Background Targeted therapies and immunotherapies are increasingly used in pediatric oncology; however, many innovative agents are prescribed off-label or through compassionate use programs due to limited pediatric approvals and restricted access to clinical trials. Real-world data on these access pathways remain limited. Methods This retrospective multicenter observational study was promoted by the Italian Association of Pediatric Hematology and Oncology (AIEOP) Working Group on New Drugs. Prescriptions made between 2018 and 2023 for patients aged ≤25 years receiving targeted therapies or immunotherapies through off-label or compassionate use were collected from 19 AIEOP pediatric oncology centers, covering approximately 80% of national pediatric cancer cases. Variables included diagnosis, indication, access modality, regulatory status, molecular rationale, treatment duration, discontinuation. Results A total of 562 prescriptions involving 70 drugs were collected. Off-label prescriptions accounted for 77% (n=431) and compassionate use for 23% (n=131). Treatments were mainly for relapsed (46%) or refractory (35%) disease. The most frequent diagnoses were acute lymphoblastic leukemia (n=119, 21%) and gliomas (n=76, 14%). Molecular alterations supporting treatment selection were reported in a subset, including FLT3, BCR::ABL1, BRAF, and MAPK alterations. Median treatment duration was 133 days (interquartile range (IQR), 42–399). Discontinuation was mainly due to disease progression (n=216, 47%), completion of planned therapy (n=175, 38%), or toxicity (n=33, 7%). Lack of clinical trials was the main driver for access (n=438, 78%). Median authorization time was 9.5 days (IQR, 5–15)., with bureaucratic complexity as the main barrier. Conclusions Off-label and compassionate use represented a common access pathway for innovative therapies in Italian pediatric oncology, particularly in relapsed or refractory disease. These findings highlight persistent challenges in pediatric drug development, clinical trial availability, and regulatory pathways.
Background In children with neuroblastoma, imaging plays a central role in staging, treatment planning and response assessment. Standardized imaging procedures, including cross-sectional imaging and MIBG scintigraphy are essential for consistency across international trials. However, the increasing use of PET tracers and variable access to imaging technologies may challenge harmonization. This study evaluated the availability, use, and challenges of neuroblastoma imaging modalities across participating centers. Methods A web-based survey was distributed to SIOPEN national delegates between August and December 2025. The survey covered respondent characteristics, sedation availability, MIBG scintigraphy with SPECT/CT and PET imaging practices, anatomical imaging modalities, and perceived challenges. Descriptive analyses were performed. Results In total, 151 responses representing 89 unique centers from 29 countries were analysed. Sedation for imaging was available in 98% of centers. In most centers MRI can be used for cross-sectional imaging of the primary tumor (73.1%). Most (74.2%) performed both planar and SPECT/CT MIBG scans, with 64.0% reporting use of the standardized SIOPEN scoring system. PET imaging was available in 84.3% of centers, most commonly using [¹⁸F]FDG (95.9%); [¹⁸F]MFBG was available in eight centers. Major challenges included limited tracer access (56.1%) and restricted cyclotron availability (25.8%). Conclusions This study reveals wide access to nuclear imaging modalities, including PET imaging, but with substantial heterogeneity in neuroblastoma imaging practices, tracer availability and image interpretation across responding centers. These findings highlight the need for broader implementation of standardized imaging criteria. While informative, these results should be interpreted with caution given the potential biases inherent to questionnaire-based studies.
