The dubious cancer “virotherapy” Rigvir returns with an equally dubious case report

About six months ago, I discussed a dubious and unproven cancer treatment that I had heard of but never looked into before that originated in, of all places, Latvia. This unproven treatment is known as Rigvir, which is represented as “virotherapy” in which an Echovirus (specifically Echovirus-7) is that, according to the IVC, seeks out cancer cells, replicates in them, and thus lyses the cancer cells (causes their membranes to break, spilling out the cancer cells contents, thus killing the cell), hence the term “oncolytic virus.” As I’ve discussed before, somehow, as I’ve mentioned before, mysteriously Rigvir was approved by the Latvian equivalent of the FDA in 2004 for the treatment of malignant melanoma despite what appears to have been grossly inadequate supporting evidence and then even more mysteriously placed on the Latvian Health Ministry’s list of reimbursable medications in 2011. Since then, it’s been increasingly marketed widely at quack cancer clinics, ranging from Dr. Antonio Jimenez’s Hope4Cancer Clinic in Mexico to various German cancer clinics, which I’ve discussed before.

Indeed, what led me to discuss Rigvir one more time was a comment in a recent post about the Hallwang Clinic. In it, a commenter going by the ‘nym DDay, probably thinking he or she was taunting me, pointed to a case report purporting to suggest that Rigvir virotherapy had greatly prolonged the life of a patient with melanoma metastatic to the brain. As you will see, it is not good evidence of the efficacy of Rigvir.

Before I discuss the study itself, in fairness I’ll mention that it isn’t beyond the realm of plausibility that an oncolytic virus could be an effective treatment of cancer. Indeed, such viruses, usually modified, are an active area of research. However, the claims made for Rigvir, both by the International Virotherapy Center and quack clinics like Hope4Cancer are selling it as a cancer cure. For instance, here’s Hope4Cancer:

Rigvir® is a product from the International Virotherapy Center (IVC) based in Riga, Latvia. In 2004, Rigvir® became the first approved oncolytic virotherapy in the world, approved and registered in Latvia as an active and specific immunotherapy. Rigvir® is the result of over 50 years of research conducted in Latvia4-7 under the leadership of legendary virologist, Dr. Aina Muceniece, and has been tested for safety and efficacy in thousands of patients in Latvia. Besides the occasional slight temporary fever, Rigvir® has virtually no side effects. These results are consistent with Hope4Cancer’s experience with Rigvir® in patients since 2014.8

Conveniently, most of the references cited above are from Latvian and Russian language journals that I cannot access, although I discussed in great detail over three posts why even secondhand accounts of this evidence are both incomplete and not compelling. I’ve also explained why the other, more recent studies, are at best preliminary and also unconvincing. Yet the irresponsible and misleading testimonials from the International Virotherapy Center keep flowing.

So let’s take a look at the case report itself. The introduction points out:

Melanoma is considered an aggressive malignancy with a tendency of forming metastasis in the brain. Less than 10% of all melanoma cases present with unknown primary tumor location. This diagnose is yet to be fully understood, because there are only theoretical assumptions about the nature of the disease. Melanoma brain metastases have many severe side effects and, unfortunately, any disease related to the brain has limited therapeutic options due to the blood–brain barrier. The course of the disease after a treatment course is complicated to predict, and it is difficult to obtain long-lasting remission.

All of the above, of course, is indeed true. Brain metastases are bad. Cancer of any kind in the brain is bad, as we learned from my many discussions of Stanislaw Burzynski. As bad as glioblastoma is, however, the most common source of cancer in the brain is metastatic spread from other primaries, like breast or lung cancer, and, yes, melanoma. As you might expect, brain metastases portend a dire prognosis. So it was that the patient described in the case report, a 64 year old woman, would not be expected to do well:

In 2014, the patient complained about severe dizziness after movements and increased fatigue. No headache was observed. The patient has a Ph.D., she is married, has three children, her hobbies include traveling and has an active lifestyle. There is no previous family history of cancer. After contrast-enhanced head and brain magnetic resonance imaging (MRI), the patient was diagnosed with a formation in the craniospinal junction. The patient underwent a planned posterolateral foramen magnum formation extirpation in 23 April 2014 (Figure 1). The surgery lasted for 12 h, and no severe complication was observed. CT scan performed 5 days after surgery showed a minimal residual caudal part of the tumor. The condition of the patient during the postoperative period was satisfactory; progressive renewal of physical endurance with no signs of new essential neurologic deficit was observed.

After surgery:

The patient declined postoperative radiation therapy, because the metastasis residue was closely located to truncus encephali and; therefore, the risk of complications was estimated as high, and efficacy of the radiotherapy uncertain (at that time, stereotactic radiosurgery was not available in Latvia). Since no BRAF mutation was found, therapy with a BRAF inhibitor was contraindicated; in 2014, CTLA-4 and PD-1 immunotherapy was not registered in Latvia (at the time when the decision on adjuvant therapy was made).

The truncus encephali is just a fancy term for the brainstem. I actually hadn’t heard anyone refer to the brainstem by that term in a very long time.

