Parasitic Plants Newsletter ISSN 1944-6969 Newsletter of the International Parasitic Plant Society, Amsterdam, Javakade 712, 1019 SH, The Netherlands: Haustorium 85, page 4.

 

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