Management Of Pediatric Cancer Research Articles

Comprehensive global collaboration in the care of 1182 pediatric oncology patients over 12 years: The Iraqi-Italian experience.

Iraq's health care system has gradually declined after several decades of wars, terrorism, and UN economic sanctions. The Oncology Unit at Children's Welfare Teaching Hospital (CWTH) in Baghdad was lacking basic facilities and support. To address this shortcoming, a humanitarian and educational partnership was established between CWTH and Sapienza University of Rome (SUR). We investigated the outcomes of 80 online and 16 onsite educational sessions and 142 teleconsultation sessions from 2006 to 2014. We also determined the outcomes of pathology reviews by SUR of 1216 tissue specimens submitted by CWTH from 2007 until 2019 for second opinions. The primary outcomes were discordance, concordance, and changes among clinical diagnoses and pathology review findings. The measures included the frequency of teleconsultation and tele-education sessions, the topics discussed in these sessions, and the number of pathology samples requiring second opinions. A total of 500 cases were discussed via teleconsultations during the study period. The median patient age was 7 years (range, 24 days to 16·4 years), and the cases comprised 79 benign tumors, 299 leukemias, 120 lymphomas, and 97 solid tumors. The teleconsultation sessions yielded 27 diagnostic changes, 123 confirmed diagnoses, and 13 equivocal impacts. The pathology reviews by SUR were concordant for 996 (81·9%) cases, discordant for 186 (15·3%), and inconclusive for 34 (2·8%). The major cause of discordance was inadequate immunohistochemical staining. The percentage of discordance markedly decreased over time (from 40% to 10%). The cause of the improvement is multifactorial: training of two CWTH pathologists at SUR, better immunohistochemical staining, and the ongoing clinical and pathologic telemedicine activities. The partnership yielded 12 publications, six posters, and three oral presentations by CWTH investigators. The exchange of knowledge and expertise across continental boundaries meaningfully improved the diagnoses and management of pediatric cancer at CWTH.

Short and Long-Term Toxicity in Pediatric Cancer Treatment: Central Nervous System Damage.

Simple SummaryThe purpose of this review is to describe central nervous system side effects in the treatment of pediatric cancer patients. Unfortunately, we must consider that the scarce data in the literature does not allow us to expand on some issues, especially those related to innovative immunotherapy. We have described the major neurotoxicities arising with the various types of treatment to help specialists who approach these treatments recognize them early, prevent them, and treat them promptly.Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely described. New therapies, such as biologic therapy and immunotherapy, are associated with better outcomes in pediatric patients but are also associated with central and peripheral nervous system side effects. Nevertheless, central nervous system (CNS) toxicity is a significant source of morbidity in the treatment of cancer patients. Some CNS complications appear during treatment while others present months or even years later. Radiation, traditional cytotoxic chemotherapy, and novel biologic and targeted therapies have all been recognized to cause CNS side effects; additionally, the risks of neurotoxicity can increase with combination therapy. Symptoms and complications can be varied such as edema, seizures, fatigue, psychiatric disorders, and venous thromboembolism, all of which can seriously influence the quality of life. Neurologic complications were seen in 33% of children with non-CNS solid malign tumors. The effects on the CNS are disabling and often permanent with limited treatments, thus it is important that clinicians recognize the effects of cancer therapy on the CNS. Knowledge of these conditions can help the practitioner be more vigilant for signs and symptoms of potential neurological complications during the management of pediatric cancers. As early detection and more effective anticancer therapies extend the survival of cancer patients, treatment-related CNS toxicity becomes increasingly vital. This review highlights major neurotoxicities due to pediatric cancer treatments and new therapeutic strategies; CNS primary tumors, the most frequent solid tumors in childhood, are excluded because of their intrinsic neurological morbidity.

