02 Case studies in cancer

Abstract
Background: Mistletoe is a complementary cancer treatment that is widely used, usually in addition to and alongside recommended conventional cancer therapy. However, little is known about its use, effectiveness, and safety in the treatment of cutaneous lymphoma. Case Report: Two patients with primary cutaneous B-cell lymphoma (pT2bcNxM0 follicle center and pT2ac-NxM0 marginal zone) either declined or postponed recommended conventional treatment and received highdose, fever-inducing mistletoe treatment; a combination of intratumoral, subcutaneous, and intravenous application was given; and one patient also underwent whole-body hyperthermia. The lymphoma regressed over a period of 12 and 8 months, respectively, and after administration of a cumulative dose of 12.98 g and 4.63 g mistletoe extract, respectively. The patients are in remission to date, 3.5 years after commencement of treatment. Neither patient received conventional cancer treatment during the entire observation period.

Citation: Orange, M., Lace, A., Fonseca, M. P., Von Laue, B. H., Geider, S., & Kienle, G. S. (2012). Durable Regression of Primary Cutaneous B-Cell Lymphoma following Fever-inducing Mistletoe Treatment: Two Case Reports. Global Advances in Health and Medicine, 1(1), 18–25. https://doi.org/10.7453/gahmj.2012.1.1.006

Background: Cutaneous squamous cell carcinoma (CSCC) is a common locally invasive skin cancer which rarely metastasises. First-line treatmentis surgical excision, which is curative in most cases. Viscum album extract (VAE) is a widely used herbal cancer treatment with cytotoxic, apoptogenic and immunological effects, but has not been investigated in CSCC.

Case presentation: A 78-year-old patient with histologically diagnosed CSCC refused surgical excision and was treated with peri-lesional high-dose VAE. After 10 months of treatment the CSCC had disappeared clinically. The patient has been recurrence-free for 4 years.

Conclusion: The presented case shows clinical response of a CSCC to high-dose peri-lesional VAE injections. Further research on VAE in CSCC is warranted.

Keywords: Keywords: Mistletoe, Viscum, Cutaneous squamous cell carcinoma, Case report

Citation: Werthmann, P. G., Sträter, G., Friesland, H., & Kienle, G. S. (2013). Durable response of cutaneous squamous cell carcinoma following high-dose peri-lesional injections of Viscum album extracts – A case report. Phytomedicine, 20(3), 324–327. https://doi.org/10.1016/j.phymed.2012.11.001

Introduction: Viscum album extract (European mistletoe), containing immuno-active compounds with dose-dependent cytotoxic activity, is being used as an adjuvant cancer treatment in Europe. Few studies have yet been done with high-dose, fever-inducing Viscum album treatment.

Objective: To explore whether subcutaneous injections of high-dose Viscum album have a preventive effect on risk of recurrence of bladder cancer.

Methods: We retrospectively analyzed the case records of patients with resectable bladder cancer who underwent initiation of high-dose Viscum album treatment at our clinic between January 2006 and December 2012.

Main Outcome Measures: We calculated tumor recurrence and progression risk and explored case records to assess whether treatment had a likely, possible, or unlikely beneficial effect.

Results: Eight patients were identified, 7 of whom had nonmuscle-invasive bladder cancer and 1 with muscle-invasive cancer. Four patients had frequently recurring tumors before treatment. Among the 8 patients, 28 episodes of recurrence were observed. Median tumor-free follow-up duration was 48.5 months. High-dose Viscum album showed a possible beneficial effect in 5 of 8 patients, could not be assessed in 2 patients, and had an uncertain effect in 1 patient. No tumor progression was observed. Treatment was generally well tolerated and no patient stopped treatment because of side effects.

Conclusion: High-dose Viscum album treatment may have interrupted frequently recurring tumors in individual patients with recurrent bladder cancer. Prospective studies are needed to assess whether this treatment offers an additional, bladder-sparing preventive option for patients with intermediate- to high-risk nonmuscle-invasive bladder cancer.