Objectives This explorative study examined perceived and received social support among grandparents of children diagnosed with cancer, factors associated with support, and unmet support needs during the first two years following diagnosis. Methods Grandparents were recruited across eight pediatric oncology clinics and completed questionnaires at 3 (T1), 6 (T2), 12 (T3), and 24 months (T4) after diagnosis. The Multidimensional Scale of Perceived Social Support (MSPSS) was administered at T1 and T3 to assess perceived support (overall scale and three subscales: Family, Friends, Significant Others). Open-ended items on received social support and unmet support needs were included at all timepoints. Quantitative data were analyzed using linear mixed models, and qualitative data using content analysis. Results A total of 41 grandparents participated (M=68 years; 60% female). MSPSS scores indicated high support at T1 and T3. Grandfathers reported less overall support than grandmothers (b=-0.43; 95%CI [−0.89, 0.04]; p = 0.071) and less support from Significant Others (b=−0.65; 95%CI [−1.22, −0.08]; p = 0.024). Grandparents living in a different locality from their grandchild reported higher Family support than those living nearby (b=0.68; 95%CI [0.10, 1.25]; p = 0.020). Those in partnerships reported more support of Significant Others than singles (b=-0.98; 95%CI [-1.28, 0.13]; p = 0.023); this support was higher when the grandchild was younger (b=−0.06; 95%CI [−0.12, −0.002]; p = 0.042). Family was the main source of support received, while additional professional help was desired. Conclusion The sources of social support varied during the first two years following a grandchild’s cancer diagnosis. Despite strong family support, most grandparents expressed a need for psychological support.
In paediatric oncology clinical trials, health-related quality of life data through patient-reported outcomes (PROs) provide valuable data on symptoms, functioning and quality of life during treatment. PROs can provide evidence on treatment tolerability and efficacy, facilitate regulatory review and cost-benefit profiling, and inform clinical decision making, treatment selection and post-treatment follow-up. Despite this, PROs are rarely implemented in paediatric oncology trials. This scoping review aimed to identify and describe the relevant methodological guidance available to support PRO implementation in paediatric oncology research. This included resources relating to adults who are less able to self-report (such as those with impaired capacity) where methodologies may apply to a paediatric population. Systematic searches were performed in Medline, Embase, PsycInfo and Web of Science from 2005 to 4th November 2024, alongside grey literature and citation hand-searching. Screening was performed independently by pairs of reviewers and data were summarised narratively. Twenty-nine articles were included. Eight articles (28%) provided a full methodological framework, whereas 21 articles (72%) provided a partial framework, addressing one or more aspects of PRO implementation. Fifteen articles (52%) specifically addressed a paediatric population; five (17%) concerned adults who were less able to self-report and nine (31%) were conducted in the general population with applicability to the paediatric oncology setting. Six methodological themes were identified: stakeholder involvement, measure selection, use of proxies, data collection methods, data management, and statistical analysis. Findings are presented and summarised. There is a need for a consensus-based approach to support PRO implementation in paediatric cancer clinical trials.
Background Adolescents and young adults (AYAs, aged 15–39 years) face cancer during a life phase marked by physical, psychological, and social development, in which body image plays a significant role. We aimed to: (1) describe body image issues among AYA cancer patients and survivors by synthesising quantitative and qualitative evidence across intrapersonal, interpersonal and societal levels, and (2) identify the negative, positive, and mixed or no/unclear impact of body image outcomes of AYA cancer patients and survivors. Methods This review is part of STRONG-AYA and builds on prior research to develop a core outcome set for young cancer patients. Titles and abstracts were screened, methodological quality was assessed, and data were extracted by three independent researchers. The results were summarised narratively and thematically analysed. Results In total, 716 articles were screened, of which 62 were included. Findings highlight the complexity of body image issues in AYAs with cancer. Quantitative studies showed mixed results. Some reported poorer body image compared to healthy peers, while others found no difference. Qualitative studies revealed both negative comparisons (e.g., to pre-cancer self or societal ideals) and positive adjustments (e.g., pride, acceptance). As studies often reported multiple types of psychosocial outcomes, the total frequency exceeds the number of included papers (N = 62). Negative impacts on body image were most common (n = 57), followed by positive (n = 39), mixed (n = 23), and unclear or no impacts (n = 15). Conclusion Our study highlights that body image issues in AYAs with cancer are deeply shaped by comparisons to their pre-cancer selves, peers, and societal ideals. These comparisons and the impact of body image can be both distressing and supportive.
