of July – radiotherapy + G-CSF

              16th of August CA15-3 60 U/mL
              4th of September CA15-3 115 U/mL

              By the way, in Immune blood tests my CD4/CD8 index has raised from 1.0 in April to 1.3 in September. Also CD19 was 15, now CD19 is 20.
              And I always had Negative test to ANA (Anti nuclear antibodies), but now in September it is Positive 1/200 (this should be negative)
              Could this be some immune response to all immune enchanced therapy I had ? (G-csf (9 x 30IU injections), Immunomax(1 full course 6 injections)) and other… or maybe rare Letrozole side effect (which I started in ~June)?
              http://factmed.com/study-FEMARA-causing-ANTINUCLEAR%20ANTIBODY%20INCREASED.php

              ————————————

              According to this scientific paper “Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner” and “Tumor burden in bone is increased after G-CSF administration and is abrogated by zoledronic acid in a second osteolytic tumor model”
              https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852257/

              I am on Zoledronic Acid every 3 weeks i/v

              http://williams.medicine.wisc.edu/nfkb_gmcsf.pdf

              Kind Regards,
              i.

            4. Thank You, Daniel!
              I saw Your comment in other topic about Basentabs. I think I will order it. (I am crazy coffee drinker, maybe I am too acidic :)?)
              How about chemotherapy – could it be used together? (I will have meeting with my oncologist next week to introduce with my news, I think She will give me some chemotherapy, maybe Cisplatin?, maybe I should ask about Metronomic protocol. But I think I must try chemotherapy, which was not used before (I had TAC protocol which includes Cyclophoshamide)). I also want to ask liver biopsy. Do You have some ideas about chemotherapy and other protocol?
              Thanks,
              i.

            5. Hi!

              I am in next level unfortunately…

              I got my Pet scan results:

              Compared to previous 18fdg PET/CT (7 month ago), significantly negative dynamics.
              FDG hypermetabolic metastatic dissemination in the liver and bone.
              In both hepatic lobes, in practically all segments, multiple hypodense metastatic lesions.

              kind regards,
              i.

            6. Hi Ieva,

              I recently came across info from trusted sources (academic) regarding some capsules called Basentabs which seem to have very good potential. It has been suggested that 8 capsules/days may strongly help for various types of cancers. Essentially, these are increasing the “alkalinity” of the body. Also, Anca (a reader of this website) is using them for her mother and she said she already saw some good signs. Basentabs are easily accessible online and cheap. I would clearly try them.

              Kind regards,
              Daniel

            7. Hi I,

              Answering you question from above: Very good question! We once discussed here https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ the fact that acidic environment around the tumors will help the absorption of some Chemo and represent a Chemo resistance mechanism for others.
              On this line using Basentabs, as it reduces acidity, should help some chemo and possibly not help Chemos that are of acidic form. Also in the post at the link above I gave some examples of various Chemos that are of acid or base type as reported in the literature. Regarding the immune system, that should clearly be helped when the acidity is reduced around the tumors.

              Regarding your last question, besides my website that discusses many different treatment approaches that I think are relevant (you would need to go through various posts) I can send you a very good report on Breast Cancer discussing many treatment approaches (conventional and alternative) which I expect you will like it a lot 🙂 I would have send it earlier but only now I realize I have it.

              Update: I just sent the report to your e-mail

              Kind regards,
              Daniel

            8. Thank You, Daniel!
              I saw Your comment in other topic about Basentabs. I think I will order it. (I am crazy coffee drinker, maybe I am too acidic :)?) How about chemotherapy – could it be used together with alkalinizig agent? (I will have meeting with my oncologist next week to introduce with my news, I think She will give me some chemotherapy, maybe Cisplatin?, maybe I should ask about Metronomic protocol. But I think I must try chemotherapy, which was not used before (I had TAC protocol which includes Cyclophoshamide)). I also want to ask liver biopsy.
              Maybe You have some ideas about chemotherapy and other protocol?
              Thanks,
              i.

            9. Hi A,

              Yes, those are the Basentabs I was speaking about.

              Regarding the e-mail, I did receive it but did not had the chance to react. I was extremely busy during the past weeks and expect to be the same for the next week. After that it should be normal again. However, I will try to react asap.

              Kind regards,
              Daniel

    1. Hi ieva, thank you for the details. Please take care with Nitroglygerine in that case -> better not. Btw, I am not sure if we discussed this but since you have low blood pressure, how is your thyroid function? Kind regards, Daniel

        1. Why do I ask – 7-8 years I am on the border – to do surgery or no of removing thyroid. I have many knots in thyroid both sides(I do not know exact name for diagnosis – (“polynodosa stroma”?), the biggest knot – cyst is 30mm x 20mm x 25mm.

            1. So I with my radiologist decided not to do surgery while there is no changes. But I will go to next ultrasound sonography soon. And yes, in PET/CT with FDG-18 there were no light spots in thyroid.

            2. Have you tried to take iodine for your thyroid nodules? Low-functioning thyroid is not good although I know T4 depletion is a strategy used by Ergin and others here. I used to have problems with TSH/TCH if I remember correctly and have a nodule, too. When I first had the symptoms in my youth (probably caused by a viral infection) I had to take a beta-blocker as my heartbeat was affected substantially. I became quite bitchy temporarily, too. Later I developed depressive symptoms, which I always attributed to this virus. The thyroid is a very important organ, I think, although I know people who had it removed and they just take pills. Still, it is better to have your own, unless it bothers you, I think. Just my two cents.

      1. Hi Ieva,

        I think it might reach bone topically more easily than orally although I am not sure. I guess, it is concentration-dependent. Also, DMSO is used as a carrier for a lot of treatments in cancer. It could work in your case as well, although it should be researched a bit.

        Best wishes,
        Helga

  7. Hi, Helga!
    Thank You for ideas!
    I am not sure about iodine, how it will affect my thyroid as there is many knots inside. From thyroid blood sample perspective my thyroid works normally, I think so. Endocrinologist suggests to take out thyroid as the biggest knot is ~3cm, but guidelines is to cut out if knot is 2 cm. I should be fat if thyroid does not work enough, but I am not. As my cancer responds to hormones I would better try T4 depletion strategy from another Daniels post. That is one one of next plans for me in my background.

    Thanks,
    ieva

    1. Hi Ieva,

      I think T4 depletion strategy is a great approach as it is so easy to implement and seems so effective plus no side effects, I think. It seems to me that Ergin implemented it and the treatments for his mom seem to be working. One more reason for you to keep your thyroid!

      I read somewhere, maybe linked to Daniel’s article about this topic that T4 and the change in its level (decrease) may be behind most “spontaneous cure/remission” cases in cancer. Amazing that doctors don’t use it but the current doctor, dr Hercberg seems to achieve great results with it.

      Best,
      Helga

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