German physicians' perceptions and views on complementary medicine in pediatric oncology: a qualitative study.

Complementary and alternative medicine (CAM) use in children with cancer has a high prevalence. If (parents of) patients bring up the topic of CAM, pediatric oncologists (POs) face considerable challenges regarding knowledge and professional behavior. In this study, we explore German POs' understanding of CAM and related attitudes as well as challenges and strategies related to CAM discussions by means of semi-structured interviews analyzed according to principles of qualitative thematic analysis with parents of children with cancer. We could conduct 14 interviews prior to theoretical saturation. The interviews had a duration of 15-82 min (M = 30.8, SD = 18.2). Professional experience in pediatric oncology was between 0.5 and 26 years (M = 13.8, SD = 7.6). Main themes identified were a heterogeneous understanding and evaluation of CAM, partly influenced by personal experiences and individual views on plausibility; the perception that CAM discussions are a possible tool for supporting parents and their children and acknowledgement of limitations regarding implementation of CAM discussions; and uncertainty and different views regarding professional duties and tasks when being confronted with CAM as a PO. Our interdisciplinary interpretation of findings with experts from (pediatric) oncology, psychology, and ethics suggests that there is need for development of a consensus on the minimal professional standards regarding addressing CAM in pediatric oncology.

Warming up for a better fever: a randomized pilot study in pediatric oncology.

BACKGROUND: Fever in children is a major problem in pediatric oncology. Usual management leads to immediate antibiotic and antipyretic therapy, although there is consensus that antipyretic therapy should not be utilized with the sole aim of reducing body temperature. Increased body temperature during fever appears to be an effective modifier in terms of viral replication and enhanced host defense mechanisms against pathogens. Therefore, it might be beneficial to support febrile patients by applying gentle heat during the onset of fever to help the body to reach its new thermoregulatory set point. METHODS: A randomized pilot study over 6 months will be conducted in a pediatric oncology department in an academic hospital in Germany. This study is a preparation for a multicenter clinical trial with two parallel groups concerning the efficacy of heat application vs. treatment as usual. One of the inclusion criteria is body temperatures ≥ 38.0 °C in n = 24 cases of patients receiving chemotherapy aged 18 months to 17 years. The first intervention consists of gentle heat application with hot water bottles at any sign of illness and onset of fever. The aim is to achieve a warm periphery equilibrated to trunk temperature of less than 0.5 °C. The second intervention is the avoidance of antipyretics. The control group receives the standard antipyretic treatment from the participating hospital. The purposes of this pilot study are proof of principle of intervention, evaluation of safety, feasibility, definition of endpoints, and to receive basic data for sample size calculation and needed resources. DISCUSSION: The main goal is to improve the care of children with cancer by providing the best possible support for febrile episodes. If fever support by heat reduces discomfort, administration of antipyretics and maybe even antibiotics, this would be an advancement in oncological fever management. This pilot study is intended to provide a basis for a main, multicenter, randomized trial and demonstrate the practicability of heat application in febrile patients in pediatric oncology. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00028273 . Registered on 14 April 2022.

Integrative medicine during the intensive phase of chemotherapy in pediatric oncology in Germany: a randomized controlled trial with 5-year follow up.

BACKGROUND: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients. METHODS: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales. RESULTS: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up. DISCUSSION: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown.

Complementary and Integrative Medicine in Pediatric Oncology - Development and Evaluation of a Blended Learning Program.

BACKGROUND: A blended learning program to promote the consultation expertise of pediatric oncologists (POs) on complementary and integrative medicine (CIM) was developed and completed by POs as part of a training program. A previous study indicated that POs in Germany were in need of information and training on CIM, and that there were no medical training offers on the subject in Germany. METHODS: Evaluation of e-learning (questionnaires) and practically oriented one-day, face-to-face workshops (questionnaires, simulation patients), the workshops were evaluated with regard to changes in quality of physician-patient interaction and with regard of the participants' feedback. RESULTS: 32 POs signed up for the program and completed the e-learning. 22 POs participated in one of the workshops. POs agreed that they had received professionally relevant content during the e-learning. The questionnaires on physician-patient interaction showed neither clear positive nor negative changes concerning the quality of interaction. The feedback from the participants on the workshop was very positive. CONCLUSION: Following the end of the blended learning program the e-learning was made available again for interested POs. 34 further applications were received for participation in this part of the training program. With around 300 POs in Germany, this shows a high demand for further training offers of this kind as well as a need for further development.

Antitumoral Effects of Curcumin (Curcuma longa L.) and Thymoquinone (Nigella sativa L.) on Neuroblastoma Cell Lines.

