Childhood Cancer Research Articles

A retrospective study on the delay in three different timescales of CT simulation among patients with pediatric cancer in a tertiary hospital.

Patients with pediatric cancer receive radiotherapy to cure several types of cancer, requiring computed tomography simulation (CT sim) for precise treatment. However, there is currently no suitable framework to reduce the inherent delays in CT sim. The present study aimed to identify the underlying causes of the delays in CT sim regarding three different time periods (duration of patient admission to CT sim, diagnosis to treatment and CT sim to treatment) among patients with pediatric cancer. A total of 58 patients with pediatric cancer who received radiation therapy under anesthesia at King Abdulaziz University Hospital (Jeddah, Saudi Arabia) between 2016 and 2021 (60 months) were included in the current study. The underlying cause of delays regarding three separate time periods was determined according to patient type, diagnosis, therapy type and year of diagnosis. The CT sim processing time averaged 73 days and was received by patients after 28.96±28.5 days. The major delays in terms of frequency and length of duration between different time points such as patient admission and CT sim, interval between diagnosis and treatment, and duration between CT sim and therapy were (mean±SD) 37.13±29.9, 58.08±24.9 and 28.15±7.9 days, respectively. Machine availability, instability of the patients' medical condition and intensity-modulated radiation therapy (IMRT) caused 66.6% of the delays. In conclusion, outpatients may experience CT sim delays. Machine availability, conditions of patients and IMRT treatment were the major reasons to cause the delay in CT sim. Strategies should be employed to prevent CT sim delays and improve patient experience.

Opportunities for Interventional Radiology in Paediatric Oncology

Interventional oncology (IO) has emerged as a pivotal field within interventional radiology (IR), gaining prominence in the past three decades. It has transcended its initial role in cancer care, expanding beyond biopsies and vascular access to offer a spectrum of percutaneous and transarterial procedures, transforming into a curative and palliative discipline. However, implementing IO in children presents distinctive challenges. While the technical aspects of IO procedures mirror those in adults, paediatric cases require specialised considerations. Radiologists must possess an in-depth understanding of the paediatric disease, tailor imaging modalities to the case, discern unique risks, and interpret disease markers specific to children. Notably, paediatric tumour biopsies demand significantly larger tissue samples for genetic sequencing, staging, and prognostication. Paediatric IO also confronts procedural disparities. Tumours in children may be larger relative to body size, necessitating precise radioembolisation dose calculations. The proximity of critical structures in small bodies amplifies the risk of collateral damage. When performing percutaneous ablation and endovascular therapies, these challenges must also be faced so that radiologists can navigate these complex clinical and technical considerations to ensure safe and effective interventions, all while prioritising the well-being of their young patients. This review summarises the current role and future opportunities for IO in paediatric cancer.

An indocyanine green-based liquid biopsy test for circulating tumor cells for pediatric liver cancer.

Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy. For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery. We assessed ICG accumulation in cell lines using fluorescence microscopy and flow cytometry. For our CTC test, we developed a panel of liver tumor-specific markers, including ICG, Glypican-3, and DAPI, and tested it with cell lines and noncancer control blood samples. We then used this panel to analyze whole-blood samples for CTC burden with a cohort of 15 patients with hepatoblastoma and HCC and correlated with patient characteristics and outcomes. We showed that ICG accumulation is specific to liver cancer cells, compared to nonmalignant liver cells, non-liver solid tumor cells, and other nonmalignant cells, and can be used to identify liver tumor cells in a mixed population of cells. Experiments with the ICG/Glypican-3/DAPI panel showed that it specifically tagged malignant liver cells. Using patient samples, we found that CTC burden from sequential blood samples from the same patients mirrored the patients' responses to therapy. Our novel ICG-based liquid biopsy test for CTCs can be used to specifically detect and quantify CTCs in the blood of pediatric patients with liver cancer.

