Pediatric Blood & Cancer[JOURNAL]
Sun
200 papers
BRAF mutations and targeted therapy in unclassified pericytic tumors: insights from genetic analysis and clinical response.
Golan H, Leitner M, Vered M … +11 more , Greenberg G, Yacobi R, Tabibian-Keissar H, Toren A, Bielorai B, Rechavi G, Amariglio N, Barshack I, Yahalom R, Hirschhorn A, Yalon M
BMC Cancer · 2025 Oct · PMID 41174508 · Full text
BACKGROUND: Pericytic tumors are a group of soft tissue neoplasms characterized by a hemangiopericytoma (HPC)-like pattern. The underlying genetic lesion of pericytic neoplasms is still obscure; however, recent advances...
BACKGROUND: Pericytic tumors are a group of soft tissue neoplasms characterized by a hemangiopericytoma (HPC)-like pattern. The underlying genetic lesion of pericytic neoplasms is still obscure; however, recent advances in molecular pathology have enabled a mechanistic understanding and accurate diagnosis of these tumors. Nevertheless, a subset of unclassified pericytic tumors continues to present substantial diagnostic challenges, potentially impacting clinical decision-making and therapeutic strategies. METHODS: Using Ion AmpliSeq Comprehensive Cancer Panel (Thermo Fisher Scientific, Inc.) assay, we searched for HPC-like-associated mutations in a newborn female with a congenital large sublingual unclassified pericytic tumor that recurred after resection and was refractory to chemotherapy treatment. Further analysis of a series of other tumors with distinctive pericytic features was performed via Sanger sequencing and the results were validated via the auto genomics INFINITI and Biocartis Assays. RESULTS: A BRAF V600D mutation was identified in the tumor tissue of the newborn patient. Treatment with the BRAF inhibitor (BRAFi) dabrafenib resulted in a dramatic response and regression of the tumor. Sequencing of 15 additional HPCs revealed the presence of a BRAF V600E mutation in 6 samples. CONCLUSIONS: Our findings suggest that BRAFi may be a useful therapy for unclassified pericytic tumors. Genetic testing for BRAFV600 mutations and other actionable oncogenic variants should be part of the evaluation for pericytic neoplasms, especially with the currently available targeted drug therapies.
OPTILATER: optimal long-term survival after cancer - a cross-sectional study protocol for a quantitative survey on the care situation of long-term cancer survivors in Germany.
Martin CN, De Lazzari N, Kersten J … +11 more , Claassen K, Jansen C, Kaminski K, Baumann F, Götte M, Palm S, Stang A, Grünwald V, Dirksen U, Teufel MA, Skoda EM
BMC Cancer · 2025 Oct · PMID 41136980 · Full text
BACKGROUND: Cancer survivors in Germany face considerable challenges related to the late and long-term effects of treatment and a lack of post-treatment support. Despite an increasing number of cancer survivors, existing...
BACKGROUND: Cancer survivors in Germany face considerable challenges related to the late and long-term effects of treatment and a lack of post-treatment support. Despite an increasing number of cancer survivors, existing healthcare systems are insufficiently adapted to meet their ongoing needs, particularly for long-term survivors who may experience physical, emotional, and socio-economic hardships. This study aims to address the knowledge gaps in the care situation of long-term cancer survivors, focusing on their experiences and the barriers they face in accessing care. METHODS: This study protocol outlines the methodology for a quantitative survey involving up to 3,300 long-term cancer survivors across various cancer types in Germany. The survey assesses their experiences with cancer care, focusing on diet, exercise, mental health, sleep, cognition, overall health-related quality of life, and somatic late effects. Special attention is given to survivors from diverse socio-demographic backgrounds, including those with a migration history, in order to explore the unique challenges they face. DISCUSSION: The results of the study will contribute to the development of needs-based care recommendations for cancer survivors, particularly those in potentially vulnerable groups. The findings will inform the design of more inclusive care strategies and interventions, leading to better long-term health outcomes for cancer survivors in Germany. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00032146, registered on 03/12/2024.
Defining and measuring tolerability in pediatric, adolescent, and young adult oncology: The essential voices.
Parsons SK, Montgomery KE, Brackett J … +9 more , Devine KA, Embry LM, Greenzang KA, Lupo PJ, Nuño MM, Rosenberg AR, Roth ME, Zupanec SM, Hinds PS
Cancer · 2025 Oct · PMID 41123581 · Full text
In this review on the status of tolerability in pediatric oncology, the authors address the relevance and meaning of this important concept and offer a definition to represent treatment tolerability experiences of pediat...
In this review on the status of tolerability in pediatric oncology, the authors address the relevance and meaning of this important concept and offer a definition to represent treatment tolerability experiences of pediatric, adolescent, and young adult oncology patients. The authors acknowledge the incomplete progress of tolerability research in pediatric oncology clinical trials while describing the recent advances in validating relevant measures and embedding these in pediatric oncology clinical trials to document the symptom burden of specific cancer treatments. They advocate for the consistent use of three voices-patient, caregiver, and clinician-in pediatric oncology to achieve accurate and comprehensive estimates of treatment tolerability while recognizing that a primary voice may be necessary to match the main aim or goal of the proposed research. Future steps include establishing the validity of tolerability measures and methods in patients younger than 7 years and a careful examination of tolerability issues into survivorship.
Association of genetic variants in mA modification core genes and neuroblastoma risk.
Jiang S, Dong S, Li Y … +14 more , Lin L, Chen L, Zhang W, Zhu J, Zhang X, Yang Z, Zhang J, Cheng J, Li L, Zhou H, Li S, Yang W, He J, Zhuo Z
BMC Cancer · 2025 Oct · PMID 41107791 · Full text
Neuroblastoma tightly linked with genetic abnormality. The core genes responsible for RNA N-methyladenosine (mA) modification are critical in tumor development. Nevertheless, few reports revealed the function of mA modif...
