Predicting immunotherapy response

1. The company OncoDNA provides test OncoDeep: 70 genes + predicting immunotherapy response.
https://www.oncodna.com/en/immunotherapy/
Price: 2990Eur.
Are there any studies predict immune therapy in other laboratories? Is this study useful?

2. By the way, in Moscow (Russia) a study of 50 genes costs $480. Can this research give some useful information? Or these 50 genes is very limited and such information is not sufficient?

http://www.genomed.ru/onkokarta/

3. Here (https://www.cegat.de/en/diagnostics/tumor-diagnostics/ovarian-cancer/) it is reported that "The detection of a somatic or germline mutation in the BRCA1 or BRCA2 genes is a requirement for treatment with Olaparib (LynparzaTM)"

There are also 4 testing options.
"Option 1: BRCA1 and BRCA2 analysis in tumor tissue only
In option 1, only mutations in the tumor are analyzed, no differentiation between germline and somatic mutations can be made. We do not recommend this option, but will perform it when it is explicitly requested by a patient."

Is it necessary to do such a study to determine the possibility of treatment with Olaparib or is it enough to study Oncodeep (by OncoDNA)? But in Oncodeep only mutations in the tumor are analyzed.

Option 1: BRCA1 and BRCA2 analysis in tumor tissue only

Option 4: Somatic Tumor Panel

Consequences of radiation therapy?

Please share your experience.

A week ago, my mother finished radiation therapy + temolozolomide.
The condition was good.

Now she has great weakness, all the time very sleepy, it's hard to walk, sometimes unnatural speech.
I can not understand, such weakness is the consequences of radiation therapy?

Also the last 2 weeks my mom takes every day Metformin (2х1000mg), DCA (2х1300mg), delagil (1х250mg), celebrex (2х200mg).

P.S. My mother also had a very low leukocyte count to 1.66 (norm 4.5-11). What do you recommend food additives for their increase?

First post- looking for advice on cocktail treatment

Hello,

This is my first time posting to this site, although I have come across it many times in my research. My name is Jenna and I am here on behalf of my father who was diagnosed at age 66 and will turn 68 this February. Although his tumor is currently stable, his symptoms appear to be worsening. He has increased confusion and sleeps on and off all day. I am here looking for some suggestions as to what we do next.

A brief history: my father was diagnosed with grade 4 GBM in August 2015 and had a successful resection on his right frontal lobe and started temozolomide and radiation treatment. We tested the tumor material with FoundationOne and found six genomic alternations: EGFR, PIK3CA, CDKN2A/B, FAT1, and TERT. We also learned that it was unmethylated. His first recurrence was in September 2016, again in the right frontal lobe. We decided to try the Tocagen immunotherapy study, but unfortunately in late March, we saw growth again in the right frontal lobe as well as new growth in the corpus callosum, making it inoperable. Since then, my dad started getting infusions of nivolumab with re-radiation and we’ve been getting scans that show a slight improvement which has given us a few small but welcome moments of relief. At the same time, the re-radiation or nivo have caused inflammation and we believed the added pressure from that was giving him balance and bladder control issues. He recently had a seizure and now we are trying to work out whether his balance issues were actually the results of something called Todd's Paralysis. It's possible he's been having several small seizures that have been going unnoticed which then cause weakness in the limbs for days to months. If this is the case, we might be able to decrease or remove the steroids. We also reduced his nivolumab infusions from every two weeks to once a month to see if it lessens his inflammation.

I read Ben Williams' book as well as some posts here about cocktail treatments. I would love to create a regimen for my Dad but am confused about where to start. I work in anti-counterfeiting as well which makes me extra wary about procuring drugs from the internet. I would love to hear from some of you about which combinations of treatments are working, where the agents can be safely obtained, what the dosage is, and whether or not there are any side effects. 

Many thanks and wishing everyone a happy new year ahead!

Jenna

P53 loss questions

Hi all,

I'm in the middle of determining what my next steps will be following my AA3 (previously thought to be an Oligo 2) diagnoses.

The tumour is listed as having P53 loss (or truncated mutation), which I know is more unusual in this type of tumour. While doing research on a ketogenic diet I repeatedly came across brief descriptions of p53 playing a role in metobolism...so I decided to look into it more. Below are a few links to different papers I've read. It's seems like you can exploit this loss in a number of different ways.

Firstly, there is evidence that it has some role in fatty acid oxidation and glutathione oxidation (I do not have a mutation to the MYC gene - which also plays a role in glutathione oxidation). According to these papers, these tumours (with p53 loss) are highly vulnerable to glucose restriction, they allow the PPP to become unchecked - which is a pathway that metabolises glucose. (I have read that p53 loss may prevent gene mutations (I think I was understanding that right), which maybe why I do not have an MYC mutation (the mutations I do have are listed in my post called Pathology Report from a few weeks ago).

It also regulates ROS homeostatsis, either through pro or anti-oxidant means (would loss of p53 mean that ROS was unchecked and how would this impact IDH1 mutant gliomas where ROS is already significantly altered, right?) In general, I'm questioning how IDH1 mutation works with loss of p53? IDH mutation metabolises glutamate at high rates, correct? So if p53 is lost (therefore the tumour would not generate GLS2 (at least through P53) and I do not have an MYC mutation (which allows the tumour to uptake large amounts of GLS1 - both GLS1 and 2 metabolise glutathione, then what others ways what the cells use glutathione?

I'm also questioning whether a ketogenic diet would be useful if I am able to use Proton therapy. I believe all radiation therapy uses ROS as one mechanism, proton therapy using more. A ketogenic diet has been said to limit ROS (sort of like antioxidants) but if it will limited it in standard therapy will more be better in Proton therapy? And then, the P53 in relationship to ROS question also comes in here.

I have read that keto may not be good for an IDH mutant tumour because of NAD+. Can someone elaborate more on that?

Just some more info - I had a gross total resection (surgeon said 99.9%). I'm considering Proton Therapy (do people have a hard time getting that covered by insurance), CBD/THC is try to block glutathione uptake during radiation, ketogenic diet to block glucose with attention to glutamate and methionine intake and DHC fatty acids, if needed boswellia and celebrex to prevent need for steroids, Stephen has recommended disulfiram, which I will look into and I'm going to look into metformin (seems to have a special interest with P53 loss), curcumin ( I was taking it before surgery) and I'm considering not taking any chemo at this time.

