Dr. Rainer Stange wrote a report that has since been published
in German in ZAEN Magazine 3+4/2023. You can download this report
here.
Below is the English translation of the text of this report. The
text has been slightly revised and translated by deepl Version
23.11.2.11449.
Photos of the symposium can be found at the folder 8th
Mistletoe Symposium.
The eightfold path - report from an unusual
symposium
Mistletoe in tumour therapy - 8th Mistletoe Symposium, 9-11
November 2023
Rainer Stange
The symposium "Mistletoe in Tumour Therapy - Basic Research and
Clinical Practice", known in the scene as the Mistletoe Symposium
for short, is the only "Olympic discipline" in phytotherapy. It has
been held every four years since 1995. As the seventh symposium
took place in 2019, it has been one of the few activities due to
this rhythm not to be restricted at all by the coronavirus
pandemic. The first mistletoe symposium was held at the "Scientific
Colloquium Centre" of Saarland University in
Homburg-Schwarzenacker, Germany, while the following seven were all
held at the European Academy Otzenhausen (EAO) in Nonnweiler,
Saarland, Germany. Its foundation in 1954 was based on the
involvement in the referendum for the Saar Statute, which envisaged
the Europeanisation of the Saarland as the seat of the future
European institutions. Unfortunately, not much came of this.
Allegedly, it was also the geographical centre of the then six
founding states of the later European Community (EC).
This year's 8th Mistletoe Symposium was again well attended with
around 110 people. In keeping with the European spirit of the
centre, the majority of them came from Switzerland and Germany,
enriched by a few speakers from the Netherlands, Belgium, Italy,
South Korea, Brazil and the USA, for whom simultaneous translation
was available. Together they presented 54 papers, 34 as lectures
and 20 as posters. All abstracts have been published in a special
issue and are freely downloadable [1]. The detailed contributions
will be published as a book by KVC Verlag, Essen, at the end of
2024 under the title "Mistletoe in Tumour Therapy 6: Current State
of Research and Clinical Application".
Traditionally, it is mainly scientists working with mistletoe,
as well as representatives of clinics, mainly from anthroposophic
medicine, who find their way to the small town in Saarland, where a
centre of the Celtic Hunsrück-Eifel culture was located over 2,000
years ago, as the Celtic ring wall shows. The format is
traditionally two half days and one full day filled with original
and overview contributions as well as a panel discussion. All
participants are offered catering in the academy, which makes for
very lively communication in the short time available. This year,
for the first time on Friday afternoon and evening, external hybrid
participants were able to take part in a broader lecture programme
as a kind of introduction to mistletoe therapy. Attendance and
online participation were free of charge thanks to the generous
commitment of several sponsors and the tireless efforts of the
nestor of the mistletoe symposia, Dr. Rainer Scheer. He is
traditionally supported by representatives of several scientific
societies as the committee responsible for the content and editors
of the abstract booklet and the congress proceedings, including the
Society of Anthroposophic Physicians in Germany (GAÄD), the Society
for Medicinal Plant and Natural Product Research (GA), the Society
for Phytotherapy (GPT) and the Zentralverband der Ärzte für
Naturheilverfahren und Regulationsmedizin (Physicians involved with
Natural and Regulatory Medicine, ZAEN).
Due to its brevity, this report inevitably only contains what
the author considers to be the important features of the scientific
discourse, particularly since the last mistletoe symposium in
2019.
Immunotherapeutics
The most significant development in internal oncology since then
has undoubtedly been the advance of immunotherapeutics. The
representatives of mistletoe therapy reacted very quickly to this,
as it was necessary to examine whether, after decades of research
into the exact description of the desired immunological effects,
there could be any interference.
The first observational data were presented in two papers,
according to which there is no evidence of either poorer
tolerability or a weakening of the effect of first-line monotherapy
with the checkpoint inhibitor pembrolizumab when mistletoe therapy
is given at the same time.
PHOENIX-3 is an observational study from the Havelhöhe Community
Hospital, Berlin, in which 43 patients with primarily inoperable,
metastasised non-small cell lung cancer have been enrolled to date.
These patients are being compared with patients from the large
KEYNOTE-024 study with regard to tolerability of the checkpoint
inhibitor pembrolizumab and the short-term oncological course. With
a median treatment duration of six months, there were no
differences in important tolerability parameters or quality of
life, at most a slight tendency in favour of mistletoe therapy
patients (abstract 22).