Radiation Dose-Volume-Response Relationships for Adverse Events in Childhood Cancer Survivors: Introduction to the Scientific Issues in PENTEC

At its very core, radiation oncology involves a trade-off between the benefits and risks of exposing tumors and normal tissue to relatively high doses of ionizing radiation. This trade-off is particularly critical in childhood cancer survivors (CCS), in whom both benefits and risks can be hugely consequential due to the long life expectancy if the primary cancer is controlled. Estimating the normal tissue-related risks of a specific radiation therapy plan in an individual patient relies on predictive mathematical modeling of empirical data on adverse events. The Pediatric Normal-Tissue Effects in the Clinic (PENTEC) collaborative network was formed to summarize and, when possible, to synthesize dose-volume-response relationships for a range of adverse events incident in CCS based on the literature. Normal-tissue clinical radiation biology in children is particularly challenging for many reasons: (1) Childhood malignancies are relatively uncommon-constituting approximately 1% of new incident cancers in the United States-and biologically heterogeneous, leading to many small series in the literature and large variability within and between series. This creates challenges in synthesizing data across series. (2) CCS are at an elevated risk for a range of adverse health events that are not specific to radiation therapy. Thus, excess relative or absolute risk compared with a reference population becomes the appropriate metric. (3) Various study designs and quantities to express risk are found in the literature, and these are summarized. (4) Adverse effects in CCS often occur 30, 50, or more years after therapy. This limits the information content of series with even very extended follow-up, and lifetime risk estimates are typically extrapolations that become dependent on the mathematical model used. (5) The long latent period means that retrospective dosimetry is required, as individual computed tomography-based radiation therapy plans gradually became available after 1980. (6) Many individual patient-level factors affect outcomes, including age at exposure, attained age, lifestyle exposures, health behaviors, other treatment modalities, dose, fractionation, and dose distribution. (7) Prospective databases with individual patient-level data and radiation dosimetry are being built and will facilitate advances in dose-volume-response modeling. We discuss these challenges and attempts to overcome them in the setting of PENTEC.

Hepatoblastoma: Experience of the paediatric haematology and oncology department, Hassan II university hospital of Fez.

Introduction: Hepatoblastoma is the most common malignant hepatic tumour in children. However, it is a rare disease, representing approximately 2% of childhood tumours. The treatment combines chemotherapy with surgical excision. The objective of this study was to describe the epidemiological, clinical, therapeutic and progressive aspects of hepatoblastoma treated in the paediatric haematology and oncology department at the University Hospital Hassan II of Fès. Patients and Methods: This was a descriptive and retrospective study conducted over a 11-year period. All patients aged 0 to 15 years who were admitted and treated for hepatoblastoma were included. Results: 24 patients met the study criteria, including 9 boys and 15 girls. The average age at diagnosis was 11.52 months ± 4.9. The most common reason for consultation was abdominal distension. Hepatomegaly was observed in 50% of cases. The average tumour size was 116 mm. At the time of diagnosis, one-third of patients had pulmonary metastases, and all patients were classified as high risk. Therapeutically, 19 patients (79.17%) received chemotherapy and 16 (66.67%) underwent surgery. On the evolutionary level, we observed a recovery without events in 10 (41.67%) patients. Conclusion: hepatoblastoma is a rare tumour, but remains the most common hepatic tumour in children. Despite progress in diagnostic and therapeutic means, the mortality rate is significant.

La gestione della piastrinopenia immune acuta in età pediatrica

This report summarizes the most relevant issues of the document that the Working Group on Coagulation Disorders of the Italian Association of Paediatric Haematology and Oncology (AIEOP) developed to gather shared expert opinions on the management of newly diagnosed idiopathic thrombocytopenic purpura (ITP), updating previous guidelines and providing recommendations to paediatricians. These recommendations are not intended to be standards or fixed rules but rather a tool to support paediatricians in the management of the diagnostic work-up and treatment of children with newly diagnosed ITP

Clinical Practice Guideline-Inconsistent Management of Fertility Preservation in Pediatric Cancer Patients in Community Settings: A Children's Oncology Group Study.

