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Vella R, Giardino A, Pizzocaro E, Frigerio I, Bannone E, Vieni S, Butturini G. Unconventional Treatments for Pancreatic Cancer: A Systematic Review. Cancers (Basel) 2025; 17:1437. [PMID: 40361364 PMCID: PMC12071172 DOI: 10.3390/cancers17091437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Revised: 04/21/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
OBJECTIVE This study aims to review the existing literature on the efficacy and safety of unconventional treatments among pancreatic cancer patients, including the use of natural products, dietary supplements, probiotics, whole medical systems, and body-based therapies. METHODS An electronic, systematic, and comprehensive literature review was conducted searching for studies up to November 2024 following the PRISMA 2020 guidelines. Randomized controlled trials and prospective and retrospective studies assessing the efficacy and safety of unconventional treatments for pancreatic cancer were considered eligible. Data on overall survival, quality of life, and treatment tolerability were extracted. RESULTS A total of 21 studies, providing data from 3095 patients, met the inclusion criteria. Various types of unconventional treatments are used in pancreatic cancer patients, including Chinese herbal medicine (CHM), mistletoe extract (ME), curcumin, and electroacupuncture. Among these, the use of CHM and curcumin concomitant with standard therapy was associated with survival and quality-of-life benefits. Electroacupuncture reduced pancreatic cancer pain intensity in a cost-effective manner. The data on ME are mixed and of insufficient quality for drawing definitive conclusions. CONCLUSIONS Some unconventional treatments showed potential benefits in improving overall survival and quality of life in pancreatic cancer patients within an integrative oncology setting. Further high-quality studies are needed to provide robust, rigorous, and ethical evidence to support their integration into future guidelines, ensuring a holistic approach to cancer treatment.
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Affiliation(s)
- Roberta Vella
- HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy; (R.V.); (A.G.); (I.F.); (E.B.); (G.B.)
- Department of Precision Medicine in Medical, Surgical, and Critical Care, (Me.Pre.C.C.), University of Palermo, 90133 Palermo, Italy;
| | - Alessandro Giardino
- HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy; (R.V.); (A.G.); (I.F.); (E.B.); (G.B.)
| | - Erica Pizzocaro
- HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy; (R.V.); (A.G.); (I.F.); (E.B.); (G.B.)
- PhD School of Applied Medical-Surgical Sciences, University Tor Vergata, 00133 Rome, Italy
| | - Isabella Frigerio
- HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy; (R.V.); (A.G.); (I.F.); (E.B.); (G.B.)
- Collegium Medicum, SAN University, 90-012 Lodz, Poland
| | - Elisa Bannone
- HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy; (R.V.); (A.G.); (I.F.); (E.B.); (G.B.)
| | - Salvatore Vieni
- Department of Precision Medicine in Medical, Surgical, and Critical Care, (Me.Pre.C.C.), University of Palermo, 90133 Palermo, Italy;
| | - Giovanni Butturini
- HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy; (R.V.); (A.G.); (I.F.); (E.B.); (G.B.)
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Schad F, Thronicke A, Hofheinz RD, Klein R, Grabowski P, Oei SL, Wüstefeld H, Grah C. Immune Checkpoint Blockade Combined with AbnobaViscum ® Therapy Is Linked to Improved Survival in Advanced or Metastatic Non-Small-Cell Lung Cancer Patients: A Registry Study in Accordance with the ESMO Guidance for Reporting Real-World Evidence. Pharmaceuticals (Basel) 2024; 17:1713. [PMID: 39770555 PMCID: PMC11677823 DOI: 10.3390/ph17121713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Recent advancements in cancer treatment have shown the potential of immune checkpoint blockade (ICB) plus Viscum album L. therapy in improving survival rates for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to investigate factors associated with improved survival in NSCLC patients treated with a combination of ICB and abnobaViscum®. Methods: Patients with advanced or metastatic NSCLC from the accredited Network Oncology registry were included in this real-world data study adhering to ESMO-GROW criteria with ethics approval. Survival outcomes were compared between patients receiving ICB therapy alone versus those receiving combinational ICB plus abnobaViscum® therapy using Kaplan-Meier and multivariable Cox proportional hazard analysis. Results: Among 300 patients (median age 68 years; male/female ratio 1.19), 222 received ICB alone (CTRL group) and 78 received combinational therapy (COMB group). Overall survival was significantly prolonged in the COMB group by 7 months compared to CTRL (13.8 months vs. 6.8 months, p = 0.005) with a survival rate of 16.5% in the COMB group vs. 8.0% in the CTRL group. In programmed death-ligand 1 positive (≥1%) patients treated with first-line ICB, the addition of abnobaViscum® reduced the adjusted hazard of death by 75% (aHR: 0.25; 95%CI: 0.11-0.60, p = 0.02). Conclusions: The addition of abnobaViscum® to ICB is significantly associated with improved survival in patients with advanced or metastatic NSCLC patients, irrespective of age, stage, Eastern cooperative oncology group status, surgery, or radiation. Potential mechanisms include immune modulation, reduced primary ICB resistance, and tumor microenvironment modifications. The findings warrant further validation in randomized controlled trials or registry-based randomized controlled trials. Trial registration: The study was registered (DRKS00013335).
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Affiliation(s)
- Friedemann Schad
- Network Oncology Registry, Research Institute Havelhöhe, Kladower Damm 221, 14089 Berlin, Germany;
- Interdisciplinary Oncological Centre, Hospital Havelhöhe, Kladower Damm 221, 14089 Berlin, Germany;
| | - Anja Thronicke
- Network Oncology Registry, Research Institute Havelhöhe, Kladower Damm 221, 14089 Berlin, Germany;
| | - Ralf-Dieter Hofheinz
- Mannheim Cancer Center, Mannheim University Hospital, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany;
| | - Reinhild Klein
- Department of Internal Medicine II, University Hospital Tübingen, Otfried-Müller Straße 10, 72076 Tübingen, Germany;
| | - Patricia Grabowski
- Interdisciplinary Oncological Centre, Hospital Havelhöhe, Kladower Damm 221, 14089 Berlin, Germany;
- Charité Fatigue Centrum, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Shiao Li Oei
- Network Oncology Registry, Research Institute Havelhöhe, Kladower Damm 221, 14089 Berlin, Germany;
| | - Hannah Wüstefeld
- Lung Cancer Center, Hospital Havelhöhe, Kladower Damm 221, 14089 Berlin, Germany; (H.W.); (C.G.)
| | - Christian Grah
- Lung Cancer Center, Hospital Havelhöhe, Kladower Damm 221, 14089 Berlin, Germany; (H.W.); (C.G.)