Citation: von Schoen-Angerer, T., Wilkens, J., Kienle, G. S., Kiene, H., & Vagedes, J. (2015). High-Dose Viscum album Extract Treatment in the Prevention of Recurrent Bladder Cancer: A Retrospective Case Series. The Permanente Journal, 19(4), 76–83. https://doi.org/10.7812/TPP/15-018

Abstract

Retroperitoneal sarcomas are rare. Dedifferentiated liposarcomas (DDLs) are high-grade tumors with a high propensity for local recurrence and metastasis and are associated with reduced survival. Radical resection remains the standard treatment of sarcomas. Meanwhile, Viscum album L. extract (VAE) is used in cancer patients owing to its cytostatic and immunomodulating effects and to its ability to improve patients’ quality of life. Case Presentation: A 68-year-old male patient underwent a resection of a DDL (T2 N0 M0, FNCLCC grade 2, stage IIIA) in the retroperitoneum. Three months after this first surgery, a recurrence occurred, and was treated with neoadjuvant and adjuvant doxorubicin plus ifosfamide and surgery (resection). A second recurrence—11 months after the second surgery—was treated with surgery and radiotherapy. The patient then began to undergo VAE treatment (0.2 mg-2 mg, subcutaneously, thrice a week). After the VAE treatment was initiated, the patient reported improved quality of life. A third recurrence—12 months after the third surgery—was treated with surgery, radiotherapy, and with an increased dose of VAE (20 mg). Sixty-nine months (5.8 years) after the fourth surgery a fourth recurrence occurred. It was again treated with surgery, along with a month of intravenous VAE infusions and subsequent subcutaneous VAE (20 mg) treatment. Finally, a fifth recurrence—5 months after the fifth surgery—was treated with subcutaneous and intravenous VAE applications and eribulin. The patient died 11 months after the last recurrence; he received a total of 103 months (8.6 years) of VAE treatment and achieved 10.5 years of survival. Conclusion: The case presented herein shows a long-time survival and a prolonged recurrence-free interval in a patient with retroperitoneal DDL treated with surgery, chemotherapy, radiotherapy, and VAE injections. On the basis of the antitumoral and immunomodulating effects of VAE and on the reported prolonged survival of VAE-treated patients with other types of tumors, the adjunct VAE treatment is presumed to have contributed to the favorable outcome. Regarding the clinical relevance of VAE treatment, further investigations are needed.

Keywords: retroperitoneal liposarcoma, dedifferentiated liposarcoma, Viscum album, recurrence, survival

Citation: Reynel, M., Villegas, Y., Werthmann, P. G., Kiene, H., & Kienle, G. S. (2021). Long-Term Survival of a Patient with Recurrent Dedifferentiated High-Grade Liposarcoma of the Retroperitoneum Under Adjuvant Treatment with Viscum album L. Extract: A Case Report. Integrative Cancer Therapies, 20, 1534735421995258. https://doi.org/10.1177/1534735421995258

SUMMARY
Adenoid cystic carcinoma (ACC) is a rare type of cancer that typically originates in the salivary glands. Surgical removal can lead to functional loss and psychological distress. Viscum album extract (VAE) is a herbal remedy with dose-dependent cytotoxic, apoptogenic and immunological effects. In some case reports, tumour regression has been observed following high-dose local applications of VAE. An active 88-year-old man with fast-growing ACC of the hard palate refused surgical removal and received high-dose intratumoural injections of VAE (alone) over a 10-month period. The tumour
decreased in size, softened and loosened from its surroundings. A biopsy during the course showed inflammation. The patient remained well and without functional limitations during the therapy and follow-up period (5 months). VAE produced no reported side effects. This aged patient exemplifies a satisfying course of ACC under VAE resulting in good quality of life and partial tumour regression.

Citation: Werthmann, P. G., Helling, D., Heusser, P., & Kienle, G. S. (2014). Tumour response following high-dose intratumoural application of Viscum album on a patient with adenoid cystic carcinoma. Case Reports, 2014, bcr2013203180. https://doi.org/10.1136/bcr-2013-203180