I apologize that I'm not as organized as I could be in asking these questions. I am experiencing aphasia following surgery.

Here are the links:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135642/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763495/
http://www.pnas.org/content/107/16/7117.full
http://www.sciencedirect.com/science/article/pii/S0005272809000115
https://www.ncbi.nlm.nih.gov/m/pubmed/21336310/

Thank you all.

Maria

Drug for a cocktail before bedtime?

Melatonin, agomelatin, imipramine, amitriptyline or something different?

As I can see, many patients take 20mg of melatonin before bedtime.

However, as written in CUSPND
"Agomelatine’s circulating half-life in humans is ~2hours versus 30 to 40 minutes for melatonin. This is a significant advantage of agomelatine. Further complicating the use of melatonin would be the variable and generally poor absorption after oral administration. Agomelatine penetrates the blood-brain barrier."

This study (https://www.ncbi.nlm.nih.gov/pubmed/28500556) compared agomelatine and other drugs and concluded that the most effective for glioblastoma - imipramine or amitriptyline.

However, here (https://www.ncbi.nlm.nih.gov/pubmed/27480195) on the contrary it is reported "that imipramine and tranylcypromine reduced the cytotoxic efficacy of temozolomide under some oxygen conditions while fluoxetine did not demonstrate such effects".

So which of these drugs should be added to the cocktail before bedtime?

CLOVA cocktail - Your opinion?

It was published in February 2017:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410264/
"The patients treated with CLOVA cocktail in combination with TMZ showed increased survival compared to the control group treated with TMZ alone."

CLOVA cocktail:
TMZ + 800 mg cimetidine, 400 mg lithium, 10 mg olanzapine, 800 mg valproate.

Perhaps one of these drugs (to inhibit the activity of GSK3β) can be replaced with more effective?

Treatment options post-RT/TMZ phase for IDH1 mutated, MGMT unmethylated GBM

Hi all,

I was diagnosed in late September with a GBM (frontal, left, with large cyst, IDH1 mutated, MGMT unmethylated), which was subsequently successfully operated (gross total resection) at the end of September. I guess as many/most here, I eventually stumbled across Ben William's book, the Glioblastoma Treatment options guide and ultimately this invaluable blog and community, which I have been studying and following closely since. I recently concluded the first phase of my treatment, following standard Stupp Protocol (6 weeks concomitant RT/TMZ) and am currently planning next steps (plus waiting for first post-RT MRI next week...).

While I did not get 'smart' in time to save my tumor material from being paraffined post-OP (unbelievably, this is still standard practice here in Germany in most hospitals), I did actively supplement my first phase of treatment with what I think is a reasonably aggressive 'cocktail' approach, including the following components:

--------------------------------------------------------------------------------------

Meds:
- Chloroquine, 1x 250mg
- Celebrex, 2x 200mg
- Disulfiram, 1x 250mg - 500mg (+4mg copper)
- Sativex (THC/CBD spray), ca. 3-4 sprays (approx. 15-20mg)

In general, I tolerated these medications without any major problems or side effects, with a few exceptions. Notably, towards the end of the treatment I developed some peripheral neuropathy in my left foot, which has now almost recovered, however (took around 3-4 weeks to recover). Nevertheless, it cause me to cease the Chloroquine and Disulfiram shortly before the end of my RT treatment phase. In addition, I found it a little hard to tolerate Sativex as I wasn't too keen on the psychoactive effect, which gave me some anxiety / mild panic attacks from time to time at night. As a result, I took it only for around 3 weeks or so.

Supplements:
- Berberine: 1000mg
- Boswellia Serrata: up to 4400mg (gradually increased dosage over course of RT to protect from Edema)
- CBD oil (8%), 5 drops (started after ceasing to take Sativex)
- PSP, 2100mg
- Curcumin (Longvida), 2000mg, increased to 3000mg towards end of treatment
- Green Tea Extract, 3625mg
- Lycopene, 20mg
- Matiake D-Fraction Pro, 65mg (3x 23 drops)
- Melatonin, 20mg
- Omega 3 DHA/EPA, 3528mg
- Probiotics, ca. 40bn units
- Pterstilbene, 250mg
- Resveratrol, 500mg
- Selenium, 200ug
- Silymarin, 1500mg
- Soy extract, 3750mg
- Vitamin D, 9000IU

In general, all of the above were well tolerated without side effects. I'd also like to mention I was able to avoid any kind of Edema / Cortisone use during my RT therapy, which I believe may have been at least in part facilitated by Boswellia in combination with Celebrex.


Other:
- Ketogenic diet, max 40 g Carbs per day; generally constant medium to high Ketone bodies when measuring. Started 1 week before RT, and continued to last day
- Caloric restriction, lost ca. 8 kilos in 6.5 weeks of RT, which I think equates approx. 600kcal or so in daily caloric restriction
- Daily morning smoothie, with variety of hopefully beneficial things like berries, broccoli sprouts, spirulina, tumeric powder, Matcha green tea, cocoa powder,  etc.
- Daily walks of ca. 1 hour to combat radiotherapy fatigue and keep fit

Ketogenic diet was somewhat difficult to maintain psychologically, but possible due to my partner's kind help in continuously seeking out new and often tasty dishes to keep things interesting. Caloric restriction much easier, since Temodal anyway caused me lack of appetite. I believe daily walks were very helpful to avoid RT fatigue, which affected me only in very minor way and much less than I expected.

--------------------------------------------------------------

NEXT STEPS & QUESTIONS

I am currently considering next steps, and having talked to various NOs and other Brain Tumor specialists, I am still not entirely convinced what the right way forward is. As expected, most doctors do not want to deviate from the Stupp Protocol (i.e. follow up the RT/TMZ phase with 6 months of 5/23 TMZ cycles). However, I am not convinced such a treatment would necessarily add much benefit in my case, since my tumor is MGMT unmethylated.