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Wode K, Kienle GS, Björ O, Fransson P, Sharp L, Elander NO, Bernhardson BM, Johansson B, Edwinsdotter Ardnor C, Scheibling U, Hök Nordberg J, Henriksson R. Mistletoe Extract in Patients With Advanced Pancreatic Cancer: a Double-Blind, Randomized, Placebo-Controlled Tial (MISTRAL). DEUTSCHES ARZTEBLATT INTERNATIONAL 2024; 121:347-354. [PMID: 38915151 PMCID: PMC11539882 DOI: 10.3238/arztebl.m2024.0080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 04/17/2024] [Accepted: 04/17/2024] [Indexed: 06/26/2024]
Abstract
BACKGROUND Patients with advanced pancreatic cancer have limited survival and few treatment options. We studied whether mistletoe extract (ME), in addition to comprehensive oncological treatment and palliative care, prolongs overall survival (OS) and improves health-related quality of life (HRQoL). METHODS The double-blind, placebo-controlled MISTRAL trial was conducted in Swedish oncology centers. The main inclusion criteria were advanced exocrine pancreatic cancer and Eastern Cooperative Oncology Group (ECOG) performance status 0-2. The subjects were randomly assigned to ME (n=143) or placebo (n=147) and were stratified by study site and by eligibility (yes/no) for palliative chemotherapy (June 2016-December 2021). ME or placebo was injected subcutaneously three times a week for nine months. The primary endpoint was overall survival (OS); one of the secondary endpoints was the HRQoL dimension global health/QoL (EORTC-QLQ-C30), as assessed at seven time points over nine months. Trial registration: EudraCT 2014-004552-64, NCT02948309. RESULTS No statistically significant benefit of adding ME to standard treatment was seen with respect to either OS or global health/ QoL. The adjusted hazard ratio for OS was 1.13 [0.89; 1.44], with a median survival time of 7.8 and 8.3 months for ME and placebo, respectively. The figures for the HRQoL dimension "global health/QoL" were similar in the two groups (p=0.86). The number, severity, and outcome of the reported adverse events were similar as well, except for more common local skin reactions at ME injection sites (66% vs. 1%). CONCLUSION ME is unlikely to have a clinically significant effect on OS or the HRQoL dimension global health/QoL when administered in patients with advanced pancreatic cancer in addition to comprehensive cancer care.
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Affiliation(s)
- Kathrin Wode
- Department of Radiation Sciences/Oncology, Umeå University, Umeå, Sweden
- Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden
- Regional Cancer Centre Stockholm Gotland, Stockholm, Sweden
| | - Gunver Sophia Kienle
- Center for Complementary Medicine, Department of Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute for Applied Epistemology and Medical Methodology at Witten/Herdecke University (IFAEMM), Freiburg, Germany
| | - Ove Björ
- Department of Radiation Sciences/Oncology, Umeå University, Umeå, Sweden
| | - Per Fransson
- Department of Nursing, Umeå University, Umeå, Sweden
| | - Lena Sharp
- Regional Cancer Centre Stockholm Gotland, Stockholm, Sweden
- Department of Nursing, Umeå University, Umeå, Sweden
| | - Nils O. Elander
- Department of Biomedical and Clinical Sciences, Linköping University, Sweden
| | - Britt-Marie Bernhardson
- Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Birgit Johansson
- Department of Oncology, Västmanlands Hospital, Västerås, Schweden
| | | | - Ursula Scheibling
- Department of Oncology, Ryhov County Hospital, Jönköping, Schweden
- Palliative Care Unit Västerås, Schweden
| | - Johanna Hök Nordberg
- Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden
- Regional Cancer Centre Stockholm Gotland, Stockholm, Sweden
| | - Roger Henriksson
- Department of Radiation Sciences/Oncology, Umeå University, Umeå, Sweden
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Schad F, Thronicke A, Hofheinz RD, Matthes H, Grah C. Patients with Advanced or Metastasised Non-Small-Cell Lung Cancer with Viscum album L. Therapy in Addition to PD-1/PD-L1 Blockade: A Real-World Data Study. Cancers (Basel) 2024; 16:1609. [PMID: 38672690 PMCID: PMC11049173 DOI: 10.3390/cancers16081609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/09/2024] [Accepted: 04/17/2024] [Indexed: 04/28/2024] Open
Abstract
Immunotherapy with PD-1/PD-L1 inhibitors has significantly improved the survival rates of patients with metastatic non-small-cell lung cancer (NSCLC). Results of a real-world data study investigating add-on VA (Viscum album L.) to chemotherapy have shown an association with the improved overall survival of patients with NSCLC. We sought to investigate whether the addition of VA to PD-1/PD-L1 inhibitors in patients with advanced or metastasised NSCLC would have an additional survival benefit. In the present real-world data study, we enrolled patients from the accredited national registry, Network Oncology, with advanced or metastasised NSCLC. The reporting of data was performed in accordance with the ESMO-GROW criteria for the optimal reporting of oncological real-world evidence (RWE) studies. Overall survival was compared between patients receiving PD-1/PD-L1 inhibitor therapy (control, CTRL group) versus the combination of anti-PD-1/PD-L1 therapy and VA (combination, COMB group). An adjusted multivariate Cox proportional hazard analysis was performed to investigate variables associated with survival. From 31 July 2015 to 9 May 2023, 415 patients with a median age of 68 years and a male/female ratio of 1.2 were treated with anti-PD-1/PD-L1 therapy with or without add-on VA. Survival analyses included 222 (53.5%) patients within the CRTL group and 193 (46.5%) in the COMB group. Patients in the COMB group revealed a median survival of 13.8 months and patients in the CRTL group a median survival of 6.8 months (adjusted hazard ratio, aHR: 0.60, 95% CI: 0.43-0.85, p = 0.004) after adjustment for age, gender, tumour stage, BMI, ECOG status, oncological treatment, and PD-L1 tumour proportion score. A reduction in the adjusted hazard of death by 56% was seen with the addition of VA (aHR 0.44, 95% CI: 0.26-0.74, p = 0.002) in patients with PD-L1-positive tumours (tumour proportion score > 1%) treated with first-line anti-PD-1/PD-L1 therapy. Our findings suggest that add-on VA correlates with improved survival in patients with advanced or metastasised NSCLC who were treated with PD-1/PD-L1 inhibitors irrespective of age, gender, tumour stage, or oncological treatment. The underlying mechanisms may include the synergistic modulation of the immune response. A limitation of this study is the observational non-randomised study design, which only allows limited conclusions to be drawn and prospective randomised trials are warranted.
