Cases of cancer therapy-related cardiac dysfunction associated with anticancer drugs will be identify and describe

use of anticancer drugs in monotherapy or in combination therapy

Joachim Alexandre, MD, PhD

Little is known about cancer therapy-related cardiac dysfunction occuring in children treated by anticancer drugs for malignancies. Here the investigators use VigiBase (http://www.vigiaccess.org/), the World Health Organization (WHO) database of individual safety case reports, to identify and describe cases of cancer therapy-related cardiac dysfunction associated with anticancer drugs.

Cancer Therapy-related Cardiac Dysfunction Occuring in Children Treated by Anticancer Drugs for Malignancies

Identification of Anticancer Drugs Associated With Cancer Therapy-related Cardiac Dysfunction Reporting in Pediatrics - Analysis of the WHO Pharmacovigilance Database

identification and description of cases of cancer therapy-related cardiac dysfunction associated with anticancer drugs in the World Health Organization (WHO) database of individual safety case reports (vigibase)

Disproportionnality analyses in Vigibase (IC025 and/or ROR) perfomed on cases reported in the World Health Organization (WHO) database of individual safety case reports (vigibase)

Cases reported in the World Health Organization (WHO) database of individual safety case reports (vigibase)

University Hospital, Caen

Behaviors and Mental Disorders

All Conditions

Symptoms and General Pathology

Anxiety Disorders

Nausea

Vomiting

Mental Disorders

Psychotic Disorders

Signs and Symptoms, Digestive

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Aprepitant

Cisplatin

Dexamethasone acetate

Granisetron

The child in the music therapy group will receive a standard antiemetic treatment procedure 15 minutes before the cisplatin infusion. Music therapy will be applied with the start of cisplatin infusion. The song "The Happiest Child", developed by creating rhythms and developed by Fulya Merve KOS, a researcher with a RhythmotherapistTM certificate issued by the Ministry of National Education, will be used in music therapy. The sound will be adjusted to 45 db. The speaker will be placed at the end of the foot, approximately 30 cm from the child's ear, five minutes before the procedure and will be played to the child during the procedure. After the infusion, music therapy will be terminated and the level of nausea, irritability and anxiety will be evaluated with data collection forms.

Standard approach; Granisetron IV 40mcg/kg/24, Aprepitant PO 125 mg/24 hour and Dexamethasone 6 mg/m2 IV/PO are administered to children receiving cisplatin treatment.

Music Therapy

antiemetic treatment

This study will be conducted with a randomized controlled study model to examine the effect of music therapy on nausea, vomiting and anxiety levels in children diagnosed with oncological cancer receiving cisplatin.

The research is planned to be carried out at Dokuz Eylül University Nevvar-Salih İşgören Children's Hospital Pediatric Hematology-Oncology Clinic between December 2023 and December 2024. There is no application for music therapy in the operation of this hospital and clinic.

This study was planned to be conducted with children aged 7-18 years old who were hospitalized in the Pediatric Oncology Clinic of Dokuz Eylül University Hospital Nevvar-Salih İşgören Children's Hospital. The sample calculation required for the study was based on a significance level of 0.05, a power of 80% and an effect size of 0.15 (medium effect size) in the GPOWER 3.1 statistical analysis program. It was determined that 33 children should be included in each group for t test analysis in dependent groups. In order to fulfill the parametric test assumptions in the study and considering the 10% loss, it was planned to include 40 children in the experimental group and 40 children in the parent and control group, who voluntarily agreed to participate in the research, for a total of 80 children.

Children with cancer who are between the ages of 7-18, receive cisplatin treatment, are diagnosed with oncological cancer, do not have mental retardation as a clinical diagnosis, receive chemotherapy during their stay in the clinic, have no hearing problems, know how to read and write in Turkish, and volunteer to participate in the study will be included in the study. . Children with cancer who are in the terminal stage and do not want to participate in the study will not be included in the study.