Background: The primary objective was to measure adherence to clinical practice guideline (CPG) recommendations for fertility preservation (FP) in pediatric cancer patients treated in National Cancer Institute Community Oncology Research Program (NCORP) sites. Secondary objectives were to describe factors such as site size associated with CPG-inconsistent care delivery and cryopreservation completion. Methods: This retrospective, multicenter study included patients 15 to 21 years old with a first cancer diagnosis from January 2014 through December 2015 who were previously enrolled to a Children's Oncology Group (COG) study and received care at a participating NCORP site. Patients were randomly selected from a list generated by the COG for chart review by participating sites. Primary outcome was care delivery that was inconsistent with a strong CPG recommendation on FP, namely discussion and offering of FP options before cancer treatment initiation, as adjudicated centrally by a panel. Results: A total of 129 patients from 25 sites were included. Among these, 48% (62/129) received CPG-inconsistent care. Most CPG-inconsistent care was due to lack of FP discussion documentation (93.5%, 58/62). Small site size, treatment at a pediatric (vs mixed adult/pediatric) site, and female sex were associated with higher odds of CPG-inconsistent care delivery. Conclusions: Newly diagnosed pediatric cancer patients often received CPG-inconsistent care for FP, with disproportionate gaps noted for females, and those treated at smaller or pediatric NCORP sites. The primary reason for CPG-inconsistent care is lack of FP discussion from clinicians. Opportunities to improve FP CPG implementation are highlighted.

Caring for children with cancer evacuated from Ukraine: The patients' perception.

Since the beginning of the war in Ukraine on February 24, 2022, many pediatric oncology centers welcomed evacuated patients. To better understanding the needs of patients and families arriving at two Lombardy hospitals in the period March to November 2022, an anonymous questionnaire investigated the families' backgrounds, feelings, and impressions about hospitality and care. Twenty questions investigated how patients had reached Italy, from whom they had received help (logistically/financially); the emotions regarding their status as war refugees; the knowledge, expectations, and opinions about Italy and Italians; the quality of medical care received and the relationships with the healthcare staff; lastly, suggestions to improve assistance. The questionnaires were completed by 19/32 patients/parents in November 2022 in two different pediatric-oncology centers. Most families had reached Italy (58%) and received medical care (95%) with the help of charities and the Italian Public Health Care System. A significant majority (69%) expressed satisfaction with the assistance provided. The Italian population demonstrated remarkable warmth, for 95% exhibiting friendliness and for 58% generosity. An improvement in their stay could be linked with the positive outcome of their children's cancer (15%), achieving complete family reunification (15%), the cessation of the conflict (10%), and the overcoming of language barriers (10%). Providing care for children from another country, not only grappling with the trauma of fleeing their homeland but also battling cancer, is an immense undertaking. It demands a diverse range of efforts and resources to ensure a positive and fulfilling outcome for this experience.

Experience in improving treatment outcomes for childhood acute lymphoblastic leukemia: real-world results for a province in China, 2011-2020.

The present study aimed to investigate the real-world results of childhood acute lymphoblastic leukemia (cALL) cases in Fujian, China. The clinical data of 1414 patients with newly diagnosed cALL in Fujian were retrospectively analyzed. Patients were treated according to the Chinese Children Leukemia Group 2008 protocol (CCLG-ALL 2008 group) or Chinese Children's Cancer Group 2015 protocol (CCCG-ALL 2015 group). Cumulative incidence of treatment abandonment (TA) at 5 years was 4.2% ± 0.6% and significantly associated with treatment period and risk stratification. The 5-OS and EFS were significantly higher in the CCCG-ALL 2015 group than in the CCLG-ALL 2008 group. Patients treated with CCCG-ALL 2015 from Fujian Medical Union Hospital had a significantly higher 4-year OS and EFS than did those from the other four hospitals. Real-world TA of cALL greatly decreased, and its long-term survival significantly increased in Fujian, which may be related to optimizing programs, multi-center collaboration, and improving treatment compliance.

Reducing ambulatory central line-associated bloodstream infections: A family-centered approach.