Neuroblastoma tightly linked with genetic abnormality. The core genes responsible for RNA N-methyladenosine (mA) modification are critical in tumor development. Nevertheless, few reports revealed the function of mA modification core gene polymorphisms and the neuroblastoma risk. We carried out this study to verify the association of 12 single-nucleotide polymorphisms (SNPs) with neuroblastoma susceptibility. This study recruited 898 cases with newly diagnosed neuroblastoma and 1734 Healthy controls from eight medical centers. We selected 12 SNPs from mA modification genes ALKBH1, TRMT6, TRMT61B, and TRMT10C, and genotypes were determined by the TaqMan method. We used univariable and multivariable logistic regression models to analyze the association of SNPs with neuroblastoma risk, followed by stratified analysis. Statistical analysis showed that TRMT6 rs236170 GG (AOR = 1.23, 95% CI = 1.02-1.50, P = 0.034), rs451571 CC (AOR = 1.46, 95% CI = 1.01-2.11, P = 0.043), rs236188 AA (AOR = 2.65, 95% CI = 1.16-6.07, P = 0.021), rs236110 AA (AOR = 1.91, 95% CI = 1.29-2.82, P = 0.001), and ALKBH1 rs6494 AA (AOR = 4.27, 95% CI = 1.31-13.93, P = 0.016), rs176942 GG (AOR = 1.98, 95% CI = 1.35-2.89, P = 0.0005) were neuroblastoma risk variants; the ALKBH1 rs1048147 CC (AOR = 0.80, 95% CI = 0.68-0.94, P = 0.007) was inverse associated with neuroblastoma risk. The eQTL analysis showed that functional annotation of rs6494 T > A may be potential function variants through decreasing ALKBH1 gene expression mRNA, rs451571 T > C, rs236188 G > A, rs236110 C > A are associated with neuroblastoma risk through increasing the expression of its nearby genes RP5-967N21.11 and lowering the expression of MCM8. Our research showed some SNPs in the mA modification core genes are related to neuroblastoma.Clinical perspectives(i) Few reports have revealed the function of mA modification core gene polymorphisms in neuroblastoma risk.(ii) After genotyping 12 SNPs with potential functions in four mA modification core genes in children with neuroblastoma and healthy controls, we found several neuroblastoma predisposition loci, including TRMT6 rs236170, rs451571, rs236188, rs236110, and ALKBH1 rs6494, rs176942, and rs1048147. The eQTL assessment demonstrated that rs6494 T > A may be a potential functional variant by decreasing ALKBH1 mRNA expression.(iii) Our research is the first to reveal mA modification core gene SNPs and neuroblastoma risk.
Incidence of chronic medical conditions among survivors of adolescent and young adult cancer compared to a population without cancer.
Keegan THM, Abrahão R, Chubak J … +14 more , Sauder CAM, Ruddy KJ, Quesenberry C, Li Q, Haupt EC, Laurent CA, Brunson AM, Casperson M, Chao C, Smitherman AB, Nichols HB, Kirchhoff AC, Kushi LH, Hahn EE
Cancer · 2025 Oct · PMID 41070762 · Full text
BACKGROUND: Few studies have assessed the burden of chronic medical conditions in adolescent and young adult (AYA) cancer survivors. This study estimated the risk of these conditions among AYA survivors compared to a mat...
BACKGROUND: Few studies have assessed the burden of chronic medical conditions in adolescent and young adult (AYA) cancer survivors. This study estimated the risk of these conditions among AYA survivors compared to a matched cohort without cancer. METHODS: This retrospective cohort study included 2-year survivors (n = 14,917) of 11 common AYA (15-39 years) cancers diagnosed at the integrated health care organizations of Kaiser Permanente (KP) Southern and Northern California during 2006-2020. A comparison cohort (n = 149,164) without cancer (matched 10:1 by age, sex, calendar year, and KP site) was included. Cumulative incidence (CMI) accounting for death as a competing risk was calculated. Poisson regression estimated the incidence rate ratio (IRR) of each condition in cancer survivors versus the matched cohort, adjusting for age, sex, and race/ethnicity. RESULTS: The 5-year CMI was highest for thyroid (17.4%), respiratory (6.6%), cardiovascular (5.0%), and liver (4.8%) diseases. At 10 years, the CMI of any condition was 39% in survivors versus 26% in the matched cohort. Survivors had a 2-fold increased risk of being diagnosed with any medical condition (IRR, 2.0; 95% confidence interval [CI], 1.9-2.0) as well as two or more conditions (IRR, 2.3; 95% CI, 2.2-2.5). Risk was highest among survivors of hematologic cancers and those diagnosed with distant stage disease. Elevated risks were observed within all sociodemographic groups of this insured population. CONCLUSION: AYAs with cancer had a higher risk of chronic medical conditions compared to those without cancer. Long-term surveillance, risk mitigation through lifestyle modifications and effective disease management are crucial to reduce premature mortality.
The relationship between urine output and time to methotrexate clearance in pediatric leukemia patients receiving high-dose methotrexate therapy.
Wang YL, Chang TY, Chen SH … +3 more , Hsiao YW, Wen YC, Jaing TH
BMC Cancer · 2025 Oct · PMID 41068669 · Full text
BACKGROUND: High-dose methotrexate (HD-MTX) is a cornerstone of pediatric acute lymphoblastic leukemia (ALL) treatment but poses a risk for delayed clearance and associated toxicities. While hydration is standard to enha...