Data Collection Process Children who will receive the intervention and their parents will be informed about the research. Children and their parents will be informed about the music therapy to be applied to their children and their verbal and written consent will be obtained. After consent is obtained, it will be determined which group the child belongs to by randomization method. The standard approach will be applied to all children.

Standard approach; Granisetron IV 40mcg/kg/24, Aprepitant PO 125 mg/24 hour and Dexamethasone 6 mg/m2 IV/PO are administered to children receiving cisplatin treatment.

The child in the control group will not undergo any additional intervention, and the standard antiemetic treatment procedure will be applied 15 minutes before the cisplatin infusion.

The child in the music therapy group will receive a standard antiemetic treatment procedure 15 minutes before the cisplatin infusion. Music therapy will be applied with the start of cisplatin infusion. The song "The Happiest Child", developed by creating rhythms and developed by Fulya Merve KOS, one of the researchers with the RhythmotherapistTM certificate issued by the Ministry of National Education, will be used in music therapy. The sound will be adjusted to 45 db. The speaker will be placed at the end of the foot, approximately 30 cm from the child's ear, five minutes before the procedure and will be played to the child during the procedure. After the infusion, music therapy will be terminated and the level of nausea, irritability and anxiety will be evaluated with data collection forms.

Randomization A total of 80 children who meet the inclusion criteria will be included in the study.

The random selection process of 80 people will be created by the computer randomization program (www.randomizer.org). The Research Randomizer program is a free resource for researchers who need a quick way to generate random numbers or assign participants to experimental conditions. This site may be used for a variety of purposes, including psychology experiments, medical experiments, and survey research.

The program can automatically generate a set of 40 numbers from 1-80 without creating any repetitions. Each child will be randomly assigned a number between 1 and 80. Children given odd numbers will be included in the control group, and children given even numbers will be included in the music therapy group.

The Effect of Music Therapy on Nausea, Vomiting and Anxiety Levels in Children

The Effect of Music Therapy on Nausea, Vomiting and Anxiety Levels in Children Diagnosed With Oncological Cancer Receiving Cisplatin: Randomized Controlled Study

The form, created by the researchers using the literature, consists of 22 questions indicating the child's age, gender, diagnosis, treatment method, medication use other than chemotherapy, medications used, parent's age, parent's education, income and employment status, and characteristics of the child's care and treatment.

It is a visual scale that measures nausea and vomiting developed by Kudubeş and Bektaş in 2022. The scale is thermometer-shaped and has five degrees. It is visualized as a smiling face (1), unresponsive face (2), sad face (3), sad face (4) and crying face (5). Additionally, as the scale score increases, the facial expression on the scale changes. It is scored as never (1), rarely (2), sometimes (3), often (4) and always (5). The lowest score from the scale is 1 and the highest score is 5. An increase in the scale score indicates that the child's degree of nausea and vomiting increases. The intraclass correlation coefficient of the scale is 0.99.

ARINVc was first developed for adult oncology patients by Rhodes and later adapted to children by Lo and Hayman. The validity and reliability study of the scale was conducted by Akçay and his colleagues in the Turkish population in 2018. The scale consists of five statements for each of 6 items measuring the child's frequency, duration and distress of nausea, frequency of vomiting and distress in the last 12 hours and is scored between 0 and 4. ARINVc consists of 6 items. The first three items in the scale question the frequency, amount, and distress caused by vomiting during the last 12 hours, and the remaining three items question the frequency, duration, and distress caused by nausea.

The scale was developed by Spielberger in 1973. Its Turkish validity and reliability was conducted by Özusta in 1995 (Özusta, 1995). In the State Anxiety Scale of ÇDSCI, children are asked to evaluate how they feel 'at that moment' and to mark one of three relevant options. The scale, consisting of 20 items, aims to evaluate emotions related to state anxiety such as tension, irritability, and uneasiness. If the child reports the presence of these feelings as a lot, the highest score is 3, and if the child reports that they do not exist, the lowest score is 1.

