Pediatric Blood & Cancer[JOURNAL]
Sun
200 papers
Fear of recurrence, secondary cancers, and health problems in long-term survivors of childhood cancer: Findings from a Canadian cohort.
Tutelman PR, Duong J, Forbes C … +8 more , Lawal OA, Fidler-Benaoudia M, Reynolds K, Giles J, Guilcher GMT, Russell B, Lebel S, Schulte FSM
Cancer · 2026 Feb · PMID 41644475 · Full text
INTRODUCTION: Survivors of childhood cancer are at lifelong risk for health problems, secondary cancers, and recurrence. However, little is known about their fears related to these risks nor the factors associated with t...
INTRODUCTION: Survivors of childhood cancer are at lifelong risk for health problems, secondary cancers, and recurrence. However, little is known about their fears related to these risks nor the factors associated with them. METHODS: A Canadian cohort of childhood cancer survivors (n = 284; 51.1% male; mean age = 22.3 years, mean time off treatment = 12.4 years) reported on their fears of health problems, secondary cancers, and recurrence; physical functioning; psychosocial symptoms; and substance use. The relationship between their fears and various demographic, physical, and psychosocial variables was assessed through multivariate logistic regression analyses. RESULTS: Thirty-seven percent of survivors reported at least one cancer fear. Fear of secondary cancer was the most reported (25.0%), followed by fear of future health problems (24.6%) and fear of recurrence (21.8%). Survivors who reported having ever drunk to intoxication were more likely to report all three cancer fears (ps < .01-<.05) and those who endorsed ever using marijuana/cannabis were more likely to report fear of health problems or secondary cancer (ps = <.01-.05). At the multivariate level, various demographic characteristics (e.g., female sex), physical (e.g., health problems), and psychosocial factors (e.g., anxiety) were associated with the presence of fears. CONCLUSION: More than one third of long-term survivors of childhood cancer endorse fears related to their risk of health problems, secondary cancers, and/or recurrence, which is associated with physical and psychosocial functioning and substance use. Multimodal interventions targeting cancer fears in long-term survivors of childhood cancer are needed to promote adaptive coping throughout survivorship.
Incidence, patterns of clinical presentation, and haematological characteristics of paediatric acute myeloid leukaemia in Uganda: a retrospective analysis.
Nyeko R, Kruger M, Niyonzima N … +5 more , Atwiine B, Zungu J, Kambugu JB, Verhulst S, van Heerden J
BMC Cancer · 2026 Jan · PMID 41549234 · Full text
BACKGROUND: Current understanding of paediatric acute myeloid leukaemia (AML) in Africa is limited. This study investigated the incidence, presentation pattern, and haematological profiles of paediatric AML in Uganda. ME...
BACKGROUND: Current understanding of paediatric acute myeloid leukaemia (AML) in Africa is limited. This study investigated the incidence, presentation pattern, and haematological profiles of paediatric AML in Uganda. METHODS: This retrospective cohort study examined the medical records of children under 18 years of age who were diagnosed with acute myeloid leukaemia (AML) at three cancer centres in Uganda from 2016 to 2022. Data included demographics, clinical features, and laboratory findings. Frequencies, bivariate analyses, and regression models were performed, with statistical significance set at p < 0.05. RESULTS: The study included 159 children diagnosed with AML, with a median age of 9.0 years (IQR 3.0–12.0). The incidence was 7.0/million children 0–17 years. The most common presenting symptoms were fever (84.3%), weight loss (44.0%), fatigue (40.9%), bleeding (35.8%), and bone pain (28.9%). Clinical findings at diagnosis included splenomegaly (40.9%), lymphadenopathy (39.6%), myeloid sarcoma (39.6%), and hepatomegaly (37.7%). The median (IQR) white blood cell (WBC) count at diagnosis was 32.0 × 10⁹/L (0.3–81.8). The predominant FAB subtype was M7 (n = 22, 24.4%), followed by M5 (n = 20, 22.2%). Acute promyelocytic leukaemia was seen in 13 (8.2%) patients, while 11 (6.9%) patients had myeloid leukaemia of Down syndrome. Cytogenetic analysis was limited to only 10 patients. There were significant differences in clinical characteristics by age with respect to splenomegaly, central nervous system involvement, and FAB subtype. CONCLUSIONS: The incidence of paediatric AML in this study mirrors global patterns, with a higher-than-expected prevalence of the M7 subtype noted. In settings with limited resources, diagnosis relies mainly on clinical and morphological assessment. Broader access to cytogenetic and molecular testing could improve subtype identification and risk profiling.
A pilot study of chemoimmunotherapy in the postconsolidation setting for high-risk neuroblastoma (ANBL19P1): A report from the Children's Oncology Group.
Desai AV, Naranjo A, LaBarre B … +11 more , Chen L, Goldsmith KC, Granger MP, States L, Green SG, Trunzo M, Fitzgerald W, DuBois SG, Bagatell R, Park JR, Marachelian A
Cancer · 2026 Jan · PMID 41527287 · Full text
BACKGROUND: Survival for patients with high-risk neuroblastoma remains poor despite current-era multimodality treatment that includes postconsolidation GD2-directed immunotherapy. Given the promising responses in patient...