BACKGROUND: High-dose methotrexate (HD-MTX) is a cornerstone of pediatric acute lymphoblastic leukemia (ALL) treatment but poses a risk for delayed clearance and associated toxicities. While hydration is standard to enhance methotrexate (MTX) excretion, the relationship between urine output (UO) and time to MTX clearance remains underexplored. METHODS: We conducted a retrospective study of pediatric ALL patients treated with HD-MTX at Chang Gung Memorial Hospital between August 2023 and February 2025. Patients were stratified into higher (H-UO) and lower urine output (L-UO) groups using a 5.0 mL/kg/hr cutoff. Clinical outcomes including time to MTX normalization, delayed MTX clearance, hospitalization duration, and use of adjunctive diuretics were analyzed. RESULTS: Thirty-nine patients were included. The H-UO group showed significantly faster MTX clearance (2.0 vs. 4.0 days, P = 0.0035), lower incidence of delayed clearance (18.2% vs. 70.6%, P = 0.0025), and shorter hospital stays (5.0 vs. 7.0 days, P = 0.019). Diuretic use was higher in the L-UO group, primarily as a reactive measure. No significant difference in MTX-related major toxicities was observed. CONCLUSIONS: Higher UO is associated with more efficient time to MTX clearance and shorter hospitalization in pediatric ALL patients receiving HD-MTX. Prospective studies are warranted to optimize supportive care protocols.
A systematic review of the last two decades of NK cell-based clinical trials: state of the art of AML therapy.
Bakhtiyaridovvombaygi M, Kheyrandish S, Safdari SM … +12 more , Eskandrian S, Rousta H, Hossaini D, Rastgar A, Yazdanparast S, Firuzpour F, Shabihi N, Izadpanah A, Parkhideh S, Roshandel E, Hajifathali A, Gharehbaghian A
BMC Cancer · 2025 Sep · PMID 41029201 · Full text
BACKGROUND: Acute myeloid leukemia (AML) remains a significant challenge in hematologic oncology, with high relapse rates and limited treatment options. Natural killer (NK) cells, as key effectors of innate immunity, hav...
BACKGROUND: Acute myeloid leukemia (AML) remains a significant challenge in hematologic oncology, with high relapse rates and limited treatment options. Natural killer (NK) cells, as key effectors of innate immunity, have shown strong anti-leukemic activity, making them promising candidates for immunotherapy. Despite increasing clinical interest, a comprehensive evaluation of NK cell-based therapies in AML is still needed. METHODS: This systematic review follows the PRISMA guidelines to analyze clinical trials evaluating NK cell therapy in AML, either as a standalone treatment or in combination with hematopoietic stem cell transplantation (HSCT). A literature search across five major databases identified relevant studies, with data extraction focusing on NK cell sources, isolation and expansion strategies, clinical efficacy, and safety outcomes. RESULTS: A total of 48 clinical trials were identified, including 27 trials specific to AML and 21 trials involving AML along with other hematologic malignancies. Peripheral blood (PB)-derived NK cells were the main source (82%), with purification methods mainly using CliniMACS-based CD3 depletion and CD56 selection. Short-term activation (≤ 24 h) and long-term expansion (> 7 days) were employed in 36% of studies each. In non-HSCT transplant settings, NK cell therapy achieved a complete remission (CR) rate of 37.1% and an event-free survival (EFS) of 71.3%, while post-HSCT overall survival (OS) reached 39.5%. Notably, graft-versus-host disease (GVHD) incidence stayed low, highlighting the favorable safety profile of NK cell therapy. CONCLUSION: NK cell-based therapy represents a promising and well-tolerated immunotherapeutic approach for AML. However, optimizing NK cell expansion, persistence, and clinical applications requires further investigation through large-scale, controlled trials.
Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma.
Anguera G, Gallego O, Llobet M … +7 more , Berga N, Moreno-Martinez ME, Leon X, Kratz C, Garcia-Escudero R, Minguillón J, Surrallés J
BMC Cancer · 2025 Aug · PMID 40859225 · Full text
BACKGROUND: Individuals diagnosed with Fanconi anemia (FA) present an incidence of 500- to 700-fold higher to develop head and neck squamous carcinomas (HNSCCs) compared to the general population. Effective anticancer tr...
BACKGROUND: Individuals diagnosed with Fanconi anemia (FA) present an incidence of 500- to 700-fold higher to develop head and neck squamous carcinomas (HNSCCs) compared to the general population. Effective anticancer treatments for FA-HNSCCs are missing. Several studies demonstrated that FA-HNSCCs overexpress the epithelial growth factor receptor (EGFR) and their viability is highly dependent on this pathway, as FA-HNSCCs cells are highly sensitive to EGFR inhibitors such as afatinib in preclinical models, which led to an orphan drug designation by EMA in 2018. METHODS: The AFAN trial is a phase Ib/II, single arm, non-randomized, open-label, multicenter study to determine whether afatinib is effective and safe in patients with FA and advanced / metastatic HNSCC. Patients could be treatment-naïve or progressed to a previous systemic treatment with immunotherapy, chemotherapy or cetuximab. Afatinib will be administered orally at a starting dose of 20 mg /day (weeks 1-2), escalating to 30 mg / day at weeks 3-4 and to 40 mg / day thereafter provided no adverse events occur. Treatment will be maintained until disease progression / secondary primary tumor, loss to follow-up, unacceptable toxicity, patient withdrawal or death. Dose reductions and delays will be allowed. All patients will undergo periodic tumor assessments by CT or MRI scan every 12 weeks (3 months) from the start of the study treatment until progression / SPT or patient withdrawal. The primary endpoint is objective response rate (ORR) after 9 months of study treatment initiation according to RECIST V1.1. Secondary endpoints include disease control rate, duration of response, disease-free survival, overall survival, safety, patient reported outcomes and ancillary studies. The expected sample size is 25 patients calculated using a Simon II stage design (α = 0.1; β = 80%), taking as null hypothesis a 9-month ORR of 20% and an alternative ORR of 40%. DISCUSSION: The AFAN trial will investigate if afatinib is an effective treatment in FA patients with unresectable and / or metastatic locoregionally advanced squamous cell carcinoma of the oral cavity, oropharynx or hypopharynx or larynx. TRIAL REGISTRATION: EU CT 20,245,114,772,900 / www. CLINICALTRIALS: gov NCT06648096 (August, 1st 2024).
MRD4U: A path to development for personalized liquid biopsy for children with central nervous system tumors.
