Pediatric Blood & Cancer[JOURNAL]
Sun
200 papers
A phase 1 dose-escalation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed/refractory neuroblastoma.
DuBois SG, Ogawa C, Moreno L … +19 more , Mossé YP, Fischer M, Ryan AL, Vo KT, De Wilde B, Rubio-San-Simon A, Macy ME, Howell L, Shusterman S, Corradini N, Luksch R, Aerts I, Foster JH, Weiss BD, Karthik CP, Yuen E, Avsar E, Park JR, Marachelian A
Cancer · 2025 Feb · PMID 39932800 · Publisher ↗
BACKGROUND: This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma. METHODS: Patients age...
BACKGROUND: This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma. METHODS: Patients aged 2-21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28-day cycles. RESULTS: Twenty-five patients were treated. No dose-limiting toxicity occurred in monotherapy; one patient had dose-limiting toxicities in the combination therapy cohort (grade 3 mucositis and grade 4 neutropenia). The recommended phase 2 dose for both monotherapy and combination therapy was 15 mg/m. Twenty-two patients (88%) had one or more treatment-related adverse event(s) (TRAEs), and 18 (72%) experienced grade ≥3 TRAEs. Myelosuppression was the most common high-grade TRAE observed in the combination therapy cohort. At both dose levels, steady-state plasma concentrations exceeded xenograft 90% inhibitory concentration levels. In the monotherapy cohort, one patient had a minor response, and one patient had stable disease, both continuing for >12 months. In the combination therapy cohort, two patients had a partial response, two had a minor response, and six had stable disease. Overall, the response rate, according to New Approaches to Neuroblastoma Therapy version 2.0 criteria, was 8%, and the disease control rate was 52%. CONCLUSIONS: LY3295668 erbumine had a manageable safety profile as monotherapy and in combination therapy. Although proof-of-concept clinical responses were observed, future studies with biomarker-selected populations and/or novel combinations may yield higher response rates with Aurora kinase A inhibition.
Reply to "Toward a reduction in the burden of therapy in patients with rhabdomyosarcoma. How much is enough?".
Mandeville HC, Bisogno G, Minard-Colin V … +16 more , Alaggio R, Ben-Arush M, Chargari C, Coppadoro B, Craigie R, Devalck C, Ferman S, Ferrari A, Glosli H, Alvaro RH, Hol M, Mudry P, Orbach D, Albiac MR, Merks JHM, Jenney MEM
Cancer · 2025 Feb · PMID 39916392 · Publisher ↗
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Toward a reduction in the burden of therapy in patients with rhabdomyosarcoma: How much is enough?
Koscielniak E, Klingebiel T
Cancer · 2025 Feb · PMID 39916357 · Publisher ↗
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Study protocol of the METAPANC trial - intensified treatment in patients with local operable but oligometastatic pancreatic cancer - multimodal surgical treatment versus chemotherapy alone: a randomized controlled trial.
Ghadimi M, Pelzer U, Besselink MG … +19 more , Siveke J, Telgmann R, Braren R, Wilmink H, Crede M, Koenig A, Koenig U, Liffers ST, Antweiler K, Uijterwijk B, Seppanen H, Nordin A, Puolakkainen P, Dajani OF, Labori KJ, Johansson M, Bratlie SO, Friede T, Jo P
BMC Cancer · 2025 Feb · PMID 39915735 · Full text
BACKGROUND: Based on current guidelines, surgical treatment of hepatic oligometastases in patients with pancreatic ductal adenocarcinoma (PDAC) is not primarily recommended. Systematic chemotherapy is the therapy of choi...
BACKGROUND: Based on current guidelines, surgical treatment of hepatic oligometastases in patients with pancreatic ductal adenocarcinoma (PDAC) is not primarily recommended. Systematic chemotherapy is the therapy of choice for these patients. The relevance of subsequent surgical resection after chemotherapy remains unclear. This multicentre, randomized, controlled phase III trial is planned to evaluate whether resection of the primary tumor and liver metastases can improve overall survival in patients with PDAC with hepatic oligometastases in a multimodal treatment setting. METHODS: After an induction therapy with eight cyles of mFOLFIRINOX and a response assessment after four and eight cycles, patients will be randomized to either Arm 1 (perioperative mFOFIRINOX plus resection of the primary tumor with resection or ablation of all hepatic metastases) or Arm 2 (continuation of 4 cycles of the standard-of-care mFOLFIRINOX chemotherapy). This clinical trial will focus on a well-defined patient group with metastatic disease limited to the liver as the target organ, with a maximum of three metastases. DISCUSSION: METAPANC is the first international, randomized, controlled, open-label, multicentre, phase III clinical trial for curative intended surgical therapy of oligometastatic pancreatic cancer in Europe and America. The multimodal surgical treatment of patients with oligometastatic pancreatic cancer could significantly extend the overall survival of this patient group. A possible recommendation of this multimodal treatment regimen outside of clinical trials requires data from randomized controlled trials first. To identify patient subgroups that might benefit from multimodal surgical therapy, additional information on tumor genetics could supplement valid parameters. TRIAL REGISTRATION: EU Clinical Trials No. 2023-503558-10-00.