Ambulatory central line-associated bloodstream infections (CLABSIs) cause significant morbidity and mortality, especially in pediatric oncology. Few studies have had interventions directed toward caregivers managing central lines (CL) at home to reduce ambulatory CLABSI rates. We aimed to reduce and sustain our ambulatory CLABSI rate by 25% within 3years of the start of a quality improvement intervention. Plan-do-study-act cycles were implemented beginning April 2016. The main intervention was a family-centered CL care skill development curriculum for external CLs. Training began upon hospital CL insertion, followed by an ambulatory teach-back program to achieve home caregiver CL care independence. Other changes included: standardizing ambulatory nurse CL care practice (audits, a train the nurse trainer process, and workshops for independent home care agencies); developing aids for trainers and caregivers; providing supplies for clean surfaces; wide dissemination of the program; and minimizing opportunities of CLABSI (e.g., standardizing timing of CL removal). The outcome measure was the ambulatory CLABSI rate (excluding mucosal barrier injury laboratory-confirmed bloodstream infection), compared pre intervention (January 2015 to March 2016) to post intervention, including 2years of sustainability (April 2016 to June 2023), using statistical process control charts. We estimated the total number of CLABSI and associated healthcare charges prevented. The ambulatory CLABSI rate decreased by 52% from 0.25 to 0.12 per 1000 CL days post intervention, achieved within 27months; 117 CLABSI were prevented, with $4.2 million hospital charges and 702 hospital days avoided. Focusing efforts on home caregivers CL care may lead to reduction in pediatric oncology ambulatory CLABSI rates.

Peculiarities of clabsi in oncologic hospitals

Currently, healthcare-associated infections (HAIs) are one of the most dangerous complications for hospitalized patients. The economic damage caused by HCAI in the Russian Federation annually is about 15 billion rubles; in addition, HCAI occupy the tenth place among the causes of mortality of the population. Catheter-associated bloodstream infection holds the leading place in the structure of ISMP morbidity. The concept of CVC-AIC (catheter-associated bloodstream infections or CLABSI), in turn, is included in CAIC. Purpose of the study. To analyze the current literature data of domestic and foreign authors for the years 2012-2022 concerning CAIC in patients of oncologic hospitals with CVCs, including subcutaneous central venous port catheters. Material and Methods. A review of 38 literature sources for the last 10 years was performed, including current information on catheter-associated bloodstream infections, measures to prevent them, and modern treatment approaches. Results. The studies have shown that the combination of drug resistance in microorganisms and immunity reduction in cancer patients, which occurs against the background of chemotherapy, makes them a risk group for the development of CAICs and episodes of their recurrence. Ensuring epidemiological safety of bloodstream catheterization in such patients is an important step in the prevention of CAIC. This is one of the priority tasks of oncoepidemiology today. Conclusion. The leading role in the occurrence of catheter-associated bleeding plays the term of catheterization and the condition of the patient, his age, stage of cancer development and concomitant chronic diseases. One of the most vulnerable risk groups are cancer patients from hemoblastosis chemotherapy and bone marrow and hematopoietic stem cell transplantation units. This may be due to the use of immunosuppressant drugs to suppress graft rejection, which significantly reduce patients' immunity. According to the results of studies, infection with drug-resistant Gram-negative microorganisms, including multidrug-resistant ones, is prevalent in cancer patients with CAIC. When using povidone iodine, there is a tendency to decrease the incidence of CAIC, but the use of chlorhexidine alcohol solution showed better results. A direct correlation was observed between the use of surgically implanted intravascular devices for long-term function and a lower incidence of CAIC, particularly in pediatric oncology.

Diagnostic and treatment strategies for pediatric acute lymphoblastic leukemia in low- and middle-income countries.

The survival rate of children and adolescents with acute lymphoblastic leukemia (ALL), the most common pediatric cancer, has improved significantly in high-income countries (HICs), serving as an excellent example of how humans can overcome catastrophic diseases. However, the outcomes in children with ALL in low- and middle-income countries (LMICs), where approximately 80% of the global population live, are suboptimal because of limited access to diagnostic procedures, chemotherapeutic agents, supportive care, and financial assistance. Although the implementation of therapeutic strategies in resource-limited countries could theoretically follow the same path of improvement as modeled in HICs, intensification of chemotherapy may simply result in increased toxicities. With the advent of genetic diagnosis, molecular targeted therapy, and immunotherapy, the management of ALL is changing dramatically in HICs. Multidisciplinary collaborations between institutions in LMICs and HICs will provide access to strategies that are suitable for institutions in LMICs, enabling them to minimize toxicities while improving outcomes. This article summarizes important aspects of the diagnosis and treatment of pediatric ALL that were mostly developed in HICs but that can be realistically implemented by institutions in countries with limited resources through resource-adapted multidisciplinary collaborations.