État des lieux des maladies onco-hématologiques pédiatriques en Corse et organisation des soins

IntroductionIn France, the management of pediatric cancers is carried out in reference hospitals that can delegate care to local health centres (LHC), forming “care networks”. There is no LHC in Corsica, forcing children and their families to leave the island for all care in the reference centre. The aim of this study was to describe the situation in Corsica and to consider this organisation. MethodsThis is a descriptive preliminary study based on databases from the National Childhood Cancer Registry, “RHeOP” network and a patient questionnaire. We included over a period of 10 years all children with onco-hematological disease who resided in Corsica. ResultsThe incidence of pediatric cancers since 2005 ranged from 5 to 12 new cases per year. The hospital centre of Timone (Marseille) was the reference centre for 73% of patients, followed by Nice University Hospital for 14%. Almost all the parents interviewed (90%) were in favour of creating an LHC and all of them highlighted many difficulties that, according to them, could be improved by the presence of a LHC in Corsica (organisation of travel, delay and distance from home…). However, there currently appears to be a lack of training for medical and paramedical staff to provide quality second-line care. ConclusionThe rates of pediatric onco-hematological diseases in Corsica may warrant the creation of an LHC on the island. Additional cost studies on the feasibility of an LHC in Corsica are needed to optimise the care and quality of life of these children and their families.

Functional and anatomical imaging in pediatric oncology: which is best for which tumors.

Functional imaging techniques are playing an increasingly important role in the management of pediatric cancer. Technological advances have pushed the development of hybrid imaging techniques, including positron emission tomography (PET)/CT, PET/MR and single-photon emission computed tomography (SPECT)/CT. Together with an increasing need to identify surrogate biomarkers for response to novel therapies, the use of functional imaging techniques, which had been reserved primarily for lymphoma patients, is now being recognized as standard of care for the management of many other pediatric solid tumors. The purpose of this review is to summarize recent data describing the use of functional and metabolic imaging strategies for the staging and response assessment of common pediatric solid tumors, and to offer some guidance as to which techniques are most appropriate for which tumor types.

D’un service à un autre

Cet article s’intéresse au parcours de soin de l’enfant atteint de cancer dans le système de santé du Mali. La prise en charge de cette maladie implique, en plus du pédiatre oncologue, différents spécialistes (chirurgiens pédiatres, anatomopathologistes, radiologues) et sites hospitaliers. Il s’agit ici de mettre à jour les formes de collaboration entre ces différents acteurs autour des soins. À partir d’une enquête ethnographique, ce travail jette les bases d’une réflexion plus large sur l’organisation des soins en oncologie pédiatrique au Mali. L’étude a permis d’éclairer le parcours de soin de l’enfant atteint de cancer en mettant en évidence les facteurs déterminants de la collaboration. Elle a montré que la prise en charge des cancers de l’enfant est révélatrice des enjeux socioéconomiques, professionnels et géopolitiques.

Neurological Complications of Childhood Cancer

Though the treatment of pediatric cancers has come a long way, acute and chronic effects of cancer are still affecting the life of many children. These effects may be caused not only by the malignancy itself but also by the interventions used for the purpose of treatment. This article focuses primarily on the indirect effects of pediatric cancers and their treatment on the central and peripheral nervous system. Chemotherapy, radiation, and stem cell transplantation cause an immune-compromised state and place the patient at risk of infection, the leading cause of mortality in pediatric cancer. The underlying cancer and the treatments also cause neurovascular changes that may lead to neurological sequelae immediately or many years in the future. Chemotherapy and radiation have both immediate and long-term neurotoxic effects on the central and peripheral nervous system. Cancers may also trigger an immune response that damages nervous system components, leading to altered mental status, seizures, abnormal movements, and even psychosis. Knowledge of these effects can help the practitioner be more vigilant for the signs and symptoms of potential neurological complications during the management of pediatric cancers.