One of the leading specialists in Germany told me that the unmethylated MGMT status is irrelevant in the case of IDH1 mutated tumors like mine, since a study (NOA-4) showed that there was no significant difference in responsiveness  between MGMT methylated or unmethylated IDH1 tumors.

https://www.ncbi.nlm.nih.gov/pubmed/19901110

However, upon further research I stumbled across the following interesting study from China, which seems to suggest that IDH1 mutated tumors might in fact be particularly resistant to TMZ (3-10x more resistant in cell culture test). The study also notes that in China they observed relatively little additional benefit of TMZ cycles for the IDH1 mutated group of patients compared to RT alone, and the authors argue that survival benefits for IDH1 mutated tumors may simply be the result of a less invasive / more benign type of tumor relative to wildtype. It makes me wonder if the fact that MGMT doesn't seemingly play as big a role for IDH1 mutated tumors is simply the result of the fact that neither responds well to TMZ...:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747376/

I'm therefore a bit hesitant to simply go ahead with TMZ therapy hoping for the best, and would like to consider other options.
One approach I am considering is Immunotherapy at the IOZK clinic in Cologne, which is not far from my house. However, because I don't have frozen tumor material, they would have to make a personalized vaccine using a liquid biopsy approach. This, in turn, could make the treatment even more unproven than vaccines anyway are even when made from tumor lysate. An additional option which could possible materialize down the road (but not yet, as no trials are running here presently to my knowledge) is to try to get hold of an IDH1 vaccine on a compassionate use basis.


My immediate next step is to see the MRI results next week, but I'd be very grateful for any advice on how to proceed from here. Especially, I'd like to try and resolve the following questions:

1. Would it be unwise to not do any additional TMZ cycles? Are there any obvious chemotherapy alternatives perhaps?

2. Would the immunotherapy using liquid biopsy at IOZK clinic be a good alternative for ongoing chemotherapy cycles? Would it be advisable to start this right away (i.e. without any additional TMZ cycles), or should I do some TMZ cycles first just to hedge my bets?

3. Any other recommendations in terms of maintenance strategies. E.g. what medication(s) could make a good maintenance therapy, without concurrent chemotherapy?


Thanks in advance for any comments, and wish you all a very happy and most importantly healthy 2018!

Best,
John

Our cocktail and treatment tactics: CCNU+TMZ (CeTeG) + CUSP9v4

Hello!

Today my mother had the last day of radiation therapy+TMZ.
(Diagnosis: Glioblastoma, MGMT methylated)

1. We plan to wait 2-3 weeks before the increase in the platelet count (now 142) and start with
CCNU+TMZ cycles (as in CeTeG trial).
Also, at the same time we want to start CUSP9v4 protocol .

But in CUSP9v4 protocol TMZ is taken daily in small doses.
I do not know how to take TMZ better. As in CUSP9v4 protocol, or as in CeTeG protocol (CCNU+TMZ)? What can you recommend?

If we take TMZ, as in CeTeG trial, we want to do intravenous injections of curcumin
every day of taking TMZ (5 days in 6 weeks).

2. Also we increased the dose very slowly, and now we take it every day:

DCA - 2x1300mg (2 x 20mg/kg/day)
Metformin - 2x1000mg
Alfacalcidol - 2,5mkg
Delagil (Chloroquine) - 1x250mg
Valdoxan (Agomelatinum) - 50mg (in the bed) (Cancel when moving to Sertraline from CUSP9v4).
_____________________________________
Extra virgin olive oil, 1 tablespoon (on an empty stomach)
CurcuBrain, Longvida Optimized Curcumin (Now Foods) - 5х400mg
Aronia (Eclectic Institute) - 1x450 mg
TransmaxTR, Trans-Resveratrol (Biotivia) - 4x500mg
pTeroPure, Pterostilbene (Life Extension) - 4x50mg
Berberine (Thorne Research)- 3x500mg
Shark Liver Oil (Norwegian Fish Oil) - 3x689mg
Max DHA (Jarrow Formulas) - 2x484mg
Silymarin, Milk Thistle Extract with Artichoke & Dandelion (Now Foods) - 1x300mg
EGCg, Green Tea Extract (Now Foods) - 1x400 mg
Brocco Max DR (Jarrow Formulas) - 3x30mg
Boswellia Extract (Now Foods) - 2x250 mg
Ashwagandha Ghan Vati - 2caps
Oxaloacetate, OAA (Fractal Health) - 1x250mg
Mito-Charger (Advanced Orthomolecular Research AOR) - 3caps
Selenium (Now Foods) - 1x100 mcg
I also ordered and waiting for the delivery of PSK/PSP.
_____________________________________
Tomato juice 1-2 cups
Young shoots Broccoli
Adding aronia (chokeberry) to the tea
_____________________________________
I think we drink a lot of food supplements, but so far there have been no side effects and I do not know what to cancel!(

3. I also with great difficulty have already ordered perillyl alcohol, and now I am studying all the instructions for treatment with it.

4. We also want to try Nivolumab. The doctor assured us that we will be able to monitor the side effects by abolishing or decreasing the dose. Our doctor suggests starting with a dose of 100 mg / 2 weeks and then increasing 200 mg / 2 weeks. I'm not yet sure about Nivolumab, since we had a large remaining tumor after the operation(((

5. Next, I want to do a test for the amplification or overexpression of the EGFR gene.
In this case, we will cancel CUSP9v4 protocol and I want to consider pulsed lapatinib (or an analogue), as in this study:
https://clinicaltrials.gov/ct2/show/NCT01591577
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965258 (I can not yet understand what kind of research was done to select niacinamide? What kind of research should I order?)

Unfortunately we did not have any tumor samples left. We signed a paper that we give samples of the tumor to the clinic where the mother was operated (University Clinic of Frankfurt on Main).
If we do not give back the remnants of the tumor, I will look for testing EGRF on the model of blood. I'm not sure that this is possible.

Stephen wrote that maybe this test will tell me about the overexpression of EGRF and maybe I'll order it: https://www.rgcc-group.com/index.php?page=test_onconomics_plus

6. I want to do a test here for the effectiveness of DCA for my mother and decide whether to take it further or cancel it: http://erweiterte-medizin.de/infusionen/dca
I do not know what exactly is being investigated in this test. Maybe someone knows? I would then have ordered this study somewhere else.