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Affiliation(s)
- Friedemann Schad
- Research Institute Havelhöhe, Network Oncology Registry, Kladower Damm 221, 14089 Berlin, Germany
- Hospital Gemeinschaftskrankenhaus Havelhöhe, Interdisciplinary Oncological Centre, Kladower Damm 221, 14089 Berlin, Germany
| | - Anja Thronicke
- Research Institute Havelhöhe, Network Oncology Registry, Kladower Damm 221, 14089 Berlin, Germany
| | - Ralf-Dieter Hofheinz
- Mannheim University Hospital, Mannheim Cancer Center, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany
| | - Harald Matthes
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Hindenburgdamm 30, 12203 Berlin, Germany
- Hospital Gemeinschaftskrankenhaus Havelhöhe, Daycare Clinic, Kladower Damm 221, 14089 Berlin, Germany
| | - Christian Grah
- Hospital Gemeinschaftskrankenhaus Havelhöhe, Lung Cancer Center, Kladower Damm 221, 14089 Berlin, Germany;
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Kim S, Chervu N, Premji A, Mallick S, Verma A, Ali K, Benharash P, Donahue T. Association of Inpatient Palliative Care Consultation with Clinical and Financial Outcomes for Pancreatic Cancer. Ann Surg Oncol 2024; 31:1328-1335. [PMID: 37957512 DOI: 10.1245/s10434-023-14528-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 10/14/2023] [Indexed: 11/15/2023]
Abstract
BACKGROUND Palliative care consultation (PCC) has been shown to improve quality of life and reduce costs for various chronic life-threatening diseases. Despite PCC incorporation into modern pancreatic cancer care guidelines, limited data regarding its specific utilization and impact on resource use is available. METHODS The 2016-2020 Nationwide Readmissions Database was used to identify all adult hospitalizations entailing pancreatic cancer. Only patients with at least one readmission within 90 days were included to account for uncaptured out-of-hospital mortality. Multivariable regression models were used to ascertain the relationship between inpatient PCC during initial hospitalization and index as well as cumulative costs, overall length of stay (LOS), readmission rate, and number of repeat hospitalizations. RESULTS Of an estimated 175,805 patients with pancreatic cancer, 11.1% had inpatient PCC during the index admission. PCC utilization significantly increased from 10.5% in 2016 to 11.6% in 2020 (nptrend < 0.001). After adjustment, PCC was associated with reduced index hospitalization costs [β: - $1100; 95% confidence interval (CI) - 1500, - 800; P < 0.001] and cumulative 90-day costs (β: - $11,700; 95% CI - 12,700, - 10,000; P < 0.001). PCC was associated with longer index LOS (β: + 1.12 days, 95% CI 0.92-1.31, P < 0.001) but significantly reduced cumulative LOS (β: - 3.16 days; 95% CI - 3.67, - 2.65; P < 0.001). Finally, PCC was linked with decreased odds of 30-day nonelective readmission (AOR: 0.48, 95% CI 0.45-0.50, P < 0.001). DISCUSSION PCC was associated with decreased costs, readmission rates, and number of hospitalizations among patients with pancreatic cancer. Directed strategies to increase utilization and reduce barriers to consultation should be implemented to encourage practitioners to maximize inpatient PCC referral rates.
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Affiliation(s)
- Shineui Kim
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Nikhil Chervu
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Alykhan Premji
- Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Saad Mallick
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Arjun Verma
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Konmal Ali
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Division of Cardiac Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Timothy Donahue
- Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
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McNearney TA, Digbeu BDE, Baillargeon JG, Ladnier D, Rahib L, Matrisian LM. Pre-Diagnosis Pain in Patients With Pancreatic Cancer Signals the Need for Aggressive Symptom Management. Oncologist 2023; 28:e1185-e1197. [PMID: 37285228 PMCID: PMC10712702 DOI: 10.1093/oncolo/oyad153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 04/28/2023] [Indexed: 06/09/2023] Open
Abstract
OBJECTIVE This study assessed the impact of pancreatic cancer (PC) pain on associated symptoms, activities, and resource utilization from 2016 to 2020 in an online patient registry. PATIENTS AND METHODS Responses from PC patient volunteers (N = 1978) were analyzed from online surveys in a cross-sectional study. Comparisons were performed between PC patient groups reporting, (1) the presence vs. absence of pre-diagnosis PC pain, (2) high (4-8) vs. low (0-3) pain intensity scores on an 11-point numerical rating scale (NRS), and (3) year of PC diagnosis (2010-2020). Descriptive statistics and all bivariate analyses were performed using Chi-square or Fisher's Exact tests. RESULTS PC pain was the most frequently reported pre-diagnosis symptom (62%). Pre-diagnostic PC pain was reported more frequently by women, those with a younger age at diagnosis, and those with PC that spread to the liver and peritoneum. Those with pre-diagnostic PC pain vs. those without reported higher pain intensities (2.64 ± 2.54 vs.1.56 ± 2.01 NRS mean ± SD, respectively, P = .0039); increased frequencies of post-diagnosis symptoms of cramping after meals, feelings of indigestion, and weight loss (P = .02-.0001); and increased resource utilization in PC pain management: (ER visits N = 86 vs. N = 6, P = .018 and analgesic prescriptions, P < .03). The frequency of high pain intensity scores was not decreased over a recent 11-year span. CONCLUSIONS PC pain continues to be a prominent PC symptom. Patients reporting pre-diagnosis PC pain experience increased GI metastasis, symptoms burden, and are often undertreated. Its mitigation may require novel treatments, more resources dedicated to ongoing pain management and surveillance to improve outcomes.
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Affiliation(s)
- Terry A McNearney
- Scientific and Medical Affairs, Pancreatic Cancer Action Network (PanCAN), Manhattan Beach, CA, USA
| | | | | | - Dennis Ladnier
- Scientific and Medical Affairs, Pancreatic Cancer Action Network (PanCAN), Manhattan Beach, CA, USA
| | - Lola Rahib
- Scientific and Medical Affairs, Pancreatic Cancer Action Network (PanCAN), Manhattan Beach, CA, USA
| | - Lynn M Matrisian
- Scientific and Medical Affairs, Pancreatic Cancer Action Network (PanCAN), Manhattan Beach, CA, USA
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Are Aspects of Integrative Concepts Helpful to Improve Pancreatic Cancer Therapy? Cancers (Basel) 2023; 15:cancers15041116. [PMID: 36831465 PMCID: PMC9953994 DOI: 10.3390/cancers15041116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/24/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023] Open
Abstract
Numerous clinical studies have been conducted to improve the outcomes of patients suffering from pancreatic cancer. Different approaches using targeted therapeutic strategies and precision medicine methods have been investigated, and synergies and further therapeutic advances may be achieved through combinations with integrative methods. For pancreatic tumors, a particular challenge is the presence of a microenvironment and a dense stroma, which is both a physical barrier to drug penetration and a complex entity being controlled by the immune system. Therefore, the state of immunological tolerance in the tumor microenvironment must be overcome, which is a considerable challenge. Integrative approaches, such as hyperthermia, percutaneous irreversible electroporation, intra-tumoral injections, phytotherapeutics, or vitamins, in combination with standard-oncological therapies, may potentially contribute to the control of pancreatic cancer. The combined application of standard-oncological and integrative methods is currently being studied in ongoing clinical trials. An actual overview is given here.
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Goel AR, Henderson CR, Reid MC. Do Palliative Care Providers Use Complementary and Integrative Medicine? A Nationwide Survey. J Pain Symptom Manage 2022; 63:599-609. [PMID: 34788656 PMCID: PMC9121789 DOI: 10.1016/j.jpainsymman.2021.11.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 11/03/2021] [Accepted: 11/07/2021] [Indexed: 11/20/2022]
Abstract
CONTEXT Given the high prevalence of burdensome symptoms in palliative care (PC) and increasing use of complementary and integrative medicine (CIM) therapies, research is needed to determine how often and what types of CIM therapies providers recommend to manage symptoms in PC. OBJECTIVES To document recommendation rates of CIM for target symptoms and assess if, CIM use varies by provider characteristics. METHODS Nationwide survey's of physicians (MD and DO), physician assistants, and nurse practitioners in PC. RESULTS Participants (N = 404) were mostly female (71.3%), physicians (74.9%), and cared for adults (90.4%). Providers recommended CIM an average of 6.82 times per-month (95% CI: 6.04-7.60) and used an average of 5.13 (95% CI: 4.90-5.36) out of 10 CIM modalities. Respondents recommended mind-body medicines (e.g., meditation, biofeedback) most, followed by massage, and acupuncture and/or acupressure. The most targeted symptoms included pain; followed by anxiety, mood disturbance, and distress. Recommendation frequencies for specific modality-for-symptom combinations ranged from little use (e.g., aromatherapy for constipation) to occasional use (e.g., mind-body interventions for psychiatric symptoms). Finally, recommendation rates increased as a function of pediatric practice, noninpatient practice setting, provider age, and proportion of effort spent delivering palliative care. CONCLUSION To the best of our knowledge, this is the first national survey to characterize PC providers' CIM recommendation behaviors and assess specific therapies and common target symptoms. Providers recommended a broad range of CIM but do so less frequently than patients report using CIM. These findings should be of interest to any provider caring for patients with serious illness.