BACKGROUND: Survival for patients with high-risk neuroblastoma remains poor despite current-era multimodality treatment that includes postconsolidation GD2-directed immunotherapy. Given the promising responses in patients who receive dinutuximab-based chemoimmunotherapy in the relapsed setting, the Children's Oncology Group ANBL19P1 study evaluated the feasibility of administering irinotecan, temozolomide, dinutuximab, and sargramostim after frontline consolidation with tandem autologous stem cell transplantation (ASCT). METHODS: Patients with high-risk neuroblastoma who received induction therapy followed by tandem ASCT and had no evidence of progressive disease (PD) were eligible. Treatment included five 28-day cycles of temozolomide and irinotecan (days 1-5), dinutuximab (days 2-5), and sargramostim (days 6-12). Isotretinoin (days 8-21) was given during cycles 1-6. Therapy was deemed feasible if the 95% confidence interval placed on the percentage of patients that completed five cycles of chemoimmunotherapy without PD within 30 weeks contained 75% in the absence of excessive toxicity. Event-free survival and overall survival were determined from the time of enrollment. RESULTS: Forty eligible patients enrolled, and 35 (87.5%; 95% confidence interval, 73.9%-94.5%) completed five cycles without PD within 30 weeks, meeting the feasibility threshold. No unacceptable toxicities occurred on protocol therapy, including no toxic deaths. Five patients discontinued therapy early because of physician determination (n = 2), patient/parent refusal of further therapy (n = 2), and PD (n = 1). The 2-year event-free and overall survival rates were 82.5% ± 6.1% and 92.5% ± 4.2%, respectively. CONCLUSIONS: The administration of chemoimmunotherapy in the postconsolidation setting after tandem ASCT is feasible and tolerable. Future studies will be needed to define the population most likely to benefit from this augmented postconsolidation therapy.
Preliminary study exploring the association between amygdala-ventral medial prefrontal-cortex connectivity and anxiety among adolescent and young adult cancer survivors.
Knoerl R, Jahn A, Grandinetti K … +7 more , Fecher LA, Henry NL, Karimi Y, Ploutz-Snyder R, Schuetze S, Walling E, Iordan A
BMC Cancer · 2025 Dec · PMID 41466204 · Full text
BACKGROUND: Up to 40% of adolescent and young adult cancer survivors (AYAs) experience anxiety after cancer treatment. Evidence from healthy controls suggests that the prefrontal cortex exerts a regulatory influence over...
BACKGROUND: Up to 40% of adolescent and young adult cancer survivors (AYAs) experience anxiety after cancer treatment. Evidence from healthy controls suggests that the prefrontal cortex exerts a regulatory influence over the amygdala, facilitating reappraisal of fear-inducing stimuli and preventing maladaptive emotional responses. Increased anxiety severity has been associated with low amygdala–ventral medial prefrontal cortex (vmPFC) connectivity, but little is known about the neural correlates of anxiety in AYA cancer survivors. The purpose of this cross-sectional study was to explore the association between amygdala-vmPFC connectivity and anxiety severity among AYA cancer survivors. METHODS: Seventeen post-treatment AYA cancer survivors were recruited from the University of Michigan. Participants completed an anxiety self-report and a 45-minute functional MRI scan that consisted of resting and task-based conditions (i.e., viewing pleasant, neutral, or unpleasant scenes). General linear models were constructed to investigate the effect of self-reported anxiety on the functional connectivity between the amygdala and vmPFC regions. RESULTS: Anxiety severity was positively associated with the functional connectivity between the right amygdala and vmPFC (MNI: -2, 54, 14; k = 323 voxels; peak t-statistic = 9.16; peak beta = 0.34; p = 0.04) while viewing pleasant images, but not other images or during rest. Analyses using the left amygdala as a seed region did not yield significant correlations. CONCLUSIONS: The positive association between anxiety severity and amygdala-vmPFC connectivity while viewing positive stimuli may suggest an overly active neural pathway linked to overall ineffective emotional regulation. Further understanding of amygdala-vmPFC connectivity as a potential mechanism underlying anxiety may provide evidence toward a viable target for intervention research.
Frequency and face validity of reported family history of cancer in first-degree relatives and genetic syndromes among children with cancer in Project:EveryChild: A report from the Children's Oncology Group.
Fuentes Bolanos NA, Lupo PJ, Tucker KM … +4 more , Hawkins DS, Porter CC, Villani A, Spector LG
Cancer · 2026 Jan · PMID 41457435 · Full text
BACKGROUND: Taking a family history of cancer (FH) is essential for identifying individuals with heritable cancer predisposition. PROJECT: EveryChild (Children's Oncology Group [COG] trial APEC14B1), the registration and...
BACKGROUND: Taking a family history of cancer (FH) is essential for identifying individuals with heritable cancer predisposition. PROJECT: EveryChild (Children's Oncology Group [COG] trial APEC14B1), the registration and biobanking protocol of the COG, includes suggested questions about FH in first-degree relatives and personal history of genetic syndromes (GS) in pediatric oncology patients. The validity of these items is unclear; therefore, the authors assessed the data quality and face validity of the responses. METHODS: The authors analyzed case report forms regarding FH and GS of 30,157 participants (aged birth to 21 years) with newly diagnosed pediatric cancer enrolled in APEC14B1. FH and GS data were manually curated to interpret the responses and group them into categories, followed by face validity assessment-defined as the extent to which the information provided represented what it was intended to capture. RESULTS: Responses were provided for 65.7% of participants (n = 19,810), with 6.1% reporting FH (n = 1204). Of those, 97.9% (n = 1178) included sufficient free-text detail to assess face validity, although 49.4% required manual interpretation. Among FH reports, 48.3% (n = 595) were suggestive of heritable cancer risk. GS was reported in 4.3% of responders (n = 863), with 93.3% (n = 780) showing face validity after curation. Down syndrome (n = 302) and neurofibromatosis type 1 (n = 93) were the most frequently reported syndromes, with neurofibromatosis type 1 most common in patients who had central nervous system tumors. CONCLUSIONS: Despite limitations and the need for manual curation, FH and GS data collected by using proposed questions were sufficient to identify known heritable cancer patterns. These findings support questionnaire-based data collection and highlight areas for improvement.