Predictive role of SLC1A5 in neuroblastoma prognosis and immunotherapy.
Cheng J, Sun M, Dong X … +7 more , Yang Y, Qin X, Zhou X, Fu Y, Wang Y, Wang J, Zhang D
BMC Cancer · 2025 Jan · PMID 39875895 · Full text
BACKGROUND: Neuroblastoma, a prevalent extracranial solid tumor in pediatric patients, demonstrates significant clinical heterogeneity, ranging from spontaneous regression to aggressive metastatic disease. Despite advanc...
BACKGROUND: Neuroblastoma, a prevalent extracranial solid tumor in pediatric patients, demonstrates significant clinical heterogeneity, ranging from spontaneous regression to aggressive metastatic disease. Despite advances in treatment, high-risk neuroblastoma remains associated with poor survival. SLC1A5, a key glutamine transporter, plays a dual role in promoting tumor growth and immune modulation. However, its contributions to neuroblastoma biology remain largely unexplored. METHODS: This study utilized clinical neuroblastoma samples from 20 patients and 1310 cases from four public datasets to investigate SLC1A5 expression, biological function, and prognostic significance. Differential expression, Kaplan-Meier survival analysis, gene set enrichment analysis, and weighted correlation network analysis were conducted. Functional validation included qPCR, immunohistochemistry, Western blotting, and cell proliferation assays using the SLC1A5 inhibitor V-9302. A prognostic signature, SRPS, was constructed and validated using machine-learning approaches. Immune infiltration analysis was performed to evaluate the tumor immune microenvironment. RESULTS: SLC1A5 expression was significantly elevated in high-risk neuroblastoma and correlated with advanced stages and poor prognosis. GSEA revealed mTORC1 signaling enrichment in high SLC1A5 expression groups, validated by increased p-p70S6K levels in tumor samples and neuroblastoma cells. V-9302 treatment suppressed mTORC1 signaling and inhibited cell proliferation. Hub-genes were identified to form the SRPS model, which demonstrated superior prognostic performance compared to existing models. Immune infiltration analysis revealed a more immunosuppressive tumor microenvironment associated with high SLC1A5 expression. Additionally, SLC1A5 negatively regulated ST8SIA1, a gene crucial for GD2 biosynthesis, suggesting that SLC1A5 inhibition may enhance GD2-directed immunotherapies. CONCLUSION: SLC1A5 plays a pivotal role in neuroblastoma by promoting tumor progression and shaping an immunosuppressive microenvironment. The SRPS model, incorporating SLC1A5-associated genes, offers robust prognostic utility. Targeting SLC1A5 through advanced drug delivery systems and combined metabolic-immunotherapeutic strategies may enhance treatment specificity and efficacy. These findings provide a foundation for novel therapeutic approaches to improve outcomes in high-risk neuroblastoma patients.
Historical redlining and survival among children, adolescents, and young adults with cancer diagnosed between 2000-2019 in Seattle and Tacoma, Washington.
Karvonen KA, Doody DR, Barry D … +6 more , Bona K, Winestone LE, Rosenberg AR, Mendoza JA, Schwartz SM, Chow EJ
Cancer · 2025 Feb · PMID 39866001 · Publisher ↗
BACKGROUND: Historical redlining has been associated with inferior survival in adult-onset cancers. However, its relationship with pediatric, adolescent, and young-adult-onset cancer outcomes is unknown. METHODS: This st...
BACKGROUND: Historical redlining has been associated with inferior survival in adult-onset cancers. However, its relationship with pediatric, adolescent, and young-adult-onset cancer outcomes is unknown. METHODS: This study identified incident cancer among individuals <40 years of age living in Seattle and Tacoma between 2000-2019 via the population-based Cancer Surveillance System. The authors determined case redlining status using Home Owners' Loans Corporation data overlaid with 2000 and 2010 census tracts. Kaplan-Meier methods and multivariable Cox proportional hazards models were used to determine 5- and 10-year overall survival and hazard ratio (HR) of death according to redlined status. Cox models adjusted for patient and tumor characteristics and area-level poverty; interaction between redlining and area-level poverty was also assessed. RESULTS: Among 4355 cases (median age at diagnosis 32 years), overall survival at 5 years was lower (85.1%; 95% confidence interval [CI], 83.5%-86.5%) among individuals residing in redlined neighborhoods compared with those in unexposed neighborhoods (90.3%; 95% CI, 89.0%-91.5%). Survival differences persisted at 10 years. The unadjusted hazard of death for redlined exposed individuals with cancer was higher than redlined unexposed (hazard ratio [HR], 1.62; 95% CI, 1.39-1.89). In the fully adjusted model, mortality remained higher for redlined cases (HR, 1.32; 95% CI, 1.12-1.56). There did not appear to be effect modification from area-level poverty in the relationship between redlining and death (p = .49). CONCLUSIONS: Among young individuals with cancer, residence at diagnosis in previously redlined neighborhoods was associated with lower survival compared with those residing in nonredlined neighborhoods, supporting the hypothesis that structural racism exerts persistent effects on contemporary health outcomes.