Miller AR, Shah T, Strawser CN … +24 more , Rivaldi A, Wilson SA, Zhong H, Lucyshyn JM, Garfinkle EA, McCoy M, Cummins S, Bravo AO, Chang P, Wheeler GL, Gordon DM, Kelly BJ, Evanovich C, Potter SL, Varga EA, Rodriguez DP, Wilson RK, Cottrell CE, Salloum R, Khan S, Fouladi M, Mardis ER, Lazow MA, Miller KE
BMC Cancer · 2025 Aug · PMID 40849662 · Full text
BACKGROUND: Liquid biopsy assays using cerebrospinal fluid (CSF) can revolutionize care for children with central nervous system (CNS) tumors by enabling precise monitoring of therapeutic responses and detecting recurren...
BACKGROUND: Liquid biopsy assays using cerebrospinal fluid (CSF) can revolutionize care for children with central nervous system (CNS) tumors by enabling precise monitoring of therapeutic responses and detecting recurrence or measurable residual disease (MRD). These assays can detect cell-free, circulating tumor DNA (ctDNA) via somatic alterations, though accurately measuring low-abundance ctDNA in CSF is challenging. METHODS: Our research focused on the optimization of next-generation sequencing library preparation from cell-free DNA (cfDNA), evaluating four commercial kits to address the low nucleic acid yield in CSF-derived cfDNA. The selected kit minimized false positives and detected somatic variants at 5% variant allele frequency using 0.1 ng input of synthetic cfDNA, suitable for low-volume CSF samples. RESULTS: We then applied our optimized workflow to six children with CNS tumors using a personalized hybrid-capture sequencing strategy ("MRD4U"), in which individualized panels were designed based on each patient's tumor sequencing. Using MRD4U, we identified ctDNA in two samples, even though neither patient had radiographic or clinical evidence of disease at the time of liquid biopsy. Notably, one ctDNA-positive patient developed radiographic recurrence four months later, demonstrating the assay's potential to detect molecular relapse ahead of conventional clinical measures. CONCLUSIONS: These findings demonstrate applicability of our personalized MRD4U assay in early detection of disease recurrence. Unlike non-targeted or tumor-agnostic CSF liquid biopsy approaches, MRD4U leverages patient-specific genomic information to enable sensitive, tumor-informed monitoring that can be deployed across a wide range of pediatric CNS tumors. Our approach is broadly applicable to any tumor type with existing genomic data, enabling ctDNA detection across diverse diagnoses. Ultimately, this strategy may inform clinical decision-making and enable earlier therapeutic intervention.
Physical fitness and clinically assessed disease burden in long-term childhood cancer survivors-The SURfit study.
Mayr AK, Zürcher S, Bänteli I … +6 more , Hebestreit H, Kasteler R, von der Weid NX, Kriemler S, Schindera C, Rueegg CS
Cancer · 2025 Sep · PMID 40831029 · Full text
BACKGROUND: Identifying disease burden among childhood cancer survivors (CCS) can guide tailored care. Physical fitness predicts health and mortality and may help reduce disease burden in CCS. This study aimed to 1) desc...
BACKGROUND: Identifying disease burden among childhood cancer survivors (CCS) can guide tailored care. Physical fitness predicts health and mortality and may help reduce disease burden in CCS. This study aimed to 1) describe the burden of clinically ascertained adverse health outcomes in long-term CCS, and 2) investigate the association between physical fitness and adverse health outcomes. METHODS: This study used baseline data of the SURfit study, a randomized controlled physical activity trial. The authors included 163 CCS, diagnosed <16 years, ≥16 years at enrollment, and ≥5 years since last cancer diagnosis. Clinically assessed health outcomes were categorized using the Common Terminology Criteria for Adverse Events. Physical fitness was assessed by cardiopulmonary-exercise-test (CPET), hand-grip strength, and the 1-minute sit-to-stand test (STS). Using multivariable Poisson regression models, this study investigated the association between physical fitness and adverse health outcomes. RESULTS: Participants (30.5 ± 8.6 years old, time since diagnosis 22.9 ± 9 years) had 1170 adverse health outcomes, with 99% CCS having at least one. Musculoskeletal disorders were most common (130 of 163 [80%]). Higher levels of physical fitness were associated with fewer adverse health outcomes of any grade (CPET: prevalence rate ratio [PRR], 0.71 per watt/kg bodyweight, 95% confidence Interval [CI], 0.63-0.81, p < .001; hand-grip: PRR, 0.60 kg/kg bodyweight; 95% CI, 0.35-1.03, p = .063; STS: PRR, 0.95 per five repetitions; 95% CI, 0.93-0.97, p < .001). CONCLUSION: CCS participating in an exercise intervention trial experienced a high burden of adverse health outcomes. Increased physical fitness was associated with reduced disease burden for all survivors, emphasizing the importance of encouraging fitness improvements, regardless of cancer history.
Investigating the nutritional status, outcomes and needs of adolescents and young adults (AYA) following a cancer diagnosis: protocol for a mixed-methods study.
Murnane A, Laing E, Steer B … +13 more , Lewin J, Gilbertson H, Mount E, Silvers MA, Loeliger J, Bartle J, Mellett K, Savva J, Fedele PL, Orme LM, Super L, Gough K, Thompson K
BMC Cancer · 2025 Aug · PMID 40826395 · Full text
BACKGROUND: Cancer treatment for adolescents and young adults (AYA) can be highly challenging and interferes with optimal nutrition, which is vital for healthy development, physical growth, and well-being. Cancer malnutr...