In addition, other immunotherapeutic agents such as PARP and
CDK4/6 inhibitors are now commonly used in breast cancer therapy,
often in combination with Herceptin, tyrosine kinase or mTOR
inhibitors. A similar observational study from Havelhöhe compared
160 non-randomised control patients with 82 mistletoe breast cancer
patients (Helixor, host tree and dosage were not specified). Each
received at least one immunotherapy. Here, too, only a preliminary
analysis was reported, according to which there were no negative
consequences of mistletoe therapy (abstract 23).
A panel discussion was also devoted to this topic, although it
was fully recognised that further careful observation was needed.
However, it was also stated that in conventional oncology there
were apparently no reservations about combining several
immunotherapeutic agents with sometimes quite different approaches.
Also in view of the rapid approval of further immunotherapeutics,
questions such as changes in tolerability and/or efficacy due to
parallel mistletoe therapy could in future be answered less and
less in carefully planned, preferably randomised individual
studies, but rather in the recording of as many individual cases as
possible with suitable data collection. This so-called real world
data will become much more important in the future.
Clinical studies and reviews
As one of the most important clinical studies, a South Korean
group led by Chang Moo Kang presented a retrospective controlled
study on pancreatic cancer of 604 patients undergoing surgery. 113
received 0.02 mg Abnobaviscum Fraxini s.c. three times a week from
the time of surgery, while criteria for their selection were not
given. A control group of 113 patients was formed from the
remaining collective using propensity score matching (PSM). After
one year, there was no difference in overall survival between the
groups. In some subgroups, disease-free survival (DFS) was
prolonged in favour of mistletoe therapy, if the initial situation
was either R0, stage I or II or if there was no lymph node
involvement. All treatments were optional for both groups. There
were also advantages for mistletoe patients with regard to DFS if
no chemotherapy, in particular with the Folfirinox regimen, had to
be given (abstract 24).
Wilfried Tröger, Arlesheim, Switzerland, gave an overview of all
systematic reviews and meta-analyses on mistletoe therapy for
cancer from the last 14 years. These describe 165 studies in 18
reviews and 7 meta-analyses. 13,807 mistletoe patients were
compared with 17,005 control patients. A total of 132 group
comparisons were made. The most frequent studies regarding organ
manifestations were breast cancer (39), lung cancer (10), ovarian
cancer (10) and pancreatic cancer ( 8). 11 reviews summarised a
gain in quality of life with good tolerability. However, there were
also considerable methodological weaknesses, when the reviews were
assessed using the standard Amstar 2 or ROBIS instruments. This
even applied to COCHRANE reviews and an HTA report (health
technology assessment with a precisely defined procedure) (Abstract
20).
Preclinical research
Some pharmaceutical mistletoe manufacturers are also looking for
more favourable galenic dosage forms. In one experimental
preparation, mistletoe lectins (ML) are embedded in nanoparticles.
For various reasons, heparin is preferred to the usual polyethylene
glycol (PGE). Gero Leneweit, Niefern-Öschelbronn, Germany, was able
to show that ML 1 can be better introduced intracellularly into
standard lines of both colon carcinoma and glioblastoma (abstracts
11 and 37).
Matthias Melzig, Berlin, Germany, has been analysing micro-RNA
(miRNA) for some time now as a potentially bioactive molecule from
medicinal plants that has received little attention to date. In
mistletoe, he has so far identified 29 different ones with lengths
between 19 and 22 nucleotides. It is unclear to what extent miRNA
are species-specific. He analysed 6 miRNA from mistletoe in
comparison to 3 that occur in many plants. Val-miR218 from
mistletoe interacts with essential target structures such as DNA
itself and DNA replication in several tumour cell lines, including
sarcoma. miRNA is thus possibly another bioactive substance group
to be considered (Abstract 12).
Sascha Markowitsch, Mainz, Germany, investigates in vitro
effects on urological tumour cell lines, in particular renal cell
and prostate cancer, with Iscucin® mistletoe preparations (WALA
Heilmittel GmbH, Bad Boll, Germany) of the 4 host trees lime,
poplar, willow and hawthorn (tiliae, populi, salicis and crataegi).