Treatment of focal anaplastic Wilms tumor: A report from the Children's Oncology Group AREN0321 and AREN03B2 studies.
Armstrong AE, Daw NC, Renfro LA … +13 more , Geller JI, Kalapurakal JA, Khanna G, Paulino AC, Perlman EJ, Ehrlich PF, Gow KW, Warwick AB, Grundy PE, Fernandez CV, Mullen EA, Dome JS, Children's Oncology Group AREN0321 and AREN03B2 Study Committees
Cancer · 2025 Jan · PMID 39803937 · Full text
BACKGROUND: In the fifth National Wilms Tumor Study, patients received vincristine and dactinomycin (VA) without radiation for stage I focal anaplastic Wilms tumor (FAWT) and VA plus doxorubicin (DD4A) and radiation for...
BACKGROUND: In the fifth National Wilms Tumor Study, patients received vincristine and dactinomycin (VA) without radiation for stage I focal anaplastic Wilms tumor (FAWT) and VA plus doxorubicin (DD4A) and radiation for stage II-IV FAWT. Four-year event-free survival (EFS) and overall survival (OS) for stage I FAWT were 67.5% and 88.9% and for stage IV FAWT were 61.4% and 71.6%, respectively. Therapy intensification for stage I and IV FAWT was evaluated as secondary objectives in AREN0321. METHODS: Central review in the AREN03B2 Renal Tumors Classification, Biology, and Banking Study confirmed patient stage and tumor histology. Patients were then enrolled in AREN0321 and received DD4A with radiation for stage I-III FAWT and vincristine, doxorubicin, cyclophosphamide, carboplatin, and etoposide (UH-1/revised UH-1) with radiation for stage IV FAWT. Outcomes of patients with FAWT who were treated in AREN0321 (n = 25) and in AREN03B2 (n = 20) treated as per AREN0321 were analyzed. RESULTS: In the pooled data analysis from AREN0321 and AREN03B2, 4-year EFS and OS were both 100% for stage I-II FAWT (n = 21), 82.4% (95% CI, 66.1%-100%) and 87.8% (95% CI, 73.4%-100%) for stage III FAWT (n = 17), respectively, and both 85.7% (95% CI, 63.3%-100%) for stage IV FAWT (n = 7). Four patients enrolled in AREN0321 had events: treatment failure occurred in three patients with stage III FAWT, and one treatment-related death was observed in a patient with stage IV FAWT following revised UH-1. No EFS or OS events occurred in patients with FAWT enrolled in AREN03B2 only. CONCLUSIONS: Patients with stage I and II FAWT have outstanding survival when treated with DD4A and radiation. Intensification of therapy may have improved survival for stage IV FAWT, albeit with an increased toxicity risk.
Impact of obesity on outcome in children diagnosed with cancer in Canada: A report from Cancer in Young People in Canada.
Sassine S, Ilinca AP, Coltin H … +17 more , Bittencourt H, Athale U, Bowes L, Brossard J, Israels S, Johnston DL, Kulkarni K, McKillop S, Rayar M, Sinha R, Truong T, Vézina C, Wheaton L, Zorzi AP, Sung L, Pelland-Marcotte MC, Tran TH
Cancer · 2025 Jan · PMID 39801179 · Publisher ↗
BACKGROUND: Childhood obesity can result in adverse health outcomes. The objectives of this study were to describe the prevalence of obesity and determine the association between obesity at cancer diagnosis and event-fre...
BACKGROUND: Childhood obesity can result in adverse health outcomes. The objectives of this study were to describe the prevalence of obesity and determine the association between obesity at cancer diagnosis and event-free survival (EFS) and overall survival (OS) in children diagnosed with cancer in Canada. METHODS: The authors conducted a retrospective cohort study using the Cancer in Young People in Canada database, including all children with newly diagnosed cancer aged 2-18 years across Canada from 2001 to 2020. Obesity was defined as age-adjusted and sex-adjusted body mass index greater than or equal to the 95th percentile. Univariate and multivariable Cox proportional hazards models compared EFS and OS between patients with and without obesity at diagnosis. RESULTS: In total, 11,291 patients were included, of whom 10.5% were obese at diagnosis. In multivariable models controlling for age, sex, ethnicity, neighborhood income quintile, treatment era, and cancer categories, obesity at diagnosis was independently associated with inferior EFS (adjusted hazard ratio [aHR], 1.16; 95% confidence interval [CI], 1.02-1.32; p = .02) and OS (aHR, 1.29; 95% CI, 1.11-1.49; p = .001). The adverse prognostic impact of obesity was particularly notable for acute lymphoblastic leukemia (ALL) and central nervous system (CNS) tumors. In children with ALL (n = 3458), obesity remained associated with inferior EFS (aHR, 1.55; p = .002) and OS (aHR, 1.75; p = .002) in multivariable analysis. In patients with CNS tumors (n = 2458), obesity was also associated with inferior EFS (aHR, 1.38; p = .008) and OS (aHR, 1.47; p = .004). CONCLUSIONS: In this population-based study, obesity at cancer diagnosis was independently associated with inferior survival across the entire cohort, and prominently in children with ALL and CNS tumors.