Bilecik Seyh Edebali Universitesi

lecturer

Infections

Neoplasms

Rare Diseases

Communicable Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Disease Attributes

Neuroepithelioma

10 children with neuroblastoma. Inclusion after verification of diagnosis and informed consent.

Sampling of fecal microbiome (Initial microbiome, microbiome under chemotherapy, final microbiome), fecal volatile organic compounds (initial fecal volatile organic compounds, fecal volatile organic compounds under chemotherapy and final fecal volatile organic compounds) and breath organic volatile compounds (initial breath organic compounds, breath volatile organic compounds under chemotherapy and final breath volatile organic compounds).

Samples will be taken after verifying diagnosis before initiation of chemotherapy, 1 week after completion of each cycle and 3 weeks after the end of chemotherapy.

10 children without gastro-intestinal or pulmonary disease as age and sex matched controls to the neuroblastoma group. Patients will be recruited from paediatric surgery. Inclusion after informed consent.

Sampling of fecal microbiome (initial fecal microbiome), fecal volatile organic compounds (initial fecal volatile organic compounds) and breath organic volatile compounds (initial breath volatile organic compounds).

Samples will be taken as age and sex matched controls for the neuroblastoma group. Sampling will be done once after obtaining informed consent.

Stool sampling for fecal microbiome analysis by 16S rDNA pyrosequencing. Neuroblastoma group and Control group.

Initial fecal microbiome

Volatile organic compound analysis of stool samples by gas chromatography/mass spectroscopy Neuroblastoma group and Control group.

Initial fecal volatile organic compounds

Breath sampling for organic compound analysis by gas chromatography/mass spectroscopy Neuroblastoma group and Control group.

Initial breath volatile organic compounds

Stool sampling under chemotherapy of children in neuroblastoma group (1 sample 1 week after completion of each chemotherapy cycle). Chemotherapy according to Société Internationale d´Onclogie Pediatrique Neuroblastoma Group (SIOPEN) guidelines

Microbiome under chemotherapy

Stool sampling under chemotherapy of children in neuroblastoma group (1 sample 1 week after completion of each chemotherapy cycle). Chemotherapy according to SIOPEN guidelines.

Neuroblastoma group

Fecal volatile organic compounds under chemotherapy

Breath sampling under chemotherapy of children in neuroblastoma group (1 sample 1 week after completion of each chemotherapy cycle). Chemotherapy according to SIOPEN guidelines.

Neuroblastoma group

Breath volatile organic compounds under chemotherapy

Stool sampling 3 weeks after completion of chemotherapy Neuroblastoma group

Final microbiome

Final fecal volatile organic compounds

Breath sampling 3 weeks after completion of chemotherapy Neuroblastoma group

Final breath volatile organic compounds

Christoph Castellani, MD

Georg Singer, MD

Daniela Sperl, MD

Background: Malignant tumors may lead to a catabolic state with loss of muscle and adipose tissue. The full picture of catabolism is termed cachexia and is associated with significant morbidity and mortality of cancer patients. Although the full picture is rarely observed up to 50% of children with cancer suffer from significant malnourishment. Additionally to tumor-induced catabolism, side-effects of chemotherapy may be problematic for the patients. In this regard up to 60% of children suffer from gastrointestinal mucositis presenting with nausea, vomiting, diarrhea or constipation and abdominal pain. In the worst case, mucositis may lead to bacterial translocation with life-threatening inflammatory response. Clinically this may require a reduction of the dosage or the number of chemotherapy cycles resulting in reduced effectivity. Up to now the therapy of mucositis is only symptomatic. Recent research of the applicant has shown a significant reduction of Lactobacilli in mice with neuroblastoma (a malignant childhood tumor). The dysbiosis was associated with catabolism, increased gut permeability and inflammation. Astonishingly, chemotherapy alone also leads to a significant reduction of Lactobacilli compared to sham mice, which may be linked to the development of mucositis clinically. Overall, the intestinal microbiome seems to play an essential role in the development of tumor-associated catabolism and chemotherapy-induced mucositis.