BACKGROUND: Cancer treatment for adolescents and young adults (AYA) can be highly challenging and interferes with optimal nutrition, which is vital for healthy development, physical growth, and well-being. Cancer malnutrition and associated negative outcomes are well-studied in adult and paediatric populations, but the specific nutrition complications and requirements for AYA with cancer are poorly understood. This study aims to explore and describe the nutritional status, needs and outcomes of AYA after a diagnosis of cancer. METHODS AND ANALYSIS: The AYCANN-study (adolescent and young adult cancer nutrition project) adopts a mixed-methods study design, conducted over three inter-related studies; (1) Prospective observational study of AYA between 15 and 25 years, following diagnosis of any cancer type, to quantitatively assess changes in body weight, muscle mass/function, nutritional status, and health related quality of life (HRQoL). Study assessments will be undertaken at four time-points (recruitment, and 2- 4- and 6-months post-recruitment) and will include screening for nutrition risk (PNST or MST); assessment of nutritional status (PG-SGA, mid-upper arm circumference); assessment of muscle strength (hand-grip strength); frequency of dietitian referral, nutrition support and symptoms; and assessment of health-related quality of life (AQoL-6D); (2) Qualitative study using focus groups with AYA to assess access to nutrition related care and preference for nutrition services; (3) Qualitative study, utilising focus groups with oncology healthcare professionals (OHP) to explore and assess current access to nutrition-related care for AYA following a cancer diagnosis along with OHP nutrition education needs, service delivery and research priority areas. For study 1, statistical analysis will be primarily descriptive, and effect size estimates (Cohen's d) will be used to characterise any differences between nutritional status groups at follow-up assessments. Thematic analysis will be undertaken for study 2 and 3 to understand patients and OHP access to and experience of nutrition-related care. DISCUSSION: This multi-site longitudinal study will explore and describe the nutritional status, needs and nutrition-related outcomes of AYA after a cancer diagnosis. Results will inform future clinical practice guidelines and interventional nutrition research targeting patients identified at greater risk of nutritional complications.
The International Soft Tissue Sarcoma Consortium: The baseline analysis of rhabdomyosarcoma data.
Bisogno G, Sparber-Sauer M, Rodeberg D … +13 more , Merks JHM, Koscielniak E, Wolden SL, De Salvo GL, Del Bianco P, Xue W, Ebinger M, Vokuhl C, Venkatramani R, Volchenboum SL, Furner B, Minard Colin V, Hawkins DS
Cancer · 2025 Jul · PMID 40632016 · Full text
BACKGROUND: The International Soft Tissue Sarcoma Consortium (INSTRuCT) was established in 2017 to enhance international collaboration. This study describes the characteristics of rhabdomyosarcoma (RMS) patients in the I...
BACKGROUND: The International Soft Tissue Sarcoma Consortium (INSTRuCT) was established in 2017 to enhance international collaboration. This study describes the characteristics of rhabdomyosarcoma (RMS) patients in the INSTRuCT database and examines differences across contributing groups. METHODS: INSTRuCT includes data Children's Oncology Group (COG), Cooperative Weichteilsarkom Studiengruppe (CWS), and European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) along with prior studies from Malignant Mesenchymal Tumour Committee (MMT) and Italian Soft Tissue Sarcoma Committee (STSC). Data standardization was supported by the University of Chicago's Pediatric Cancer Data Commons. Pseudonymized patient-level data from clinical trials were harmonized. Differences across groups were assessed using χ or Kruskal-Wallis tests. RESULTS: As of March 2025, INSTRuCT includes 6972 RMS patients from 16 trials (1990-2016). Embryonal RMS was the most common histology in all groups (range, 45.4%-62.2%). Alveolar RMS was less frequent in EpSSG (26.8%) although the rate of RMS fusion-positive was comparable across groups (74.6%-81.9%). COG and EpSSG had more T1 tumors, (53.2% and 51.4%) with COG reporting more tumors <5 cm (52%). Nodal involvement was least reported in MMT (15.4%). Metastatic patients were less represented in MMT (11%) and EpSSG (13.3%). Tumor site distribution varied: genitourinary nonbladder/prostate RMS was more common in COG, whereas head and neck nonparameningeal and orbital RMS were more represented in MMT and STSC. MMT had fewer completely resected tumors (8.9%). CONCLUSION: Differences among RMS study populations reflect evolving diagnostic criteria and treatment strategies that should be considered in future analyses. INSTRuCT offers a valuable international data set for RMS research.
Comprehensive assessment of sexual function in male survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Marchak JG, Seidel KD, Cherven BO … +9 more , Klosky JL, Ritenour CWM, Leisenring WM, Sklar CA, Ford JS, Krull KR, Robison LL, Armstrong GT, Meacham LR
Cancer · 2025 Jul · PMID 40614134 · Full text
BACKGROUND: Assessment of sexual dysfunction among adult male survivors of childhood cancer has primarily been limited to erectile dysfunction. This study aimed to characterize sexual functioning more comprehensively amo...
BACKGROUND: Assessment of sexual dysfunction among adult male survivors of childhood cancer has primarily been limited to erectile dysfunction. This study aimed to characterize sexual functioning more comprehensively among a large population of male survivors of childhood cancer. METHODS: Male survivors (N = 1595, 22.0-59.4 years, median age, 37.8 years) and siblings (N = 269, 21.5-60.8 years, median age, 38.9 years) from the Childhood Cancer Survivor Study completed the Sexual Functioning Questionnaire (SFQ) to assess interest, desire, arousal, satisfaction, activity, orgasm, masturbation, relationship, and problems. Poor sexual functioning was defined as SFQ Total scores >2 standard deviations below siblings' mean. Multivariable logistic regression identified risk factors for poor sexual function. RESULTS: Survivors (8.3%) were more likely to report poor sexual functioning as compared to siblings (4.9%, odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.4) and reported lower SFQ total scores (p < .001) and lower means on seven subscales. Poor sexual functioning among survivors was associated with older age (40-49 years: OR, 3.81; 95% CI, 1.78-8.18; 50-59 years: OR, 6.45; 95% CI, 2.28-18.30), not being married (OR, 4.39; 95% CI, 2.66-7.26), lower education (OR, 3.07; 95% CI, 1.32-7.14), learning/memory problems (OR, 1.83; 95% CI, 1.02-3.27), and high-dose cranial (≥40 Gy: OR, 3.45; 95% CI, 1.58-7.51) or high-dose testicular (≥10 Gy: OR, 4.16; 95% CI, 1.66-10.39) radiation. CONCLUSIONS: Adult male survivors report poor sexual functioning at twice the rate expected before age 60 years. High-dose cranial or testicular radiation, as well as social and cognitive factors, contributes to risk. Improved awareness of sexual dysfunction prevalence and risk factors in male childhood cancer survivors can help clinicians better assess and treat those at highest risk.