From childhood cancer to metabolic syndrome.
Wadhwa A
Cancer · 2025 Jan · PMID 39749661 · Publisher ↗
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Prevalence and determinants of metabolic syndrome in 2338 childhood cancer survivors: A Dutch Childhood Cancer Survivor LATER 2 study.
Bolier M, de Winter DTC, Pluimakers VG … +18 more , Fiocco M, van den Berg SAA, Bresters D, van Dulmen-den Broeder E, van der Heiden-van der Loo M, Höfer I, Janssens GO, Kremer LCM, Loonen JJ, Louwerens M, van der Pal HJ, Pluijm SMF, Tissing WJE, van Santen HM, de Vries ACH, van der Lely AJ, van den Heuvel-Eibrink MM, Neggers SJCMM
Cancer · 2025 Jan · PMID 39748458 · Full text
BACKGROUND: Because the occurrence of metabolic syndrome (MetS) might contribute to childhood cancer survivor's excess risk of cardiovascular disease, the authors assessed the prevalence and determinants of MetS in the D...
BACKGROUND: Because the occurrence of metabolic syndrome (MetS) might contribute to childhood cancer survivor's excess risk of cardiovascular disease, the authors assessed the prevalence and determinants of MetS in the Dutch Childhood Cancer Survivor Study (DCCSS-LATER2) cohort. METHODS: In total, 2338 adult childhood cancer survivors (CCS) were cross-sectionally assessed for the prevalence of MetS, using the Lifelines cohort (N = 132,226 adults without a history of cancer) as references. The prevalence of MetS was clinically assessed using existing classifications, as well as an alternative method using dual-energy x-ray absorptiometry fat% instead of waist circumference to define abdominal adiposity. Logistic regression models, adjusted for age and sex, were used to investigate the association between the presence of MetS and both cohorts. Demographic, lifestyle, and treatment determinants of MetS were identified through multivariable logistic regression. RESULTS: The survivor cohort (median age, 34.7 years, median follow-up time, 27.1 years) showed increased adjusted odds ratio (aOR) for MetS (modified National Cholesterol Education Program Adult Treatment Panel III criteria), as compared to the reference cohort (aOR, 2.07; 95% confidence interval [CI], 1.85-2.32). Compared to these criteria, the alternative method identified 57 additional survivors with MetS (395 of 2070 [19.1%] vs. 452 of 1960 [23.1%], respectively). Age (odds ratio [OR], 1.07; 95% CI, 1.04-1.10, per year increase), smoking (OR, 1.46; 95% CI, 1.04-2.04), low physical activity (OR, 1.48; 95% CI, 1.05-2.09), abdominal radiotherapy (OR, 2.13; 95% CI, 1.01-4.31; >30 Gy), cranial radiotherapy (OR, 2.89; 95% CI, 1.67-4.96; 1-25 Gy; and OR, 2.44; 95% CI, 1.30-4.47; >25 Gy), total body irradiation (OR, 6.17; 95% CI, 3.20-11.76), and underlying central nervous system tumor (OR, 1.78; 95% CI, 1.21-2.60) were associated with MetS. CONCLUSION: The high risk of MetS in CCS, combined with several potential modifiable factors, underscores the need for timely identification and intervention strategies to mitigate the long-term cardiovascular risks in CCS.
Post-transplant complications revealed by mycophenolate mofetil related transporters and metabolic enzymes gene polymorphisms in pediatric patients with hematological disorders.
Ji Q, Hu Y, Liu M … +15 more , Liu L, Zheng J, Du Z, Gao L, Xiao P, Ling J, Fan L, Bian X, Lou F, Cao S, Li J, Tian Y, Lu J, Qin J, Hu S
BMC Cancer · 2024 Dec · PMID 39696070 · Full text
BACKGROUND: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) serves as an important option for patients without an HLA matched donor in treating hematological disorders, while patients may experience v...
BACKGROUND: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) serves as an important option for patients without an HLA matched donor in treating hematological disorders, while patients may experience various complications after transplantation. Mycophenolate mofetil (MMF), a cornerstone drug for graft-versus-host disease (GvHD) prophylaxis, effectively reduces the incidence of acute GvHD, and the efficacy of MMF varies among individuals associated with MMF-related transporters and metabolic enzymes single nucleotide polymorphisms (SNPs). However, limited studies have systematically reported the correlations between the MMF-related SNPs and post-transplant complications. METHODS: Here, we conducted a retrospective study involving 90 pediatric patients with hematological disorders who underwent haplo-HSCT at a single center. All patients were subjected to MMF-related SNP testing, combined with common clinical characteristics, to be correlated with post-transplant complications. RESULTS: We observed that all 15 MMF-related SNPs were in Hardy-Weinberg equilibrium. Based on multivariate Cox regression analysis of post-transplant complications, we discovered that SLCO1B1 (521T > C) variant genotype was an independent protective factor for chronic GvHD (HR = 0.25, 95% confidence interval (CI) (0.08-0.84)). For viral infection, CYP2C8 (1291 + 106T > C) variant genotype was an independent risk factor for cytomegalovirus infection (HR = 2.98, 95% CI (1.18-7.53)). As to hemorrhagic cystitis, SLCO1B1 (1865 + 4846T > C) variant genotype was an independent protective factor, while older age was considered as an independent risk factor (HR = 0.41, 95% CI (0.19-0.85); HR = 2.52, 95% CI (1.14-5.54), respectively). No statistical significance was discovered between common clinical characteristics and MMF-related SNPs with other complications, including grade II-IV/III-IV acute GvHD, Epstein-Barr virus infection, peri-engraftment syndrome, and capillary leak syndrome. We also discovered SLCO1B1 (597 C > T) and SLC29A1 (-162 + 228 A > C) variant genotypes are both independent factors for cumulative incidence of relapse after haplo-HSCT (HR = 4.02, 95% CI (1.42-11.44); HR = 0.18, 95% CI (0.07-0.43), respectively). CONCLUSIONS: Our findings highlight the significance of MMF-related transporters and metabolic enzymes SNPs in the development of post-transplant complications, contributing to facilitating personalized risk assessment and improving the clinical management in haplo-HSCT patients.