Aim: The aim of this project is to determine if the changes in the intestinal microbiome observed in mice can also be seen in children with neuroblastoma.

Methods: One part of the study will include 10 children with neuroblastoma (inclusion after verification of the diagnosis) and 10 healthy controls. The fecal microbiome will be determined by 16S-ribosomal deoxyribonucleic acid (rDNA) pyrosequencing. Volatile organic compounds in the breath will be sampled and measured by Gas Chromatography/Mass Spectroscopy. A basic science human work package will address the question if there are differences.

In the second part serial investigations in children with neuroblastoma will assess whether or not these patients show alterations of the intestinal microbiome under chemotherapy.

Neuroblastoma group: Children with neuroblastoma enrolled after verification of diagnosis. Sampling before initiation of chemotherapy and under chemotherapy.

Control group: healthy children without gastro-intestinal or pulmonary disease recruited from paediatric surgery.

Investigating the Microbiome and Volatile Organic Compound Profile of Children With Neuroblastoma

Investigating the Microbiome and Volatile Organic Compound Profile of Children With Neuroblastoma - a Pilot Study

Alpha and beta diversity, relative bacterial abundance at different levels in percent.

Body weight (in kg) and height (in m) will be determined to calculate the body mass index (BMI in kg/m\^2).

Body weight (in kg) and height (in m) will be determined to calculate the Body mass index (BMI in kg/m\^2).

Assessment of the mucositis score according to the WHO criteria (WHO handbook for reporting results of cancer Treatment; WHO Offset publication no 48) The score contains 5 subitems which are evaluated separately. At the end a total score is derived by adding the results of all items.

Subitem 1: oral mucosa; range 0 (best) to 4 (worst) Subitem 2: nausea and vomiting; range from 0 (best) to 4 (worst) Subitem 3: diarrhea; range from 0 (best) to 4 (worst) Subitem 4: constipation; range from 0 (best) to 4 (worst) Subitem 5: abdominal pain; range from 0 (best) to 4 (worst)

Volatile organic compounds in ppb in the exhaled breath.

Volatile organic compounds in ppb in stool samples.

Medical University of Graz

Nervous System Diseases

Eye Diseases

Brain Neoplasms

Hemianopsia

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Vision Disorders

Sensation Disorders

Neurologic Manifestations

Blindness

Immersive virtual-reality stimulation (IVR): 1 session of 3 blocks of 15 trials of 20 seconds each. Rest time is 1-2 minute(s) between blocks. 1 session lasts 19 minutes.1 session every 2 days for 4 weeks (15 sessions total).

IVR stimulation every 2 days (± 1 day) at any time during the day (delivery).

Immersive Virtual-Reality Stimulation

There are currently no visual rehabilitation strategies for children presenting visual field defects consecutive to a brain tumor or its treatment. This study seeks to investigate the use of a home-based stimulation visual rehabilitation program using immerse-virtual reality (IVR) in children aged 4-10 years old with a diagnosis of hemianopia

A brain tumor and its treatment can affect the visual system at different levels, from the optic nerves (through compression or infiltration). Children with brain tumors can present visual impairments like decreased visual acuity and contrast sensitivity, loss of color vision, and visual field loss such as hemianopias. Patients with hemianopia present difficulties in detecting stimuli in the defective visual field and show defective scanning and exploration. Moreover, they show a rotation and compression of the auditory space leading to imprecise localization of sound across both hemispaces. Patients with hemianopia naturally develop oculomotor strategies to compensate for visual field loss, but visual rehabilitation procedures must still be developed to optimize/improve visual perception in the blind field. Several studies demonstrated that these patients could improve visual perception in the damaged hemifield after a stimulation procedure where auditory and visual stimuli were temporally and spatially correlated. Such audiovisual stimulation programs induce a functional and anatomical reorganization of the visual connectivity in subcortical and cortical structures over time.