Background Few population-based studies have examined the influence of socioeconomic status (SES) on survival from childhood cancers, especially neuroblastic tumours (NT). This study investigated a possible association between SES and survival from NT in children diagnosed in northern England. Methods All 102 cases of NT, aged 0–14 years and diagnosed 1993–2014, were extracted from the population-based Northern Region Young Persons’ Malignant Disease Registry. Kaplan-Meier estimation and Cox regression were used to analyse survival in relation to paternal SES and clinical characteristics. Results Survival differed between age-groups, with infants having the least risk of death. Increased risk of death was seen for children diagnosed with International Neuroblastoma Staging System stage 4 neuroblastoma compared to stage 1, 2, 3 and 4S (HR=6.8; 95% CI: 2.8–16.6), MYCN amplified versus non-amplified (Hazard Ratio (HR)= 3.4; 95% CI: 1.7–6.8) and high risk versus low and intermediate risk cases (HR=9.1; 95% CI: 3.2–25.9). There were no differences between paternal SES, gender, site of primary tumour, or diagnostic period. Conclusions This study did not find a socio-economic effect on survival from NT diagnosed in northern England. This contrasts with other studies of NT elsewhere in the world where socioeconomic inequality has been shown to affect outcome.
Background Bone marrow aspiration (BMA) is performed to determine bone marrow involvement (BMI) in paediatric non-Hodgkin lymphoma (NHL). In adult patients, non-invasive imaging with positron emission tomography ([18F]FDG PET-CT) is used instead of BMA. This is not the case in paediatric NHL. The study’s primary objective is to compare the agreement of imaging ([18F]FDG PET-CT and WB-DW-MRI) versus BMA in paediatric NHL for BMI assessment, while also exploring the impact on tumour staging and subtype-specific differences. Procedure This single-center retrospective review included children diagnosed with NHL between 2018-2022, 0-18 years, received a BMA, an [18F]FDG PET-CT and/or WB-DW-MRI before treatment. Data analysis included calculating sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy. BMA was considered the gold standard. Results In 79 patients (mean age 10 years, 76% male), combined [18F]FDG PET-CT and WB-DW-MRI was concordant with BMA in 52 patients (66%). Combined imaging techniques demonstrated high SN, SP, NPV, and accuracy (respectively 80%, 73%, 97%, and 74%) for BMI. Imaging-based approach led to stage IV reclassification in 17 patients. Accuracy in assessing BMI varied across lymphoma subtypes. Conclusions Compared to BMA, [18F]FDG PET-CT, and WB-DW-MRI were highly accurate in determining BMI in paediatric NHL with notable high NPVs. These imaging techniques offer viable alternatives for BMA in the evaluation of BMI.
Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous malignancies with different histopathological characteristics. Distinct molecular findings help to classify NRSTS into subtypes. Further new molecular subtypes give insight into the heterogeneity of these rare tumours. Over the past 25 years, five large international prospective clinical trials have been conducted to improve prognosis for pediatric, adolescent, and young adult patients (< 25 years) with NRSTS and rare soft tissue neoplasms. The overall cure rate is around 70% but varies dramatically between the different entities. New treatment approaches are still needed for some histotypes and for metastatic tumors to improve outcome.The European paediatric soft tissue sarcoma study Group (EpSSG) proposes guidelines developed by an European NRSTS group supported by the European Reference Network on Paediatric Cancer (ERN PaedCan). This consensus summarizes the standard of care, diagnostic work up, multimodal treatment and surveillance recommendations for pediatric, adolescent, and young adult patients with NRSTS and rare soft tissue neoplasms, according to the Consensus Conference Standard Operating Procedure methodology. The unique features of selected histotypes are discussed.
Background Wilm’s tumor is a malignant renal neoplasm that primarily affects children and accounts for approximately 80–90% of pediatric renal cancers. The standard treatment protocols, NWTS-5 and SIOP-2001, report five-year survival rates greater than 90%. Objective This study evaluated the effectiveness and safety of a chemotherapy-first approach followed by surgical resection in treating children with stage II-IV Wilm’s tumors. Methods A prospective cohort study was conducted on 64 pediatric patients treated at Children's Hospital No. 2, Ho Chi Minh City, from April 2013 to June 2019. Tumor volume was calculated using the ellipsoid formula, and radiologic response was assessed by RECIST 1.1. Kaplan estimated event-free survival (EFS), and predictors were evaluated by Cox regression. Results The median age at diagnosis was 23.8 months, with a male-to-female ratio of 1.2:1. Children with imaging-defined risk features at presentation were II-type (78.1%), III-type (18.8%), and IV-type (3.1%). Preoperative chemotherapy significantly increased tumor necrosis from 4.7% to 100% and reduced tumor volume from 487.9 cm³ to 206.8 cm³ (p < 0.001). Preoperative chemotherapy resulted in significant tumor necrosis and reduced tumor volume. Surgical complications were minimal, with an incidence of tumor rupture during surgery of 1.6%. Chemotherapy-related toxicities were manageable, with leukopenia (26.6%) and mucositis (35.9%) being the most common. The 4-year event-free survival (EFS) rate was 92.2%, with a recurrence rate of 7.8%. Factors influencing outcomes included tumor stage, vascular invasion, and the histological response to chemotherapy. Conclusion The chemotherapy-surgery strategy showed promising results, with high survival rates and low recurrence rates. This approach is recommended for pediatric oncology centers, especially in resource-limited settings.