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Affiliation(s)
- Anurag Ratan Goel
- Departments of Medicine and Pediatrics (A.R.G.), Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Charles R Henderson
- Department of Human Development (C.R.H.), Cornell University, Ithaca, New York, USA
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Thronicke A, Schad F, Debus M, Grabowski J, Soldner G. Viscum album L. Therapy in Oncology: An Update on Current Evidence. Complement Med Res 2022; 29:362-368. [PMID: 35325897 DOI: 10.1159/000524184] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 03/18/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND A majority of oncological patients apply add-on white-berry European mistletoe (Viscum album L., VA) extracts to reduce disease- and treatment-related symptoms and to improve health-related quality of life (HRQL). VA extracts exert various antitumor, pro-apoptotic, anti-proliferative, and immunomodulatory effects. Two current meta-analyses attribute life-prolonging and HRQL-improving properties to additive VA therapy. The aim of the present update was to review the current knowledge on VA extracts in clinical oncology. Hereby, we concentrated on studies with the highest clinical relevance in the field of lung, gastric, colorectal and pancreatic, gynaecological, as well as breast cancer applying the anthroposophical mistletoe preparations. SUMMARY The present update provides a brief overview regarding the use of VA preparations in clinical oncology reviewing current guidelines, systematic reviews, randomized controlled and real-world data studies. We have searched the pubmed.gov database of the National Library of Medicine with the search terms "mistletoe" and "cancer." We found good evidence of add-on VA therapy to improve the HRQL of patients with breast cancer (American Society of Clinical Oncology - endorsed Society for Integrative Oncology guideline) and of HRQL-improving and survival-prolonging properties of VA therapy in pancreatic cancer. In the field of gastrointestinal, gynaecological, and lung cancer, new or updating integrative and/or oncological guidelines should consider clear recommendations on integrative therapies including VA therapy. Nevertheless, further clinical and real-world data trials need to be performed in this field. KEY MESSAGES Evidence for add-on VA treatment for the improved management of cancer and cancer-related side effects is accumulating. Patients with breast cancer: good evidence for add-on VA therapy to improve the HRQL of oncological patients. Patients with pancreatic cancer: good evidence for add-on VA to improve HRQL and prolong survival. Patients with gastrointestinal, gynaecological, and lung cancer: update of guidelines is recommended with regards to integrative oncological therapies including add-on VA.
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Affiliation(s)
- Anja Thronicke
- Research Institute Havelhöhe at the Hospital Gemeinschaftskrankenhaus Havelhöhe, Berlin, Germany
| | - Friedemann Schad
- Research Institute Havelhöhe at the Hospital Gemeinschaftskrankenhaus Havelhöhe, Berlin, Germany
- Interdisciplinary Oncology and Palliative Care, Hospital Gemeinschaftskrankenhaus Havelhöhe, Berlin, Germany
| | | | | | - Georg Soldner
- School of Spiritual Science, Medical Section at the Goetheanum, Dornach, Switzerland
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Loef M, Walach H. Survival of Cancer Patients Treated with Non-Fermented Mistletoe Extract: A Systematic Review and Meta-Analysis. Integr Cancer Ther 2022; 21:15347354221133561. [PMID: 36324298 PMCID: PMC9634211 DOI: 10.1177/15347354221133561] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 09/19/2022] [Accepted: 09/30/2022] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Mistletoe extracts (ME) are used in integrative cancer care to improve quality of life and to prolong survival. ME are available from different producers and differ in pharmaceutical processing, such as fermentation. In contrast to fermented ME, the impact of unfermented extracts on the survival of cancer patients has not yet been assessed in a meta-analysis. METHODS We searched the databases Embase, CENTRAL, Europe PMC, Clinicaltrials.gov, Opengrey and Google Scholar, and selected controlled studies on cancer patients treated with non-fermented ME. We included randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs). The risk of bias was assessed with Cochrane's ROB2 and ROBINS-I; a meta-analysis was conducted. RESULTS Eleven RCTs and eight NRSIs met the inclusion criteria. The studies were heterogeneous and their ROB2 and ROBINS-I displayed a moderate and high risk of bias, respectively. For RCTs, the pooled effect estimate of non-fermented ME on survival was HR = 0.81 (95% CI 0.69-0.95, P = .01). Subgroup analyses as well as the NRSIs estimation support the robustness of the finding. When active comparators are added to the analysis, the effect estimates become non-significant. CONCLUSION The results may indicate a positive impact of non-fermented ME on the overall survival of cancer patients. High quality RCTs are necessary to substantiate our results. PROSPERO REGISTRATION CRD42021233177.
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Affiliation(s)
| | - Harald Walach
- CHS-Institute, Berlin, Germany
- Next Society Institute, Kazimieras
Simonavicius University, Vilnius, Lithuania
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11
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Huffman DL, Vusqa UT, Shankar K, Alnimer L, Samhouri Y, Srinivasamaharaj S, Malayala SV, Monga D. An Internal Review of Rates of Palliative Medicine Referral for Patients With Advanced Pancreatic Cancer. Cureus 2021; 13:e19670. [PMID: 34976460 PMCID: PMC8682948 DOI: 10.7759/cureus.19670] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/16/2021] [Indexed: 12/12/2022] Open
Abstract
Background The American Society of Clinical Oncology recommends that patients with advanced cancer receive palliative care services in concurrence with active treatment. While the benefits of palliative care are clear, integration of palliative care can be challenging. We aim to review rates of palliative care consultation in patients with advanced pancreatic cancer at our institution, intending to improve these rates. Methods We retrospectively reviewed the electronic records of all patients with pancreatic cancer treated at Allegheny General Hospital diagnosed between 2009-2020. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Results Of the 171 patients reviewed, 121 completed all treatment and evaluation within our health network (Pittsburgh, United States). The median age was 63 years (IQR 40-91 years); 55 patients (45%) were male; the majority were white (107 patients, 88%). At the time of diagnosis, 28% of our patients had stage IV disease (34 patients), and 19.8% of patients who developed stage IV disease had palliative care referrals. Conclusions Palliative care is an integral part of usual care for advanced pancreatic cancer. Our analysis showed that palliative care is underutilized in our hospital. We aim to improve palliative care integration in our patients’ care by adding a hard stop to electronic medical records to remind physicians to offer palliative care to our patients with pancreatic cancer and to arrange lecture series to emphasize the importance of palliative care in this setting.