Abstract PR01: Precision in Pediatric Sequencing (PIPseq): Clinical implementation of genomic sequencing into pediatric hematology-oncology practice

Abstract Background: Molecular characterization of tumor and/or host has the potential to advance the management of pediatric cancer and high risk hematologic disease, but the clinical utility of integrating genomic profiling into standard clinical practice has been limited. The PIPseq Program at Columbia University has instituted prospective CLIA-compliant genomic sequencing for newly diagnosed, high risk, relapsed or refractory pediatric cancer patients and patients referred for bone marrow transplantation. Methods: Families are consented for clinical cancer whole-exome sequencing (cWES) or constitutional whole-exome sequencing (WES) with opt out options for return of results, exclusion of results from medical records, receipt of American College of Medical Genetics (ACMG) recommended secondary germline variants, and data/ sample use in research. Molecular characterization utilizes next generation cWES, WES, RNAseq (transcriptome), or targeted sequencing of select cancer genes. Clinical cancer reports include: known tumor type-specific actionable somatic mutations (Tier 1); somatic mutations actionable in other tumor types, in targetable pathways, or in well-established cancer genes (Tier 2); other somatic mutations in cancer genes (Tier 3); and somatic variants of uncertain significance (VUS; Tier 4). Reports for cWES testing also note translocations, significantly over expressed genes, segmental copy number variation, and germline variants. Institutional Review Board approval was obtained to conduct a retrospective review of results to date. Five categories were developed to assess clinical utility and describe significance: 1) diagnostic, 2) prognostic, 3) potentially actionable target, 4) other critical role in decision making, and 5) implications for health maintenance and genetic counseling. Results: Since January 2014, adequate tissue samples were available for 47 patients, including 31 (66%) with solid tumors and 16 (34%) with hematologic conditions. Testing included cWES (n=8), cWES with transcriptome (n=15), transcriptome only (n=1), targeted somatic panel (n=8), constitutional WES only (n=6), and multiple sequencing platforms (n=7). Normal tissue was obtained from buccal swab (n=8), blood (n=18), and unaffected tissue (n=1). Three families opted out of receiving secondary findings. Genomic aberrations were reported in 41/47 patients. Of the 127 cancer alterations found, 70 (55%) were in 15 patients with hematologic disease (median 2, range 1-11) and 57 (45%), were in 26 patients with solid tumors (median 1, range 1-6). Among the hematologic cases, alterations of known or potential clinical relevance were categorized as Tier 1 (n=0), Tier 2 (n=27), Tier 3 (n=2) mutation, or translocation (n=4); whereas in solid tumors these were categorized as Tier 1 (n=1), Tier 2 (n=14), Tier 3 (n=3) mutation, or translocation (n=9). Twenty-four Tier 4 somatic VUS were identified in hematologic specimens and 26 in solid tumor specimens. Genomic interrogation informed diagnosis in 10 patients (3 previously unknown); provided new prognostic information in 4; identified potentially actionable targets in 15; influenced clinical decision making regarding bone marrow transplant in 2; and revealed cancer or other disease predisposition in 7. Secondary germline ACMG findings in BRCA1 and PMS2 were found. Germline APC mutation was confirmed in one patient and germline VUS in SDHC was seen in another. Novel germline findings were also observed in RUNX1, MLL2 and DICER1. Overall, the PIPseq platform provided clinically impactful results in 30/47 cases (64%). Conclusions: Utilizing a CLIA-compliant prospective WES-based platform, more than half of selected patients derived clinically impactful information. The potential clinical utility of genomic sequencing in pediatric hematology-oncology has likely been underestimated. This abstract is also presented as Poster 50. Citation Format: Julia L. Glade Bender, Jennifer A. Oberg, Maria Luisa Sulis, Filamon Dela Cruz, Anthony N. Sireci, Susan J. Hsiao, Darrell J. Yamashiro, Carrie Koval, Wendy K. Chung, Stephen G. Emerson, Rebecca Zylber, Samantha Cano, Danielle P. Denney, Stuart Andrews, Peter L. Nagy, Mahesh M. Mansukhani, Andrew L. Kung. Precision in Pediatric Sequencing (PIPseq): Clinical implementation of genomic sequencing into pediatric hematology-oncology practice. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr PR01.