Landscape of invasive fusariosis in pediatric cancer patients: Results of a multicenter observational study from Latin America

Abstract Invasive fusariosis (IF) is a life-threatening opportunistic infection that affects vulnerable hosts. We conducted a multicenter and multinational retrospective study to characterize the natural history and clinical management of IF in pediatric cancer patients. We selected patients under 18 years who were sequentially hospitalized in ten Latin American medical centers with a diagnosis of IF between 2002 and 2021. Data were collected using an electronic case report form complemented by a dictionary of terms. We assessed mortality at 30, 60, and 90 days. We collected data from 60 episodes of IF (median age of 9.8 years) that were mostly documented in hematologic malignancies (70%). Other risk conditions found were lymphopenia (80%), neutropenia (76.7%), and corticosteroid exposure (63.3%). IF was disseminated in 55.6% of patients. Skin lesions was present in 58.3% of our patients, followed by pulmonary involvement in 55%, sinusitis in 21.7%, bone/joint in 6.7% and one case each of endocarditis and brain abscess. Positive blood and skin biopsy cultures were detected in 60% and 48.3% of cases, respectively. Fusarium solani complex was the most commonly identified agent (66.6%). The majority of patients received monotherapy within the first 72h hours (71.6%), either with voriconazole or amphotericin B formulation. The mortality rates at 30, 60, and 90 days were 35%, 41.6% and 45%, respectively. Important factor impacting mortality appears to be disseminated disease. The high percentage of patients with fungal involvement in multiple organs and systems highlights the need for extensive work-up for additional sites of infection in severely immunocompromised children.

Genomic sequencing research in pediatric cancer care: Decision-making, attitudes, and perceived utility among adolescents and young adults and their parents.

Professional guidelines recommend engaging adolescents and young adults (AYAs) in medical decision-making (DM), including whether to undergo genomic sequencing (GS). We explored DM around GS and attitudes after return of GS results among a diverse group of AYAs with cancer and their parents. We surveyed AYAs with cancer (n=75) and their parents (n=52) six months after receiving GS results through the Texas KidsCanSeq Study. We analyzed AYAs' DM role in GS research enrollment and their satisfaction with that role. We compared AYAs' and parents' self-reported understanding of, attitudes toward, and perceived utility of the AYAs' GS results. Most AYAs reported equally sharing DM with their parents (55%) or leading DM (36%) about GS research. Compared to their cancer care DM role, 56% of AYAs reported the same level of involvement in GS research DM while 32% were more involved and 13% were less involved (p=0.011). AYAs were satisfied (99%) with their DM role regarding GS study participation. AYAs and parents had similar self-reported understanding of, attitudes toward, and perceived utility of the GS results. Our results support engaging AYAs in DM about GS research and provide insights into AYAs' DM preferences and positive attitudes toward GS.

Prognosis of Second Primary Malignancies in Pediatric Acute Lymphoblastic Leukemia Survivors: A Multicenter Study by the Turkish Pediatric Hematology Society.

The improved survival rates of childhood cancers raise the long-term risk of second primary malignancy (SPM) in childhood and adolescent cancer survivors. The intensity of the treatment protocol used, the use of some groups of chemotherapeutics, and radiotherapy were found to be risk factors for the development of second primary malignancies (SPMs). Forty-one patients who developed acute myelocytic leukemia or any solid organ cancer within 25 years of follow-up, after completion of pediatric acute lymphoblastic leukemia (ALL) treatment, were included in the study. The mean duration of initial ALL diagnosis to SPM was 9.3 ± 6.1 years. The 3 most common SPMs were acute myelocytic leukemia, glial tumors, and thyroid cancer. Thirteen (81%) of 16 patients exposed to cranial irradiation had cancer related to the radiation field. In total 13/41 (32%) patients died, and the 5-year overall survival rate was 70 ± 8%. Patients older than 5 years old at ALL diagnosis had significantly worse overall survival than cases younger than 5 years old. In conclusion, children and adolescents who survive ALL have an increased risk of developing SPM compared with healthy populations, and physicians following these patients should screen for SPMs at regular intervals.

