02 Case studies in cancer

by Paul G. Werthmann, Lothar Kindermann, Gunver S. Kienle

ABSTRACT

Background: Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine skin tumor with frequent local recurrence, lymph node involvement, distant metastasis, and a high mortality rate. Viscum album extracts (VAE) are a widely used adjunct in cancer treatment and show cytotoxic and immune-modulating effects. Case presentation: A 64-year-old woman was diagnosed with a MCC of the left forearm. In the following course of 21 years, she experienced 4 episodes of lymph node relapse (axillary, submandibular, axillary, clavicular). All lesions were surgically excised. The patient declined chemotherapy and radiation and opted for adjuvant treatment with local subcutaneous VAE injections. Currently—21 years after first diagnosis and 9.5 years after the last relapse—the patient is tumor-free, in good health, and without functional limitations. Conclusion: The presented case shows long-time survival in a patient with MCC treated with surgery and VAE injections. The immune system plays a key role in tumorigenesis of MCC. VAE enhances several immune pathways and might therefore contribute to immunologic tumor control in MCC. The role of VAE in MCC should further be investigated.

Keywords: Merkel cell carcinoma, Viscum album, Immune stimulation, Tumor control

Citation: Werthmann, P. G., Kindermann, L., & Kienle, G. S. (2018). A 21-year course of Merkel cell carcinoma with adjuvant Viscum album extract treatment: A case report. Complementary Therapies in Medicine, 38, 58–60. https://doi.org/10.1016/j.ctim.2018.04.001

Background: Bilateral asynchronous renal cell carcinoma (RCC) is infrequent. Immunotherapy is the first-line treatment for advanced RCC not controlled by locoregional therapy. Viscum album extracts (VAE) have been shown to improve quality of life as well as immunological and antineoplastic properties in different types of cancers. Case Report: A 67-year-old man was diagnosed with Fuhrman grade 3/4 RCC, stage pT1bN0M0 in the right kidney. During the subsequent 6 years, he underwent a right nephrectomy and two metastasectomies (lung). Then an RCC lesion of the left kidney was detected. The patient refused a second nephrectomy and was treated solely with high-dose intravenous and subsequent subcutaneous VAE. A central necrotic area and a peritumoral halo were seen on an ultrasound follow-up from month 7. The patient showed no further progression of RCC during the next 2.5 years. Conclusion: As far as we are aware of, this is the first report of a patient with metastatic RCC with an RCC lesion of the second kidney treated solely with high-dose intravenous and subcutaneous VAE, associated with 2.5 years of progression-free survival and a good quality of life. The use of VAE in RCC should be carefully documented and published to determine future research.

Key Words: Renal cell carcinoma, clear-cell, Viscum album, bilateral, asynchronous.

Citation: Reynel, M., Villegas, Y., Kiene, H., Werthmann, P. G., & Kienle, G. S. (2019). Bilateral Asynchronous Renal Cell Carcinoma With Lung Metastases: A Case Report of a Patient Treated Solely With High-dose Intravenous and Subcutaneous Viscum album Extract for a Second Renal Lesion. Anticancer Research, 39(10), 5597–5604. https://doi.org/10.21873/anticanres.13754

Introduction: Metastatic renal cell carcinoma has a poor prognosis. Treatment approaches with immunotherapy show promising results in subpopulations. Viscum album extracts – used as an adjunct to cancer treatment – have cytotoxic, apoptogenic, and immune-stimulating properties and show synergistic effects with chemotherapy agents. Case Report: A 51-year-old man was diagnosed with metastatic renal cell carcinoma of clear cell histology which was classified as pT3a, N1, M1, G3. Nephrectomy was performed, and the patient received chemoimmunotherapy (interferon-?2a, interleukin-2, fluorouracil, isotretinoin). Additionally, he received V. album extracts as intravenous infusions and subcutaneous injections. One year after surgery, the patient was in complete remission, which is ongoing 18 years after the initial diagnosis. Discussion: This case shows an extraordinarily long survival of a metastasized renal cell carcinoma patient under chemoimmunotherapy and fever-inducing V. album extracts. This combined treatment might have synergistically contributed to tumor remission and control. With regard to clinical relevance, further investigations are needed.