Addressing survivorship care gaps through digital innovation: opportunities, challenges, and ethical considerations in the e-QuoL project.
Demoor-Goldschmidt C, Michel G, Roganovic J … +10 more , Thierry-Chef I, Lähteenmäki PM, Muraca M, Jakab Z, Chevenez L, Potter EJ, Garami M, Thornton KET, Lie HC, e-QuoL consortium
BMC Cancer · 2025 Dec · PMID 41419816 · Full text
BACKGROUND: Childhood, adolescent, and young adult cancers (CAYAC) present unique challenges in oncology. Advances in treatment Have led to an 80% 5-year survival rate; however, CAYAC survivors (CAYACS) remain at high ri...
BACKGROUND: Childhood, adolescent, and young adult cancers (CAYAC) present unique challenges in oncology. Advances in treatment Have led to an 80% 5-year survival rate; however, CAYAC survivors (CAYACS) remain at high risk of long-term medical and psychosocial complications, significantly impacting their quality of life. Short and long-term follow-up care is recommended, but is often fragmented, with considerable disparities in availability and accessibility across Europe. Many existing digital tools primarily address medical needs, leaving psychosocial challenges unaddressed. The e-QuoL project aims to bridge these gaps by leveraging existing digital health solutions to provide equitable, person-centered survivorship care. METHODS: The e-QuoL project employs a participatory approach involving survivors, families, healthcare professionals (HCP), and researchers. Using the FormIT methodology, the project follows three phases: Explore, Create, and Evaluate. The Explore phase includes a large-scale cross-sectional survey across 15 European countries to assess the unmet needs of CAYACS and their families. The Create phase involves co-creation workshops to develop and refine digital tools, including MyCaree-QuoL tool, which will supplement survivorship care passports, to provide personalized medical and psychosocial support. The Evaluate phase comprises usability testing and clinical studies in at least seven European countries to assess effectiveness, scalability, and real-world applicability. DISCUSSION: The e-QuoL project builds on existing digital health innovations while adapting them to diverse European healthcare systems. By developing MyCaree-QuoL, the project fosters a decentralized, person-centered model of survivorship care to promote equal access to quality survivorship support for CAYACS and HCPs. Ethical considerations, including data privacy, patient consent, and equitable access, are central to the project, with dedicated Ethics and Social Challenge Groups guiding implementation. Digital disparities remain a challenge, particularly for survivors from lower socio-economic backgrounds or remote areas. To mitigate this, e-QuoL will work with healthcare professionals to offer additional in-person support to complement digital interventions. The project aligns with Europe’s Beating Cancer Plan, aiming to improve quality of life and reduce disparities in care. By fostering collaboration among 30 partners across 15 countries and hosting resources on the PanCare website, e-QuoL seeks to ensure long-term impact, contributing to the goal of high-quality, equitable survivorship care across Europe.
Treatment outcomes and prognostic factors in children diagnosed with acute myeloid leukaemia in Uganda.
Nyeko R, Kruger M, Niyonzima N … +5 more , Atwiine B, Zungu J, Kambugu JB, Verhulst S, van Heerden J
BMC Cancer · 2025 Dec · PMID 41413799 · Full text
BACKGROUND: Treatment of paediatric acute myeloid leukaemia (AML) is challenging in low- and middle-income countries (LMICs) due to resource constraints with subsequent poorer outcome. This study evaluated treatment outc...
BACKGROUND: Treatment of paediatric acute myeloid leukaemia (AML) is challenging in low- and middle-income countries (LMICs) due to resource constraints with subsequent poorer outcome. This study evaluated treatment outcomes and the determinants of survival in paediatric AML patients in Uganda. METHODS: This retrospective cohort study reviewed data from children with AML treated at three centres in Uganda between January 2016 and December 2022. Treatment comprised induction with daunorubicin and cytarabine and consolidation with high-dose cytarabine. Patients with acute promyelocytic leukaemia were treated on protocols adapted from Children's Oncology Group AAML 1331. All patients received supportive care. The data were analysed using SPSS Version 20. RESULTS: One-hundred and fifty-nine children with AML were included with a median age at diagnosis of 9.0 years (IQR: 3.0-12.0). Of the 149 patients who initiated therapy, 69 (46.3%) achieved complete remission after the first induction therapy (CR1), and 81 (54.4%) achieved complete remission (CR) overall. Treatment-related mortality occurred in 50 (31.4%) of the patients, with an early death rate of 27.7% (n = 44). Among the 81 patients who achieved CR, 37 (45.7%) relapsed, of whom 27 (73.0%) subsequently died. The one-, three-, and five-year OS were 39.0%, 25.1%, and 16.7%, respectively. The corresponding EFS were 37.0%, 22.9%, and 15.2%, respectively. Median OS and EFS were 7.4 months (95% CI: 4.3-10.6) and 6.9 months (95% CI: 4.4-9.6), respectively. Factors significantly associated with poor OS included poor nutritional status (p = 0.026), delayed neutrophil recovery following induction (p = 0.030), failure to achieve CR1 (p = 0.031), and failure to complete treatment (p < 0.001). CONCLUSIONS: Survival rates among children with AML in this study were low. Several clinical and biological prognostic factors influenced survival outcomes in this resource-limited setting. Improving outcomes will require improving supportive care or adopting resource-adapted treatment protocols that address the supportive care challenges in such a resource-limited setting.
Real-world efficacy and adverse events of frontline nilotinib in pediatric chronic myeloid leukemia in chronic phase: A prospective multicenter study from SCCCG[PLUS]-CML 2023.