He dilutes these in proportions between 1:8,000 and 1:800,000 of
the mother tincture and can demonstrate an effect of up to
1:160,00. The renal cell carcinoma line CAki-1 786 showed
apoptosis, integrin expression and CD44 expression. Aqueous
mistletoe solutions performed better than alcoholic solutions
(Abstract 13).
Proponents of mistletoe therapy not only analyse it with the
methods of evidence based medicine, but also with analyses based on
associations: Johannes Wilkens, Bad Steben, Germany, has been
pursuing possible categorisations of the mistletoe used to date
from 13 host trees in the meridian system of traditional Chinese
medicine for many years (Abstract 8). The aim is always to find a
therapy that is optimally tailored to the individual patient's
choice of host tree and dose as the basis for mistletoe
therapy.
Veterinary medicine
There are also regular presentations on this topic at the
symposia. This will come as a surprise to human physicians.
However, there is the relatively unusual situation here of gaining
knowledge from therapy in pets that could be transferable to human
medicine.
Anke Beermann, Frick, Switzerland, from the internationally
based Research Institute of Organic Agriculture (FiBL) treats
equine sarcoid, a semi-malignant tumour with a prevalence of 12% in
three-year-old horses, regularly with subcutaneous mistletoe
therapy. A previously presented placebo-controlled study suggests
the benefit of this therapy, in which up to 41% of horses showed
partial or complete remission after one year, compared to 14%
apparently spontaneous remission in the control group [2]. However,
subcutaneous therapy three times a week over several months is,
among other things, very labour-intensive. She therefore tested the
hypothesis, almost ruled out in human medicine, whether peroral
therapy as a feed supplement could be similarly effective here
(abstract 25). In the double-blinded, three-armed study with a
total of 45 randomised horses (kept individually and privately,
5-12 years old), peroral therapy was compared with s.c.
administration three times a week or placebo over 28 weeks using a
double-dummy approach. 328 sarcoids were analysed. Out of 15 per
group, 4 horses showed complete remissions under oral therapy, 3
under s.c. therapy and 2 under placebo. Both routes of
administration proved to be well tolerated, but the author
recommends the peroral route due to the slightly better results and
much easier handling. Due to the different gastrointestinal
conditions between horses and humans, as well as the special tumour
biology of sarcoid, which is very rare in humans, this very
astonishing result cannot be transferred to tumour therapy in
humans, but should stimulate corresponding research.
Summary
The 8th Mistletoe Symposium once again presented a wealth of
news. Mistletoe therapy still seems to have a firm place,
particularly in view of the increasing importance of oncological
immunotherapeutics. Convincing studies that could ensure an
improvement in the usual parameters of oncological prognosis
through to overall survival under current therapy standards are
still lacking. As desirable as they would be, they represent less
and less of a justification for an additional therapy in times of
very rapid introduction of new immunotherapeutic agents or are to
be included in guidelines. The conventional primary therapy for the
publication of such a mistletoe study, perhaps designed for 10
years, has already changed decisively. In this respect, questions
of gain in quality of life and tolerability of conventional
therapies remain predominant for the majority of oncological
situations.
The four-year rhythm, which is somewhat unusual for some, seems
to be very successful - in this period, enough new research results
are obtained and presented for a two-day symposium. Speakers and
participants have adapted well to this. At this symposium, Friday
afternoon and evening were offered as a hybrid for the first time,
deliberately focusing on the presentation of established knowledge
and procedures. The scientific committee felt that this experiment
was a success and would like to repeat it.
Author:
Dr. med. Rainer Stange
Charité-Universitätsmedizin Berlin
and Immanuel Krankenhaus
Abt. f. Naturheilkunde
Königstr. 63
D-14109 Berlin-Wannsee
Phone: +49 30 80505-691; fax: +49 30 80505-692
E-mail address: r.stange@immanuel.de
[1] Mistletoe in tumour therapy: Basic research and clinical
practice. 8th Mistletoe Symposium 9-11 November 2023
Nonnweiler-Otzenhausen, Germany. Journal of Integrative and
Complementary Medicine, Vol 29, Supplement 1, 2023. https://doi.org/10.1089/jicm.2023.29117.abstracts
[2] Christen-Clottu O, Klocke P, Burger D et al. Treatment of
clinically diagnosed equine sarcoid with a mistletoe extract
(Viscum album austriacus). J Vet Intern Med 2010; 24(6):
1483-1489