Keywords: Renal clear cell carcinoma · Interleukin-2 · Interferon-?2a · 13-cis-Retinoic acid · Viscum album

Citation: Werthmann, P. G., Kindermann, L., & Kienle, G. S. (2019). Chemoimmunotherapy in Advanced Renal Cell Carcinoma: A Case Report of a Long-Term Survivor Adjunctly Treated with Viscum album Extracts. Complementary Medicine Research, 26(4), 276–279. https://doi.org/10.1159/000496866

Background: A nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL) is a lymphoproliferative neoplasm with a fair prognosis, but the possibility of a malignant transformation into a diffuse large B-cell lymphoma (DLBCL) is high. DLBCL progresses aggressively. Introduction of rituximab into therapy had led to improved outcomes. The use of Viscum album extracts (VAE) in cancer is established, but their application in lymphoma are rare.

Case Presentation: A 65-year-old patient was diagnosed with DLBCL stage IIa with splenomegaly, transformed from a NLPHL, after a 30-year history of repeatedly enlarged inguinal lymph nodes. The patient initially rejected chemotherapy. After his tumor pain increased, he accepted the consecutive therapies bendamustine plus vincristine plus prednisolone, trofosfamide, and rituximab plus cyclophosphamide plus hydroxydaunorubicin plus vincristine plus prednisone (R-CHOP), inducing only a slight regression of the splenic lesions. VAE was additionally applied to R-CHOP. Five months after termination of chemotherapy — under continued VAE therapy in increasing dosage—regression of paraaortal lesions was found. The patient fully recovered under continuous VAE application and is in ongoing complete remission and in a good state of health 17 years after the initial diagnosis.

Conclusion: As complete remission of lymphoproliferative disorders after VAE treatment has been previously reported, further investigations of VAE in lymphoma seem highly worthwhile.

Keywords: Diffuse large B-cell lymphoma, Viscum album, mistletoe, nodular lymphocyte predominant Hodgkin’s lymphoma, malignant transformation.

Citation: Gutsch, J., Werthmann, P. G., Rosenwald, A., & Kienle, G. S. (2018). Complete Remission and Long-term Survival of a Patient with a Diffuse Large B-cell Lymphoma Under Viscum album Extracts After Resistance to R-CHOP: A Case Report. Anticancer Research, 38(9), 5363–5369. https://doi.org/10.21873/anticanres.12865

Introduction: Metastatic malignant cutaneous melanoma (MCM)—a highly immunogenic cancer—typically has a poor prognosis. Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects.

Case presentation: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment. VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and intralesionally. The metastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional and hilar lymph nodes). The patient has been tumor free for 3.5 years at the time of publication (and for 5 years since initiation of intensified VAE treatment). Besides fever and flu-like symptoms, no side effects occurred.

Discussion: We presume that VAE triggered an increased release of tumor-associated antigens, enhanced immunologic recognition, and increased immune response against the tumor tissue and induced tumor remission.

Abbreviations: AJCC = American Joint Committee on Cancer, BRAF = rapidly growing fibrosarcoma type B gene, FDG = Fludeoxyglucose (18F), MCM = malignant cutaneous melanoma, ML = mistletoe lectin, PET-CT = positron emission tomography–computed tomography, UICC = Union internationale contre le cancer, VAE = Viscum album extracts, VT = viscotoxin.

Keywords: complete remission, fever, malignant cutaneous melanoma, Mistletoe, Viscum album extract

Citation: Werthmann, P. G., Hintze, A., & Kienle, G. S. (2017). Complete remission and long-term survival of a patient with melanoma metastases treated with high-dose fever-inducing Viscum album extract: A case report. Medicine, 96(46), e8731. https://doi.org/10.1097/MD.0000000000008731

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Background & Aim: Extracts of Viscum album (European mistletoe) have immune-stimulatory and cytotoxic eects, with trials showing a well-established effect on the quality of life and prolonged survival in patients with advanced pancreatic cancer. Regression of tumours following intratumoural injection with Viscum album extract has been documented in individual cases. However, its influence on colon polyps has not been investigated.