Genetic predisposition meets cytokine imbalance: the influence of TNF-α (-308) polymorphism and TGF-β levels in pediatric acute lymphoblastic leukemia in Egypt.
Radwan RE, El-Kholy WM, Elsaed A … +1 more , Darwish A
BMC Cancer · 2024 Dec · PMID 39658797 · Full text
Evading apoptosis fuels the aggressive nature of acute lymphoblastic leukemia (ALL). This study explored the potential roles of TNF-α, a pro-apoptotic cytokine, and TGF-β, a pro-proliferative factor, in the risk of devel...
Evading apoptosis fuels the aggressive nature of acute lymphoblastic leukemia (ALL). This study explored the potential roles of TNF-α, a pro-apoptotic cytokine, and TGF-β, a pro-proliferative factor, in the risk of developing ALL in Egyptian children. We investigated the TNF-α rs1800629 polymorphism and serum TGF-β levels in 100 ALL patients and 100 healthy controls. Notably, specific variations in TNF-α (GA, AA genotypes, and dominant model) were associated with an increased risk of ALL, suggesting impaired apoptosis. Conversely, ALL patients exhibited significantly lower TGF-β levels, potentially promoting uncontrolled proliferation. Our findings suggest that lower TGF-β and the TNF-α (-308) dominant model are associated with an increased risk of ALL. Additionally, TGF-β demonstrated exceptional accuracy (AUC 0.995) as a potential marker, with 100% sensitivity and 96% specificity. These findings suggest that TNF-α and TGF-β may be associated with ALL susceptibility, though further research with larger and more diverse populations is necessary to confirm these results.
Re-envisioning genetic predisposition to childhood and adolescent cancers.
Kratz CP
Nat Rev Cancer · 2025 Feb · PMID 39627375 · Publisher ↗
Although cancer is rare in children and adolescents, it remains a leading cause of death within this age range, and genetic predisposition is the main known risk factor. Since the discovery of retinoblastoma-predisposing...
Although cancer is rare in children and adolescents, it remains a leading cause of death within this age range, and genetic predisposition is the main known risk factor. Since the discovery of retinoblastoma-predisposing RB1 pathogenic germline variants in 1985, several additional high-penetrance cancer predisposition genes (CPGs) have been identified. Although few clinically recognizable genetic conditions display moderate cancer phenotypes, burden testing has revealed low-to-moderate penetrance CPGs. In addition to germline pathogenic variants in CPGs, postzygotic somatic mosaic CPG pathogenic variants acquired during embryonic development are increasingly recognized as factors that predispose children and adolescents to malignancies. Genome-wide association studies of various childhood and adolescent cancer types have identified some common low-risk cancer susceptibility alleles. Although the clinical utility of polygenic risk scores is currently limited in children and adolescents, polygenic risk scores developed for adults can predict subsequent cancer risks in childhood and adolescent cancer survivors. In this Review, I describe our current knowledge of genetic predisposition to childhood and adolescent cancers. Survival rates in children and adolescents with cancer and CPGs are often poor, necessitating better integration of genomic testing into clinical care to improve cancer prevention, surveillance and therapies.
Ultrasound characteristics of alveolar soft part sarcoma in pediatric patients: a retrospective analysis.
Wang S, Wang Y, Xu J … +4 more , Ren Q, Hu Y, Jia L, Wang X
BMC Cancer · 2024 Dec · PMID 39623317 · Full text
OBJECTIVE: This study aims to review and summarize the ultrasound characteristics of alveolar soft part sarcoma (ASPS) in children. METHODS: We retrospectively analyzed 20 pediatric ASPS cases confirmed by surgery or bio...
