Impacts of platinum-based chemotherapy on subsequent testicular function and fertility in boys with cancer

Abstract BACKGROUND Children with cancer often face infertility as a long-term complication of their treatment. For boys, compromised testicular function is common after chemotherapy and currently there are no well-established options to prevent this damage. Platinum-based agents are used to treat a wide variety of childhood cancers. However, platinum agents are not currently included in the cyclophosphamide equivalent dose (CED), which is used clinically to assess the risks to fertility posed by combination chemotherapy in children with cancer. OBJECTIVE AND RATIONALE This was a systematic search of the literature designed to determine the evidence for effects of platinum-based cancer treatment on the prepubertal human testis in relation to subsequent testicular function and fertility. SEARCH METHODS PubMed and EMBASE were searched for articles published in English between 01 January 1966 and 05 April 2020 using search terms including ‘cancer treatment’, ‘chemotherapy’, ‘human’, ‘prepubertal’, ‘testis’, ‘germ cells’, ‘testosterone’ and related terms. Abstracts were screened and full-text articles were obtained for those that met the three major inclusion criteria (age ≤12 years at treatment, exposure to platinum-based chemotherapeutic and measure of reproductive function). Screening of bibliographies for full-text articles was used to identify additional studies. OUTCOMES Our initial search identified 1449 articles of which 20 (1.3%) studies (n = 13 759 males) met all inclusion criteria. A control group (healthy individuals or siblings) was included for 5/20 (25%) studies. A total of 10/20 (50%) studies provided sub-analysis of the relative gonadotoxicity of platinum-based agents. The primary outcome measures were: pregnancies and fatherhood; semen analysis; and hormonal function. For pregnancies and fatherhood, three studies (n = 10 453 males) reported negative associations with platinum-agents, including the largest (n = 5640) controlled study (hazard ratio = 0.56, P = 0.0023), whilst two other studies (n = 1781) with platinum sub-analysis reported no association. For semen analysis (based on World Health Organization criteria), platinum-based chemotherapy was associated with azoospermia in one study (n = 129), whilst another (n = 44) found no association and the remainder did not perform platinum-based sub-analysis. For hormone analysis, conflicting results were obtained regarding potential associations between platinum-based agents and elevated FSH (a proxy for impaired spermatogenesis); however, the majority of these studies were based on low numbers of patients receiving platinum-based chemotherapy. WIDER IMPLICATIONS Overall, these results indicate that platinum-based chemotherapy should be included in clinical calculators, for example CED, used to determine gonadotoxicity for childhood cancer treatment. These findings have important implications for clinicians regarding counselling patients and their carer(s) on fertility risk, guiding requirements for fertility preservation strategies (e.g. testicular tissue cryopreservation) and modification of treatments to reduce or eliminate the risk of infertility in childhood cancer survivors.

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Effects of the application of therapeutic massage in children with cancer: a systematic review

Revista Latino-Americana de Enfermagem ◽

10.1590/1518-8345.1774.2903 ◽

2017 ◽

Vol 25 (0) ◽

Cited By ~ 4

Author(s):

Juan Rodríguez-Mansilla ◽

Blanca González-Sánchez ◽

Silvia Torres-Piles ◽

Jorge Guerrero Martín ◽

María Jiménez-Palomares ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Childhood Cancer ◽

Blood Cells ◽

White Blood Cells ◽

Inclusion Criteria ◽

Controlled Clinical Trials ◽

Children With Cancer ◽

Therapeutic Massage

ABSTRACT Objective: to learn about the effects of the use of therapeutic massage in children with cancer. Method: systematic review of controlled clinical trials The search was conducted in November 2014 in the following databases: Pubmed, CSIC, Dialnet, Scopus, Cochrane and PEDro. Inclusion criteria were: clinical trials, published in English or Spanish, analyzing the effects of massage on the different stages and types of childhood cancer (between 1 and 18 years old). Results: of 1007 articles found, 7 met the inclusion criteria. Their authors use different massage techniques (Swedish massage, effleurage, petrissage, frictions, pressures), obtaining benefits in the symptoms present during the illness (decrease of pain, nausea, stress, anxiety and increase of white blood cells and neutrophils). Conclusion: therapeutic massage improves the symptoms of children with cancer, but there is a need for more research that may support the effects attributed to it.