Fan Z, Chen QW, Huang XY … +28 more , Fu Q, Mai HR, Long XJ, Li QR, Liu LL, Liu RY, He F, Guo BY, Zeng MH, Wan WQ, Zhang WN, Guo HX, Zhou DH, Zou YW, Xiong WJ, Zhou XB, Chen HQ, Lin LM, Ren HY, Tian X, Wei HY, Lan HK, Jin J, Liang C, Luo XQ, Huang LB, Yang LH, Zhang XL
Cancer · 2025 Dec · PMID 41405208 · Full text
BACKGROUND: Chronic myeloid leukemia (CML) is rare in children and often shows more aggressive features than in adults. Real-world data on the efficacy and safety of frontline nilotinib in pediatric CML in chronic phase...
BACKGROUND: Chronic myeloid leukemia (CML) is rare in children and often shows more aggressive features than in adults. Real-world data on the efficacy and safety of frontline nilotinib in pediatric CML in chronic phase (CML-CP) remain limited. METHODS: This prospective multicenter real-world study evaluated the efficacy, safety, and pharmacokinetics of frontline nilotinib in newly diagnosed pediatric CML-CP across 26 hospitals in China between January 2023 and April 2025. Patients received nilotinib 230 mg/m twice daily. Primary end points were complete cytogenetic response (CCyR) at six cycles and major molecular response (MMR) at 12 cycles. Secondary end points included time to MMR, event-free survival (EFS), and safety. RESULTS: Among 59 enrolled patients (median age, 10.6 years), 71.8% (28/39) achieved MMR at 12 cycles and all achieved CCyR at six cycles. Median time to MMR was 6.2 (3.3, 12.2) months, and 2-year EFS was 93.3% (84.4%-100%). Nilotinib trough concentrations (Ctrough) correlated negatively with BCR::ABL1 transcript levels at cycles 6 and 12. Patients with Ctrough >950 ng/mL were three to five times more likely to reach MMR, whereas those with Ctrough ≥1500 ng/mL had a 6.5-fold higher risk of hyperbilirubinemia. CONCLUSIONS: Frontline nilotinib thus shows strong efficacy and manageable safety in pediatric CML-CP. Higher drug exposure predicts deeper molecular responses but increases toxicity, supporting the potential role of therapeutic drug monitoring.
Primary hypothyroidism after treatment for childhood cancer in the Dutch Childhood Cancer Survivor Study: Hypothyroidism in childhood cancer survivors.
van der Leij S, Teepen JC, Kremer LCM … +11 more , van der Pal HJH, van den Heuvel-Eibrink MM, Bresters D, de Vries ACH, Keijzer-Schellekens AJ, Ronckers CM, Hermens R, Louwerens M, Neggers S, Valk GD, van Santen HM
Cancer · 2025 Dec · PMID 41370183 · Publisher ↗
PURPOSE: Primary hypothyroidism is common in childhood cancer survivors (CCS). Exposure to radiation and hematopoietic stem cell transplantation (HSCT) are known risk factors; however, the impact of chemotherapy and the...
PURPOSE: Primary hypothyroidism is common in childhood cancer survivors (CCS). Exposure to radiation and hematopoietic stem cell transplantation (HSCT) are known risk factors; however, the impact of chemotherapy and the role of thyroid peroxidase antibodies (anti-TPO) remain unclear. The prevalence of primary hypothyroidism, anti-TPO, and treatment-related risk factors in a cohort of CCS was assessed. METHODS: In total, 1774 five-year CCS were included. The prevalence of primary hypothyroidism according to treatment strategy was evaluated: radiotherapy involving the thyroid gland (±chemotherapy), chemotherapy only, HSCT, and controls. Multivariable logistic regression was performed to identify risk factors for hypothyroidism. RESULTS: After a median follow-up time of 25.3 years (range, 14.8-54.7), primary hypothyroidism was present in 8.2%. When evaluating subgroups specifically, the prevalence of primary hypothyroidism increased to 28% in CCS treated with radiotherapy and 30.6% after HSCT. In multivariable analyses, survivors treated with chemotherapy only were not at increased risk of hypothyroidism (odds ratio [OR], 0.74; 95% CI, 0.28-2.00), whereas survivors treated with radiotherapy had an almost 14-fold increased risk (OR, 13.91; 95% CI, 5.34-36.22). In irradiated CCS, the use of platinating agents was associated with an increased risk of hypothyroidism (OR, 3.25; 95% CI, 1.39-7.59). The prevalence of anti-TPO did not differ between the treatment groups (p = .42). CONCLUSIONS: Primary hypothyroidism is prevalent after radiation exposure and HSCT. Chemotherapy only does not increase the risk for primary hypothyroidism. The use of platinating agents combined with radiotherapy may increase its risk. Treatment for childhood cancer does not increase the risk of anti-TPO.
Smart exercise in pediatric oncology: enhancing executive functions through cognitively challenging physical activity- a non-randomized controlled trial.
Schneider AC, Hillebrecht L, Rehbein L … +9 more , Schmid J, Pallivathukal S, von der Weid N, Furtwängler R, Brekenfeld RE, Greiner J, Schindera C, Brack EK, Benzing V
BMC Cancer · 2025 Dec · PMID 41351152 · Full text
INTRODUCTION: Children and adolescents, diagnosed with cancer, frequently develop physical and cognitive impairments. Hence, cancer and its treatments contribute to reduced physical activity (PA) and cognitive impairment...