This is what’s known as metastatic melanoma of unknown primary. The patient had never been diagnosed with melanoma before. She had, however, had a basal cell carcinoma excised five years before her diagnoses with brain metastases, but nothing else that might even remotely be related. The authors speculate that maybe the basal cell carcinoma was misdiagnosed. Another possibility is that there was a small primary melanoma that regressed. (Melanomas do sometimes spontaneously regress; it’s not that common, but it has been observed.) Whatever the origin of this woman’s brain metastasis, it is known that somewhere between 2%-6% of metastatic melanomas have an unknown primary tumor, and an extensive workup, with imaging, skin examinations, and other tests, was undertaken to find the primary tumor. None was found. The authors point also out that metastatic melanoma with an unknown primary might have a somewhat better prognosis than your standard, run-of-the-mill melanoma.

In any case, because the patient wasn’t deemed a candidate for radiation therapy and was definitely not a candidate for BRAF inhibiting drugs, it was only natural that, being in Latvia, this patient would get Rigvir. After all, Rigvir seems to be a matter of national pride (how else it was approved for use in Latvia, I can’t figure out), and it seemingly can cure any cancer if you believe the International Virotherapy Center. Treatment with Rigvir was begun in July 2014 with a three-day series of doses followed by doses once a week. In January 2015, the injections were changed to every two weeks, and then in December 2016 to every three weeks. The patient has not received any other treatment.

The case report shows a series of MRI scans, which are characterized as showing “minimal residual tissue of a melanoma metastasis in the anterior spinal cord located in the craniospinal junction without significant changes in structure and size.” I’m a bit skeptical. Yes, there is a small lesion there that hasn’t changed, but I’m lacking one huge piece of information I need to evaluate the case report. Surgeons who actually read the case report will know right away what I’m talking about because, as surgeons, when reading of any resection of any tumor it’s something we look for right away in the pathology report. I’m referring, of course, to the surgical margins. Nowhere is it mentioned whether the surgical margins were clear. By “clear margins,” I mean that no tumor is seen at the edge of the resected specimen, meaning that the tumor has been completely resected. Given that there’s no histologic confirmation or confirmation on other scans that the lesion seen on the followup MRIs is actually tumor, we don’t even know if there was residual tumor.

The authors also play a deceptive game with selective citations:

The median expected overall survival from the time of melanoma brain metastasis diagnosis is approximately 5 months (15). A meta-analysis suggests that the prognosis of melanoma unknown primary is better than that of melanoma known primary (4). The patient described here has been stable for more than 3 years and 9 months, and the virotherapy is still ongoing.

Let’s look at reference 15, which is a report from the British Journal of Cancer from last year examining the effect of immunotherapy on melanoma brain metastases. It was a retrospective study examining the effect of anti-PD1 therapy, and citing it was very deceptive. Why? Simple. This was a study of all comers, most of whom did not undergo surgical resection and many of whom had multiple brain metastases. It’s a study that was not well-suited to serve as a comparison to this patient.

Annoyed, I looked for studies more appropriate to compare this woman’s outcome to. One study I found looked at the survival of patients treated with stereotactic radiosurgery and ipilimumab, an immunotherapy. Stereotactic radiosurgery is a technique used to closely target brain metastases using precisely focused radiation beams. It’s not surgery in the traditional sense in that there’s no incision. Rather, it uses 3D imaging to aim high doses of radiation to the tumor with minimal “bleed” over to normal surrounding healthy tissue. Basically, it cooks the tumor. This study noted a median survival of 29.3 months when brain metastases were present. Now, this study is an outlier and retrospective. It also has immunotherapy added. Most studies show median survival for melanoma brain metastases of a year or less. Even so, there are outliers, and the very fact that this patient’s tumor could be resected successfully and that she had no known primary already made it a lower risk tumor.

So did Rigvir have anything to do with this patient’s good fortune? This case report sure isn’t any good evidence that it did. Why? Because it’s a case report. That means it is almost certainly not reflective of what usually happens, because if it were (e.g., the patient died less than a year after her surgery) it almost certainly would not have been reported as a case report. That’s why randomized clinical trials are done; case reports and small case series can mislead.

Case reports, however, are what the International Virotherapy Center bases its entire advertising model on. For instance, I just learned of a documentary:

And here’s a trailer from November:

It’s all part of a propaganda film called Climb for Cancer:

The Aina Muceniece Virotherapy Foundation has launched an initiative to involve oncology patients in voluntary activities, supported by doctors, in order to prove that they can still make the most of life while undergoing treatment.

For this purpose, the Aina Muceniece Virotherapy Foundation and the “Kalnu Grupa” (Mountain Group) organised a climbing expedition to the Alps from 29 July to 12 August 2017.

Participants did include existing and former virotherapy patients as well as other oncology patients who are currently fighting the disease or have already overcome cancer in different forms and stages. The trip will also involved patients who were prescribed palliative care and who didn’t have much hope before they found virotherapy.

You can see the message. It’s the same message that dubious and quack cancer clinics peddle on a routine basis, namely that these patients were “written off” by conventional medicine but were saved by Rigvir. It’s the same message peddled by Stanislaw Burzynski and German cancer clinics. I will give them credit, though. They have a more flamboyant way of making a propaganda movie than any I’ve ever seen before.

More and more, I’m convinced that Rigvir virotherapy has many of the hallmarks of cancer quackery. There’s nothing in the way of rigorous evidence in the form of well-designed randomized clinical trials to support its efficacy for anything, and what is out there is of low quality or inaccessible, having been published decades ago in journals from Eastern Europe. Its entire marketing campaign relies on anecdotes and case reports. Increasingly, it’s being marketed to alternative cancer clinics. What more do you need to conclude that Rigvir is quackery?