Case presentation: We present the case of a 78-year-old Caucasian male who had undergone hemi-colectomy for a stage IIIC colon cancer but who refused adjuvant chemotherapy. Five years later a newly detected high-grade dysplasia colon adenoma was discovered; however, the adenoma could not be resected endoscopically and the patient did not consent to surgery. Intratumoural injections with Viscum album L extract (Quercus; Iscador®Qu) were administered twice in an attempt to limit tumour growth. Eight months after the second intratumoural injection the adenoma had disappeared and biopsy revealed no intraepithelial dysplasia or adenoma.

Conclusions: This is the first report showing complete regression of a colon adenoma aer intratumoural injection with Viscum album extract. Prospective studies should evaluate if the treatment effect is reproducible and if this approach could be a useful pre-operative measure for colon adenomas too large for endoscopic resection.

Key words: colon polyp – colorectal adenoma – Viscum album – European mistletoe – tumour regression.

Citation: Schoen-Angerer, T. von, Goyert, A., Vagedes, J., Kiene, H., Merckens, H., & Kienle, G. S. (2014). Disappearance of an Advanced Adenomatous Colon Polyp aer Intratumoural Injection with Viscum album (European mistletoe) Extract: A Case Report. Journal of Gastrointestinal and Liver Diseases, 23(4), Article 4. https://doi.org/10.15403/jgld.2014.1121.234.acpy

Background: Skull metastases are rare, they can eventually cause pain, and can invade the brain. Viscum album extracts (VAEs) are used as an adjuvant treatment in cancer.

Methods and Results: A 68-year-old patient with rectal cancer presented with lung metastases, and metastases to multiple bone sites, the chest wall, and the liver were later identified. Histological examination of one of the bone lesions revealed an additional thyroid carcinoma. An osteolytic parietal bone lesion progressed to a painful metastasis of the skull despite radiotherapy and chemotherapy. The VAEs were applied weekly into the metastasis, followed by pain relief and softening of the lesion. The lesion partially regressed (>50%) after 8 months of continued VAE treatment and remained stable for 2 years.

Conclusion: This case shows a durable clinical remission of a skull metastasis under VAE. Further investigations of intratumoral VAE treatment seem worthwhile—especially in symptomatic skull metastases not responding to radiotherapy or systemic therapies.

KEYWORDS: mistletoe, rectal cancer, skull metastasis, thyroid carcinoma, Viscum album

Citation: Werthmann, P. G., Huber, R., & Kienle, G. S. (2018). Durable clinical remission of a skull metastasis under intralesional Viscum album extract therapy: Case report. Head & Neck, 40(7), E77–E81. https://doi.org/10.1002/hed.25320

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

Rationale: Carcinoma in situ (CIS) of the uterine cervix is a premalignant condition of squamous epithelium. The standard treatments are excision and ablation procedures; for women with positive margins, hysterectomy is recommended.

Patient concerns: A 47-year-old Peruvian woman with recurrent candidal vaginitis had been diagnosed with colpocervicitis and squamous metaplasia 8 years ago, which were not treated.

Diagnoses: The patient was diagnosed with CIS after cervical conization procedure. She refused radical hysterectomy and opted for integrative medicine treatment.

Interventions: She was treated with intralesional and subcutaneous Viscum album L. extract (VAE) injections. VAE is a widely used herbal cancer treatment with cytotoxic, apoptogenic, and immunological effects, but it has not been investigated in cervical CIS.

Outcomes: Ending month 5 of treatment, complete remission of cervical CIS was observed. The patient is still in remission after 30 months (until publication).

Lessons: This is the first report on complete remission of cervical CIS after intralesional and subcutaneous injection with VAE. Prospective studies should evaluate to what degree the treatment effect is reproducible.

Abbreviations: CIN = cervical intraepithelial neoplasia, CIS = carcinoma in situ, HPV = human papillomavirus, IL = interleukin, ML = mistletoe lectins, Pap = Papanicolaou, VAE = Viscum album L. extract.