INTRODUCTION: Overall survival of high-risk neuroblastoma patients is still poor, emphasizing the need for novel therapeutic options. There is evidence for anti-cancer properties of the herbal substances thymoquinone and curcumin. These substances are isolated from Nigella sativa L. and Curcuma longa L., respectively, which are used in traditional medicine. OBJECTIVE: We investigated cytotoxic effects of thymoquinone and curcumin on neuroblastoma cell lines NLF, NB69, and SK-N-BE(2), in vitro. METHODS: Cytotoxicity of compounds was investigated by MTT cell viability assays. For analyzing effects on cell proliferation BrdU assays were employed and induction of apoptosis was detected by Cell Death ELISA assays. RESULTS: Both substances showed cytotoxic effects in all three neuroblastoma cell lines, whereby primary human fibroblast cells reacted less sensitively. Overall, lower IC50 values could be calculated for curcumin (3.75-7.42 µM) than for thymoquinone (5.16-16.3 µM). Decreased proliferation and increased apoptosis rates were observed under treatment. CONCLUSIONS: Both substances showed anti-tumoral properties on neuroblastoma cell lines and should be further investigated as therapeutic agents.

Perception of integrative care in paediatric oncology-perspectives of parents and patients.

PURPOSE: For some years now, a programme for the use of integrative care in paediatric oncology has been established in a German university hospital and offers patients and parents complementary treatment options. According to their medical condition and wishes. A variety of external applications such as medical wraps, warm oil compresses and rhythmic embrocations are offered. This article analyses how patients and parents perceived and experienced the integrative care program. METHODS: In this qualitative study, data consists of field notes conducted through participant observation, informal conversations and interviews with parents (n = 25) during the implementation phase of the program. Data was analysed on basis of thematic analysis and organized with the analysis software MAXQDA. RESULTS: Parents and families intuitively developed strategies for dealing with crisis situations such as childhood cancer. In addition, many of the families brought with them a wealth of experience in complementary medicine. Parents perceived the integrative care treatments as soothing, relaxing and pain-relieving for their child. Patients could relax and side effects of chemotherapy were alleviated. However, children, who undergoing chemotherapy were not always open for physical touch and thus sometimes also rejected the treatments sometimes. CONCLUSION: The analysed integrative care programme is perceived as a strong patient and family-centred approach of support during the oncological paediatric treatment. From a salutogenetic viewpoint, this program aims to strengthen the dimension of manageability within the concept of sense of coherence. Parents are given supportive means to manage side effects and ease their child's suffering, through touch and attention that can be very beneficial.

Evaluation of an Integrative Care Program in Pediatric Oncology.

Purpose: This article discusses the results of an evaluation of the one-year implementation period of an integrative care program at a pediatric oncology ward, which consists of integrative care treatments offered three times a week to the patients. The guiding questions are how the model was implemented, which factors have to be considered for successful implementation, and which factors showed to be obstacles during implementation. Methods: A mixed-methods approach was applied for data saturation. Qualitative data consist of participant observations and informal conversations during the implementation phase. All observational records were filed in the data program MAXQDA. For the quantitative data, all integrative care treatments applied on the intensive care unit were documented and subsequently filed in an Excel sheet. Both sets of data were analyzed for the evaluation. Results: Four main thematic clusters influenced the implementation: (1) the organization and structure of the intensive care unit; (2) mood and atmosphere; (3) feedback on treatment; and (4) time and experience. All factors are interlinked and cannot be looked at independently. Results of the quantitative data show that the most frequent used treatments were those with calming and relaxing effects, followed by treatments for stomachache, nausea, and obstipation. Conclusions: The implementation of an integrative model of care is a process that demands thorough understanding of the complex setting of the ward, ongoing adaptation to the structures and organization of the ward, and the integration of factors like feedback, time, atmosphere, and the mood of parents, patients, and nurses.

Defining Criteria for Guiding Cancer Patients to Find a Reputable Complementary Medicine Provider: Results of a Literature Review and a Consensus Procedure.

PURPOSE: Even in cases of positive evidence for complementary medicine (CM) therapies, it is still difficult for cancer patients to identify reputable providers. The aim of this study was to develop and evaluate a criteria list to provide guidance to cancer patients seeking a reputable CM provider. METHODS: The design combined a literature review, an expert consensus procedure (n=15) and an assessment from three stakeholder perspectives (patients (n=18), CM providers (n=26) and oncology physicians (n=20)). RESULTS: A total of 30 existing CM criteria were extracted from the literature, and 12 more were added by the experts. The main challenge was to define criteria that could easily be applied by the patients. A final comprehensive list of 8 criteria guiding cancer patients to find a reputable CM provider was developed. CONCLUSION: Health professionals and cancer information services might find the criteria list helpful when aiming to strengthen patients' awareness of quality-related factors associated with CM providers. The criteria developed might be helpful when standards are established for quality assurance in CM in oncology.