SU-E-T-221: Investigation of Lower Energy (< 6 MV) Photon Beams for Cancer Radiotherapy

Purpose: To study the potential applications of the lower energy (< 6MV) photon beams in the radiotherapeutic management of pediatric cancer and lung cancer patients. Methods: Photon beams of 2, 3, 4, 5 and 6MV were first simulated with EGS4/BEAM and then used for Monte-Carlo dose calculations. For four pediatric patients with abdominal and brain lesions, six 3D-conformal radiotherapy (3DCRT) plans were generated using single photon energy (2 to 6MV) or mixed energies (3 and 6MV). Furthermore, a virtual machine of 3 and 6MV was commissioned in a treatment planning system (TPS) based on Monte-Carlo simulated data. Three IMRT plans of a lung cancer patient were generated on this virtual machine. All plans were normalized to D95% of target dose for 6MV plan and then compared in terms of integral dose and OAR sparing. Results: For the four pediatric patients, the integral dose for the 2, 3, 4 and 5MV plans increased by 9%, 5%, 3.5%, 1.7%, respectively as compared to 6MV. Almost all OARs in the 2MV plan received more than 10% more doses than 6MV. Mixed energy 3DCRT plans were of the same quality as 6MV plans. For the lung IMRT plans, both the 3MV plan and the mixed beam plan showed better OAR sparing in comparison to 6MV plan. Specifically, the maximum and mean doses to the spinal cord in the mixed energy plan were lower by 21% and 16%, respectively. Conclusion: Single lower energy photon beam was found to be inferior to 6MV in the radiotherapy of pediatric patients and lung cancer patients when the integral doses and the doses to the OARs were considered. However, mixed energy plans combining low with high energy beams showed significant OAR sparing while maintaining the same PTV coverage. Investigation with more patient data is ongoing for further confirmation.

SIOP PODC Adapted Treatment Regimens for Hodgkin Lymphoma: A Framework for Management of Pediatric Cancer in Low- and Middle-income Countries

SIOP PODC Adapted Treatment Regimens for Hodgkin Lymphoma: A Framework for Management of Pediatric Cancer in Low- and Middle-income Countries

Clinical and Demographic Characteristics of Seasonal Influenza in Pediatric Patients With Cancer

Changes in oncology care and the diagnosis and management of influenza over the past several decades may have altered the epidemiology and outcomes of influenza in pediatric oncology patients. The clinical features and outcomes of 102 pediatric patients undergoing cancer therapy during 107 episodes of influenza between January 2002 and April 2009 were retrospectively ascertained. Median age at the time of influenza was 7.2 years (interquartile range: 3.8-11.2 years); 46% of patients were male. Nineteen patients (18%) were recipients of hematopoietic stem cell transplants. Patients' median absolute neutrophil and lymphocyte counts were 1300/μL (interquartile range: 500-2967/μL) and 360/μL (interquartile range: 180-836/μL), respectively. Twelve patients (11%) had coinfections with influenza and one or more other respiratory pathogens. Influenza prompted patients' hospitalization during 64% of episodes, and 75% received antiviral therapy. Complications occurred in 30% of infections and serious complications occurred in 7%. Three patients died, but no deaths were directly attributable to influenza. Most patients had delays in cancer therapy; the median delay was 5 days. Neutropenia, concurrent infection, increasing age and having received hematopoietic stem cell transplant increased the risk of serious complications. Advances in the management of pediatric cancer and influenza have not altered the epidemiology and outcome of influenza in oncology patients. Clinical features identify subgroups of patients with influenza who are at risk of poor outcomes and those with a good prognosis.