Keywords: case report, cervical carcinoma in situ, cervical intraepithelial neoplasia, complete remission, european mistletoe, fraxini, Viscum album L

Citation: Reynel, M., Villegas, Y., Kiene, H., Werthmann, P. G., & Kienle, G. S. (2018). Intralesional and subcutaneous application of Viscum album L. (European mistletoe) extract in cervical carcinoma in situ: A CARE compliant case report. Medicine, 97(48), e13420. https://doi.org/10.1097/MD.0000000000013420

BACKGROUND: Advanced pancreatic cancer (aPC) has a poor prognosis with limited survival benefit from current standard treatment. Viscum album extracts (VAE) are used by many cancer patients, showing immune-stimulating effects, improved quality of life, and a survival benefit in patients with aPC.

CASE SUMMARY: A 59-year-old architect developed epigastric pain. A cystic lesion of the pancreas of 45-mm diameter was detected. In a follow-up magnetic resonance imaging, about one year later, multiple lesions were seen in the corpus and the tail of the pancreas; CA-19-9 was elevated to 58.5 U/mL. A distal pancreatectomy with splenectomy was performed, and a tumor of 7 cm × 5 cm × 3.5 cm was excised. Histologic investigation showed an intraductal papillary mucinous neoplasm-associated invasive adenocarcinoma with invasion of the lymph vessels, perineural invasion, and positive nodes (2/27); surgical margins showed tumor cells, and the tumor was classified as pT3 N1 M0 R1. The patient was treated with radiation of the tumor bed and capecitabine/oxaliplatin followed by gemcitabine and FOLFIRINOX. Seven months after surgery, a liver metastasis was detected and treatment with FOLFIRINOX was started. Four months after detection of the metastasis, the patient opted for additional treatment with VAE. Another month later, the metastasis was treated with radiofrequency ablation (RFA). Eight months later, the hepatic lesion recurred and was again treated with RFA. The continuous VAE treatment was increased in dose, and the patient stayed
recurrence-free for the next 39 mo in good health and working full-time (as of the time this case report was written).

CONCLUSION: We present the case of a patient with aPC with R1-resection with development of liver metastasis during the course of treatment who showed an overall survival of 63 mo and a relapse-free survival of 39 mo under increasing VAE therapy. The possible synergistic effect on tumor control of RFA treatment and immune-stimulatory effects of VAE should be further investigated.

Key words: Pancreatic cancer; Integrative medicine; Viscum album extract; Radiofrequency ablation; Case report

Citation: Werthmann, P. G., Kempenich, R., Lang-Avérous, G., & Kienle, G. S. (2019). Long-term survival of a patient with advanced pancreatic cancer under adjunct treatment with Viscum album extracts: A case report. World Journal of Gastroenterology, 25(12), 1524–1530. https://doi.org/10.3748/wjg.v25.i12.1524

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

Rationale: Metastatic pancreatic cancer has a dismal prognosis. Many patients seek integrative care as an add-on to their conventional cancer treatment. Viscum album extracts (VAE)—widely used as an adjunct to cancer treatment—have cytotoxic, apoptogenic, and immune stimulatory properties. A statistically significant survival benefit has been demonstrated for VAE in advanced pancreatic cancer. Patient concerns and diagnosis: A 28-year old patient presented with painless jaundice and was subsequently diagnosed as pancreatic adenocarcinoma with liver metastases.

Interventions: He was treated with FOLFIRINOX/Mitomycin, hyperthermia and fever-inducing VAE.

Outcomes: Subsequently, the liver metastases regressed. Surgical intervention involved successful R0-resection of the primary tumor, as well as an atypical liver resection. A relapse was again treated with FOLFIRINOX/Mitomycin and hyperthermia. As of publication of this report, 49 months after initial diagnosis, the patient exhibits good condition, and is unrestricted in quality of life (till publication).

Lessons: This case demonstrates the favorable outcome of a patient with metastatic pancreatic cancer following treatment with chemotherapy, integrative medicine, and surgical excision. As other positive outcomes in pancreatic cancer patients are related to inflammatory events, we presume the immunologic effects of VAE to have contributed to the favorable outcome here. Based on this case, and the other positive results of VAE use in pancreatic cancer, further investigations seem highly worthwhile. Abbreviations: CT = computed tomography, FOLFIRINOX = folinic acid, fluorouracil, irinotecan, oxaliplatin, FOLFOX = folinic acid, fluorouracil, oxaliplatin, ML = mistletoe lectin, PC = pancreatic cancer, UICC = Union for International Cancer Control, VAE = viscum album axtracts.