Circulating tumor cells and clusters as liquid biomarkers for the diagnosis and prognosis of neuroblastoma.
Xu H, Cao N, Dai W … +27 more , Sima C, Yi M, Chen S, Chen X, Liu C, Yu U, Lang H, Zhou Z, Yang N, Wang C, Jiang X, Gan Y, Wang J, Wang Y, Yao N, Xiao L, Zhang Q, Sun J, Lin Z, Zhang G, Zhang J, Feng H, Song J, Liu S, Liu Z, Wen F, Yuan X
BMC Cancer · 2025 Jul · PMID 40597797 · Full text
BACKGROUND: The clinical significance of circulating tumor cell (CTC) clusters in highly metastatic tumors hasn't yet been revealed. Here, we demonstrated the diagnostic and prognostic value of CTC clusters in neuroblast...
BACKGROUND: The clinical significance of circulating tumor cell (CTC) clusters in highly metastatic tumors hasn't yet been revealed. Here, we demonstrated the diagnostic and prognostic value of CTC clusters in neuroblastoma (NB) which is the most prevalent childhood extracranial solid tumor. METHODS: We employed cascaded filter deterministic lateral displacement microfluidic chips to enrich CTCs and CTC clusters in 64 newly diagnosed NB patients. CTCs and CTC clusters were identified by CD45-, GD2+/PHOX2B+, DAPI + immunofluorescence staining, with cells displaying characteristic neoplastic morphology. RESULTS: Among NB patients, 85.94% and 50.00% were positive for CTCs and CTC clusters, respectively; no CTCs or CTC clusters were detected in healthy children. Moreover, CTC and CTC cluster numbers differed significantly across different primary sites, clinical and pathologic features, and risk stratifications, while no significant differences in CTC and CTC cluster counts were observed in relation to sex, age, and MYCN gene amplification. CTCs and CTC clusters indicated metastasis and strongly correlated with minimal residual disease. Of note, CTC clusters ≥ 2.5/2 mL were closely associated with bone marrow metastasis and demonstrated significant differences in the hazard ratio of overall survival. CONCLUSIONS: CTCs and CTC clusters are sensitive non-invasive biomarkers for NB diagnosis and prognosis, especially the prominent role in tumor emergencies. CTC clusters closely correlate with bone marrow metastasis and represent promising indicator for the monitoring of metastasis in NB emergencies. The mechanisms of CTC cluster formation and their specific role in the metastasis cascade deserve further elucidation which may serve as targets to inhibit NB bone marrow metastasis.
Impact of neoadjuvant chemotherapy on tumour volume in unilateral Wilms tumour histotypes: a retrospective study.
Benlhachemi S, Khattab M, Hattoufi K … +2 more , Abouqal R, El Fahime E
BMC Cancer · 2025 Jul · PMID 40597778 · Full text
BACKGROUND: Wilms tumour (WT), the most common paediatric kidney tumour, is treated in Morocco following the SIOP protocol, which practices neoadjuvant chemotherapy (NAC). The response to NAC can be assessed by consideri...
BACKGROUND: Wilms tumour (WT), the most common paediatric kidney tumour, is treated in Morocco following the SIOP protocol, which practices neoadjuvant chemotherapy (NAC). The response to NAC can be assessed by considering both tumor volume reduction and the proportion of therapy-induced changes observed in histological specimens, including necrosis. This retrospective study assesses the impact of NAC on tumour volume across various WT histotypes and correlates these changes with proportions of therapy-induced necrosis. METHODS: We analysed imaging data and anatomopathological reports, before and after NAC, of 56 patients with unilateral WT, admitted to the children's hospital in Rabat, from January 2014 to February 2018. RESULTS: NAC significantly reduced tumour volume in 82% of WT cases, with an average decrease of 65% in tumour size, with a p < 0.001. Notably, the regressive, blastemal, and mixed types exhibited the most significant response to NAC, in 94%, 82%, and 92% of cases, with p < 0.001, 0.010, 0.002, respectively. The epithelial type showed a decrease in tumour volume in 73% of cases, with p = 0.041. Whereas, the stromal type did not exhibit a significant decrease in tumour volume following NAC (p = 0.790). Moreover, tumor volume decreased by 43% in one case with focal anaplasia and blastemal type, but increased by 7% in the other case with focal anaplasia and regressive type. The change in tumour volume and necrosis demonstrates a moderate negative correlation (Rho = -0.428; p < 0.001). An increase in the proportion of necrosis is associated with a decrease in tumor volume. CONCLUSION: Our findings show a significant reduction in tumour size following NAC in all WT histotypes, with the exception of the stromal type, suggesting the need for alternative strategies, such as intensified treatment or initial nephrectomy for operable tumours.
Measurable residual disease (MRD) as a surrogate end point for clinical drug approval in acute myeloid leukemia (AML): Perspectives from the MRD Partnership and Alliance in AML Clinical Treatment Consortium.
Boyiadzis M, Wei AH, Paiva B … +18 more , Freeman SD, Kaspers G, Chyla B, Hersey S, Patel R, Maloney B, Blanchet Zumofen MH, Van Hoef M, Wulff B, Obourn V, Patel S, Lopes de Menezes D, Shi Q, Bengoudifa BR, Dimier N, Prior TJ, Roboz GJ, Prebet T
Cancer · 2025 Jul · PMID 40576165 · Full text
Despite advances in acute myeloid leukemia (AML) treatment, significant unmet medical needs remain. Surrogate end points for overall survival can accelerate the approval of novel therapies. Measurable residual disease (M...
