The case of the best performing glioblastoma patient in the world and Frontiers in Nutrition

Dr. Csaba Tóth,  Dr. Zsófia Clemens

 

The case of the best performing glioblastoma patient in the world and Frontiers in Nutrition

It seems that “prestigious” medical journals are notoriously hindering reliable scientific medical information. This is, of course, nothing new and also applies to less prestigeous journals. Yet, still shocking when it comes to a cure of a deadly disease, namely glioblastoma. Here we tell the story in the form of questions and answers.

 

What kind of disease is glioblastoma?

Glioblastoma is one of, if not, the deadliest cancer type. Glioblastoma results in epileptic seizures, nausea, vomiting, trouble with walking, paralysis of the muscles, personality changes, problems with speaking and memory. In more advanced stages of the disease, it causes an inability to swallow, incontinence, somnolence, unstoppable epileptic seizures, coma, and ultimately death. This is the disease that took the life of John McKain, Edward Kennedy, and Beau Biden, son of the current American president. As shown by the so-called Kaplan-Meier curves, glioblastoma survival after 4 years is less than 3%. The below figure also shows the ”on the diet” survival and overall survival of our glioblastoma patient.

Figure: The Our glioblastoma case vs. the Kaplan-Meier curve for survival

To what extent is glioblastoma affecting people?

There are 250,000 new cases in the world annually, and the numbers are increasing.

 

Why do you use an unconventional approach to treat glioblastoma when you are supposed to use the standard one?

Because we know from experience that the standard therapy (chemotherapy and radiotherapy) only worsens the outcome. We also know that the PKD (paleolithic ketogenic diet) gives the best chances to live as long as possible. As a physician, you took an oath (aka Hippocratic Oath) to strive for your patients’ recovery and life. The Hippocratic Oath is about the patient’s interest and not about following certain guidelines and standards.

 

What does recurrent glioblastoma mean?

“Reccurent” means that cancer has already been treated by standard modalities (surgery, chemotherapy, and radiotherapy), but despite all these “efforts” the disease recurred. 

 

What are the prospects with recurrent glioblastoma?

Somebody with a new glioblastoma diagnosis has six months to live on average. When we first met this patient it was already 8 months after his initial diagnosis. You can do the math about the prospects of this patient. 

 

What are the results you had with this patient?

The patient had remained progression-free, completely seizure-free, completely medication-free, and completely symptom-free. Currently, already for 4 and a half years.

Figure: MRI and CT scans performed during the course of the disease. 

 

What was the reaction from your colleagues when they learned about the unusual survival time of your patient?

  • You are going to kill this patient!
  • You are irresponsible! 
  • Don’t be too happy. The patient will the”in the end”.
  • This is a miracle from God
  • It is ok that the patient is still alive, but he cannot live without his antiepileptic medication
  • The initial diagnosis was wrong
  • The patient has a rare genetic feature that predisposed him to live that long despite glioblastoma

 

What reactions did you get from laypeople?

Mixed ones. More negative than positive ones. A lot of people were outraged and reacted in a highly offensive way. When we started the diet therapy with this patient back in 2016, we were the only ones saying that stopping eating plants is the way to go if you want to stay alive with glioblastoma or any other advanced cancer. Today’s carnivore influencers were nowhere at that time, so we were quite alone with our opinion. Some of these carnivore influencers were still following a vegetarian diet at this point. We were also the only ones telling the patients that chemotherapy and radiotherapy would shorten their lives. As a result, we received an immense amount of emotionally charged attacks.

 

Why did you want to publish in a scientific journal? Why is it not enough that you know you saved this patient?

Because we aim to help as many patients as possible. Publishing in a scientific journal is normally the way to introduce new scientific results in the field. This is how you disseminate your scientific result if you are a scientist. It is also the Health Law that tells you that publishing at scientific forums is the preferred way to make your results visible. Of course, nobody will pay you for the unique contribution that you want to share with others. On the contrary, you have to pay a large amount of money to get your article published. If you are not particularly wealthy, you may not be able to cover the publishing fee yourself. 

 

Where did you try to publish your results? 

We tried Frontiers in Nutrition.

 

Why did you pick Frontiers in Nutrition?

As the journal’s name implies, we thought that this journal is interested in publishing cutting-edge research. Also, because it is known as a low-carb friendly journal, we thought they would not immediately decline our manuscript with a knee-jerk reaction. An additional reason for picking Frontiers in Nutrition is because this journal was suggested by the author of the “other” case report that we will speak about later.

 

Did you publish your paper as a preprint beforehand?

Yes, we published the manuscript preprint at preprints.org in 2019. To tell you the whole story, preprints.org first also rejected publishing the manuscript, we guess, as a knee-jerk reaction. Since there was no formal reason to reject it, after some correspondence, they did post it.

https://www.preprints.org/manuscript/201912.0264/v2

Figure: Preprint

 

Why is it important to publish a paper as a preprint?