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Long-term effects of childhood cancer treatment on hormonal and ultrasound markers of ovarian reserve

Yearbook of Paediatric Endocrinology ◽

10.1530/ey.16.9.8 ◽

2019 ◽

Author(s):

van den Berg MH ◽

Overbeek A ◽

Lambalk CB ◽

Kaspers GJL ◽

Bresters D ◽

...

Keyword(s):

Cancer Treatment ◽

Childhood Cancer ◽

Ovarian Reserve ◽

Long Term Effects

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Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy

Communications Biology ◽

10.1038/s42003-021-02136-8 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Katrina Kildey ◽

Neha S. Gandhi ◽

Katherine B. Sahin ◽

Esha T. Shah ◽

Eric Boittier ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Genome Instability ◽

Small Cell ◽

Small Cell Lung ◽

Protein Levels ◽

Platinum Based Chemotherapy ◽

Platinum Agents

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.

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Proportion of children with cancer that have an indication for genetic counseling and testing based on the cancer type irrespective of other features

Familial Cancer ◽

10.1007/s10689-021-00234-4 ◽

2021 ◽

Author(s):

Thi Minh Kha Nguyen ◽

Astrid Behnert ◽

Torsten Pietsch ◽

Christian Vokuhl ◽

Christian Peter Kratz

Keyword(s):

Childhood Cancer ◽

Rhabdoid Tumor ◽

Juvenile Myelomonocytic Leukemia ◽

Cancer Type ◽

Nerve Sheath Tumor ◽

Children With Cancer ◽

Pediatric Pathology ◽

Cancer Trial ◽

Cancer Predisposition Syndrome ◽

Cancer Types

Abstract In children with cancer, specific clinical features such as physical anomalies, occurrence of cancer in young relatives, specific cancer histologies, and unique mutation/methylation signatures may indicate the presence of an underlying cancer predisposition syndrome (CPS). The proportion of children with a cancer type suggesting a CPS among all children with cancer is unknown. To determine the proportion of children with cancer types suggesting an underlying CPS among children with cancer. We evaluated the number of children with cancer types strongly associated with CPS diagnosed in Germany between 2007 and 2016. Data were obtained from various sources including two national pediatric pathology reference laboratories for brain and solid tumors, respectively, various childhood cancer trial offices as well as the German Childhood Cancer Registry. Among 21,127 children diagnosed with cancer between 2007 and 2016, 2554 (12.1%) had a cancer type strongly associated with a CPS. The most common diagnoses were myelodysplastic syndrome and juvenile myelomonocytic leukemia, retinoblastoma, malignant peripheral nerve sheath tumor, infantile myofibromatosis, medulloblastomaSHH, rhabdoid tumor as well as atypical teratoid/rhabdoid tumor. Based on cancer type only, 12.1% of all children with cancer have an indication for a genetic evaluation. Pediatric oncology patients require access to genetic counselling and testing.

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Selection criteria for assembling a pediatric cancer predisposition syndrome gene panel

Familial Cancer ◽

10.1007/s10689-021-00254-0 ◽

2021 ◽

Author(s):

Anna Byrjalsen ◽

Illja J. Diets ◽

Jette Bakhuizen ◽

Thomas van Overeem Hansen ◽

Kjeld Schmiegelow ◽

...