7. I do not quite understand the results of our immunohistochemical study. Maybe there is something special about this data?
IDH-wild type,
IDH: IDH1 (R132H) negative (IHC),
ATRX: Preservation of nuclear expression (IHC)
H3.3: No evidence of K27M mutation (IHC)
P53: no accumulation of p53 (IHC)

P.S. I would like to write about my admiration and my great gratitude to Stephen, for devoting himself to helping other people fighting this deadly disease.

New cytomegalovirus-directed vaccine trial for recurrent GBM

This phase 1 trial opened this month in New York, and will be opening in Virginia as well.

The vaccine is called VBI-1901 and consists of two CMV antigens (gB and pp65), delivered via enveloped virus-like particles (eVLP), plus GM-CSF as an adjuvant.

View trial outline here.

NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting “stemness”

Has anyone seen this? Can someone please help me to understand it? You know, post-surgery brain an all.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400535/#!po=73.8372

Prepare perillyl alcohol (POH)

Dear friends!



Can you please advice witch product № ...code we should buy to prepare perillyl alcohol (POH) from picture below?



Who knows trustful  instruction how it should be prepared/diluted?



Company wich sell https://www.sigmaaldrich.com/catalog/papers/24324108



Many thanks in advance !



Leonid

The test of the effectiveness of specific drugs on cancer cells obtained from one patient

Hello!

My mother has glioblastoma. The doctor offered us a test - "Onconomics Plus" (the test of the effectiveness of specific drugs on cancer cells obtained from one patient).

https://www.rgcc-group.com/index.php?page=test_onconomics_plus
Price: 1900 €
This laboratory has branches in many countries.

As written on their website:
Test "Onconomics Plus"
Provides information about the efficacy of specific drugs on the patient. The method includes two procedures (epigenetic analysis and viability assays) to validate the data. The efficacy of natural biological substances or extracts on cancer cells. The assessment is based on the three methods: the direct cytotoxic effect, the stimulation of the immune system and the inhibition of proliferative signals in the cancer cells.

Sample of the report:
https://www.rgcc-group.com/assets/PDF/Test.SamplesOfTheReport/OnconomicsPlus/Chemoagents-patient's-name.pdf

What do you think? Is this test necessary?
Can there be more effective tests?

(AVASTIN+CCNU) + Nivolumab after standard chemoradiotherapy?

Hello!

I, like many of you, need optimal treatment for my mother.
My mother has glioblastoma (MGMT methylated). She just finished the standard course of radiotherapy + TMZ. At the moment I'm looking for how to be treated more effectively.

Our doctor advises adding 8 courses of Nivolumab together with AVASTIN + CCNU.
He says that with such a combination, the probability of a complete cure is 30%.
Also, with such a combination, the doctor suggests not using TMZ.
All this seems to me very doubtful!

What would you suggest?

With respect to all and best wishes, Semyon

Pathology Report

Hi all,

I had the tumour out on Nov. 10 and just received my completed pathology report today. I’m diagnosed with an AA3, not an Oligo 2 as previously thought. Can you all review the report and help me make my next steps from here? Thanks.

IDH1 R132H positive
ATRX - negative (lost, suggestive of mutation)
P53 - highlights scattered background of glial cells (negative in tumour, suggestive of try care by mutation)
MIB-1 proliferation index is 7.7%
504 kb gain of SOX2
1.9 mb gain of OKI (no gene disruption)
21.2 Mb broad gain of 7q, an
8.7 Mb gain of 12q

Let me know if I should give you anything else. That’s is all that is listed though.

Thank you!

Marrow Plus 

Morning - Does any one have experience with a product named Marrow Plus by Health Concerns? A reader of my original post suggested I look into it as a way of boosting blood levels in my wife. Her platelet counts are really low. Thanks and gratitude. Rick 

Full results of EF-14 phase 3 Optune trial published in JAMA

Click here to see the abstract

I uploaded the study to the Brain Tumor Library -> Optune folder.  The file is called "2017.12 Stupp EF-14 Optune phase 3".

Dear friends, It is URGENT!!

My sister has 3 kids (41
years) in May 2017 was diagnosed in Anoplastic multiform glioma.

Pathology report shows:
MGMT – Non methylated

IDH1 (R132) negativ (IHC)

PCR signal unmethylierte sequenz – positiv

PCR signal methylierte sequenz – negativ

ATRX: partieller Verlust (IHC)

H3K27M: negativ (IHC)

From August 2017 she got
Temodal for 3 months (7 days in, 7 days off).
growing continue.

In November she got Avastin +
Ironatecan
growing continue

December: just Avastin

Now she is getting:

Kepra 3000
Vimpat 100
Dexamethason 8 mg
Vitamin C, B, D
L-Carnitin+Lymphdiaral
Boswellia serrata
Unizink
Kytta Sedativu
RSO – 0,5 a day
Ajurvedic treatment

Plan to have Optune in 10
days.

So far we cant stop the
growth.

Can you please advice useful
protocol/treatment plan which can help stop tumor grow?

Many thanks  in advance.

Best regards,
Leonid 

Our Clinical Trials Exploration Update/ What to stop when? Cannabis oil and kinase inhibitors?

We have spent the last couple of weeks traveling to explore Clinical Trials for a recurrence of my husband's GBM tumor. At MD Anderson we were offered Val-083 (3 days of infusions every 21 days), Abemaciclib to target a CDK2NA copy loss and LIT surgery.

I still have not heard much about Val-083, pros or cons, side effects...

At Duke he was offered the polio virus and we very excited but as we were about to sign the paperwork and asked more questions about side effects our guts told us not to do it. We were told it will get worse before it gets better, inflammation is almost a definite and worsening of symptoms. My husband has had very little pain and wants to avoid it at all costs. We were told they have the dosage correct and can manage the swelling with Dex or a tiny amount of Avastin but we still did not think the risk was worth it. They also offered daily Temodar.

This brings us back to Northwestern where he is currently being treated. They have a Basket Trial of Entrectinib to target his FIG-ROS1 mutation. It is supposed to be have very low side effects. We were there Friday and still have yet to hear back from the drug sponsor to see if he is accepted. They inquired as to the actual location of his mutation.

