Rehabilitation Management of Five Common Clinical Problems in Pediatric Cancer: a Narrative Review

The development of curative therapy for most pediatric malignancies has produced a growing population of childhood cancer survivors who are at increased risk for a variety of health problems resulting from their cancer or its treatment. Because of the fact that many treatment-related sequelae may not become clinically apparent until the survivor attains maturity or begins to age, the ability of primary care providers to anticipate late effects of treatment is essential for providing timely interventions that prevent or correct these sequelae and their adverse effects on quality of life. Altered bone metabolism during treatment for childhood cancer may interfere with attainment of peak bone mass, potentially predisposing to premature onset of and more severe complications related to osteopenia and osteoporosis. Bone mineral deficits have been reported after treatment for a variety of pediatric malignancies and represent morbidity that can be reduced or prevented through lifestyle changes and attention to other common cancer-related sequelae such as hypogonadism. The Children's Oncology Group long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers provide risk-based surveillance recommendations that are based on expert opinion and review of the scientific literature for potential late effects of pediatric cancer therapy including osteopenia. This review summarizes the existing literature that has defined characteristics of cancer survivors at risk for bone mineral deficits and contributed to the surveillance and counseling recommendations outlined in the Children's Oncology group long-term follow-up guidelines.

Childhood cancer is an urgent priority in Egypt, owing to a large number of children with cancer, the great need and demand for paediatric oncology services, limited resources/funds and inferior survival outcomes. Therefore, an overview of the status of childhood cancer care in Egypt and an evidence-based approach towards optimal utilisation of resources/funds to improve this care are needed. This paper summarises key evidence about childhood cancer care and outcomes in Egypt. We conducted a narrative literature review using a structured search strategy of the MEDLINE database through the PubMed interface. All relevant evidence was summarised under five main sub-topics: (1) burden of childhood cancer in Egypt; (2) treatment approaches; (3) health outcomes; (4) costs and cost-effectiveness of treatment; and (5) barriers and facilitators to optimal childhood cancer care. We found high estimates of disease burden of childhood cancer in Egypt. Furthermore, childhood cancer treatment in Egypt is based on either implementing intensity-regulated protocols or adopting international protocols with or without adaptations to local contexts, leading to varying standards of care among the different treating centres. Limited data about the survival outcomes, costs and cost-effectiveness of treatment exist, although high-quality data from retrospective cohort studies were published from a large paediatric oncology centre (Children's Cancer Hospital Egypt-57357). As Egypt joins the WHO Global Initiative for Childhood Cancers as a focus country, it is prepared to move towards streamlining national efforts to implement a national childhood cancer plan to advance care, improve health outcomes and optimise resource use. Through these efforts, Egypt could become a beacon of hope and a role model to other low- and middle-income countries seeking to improve their childhood cancer care.

Aim: Video-assisted thoracoscopic surgery (VATS) has been widely used in the last decades. Nevertheless, the pros and cons of thoracoscopy vs. open surgery in pediatric oncology are still under debate. In literature, VATS has been applied for both diagnostic and ablative surgery to treat neurogenic tumors, thymic neoplasms, lung tumors and metastases, germ cell tumors, lymphoproliferative diseases, and other rare tumors. Recent reviews described excellent outcomes in pediatric oncology as well as in the treatment of adult lung cancer, with a significantly higher rate of mortality and complication in thoracotomy compared to VATS. We reviewed our experience on thoracoscopy in pediatric malignancy and compared it to the literature.Materials and Methods: This was a retrospective cohort-study of pediatric oncological patients who underwent VATS at our institution from 2007 to 2020, and a review of the recent literature on the topic.Results: A total of 43 procedures were performed on 38 oncological patients (18 males, 20 females). Median age was years 7.72 (0.35–18.6). Diagnosis: 10 neurogenic tumors, nine hematological diseases, five metastases, four lypoblastomas, three thymic pathologies, three germ cell tumors, two pleuropneumoblastomas, two myofibroblastic tumors, one myoepithelial carcinoma, one liposarcoma, and three suspected oncological mass. In three cases, a 3D model was elaborated to better plan the surgical approach. Diagnostic biopsies were 22 (51.1%), and ablative surgeries, 21 (48.9%). One neurogenic tumor was resected with the Da Vinci Robot. Median operative time was 120 min (30–420). A drain was left in place in 20 (46.5%) for a median of 4 days. Median length of hospitalization was 5 days (1–18). One case (2.3%) was converted (intraoperative bleeding). There were three post-operative complications (7.0%): one pneumonia, one pleural effusion, and one diaphragmatic paralysis (need for plication). Results were compared to recent literature, and morbidity and conversion rate were comparable to reviewed publications.Conclusion: VATS represents a valuable tool for diagnostic and therapeutic procedures in pediatric oncology. Nonetheless, it is a challenging technique that should be performed by expert surgeons on oncological and mini-invasive surgery. Three-dimensional reconstruction can optimize the pre-operative planning and guarantee a safer and more targeted treatment. Finally, the advent of robotics-assisted surgery represents a new challenge that may further implement the advantages of VATS.