Keywords: fever, integrative medicine, mistletoe, pancreatic cancer, Viscum album

Citation: Werthmann, P. G., Inter, P., Welsch, T., Sturm, A.-K., Grützmann, R., Debus, M., Sterner, M.-G., & Kienle, G. S. (2018). Long-term tumor-free survival in a metastatic pancreatic carcinoma patient with FOLFIRINOX/Mitomycin, high-dose, fever inducing Viscum album extracts and subsequent R0 resection: A case report. Medicine, 97(49), e13243. https://doi.org/10.1097/MD.0000000000013243

Abstract: Malignant pleural mesothelioma (MPM) is a rare cancer with a dismal prognosis. Viscum album extracts (VAE) have strong immune stimulatory properties, cytotoxic effects, can downregulate cancer genes and inhibit angiogenesis. VAE are often used as an adjunct treatment in cancer patients but have rarely been investigated in MPM. Helleborus niger extracts (HNE) have been used in anticancer therapy since antiquity, and also show tumor specific cytotoxic effects. We present a case of a 64-year old woman with epithelioid MPM of the right chest with node involvement (T2N1M0, stage III). Deciding against the recommended radio-chemotherapy, surgery and pleurodesis, she opted for an integrative treatment approach and was treated with VAE and HNE. After 6 weeks’ treatment, the pleural and nodal MPM manifestations were reduced by about 15%. Subsequent tumor growth was slow, and the patient remained in good health, enabling her to remain physically active until shortly before her death 56 months after the initial diagnosis. This is a rare case of an MPM patient not receiving any standard anticancer treatment; it still shows an extraordinary long survival and good performance status. We presume that VAE and HNE might had an impact on this clinically relevant outcome and therefore should be further investigated in MPM.

Keywords: Malignant pleural mesothelioma (MPM); Viscum album extract (VAE); Helleborus niger extract (HNE); GM-CSF; dendritic cells

Citation: Werthmann, P. G., Saltzwedel, G., & Kienle, G. S. (2017). Minor regression and long-time survival (56 months) in a patient with malignant pleural mesothelioma under Viscum album and Helleborus niger extracts—A case report. Journal of Thoracic Disease, 9(12). https://doi.org/10.21037/jtd.2017.11.56

Abstract: Cancer-related fatigue (CRF) is a major and very common disabling condition in cancer patients. Treatment options do exist but have limited therapeutic effects. Mistletoe extracts are widely-used complementary cancer treatments whose possible impact on CRF has not been investigated in detail. A 36-year-old Swedish woman with a 10-year history of recurrent breast cancer, suffering from severe CRF, started complementary cancer treatment with mistletoe extracts. Over two and a half years a correspondence was observed between the intensity of mistletoe therapy and the fatigue. Mistletoe extracts seemed to have a beneficial, dose-dependent effect on CRF. Although such effect has also been noted in clinical studies, it has never been the subject of detailed investigation. More research should clarify these observations.

Citation: Wode, K., Schneider, T., Lundberg, I., & Kienle, G. S. (2009). Mistletoe treatment in cancer-related fatigue: A case report. Cases Journal, 2(1), 77. https://doi.org/10.1186/1757-1626-2-77

Simple Summary

Pancreatic cancer is associated with poor survival, despite advances in anti-cancer treatment. Most patients are diagnosed at an advanced stage, so the treatment goal is prolongation of survival and maintenance of quality of life instead of cure. In this context, integrative therapeutic approaches have become increasingly important in recent years. Integrative therapies are usually not used alone but complementary to conventional treatment to optimize its effect. Positive effects have been described for symptom alleviation, e.g., pain and quality of life improvement by the additional use of integrative therapies. However, the available data are not sufficient for a conclusive assessment regarding a possible influence on survival. The present work sought to describe the outcome of patients with advanced or metastatic pancreatic cancer not amenable to curative treatment, who received either conventional therapy or additional complementary integrative mistletoe and/or hyperthermia.