I have read that cannabis oil is not a good idea with immunotherapies. Has anyone heard if there is a contraindication with kinase inhibitors?

Lastly I was curious when people stop cocktail drugs or supplements? I know a lot of the cocktails are designed to help radiation and TMZ work so I am wondering after you have done all the supplements and additional cocktail drugs and cannabis oil and Optune and  positive thinking and everything else you can think of and the tumor still comes back, what do you continue? Do you believe that those treatments didn't help if the tumor comes back or did they maybe help a little and you should continue? There really is no way to tell. I also wonder this as many Clinical Trials make you stop all of the above.

Thanks for any insights. My husband is doing well but his tumor has doubled and spread in the last 5 weeks and his symptoms are getting worse so we need to make some sort of decision. Best to all.

IDH1-mutant, 1p/19q non codeleted oligoastrocytoma, needs help

This came in to my inbox, and I was asked to post it to the blog:

My son was diagnosed at age 17 with IDH+ 1p/19q negative left frontal lobe oligoastrocytoma...possible recurrence (vs. incomplete resection) at age 18 treated with surgery and proton therapy (no chemo). At the time of starting proton therapy, it was felt that there might a small left-over area in the middle of his tumor bed--but all scans clean for years. He has done fairly well for years with no treatment.  His aim has been to be a neurologist...graduated college Phi Beta Kappa, very good MCAT scores, and now first year medical student.  6 month scan today shows a 6.6 mm nodule enhancing in the middle of his tumor bed.  Never had enhancement before.  Understandably, I am devastated.  He is not certain that he wants more surgery.  However, it is not near a critical structure.  BUT....if there is treatment after surgery, want surgery done at place where could be coordinated with further treatment.  I have been reading your blog daily for years and greatly value your wisdom (based on evidence-based medicine) and that of many of your commentators.
Thank you so much for any help!!

Understanding Cannibas benefits/dosage (separating out CBD from THC)

Hello Lovely Group,

In need of some cannabis education!

There seems to be LOTS of info on using Cannibas in Brain Tumors for various reasons.  I'd like to understand this more so that my husband can get some relief (who's biggest issue lately is sleep disturbance).  However, I'd like to learn all the benefits of Cannibas for brain tumors and learn best doses to get the most healing out of this substance.

Here are the issues that we hope to improve and/or resolve with cannabis:
1. Improve night time sleep (less waking up and less trouble falling back to sleep)
2.  Decrease inflammation/swelling:  He's post 2nd tumor removal surgery and it takes longer to heal 2nd time around (especially after all that radiation and he was on plerixafor study which exacerbates radiation effect) so he's had lots of treatment swelling (results in speech stumbling and word finding issues).
3.  Improve Daytime alertness:  He's back to work at a busy job and could CBD give him more alertness and  energy for the day.
4.  Decrease risk of seizures (he hasn't had any lately, but hoping the cannabis on board will keep his seizure risk low. 

NEXT Question is How Much?  Dose, Dose Range, in what form-edible, oil, leaf, smoke, ingest?

I've heard that it's best to separate out the THC from the CBD.  (THC for night/sleep)\ CBD for Day use).  Is that a correct understanding? 

THC (Indica vs Sativa)
THC for Night (How much?  what dose? AND in what form?  Chewables?, Oil (is oil smoked or put into food?) other??? I know we'll probably have to play with this a bit, but is there a range to start with?  Also, should it be the Indica/Setiva combo or separate out Indika (just use that) or Just Setiva?  

CBD:  How much, what dose? What dose range? Chewables? oil? other ???  Especially for someone who is working all day and wants to maintain high functionality, focused thinking, good memory, good concentration?  

Best research literature on these topics that you recommend?  Please send links :-)


This Quote seems perfect for all my questions today:

"Perhaps the secret of living well is not in having all the answers but in pursuing unanswerable questions in good company."    Rachel Naomi Remen

Thank You fellow bloggers for your Good Company on this Journey.

Sending Love, Light and Healing to ALL.

Kelly

Update Temodar + methadone + Optune TTF

Finally I can post an update of my Dad's treatment. He was diagnosed with an inoperable glioblastoma in December 2015. So it's his second anniversary this month :)
So far we've been lucky (neither growth nor recurrence but shrinkage and stable MRIs). His latest MRI showed that the edema has increased in size and causes speech issues. Unfortunately the latest MRI was done without any contrast agent so my Dad has to do another one in January. However, the doctor told us that the tumour itself looks pretty much the same but he's a bit worried about the edema as its growth suggests that something might be going on with the tumour. But he couldn't detect any significant growth or a new tumour so we're happy with the preliminary result  ('stable').
Compared to most inoperable glioblastomas my Dad seems to be doing really well, so I'm very grateful for that. Hopefully we'll know more in January!
My Dad's current treatment:
Temodar
Methadone
Optune TTF
Levetiracetan
Vitamin D
Omega 3
PSK (Coriolus versicolor)
Sulforaphane  (Broccoli sprouts)
All the best
Steffi

New Diagnosis (GBM Grade IV)
All – my wife (51) was diagnosed in July 2017 with a GBM grade IV. The tumors were in her frontal lobe, are IDH wildtype and positive for amplification of EGFR sequences. Subsequent testing indicated MGMT Gene Promoter Methylation was not detected. Stacey’s tumor is multifocal. There are other characteristics (like PTEN) that I understand less. I do understand enough to know her tumor is much worse than most. 

Surgeon stated the larger was baseball size. Neurosurgeon stated he removed approx. 60% 

Stacey had stroke symptoms as she emerged from surgery. Deficits in speech and left arm and leg. She went thru rehab and is much better.

She is receiving treatments at UC Health Aurora ( Anschutz Cancer Center) which is a NCI center ( only one in Colorado) 

Early on we sought out second opinions from Barrows in Phoenix, and Dana Farber back East (we did this via correspondence as Stacey was too sick to travel). Both told us the standard of care we were getting in Colorado was their recommendation. Only in the event of recurrence would they have something more to offer. 