Despite advances in acute myeloid leukemia (AML) treatment, significant unmet medical needs remain. Surrogate end points for overall survival can accelerate the approval of novel therapies. Measurable residual disease (MRD) is a promising surrogate end point candidate, providing a sensitive and quantitative assessment of disease burden. Numerous studies have demonstrated that negative MRD status-across diverse methodologies, assessment timepoints and thresholds, patient subgroups, and clinical settings-independently predicts improved survival. Although MRD can inform therapeutic decisions at the patient level, its formal integration as a primary surrogate end point in regulatory frameworks for clinical trials requires rigorous validation. MRD Partnership and Alliance in AML Clinical Treatment (MPAACT) is a research consortium among industry and academic leaders. MPAACT actively engages with regulatory agencies, health technology assessment bodies, technology vendors, and patient groups to establish a pathway for validating MRD as a surrogate end point in AML clinical trials. For the current article, the authors reviewed the status of MRD assessment, its use in recent clinical trials, current MRD assessment methodologies, standardization, regulatory guidance, statistical approaches, and patient access considerations necessary for MRD to become a surrogate clinical trial end point. The extensive collaboration between MPAACT, global industry, and academic partners-including data sharing and resource integration-underscores the collective commitment to advancing AML therapies. Establishing MRD as a surrogate end point could accelerate the development and approval of innovative treatments, ultimately improving patient outcomes.
Extremity rhabdomyosarcoma in children, adolescents and young adults: A report from Children's Oncology Group trials.
Oberoi S, Xue W, Qumseya A … +9 more , Scharschmidt T, Binitie O, Sorger JI, Kumar KA, Wong K, Donaldson SS, Teot L, Rudzinski ER, Venkatramani R
Cancer · 2025 Jun · PMID 40464368 · Full text
BACKGROUND: Long-term survival and prognostic factors for patients with extremity rhabdomyosarcoma (RMS) treated on contemporary Children's Oncology Group (COG) trials are unknown. METHODS: Data of extremity RMS patients...
BACKGROUND: Long-term survival and prognostic factors for patients with extremity rhabdomyosarcoma (RMS) treated on contemporary Children's Oncology Group (COG) trials are unknown. METHODS: Data of extremity RMS patients enrolled on COG trials from 1998 to 2014 were analyzed to estimate event-free survival (EFS) and overall survival (OS), and factors associated with survival. RESULTS: The authors identified 264 extremity RMS patients, 159 (60%) localized and 105 (40%) metastatic. The 5-year EFS and OS of patients with localized disease was 62.6% (54%, 71.2%), and 78.7% (71.4%, 85.9%) and of those with metastatic disease was 7.7% (2.2%, 13.2%) and 22.7% (13.9%, 31.4%). Age at diagnosis was associated with EFS, whereas both sex and age at diagnosis were associated with OS. In metastatic patients, a lower Oberlin score was associated with improved EFS and OS, and females had improved OS. The 5-year EFS of patients with localized disease treated on the D9803 trial was not statistically different from those treated on ARST0531, but 5-year OS was statistically superior (adjusted hazard ratio [adjHR] 0.43 [0.21, 0.86]) after adjusting for potential confounders. The 5-year EFS of group 3 patients undergoing delayed primary excision (DPE) with R0 margins was better than those with DPE with positive margins (adjHR 0.31 [0.11, 0.87]) and comparable to group 2 RMS patients. CONCLUSIONS: Outcomes for metastatic extremity RMS remain poor. Among patients with localized disease, younger age, female sex, and treatment on D9803 were associated with improved OS, whereas DPE with R0 margins led to better EFS compared to DPE with positive margins in group 3 patients.
Impact of maintenance treatment on male gonadal function in patients treated for localized rhabdomyosarcoma in RMS2005 trial in France.
Rossillon L, Thomas-Teinturier C, Orbach D … +18 more , Tabone MD, Bertrand A, Ansoborlo S, Defachelles AS, Rome A, Haouy S, Plantaz D, Bolle S, Bernier-Chastagner V, Guerin F, Sarnacki S, Philippe-Chomette P, Allodji R, Lenez L, Métayer L, Barraud-Lange V, Minard-Colin V, Fresneau B
Cancer · 2025 Jun · PMID 40433871 · Full text
BACKGROUND: Maintenance treatment with vinorelbine and oral cyclophosphamide (oral-CPM) improves outcome of nonmetastatic high-risk (HR) and very-high risk (VHR) rhabdomyosarcoma (RMS) patients. However, gonadal toxicity...
BACKGROUND: Maintenance treatment with vinorelbine and oral cyclophosphamide (oral-CPM) improves outcome of nonmetastatic high-risk (HR) and very-high risk (VHR) rhabdomyosarcoma (RMS) patients. However, gonadal toxicity of maintenance was not yet investigated. METHODS: The authors focused their analysis on male gonadal toxicity in HR/VHR groups of RMS2005 trial, in France. In the HR group, patients were randomized to receive or not receive 6 months of maintenance (after nine or four IVADo] + five IVA). In the VHR group, patients received 6 months of maintenance (after four IVADo + five IVA). Exocrine gonadal dysfunction (EGD) was defined as followed: follicle-stimulating hormone level >10 IU/L and/or inhibin-B <80 pg/mL and/or oligoasthenozoospermia/azoospermia. RESULTS: Among 86 eligible 5-year RMS survivors ≥12 years old, 49 had available gonadal evaluation (median age at diagnosis = 6.4 years, median age at evaluation = 18.7 years, 41 HR/8 VHR). Twenty-six (53%) received oral-CPM (median cumulative dose = 4.2 g/m, range = 0.7-9.0). EGD was reported in 18 of 49 (37%). Exposure to oral-CPM (odds ratio [OR], 5.45; 95% confidence interval [CI], 1.30-22.92, p = .021) and older age at diagnosis (compared to 0-5 years, OR, 9.61; 95% CI, 1.49-62.15 and OR, 14.10; 95% CI, 1.89-105.33, p = .025) were significantly associated with EGD. Higher cumulative dose of oral-CPM (>4.5 g/m) tended to be more toxic (compared to nonexposure, OR, 2.95; 95% CI, 0.78-11.09 and OR, 7.20; 95% CI, 1.01-51.39, p = .094). CONCLUSIONS: Oral-CPM induces additional gonadal damage to the ifosfamide-based induction regimen. Fertility preservation could be considered in patients exposed to maintenance, especially those >5 years old and exposed to ≥12 months of oral-CPM.