ZMIZ1::ABL1 Fusion: An Uncommon Molecular Event With Clinical Implications in Pediatric Cancer.

Pediatric B-cell acute lymphoblastic leukemia is genetically and phenotypically heterogeneous, with a genetic landscape including chromosomal translocations that disrupt ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1). To characterize an uncommon chromosomal translocation in acute leukemia. Genetic testing, including karyotype and fluorescence in situ hybridization (FISH) analysis, was used to determine the underlying genetic aberration driving the disorder and to guide disease classification and risk stratification. More-detailed testing using RNA sequencing was performed, based on the results from these assays. Three-dimensional molecular modeling was used to visualize the impact of aberrant fused transcripts identified by transcriptome profiling. Karyotype analysis of the bone marrow demonstrated a complex karyotype with, most notably, a t(9;10)(q34.1;q22) translocation. ABL1 break-apart probe FISH findings supported ABL1 disruption. Bone marrow transcriptome analysis revealed mutant ZMIZ1::ABL1 (ZMIZ1, zinc finger MIZ-type containing 1) fusion transcripts as a consequence of t(9;10)(q34.1;q22). Three-dimensional modeling of the mutant ZMIZ1::ABL1 fusion protein confirmed an altered ABL1 protein structure compared to that of the wild type, suggesting a constitutively active conformation. The t(9;10) translocation resulting in ZMIZ1::ABL1 fusion transcripts is an uncommon form of BCR::ABL1-like (BCR, BCR activator of RhoGEF and GTPase) acute lymphoblastic leukemia. Although the karyotype was complex, identifying the t(9;10)(q34.1;q22) translocation, ABL1 disruption, and ZMIZ1::ABL1 transcript enabled effective ABL1-targeted treatment. Our data support the use of tyrosine kinase inhibitors to treat ZMIZ1::ABL1-derived B-cell acute lymphoblastic leukemia.

Whole genome and transcriptome integrated analyses guide clinical care of pediatric poor prognosis cancers

The role for routine whole genome and transcriptome analysis (WGTA) for poor prognosis pediatric cancers remains undetermined. Here, we characterize somatic mutations, structural rearrangements, copy number variants, gene expression, immuno-profiles and germline cancer predisposition variants in children and adolescents with relapsed, refractory or poor prognosis malignancies who underwent somatic WGTA and matched germline sequencing. Seventy-nine participants with a median age at enrollment of 8.8 y (range 6 months to 21.2 y) are included. Germline pathogenic/likely pathogenic variants are identified in 12% of participants, of which 60% were not known prior. Therapeutically actionable variants are identified by targeted gene report and whole genome in 32% and 62% of participants, respectively, and increase to 96% after integrating transcriptome analyses. Thirty-two molecularly informed therapies are pursued in 28 participants with 54% achieving a clinical benefit rate; objective response or stable disease ≥6 months. Integrated WGTA identifies therapeutically actionable variants in almost all tumors and are directly translatable to clinical care of children with poor prognosis cancers.

Access to legacy-oriented interventions at end of life for pediatric oncology patients: A decedent cohort review.

Legacy-oriented interventions have the potential to offer pediatric oncology patients and families comfort at end of life and during bereavement. Certified child life specialists often provide these services, and presently little is known about whether disparities exist in the provision of legacy-oriented interventions. In this retrospective decedent cohort study, we examined demographic and clinical characteristics from a sample of 678 pediatric oncology patients who died between 2015 and 2019. Bivariate analysis assessed differences between patients who received any versus no legacy-oriented intervention. Uni- and multivariable logistic regression models assessed associations of baseline characteristics and likelihood of receiving legacy-oriented intervention. Further multivariable analysis explored joint effects of significant variables identified in the univariable analysis. Fifty-two percent of patients received a legacy-oriented intervention. Older adolescents (≥13years) were less likely (odds ratio [OR]: 1.73, p=.007) to receive legacy-oriented interventions than younger ones. Patients with home/hospice deaths were also less likely (OR: 19.98, p<.001) to receive interventions compared to patients who passed away at SJCRH locations. Hispanic patients (OR: 1.53, p=.038) and those in palliative care (OR: 10.51, p<.001) were more likely to receive interventions. No significant race association was noted. All children and adolescents with cancer deserve quality care at end of life, including access to legacy-oriented interventions, yet nearly half of patients in this cohort did not receive these services. By identifying demographic and clinical characteristics associated with decreased odds of receiving legacy-oriented interventions, healthcare professionals can modify end-of-life care processes to improve access. Introducing legacy-oriented interventions early and increasing exposure in community spaces may enhance access to legacy-oriented interventions for pediatric oncology patients.