Multi-modality therapy has resulted in improved survival for childhood malignancies. The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers provide practitioners with exposure- and risk-based recommendations for the surveillance and management of asymptomatic survivors who are at least 2years from completion of therapy. This review outlines the pathophysiology and risks for oral and dental late effects in pediatric cancer survivors and the rationale for oral and dental screening recommended by the Children's Oncology Group. An English literature search for oral and dental complications of childhood cancer treatment was undertaken via MEDLINE and encompassed January 1975 to January 2013. Proposed guideline content based on the literature review was approved by a multi-disciplinary panel of survivorship experts and scored according to a modified version of the National Comprehensive Cancer Network "Categories of Consensus" system. The Children's Oncology Group oral-dental panel selected 85 relevant citations. Childhood cancer therapy may impact tooth development, salivary function, craniofacial development, and temporomandibular joint function placing some childhood cancer survivors at an increased risk for poor oral and dental health. Additionally, head and neck radiation and hematopoietic stem cell transplantation increase the risk of subsequent malignant neoplasms in the oral cavity. Survivors require routine dental care to evaluate for potential side effects and initiate early treatment. Certain childhood cancer survivors are at an increased risk for poor oral and dental health. Early identification of oral and dental morbidity and early interventions can optimize health and quality of life.

Purpose: Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries. Precise diagnosis and successful treatment of pediatric cancer in low-resourced settings is often hindered by insufficient pathology infrastructure, including lack of laboratory platforms for molecular analysis. Given the high frequency of gene fusions in pediatric cancers, identifying such fusions would greatly aid cost-effective pediatric cancer diagnosis, risk stratification, and precision medicine in low-resourced settings. Methods: To allow for implementation of gene fusion detection at Global HOPE sites in Sub-Saharan Africa (SSA), methodologies were reviewed to consider minimal technical expertise required, the ability to utilize samples with sub-optimal RNA quality, and rapid turn-around-time. Literature review, clinical laboratory results, public databases, and large-scale genomic studies were used to obtain exact breakpoint sequence information for gene fusions associated with pediatric and adolescent cancers. Results: Two custom pediatric gene fusions panels were designed using the NanoString Elements technology. The hematologic malignancy panel was designed to detect 439 breakpoints for 223 non-IGH/TCR fusions reported in ALL, AML, lymphomas, and histiocytosis. The solid tumor panel was designed to detect 204 breakpoints for 436 fusions associated with pediatric sarcomas, brain tumors, and renal malignancies. Each panel was tested using 96 samples with known fusion status at Texas Children's Hospital to determine specificity, sensitivity, precision, and ease of workflow. Conclusions: The design, testing, and implementation of a rapid assay to detect gene fusions with diagnostic, prognostic, and therapeutic impact would be transformational in the care of pediatric cancer patients in low-resourced settings. The custom designed panels will allow for large-scale fusion detection in 2-3 days with only 15 minutes of technician time after RNA isolation. Additional steps are needed to identify and address any challenges upon initiation in SSA to fully realize the potential of such technology. Citation Format: Julie Gastier-Foster, Fredrick Lutwama, Joseph Lubega, Kevin Fisher, Dolores Lopez-Terrada, Angshumoy Roy, Nmazuo Ozuah, Jeremy Slone, Peter Wasswa, Carl Allen, David Poplack. Custom Gene Fusion Assays for the Rapid Diagnosis of Pediatric Cancers in Low-Resourced Settings [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 98.