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Affiliation(s)
| | - Urwat T Vusqa
- Internal Medicine, Allegheny Health Network, Pittsburgh, USA
| | - Karthik Shankar
- Internal Medicine, Allegheny Health Network, Pittsburgh, USA
| | - Lynna Alnimer
- Internal Medicine, Ascension Providence Hospital, Southfield, USA
| | - Yazan Samhouri
- Department of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, USA
| | | | | | - Dulabh Monga
- Department of Hematology and Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, USA
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12
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Thronicke A, Matthes B, von Trott P, Schad F, Grah C. Overall Survival of Nonmetastasized NSCLC Patients Treated With Add-On Viscum album L: A Multicenter Real-World Study. Integr Cancer Ther 2020; 19:1534735420940384. [PMID: 32856476 PMCID: PMC7457695 DOI: 10.1177/1534735420940384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background: Recent data suggest a beneficial effect of add-on treatment with Viscum album L (VA) on the survival in cancer patients. The objective of this study was to compare the impact of standard oncological therapy plus add-on VA treatment (S+VA) versus standard oncological therapy alone (S) on the overall survival (OS) of patients with nonmetastasized non–small cell lung carcinoma (NSCLC). Methods: The multicenter real-world data study was conducted using data from the Network Oncology Clinical Registry. The primary end point was OS. OS and impact on hazard in both treatment groups were compared. Results: A total of 275 patients with stages I to IIIA NSCLC were enrolled (mean age = 67.6 years, 57.2% male patients). No significant difference of OS was observed between both groups. Even though not significant, for a subgroup of unresected patients with stage I NSCLC, adenocarcinoma or squamous cell carcinoma, a medium effect size OS improvement was observed for S+VA compared to S. Conclusions: Our findings support the importance of surgery as the most effective intervention in nonmetastasized NSCLC patients. Add-on VA therapy shows here no additional effect in resected patients. However, a small subgroup analysis suggests a possible role of add-on VA for nonresected subgroups. Our results complement existing knowledge on the clinical impact of add-on VA therapy in NSCLC patients and may serve as hypothesis-generating data for further examinations in this cohort. Further research could be directed towards the role of combined therapy for nonresected early-stage NSCLC.
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Affiliation(s)
| | - Burkhard Matthes
- Research Institute Havelhöhe, Berlin, Germany.,Interdisciplinary Oncology and Palliative Care, Hospital Havelhöhe, Berlin, Germany
| | - Philipp von Trott
- Interdisciplinary Oncology and Palliative Care, Hospital Havelhöhe, Berlin, Germany
| | - Friedemann Schad
- Research Institute Havelhöhe, Berlin, Germany.,Interdisciplinary Oncology and Palliative Care, Hospital Havelhöhe, Berlin, Germany
| | - Christian Grah
- Research Institute Havelhöhe, Berlin, Germany.,Lung Cancer Center and Department of Pneumology, Hospital Havelhöhe, Berlin, Germany
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13
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Cost-Effectiveness of Real-World Administration of Concomitant Viscum album L. Therapy for the Treatment of Stage IV Pancreatic Cancer. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:3543568. [PMID: 32256640 PMCID: PMC7093905 DOI: 10.1155/2020/3543568] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 02/14/2020] [Indexed: 12/30/2022]
Abstract
Background For patients receiving add-on Viscum album L. (VA) treatments for late-stage pancreatic cancer, an improved overall survival (OS) was observed. Only limited information regarding cost-effectiveness (CE) for comparisons between standard of care and standard of care plus add-on VA in stage IV pancreatic cancer treatment is available. The present study assessed the costs and cost-effectiveness of standard of care plus VA (V) compared to standard of care alone (C) for a hospital in Germany. Methods An observational study was conducted using data from the Network Oncology clinical registry. Patients included had stage IV pancreatic cancer at diagnosis and received C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. Results 88 patients (C or n = 34; V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. n = 34; C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. C or Conclusion Based on this CEA analysis, from the hospital's point of view, the costs per mean month of OS and per mean hospital stay were lower for patients under combinational standard of care plus VA compared to patients receiving standard of care alone for the treatment of stage IV pancreatic cancer. Further prospective cost-effectiveness studies are mandatory to reevaluate our findings.
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14
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Testoni SGG, Healey AJ, Dietrich CF, Arcidiacono PG. Systematic review of endoscopy ultrasound-guided thermal ablation treatment for pancreatic cancer. Endosc Ultrasound 2020; 9:83-100. [PMID: 32295966 PMCID: PMC7279078 DOI: 10.4103/eus.eus_74_19] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 11/18/2019] [Indexed: 12/15/2022] Open
Abstract
The development of curvilinear-array EUS and EUS-guided fine-needle aspiration (EUS-FNA) has led these approaches to become interventional procedures rather than purely diagnostic, as a minimally invasive antitumor therapeutic alternative to radiological and surgical treatments. The possibility to accurately position needle devices and to reach a deep target like the pancreas gland under real-time imaging guidance has expanded the use of EUS to ablate tumors. Currently, a variety of probes specifically designed for EUS ablation are available, including radiofrequency, hybrid cryothermal ablation (combining radiofrequency with cryotechnology), photodynamic therapy, and laser ablation. To date, several studies have demonstrated the safety and feasibility of these ablation techniques in the pancreatic setting, but only a few small series on pancreatic thermal ablation under EUS guidance are available. EUS-guided thermal ablation is primarily used for pancreatic cancer. It is well suited to this disease because of its superior anatomical access compared with other imaging modalities and the dismal prognosis despite improvements in chemoradiotherapy and surgery in the management of pancreatic cancer. Other targets are pancreatic neuroendocrine tumors and pancreatic cystic neoplasms, which are curable by surgical resection, but some patients are poor surgical candidates or prefer conservative management. This is a literature review of previously published clinical studies on EUS-guided thermal ablative therapies. Data on the long-term efficacy of EUS-guided antitumor thermal ablation therapy and large prospective randomized studies are still needed to confirm the real clinical benefits of these techniques for the management of pancreatic neoplasms.
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Affiliation(s)
- Sabrina Gloria Giulia Testoni
- Division of Pancreato-Biliary Endoscopy and Endosonography, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Andrew James Healey
- Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, Scotland
| | - Christoph F. Dietrich
- Department of Internal Medicine, Hirslanden Hospitals Berne Beau Site, Salem and Permanence, Berne, Switzerland
| | - Paolo Giorgio Arcidiacono
- Division of Pancreato-Biliary Endoscopy and Endosonography, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
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15
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Mistletoe and Immunomodulation: Insights and Implications for Anticancer Therapies. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:5893017. [PMID: 31118962 PMCID: PMC6500636 DOI: 10.1155/2019/5893017] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 03/20/2019] [Accepted: 04/14/2019] [Indexed: 02/06/2023]
Abstract
In early tumor development, cancer cells develop a plethora of strategies to escape surveillance from the adaptive and innate immune system. Cancer immunotherapies, in particular immune checkpoint inhibitors, are becoming a highly promising cancer therapeutic approach that has remarkable increased progress in combating various cancer types. Unfortunately, their mechanisms of action induce some complications, such as inflammatory reactions and immune-related adverse events. In the management of side effects during anticancer therapy, complementary and integrative therapy approaches are becoming of growing interest. Particularly, mistletoe, Viscum album L. (VA), has a long traditional history of about 100 years as an add-on therapy of cancer treatment in German-speaking countries. Besides antitumoral and quality of life-promoting activities, VA applications reduce side effects of modern conventional anticancer therapies and exert immunomodulatory characteristics. As these properties may provide a good basis for a combination with modern oncological therapies, the biological activities of VA applications and mechanisms involved have to be understood. In this review, the impact of VA compounds on different cellular pathways and immunological reactions in the fight against cancerous cells is discussed.