The safety and feasibility of multiple intrathecal injections of allogenic NK cells in pediatrics with refractory/recurrent brain tumors.
Mahdizadeh H, Izadpanah A, Nouri Y … +14 more , Shams P, Daneshjou D, Ahari AA, Tabibkhooei A, Haghighatkhah H, Vosough M, Faranoush P, Azimi M, Yousefi S, Barzegari A, Khosravani A, Asl NS, Faranoush M, Ebrahimi M
BMC Cancer · 2025 May · PMID 40426086 · Full text
BACKGROUND: Pediatric glioma is a rare condition that can lead to significant mortality and morbidity due to its high recurrence rate. This study is a phase I nonrandomized clinical trial that was conducted to assess the...
BACKGROUND: Pediatric glioma is a rare condition that can lead to significant mortality and morbidity due to its high recurrence rate. This study is a phase I nonrandomized clinical trial that was conducted to assess the safety, feasibility, and potential efficacy of the intrathecal (IT) injection of multiple doses of allogenic NK cells in pediatric patients with refractory/recurrent gliomas. METHODS: Allogeneic NK cells were isolated from random healthy unrelated donors via positive selection of CD56 + cells. Nine patients were selected according to the inclusion criteria and received weekly doses of up to 10 doses of 5 × 10 NK cells/injection. Adverse events grading was done based on Common Terminology Criteria for Adverse Events (CTCAE) Check lists. The size of the tumor, degree of spinal spreading and duration of relapse during 18 month followup were considered components of efficacy. Additionally, six patients who received conventional treatment were selected retrospectively. RESULTS: Multiple intrathecal injections of allogeneic NK cells in pediatric gliomas were safe, without any serious adverse events (SAEs). The most prevalent AEs were headache [29% (17% grade 1 and 13% grade 2)], fever and chills [21% (17% grade 1 and 4% grade 2)], vomiting [13% grade 2], and back pain [12% (4% grade 1 and 8% grade 2)]. 18 months of follow-up, among the five patients in the intervention group who were still alive (August 7, 2024), three exhibited stable disease (SD), one had progressive disease (PD), and one experienced a partial response (PR) with a reduction in tumor size. Among the four deceased patients, two died due to tumor progression, and two died due to infections. In the retrospective control group, five out of six patients developed PD and leptomeningeal spread (LMS), four of whom died, and one patient showed radiological evidence of a complete response (CR). Cerebrospinal fluid (CSF) analysis revealed increases in the percentages of NK and T cells and significant reductions in the levels of IFN-γ and TNF-α. CONCLUSIONS: Multiple intrathecal injections of allogeneic NK cells are safe and feasible in pediatric patients with refractory/recurrent gliomas. Although we reported a reduction in recurrence episodes and an increase in overall survival, further studies with extended follow-up periods and appropriate control groups are necessary to assess the efficacy of NK cell therapy in these patients. TRIAL REGISTRATION: The trial was registered on the Iranian Registry of Clinical Trials (IRCT20170122032121N6), Date 2021-11-19.
Evaluation and implementation of multidisciplinary, standardized, guideline-based long-term follow-up care for adult survivors of childhood cancer in Germany: protocol of a prospective, multi-center, nationwide study (LE-Na).
Cytera C, Baust K, Borgmann-Staudt A … +16 more , Calaminus G, Egger-Heidrich K, Faber J, Grabow D, Halbsguth T, Kock-Schopenhauer A, König IR, Michaelis S, Neumann A, Puzik A, Schuster S, Wolters F, Arendt C, Sleimann M, Langer T, Gebauer J
BMC Cancer · 2025 May · PMID 40405095 · Full text
BACKGROUND: Late effects can occur years to decades after cancer therapy, resulting in morbidity and reduced health-related quality of life. Clinical long-term follow-up (LTFU) enables timely diagnosis and treatment of t...
BACKGROUND: Late effects can occur years to decades after cancer therapy, resulting in morbidity and reduced health-related quality of life. Clinical long-term follow-up (LTFU) enables timely diagnosis and treatment of these sequelae. So far, only a minority of childhood cancer survivors (CCS) in Germany regularly visit LTFU care facilities. The LE-Na study aims to: 1. implement and/or improve LTFU care structures for adult CCS in Germany, 2. inform former patients about late effects and LTFU care centers, 3. create a basis for future research by building up a central database, consent management and infrastructure, 4. establish a clinical LTFU cohort of adult CCS in Germany, 5. evaluate the implementation of the LFTU care, 6. enable the expansion of LTFU care structures nationwide, 7. integrate the developed LTFU care structures into the standard health care system. METHODS: Within five years, approximately 5000 CCS will be invited to visit one of the 10 LTFU centers in Germany. Study participants are either contacted by the German Childhood Cancer Registry (GCCR), transitioned from the local pediatric oncology care unit, or recruited via media. They are assigned to one of three different risk groups based on an evidence-based risk stratification and receive standardized multidisciplinary follow-up care. Primary outcomes are satisfaction with the LTFU care offer as well as degree of health-related self-efficacy expectation. They will be assessed at two time points. A scientific evaluation of the implemented LTFU care will be enabled by a waitlist control group. The harmonized outcome data are documented in a standardized database. DISCUSSION: By addressing CCS in Germany who have not received standardized LTFU care yet, the LE-Na study expects to improve nationwide LTFU care and therewith patient's satisfaction with the LTFU care offer as well as their health-related self-efficacy expectation.
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