OBJECTIVE: This study aims to review and summarize the ultrasound characteristics of alveolar soft part sarcoma (ASPS) in children. METHODS: We retrospectively analyzed 20 pediatric ASPS cases confirmed by surgery or biopsy at our hospital between January 2014 and January 2024. Clinical data, including age, sex, symptoms, and tumor location, were collected. Ultrasound reports and images were reviewed to extract data on tumor size, boundaries, echogenicity, and vascularity. RESULTS: The study included 20 children with ASPS. The tumors were located in the trunk and limbs (50%), as well as in the head and neck (50%). Compared with tumors in the trunk and limbs, head and neck tumors were smaller in size, had more pronounced symptoms, and had a lower incidence of metastasis. Ultrasound features predominantly included hypoechoic masses with clear boundaries, heterogeneous echogenicity, and rich internal and surrounding vascularity, often with tortuous and dilated blood vessels. Eight patients had distant metastases at diagnosis, seven of which involved the lungs. There was a moderate correlation between tumor size and the risk of distant metastasis (r = 0.64). CONCLUSION: Understanding the clinical and ultrasound characteristics of pediatric ASPS can facilitate earlier and more accurate diagnosis.
Predictors of abemaciclib discontinuation in patients with breast cancer: a multicenter retrospective cohort study.
Kataoka N, Hata T, Hosomi K … +7 more , Hirata A, Ota R, Nishihara M, Kimura K, Iwamoto M, Ashida A, Neo M
BMC Cancer · 2024 Oct · PMID 39478497 · Full text
OBJECTIVE: This study explored the predictors of abemaciclib discontinuation, a cyclin-dependent kinase 4 and 6 inhibitor, in patients with breast cancer. MATERIAL AND METHODS: Between November 2018 and March 2023, 147 p...
OBJECTIVE: This study explored the predictors of abemaciclib discontinuation, a cyclin-dependent kinase 4 and 6 inhibitor, in patients with breast cancer. MATERIAL AND METHODS: Between November 2018 and March 2023, 147 patients with breast cancer treated with abemaciclib at Osaka Medical and Pharmaceutical University Hospital and Kindai University Nara Hospital were included. The exclusion criteria were as follows: lack of blood testing within 2 weeks prior to starting abemaciclib therapy, transfer to another facility after the commencement of abemaciclib therapy, and discontinuation of abemaciclib therapy due to the diagnosis of another cancer. The duration from the initiation of abemaciclib to discontinuation for any reason and to temporary suspension or dose reduction due to adverse events were analyzed as outcome variables using multivariate Cox regression analysis. RESULTS: Baseline weight < 54 kg, bone metastases, and hemoglobin level ≤ 12.4 g/dL were independent predictors of abemaciclib discontinuation for any reason. The main adverse events leading to abemaciclib discontinuation were liver enzyme elevation and gastrointestinal symptoms. Additionally, focusing on the adverse event of abemaciclib, a baseline weight < 54 kg was an independent predictor of temporary suspension or dose reduction due to adverse events. The most common adverse events leading to temporary suspension or dose reduction were neutropenia and diarrhea. CONCLUSION: Patients with lower body weight are more susceptible to the adverse events of abemaciclib, increasing their risk of treatment discontinuation. In such patients, strict monitoring of adverse events and consideration of more frequent medical visits are necessary from the start of abemaciclib therapy.
Clinical impact of large genomic explorations at diagnosis in 198 pediatric solid tumors: a monocentric study aiming practical feasibility of precision oncology.
Simon J, Reita D, Guerin E … +14 more , Lhermitte B, Weingertner N, Lefebvre F, Karanian M, Masliah-Planchon J, Lindner V, Onea A, Jannier S, Salmon A, Bergthold G, Vincent F, Deschuyter M, Barbaza MO, Entz-Werlé N
BMC Cancer · 2024 Oct · PMID 39433989 · Full text
INTRODUCTION: Faced to the growing development of collecting systematic molecular analyses in relapsed pediatric cancers to transform their targeted matched therapies, this study aimed to assess the clinical and therapeu...
INTRODUCTION: Faced to the growing development of collecting systematic molecular analyses in relapsed pediatric cancers to transform their targeted matched therapies, this study aimed to assess the clinical and therapeutic indications of systematic diagnostic genomic explorations performed in pediatric solid cancers to determine which type of screening and if it afford at relapse time an accurate targeted strategy. METHODS: A total of 280 patients less than 22 years, referred at the University Hospitals of Strasbourg for a newly diagnosed solid tumor from January 2015 to December 2021, were prospectively genomically investigated since diagnosis. Using 7 different molecular tests going from single-gene methods (IHC, FISH, RT-PCR, Sanger sequencing, droplet digital PCR) to largescale analyses (Next-Generation sequencing, RNAsequencing and FoundationOne®CDx), we explored retrospectively the molecular findings in those pediatric solid tumors (except hematolymphoid cancers) to improve diagnosis, prognosis assessment and relapse therapeutics. RESULTS: One hundred and ninety-eight patients (71%) underwent molecular biology (MB) at diagnosis. Thirty-eight different histologies were grouped into cerebral tumors (30%), sarcomas (26%, bone and soft tissues), various blastomas (27%), and other entities (17%). Over a median 40-month follow-up, the overall survival rate of patients was 85% and the relapse rate 28%. Of the 326 analyses carried out, 245 abnormalities (single nucleotide variations: 50%, fusions: 25%, copy number alteration: 20%) concerning 70 oncogenes were highlighted. The overall clinical impact rate was 84%. Broad-spectrum analyses had a higher therapeutic impact (57%) than the targeted analyses (28%). 75% of broad-spectrum tests found an actionable variant conducting 23% of patients to receive rapidly a matched targeted therapy since first relapse. CONCLUSION: Our experience highlighted the clinical utility of molecular profiling of solid tumors as soon as at diagnosis in children to expect improving access to innovative agents at relapse.