A systematic literature review was conducted to evaluate the clinical effectiveness and safety of treatments for paediatric patients, up to the age of 18 years, with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (NHL), including Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) but excluding primary mediastinal B-cell lymphoma (PMBCL). A search of Medline, Embase and the Web of Science databases was conducted to identify any prospective study or case series published from January 1st 2016–31 st December 2024. On-going clinical trial databases were also searched. Articles were included if they evaluated any single agent or combination of treatments in paediatric patients with relapsed/refractory NHL who had received at least one prior line of therapy. Four studies were identified, only one of which was a randomised controlled trial (RCT). No treatment appeared in more than one trial and therefore results from each trial could not be quantitatively pooled by meta-analysis. Differences in study design, baseline characteristics and inclusion and exclusion criteria made comparison of results difficult. There is a noticeable lack of RCTs evaluating treatments for paediatric patients with relapsed/refractory mature B-cell NHL making meaningful comparisons of effectiveness across trials rather difficult. This trend continues as all except one of the 9 on-going trials in this area are single arm studies. RCTs are required to enable better evaluation of the optimal treatment regimen for this group of patients.
Background Long-term survivors of non-central nervous system (CNS) pediatric cancers may experience neuropsychological deficits, but little is known about earlier post-diagnosis functioning. Risk factors for poorer neuropsychological outcomes may include CNS complications and peripheral neuropathy. This study describes neuropsychological functioning over time after non-CNS cancer diagnosis and explores the role of CNS complications and peripheral neuropathy on neuropsychological outcomes. Methods This prospective longitudinal study included 117 patients with non-CNS cancer aged 6-18 years. They underwent neuropsychological testing 3-6 months after diagnosis and approximately 2 years later. Neuropsychological performance at the final timepoint was compared to the normal population and to patients’ own estimated IQ using t-tests. Linear mixed models and logistic regression were performed to study change or decline over time, and associations with CNS complications and peripheral neuropathy. Results Attention, verbal fluency and reading fluency scores were below participants’ estimated IQ (p<0.05). Performance over time was stable on most outcomes, although variability was high. Patients who experienced a CNS complication had lower memory scores at 3-6 months, but scores normalized 2 years later (p=0.020). Patients treated with high-risk chemotherapy remained stable on impulsivity/inattentiveness, while patients treated without high-risk chemotherapy improved over time (p=0.010). Younger age at diagnosis was associated with declining neuropsychological scores (p=0.011). Conclusion On average, neuropsychological performance remains stable within the first 2-3 years after non-CNS cancer diagnosis. CNS complications, high-risk chemotherapy, and younger age at diagnosis may be risk factors for poorer outcome. High variability among patients stresses the importance of individual follow-up.