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Werthmann PG, Kempenich R, Lang-Avérous G, Kienle GS. Long-term survival of a patient with advanced pancreatic cancer under adjunct treatment with Viscum album extracts: A case report. World J Gastroenterol 2019; 25:1524-1530. [PMID: 30948915 PMCID: PMC6441914 DOI: 10.3748/wjg.v25.i12.1524] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 02/22/2019] [Accepted: 03/02/2019] [Indexed: 02/06/2023] Open
Abstract
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.
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Affiliation(s)
- Paul G Werthmann
- Department of Methodology, Institute for Applied Epistemology and Medical Methodology (IFAEMM), Freiburg 79111, Germany
- Center for Complementary Medicine, Institute for Environmental Health Sciences and Hospital Infection Control, Medical Center - University of Freiburg, Freiburg 79106, Germany
| | - Robert Kempenich
- Private Praxis, General Practitioner with Specialization in Oncology, Strasbourg F-67000, France
| | - Gerlinde Lang-Avérous
- Department of Pathology, Hôpital de Hautepierre, University Hospital of Strasbourg, Strasbourg F-67000, France
| | - Gunver S Kienle
- Department of Methodology, Institute for Applied Epistemology and Medical Methodology (IFAEMM), Freiburg 79111, Germany
- Center for Complementary Medicine, Institute for Environmental Health Sciences and Hospital Infection Control, Medical Center - University of Freiburg, Freiburg 79106, Germany
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17
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Schad F, Thronicke A, Steele ML, Merkle A, Matthes B, Grah C, Matthes H. Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis. PLoS One 2018; 13:e0203058. [PMID: 30148853 PMCID: PMC6110500 DOI: 10.1371/journal.pone.0203058] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 08/14/2018] [Indexed: 12/15/2022] Open
Abstract
Background Stage IV non-small cell lung cancer (NSCLC) is associated with a five-year survival rate of around 1%. Treatment with Viscum album L. (VA) extracts has been shown to reduce chemotherapy (CTx)-related adverse events, decrease CTx dose reductions and improve quality of life in a number of cancers. Recent data suggest a beneficial effect of add-on treatment with Viscum album L. (VA, European mistletoe) on survival in cancer patients. The objective of this study was to evaluate the effect of VA in addition to chemotherapy on survival in stage IV NSCLC patients. Methods The observational study was conducted using data from the Network Oncology clinical registry which is an accredited conjoint clinical registry of German oncological hospitals, practitioners and out-patient centers.Patients were included if they had stage IV NSCLC at diagnosis, lived at least for four weeks post-diagnosis and received chemotherapeutic treatment. Patients with EGFR mutations as well as patients receiving tyrosine kinase inhibitors or immune checkpoint inhibitors were not included. Overall survival and impact on hazard in patients with chemotherapy (CTx) to patients receiving CTx plus VA were compared. To identify factors associated with survival and to address potential sources of bias a multivariate analyses using Cox proportional hazard model was performed. Results The median age of the population was 64.1 years with 55.7% male patients. The highest proportion of patients had adenocarcinoma (72.2%) and most of the patients were current or past smokers (70.9%). Of 158 stage IV NSCLC patients, 108 received CTx only and 50 additional VA. Median survival was 17.0 months in the CTx plus VA group (95%CI: 11.0–40.0) and was 8.0 months (95%CI: 7.0–11.0) in the CTx only group (χ2 = 7.2, p = .007). Overall survival was significantly prolonged in the VA group (HR 0.44, 95%CI: 0.26–0.74, p = .002). One-year and three-year overall survival rates were greater with CTx plus VA compared to CTX alone (1y: 60.2% vs. 35.5%; 3y: 25.7% vs. 14.2%). Conclusion Our findings suggest that concomitant VA is positively associated with survival in stage IV NSCLC patients treated with standard CTx. These findings complement pre-existing knowldedge of add-on VA’s clinical impact, however, results should be interpreted with caution in light of the study’s observational character.
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Affiliation(s)
- Friedemann Schad
- Research Institute Havelhöhe, Hospital Havelhöhe, Berlin, Germany
- Interdisciplinary Oncology and Palliative Care, Hospital Havelhöhe, Berlin, Germany
- * E-mail:
| | - Anja Thronicke
- Research Institute Havelhöhe, Hospital Havelhöhe, Berlin, Germany
| | - Megan L. Steele
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Antje Merkle
- Research Institute Havelhöhe, Hospital Havelhöhe, Berlin, Germany
- Interdisciplinary Oncology and Palliative Care, Hospital Havelhöhe, Berlin, Germany
| | - Burkhard Matthes
- Research Institute Havelhöhe, Hospital Havelhöhe, Berlin, Germany
- Interdisciplinary Oncology and Palliative Care, Hospital Havelhöhe, Berlin, Germany
| | - Christian Grah
- Research Institute Havelhöhe, Hospital Havelhöhe, Berlin, Germany
- Lung Cancer Center and Department of Pneumology, Hospital Havelhöhe, Berlin, Germany
| | - Harald Matthes
- Research Institute Havelhöhe, Hospital Havelhöhe, Berlin, Germany
- Medical Clinic for Gastroenterology, Infectiology and Rheumatology CBF and Institute of Social Medicine, Epidemiology and Health Economics CCM, Charité University Medicine Berlin, Berlin, Germany
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Werthmann PG, Huber R, Kienle GS. Durable clinical remission of a skull metastasis under intralesional Viscum album extract therapy: Case report. Head Neck 2018; 40:E77-E81. [PMID: 29885069 PMCID: PMC6055724 DOI: 10.1002/hed.25320] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 04/11/2018] [Indexed: 01/30/2023] Open
Abstract
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.
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Affiliation(s)
- Paul Georg Werthmann
- Institute for Applied Epistemology and Medical Methodology (IFAEMM) at the University of Witten/Herdecke, Freiburg, Germany
| | - Roman Huber
- Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Gunver Sophia Kienle
- Institute for Applied Epistemology and Medical Methodology (IFAEMM) at the University of Witten/Herdecke, Freiburg, Germany.,Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Thronicke A, Oei SL, Merkle A, Herbstreit C, Lemmens HP, Grah C, Kröz M, Matthes H, Schad F. Integrative cancer care in a certified Cancer Centre of a German Anthroposophic hospital. Complement Ther Med 2018; 40:151-157. [PMID: 30219441 DOI: 10.1016/j.ctim.2018.03.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 03/19/2018] [Accepted: 03/31/2018] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE The concept of integrative oncology (IO) comprising guideline-oriented standard and add-on complementary medicine has gained growing importance. The Anthroposophic-integrative Cancer Centre (CC) at the hospital Gemeinschaftskrankenhaus (GKH) in Berlin has been implementing IO concepts during recent years. Furthermore, it is a certified CC and has been annually audited by national cancer authorities since 2012. The objective of the present study was to evaluate IO concepts of the certified CC GKH. METHODS Clinical, demographic, integrative treatment and follow-up data were analyzed between 2011 and 2016. In addition, CC GKH quality measures were compared with those of nationwide benchmarking CCs. RESULTS Between 2011 and 2016, 2.382 primary cancer patients, median age 66 years, were treated at the CC GKH. 70.1% of the patients showed either Union for International Cancer Control (UICC) stage 0, I, II or III and 25.6% were in UICC stage IV. IO therapies included surgery (64.4% of patients), radiation (41.2%), and application of cytostatic drugs (53.9%), add-on mistletoe therapy (30.5%), and non-pharmacological interventions (87.3%). Regarding psycho-oncological support and quota of patient's enrollment in studies the CC GKH performs above nationwide benchmarks. Research outcomes including safety issues, clinical impact as well as patient's health-related quality of life are continuously evaluated and integrated into hospital's decision-management. CONCLUSION This analysis reveals that IO concepts are applied to a high proportion of male and female primary cancer patients of all age groups, indicating a successful implementation at the certified CC GKH. Ongoing clinical evaluations have been initiated and cost-effectiveness comparisons are under analyses.