Social inequalities in the participation and activity of children and adolescents with leukemia, brain tumors, and sarcomas (SUPATEEN): a protocol for a multicenter longitudinal prospective observational study.

BACKGROUND: About 2000 children and adolescents under the age of 18 are diagnosed with cancer each year in Germany. Because of current medical treatment methods, a high survival rate can be reached for many types of the disease. Nevertheless, patients face a number of long-term effects related to the treatment. As a result, physical and psychological consequences have increasingly become the focus of research in recent years. Social dimensions of health have received little attention in health services research in oncology so far. Yet, there are no robust results that allow an estimation of whether and to what extent the disease and treatment impair the participation of children and adolescents and which factors mediate this effect. Social participation is of great importance especially because interactions with peers and experiences in different areas of life are essential for the development of children and adolescents. METHODS: Data are collected in a longitudinal, prospective, observational multicenter study. For this purpose, all patients and their parents who are being treated for cancer in one of the participating clinics throughout Germany will be interviewed within the first month after diagnosis (t1), after completion of intensive treatment (t2) and half a year after the end of intensive treatment (t3) using standardized questionnaires. Analysis will be done by descriptive and multivariate methods. DISCUSSION: The results can be used to identify children and adolescents in high-risk situations at an early stage in order to be able to initiate interventions tailored to the needs. Such tailored interventions will finally reduce the risk of impairments in the participation of children and adolescents and increase quality of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04101123.

KOKON: A Germany-Wide Collaborative Research Project to Identify Needs, Provide Information, Foster Communication and Support Decision-Making about Complementary and Alternative Medicine in Oncology.

BACKGROUND: The German Cancer Aid set up a priority research programme with the intention to generate high-quality information based on evidence and to make this information easily accessible for health-care professionals and advisors, researchers, patients, and the general public. SUMMARY: The Kompetenznetz Komplementärmedizin in der Onkologie (KOKON) received 2 funding periods within this programme. During the first funding period, KOKON assessed patients' and health-care professionals' informational needs, developed a consulting manual for physicians, developed an education programme for self-help groups, set up a knowledge database, and developed a pilot information website for patients. Funding period 2 continues with work that allows cancer patients and health-care professionals to make informed decisions about complementary and alternative medicine (CAM). For this aim, KOKON evaluates training programmes for physicians (oncology physicians, paediatric oncologists, and general practitioners) and for self-help groups. All training programmes integrate results from an analysis of the ethical, psychological, and medical challenges of CAM in the medical encounter, and the knowledge database is being extended with issues related to CAM for supportive and palliative care. Key Message: A Germany-wide collaborative research project to identify needs, provide information, foster communication, and support decision-making about CAM in oncology is being set up.

Information and Training Needs of Pediatric Oncologists in Complementary and Integrative Medicine: A Cross-Sectional Study.

More than one third of all German pediatric patients with cancer use complementary and integrative medicine (CIM). Parents want to discuss the topic of CIM with their pediatric oncologists (POs); however, POs mostly do not feel confident discussing these topics. POs report openness to receiving further information and training, but CIM training opportunities in medical education seem rare. We investigated POs' information and training needs and preference patterns regarding CIM training content with a paper-based or online survey. A total of 101 POs from Germany completed the survey. Only 11.4% agreed to being sufficiently informed of CIM. The participants stated needing further CIM information very often (8.6%), often (38.7%), or occasionally (44.1%). They considered an overview of CIM therapies and information about relaxation methods, herbal remedies, and acupuncture for cancer-related symptoms such as lack of appetite, nausea, or vomiting as most important in CIM training material, and also the topics of adverse effects and summary of evidence. Finally, POs reported on clinical situations in which a need for further information on CIM emerged. The results of our study indicate that there is a need for a structured training that offers knowledge and skills on the subject of patient counseling on CIM in pediatric oncology.

Integrative care for children with cancer. Project design for the development of an integrative care programme for use in paediatric oncology.