The self-reported experiences of siblings who have a brother or sister diagnosed with childhood cancer: a systematic review protocol of qualitative evidence

Introduction: Recurrent somatic alterations associated with pediatric, childhood, and young adult cancers have not been as intensively studied as those associated with adult cancers. Consequently, whole-exome and transcriptome approaches are still being used to support discovery efforts. However, due to several initiatives aimed at profiling genomic alterations associated with childhood cancers, a set of recurrent somatic alterations has been defined. To accelerate research in this area, we have developed a novel targeted next-generation sequencing (NGS) assay to detect relevant somatic alterations previously reported in these cancer types. Methods: The assay was developed using Ion AmpliSeq targeted sequencing technology to cover the major gene variants associated with childhood cancers, including both solid tumor and hematologic cancer types. Over 200 gene targets were included on the basis of consultation with expert pediatric oncologists, literature review of the recent pediatric cancer genomic publications, as well as inclusion of relevant markers from adult cancers that are also observed in childhood cancers. Variant classes include mutations, copy number variations, gene fusions, and gene expression. Mutations in 130 genes, copy number variants in 28 genes, and over 1,400 distinct fusion isoforms in 88 fusion driver genes are analyzed. Variant calling algorithms for both DNA and RNA were optimized and combined into a single Ion Reporter workflow. Results: The assay generated an average read depth of >3,000 reads per DNA amplicon with high uniformity (>95%), when up to 7 sample DNA-RNA pairs were analyzed with the 540 chip of the Ion S5 sequencing instrument. Minimal allele frequency detected for key hotspots was 5%. Sensitive and reproducible detection of CNV and fusion variants associated with pediatric solid tumors (EWSR1-FL1 and KIAA1549-BRAF fusions, MYC and EGFR amplification) and hematologic cancers (ETV6-RUNX1 and PML-RARA fusions) was demonstrated in orthogonally profiled FFPE, blood, and bone marrow samples. Performance was robust across sample types. Similar results were observed with manual and automated library preparation. Conclusions: A novel NGS assay, designed specifically for pediatric, childhood, and young adult cancers, and capable of detecting relevant DNA and RNA alterations from the same sample, was developed and validated. The assay is useful for characterizing relevant alterations in a wide range of cancers, including childhood leukemias and lymphomas as well as solid tumors including neuroblastoma, rhabdomyosarcoma, retinoblastoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and brain and spinal cord tumors. A review of the analytical studies will be presented. Citation Format: Nickolay A. Khazanov, Chaitali Parikh, Habib Hamidi, Scott P. Myrand, Efren Ballesteros-Villagrana, Jingwei Ni, Paul D. Williams, Karen L. Clyde, Dinesh Cyanam, Armand Bankhead, III, Manimozhi Manivannan, Mark Tomilo, Susan Ewald, Jon K. Sherlock, Janice K. Au-Young, Jaclyn Biegel, Jonathan Buckley, Matthew Hiemenz, Dejerianne Ostrow, Alex Judkins, Xiaowu Gai, Tracy Busse, Alan Wayne, Deepa Bhojwani, Raca Gordana, Matthew Oberley, David Parham, Seth Sadis, Timothy Triche. Development of a next-generation sequencing (NGS) assay for pediatric, childhood, and young adult cancer research with comprehensive DNA and RNA variant detection [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B45.

In pediatric oncology, genetic and genomic tests are proposed throughout the care pathway for many reasons (e.g., cancer characterization, identification of the most appropriate treatment, patient selection for clinical trials, identification of tissue/organ donors, or risk of relapse prediction). Despite the many different approaches (somatic or germline testing, targeted gene or genome sequencing), the implicated individuals are confronted with situations that may intersect and that are interesting to compare. No study has identified and analyzed the available works on these new practices in pediatric oncology. The aim of this narrative literature review was to describe the ethical and psychological perspectives of children with cancer, parents, and healthcare professionals when genetic or genomic testing is proposed as part of the cancer management. Eighteen articles met the inclusion criteria and were comprehensively coded using MAXQDA. Their analysis showed that concerning the subjective implications of genetic and genomic testing, the areas of ambivalence (desire of treatment, desire for knowledge, uncertainty, and guilt) reported by patients and their parents seem to mirror the healthcare professionals' concerns. The ethical and psychological issues about predisposition testing, long discussed in the context of hereditary retinoblastoma and Li‐Fraumeni syndrome, represent a useful starting point for a wider discussion of a genetic and genomic testing pathway in pediatric oncology more broadly.

Nurses' perceptions of phase I clinical trials in pediatric oncology: a review of the literature.