INTRODUCTION: Children and adolescents, diagnosed with cancer, frequently develop physical and cognitive impairments. Hence, cancer and its treatments contribute to reduced physical activity (PA) and cognitive impairments, particularly in executive functions (EFs). Research indicates that PA in school children improves EFs, with cognitively challenging PA offering potential additional benefits. The aim of this study is to investigate the effects of cognitively challenging PA during acute cancer care on cognitive and physical performance, as well as mental health. METHODS: This prospective, two-arm, non-randomized, multicenter controlled study will take place at four pediatric oncology centers in Switzerland. In the intervention group the effect of cognitively challenging PA (n = 35) will be compared with standard care plus PA recommendations in the control group (n = 35) in newly diagnosed pediatric patients with cancer aged 6-17.99 years. The twelve-week cognitively challenging PA intervention consists of three-weekly 45-minute individualized and supervised sessions incorporating cognitive elements. Assessments of EFs, motor abilities, cardiovascular health, health-related quality of life, fatigue, and physical and psychosocial functioning will be conducted at baseline, six weeks, twelve weeks, and a six month follow-up. All participants in the intervention and control group will receive PA recommendations during the intervention period and an offer for post-therapy PA counseling. DISCUSSION: Childhood is a crucial period for brain and motor development, rendering young cancer patients especially vulnerable to cognitive and physical impairments from the disease and its treatment. This study is the first to implement cognitively challenging PA tailored to pediatric cancer patients with the aim to enhance EFs by activating brain networks responsible for higher-order processes, physical performance and mental health. The findings will provide insights into the role of cognitively challenging PA and explore its integration into standard care to improve quality of life for childhood cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06839794) and German Clinical Trial Register (DRKS00036573).
Pharmacological targeting and characterization of Voltage-Gated Sodium Channels (VGSCs) expressed in the high-grade glioma microenvironment.
Fletcher EV, Shard C, Boyle Y … +20 more , Milligan CJ, Cross RSN, Jones AC, Francis A, Dewdney B, Barker M, Rezaeiravesh S, Ng ZY, Yeow Y, Kuznetsova I, Jones ME, Ormsby RJ, Poonnoose SI, Patil A, Valvi S, Jenkins MR, Forrest ARR, Petrou S, Gomez GA, Johns TG
BMC Cancer · 2025 Dec · PMID 41331425 · Full text
BACKGROUND: High-grade glioma (HGG) cells reactivate neurodevelopmental programs regulated by ion channels to drive tumor progression. The activity of voltage-gated sodium channels (VGSCs) is fundamental to development,...
BACKGROUND: High-grade glioma (HGG) cells reactivate neurodevelopmental programs regulated by ion channels to drive tumor progression. The activity of voltage-gated sodium channels (VGSCs) is fundamental to development, a target of blood-brain barrier (BBB)-permeable FDA-approved drugs, and aids tumor advancement in several cancers. However, the contribution of VGSC activity to HGG pathology remains unknown. METHODS: Using single-cell and spatial transcriptomics, proteomics, and immunohistochemistry, we profiled the expression landscape of the VGSC family in patient tumors from two HGGs: adult glioblastoma and pediatric diffuse midline glioma (DMG). We further validated VGSC expression and function in HGG patient-derived cell lines using RNA, protein, and electrophysiological analyses, and assessed the anticancer efficacy of VGSC-modulating drugs in vitro through cell viability and invasion assays. RESULTS: VGSCs α subunits targeted by different classes of VGSC-drugs are differentially expressed within DMG and glioblastoma. Overall, VGSCs that are sensitive to the neurotoxin, tetrodotoxin (TTX), and in normal physiology are expressed in the nervous system were upregulated by invasive HGG cells at the leading edge of DMG and glioblastoma tumors. Whereas the TTX-insensitive cardiac VGSC NaV1.5 was distinctly more abundant within the cellular tumor of the DMG microenvironment. VGSC-expressing HGG cells within both microenvironments receive oncogenic glutamatergic inputs from surrounding neurons. RNA, protein and electrophysiological analysis of patient-derived HGG cells supported our in vivo findings, where NaV1.5 plays a significant role in DMG cell lines, conducting TTX-insensitive transient and persistent sodium currents. Overall, VGSC-targeting drugs had limited anticancer efficacy; however, GS967 a persistent current blocker, significantly inhibited the invasiveness of a DMG cell line by ~ 33%. CONCLUSION: Inhibiting intrinsic VGSC persistent currents suppresses invasiveness in DMG subpopulations and may further hinder HGG progression by buffering oncogenic depolarizations from neuron-glioma synaptic activity. Therefore, VGSC-drugs targeting persistent sodium currents offer untapped therapeutic options for treating HGG.
Comparative survival outcomes between therapy-related and de novo acute lymphoblastic leukemia in adults: a systematic review and meta-analysis.
Mesilhy R, Khan MN, Syed A … +9 more , Hourani R, Cherif H, Elsalkawi Y, Khalid H, Al-Mashdali A, Soliman D, Mudwai D, Doi SA, Mohamed SF
BMC Cancer · 2025 Nov · PMID 41318424 · Full text
BACKGROUND: Therapy-related acute lymphoblastic leukemia (t-ALL) is an aggressive subtype of ALL that arises after cytotoxic therapy. It is associated with adverse cytogenetics and older age, but survival outcomes compar...