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Affiliation(s)
| | - Shiao Li Oei
- Research Institute Havelhöhe, 14089 Berlin, Germany.
| | - Antje Merkle
- Research Institute Havelhöhe, 14089 Berlin, Germany; Oncological Centre, Hospital Gemeinschaftskrankenhaus Havelhöhe, 14089 Berlin, Germany.
| | - Cornelia Herbstreit
- Oncological Centre, Hospital Gemeinschaftskrankenhaus Havelhöhe, 14089 Berlin, Germany; Breast Cancer Centre, Hospital Gemeinschaftskrankenhaus Havelhöhe, 14089 Berlin, Germany.
| | - Hans-Peter Lemmens
- Oncological Centre, Hospital Gemeinschaftskrankenhaus Havelhöhe, 14089 Berlin, Germany; Colon and Rectum Cancer Centre, Hospital Gemeinschaftskrankenhaus Havelhöhe, 14089 Berlin, Germany.
| | - Christian Grah
- Oncological Centre, Hospital Gemeinschaftskrankenhaus Havelhöhe, 14089 Berlin, Germany; Lung Cancer Centre, Hospital Gemeinschaftskrankenhaus Havelhöhe, 14089 Berlin, Germany.
| | - Matthias Kröz
- Research Institute Havelhöhe, 14089 Berlin, Germany; Institute for Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, 10098 Berlin, Germany; Institute for Integrative Medicine, University of Witten/Herdecke, 58313 Witten, Herdecke, Germany.
| | - Harald Matthes
- Oncological Centre, Hospital Gemeinschaftskrankenhaus Havelhöhe, 14089 Berlin, Germany; Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
| | - Friedemann Schad
- Research Institute Havelhöhe, 14089 Berlin, Germany; Oncological Centre, Hospital Gemeinschaftskrankenhaus Havelhöhe, 14089 Berlin, Germany.
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Schad F, Thronicke A, Merkle A, Steele ML, Kröz M, Herbstreit C, Matthes H. Implementation of an Integrative Oncological Concept in the Daily Care of a German Certified Breast Cancer Center. Complement Med Res 2018; 25:85-91. [PMID: 29510405 DOI: 10.1159/000478655] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND In recent decades the concept of integrative medicine has attracted growing interest in patients and professionals. At the Gemeinschaftskrankenhaus Havelhöhe (GKH), a hospital specialized in anthroposophical medicine, a breast cancer center (BCC) has been successfully certified for more than 5 years. The objective of the present study was to analyze how integrative strategies were implemented in the daily care of primary breast cancer patients. METHODS Clinical, demographic, and follow-up data as well as information on non-pharmacological interventions were analyzed. In addition, BCC quality measures were compared with data of the National Breast Cancer Benchmarking Report 2016. RESULTS Between 2011 and 2016, 741 primary breast cancer patients (median age 57.4 years) were treated at the GKH BCC. 91.5% of the patients showed Union for International Cancer Control (UICC) stage 0, I, II, or III and 8.2% were in UICC stage IV. 97% of the patients underwent surgery, 53% radiation, 38% had hormone therapy, and 25% received cytostatic drugs. 96% of the patients received non-pharmacological interventions and 32% received Viscum album L. THERAPY Follow-up was performed in up to 93% of the patients 2 years after first diagnosis. Compared to nationwide benchmarking BCCs, the GKH BCC met the requirements in central items. CONCLUSIONS The results of the present study show that integrative therapies offered by the concept of anthroposophical medicine can be implemented in the daily care and treatment of a certified BCC. However, as national guidelines on integrative concepts in oncology are missing, further studies are needed for a systematic evaluation of integrative treatment and care concepts in this field.
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Vogl TJ, Panahi B, Albrecht MH, Naguib NNN, Nour-Eldin NEA, Gruber-Rouh T, Thompson ZM, Basten LM. Microwave ablation of pancreatic tumors. MINIM INVASIV THER 2017; 27:33-40. [PMID: 29278340 DOI: 10.1080/13645706.2017.1420664] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To evaluate the clinical performance of percutaneous microwave ablation (MWA) for treatment of locally-advanced-pancreatic-cancer (LAPC). MATERIAL AND METHODS Twenty-two MWA sessions (August 2015-March 2017) in 20 patients with primary pancreatic cancer (13 men, 7 women, mean-age: 59.9 ± 8.6 years, range: 46-73 years), who had given informed consent, were retrospectively evaluated. All procedures were performed percutaneously under CT-guidance using the same high-frequency (2.45-GHz) MWA device. Tumor location and diameter, ablation diameter and volume, roundness, duration, technical success and efficacy, output energy, complications, and local tumor progression defined as a tumor focus connected to the edge of a previously technically efficient ablation zone were collected. RESULTS Seventeen pancreatic malignant tumors (77.3%) were located in the pancreatic head and five (22.7%) in the pancreatic tail. Initial Mean Tumor Diameter was 30 ± 6 mm. Technical success and efficacy were idem (100%). No major complications occurred. Two patients (9.1%) showed minor complications of severe local pain related to MWA. Post-ablation diameter was on average 34.4 ± 5.8 mm. Mean ablation volume was 7.8 ± 3.8 cm³. The mean transverse roundness index was 0.74 ± 0.14. Mean ablation time was 2.6 ± 0.96 min. The mean applied energy per treatment was 9627 ± 3953 J. Local tumor progression was documented in one case (10%) of the 10/22 available three-month follow-up imaging studies. CONCLUSION High-frequency (2.45 GHz) microwave ablation (MWA) for treatment of unresectable and non-metastatic locally-advanced-pancreatic-cancer (LAPC) shows promising results regarding feasibility and safety of percutaneous approach after short-term follow-up and should be further evaluated.