PURPOSE: Purpose of this paper is to describe the project design for the development of a context-specific and patient-focused integrative care programme for an intensive care unit for paediatric oncology to ease the strain of the treatments for patients and their families. Integrative care interventions based on anthroposophical medicine such as wraps, compresses and rhythmic body oiling can be used to ease typical side effects such as nausea, pain and agitation. METHODS: Conduct of a literature research on existing integrative care programmes in medical hospitals and biomedical settings and the identification of appropriate methods to achieve the research aim. RESULTS: A project design was developed which can be used as a basis for developing, introducing and evaluating an integrative care programme for a paediatric oncological intensive care unit in a German university hospital. A qualitative study design was chosen to develop this programme. This included participant observations and interviews with all stakeholders at the respective oncology ward as well as in existing oncology wards that work with an integrative care programme. The primary emphasis was on the criteria appropriateness for the specific setting, sustainability and financial viability as well as on the development of an appropriate evaluation model. CONCLUSIONS: When developing an integrative care programme for use in the specific setting of a paediatric oncology ward and selecting the appropriate interventions for inclusion in the programme, particular attention should be paid to the needs of the patients as well as to the practicability for the nursing staff, particularly with regard to resources such as time and personnel. Both the nursing team and nursing management should be actively involved in the project design from the outset. In the evaluation particular importance is attached to feasibility. The challenge for the economic evaluation is to create a robust database for negotiation of financing possibilities.

Safety of high-dose intravenous mistletoe therapy in pediatric cancer patients: A case series.

BACKGROUND: Long-term survival of children with cancer has reached rates of up to 80%. Nevertheless, continued research devoted to further improvement of survival rates especially for patients with high-risk illnesses is necessary. Recent studies have shown direct positive effects on tumor reduction through Viscum album (mistletoe) extracts in adults, mainly as a result of higher dosage treatment and intravenous or intratumoral application. PATIENTS AND METHOD: A retrospective analysis of data was carried out of all oncological, pediatric patients treated with intravenous high-dose mistletoe therapy for a period of two years (11/2013-11/2015). RESULTS: A total of ten non-coherent cases were examined, all suffering from advanced and/or relapsed forms of cancer (leukemia, neuroblastoma, nephroblastoma, osteosarcoma, lymphoma, anaplastic astrocytoma, atypical teratoid rhabdoid tumor and soft tissue sarcoma). Patients were treated for an average period of 48 days with a mean survival rate of 130 days after beginning the mistletoe therapy. Partial remission was observed in four and a slowed disease progression was monitored in two patients. However, unrestricted progression of disease was documented in two other patients. Patients showed side effects including fever as well as fatigue and in some cases systemic inflammatory reactions with transient organ impairment occurred. CONCLUSION: Our study underpinned the safety and feasibility of high-dose mistletoe infusion in children with advanced stages of cancer and showed noteworthy antineoplastic effects, which should be verified in a prospective clinical phase II/III-study. Because of possible side effects, the treatment should be implemented only in an in-patient setting in experienced pediatric oncology centers.

Contributing factors and outcomes of treatment refusal in pediatric oncology in Germany.

BACKGROUND: In Germany, about 1,800 new cases of pediatric cancer under 15 years of age are diagnosed each year and survival rates approach 80%. Although treatment is covered by health insurance and is thus available for all patients at no cost, treatment refusal and treatment discontinuation have been observed. However, no data providing numbers and outcomes for developed countries have been published thus far. PROCEDURE: A questionnaire-based survey was performed among German pediatric oncology centers to ascertain the number of treatment refusals among pediatric patients who were diagnosed between January 2008 and December 2009 in Germany. RESULTS: Questionnaires from 70 of 73 centers were available, and of these 13 centers reported a total of 15 cases of treatment refusal or discontinuation within this 2-year period. Five of the 15 patients died, 7 of 15 were still alive, and the current status of 3 of 15 patients was unknown. Diseases were heterogeneous. Six of the 15 parents refused treatment for their children initially, 8 of 15 discontinued during the course of treatment. Five patients were treated after parental custody had been withdrawn due to the lack of compliance. All these five patients survived. Parents' reasons given for refusal or discontinuation of treatment were related to personal health beliefs and coping strategies. CONCLUSIONS: Although treatment refusal or discontinuation is rare, it is accompanied by a high mortality rate. Parents' personal health beliefs play a primary role in treatment refusal or discontinuation in Germany. This emphasizes the importance of sustaining a functioning and mutually communicative physician-parent-patient relationship.

Use of complementary and alternative medicine by pediatric oncology patients during palliative care.