BACKGROUND: Therapy-related acute lymphoblastic leukemia (t-ALL) is an aggressive subtype of ALL that arises after cytotoxic therapy. It is associated with adverse cytogenetics and older age, but survival outcomes compared with de novo ALL remain uncertain. We aimed to systematically evaluate survival differences in adults with t-ALL versus d-ALL. METHODS: We performed a systematic review and meta-analysis according to PRISMA guidelines. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were searched to Dec 31, 2024. Eligible studies included adults (≥ 18 years) with t-ALL or de novo ALL reporting survival. Pediatric studies, case reports, reviews, and abstracts were excluded. Two reviewers independently screened and extracted data. Quality was assessed with the MASTER scale. Hazard ratios (HRs) for overall survival were pooled using Doi’s quality effects model. The protocol was registered with PROSPERO (CRD42025625294). RESULTS: From 3,325 records, 27 retrospective cohort studies (169,237 patients; 1,827 with t-ALL) were included. Nine studies (30,527 patients) were eligible for meta-analysis. The pooled HR for mortality in t-ALL versus d-ALL was 1.07 (95% CI 0.94–1.23), showing no significant survival difference. Median survival ranged from 6 to 32 months in t-ALL and 11–50.6 months in d-ALL. Poor-risk cytogenetics were more frequent in t-ALL (43–100% vs. 31–66%), with higher TP53 mutations (38% vs. 10%) and complex karyotypes. Complete remission was lower in t-ALL (60–88.9% vs. 81.5–93%). Heterogeneity was moderate (I²=50.5%) with evidence of small-study effects. CONCLUSION: Despite adverse biology, t-ALL demonstrates survival comparable to d-ALL with modern therapies, particularly allogeneic transplantation.
Prognostic implication of serum levels of IL-6 and IL-10 in children and adolescents with aggressive mature B-cell non-Hodgkin lymphoma.
Zeng C, Wei Z, Huang J … +7 more , Zhu J, Sun F, Wang J, Lu S, Zhang Y, Sun X, Zhen Z
BMC Cancer · 2025 Nov · PMID 41299342 · Full text
BACKGROUND: Aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is the most common subtype of non-Hodgkin lymphoma in children and adolescents. However, little progress has been made in determining the prognostic facto...
BACKGROUND: Aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is the most common subtype of non-Hodgkin lymphoma in children and adolescents. However, little progress has been made in determining the prognostic factors of children and adolescents with B-NHL. Based on the effect of cytokines in other cancer types, this study explored the effect of cytokines on the prognosis of children and adolescents with B-NHL. METHODS: The levels of serum cytokines including interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were detected at diagnosis. Correlations between cytokines, clinical characteristics, and treatment outcomes were retrospectively analyzed. RESULTS: In total, 139 patients aged < 18 years with newly diagnosed mature B-NHL were enrolled. Patients with elevated IL-6 levels at diagnosis (n = 35) had worse 5-year event-free survival (85.3% vs. 97.1%, p = 0.01) and overall survival (OS) rates (91.2% vs. 99.0%, p = 0.02) than those with normal IL-6 levels. Patients with elevated IL-10 (n = 35) had worse 5-year OS rates (91.4% vs. 99.0%, p = 0.02) than those with normal IL-10 levels. Cox multivariate analysis identified elevated IL-6 levels at diagnosis as an independent adverse prognostic factor in pediatric B-NHL. Elevated IL-6 levels correlated positively with IL-10 levels, and patients with simultaneously elevated IL-6 and IL-10 levels had the worst prognosis in the entire cohort. CONCLUSIONS: Our study suggests that elevated serum IL-6 and IL-10 levels at diagnosis are associated with poor prognosis in pediatric mature B-NHL and may have the potential to inform risk stratification. Future prospective, multi-center studies are required to validate these findings.
Bone marrow aspirate Cit-H3 was identified as a novel biomarker of minimal residual disease in neuroblastoma.
Zhang M, Wang X, Liu L … +7 more , Ni Y, Zhang Y, Hu X, Huang C, Gong B, She T, Chen C
BMC Cancer · 2025 Nov · PMID 41291543 · Full text
BACKGROUND: Neuroblastoma (NB) is the most prevalent extracranial solid tumor in children. Neutrophils release neutrophil extracellular traps (NETs) following intense or prolonged activation. Neutrophil elastase (ELA2) a...
BACKGROUND: Neuroblastoma (NB) is the most prevalent extracranial solid tumor in children. Neutrophils release neutrophil extracellular traps (NETs) following intense or prolonged activation. Neutrophil elastase (ELA2) and citrullinated histone H3 (Cit-H3) are specific markers of NETs. Additionally, neuron-specific enolase (NSE) serves as a biomarker and can be used to monitor the condition of NB progression, assess treatment response, and predict recurrence. METHODS: This study employed a retrospective study design, and all samples were collected prior to bone marrow aspiration for diagnosis. A total of 39 serum samples from patients diagnosed with NB by postoperative pathological bone marrow aspiration were included as the study subjects, and neutrophils, ELA2, and Cit-H3 were detected in the study subjects using ELISA. The blood routine data of 99 patients diagnosed with NB were collected, and these data were from patients different from those of the aforementioned 39 serum samples. And patients were divided into two groups, namely NB patients with positive bone marrow metastasis and those without metastasis, based on the result of bone marrow GD2 immunohistochemical staining. All data were statistically analyzed using IBM SPSS Statistics 26.0 and GraphPad Prism 9.0 software. RESULTS: A positive correlation was identified between NB bone marrow minimal residual disease (MRD) positivity and haematological indices, including interleukin-2 (IL-2) (p = 0.021), IL-6 (p = 0.030), NSE (p < 0.001), and Cit-H3 (p < 0.001). And MRD was positively associated with blood neutrophils in bone marrow (p < 0.05). CONCLUSIONS: This study demonstrates a significant correlation between NETs and MRDs, and found a positive correlation between bone marrow MRD and the indicators of IL-2, IL-6, and NSE, as well as a positive correlation with bone marrow neutrophils. And Cit-H3 was identified as a new biomarker and found a positive correlation between Cit-H3 and bone marrow MRD.
Rethinking cancer clinical trial eligibility-Inclusion is a scientific and moral imperative.
Mittal N
Cancer · 2025 Dec · PMID 41288245 · Publisher ↗
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Genetic insights into acute lymphoblastic leukemia: the role of MDR1 and IL18 polymorphisms in Egyptian children.