Keyword(s):

Childhood Cancer ◽

Pediatric Cancer ◽

Causal Relation ◽

Evaluation Criteria ◽

Cancer Predisposition ◽

Gene Panel ◽

Childhood Onset ◽

Children With Cancer ◽

Cancer Predisposition Syndrome ◽

A Prospective Study

AbstractIncreasing use of genomic sequencing enables standardized screening of all childhood cancer predisposition syndromes (CPS) in children with cancer. Gene panels currently used often include adult-onset CPS genes and genes without substantial evidence linking them to cancer predisposition. We have developed criteria to select genes relevant for childhood-onset CPS and assembled a gene panel for use in children with cancer. We applied our criteria to 381 candidate genes, which were selected through two in-house panels (n = 338), a literature search (n = 39), and by assessing two Genomics England’s PanelApp panels (n = 4). We developed evaluation criteria that determined a gene’s eligibility for inclusion on a childhood-onset CPS gene panel. These criteria assessed (1) relevance in childhood cancer by a minimum of five childhood cancer patients reported carrying a pathogenic variant in the gene and (2) evidence supporting a causal relation between variants in this gene and cancer development. 138 genes fulfilled the criteria. In this study we have developed criteria to compile a childhood cancer predisposition gene panel which might ultimately be used in a clinical setting, regardless of the specific type of childhood cancer. This panel will be evaluated in a prospective study. The panel is available on (pediatric-cancer-predisposition-genepanel.nl) and will be regularly updated.

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P9 A study to investigate the impact of the COVID-19 pandemic on paediatric cancer patients: an international, multicentre, observational cohort study (COVIDPaedsCancer)

BJS Open ◽

10.1093/bjsopen/zrab032.008 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

Author(s):

◽

Soham Bandyopadhyay

Keyword(s):

Cohort Study ◽

Cancer Treatment ◽

Childhood Cancer ◽

Multivariate Logistic Regression Analysis ◽

Global Health Research ◽

Cancer Outcomes ◽

Paediatric Cancer ◽

Cancer Management ◽

Anti Cancer ◽

The Impact

Abstract Introduction Childhood cancers are a leading cause of non-communicable disease deaths for paediatric patients around the world. The COVID-19 pandemic may have impacted on global children’s cancer services, which can have consequences for childhood cancer outcomes. The Global Health Research Group on Children’s Non-Communicable Diseases (Global Children’s NCDs) is currently undertaking the first international study to determine the variation in paediatric cancer management during the COVID-19 pandemic, and the short to medium term impacts on childhood cancer outcomes. Methods and analysis This is a multicentre, international, cohort study that will use routinely collected hospital data in a de-identified and anonymised form. Patients will be recruited consecutively into the study, with a 12 -month follow-up period. Patients will be included if they are below the age of 18 years and undergoing anti-cancer treatment for the following cancers: Acute lymphoblastic leukaemia, Burkitt’s Lymphoma, Hodgkin's lymphoma, Wilms Tumour, Sarcoma, Retinoblastoma, Gliomas, Medulloblastomas and Neuroblastomas. Patients must be newly presented or be undergoing active anti-cancer treatment from the 12th March 2020 to the 12th December 2020. The primary objective of the study is to determine 30- and 90-day all-cause mortality rates. This study will examine the factors that influenced these outcomes. Chi-squared analysis will be used to compare mortality between low and middle-income countries and high-income countries. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors. Ethics and dissemination At the host centre, this study was deemed to be exempt from ethical committee approval due to the use of anonymised registry data. At other centres, participating collaborators have gained local approvals in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally, and internationally. The results will be submitted for publication in a peer reviewed journal.

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The role of rehabilitation measures in reintegration of children with brain tumours or leukaemia and their families after completion of cancer treatment: a study protocol

BMJ Open ◽

10.1136/bmjopen-2016-014505 ◽

2017 ◽

Vol 7 (8) ◽

pp. e014505 ◽

Cited By ~ 5

Author(s):

Mona Leandra Peikert ◽

Laura Inhestern ◽

Corinna Bergelt

Keyword(s):