Event-free survival in neuroblastoma with MYCN amplification and deletion of 1p or 11q may be associated with altered immune status.
Wei Z, Gong B, Li X … +2 more , Chen C, Zhao Q
BMC Cancer · 2024 Oct · PMID 39407175 · Full text
BACKGROUND: Neuroblastoma exhibits substantial heterogeneity, which is intricately linked to various genetic alterations. We aimed to explore immune status in the peripheral blood and prognosis of patients with neuroblas...
BACKGROUND: Neuroblastoma exhibits substantial heterogeneity, which is intricately linked to various genetic alterations. We aimed to explore immune status in the peripheral blood and prognosis of patients with neuroblastoma with different genetic characteristics. METHODS: We enrolled 31 patients with neuroblastoma and collected samples to detect three genetic characteristics. Peripheral blood samples were tested for immune cells and cytokines by fluorescent microspheres conjugated with antibodies and flow cytometry. Event-free survival (EFS) was analyzed using the Kaplan‒Meier method. RESULTS: Twenty-two patients had genetic aberrations, including MYCN amplification in 6 patients, chromosome 1p deletion in 9 patients, and chromosome 11q deletion in 14 patients. Two genetic alterations were present in seven patients. The EFS was worse in patients with MYCN amplification or 1p deletion than in the corresponding group, whereas 11q deletion was a prognostic factor only in patients with unamplified MYCN. Changes in immune status revealed a decrease in the proportion of T cells in blood, and an increase in regulatory T cells and immunosuppression-related cytokines such as interleukin (IL)-10. The EFS of the IL-10 high-level group was lower than that of the low-level group. Patients with concomitant genetic alterations and a high level of IL-10 had worse EFS than other patients. CONCLUSIONS: Patients with neuroblastoma characterized by these genetic characteristics often have suppressed T cell response and an overabundance of immunosuppressive cells and cytokines in the peripheral blood. This imbalance is significantly associated with poor EFS. Moreover, if these patients show an elevated levels of immunosuppressive cytokines such as IL-10, the prognosis will be worse.
Hsa_circ_0006010 and hsa_circ_0002903 in peripheral blood serve as novel diagnostic, surveillance and prognostic biomarkers for disease progression in chronic myeloid leukemia.
Zhao J, Wang G, Yan G … +5 more , Zheng M, Li H, Bai Y, Zheng X, Chen Z
BMC Cancer · 2024 Sep · PMID 39304860 · Full text
BACKGROUND: In the era of tyrosine kinase inhibitor (TKI) treatment, the progression of chronic myeloid leukemia (CML) remains a significant clinical challenge, and genetic biomarkers for the early identification of CML...
BACKGROUND: In the era of tyrosine kinase inhibitor (TKI) treatment, the progression of chronic myeloid leukemia (CML) remains a significant clinical challenge, and genetic biomarkers for the early identification of CML patients at risk for progression are limited. This study explored whether essential circular RNAs (circRNAs) can be used as biomarkers for diagnosing and monitoring CML disease progression and assessing CML prognosis. METHODS: Peripheral blood (PB) samples were collected from 173 CML patients (138 patients with chronic phase CML [CML-CP] and 35 patients with accelerated phase/blast phase CML [CML-AP/BP]) and 63 healthy controls (HCs). High-throughput RNA sequencing (RNA-Seq) was used to screen dysregulated candidate circRNAs for a circRNA signature associated with CML disease progression. Quantitative real-time PCR (qRT-PCR) was used for preliminary verification and screening of candidate dysregulated genes, as well as subsequent exploration of clinical applications. Receiver operating characteristic (ROC) curve analysis, Spearman's rho correlation test, and the Kaplan-Meier method were used for statistical analysis. RESULTS: The aberrant expression of hsa_circ_0006010 and hsa_circ_0002903 during CML progression could serve as valuable biomarkers for differentiating CML-AP/BP patients from CMP-CP patients or HCs. In addition, the expression levels of hsa_circ_0006010 and hsa_circ_0002903 were significantly associated with the clinical features of CML patients but were not directly related to the four scoring systems. Furthermore, survival analysis revealed that high hsa_circ_0006010 expression and low hsa_circ_0002903 expression indicated poor progression-free survival (PFS) in CML patients. Finally, PB hsa_circ_0006010 and hsa_circ_0002903 expression at diagnosis may also serve as disease progression surveillance markers for CML patients but were not correlated with PB BCR-ABL1/ABL1. CONCLUSIONS: Our study demonstrated that PB levels of hsa_circ_0006010 and hsa_circ_0002903 may serve as novel diagnostic, surveillance, and prognostic biomarkers for CML disease progression and may contribute to assisting in the diagnosis of CML patients at risk for progression and accurate management of advanced CML patients.