Mahdi AN, Elsaid AM, Mohammed MA … +2 more , Madkour MM, Abdel-Aziz AF
BMC Cancer · 2025 Nov · PMID 41257666 · Full text
BACKGROUND: The most prevalent cancer in pediatric is acute lymphoblastic leukemia (ALL). The multidrug resistance gene (MDR1) encodes the membrane transport protein P-glycoprotein (P-gp), which acts as an efflux pump. I...
BACKGROUND: The most prevalent cancer in pediatric is acute lymphoblastic leukemia (ALL). The multidrug resistance gene (MDR1) encodes the membrane transport protein P-glycoprotein (P-gp), which acts as an efflux pump. Interleukin 18 (IL18), an 18-kilodalton cytokine, plays a complex role in cancer, exhibiting both anti-cancer and pro-cancer properties. This study aims to investigate the association between polymorphisms in the MDR1 gene (G2677T, rs2032582) and IL18 gene variants (607C > A, rs1946518 and - 137G > C, rs187238) and their potential role in susceptibility to pediatric ALL in an Egyptian population. We hypothesize that specific polymorphisms in MDR1 and IL18 genes are significantly associated with an increased risk of developing pediatric ALL, and that these genetic variants may serve as potential biomarkers for early detection and prognosis. METHODS: MDR1 (G2677T) rs2032582, IL18 (607C > A) rs1946518, and IL18 (-137G > C) rs187238 variants were genotyped in 100 childhood ALL (58 male and 42 female) cases and 100 healthy controls (49 male and 51 female) using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique. RESULTS: The statistical analysis of the results indicated that the MDR1 (G2677T) rs2032582 genotypes (p = 0.051) and allele distribution (p = 0.217) showed no discernible variations between the controls and cases. The data indicate a strong correlation between the TT genotype and an elevated risk of ALL in both sexes. The allele frequency and genotype of IL18 (607C > A) rs1946518 exhibited a significant difference (p = 0.001) between the controls and cases. The results indicated a substantial difference in allele frequency (p = 0.0006) and genotype of the IL18 (-137G > C) polymorphism (p = 0.001) between the controls and cases. CONCLUSIONS: The results suggest that the MDR1 (G2677T) rs2032582 polymorphism may not serve as a dependable prognostic indicator of the disease. In contrast, IL18 (607C > A) rs1946518 and IL18 (-137G > C) rs187238 polymorphisms may affect susceptibility to pediatric leukemia, indicating that IL18 could be a possible biomarker for the early identification of ALL.
Time from symptom recognition to cancer diagnosis and factors linked to delayed diagnosis of hematological childhood cancers at a tertiary hospital in uganda: a mixed methods study.
Nakabiri J, Agaba B, Naitala R … +7 more , Najjuuko B, Asiimwe C, Alamo H, Mafabi B, Hockenberry M, Ssenkusu JM, Nankabirwa V
BMC Cancer · 2025 Nov · PMID 41225414 · Full text
BACKGROUND: Late presentation of childhood cancers is prevalent across several Sub-Saharan African countries, including Uganda, and is largely driven by delays in diagnosis. These delays often result in disease progressi...
BACKGROUND: Late presentation of childhood cancers is prevalent across several Sub-Saharan African countries, including Uganda, and is largely driven by delays in diagnosis. These delays often result in disease progression and poorer clinical outcomes. However, data on diagnostic timelines and the underlying factors contributing to these delays remain limited in Uganda. This study aimed to estimate the median duration from initial symptom recognition to confirmed diagnosis and to explore the determinants of diagnostic delays among pediatric cancer patients at Mulago National Referral Hospital in Uganda. METHODS: This mixed-methods study combined quantitative and qualitative data collection approaches. The quantitative component involved reviewing records of children diagnosed with leukemia or lymphoma at the hospital's Pediatric Hematology Oncology department between February 2019 and June 2023. In the qualitative component, six key informant interviews and four focus group discussions were conducted with health workers and caregivers of children diagnosed with cancer. Quantitative data were collected using a tool in Open Data Kit, then analyzed using descriptive statistics, and Kaplan Meier curves. Qualitative data were analyzed through thematic analysis. RESULTS: We analyzed records of 387 pediatric cancer patients, of whom 65.4% (253/387) were male. The median age at diagnosis was 8 years (interquartile range [IQR]: 4.7-11.7 years). The overall median duration from symptom onset to diagnosis was 47 days. Among specific cancer types, the median time to diagnosis was 31 days (IQR: 16-85 days) for leukemia and 68 days (IQR: 32.3-175.8 days) for lymphoma. Qualitative data identified several factors contributing to diagnostic delays, including caregiver-related challenges-such as limited knowledge, financial constraints, suboptimal health-seeking behaviors, and cultural beliefs-and health system barriers, including insufficient provider expertise, misdiagnoses, limited diagnostic infrastructure, and weak referral pathways. CONCLUSION: The median time to diagnosis among pediatric cancer patients was prolonged, largely attributable to suboptimal caregiver health-seeking behaviors, limited awareness among both caregivers and healthcare providers, inadequate diagnostic capacity, and inefficient referral systems. Targeted interventions to address these barriers are essential to enhance timely diagnosis and initiation of treatment, thereby improving clinical outcomes for children with cancer.
MYC amplification and MYC protein expression are poor prognostic markers in pediatric and young adult osteosarcoma.
Nagy MR, Puopolo O, Alston E … +8 more , Challa S, Ceca E, Li Y, Cherniack AD, Lazo de la Vega L, Meyerson M, Church AJ, Janeway K
Cancer · 2025 Nov · PMID 41199591 · Publisher ↗
BACKGROUND: Prognostication in pediatric and young adult osteosarcoma is typically limited to metastatic status at diagnosis and tumor necrosis after chemotherapy. Despite a complex genomic landscape, few molecular bioma...