Because if you publish your manuscript as a preprint, then it becomes citable to other researchers.

 

Have you presented the case of this patient elsewhere?

Yes, we did present this case at several international conferences, including Italy, Germany, and the US.

 

What was the reaction at these conferences?

We tell you one typical story. In 2019, the Low Carb Denver Conference committee first declined the abstract of our poster, saying that it is highly “controversial” that the patient received no chemotherapy and radiotherapy. Later on, they did accept it.

 

What did you expect from Frontiers in Nutrition?

We expected that the publication process would be complicated, but we thought it would be fair.

 

Did you receive positive reviews from Frontiers in Nutrition reviewers?

The first reviewer said “everything is a limitation” then answered 13 times “no” to the 13 review questions. That was the whole review in this prestigious journal. The other review was correct. After this first round, the Editor decided to decline the manuscript based on the review’s suggestions. We decided to appeal the Editor’s decision and replied to the journal that that review may have included certain flaws and maliciousness, and we would appreciate another reviewer who can be fair. After this, a new Editor was appointed, and new reviewers were invited, altogether 4 more reviewers. Some of them were quite positive.

 

How long was the publication process at Frontiers in Nutrition?

It was 18 months long. It included two editors, six reviewers, and four rounds of resubmission. We were in the midst of preparing the 5th revision of the manuscript. We have to do so as one of the reviewers raised concerns about the diagnosis (at 14 months after initial submission!) and asked for additional histopathological exams from a sample that was more than 5 years old at this time. The reviewer specifically asked for checking for IDH mutation and MGMT methylation status. Considering all the associated legal aspects, this is a huge task because this necessitated obtaining a bunch of approvals from many parties. With all this amid the corona pandemic, we needed more time and asked for an extension of the deadline. Interesting things started to happen at this point.

 

What kind of interesting things happened?

Frontiers in Nutrition wrote that they are unwilling to extend the deadline because the review process has already been “too long”. After a few days, another interesting thing happened. Frontiers in Nutrition published a case study with a very long glioblastoma survival due to a ketogenic diet therapy. It was not our case report.

 

Was there anything else interesting with this paper?

Honestly, this alone was quite a shock. Moreover, there was no reference to our glioblastoma manuscript in this paper, even though our manuscript is formally citable as a preprint. 

 

Not that that’s not enough, but has there been anything else interesting?

Yes. We sent the case of our glioblastoma patient to one of the authors of this group in January 2018 (that is 3 and half years ago!). In an absolutely selfless way, we provided very specific information to this other group. Upon the request of this group, we sent original, yet unpublished data too. We genuinely thought that we should not withhold any crucial information from like-minded colleagues. Very soon after this, the first version of our glioblastoma manuscript was also sent to this group. The “other” case report not only did not reference our glioblastoma manuscript, but there was no reference to any of our previous case reports in the context of cancer. We also have a paper where we discussed the standard therapy vs. no standard therapy.

approach in cancer, which was a first of its kind that points to the likely adverse effects on cancer, based on direct clinical experience. Although the “other” case study also attributed long-term survival to not having chemo- and radiotherapy, the authors did not cite this paper either.

 

Has there been anything else as an “interesting” circumstance?

Yes, it was quite interesting to see that the last reviewer of our manuscript asked for checking for IDH status in our patient while the “other” case report was about a glioblastoma patient with IDH 1-mutant glioblastoma. This is an interesting coincidence that may raise the possibility of a conflict of interest. Of course, reviewers are anonymous, and we cannot be entirely sure about this. Anyway, the IDH status, in our opinion, is not at all a central issue, or we should rather say, is entirely irrelevant. Also, it is not too frequently discussed elsewhere as an attribute of glioblastoma.

 

Why do you think IDH status is irrelevant?

In our opinion, the IDH status and the other two molecular markers the reviewer asked for are irrelevant. In our experience, no matter what mutation the glioblastoma patient has, this will not affect the outcome of the diet therapy. It is only diet adherence and the presence/absence of other standard treatments that matter. Despite all these, we opted to do this additional histopathological exam to accommodate the reviewer, even if we knew this would significantly delay publication.

 

 

Why did the reviewer ask about the IDH status?

This was also about the correctness of the diagnosis. This reviewer also asked whether the histopathologist was independent from us. We assured the reviewer that the histopathologist who did the report was completely independent from us, as it was 8 months before we met the patient himself. We also replied that the diagnosis of glioblastoma, as stated in the histopathological report, was presented at the specialists’ consultation where all the attendant specialists of the hospital agreed with the diagnosis of glioblastoma (WHO grade IV). Apart from this, the review was very positive.

 

Why do you think Frontiers in Nutrition favored this glioblastoma manuscript over yours?