PURPOSE: Although the popularity of complementary and alternative medicine (CAM) has risen in the last decade, information about its use by pediatric patients in palliative care is still scarce. The purpose of the study was to assess the frequency and types of CAM administered by parents with children suffering from cancer during the palliative phase. METHODS: All parents who lost their child due to cancer in the federal state North Rhine Westfalia/Germany were eligible for the study. The first group of eligible parents was contacted in 1999-2000 and a second group of parents in 2005-2006. Upon agreement, parents were asked to complete a semi-structured questionnaire about the frequency of CAM use and the specific treatments that had been used. The types of CAM were categorized according to the National Center for Complementary and Alternative Medicine (NCCAM). RESULTS: A total of 96 parents participated in the study (48 in each cohort). Forty-three percent of all parents in both groups reported CAM use. The results show an increase of CAM use from 38 % in the first group to 49 % in the second cohort of pediatric patients during palliative care. The most common types of CAM used in both groups were homeopathy and treatment with mistletoe preparations. CONCLUSIONS: The study provides information about usage of CAM in children suffering from cancer during the palliative phase of the disease. Further research is required to investigate benefits, potential adverse effects, and the potential efficacy of CAM in this population.

Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents.

Haemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome. Haemophagocytic lymphohistiocytosis was considered triggered by the malignancy (M-HLH) in 21 patients, most of whom had T- (n = 12) or B-cell neoplasms (n = 7), with Epstein-Barr virus as a co-trigger in five patients. In eight patients, HLH occurred during chemotherapy (Ch-HLH) for malignancy, mainly acute leukaemias (n = 7); an infectious trigger was found in seven. In M- and Ch-HLH, median overall survival was 1·2 and 0·9 years, and the 6 month survival rates were 67% and 63%, respectively. Seven of 11 deceased M-HLH patients exhibited active malignancy and HLH at the time of death, while only two out of five deceased Ch-HLH patients had evidence of active HLH. To overcome HLH, malignancy- and HLH-directed treatments were administered in the M-HLH cohort; however, it was not possible to determine superiority of one approach over the other. For Ch-HLH, treatment ranged from postponement of chemotherapy to the use of etoposide-containing regimens.

Complementary and alternative medicine in pediatrics in Turkey.

BACKGROUND: Complementary and alternative medicine (CAM) is applied both to children and adults widely throughout the world. A previous pan-European survey showed a surprisingly high CAM-use in Turkish children. This review aimed to survey information on the use of CAM in pediatrics in Turkey. DATA SOURCES: A narrative, non-systematic review was conducted by melding expert opinions with a thorough and balanced review of available evidence. An unrestricted literature search using the key words, "alternative", "complementary", "integrative", "prevalence" and "pediatric" or "children" and "Turkey" was performed by internet search in March, 2012 using PubMed and Google Scholar. RESULTS: CAM use was examined in general pediatrics, pediatric oncology, patients with asthma, and patients with diabetes. A frequency of CAM use was 87% in Turkish pediatric patients, with a mean of 60%. The primary sources of information about CAM are family and friends. Communication with patients/parents and health care professionals showed that most parents do not speak about CAM use with their physicians or nurses. CONCLUSIONS: CAM is extensively used in Turkish pediatric patients. This might be due to Turkey's status as a developing country in which a traditional medical system still dominates in comparison to developed countries. Thus, larger studies are required to prove an extensive use of CAM in Turkey, as this review article does not have the capacity for in-depth analysis. Knowledge about CAM and its related topics is essential for physicians and nurses in order to meet the patients' wish for a competent consultation concerning all aspects of a possible therapy.

Differences in use of complementary and alternative medicine between children and adolescents with cancer in Germany: a population based survey.

BACKGROUND: Use of complementary and alternative medicine (CAM) in children with cancer is common and probably increasing. However, data concerning differences between children and adolescents focusing on prevalence, reasons for use/non-use, costs, adverse effects, and socio-demographic factors are lacking. PROCEDURE: A population-based survey over a 1 year period with 497 participants was conducted. RESULTS: Of the 457 respondents (92%) 322 were children and 135 adolescents (>16 years of age) with malignancies. 31% reported CAM use from the time when being diagnosed, compared to an overall lifetime prevalence rate of 41% before cancer diagnosis. Among CAM users the most prevalent therapies were homeopathy, massage, anthroposophic medicine, acupuncture, and Bach flowers. The main reasons for use were to reduce therapy-related side effects, to strengthen the immune system, to achieve physical stabilization and to increase healing chances. Socio-demographic factors associated with CAM use were higher parental education and higher family income. A majority of CAM users (97%) would recommend CAM use. Most users (78%) informed a physician about CAM use. Side effects were rarely reported (5%), minor and self-limiting. CONCLUSIONS: The high prevalence rates seem to represent the parental or patients needs for additional treatment perceived as successful and devoid of side-effects. Clinical care and the physician-patient relation would profit from an enhanced understanding of CAM and a greater candidness towards the parental needs. Safety and efficacy - especially of CAM with high prevalence rates - should be studied in rigorous basic and clinical research.