Introduction: Permanent radiation-induced alopecia (RIA) is a distressing late effect of pediatric craniospinal irradiation (CSI). Recent studies in adults suggest a dose-dependent relationship with identifiable thresholds, but pediatric-specific scalp segmentation methods and photon-based constraints remain poorly defined. The Pediatric Atlas-Based Scalp Segmentation Technique (PAST) and the Hair loss Outcome Prediction and Evaluation (HOPE) projects aim to address these gaps. Materials and Methods: A monocentric retrospective study included 48 pediatric patients treated with CSI between 2006 and 2021. An atlas-based automated contouring protocol was developed in RayStation v12A-SP1 using 52 CT datasets and validated on eight test cases. Two scalp volumes were defined: whole scalp (WS) and posterior cranial fossa scalp (PCFS). Permanent alopecia was graded according to CTCAE v4.0. Predictors were analyzed through univariate statistics and ROC/AUC analyses using DVH parameters recalculated with standardized atlas-based contours. Results: The PAST atlas achieved a 3D Dice Similarity Coefficient of 0.76 +/- 0.05 for WS and 0.77 +/- 0.04 for PCFS, with approximately 80% operator time reduction. Permanent RIA occurred in 22/48 patients (45.8%). Significant predictors were high-dose thiotepa (p = 0.010) and twice-daily fractionation (p = 0.004), while endocrinological deficits were not associated with alopecia. Optimal dosimetric thresholds were: D0.03ccWS > 55.2 Gy (AUC 0.76, p = 0.002) and PCFS D50% > 32.8 Gy (AUC 0.74, p = 0.005). D2% WS cut-off was 40.62 Gy (AUC 0.75). Conclusions: The PAST atlas enables reproducible and time-efficient scalp segmentation. Permanent RIA appears mainly driven by radiation dose and treatment intensity. Identified dosimetric thresholds support scalp-sparing CSI planning in pediatric combined-modality settings.
Advances in paediatric oncology (PO) have substantially improved survival rates in childhood cancer, yet an increasing complexity has generated new clinical, psychosocial and ethical challenges. Integrating paediatric palliative care (PPC) early in the oncological trajectory has been shown to enhance quality of life for patients and families, but conceptual barriers often hinder collaboration between the two disciplines. This project aimed to develop a shared European glossary of key terms used in PO and PPC, fostering a common language to facilitate communication, collaboration and integration across culturally and resource diverse healthcare systems. Building upon an existing Italian glossary, a European version was developed in 2024. The process included English translation, expert review and multiple consensus rounds involving representatives from the European Society for Paediatric Oncology (SIOPE) PPC Working Group and the Italian interdisciplinary team. Each term was critically evaluated for conceptual clarity, cross-cultural applicability and alignment with international practice. The glossary evolved from 30 to 21 final terms, reflecting consensus on definitions and the removal or adaptation of items not generalizable to the European context (e.g., terms linked to Italian legislation). The final document underwent editorial and graphical revision, and was submitted to the SIOPE Executive Board for endorsement and dissemination. The European Glossary of PO and PPC provides a foundational framework for harmonising language and practice across Europe. It supports education, clinical integration and policy dialogue, representing a key step towards shared understanding and patient-centred care for children with cancer and their families.
Background and aims: Glioblastoma multiforme (GBM) is a highly malignant brain tumour and a leading cause of cancer-related deaths in children, adolescents, and young adults. Due to the limited efficacy of current therapies, novel strategies are needed to improve GBM outcomes. B7-H3 is an immune checkpoint molecule that drives tumour immune evasion and metastasis, contributing to poor prognosis in several cancers. Ezrin-radixin-moesin (ERM) support the plasma membrane localisation of transmembrane proteins as scaffolds. We aimed to elucidate the role of ERM in B7-H3 plasma membrane expression and analyse the prognostic significance of B7-H3 and ERM using cell lines and clinical databases derived from GBM patients. Methods: mRNA and protein expression, intracellular localisation, and molecular interaction of B7-H3 and ERM in human GBM cells were determined using quantitative RT-PCR, western blot, immunofluorescence, and co-immunoprecipitation, respectively. Plasma membrane expression and localisation of B7-H3 were measured five days after transfection with small interfering RNAs against each ERM. The expressions and prognostic impacts of B7-H3 and ERM in GBM tumour tissues were assessed using a clinical RNA-sequencing database. Results: Knockdown of moesin, but not ezrin or radixin, reduced plasma membrane localisation of B7-H3 without affecting its mRNA expression. B7-H3 colocalised and interacted with moesin in the plasma membrane of human GBM cells. B7-H3 and moesin expressions in tumour tissues were significantly higher than in normal brain tissues and associated with decreased disease-free survival time in GBM patients. Conclusions: Moesin contributes to the poor prognosis of GBM by acting as the dominant scaffold responsible for B7-H3 overexpression.