The current strategies rely on a significant workload, over 30 hours of audiovisual stimulation using static, spatially, and temporally coherent stimuli displayed on large screens/panels in a clinical setting. These strategies require frequent visits to the clinic impeding the patients' adherence and compliance and increasing the burden of disease. We seek to develop an audiovisual stimulation procedure using immersive virtual reality (IVR) using a head-mounted display (HMD). This is an emerging and very promising visual rehabilitation approach using high-technology devices. It is developed to provide sensory stimulation with better ecological validity due to virtual reality, greater flexibility due to home-based programs, and improved efficiency due to patient-tailored protocols. IVR is a versatile technology, allowing its potential use for the rehabilitation of a variety of low-vision conditions. There are currently limited practical results on whether this technology is suitable for low-vision patients to use at home and if it can be deployed on a large scale. A few case reports/series studies suggested the potential effectiveness of IVR on visual perception in teenagers, adults, and the elderly but more information as to the potential of use and effectiveness of this technology in children and young teenagers is necessary

Visual rehabilitation using home based audiovisual rehabilitation in immersive virtual reality.

Visual Rehabilitation in Children With Homonymous Hemianopia: a Pilot Study on Virtual-reality Stimulation

Visual Rehabilitation in a Pediatric Population of Patients With Homonymous Hemianopia: a Pilot Study on Virtual-reality Stimulation

Feasibility objectives for our pilot study to be considered successful

1. . Number of patients completing the stimulation protocol: ≥ 8 out of 10 patients (80%).
2. . Number of IVR sessions performed by the patients to consider the stimulation protocol complete: ≥ 12 sessions out of 15 (80%).
3. . Number of consecutive virtual-reality induced symptoms and effects (VRISE) scores \< 25: ≤ 3 per patient during the treatment period.
4. . Number of patient drop-outs due to cybersickness (discomfort symptoms experienced in VR): ≤ 2 (20%) during the treatment period.

Corresponds to the potential effectiveness of IVR stimulation in visual acuity assessed by standard procedures by ophthalmologists.

-Best Corrected Visual Acuity, distance, and near vision (range 20/12.5 to \<20/1000, higher score = better outcome)

This corresponds to the potential effectiveness of IVR stimulation in reading speed assessed by standard procedures by ophthalmologists.

Endpoints will measure change from baseline at 2 and 4 weeks in:

-Mean reading speed (Minnesota Low Vision Reading test, MNREAD - range 0 words/minute to 280 words/minute, higher score = better outcome)

This corresponds to the potential effectiveness of IVR stimulation in the field of vision assessed by standard procedures by ophthalmologists.

Endpoints will measure change from baseline at 2 and 4 weeks in:

-Mean contrast sensitivity (Functional Acuity Contrast Test, FACT - range 0.48 cyc./deg. to 2.41 cyc./deg., higher score = better outcome)

This corresponds to the potential effectiveness of IVR stimulation in the quality of life.

Endpoints will measure change from baseline at 2 and 4 weeks in:

-Quality of life scores (Children's Vision Function Questionnaire, higher score = better outcome).

University Health Network, Toronto

The Hospital for Sick Children

Head of Pediatric Neuro-oncology

Necrosis

Hernia

Hernia, Inguinal

Pathological Conditions, Anatomical

Hernia, Abdominal

Patients operated laparoscopically - PIRS technique

Patients operated by open modified Marcy technique

Operation by its known design for PIRS group

Operation - PIRS

Operation by its known design for MARCY group

Operation - MARCY

Today there are various surgical techniques for inguinal hernia. In this study, investigators want to compare the ''PIRS'' operating technique laparoscopy and modified "Marcy" operating technique with open inguinal access. Investigators would compare both groups to find out witch one does the lesser inflammatory stress response on the organism.