We currently have her enrolled in the ABT-414 clinical trial thru UC Health . We enrolled prior to the 6 week course of Radiation and Chemo. We are currently evaluating whether to drop from this CT and move to Optune

She has finished her 6 weeks chemo and radiation fine. Some hair loss, fatigue and fogginess. No nausea ( on Zofran).  Blood counts on platelets and white cells plummeted the last week, but rebounded to reasonable ( not optimal levels ) 

She just finished her first adjuvant cycle of Chemo ( TMZ 260 mg) ( 5days on, 23d off) and did fine.  

She had an MRI before the cycle started on 11/22. Report from the NO was the scan was good, no issues and no recurrence. Next MRI in January

My initial questions are : 

1). Stacey’s platelet count plummeted since the 11/22 test. 59 10*9/L as of 12/13 ( Was 114 on 11/22). I don’t know if this was a result of the Cycle 1 TMZ treatment, or some side effect of the last ABT-414 trial infusion. I’m concerned low numbers might delay the next cycle of TMZ (12/21). Are there any recommendations to increase platelet numbers in the interim? I have questions into the NO including possibility of a transfusion or other options . 

2). I have read several papers by Mr Williams and his book. I’m also learning a huge amount from online resources like this blog. Obviously overwhelming especially since I am not in the medical field. I feel like this is my battle and obligation to find options to try as the medical community has little clarity to offer other than stand of care. 

        a). Is the certainty of results in Optune better than the uncertainty of if she actually receiving ABT414 (double blind study). We’ve been told we cannot do both . I’d appreciate opinions 

        b). should we be exploring consultations at another Cancer center like MD Anderson, UCSF or Dana Farber now that she’s more able to travel ? I’d like to maximize opportunities before recurrence, but NO wants to stay the course. I haven’t ventured yet into conversation about adding other prescription meds, but need to assembly that case . 

Stacey is aware of the situation and cognitively getting better. She gets the danger she’s in but because of surgical and/or tumor damage, she is not able to actively pursue options. Thus, I’m trying to do what I can to care give, stay employed, and find solutions. I am certainly grateful for people like you that I can reach out to for information. This would feel like a lonely battle otherwise.

With Gratitude 

Rick 

Optimizing TMZ

My 64-year-old husband was diagnosed with GBM in his left temporal lobe after a successful resection in 1/2016. His tumor is unmethylated and IDH negative. He is TMZ-naive and has been on Keytruda and Optune for a year. The tumor was stable until late October, when it extended into a new area.  It is slow-growing according to a PET scan yesterday.

Genomic testing of tissue retrieved from a second resection 11/16 highlighted mutations in NF1, PTEN, ASXL1, HNF1A, MLH1, NOTCH1 and SPEN. My husband's NO suggested Temsirolimus because of the PTEN mutation and TMZ starting in January.

My big research question is how to get the most kick out of TMZ, given his methylation status. It seems that either daily or 7-day/alternating Temodar have better clinical results than the standard protocol. I also wondering how best to sensitize GBM cells to TMZ and potentiate the treatment. Different studies suggest adding:
- Tamoxifen
- MGMT inhibitor O6-benzylguanine (O6-BG)
- Interferon-β (IFN-β)
- oncolytic adenovirus
- excision repair pathway enzyme apurinic/apyrimidine endonuclease/redox factor-1 (APE)
- Prozac/Fluoxetine
- antabuse/disulfiram
-Metformin

This all makes my head swim. Have any of you tried an alternative TMZ dosing schedule along with something to enhance its effectiveness against a unmethylated tumor?

Thanks for all your information and help.

Plerixafor - new drug to cocktail?

Hello!

1. There is one promising report on the treatment of TMZ+Plerixafor (+Lapatinib  pulse dosing) for glioblastoma:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965258/
Plerixafor was administered subcutaneously 1 time per week for 2 years.

2. And one ongoing trial studie at phase II:
https://clinicaltrials.gov/ct2/show/study/NCT01977677?term=AMD3100+glioblastoma&rank=1

Plerixafor was administered via continuous intravenous infusion of 400 micrograms/kg/day starting one week prior to end of RT and continuing for 4 weeks.

Here are published abstratcs:
http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.2058
http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.2068

3. There are also several articles about Plerixafor:
https://www.ncbi.nlm.nih.gov/pubmed/27863376
https://www.ncbi.nlm.nih.gov/pubmed/27015814
https://www.ncbi.nlm.nih.gov/pubmed/26023083
https://www.ncbi.nlm.nih.gov/pubmed/25676691
https://www.ncbi.nlm.nih.gov/pubmed/25860928

Stephen wrote that 1 shot of Plerixafor is very expensive, but I am in Delhi (India) and here Plerixafor 24mg/1.2 ml (Celrixafor by Celon Labs) is $ 1000.

What do You think about this medication and what are the tactics of its use more effective?

What do You think about Lapatinib used in the first case, pulse dosing? If it is suitable for all types of glioblastoma? clinical research is also going on:
https://clinicaltrials.gov/show/NCT01591577

7 year old Vasiliy: help is needed with his case of bridge glioma

Dear All,

I am sincerely grateful to Stephen and everyone for all the useful information on this blog, which I've been reading for many months now. I am posting on behalf of a good friend who really wants to help Vasiliy...

It's heartbreaking when a little child is diagnosed with malignant cancer… if someone would be able to help with any advice on the additional treatment options , clinics or methods for alternative treatment, PLEASE DO SO!

Vasiliy is a brave 7 year old Ukrainian boy and he's got malignant brain tumour…I've got limited information at the moment but in case any further clarifications are required, I'd be able to get additional information. 

In August 2016, it became obvious that Vasiliy's right side got weaker. 
Doctor's note says: Left-sided peripheral facial paresis with double vision. There is also a case of dysphagia. MRI has proven bridge glioma of the brain. There are no signs of cerebrovascular accident.