Observational Study ◽

Cancer Treatment ◽

Childhood Cancer ◽

Quantitative Study ◽

Prospective Observational Study ◽

Daily Life ◽

Oncological Rehabilitation ◽

Rehabilitation Measures

IntroductionFor ill children as well as for their parents and siblings, childhood cancer poses a major challenge. Little is known about the reintegration into daily life of childhood cancer survivors and their families. The aim of this prospective observational study is to further the understanding of the role of rehabilitation measures in the reintegration process of childhood leukaemia or brain tumour survivors and their family members after the end of cancer treatment.Methods and analysisThis prospective observational study consists of three study arms: a quantitative study in cooperation with three German paediatric oncological study registries (study arm 1), a quantitative study in cooperation with a rehabilitation clinic that offers a family-oriented paediatric oncological rehabilitation programme (study arm 2) and a qualitative study at 12-month follow-up including families from the study arms 1 and 2 (study arm 3). In study arm 1, children, parents and siblings are surveyed after treatment (baseline), 4–6 months after baseline measurement and at 12-month follow-up. In study arm 2, data are collected at the beginning and at the end of the rehabilitation measure and at 12-month follow-up. Families are assessed with standardised questionnaires on quality of life, emotional and behavioural symptoms, depression, anxiety, fear of progression, coping and family functioning. Furthermore, self-developed items on rehabilitation aims and reintegration into daily life are used. Where applicable, users and non-users of rehabilitation measures will be compared regarding the outcome parameters. Longitudinal data will be analysed by means of multivariate analysis strategies. Reference values will be used for comparisons if applicable. Qualitative data will be analysed using thematic analysis.Ethics and disseminationThis study has been approved by the medical ethics committee of the Medical Chamber of Hamburg. Data will be published in peer-reviewed journals and presented at conferences.

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Navigating conversations in childhood cancer treatment: review of Uncertain Futures

Health Communication ◽

10.1080/10410236.2018.1536944 ◽

2018 ◽

Vol 34 (14) ◽

pp. 1845-1846

Author(s):

Olivia Hirschey

Keyword(s):

Cancer Treatment ◽

Childhood Cancer ◽

Treatment Review

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Consensus Recommendations From the Children’s Oncology Group Nursing Discipline’s State of the Science Symposium: Symptom Assessment During Childhood Cancer Treatment

Journal of Pediatric Oncology Nursing ◽

10.1177/1043454219854983 ◽

2019 ◽

Vol 36 (4) ◽

pp. 294-299

Author(s):

Janice S. Withycombe ◽

Maureen Haugen ◽

Sue Zupanec ◽

Catherine F. Macpherson ◽

Wendy Landier

Keyword(s):

Clinical Practice ◽

Cancer Treatment ◽

Childhood Cancer ◽

Symptom Assessment ◽

Self Report ◽

Oncology Group ◽

Symptom Trajectories ◽

Science Symposium ◽

State Of The Science ◽

Core Symptoms

Background: Recognizing and addressing illness-related distress has long been a priority for pediatric oncology nurses and the Children’s Oncology Group. Although symptoms are known to be highly prevalent during treatment for childhood cancer, there is currently no guidance for how often symptoms should be assessed, which symptoms should be prioritized for assessment, and how the data should be collected. Methods: The Nursing Discipline, within Children’s Oncology Group, hosted a one-day Interprofessional seminar titled “Symptom Assessment During Childhood Cancer Treatment: State of the Science Symposium.” Following the symposium, an expert panel was assembled to review all available evidence, including information presented and collected during the symposium. Consensus-building discussions were held to identify common themes and to produce recommendations for clinical practice. Results: Four recommendations emerged including (1) the identification of priority “core” symptoms for assessment; (2) inclusion of the child’s voice through self-report, when possible; (3) consistent documentation and communication of symptom assessment results; and (4) implementation of patient/family education related to symptoms. Discussion: Symptom recognition, through appropriate assessment, is the first step in symptom management. The goal for developing and sharing these recommendations is to promote consistent and comparable clinical practice across institutions in regard to symptom assessment during childhood cancer therapy. Integration of these recommendations will set the stage for future studies related to the frequency of symptoms across disease groups, projection of anticipated symptom trajectories, development of evidence-based teaching tools for common symptoms, and evaluation of patient outcomes with enhanced symptom assessment and management.

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