Anaphylaxis during the first course of high-dose methotrexate: a case report and literature review

Methotrexate (MTX) is widely used in the management of paediatric cancer with a generally favourable benefit/risk profile. We report an unusual adverse drug reaction with the first course of high-dose MTX in a paediatric patient and review the literature for similar cases. An 11-year-old boy with small-cell osteoblastic osteosarcoma in the lower limb experienced a case of life-threatening anaphylaxis during the first course of high-dose MTX. The adverse event occurred during the first course, likely due to an immune-mediated mechanism. We postulate that prior antineoplastic treatment might have contributed to the immune response to MTX. Given that this reaction has rarely been reported, we discuss the present case with a review of other similar cases. Further studies are needed to substantiate this 'signal alarm' for serious MTX-related hypersensitivity reactions.

Pharmacotherapy update in the management of paediatric cancer

Great advances in the treatment of childhood cancer have been made over the last 30 years because of developments in supportive care, the increasing use of advanced technology to detect and diagnose disease, developments in the understanding and relevance of cell biology and by the successful recruitment of children into nationally co-coordinated clinical trials. For some childhood malignancies where the survival rate is high, trials are ongoing to see if treatment can be stratified and directed according to patient risk, with those that fall into a favourable risk category potentially being cured with less treatment and therefore less short term and long term toxicity.

Baseline status of paediatric oncology care in ten low-income or mid-income countries receiving My Child Matters support: a descriptive study

Childhood-cancer survival is dismal in most low-income countries, but initiatives for treating paediatric cancer have substantially improved care in some of these countries. The My Child Matters programme was launched to fund projects aimed at controlling paediatric cancer in low-income and mid-income countries. We aimed to assess baseline status of paediatric cancer care in ten countries that were receiving support (Bangladesh, Egypt, Honduras, Morocco, the Philippines, Senegal, Tanzania, Ukraine, Venezuela, and Vietnam). Between Sept 5, 2005, and May 26, 2006, qualitative face-to-face interviews with clinicians, hospital managers, health officials, and other health-care professionals were done by a multidisciplinary public-health research company as a field survey. Estimates of expected numbers of patients with paediatric cancer from population-based data were used to project the number of current and future patients for comparison with survey-based data. 5-year survival was postulated on the basis of the findings of the interviews. Data from the field survey were statistically compared with demographic, health, and socioeconomic data from global health organisations. The main outcomes were to assess baseline status of paediatric cancer care in the countries and postulated 5-year survival. The baseline status of paediatric oncology care varied substantially between the surveyed countries. The number of patients reportedly receiving medical care (obtained from survey data) differed markedly from that predicted by population-based incidence data. Management of paediatric cancer and access to care were poor or deficient (ie, nonexistent, unavailable, or inconsistent access for most children with cancer) in seven of the ten countries surveyed, and accurate baseline data on incidence and outcome were very sparse. Postulated 5-year survival were: 5-10% in Bangladesh, the Philippines, Senegal, Tanzania, and Vietnam; 30% in Morocco; and 40-60% in Egypt, Honduras, Ukraine, and Venezuela. Postulated 5-year survival was directly proportional to several health indicators (per capita annual total health-care expenditure [Pearson's r(2)=0.760, p=0.001], per capita gross domestic product [r(2)=0.603, p=0.008], per capita gross national income [r(2)=0.572, p=0.011], number of physicians [r(2)=0.560, p=0.013] and nurses [r(2)=0.506, p=0.032] per 1000 population, and most significantly, annual government health-care expenditure per capita [r(2)=0.882, p<0.0001]). Detailed surveys can provide useful data for baseline assessment of the status of paediatric oncology, but cannot substitute for national cancer registration. Alliances between public, private, and international agencies might rapidly improve the outcome of children with cancer in these countries.

Management of pediatric cancer.

Only a few decades ago the prognosis for children with cancer was uniformly poor. Today approximately 50% are long-term survivors, potentially or actually cured. Two basic questions are addressed: What problems remain to be overcome? Does pediatric cancer provide a model for treatment of adults? Therapeutic accomplishments in hematologic and solid tumors of childhood are reviewed.