BACKGROUND: Prognostication in pediatric and young adult osteosarcoma is typically limited to metastatic status at diagnosis and tumor necrosis after chemotherapy. Despite a complex genomic landscape, few molecular biomarkers are used clinically. This study evaluates the prognostic relevance of MYC amplification and MYC protein expression. METHODS: This study analyzed 105 patients with high-grade osteosarcoma. MYC copy number was assessed via targeted sequencing, and MYC protein expression was assessed via immunohistochemistry H score. Amplification (AMP) was defined as >7 copies; high expression (EXP) was defined as an H score of >150. Correlation between AMP and EXP was calculated, and overall survival (OS) was analyzed with Kaplan-Meier and Cox models. RESULTS: Among the 105 patients (42% female; median age, 14 years; interquartile range, 11-17 years), 16% had AMP, 22% had high EXP, and 8% had both AMP and high EXP. MYC copy number positively correlated with protein expression (r = 0.53; p < .0001). With accounting for metastatic status, AMP and high EXP had lower OS (AMP vs. non-AMP: 3-year OS, 27% vs. 74%; adjusted hazard ratio [HR], 3.4; high EXP vs. low EXP: 35% vs. 77%; adjusted HR, 4.9; both p < .0001). Patients with both AMP and high EXP had markedly lower survival compared to those with non-AMP and low EXP (3-year OS, 0% vs. 79%; adjusted HR, 17.7; p < .0001). CONCLUSIONS: MYC amplification and high protein expression both independently and concurrently predict poor survival in pediatric and young adult osteosarcoma, beyond metastatic status. Incorporating MYC status into risk stratification may enhance prognostic accuracy and inform targeted therapeutic development.
Development and internal validation of a lymphoma-specific nomogram for predicting venous thromboembolism: a retrospective cohort of 790 patients.
Pan L, Lin W, Qiu Y … +3 more , Chen J, Li N, Liu T
BMC Cancer · 2025 Nov · PMID 41194009 · Full text
BACKGROUND: Thromboembolism (TE) is a serious complication in lymphoma, driving excess morbidity and mortality. Existing prediction tools perform suboptimally in lymphoma-specific settings. METHODS: We retrospectively an...
BACKGROUND: Thromboembolism (TE) is a serious complication in lymphoma, driving excess morbidity and mortality. Existing prediction tools perform suboptimally in lymphoma-specific settings. METHODS: We retrospectively analysed 790 newly diagnosed lymphoma patients (January 2019-December 2021). Patients were randomly split 7:3 into development and internal-validation cohorts. Forty-eight candidate predictors were screened with LASSO, followed by multivariable Cox modelling to construct a nomogram. Discrimination and calibration were assessed at 6, 12 and 24 months using time-dependent ROC analysis and bootstrap calibration. RESULTS: TE occurred in 77/790 patients (9.8%). Independent predictors were ECOG performance status, prior venous thromboembolism (VTE), coronary artery disease, central venous catheterisation, and APTT category. The nomogram showed good discrimination: AUCs were 0.813, 0.818 and 0.733 at 0.5, 1.0 and 2.0 years in the development cohort, and 0.724, 0.731 and 0.659 in the validation cohort. Conventional scores performed poorly in this population (e.g., at 1 year ThroLy 0.587 vs. Khorana 0.527). Calibration plots indicated close agreement between predicted and observed risks. Patients who experienced TE had poorer overall survival, with the greatest divergence in survival curves occurring within the first six months after diagnosis. CONCLUSIONS: This lymphoma-specific model improves TE risk stratification and can inform individualised prophylaxis and early monitoring. External, multi-centre validation is warranted to confirm generalisability.
Development and prospective evaluation of a machine learning model to predict vomiting among pediatric cancer and hematopoietic cell transplant patients.
Yan AP, Guo LL, Patel P … +9 more , Schechter T, Arciniegas SE, Inoue J, Vettese E, Jessa K, Cardiff B, Tomlinson GA, Dupuis LL, Sung L
BMC Cancer · 2025 Oct · PMID 41174551 · Full text
PURPOSE: Objectives were to develop a machine learning (ML) model based on electronic health record (EHR) data to predict the risk of vomiting within a 96-hour window after admission to the pediatric oncology and hematop...
PURPOSE: Objectives were to develop a machine learning (ML) model based on electronic health record (EHR) data to predict the risk of vomiting within a 96-hour window after admission to the pediatric oncology and hematopoietic cell transplant (HCT) services using retrospective data and to evaluate the model prospectively in a silent trial. PATIENTS AND METHODS: Admissions between 2018-06-02 to 2024-02-17 (retrospective) and 2024-05-09 to 2024-08-05 (prospective) to the oncology or HCT services were included. Data source was SEDAR, a curated and validated approach to deliver EHR data for ML. Prediction time was 08:30 the morning following admission. The outcome was any vomiting within 96 h following prediction time. We trained models using L2-regularized logistic regression, LightGBM and XGBoost. Training cohorts include the target cohort and all inpatient admissions. RESULTS: There were 7,408 admissions in the retrospective phase and 340 admissions in the prospective silent trial phase. The best-performing model in the retrospective phase was the LightGBM model trained on all inpatients. The number of features in the final model was 2,859. The area-under-the-receiver-operating-characteristic curve (AUROC) was 0.730 (95% confidence interval (CI) 0.694-0.765) for the retrospective phase and 0.716 (95% CI 0.649-0.784) for the prospective silent trial phase. CONCLUSIONS: We found that data in the EHR could be used to develop a retrospective ML model to predict vomiting among pediatric oncology and HCT inpatients. This model retained satisfactory performance in a prospective silent trial. Future plans will include deployment into clinical workflows and determining if the model improves vomiting control.
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