TREATMENT:
• There have been no neurosurgery interference
• 31/08/16 - 07/10/16 - Radiotherapy 1.8 GY/day (45 fractions) followed by Boost 1.8GY/day (9 fractions) + Temozolomide
• There have been additional treatment of Avastin

In May 2017 the dimensions of tumour were: 46*52mm

At present, Vasiliy takes the following coctail from what is available in Eastern Europe: 

Morning: 
Vidatox 3 capsules
Peroxide with water 10 drops
Levain 1 tablet
Licam 1 tablet
Spiruflor 1tablet
Ensil 1 tablet
Megamin 1 tablet
Laminin 2 tablets
succinic acid 1tablet
Reviplant 1 teaspoon
Stone oil 50ml

3pm: 
Levain 1 tablet
Licam 1 tablet
Reviplant 1 teaspoon
Ensil 1 tablet
Laminin 2 tablets
Stone oil 50ml

Evening:
Reviplant 1 teaspoon
Stone oil 50ml
Spiruflor 1tablet
Vidatox 3 capsules

I have clarified with puredca whether DCA can be considered, as an alternative treatment for small kids and they have confirmed that it should be added. But I, personally have some doubts now.. My husband has been taking DCA, Avastin and Valgancyclovir for nearly 1.5 years now for his Grade IV glioblastoma and he's got neuropathy developed, as either the result of any of those or a combination of all. Has anyone heard of any neuropathy symptoms in pediatric glioma and whether DCA is really safe to give to a small child?

Would anyone happen to know what could be also added to the above coctail to help with tumour fight for little Vasiliy? We'd welcome any advice and help.

God Bless You All!

Thank you for all your kindness and help, 
Nina

It is not the healthy who need a doctor, but the sick. I have not come to call the righteous, but sinners.
~ Mark 2:17

Medications no longer needed. Any takers?

I spent the day helping Starr's mom sort through her belongings and they sent me home with her unused meds.  I would very much like them to go to someone who can use them.  I have:

Depakote
Keppra
Depakote in sprinkle format (helped my dad when he could no longer swallow pills)
Keppra in liquid format (also helpful for difficulty swallowing)
Metformin

I'm sure there are others I'm forgetting.  I'll update the list when I'm less tired :-)
Please let me know if you could use any of these and I will get back to you with the strengths, quantity, etc.

Best.
Annie

Rest sweetly, Starr Korvin

I realize I haven't posted in quite awhile, but I wanted to share that my dear friend Starr Korvin passed away early Tuesday morning.  Starr was diagnosed with GBM two months after my father Allen died, in September of 2016.  I consider you all my people when it comes to brain cancer and understanding the challenges and feelings that come with this diagnosis.  I wanted to share the brief obit I wrote for her with each of you.

Love to each of you.  May your loved ones reach heights further than mine did.  I mean that with complete sincerity.  xoxo Annie

My dear friend Starr Korvin has passed away. It's still sinking in that I'll never see her again :( Starr was a great friend. She had more 'best friends' than anyone I've ever met. I can think of at least 5 girls, without trying, that would call her their best friend. I'm thinking of even more as I sit here. She has been in more weddings than most rom-com leads. Starr was a "Nordstrom All-Star". Which those in the know, know was a coveted title (and discount). She went back to school to work on her Masters in teaching while the rest of us went out to dinner and fucked around. She loved purses (one of our special bonds). She loved makeup. She had that edgy style that she and I both adored. She was funny and thoughtful. She would bring me a birthday gift every December, or even January, when I had already long forgotten about my birthday. She organized our group and kept our friend group connected with annual trips to the bear cabins and to celebrate our birthdays, even when we didn't ask - always when we didn't ask. She gave me a pair of boots we both had (and loved) because mine wore down on the heel and she remembered how much we both loved them. When my Dad was diagnosed with brain cancer she and Mary came to my house for hours with internet tamales (the best) and wine and sat with me while I crazily researched everything under the sun. That may not seem like much, but that was absolutely the WORST time of my life and their support (and stamina) was major. No one else would even pretend to understand any of that shit. 
It breaks my heart that she suffered the same fate with a glioblastoma diagnosis just 2 months after my father died of the same cancer.
I love you Starr Korvin. I hope there is a heaven, and that it's filled with puppies and babies and 'fuck yeah' purses and Benicio look-a-likes and real housewives and mint mochas and gold jewelry and lip injections. I miss you already ❤️

SNO summary: Durable responses with Toca 511 + Toca FC

I already posted on this data at the end of October, but here is my long form write-up.

Durable responses observed in IDH1 wildtype and mutant recurrent high grade glioma (rHGG) with Toca 511 & Toca FC treatment

Timothy Cloughesy of UCLA presented updated results for the phase 1 trial of tumor resection followed by injection of Toca 511 into the tumor resection cavity.  This trial (NCT01470794) treated 56 patients with recurrent glioblastoma or anaplastic astrocytoma (WHO grades 3 and 4).  

Pooling results across all three phase 1 dose escalation trials (n=127 patients), Toca 511 was found to be well tolerated, with only 25% of patients experiencing grade 1 or 2 treatment-related adverse events (including fatigue in 11%), and 7% of patients experiencing a grade 3 or higher treatment-related adverse event (including one case of headache, one case of fatigue, and two cases of vasogenic cerebral edema). Administration of the fluorouracil prodrug, Toca FC, was also associated with a low incidence (3.3%) of grade 3 or higher treatment-related adverse events.  Only three out of 122 patients discontinued therapy due to adverse events associated with Toca FC.

In the NCT01470794 trial of resection followed by injection of Toca 511 into the resection cavity, 46/56 (82%) of patients had recurrent glioblastoma, and the remainder had anaplastic (grade 3) or other gliomas.  50% were at first recurrence, 23% were at second recurrence, and 27% were at third or more recurrence.  

This trial included the endpoint of durable response rate, defined as a response lasting at least 24 weeks (5.5 months).  Remarkably, all responders (6 out of 53 patients evaluable for efficacy, 11.3%) are in complete response and still alive, with a median duration of response of at least 35.1 months (nearly 3 years). An additional 18.9% had stable disease as best response, for a clinical benefit rate of 30.2% (response plus stable disease).