We don’t know. Our case report is superior over the “other” case as regards all relevant medical aspects. Our overwhelming experience is that journals massively sabotage researchers from Eastern-Europe and Russia.

 

Why do you think your glioblastoma case is superior to the “other” one?

First of all, our patient remained completely progression-free now already for 4 and a half years. At the same time, the “other” case, even if slowly, continuously progressed over the years.

 

In what other aspects is your case superior to the “other” case?

Our patient did not receive any other treatment after starting the diet therapy. The other patient underwent surgery because of tumor progression. Our patient did not have a single epileptic seizure in the last 4 and half years. The other patient did have seizures. Our patient did not receive antiepileptic or any other medicines. The other patient has been receiving antiepileptic and other medicines. Our patient is indeed “our” patient, meaning that we advised and followed him very closely and continuously, including several hundreds of email exchanges, phone and personal consultations during the 4 and half years. The “other” patient self-applied the diet without any professional guidance but relied on internet-based information of variable reliability, some of them not even qualifying as being scientific. The thing is that our patient is currently the best performing glioblastoma patient that ever received a dietary therapy in the world (but likely also the best performing one considered all other glioblastoma patients).

 

Your case report was reviewed for 18 months without a result. How long was the other case report reviewed?

The other paper took only 2 and half months to be published from submission.

 

Aren’t you happy about the result from the other case?

We are not happy with Frontiers in Nutrition very trickily delaying the publication of our manuscript for 1 and half years. This is 3 times the rest of your life if you are a glioblastoma patient. Given the annual number of new cases worldwide, this information theoretically could have affected 375,000 glioblastoma patients. What if it is your mother, wife or daughter the one who could have benefited out of these 375,000 patients? Of course, we are glad that there are other research groups on the same side, even if these groups are, as it turned out, “rival” research groups. It is ok if results, ideas, and methodologies compete with each other. But this should be done in an ethical and correct way. We think it is entirely unacceptable from a publisher or a journal to deceive and silence a research group and favor another.

 

Do you have any other glioblastoma patient who is that successful?

Yes, we do have many who are progression-free for a long time, not taking medications, and experience a high quality of life. Only in the last 12 months, we had more than 10 new glioblastoma patients. And many more with brain cancers of other types. Most of them are progression-free, medicine-free, and symptom-free. As you can imagine, with a dietary and non-standard therapy, the “human factor” is enormous. Therefore not all patients are adherent enough to the diet or the medical suggestions given to them, and not all patients are as successful as the patient from the case report.

 

Why did you go public about this issue?

The “other” case study was published “publicly”. Why shouldn’t we react publicly?

 

Are you going to publish about your other glioblastoma cases after all?

What would be your suggestion? 

 

  Journal Decision What did we do?
07.12.2019 Preprints   Submitted
09.12.2019   Declined without explanation Asked for explanation
10.12.2019   Answered that we did not upload one of the documents  
10.12.2019     We answered that we did upload the requested document
17.12.2019   Accepted the preprint  
26.12.2021 Frontiers in Nutrition   1st submission
      2 reviewers involved
05.02.2020   Rejected by the Editor  
14.03.2021     We raised concerns about serious “flaws” in the review process: one reviewer answered “no” 13 times, that was the review!
24.04.2020   New Editor was assigned and review started again with 2 new reviewers  
    Asked for revision We did the revision
17.09.2020     2nd submission
    Asked for revision Did the revisions
15.10.2020     3rd submission
    Asked for revision Did the revisions
11.02.2020     4th submission
    Asked for revision, reviewer questioned the diagnosis of the patient, and asked for additional histopathology. Started working on the revision including doing the new histopathology
      We asked for deadline extension because the scale of the requested extra work was impossible to finish in time
20.05.2020   Frontiers declined deadline extension because of the “delayed” state of the manuscript  
20.05.2020     We asked for considering deadline extension after all, because of the scale of the modifications asked by the reviewer
31.05.2021   Case study got accepted by Frontiers in Nutrition!!! The only “problem” that it was not ours, it was another glioblastoma case study but with a strikingly similar methodology. This case study took only 2.5 months to review! This case study included no reference to our study, even though the online preprint is citable.  
02.06.2021   Frontier in Nutrition wrote that we may complete the revision and submit the new version of the manuscript ???

Table: Overview of the 18-months review process at Frontiers in Nutrition

 

Dr. Zsófia Clemens and Dr. Csaba Tóth

 

How to cite:

Tóth, C.; Dabóczi, A.; Chanrai, M.; Schimmer, M.; Horváth, K.; Clemens, Z. 4-Year Long Progression-Free and Symptom-Free Survival of a Patient with Recurrent Glioblastoma Multiforme: A Case Report of the Paleolithic Ketogenic Diet (PKD) Used as a Stand-Alone Treatment After Failed Standard Oncotherapy. Preprints 2019, 2019120264 (doi: 10.20944/preprints201912.0264.v2).