Clinical features and outcomes of young patients with low-grade non-rhabdomyosarcoma soft tissue sarcomas treated with a risk-based strategy: A report from Children's Oncology Group study ARST0332.

In retrospective analyses, the Pediatric Oncology Group [POG) and the Federation National des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade predict outcome in pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), but prospective data on grading, clinical features, and outcomes of low-grade NRSTS are limited. We analyzed patients less than 30years of age enrolled on Children's Oncology Group (COG) study ARST0332 (NCT00346164) with POG grade 1 or 2 NRSTS. Low-risk patients were treated with surgery alone. Intermediate-/high-risk patients received ifosfamide/doxorubicin and radiotherapy, with definitive resection either before or after 12weeks of chemoradiotherapy. Estimated 5-year event-free and overall survival were 90% and 100% low risk (n=80), 55% and 78% intermediate risk (n=15), and 25% and 25% high risk (n=4). In low-risk patients, only local recurrence was seen in 10%; none with margins greater than 1mm recurred locally. Sixteen of 17 intermediate-/high-risk patients who completed neoadjuvant chemoradiotherapy underwent gross total tumor resection, 80% with negative margins. Intermediate-/high-risk group events included one local and seven metastatic recurrences. Had the FNCLCC grading system been used to direct treatment, 29% of low-risk (surgery alone) patients would have received radiotherapy ± chemotherapy. Most low-risk patients with completely resected POG low-grade NRSTS are successfully treated with surgery alone, and surgical margins greater than 1mm may be sufficient to prevent local recurrence. Patients with intermediate- and high-risk low-grade NRSTS have outcomes similar to patients with high-grade histology, and require more effective therapies. Use of the current FNCLCC grading system may result in overtreatment of low-risk NRSTS curable with surgery alone.

Protocol for the 'Supporting Young Cancer Survivors who Smoke' study (PRISM): Informing the development of a smoking cessation intervention for childhood, adolescent and young adult cancer survivors in England.

Childhood, adolescent and young adult (CAYA) cancer survivors are vulnerable to adverse late-effects. For CAYA cancer survivors, tobacco smoking is the most important preventable cause of ill-health and early death. Yet, effective strategies to support smoking cessation in this group are lacking. The PRISM study aims to undertake multi-method formative research to explore the need for, and if appropriate, inform the future development of an evidence-based and theory-informed tobacco smoking cessation intervention for CAYA cancer survivors. PRISM involves three phases of: 1) an environmental scan using multiple strategies to identify and examine a) smoking cessation interventions for CAYA cancer survivors that are published in the international literature and b) current smoking cessation services in England that may be available to, or tailorable to, CAYA cancer survivors; 2) a qualitative study involving semi-structured interviews with CAYA cancer survivors (aged 16-29 years and who are current or recent ex-smokers and/or current vapers) to explore their views and experiences of smoking, smoking cessation and vaping; and 3) stakeholder workshops with survivors, healthcare professionals and other stakeholders to consider the potential for a smoking cessation intervention for CAYA cancer survivors and what such an intervention would need to target and change. Findings will be disseminated to patient groups, healthcare professionals and researchers, through conference presentations, journal papers, plain English summaries and social media. PRISM will explore current delivery of, perceived need for, and barriers and facilitators to, smoking cessation advice and support to CAYA cancer survivors from the perspective of both survivors and healthcare professionals. A key strength of PRISM is the user involvement throughout the study and the additional exploration of survivors' views on vaping, a behaviour which often co-occurs with smoking. PRISM is the first step in the development of a person-centred, evidence- and theory-based smoking cessation intervention for CAYA cancer survivors who smoke, which if effective, will reduce morbidity and mortality in the CAYA cancer survivor population.