Purpose: Ewing sarcoma (ES) of the head and neck is rare, and optimal management remains uncertain. We evaluated outcomes of patients treated with curative intent using a uniform multimodality protocol at our institute. Materials and Methods: Between January 2005 and December 2020, 102 patients with histologically confirmed head and neck ES were retrospectively analysed. Median age was 14 years (range, 2 months-42 years), and median tumour size was 5 cm (range, 2-12 cm). All patients received systemic chemotherapy (CTh) combined with local therapy: surgery (n = 10), radiotherapy (RT) alone (n = 44), or surgery followed by RT (n = 47), followed by maintenance chemotherapy. RT alone was offered when surgery was infeasible or associated with significant morbidity. Survival outcomes, prognostic factors, failure patterns, and toxicity were assessed. Results: One patient died during induction chemotherapy. At a median follow-up of 79 months, 7-year local control (LC), event-free survival (EFS), and overall survival (OS) were 81.2%, 73.2%, and 86.2%, respectively. LC did not significantly differ by local modality (surgery vs RT vs surgery + RT: 87.5% vs 71.9% vs 88.2%; p = 0.34). On univariable analysis, metastatic status, anaemia, elevated platelet-to-lymphocyte ratio, local modality, R1 resection, and partial RT response predicted OS. Failures included isolated local relapse (n = 9), distant metastases (n = 9), and combined relapse (n = 6). Conclusion: Multimodality therapy yields favourable long-term outcomes with acceptable toxicity. Surgery should be considered when feasible, with adjuvant RT as indicated. Definitive RT remains appropriate for unresectable disease.
An analysis of regulatory approvals since 2010 for oncological drugs with studies enrolling fewer than 50 patients was undertaken. An electronic search of the EMA database was performed to identify all oncology drug approvals. An examination of the approvals was performed to identify those approvals with studies with 50 or fewer patients. All notifications of oncology drug approvals from the FDA website between January 2010 and May 2025 were reviewed. 14 oncology drugs were approved by either the EMA or FDA or both during this timeframe. Among the 14 studies reported, only one was a randomised comparative study. The FDA approved 13 drugs for paediatric indications (7 of the drugs also had adult indications) and one for adults only (avapritinib). In contrast the EMA only approved 8 drugs for use in children of various ages and similarly to the FDA avapritinib was approved for adults only. Tagraxofusp was only approved for adult use by the EMA, whereas it was extended for use in children by the FDA. There was some disparity between the FDA and EMA when approving the age at which the drugs could be used in children, with the FDA generally approving use from a younger age. Although the review included studies which had enrolled 50 patients or fewer, the studies resulting in an approved paediatric indication by either the FDA or EMA enrolled far fewer than 50 patients in many instances. All paediatric indications were approved based on studies with efficacy outcomes based on ORR which were generally achieved at early timepoints in the study. The ORR was below 50% in 2 of the studies.
Purpose: This study assessed the prevalence and type of information and support needs among European childhood, adolescent, and young adult cancer survivors (CAYACS), their socio-demographic and clinical predictors, and associations with patient activation and health-related quality of life (HRQoL). Methods: The e-QuoL Needs Study is a cross-sectional survey conducted in 15 European countries. Adult CAYACS (>= 18 years, diagnosed before age 25 years) completed the modified Childhood Cancer Survivor Study-Needs Assessment Questionnaire (CCSS-NAQ), Patient Activation Measure (R) (PAM (R)), and PROMIS Global Health scales (HRQoL). Logistic and linear regression models were used to examine associations between socio-demographic and clinical characteristics, patient activation, and HRQoL. Results: Overall, 571 CAYACS who completed >= 50% of the items in at least one CCSS-NAQ domain were included (71% female; 75% in the age group 18-35 years; 47% diagnosed > 10 years ago). In all domains, except spirituality, most participants (62-90%) reported at least one need, with the highest prevalence found for cancer-related health information (90%), psycho-emotional consequences (87%), and health system concerns (84%). Females, survivors residing in Eastern Europe, and those with neurocognitive late effects were most likely to report needs (p < 0.05). Reporting needs was associated with lower patient activation and poorer mental and physical HRQoL. Conclusions: Information and support needs remain highly prevalent among European CAYACS, even long after diagnosis. Routine assessment of individual needs and targeted information strategies tailored to survivor groups identified as having higher needs may help reduce regional inequities, improve patient activation, and optimize HRQoL.