In the subset of patients (n=23) treated with higher doses of Toca 511 and meeting the eligibility criteria for the ongoing phase 3 Toca 5 trial (at first or second recurrence, no prior Avastin, and tumor no larger than 5 cm), there were 5 out of 23 patients (21.7%) with durable complete response lasting for a median of 35.7+ months.  An additional 21.7% had stable disease as best response, for a total clinical benefit rate (response + stable disease) of 43.5%.  In this subgroup of 23 patients, three of the complete responders had wild-type IDH1, and two had anaplastic astrocytoma with mutant IDH1. These responses occurred gradually over 6-19 months, consistent with an immunologic mechanism of action.  Median survival from Toca 511 treatment in this subgroup is 14.4 months, which compares favorably with historical benchmarks of 9-10 months for recurrent GBM with standard treatments.

The safety profile, increased median survival relative to historical benchmarks, and relatively high rate of complete durable responses lasting for a median of at least three years is encouraging.  The randomized phase 2/3 Toca 5 trial for recurrent glioblastoma or anaplastic astrocytoma (NCT02414165) recently re-opened in November 2017 to new recruitment and the phase 1 Toca 7 trial for newly diagnosed high grade glioma (NCT02598011) is scheduled to open sometime in 2018.

Olaparib + radiation for recurrent glioma?

Hello all,

My sister is currently preparing for treatments after a successful surgery. She has recurrent IDH1mut, MGMT methylated astrocytoma, previously grade 3, we're still waiting for pathology report from the latest surgery. Preliminary treatment plan is to have radiation therapy (recurrence is outside of the original tumor location) and then continue with CCNU.

I found this one study (Paradigm-trial) that studies olaparib in combination with RT.
Do you think it would be worth a try? This could be possible for us financially since the RT last only about a month so cost of olaparib would be reasonable.

Br,
Juha

Levi's cocktail update & pretty good MRI at 8 months

Luckily my husband (who is MGMT methylated, wild type and has a multifocal tumor) got a quite promising MRI report today after a slight progression in late August following radiation therapy. We need to wait for the NO's opinion till 12/18 but it's clear for us that this is good news because the report contains words like regression (both in the thalamic and frontobasal areas), reduced T2 signaling, reduced edema. 

The only negative statement mentions increased rCBV at some parts of the frontobasal tumor. Good results were not so surprising since he is doing very well. He basically slept through the 2 months after radiation therapy but now he is is back to normal. His only deficiency is left-side peripheral vision loss due to surgery. 

Since my previous post we made some changes to his cocktail. Thanks to a nice blog member's guidance my husband started to take D,L methadone a month ago. He will reach the therapeutic dose (2 x 35 drops) soon. It didn't have enough time to make a difference yet so I chalk the fairly good MRI results up to the cocktail approach. I hope that the next MRI in late February / early March will be even better thanks to methadone. 

With mebendazole, we try to follow Care Oncology's protocol so after the 3 months course of mebendazole which he we'll complete within days we'll alternate it with minocycline (instead of doxycyclin). Somebody stated on a forum that mebendazole and minocycline do the same job. I suppose mebendazole isn't the strongest part of our cocktail considering its bioavailability and the fact that he takes way less than the dosage used in clinical trials. So maybe it would be wiser to choose minocycline on the long term. What do you think, dear fighters & relatives, should we pick the substitution alternative or should we favour minocycline? If so, which one would be better, 100 mg or 200 mg? I have concerns about putting all our eggs in one basket. Maybe if the current cocktail works we can keep up with it, otherwise what will we have left in case of a progression if we blow all our ammunition now?

Current cocktail:

- TMZ 280 mg (5th cycle completed)

Tried to increase it to 380 mg for one cycle but BP dropped to 40,000 so it turns out that he can tolerate only 280 mg.

Morning, on an empty stomach: 

1,5 g PSK mushroom

250 mg EGCG (500 mg on TMZ days + fresh green tea)

1000 mcg sulforaphane from dried broccoli sprouts (2000 mcg on TMZ days)

2000 mg Fish Oil

250 mg vitamine C

D,L methadone 25 drops 

0.5 liter of beetroot-carrot-apple-orange juice ( I don't really believe that it can help but at least it's delicious.) I used to make fresh pomegranate juice daily but then I read that it can increase the concentration of corticosteroids so we stopped it. 

After breakfast:

Curcumin 1000 mg

Fluoxetine 40 mg

Alfacalcidol 2.5 mcg 

Metformin 500 mg 

After lunch:

mebendazole 100 mg / minocycline 100 mg

methylprednisolone 16 mg (I hope it'll be reduced after the next meeting with the NO) 

cimetidine 2 x 200 mg 

During the afternoon & evening 

cimetidine 1 x 200 mg

silymarin 630 mg (I increase it on TMZ days to 850 mg but just like everybody else I'm just guessing with the dosage)

celebrex 400 mg

metformin 500 mg (1500 mg on TMZ days in total) 

DCA 500 mg x 2 + 500 mg B1, 2 weeks on, 1 week off

This means 15.6 mg/ kg. He was on 500 mg x 3 / 20.4 mg/ kg for several weeks, parallel with his Temodal cycle increased to 380 mg but it caused neuropathy in his hands and feets and balance issues so we decreased DCA to 15.6 mg/ kg and symptoms disappeared. I'm not sure if it was Temodal or DCA because both of them were decreased after these issues. Now, we try DCA without B1. We'll see...

After dinner:

Chloroquine (Delagil) 250 mg (Only every other day since he takes cimetidine.) 

Selenium 200 mcg

cup of tomato juice as Lycopene source

Before bedtime:

D,L methadone 25 drops 

melatonin 20 mg 

PSK 1.5 g

cimetidine 1 x 200 mg

- Omeprazole 40 mg x 2 (2 days before and 2 days after TMZ days) 

PAC-1 trials

New human trial based on canine/rodent studies with PAC-1

Any thoughts or perspectives on this approach? - I see a PAC-1/TMZ combo planned.

Aimed at AA3.

http://medical-newspaper.com/cancer-drug-starts-clinical-trials-in-human-brain-cancer-patients/

LAST MRI IS CLEAN.

HELLO everyone,
My husband  is doing very well, thanks to God
back in 2014 had 3 surgery, after the third surgery , made radiotherapy and continued with cocktail,
this year 2017 , stopped TMZ , and continued cocktail withouth TMZ. and he is doing well, feeling well. hope he is going after steps of long term survivors, :)

wishing all the best to everyone with this awful disease. and don't lose hope!
Melinda Voicu