Abstract

This retrospective analysis investigated the influence of integrative therapies in addition to palliative chemotherapy in patients with advanced pancreatic cancer, treated at a single institution specialized in integrative oncology between January 2015 and December 2019. In total, 206 consecutive patients were included in the study, whereof 142 patients (68.9%) received palliative chemotherapy (gemcitabine/nab-paclitaxel 33.8%; FOLFIRINOX 35.9%; gemcitabine 30.3%) while the remainder were treated with best supportive and integrative care. Integrative therapies were used in 117 of 142 patients (82.4%) in addition to conventional chemotherapy, whereby mistletoe was used in 117 patients (82.4%) and hyperthermia in 74 patients (52.1%). A total of 107/142 patients (86.3%) died during the observation period, whereby survival times differed significantly depending on the additional use of integrative mistletoe or hyperthermia: chemotherapy alone 8.6 months (95% CI 4.7–15.4), chemotherapy and only mistletoe therapy 11.2 months (95% CI 7.1–14.2), or a combination of chemotherapy with mistletoe and hyperthermia 18.9 months (95% CI 15.2–24.5). While the survival times observed for patients with advanced pancreatic cancer receiving chemotherapy alone are consistent with pivotal phase-III studies and German registry data, we found significantly improved survival using additional mistletoe and/or hyperthermia.

Keywords: integrative oncology; mistletoe therapy; hyperthermia; advanced pancreatic cancer

Citation: Hohneck, A. L., Sadikaj, L., Heinemann, L., Schroeder, M., Riess, H., Gerhards, A., Burkholder, I., Heckel-Reusser, S., Gottfried, J., & Hofheinz, R.-D. (2023). Patients with Advanced Pancreatic Cancer Treated with Mistletoe and Hyperthermia in Addition to Palliative Chemotherapy: A Retrospective Single-Center Analysis. Cancers, 15(20), Article 20. https://doi.org/10.3390/cancers15204929

Abstract

Introduction: Complementary and alternative medicine usage, though rising, remains largely devoid of a sound scientific basis; however, there is increasing evidence to support its use in cancer therapy.

Aim: To present the case of a patient with laryngeal carcinoma who made a full recovery following mistletoe therapy, despite failing to respond to chemoradiotherapy and salvage laryngectomy.

Design: Case report with relevant literature review.

Results: The patient developed extensive, unresectable stomal recurrence, and it was deemed appropriate to supply palliative care only. Following treatment with mistletoe extract injections after palliative radiotherapy, he recovered fully and was eventually discharged from care.

Conclusion: The benefit of mistletoe in laryngeal cancer treatment requires further investigation, and might be considered in selected patients, as an adjunct or when other conventional therapies have failed.

Keywords: Mistletoe; Laryngeal Neoplasms; Carcinoma; Complementary Medicine

Citation: Shakeel, M., Trinidade, A., Geider, S., & Ah-See, K. W. (2014). The case for mistletoe in the treatment of laryngeal cancer. The Journal of Laryngology & Otology, 128(3), 302–306. https://doi.org/10.1017/S0022215114000103

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

Abstract

Viscum album (European mistletoe) extracts have known immunomodulatory effects but little data exist on anticonvulsant activity despite its usefulness having been reported for centuries. A 4½-year-old girl with childhood absence epilepsy and global developmental delay was treated with different antiepileptic drugs and ketogenic diet but failed to become seizure free over a 2-year period. She also received different herbal remedies as part of an integrative medicine approach. Initial improvement occurred on valproate-ethosuximide, a further improvement was seen after adding clobazam to valproate. Final cessation of absence activity occurred after a dose increase of V album. She was still seizure free at the 12-month follow-up. V album appears to have been a necessary adjunct treatment for this child to become seizure free. We call on physicians to report their experiences of V album in epilepsy and suggest further study.

Citation: von Schoen-Angerer, T., Madeleyn, R., Kienle, G., Kiene, H., & Vagedes, J. (2015). Viscum Album in the Treatment of a Girl With Refractory Childhood Absence Epilepsy. Journal of Child Neurology, 30(8), 1048–1052. https://doi.org/10.1177/0883073814541473