Background and Aims: Stereotactic ablative radiotherapy (SAbR) has been used in the adult population for decades, providing local control (LC) and, in some cases, overall survival (OS) advantage. It can also extend the time to subsequent systemic therapy, reducing side effect burden and improving quality of life. This retrospective study aimed to evaluate the effectiveness of SAbR in prolonging time to subsequent systemic therapy in children. Methods: We performed a single-institution retrospective analysis of children who underwent extracranial SAbR over 2-5 fractions (dose per fraction > 5 Gray [Gy]) for recurrent or progressive cancer between 2009 and 2024. The primary endpoint was time from SAbR to next use of systemic therapy. Secondary endpoints included LC and OS, as well as the impact of biological effective dose (BED) and equivalent dose in 2-Gy fractions (EQD2) thereon. Results: Thirty-five pediatric patients with cancer had 97 lesions that received at least one course of SAbR meeting minimum dose criteria (BED10 >= 30 Gy). The cumulative incidence of any systemic therapy change at 12 months was 0.58 (95% CI 0.47-0.68). The cumulative incidence of IV systemic therapy change at 12 months was 0.36 (95% CI 0.26-0.47), with a median time to IV systemic therapy change of 11.9 months. Risk of local progression was associated with non-sarcoma histology compared with soft tissue sarcoma (Hazard Ratio [HR] 4.19; 95% Confidence Interval [CI] 1.25-14.06; p = 0.021). Median OS from first SAbR was 12.8 months (95% CI 7.82-26.20). There was no statistically significant association of LC with BED or EQD2. Conclusions: In this single-institution case series, SAbR was associated with a delay to subsequent IV systemic therapy change in pediatric cancer patients and may serve as a means to manage disease progression while minimizing burden of therapy. Prospective studies are needed to confirm these findings.
Introduction Fatigue is common, yet poorly understood in childhood cancer survivors, hampering effective long-term management. We aimed to compare fatigue in adult survivors of childhood cancer with the general population; and identify potentially modifiable associated factors. Methods Inclusion: childhood cancer survivors from the population-based NOR-CAYACS study (except survivors of central nervous system tumors) diagnosed 1985-2000. Normative data were available from a separate population-based study weighted according to current age and sex distribution. We assessed chronic fatigue and severity (Chalder's Fatigue Questionnaire; score >= 4) and compared chronic fatigue occurrence (total score), and fatigue duration (>= 6months), in survivors and the general population using linear regression and chi-squared tests. Multivariable linear regressions with blockwise variable addition based on a directed acyclic graph identified associated modifiable factors of fatigue severity. Results 583 survivors (57% female, mean=19.1years post-diagnosis, 34% response) and 642 from the general population (35% response) were included. Significantly more survivors reported chronic fatigue than the general population (score >= 4; 25% vs 17%, p = 0.022), greater fatigue severity and symptom duration (>= 6months, 53% vs 39%, p < 0.001). Less fatigue severity was associated with male, not female, sex (beta=-1.4, 95%CI=-2.4 to -0.5, p = 0.002) and a university, not no university, degree (beta=-1.2, 95%CI=-2.1 to -0.2, p = 0.015). Higher fatigue severity was associated with >= 1 self-reported late-effects (versus none), (beta=2.6, 95%CI=1.6-3.6, p < 0.001), more hours of daily sleep (beta=0.5, 95%CI=0.2-0.9, p = 0.002), greater pain interference (versus none/little) (beta=3.9, 95%CI=2.7-5.1, p < 0.001), and higher depressive symptoms (beta=0.7, 95%CI=0.6-0.8, p < 0.001) in the multivariable model, explaining 52% of variance. Conclusions Survivors reported chronic fatigue more often than the general population. Fatigue severity was associated with modifiable factors that may be targeted to mitigate the impact of fatigue on survivors' well-being.