Inguinal hernia represents the protrusion of the abdominal cavity contents through the inguinal canal. Today there are various surgical techniques for inguinal hernia. In this study, investigators want to compare two standard methods that are regularly performed at the University hospital of Split at department of pediatric surgery. These are the ''PIRS'' operating technique laparoscopy and modified "Marcy" operating technique with open inguinal access. The choice of operating technique depends solely on the choice of a chosen pediatric surgeon. Given the fact that the child is indicated for an operation, regardless of participation in the study, there are no significant risks of participating in this study, except for possible but rare complications resulting from the peripheral venous blood draw (haematoma, soreness and pain). To carry out this study, the child should be taken (drawn) 3 peripheral venous blood samples (on day of operation, 24 hours after surgery and 6 days after surgery) from which the laboratory parameters are taken and counted (Leukocytes, C - Reactive Protein, Interleukin 6 and Tumor necrosis factor α).

Lab results would be compared between both groups to find out witch one does the lesser inflammatory stress response on the organism.

Inflammatory Stress Response in Pediatric Inguinal Hernia Repair

Comparison of Inflammatory Stress Response Between Laparoscopic and Open Approach for Pediatric Inguinal Hernia Repair

Just investigators have insight in patient data, no such data (names and private data) would be written in the study for publishing

measurement of IL6 in pg/mL (according to manufacturer), change of the value in three time frames like mentioned below

measurement of C - reactive protein in mg/L, change of the value in three time frames like mentioned below

measurement of Tumor necrosis factor alpha in pg/mL (according to manufacturer), change of the value in three time frames like mentioned below

measurement of white blood cell count in 10\^9/L, change of the value in three time frames like mentioned below

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cancer Therapy-related Cardiac Dysfunction Occuring in Children Treated by Anticancer Drugs for Malignancies	NCT05602103	Malignancies Cardiovascular ... Children, Only	use of anticanc...	0 Years - 18 Years	University Hospital, Caen
The Effect of Music Therapy on Nausea, Vomiting and Anxiety Levels in Children	NCT06224894	Music Therapy Nausea Anxiety Cancer Vomiting Children, Only	Music Therapy antiemetic trea...	7 Years - 18 Years	Bilecik Seyh Edebali Universitesi
Investigating the Microbiome and Volatile Organic Compound Profile of Children With Neuroblastoma	NCT03545542	Microbial Colon... Neuroblastoma Children, Only	Initial fecal m... Initial fecal v... Initial breath ... Microbiome unde... Fecal volatile ... Breath volatile... Final microbiom... Final fecal vol... Final breath vo...	1 Month - 8 Years	Medical University of Graz
Investigating the Microbiome and Volatile Organic Compound Profile of Children With Neuroblastoma	NCT03545542	Microbial Colon... Neuroblastoma Children, Only	Initial fecal m... Initial fecal v... Initial breath ... Microbiome unde... Fecal volatile ... Breath volatile... Final microbiom... Final fecal vol... Final breath vo...	1 Month - 8 Years	Medical University of Graz
Visual Rehabilitation in Children With Homonymous Hemianopia: a Pilot Study on Virtual-reality Stimulation	NCT05065268	Hemianopia Brain Tumor Children, Only	Immersive Virtu...	8 Years - 21 Years	The Hospital for Sick Children
Cancer Therapy-related Cardiac Dysfunction Occuring in Children Treated by Anticancer Drugs for Malignancies	NCT05602103	Malignancies Cardiovascular ... Children, Only	use of anticanc...	0 Years - 18 Years	University Hospital, Caen
Inflammatory Stress Response in Pediatric Inguinal Hernia Repair	NCT03203343	Inguinal Hernia... Children, Only Inflammatory Re... Surgery Interleukin-6 Tumor Necrosis ... C Reactive Prot... White Blood Cel...	Operation - PIR... Operation - MAR...	3 Years - 7 Years	University Hospital of Split
Inflammatory Stress Response in Pediatric Inguinal Hernia Repair	NCT03203343	Inguinal Hernia... Children, Only Inflammatory Re... Surgery Interleukin-6 Tumor Necrosis ... C Reactive Prot... White Blood Cel...	Operation - PIR... Operation - MAR...	3 Years - 7 Years	University Hospital of Split

Spots Global Cancer Trial Database for children, only