The quality of adult end-of-life (EOL) cancer care has benefited from quality measures, but corresponding pediatric measures are lacking. Therefore, the authors used a validated expert panel method to recommend EOL quality measures for pediatric oncology. The authors used the modified Delphi method to assess potential quality measures. Panelists were selected on the basis of professional organization nominations and expert qualifications. Pediatric and adult oncology, pediatric palliative care, social work, nursing, and hospice were represented. The authors provided the panel with a literature review on 20 proposed measures derived from adult measures and bereaved family interviews. The panel first scored the importance of each measure on a 9-point scale and then discussed the measures via a conference call. The panel then rescored the measures. According to a priori standards, measures with median scores ≥ 7 with at least 7 of 9 experts ranking it as ≥4 were endorsed. The 16 endorsed measures included measures related to avoidance of medically intense care (eg, intensive care unit death and intubation in the last 14 days of life), death location (eg, death in the preferred location), hospital policies/programs (eg, the removal of visitor restrictions at EOL and the presence of a bereavement program), and supportive care services (eg, pediatric palliative care involvement and sibling needs assessment). Unendorsed measures included avoidance of chemotherapy at EOL and home death. Expert panel-endorsed quality measures have been developed for EOL care in pediatric oncology. The measures need validation with bereaved families and further refinement before they are ready for real-world application as a tool for standardizing EOL care in pediatric oncology. Quality measures for end-of-life care for children with cancer lag behind adult quality measures. Therefore, the authors have conducted an expert panel to develop an endorsed list of quality measures for end-of-life care for children with cancer. The 16 endorsed measures include measures related to avoidance of medically intense care (eg, intensive care unit death and intubation in the last 14 days of life), location of death (eg, death in the preferred location), hospital policies/programs (eg, the removal of visitor restrictions at the end of life and the presence of a bereavement program), and supportive care services (eg, pediatric palliative care involvement and sibling needs assessment).

Purpose of the reviewChildren and adolescents with cancer, along with their parents and other informal caregivers, often report using complementary and alternative medicine (CAM) during active oncology and hemato-oncology treatment. Some adopt an “alternative” approach to conventional medical care, which often entails the use of these practices without the knowledge of the treating pediatrician. In contrast, many others search for consultation provided by a pediatric integrative oncology (IO) practitioner working with the conventional medical team. IO seeks to provide evidence-based complementary medicine therapies, many of which have been shown to augment conventional supportive and palliative care, while ensuring the patient’s safety. The present narrative review examines the current state of and future direction for the IO setting of care.Recent findingsA large body of published clinical research supports the effectiveness of leading Pediatric IO modalities, while addressing potential safety-related concerns.SummaryDespite the growing amount of clinical research supporting the beneficial effects and implementation of Pediatric IO models of care, there is still a need for further studies in order to establish clinical guidelines in the treatment of children and adolescents with cancer. Such IO-directed guidelines will need to address both the effectiveness and the safety of the CAM modalities being used in pediatric oncology and hemato-oncology settings, promoting a better understanding among pediatric healthcare professionals and helping them understand the indications for referral to the IO treatment service.

Many healthcare systems overlook the importance of enrolling a child life specialist (CLS) on board, possibly due to the lack ofknowledge and awareness on the impact they might yield. This study highlights the essential contributions of CLS in improving pediatric oncology healthcare experiences. A thorough search of numerous databases was performed to identify English-language publications between 2005 and 2024, using a variety of study methods to establish a diverse evidence base. CLSs offer emotional support, educate patients and their families, implement distraction techniques, and collaborate with healthcare personnel to assist patients throughout their treatment journey. They also aid in providing adequate knowledge to patients and their families regarding medical procedures and treatment outcomes. Hence, CLSs play a vital role to play in the care of pediatric hematology oncology patients. A comprehensive interdisciplinary approach is needed to extend the role of CLS and ensure that every child receives the support and care they deserve.

Childhood cancer in Latin America: from detection to palliative care and survivorship

Cognitive impairment is frequent in pediatric cancer, and behavioral and psychological disturbances often also affect children who have survived cancer problems. Furthermore, pediatric tumors are also often associated with sleep disorders. The interrelationship between sleep disorders, neurodevelopmental disorders and pediatric cancer, however, is still largely unexplored. In this narrative review we approach this important aspect by first considering studies on pediatric cancer as a possible cause of neurodevelopmental disorders and then describing pediatric cancer occurring as a comorbid condition in children with neurodevelopmental disorders. Finally, we discuss the role of sleep disorders in children with cancer and neurodevelopmental disorders. Even if the specific literature approaching directly the topic of the role of sleep in the complex relationship between pediatric cancer and neurodevelopmental disorders was found to be scarce, the available evidence supports the idea that in-depth knowledge and correct management of sleep disorders can definitely improve the health and quality of life of children with cancer and of their families.

Paediatric Oncology System Integration Tool (POSIT) for the joint analysis of the performance of childhood cancer programs and health systems