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Affiliation(s)
- Thomas J Vogl
- a Department of Diagnostic and Interventional Radiology , Frankfurt-University Hospital , Frankfurt am Main , Germany
| | - Bita Panahi
- a Department of Diagnostic and Interventional Radiology , Frankfurt-University Hospital , Frankfurt am Main , Germany
| | - Moritz H Albrecht
- a Department of Diagnostic and Interventional Radiology , Frankfurt-University Hospital , Frankfurt am Main , Germany
| | - Nagy Naguib Naeem Naguib
- a Department of Diagnostic and Interventional Radiology , Frankfurt-University Hospital , Frankfurt am Main , Germany
| | - Nour-Eldin A Nour-Eldin
- a Department of Diagnostic and Interventional Radiology , Frankfurt-University Hospital , Frankfurt am Main , Germany
| | - Tatjana Gruber-Rouh
- a Department of Diagnostic and Interventional Radiology , Frankfurt-University Hospital , Frankfurt am Main , Germany
| | - Zachary M Thompson
- b Department of Radiology and Radiological Science , Medical University of South Carolina , Charleston , SC , USA
| | - Lajos M Basten
- a Department of Diagnostic and Interventional Radiology , Frankfurt-University Hospital , Frankfurt am Main , Germany
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Thronicke A, Steele ML, Grah C, Matthes B, Schad F. Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L. therapy in patients with advanced or metastatic cancer. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 17:534. [PMID: 29237435 PMCID: PMC5729272 DOI: 10.1186/s12906-017-2045-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 12/05/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Despite improvement of tumour response rates in patients with progressive and metastatic cancer, immune checkpoint inhibitors (ICM) induce toxicities in cancer patients. Viscum album L. (VA, mistletoe) extracts are applied as add-on cancer therapy especially in German speaking countries and within integrative and anthroposophical concepts with the goal to improve quality of life. The primary objective of this pilot observational cohort study was to determine the rate of adverse events (AE) related to ICM therapy with and without VA in patients with advanced or metastatic cancer in a certified Cancer Center. METHODS ICM or combined ICM/VA therapies were applied in patients with progressive or metastatic cancer. AE rates of both therapy groups were compared. RESULTS A total of sixteen cancer patients were treated with ICM: nivolumab (75%), ipilimumab (19%) or pembrolizumab (6%). The median age of the study population was 64 years (IQR 57.8; 69.3); 44% were male. Of the sixteen patients receiving ICM, nine patients received additional VA (56%; ICM/VA group) and seven did not (44%; ICM group). No statistically significant differences were seen between groups with respect to AE-rates (67% ICM/VA versus 71% ICM). Adjusted multivariate regression analysis revealed that concomitant application of VA did not alter the AE rate in ICM treated patients. 85% of AEs were expected ICM reactions. No AEs of grade 3 or greater were documented for the total study cohort. CONCLUSIONS This is the first study evaluating the clinical safety profile of ICM in combination with VA in patients with advanced or metastatic cancer. The overall AE rate of the study cohort is comparable to AE rates of ICM treatment in the literature. Our data indicate a first impression that concomitant VA application may not alter ICM-induced AE rates. However, the nature of this study does not allow excluding possible immunological interactions between ICM and VA. Further prospective trials in larger study cohorts should focus on the assessment of safety aspects, clinical efficacy and health related quality of life in patients with combined ICM/VA therapy. TRIAL REGISTRATION DRKS00013335 , retrospectively registered (November 27th, 2017) at the German Clinical Trials Register ( www.drks.de ).
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Schad F, Thronicke A, Merkle A, Matthes H, Steele ML. Immune-related and adverse drug reactions to low versus high initial doses of Viscum album L. in cancer patients. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2017; 36:54-58. [PMID: 29157828 DOI: 10.1016/j.phymed.2017.09.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 07/18/2017] [Accepted: 09/19/2017] [Indexed: 06/07/2023]
Abstract
BACKGROUND Immune-related adverse drug reactions (ADRs) to immunotherapy agents have been associated with beneficial clinical outcomes in oncology. Viscum album L. (VA, European mistletoe) is frequently used as an immunomodulatory agent alongside conventional cancer treatment in Europe. VA has been associated with improved quality of life and a reduction in chemotherapy-related ADRs. Beneficial effects of VA are believed to be related to its immunomodulatory properties. Current guidelines recommend commencing with a low dose and increasing slowly overtime, however, off-label prescribing of high initial doses is common. PURPOSE We investigated ADR profiles related to subcutaneous VA therapy commencing with low, recommended doses versus higher than recommended doses. STUDY DESIGN Retrospective cohort study. METHODS Medical records of 1361 cancer patients treated between 2003 and 2013 were assessed. Patients were divided into two groups based on whether the dose of their first VA injection adhered to current guidelines. Patient characteristics and suspected VA-related ADRs were compared between dose groups. RESULTS Of 1361 cancer patients, 516 (38%) started with a recommended, low dose of VA(≤0.02 mg) and 845 (62%) started with a higher dose(>0.02 mg). Groups did not differ by age or gender, but significant differences were observed for type (p < 0.001) and stage of cancer (p = 0.05). Starting with a high dose of VA was significantly associated with a higher incidence of VA-related ADRs compared to starting with a low dose (20.7% versus 0.8%, p < 0.001). Adjusting for age, gender, tumour type and stage of disease, produced an odds ratio of 37.5 (95% CI = 15.7-122.8, p < .001). Almost all ADRs, irrespective of the initial VA dose, were of mild or moderate intensity. Most ADRs were immune-related, general disorders and administration site conditions, many of which are desired reactions, such as pyrexia and local reactions. Overall, no serious ADRs occurred. CONCLUSIONS Starting VA therapy with a higher than recommended dose was associated with a high frequency of ADRs, however, nearly all ADRs were expected, of mild to moderate intensity and most were desired reactions. Future research is necessary to investigate whether higher incidences of immune-related events are indicators of beneficial immunomodulation and better clinical outcomes.
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Affiliation(s)
- Friedemann Schad
- Research Institute Havelhoehe, Berlin, Germany; Department of Oncology, Hospital Havelhoehe, Berlin, Germany
| | | | | | - Harald Matthes
- Research Institute Havelhoehe, Berlin, Germany; Department of Oncology, Hospital Havelhoehe, Berlin, Germany
| | - Megan L Steele
- Research Institute Havelhoehe, Berlin, Germany; Institute of Health and Biomedical Innovation, School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia.
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Signoretti M, Valente R, Repici A, Delle Fave G, Capurso G, Carrara S. Endoscopy-guided ablation of pancreatic lesions: Technical possibilities and clinical outlook. World J Gastrointest Endosc 2017; 9:41-54. [PMID: 28250896 PMCID: PMC5311472 DOI: 10.4253/wjge.v9.i2.41] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 10/12/2016] [Accepted: 12/09/2016] [Indexed: 02/05/2023] Open
Abstract
Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP)-guided ablation procedures are emerging as a minimally invasive therapeutic alternative to radiological and surgical treatments for locally advanced pancreatic cancer (LAPC), pancreatic neuroendocrine tumours (PNETs), and pancreatic cystic lesions (PCLs). The advantages of treatment under endoscopic control are the real-time imaging guidance and the possibility to reach a deep target like the pancreas. Currently, radiofrequency probes specifically designed for ERCP or EUS ablation are available as well as hybrid cryotherm probe combining radiofrequency with cryotechnology. To date, many reports and case series have confirmed the safety and feasibility of that kind of ablation technique in the pancreatic setting. Moreover, EUS-guided fine-needle injection is emerging as a method to deliver ablative and anti-tumoral agents inside the tumuor. Ethanol injection has been proposed mostly for the treatment of PCLs and for symptomatic functioning PNETs, and the use of gemcitabine and paclitaxel is also interesting in this setting. EUS-guided injection of chemical or biological agents including mixed lymphocyte culture, oncolytic viruses, and immature dendritic cells has been investigated for the treatment of LAPC. Data on the long-term efficacy of these approaches, and large prospective randomized studies are needed to confirm the real clinical benefits of these techniques for the management of pancreatic lesions.
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