Central nervous system pediatric multi-disciplinary tumor board: a single center experience.
Russo R, Verdolotti T, Perna A … +13 more , Ruscelli L, D'Abronzo R, Romano A, Ferrara G, Parisi D, Infante A, Chiesa S, Massimi L, Tamburrini G, Ruggiero A, Gessi M, Martucci M, Gaudino S
BMC Cancer · 2024 Sep · PMID 39272048 · Full text
BACKGROUND: The Multidisciplinary Tumor Board (MTB) is a collaborative platform involving specialists in oncology, surgery, radiology, pathology, and radiotherapy, and aims to optimize diagnostics and treatments. Despite...
BACKGROUND: The Multidisciplinary Tumor Board (MTB) is a collaborative platform involving specialists in oncology, surgery, radiology, pathology, and radiotherapy, and aims to optimize diagnostics and treatments. Despite MTB's widespread benefits, limited literature addresses its application in pediatric neuro-oncology. After a literature revision on pediatric neuro-oncology MTB, our study describes our institute's pediatric neuro-oncology MTB, focuses on evaluating its impact and the neuroradiologist's role in patient-centric approaches, considering recent genetic insights into pediatric brain tumors. MATERIALS AND METHODS: Literature Review concerning pediatric neuro-oncology MTB from January 2002 to June 2024. CLINICAL DATA: retrospective study of all patient files presented in the pediatric neuro-oncology MTB (pnMTB) between 2019 and 2022. Statistical analysis was mainly carried out by directly comparing the absolute or relative values of the respective parameters examined; qualitative variables compared mainly with the chi-square test, quantitative variables mainly with the t-test. RESULTS: Literature Review: 7 papers encompass a multidisciplinary approach for the pediatric CNS tumors. CLINICAL DATA: A total of 236 discussions were analyzed representing 107 patients. Median age was 14,3 years (range: 6 months - 17 years). The requests for case evaluations primarily came from the pediatric oncologists (83%) and neurosurgeons (14.8%), and they were mainly addressed to the neuroradiologists (70.3%). Proposals during pnMTB mainly involved imaging follow-up (47.8%) and management with chemotherapy (34.7%). Changes in patient treatment (CPT) occurred in 115 cases, and pediatric neuroradiologist intervention contributed to 72.4% of these changes. CONCLUSION: Thanks to their multidisciplinarity, high number of cases discussed, and usual respect for their proposals, the pnMTB has made it possible to improve the coordination among specialties involved in patient management, to apply the recent protocols, and to exchange knowledge among teams managing pediatric CNS tumors.
Prognostic significance and treatment strategies for IKZF1 deletion in pediatric B-cell precursor acute lymphoblastic leukemia.
Pan L, Chen Y, Weng K … +7 more , Guo B, Zhuang S, Huang S, Lian Z, Wang X, Li N, Zheng Y
BMC Cancer · 2024 Aug · PMID 39210321 · Full text
BACKGROUND: The predictive importance of IKZF1 in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has shown variability across different studies. Thus, the optimal treatment approach for children with I...
BACKGROUND: The predictive importance of IKZF1 in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has shown variability across different studies. Thus, the optimal treatment approach for children with IKZF1 BCP-ALL remains contentious, with the ongoing debate surrounding the use of IKZF1-based high-risk stratification versus a minimal residual disease (MRD)-guided protocol. METHODS: IKZF1 status was reliably determined in 804 patients using multiplex ligation-dependent probe amplification (MLPA) data obtained from four hospitals in Fujian, a province of China. In the Chinese Children Leukemia Group (CCLG)-ALL 2008 cohort, IKZF1 status was included in the risk assignment, with all IKZF1 patients receiving a high-risk regimen. Conversely, in the Chinese Children's Cancer Group (CCCG)-ALL 2015 cohort, IKZF1 was not incorporated into the risk assignment, and patients were treated based on an MRD-guided risk stratification protocol. RESULTS: IKZF1 was found in 86 patients (86/804, 10.7%) overall and in 30 (30/46, 65.2%) BCR::ABL1-positive patients. Overall, IKZF1 was a poor prognostic predictor for patients, though the significance diminished upon age adjustment, white blood cell (WBC) count at diagnosis, treatment group, and MRD status. In the CCLG-ALL 2008 cohort, IKZF1 conferred a notably lower 5-year overall survival (OS) and event-free survival (EFS) and a significantly higher 5-year cumulative incidence of relapse (CIR) than IKZF1. In the CCLG-ALL 2015 cohort, IKZF1 conferred a lower 5-year OS and EFS and a higher 5-year CIR than IKZF1, but the differences were insignificant. The IKZF1 patients treated with higher intensity chemotherapy (CCLG-ALL 2008 high-risk regimen) had a markedly lower 5-year OS and EFS compared with those treated with the MRD-guided protocol (CCCG-ALL 2015 protocol). Furthermore, patients treated with the CCLG-ALL 2008 high-risk regimen experienced a higher frequency of serious adverse events (SAEs), especially infection-related SAEs, compared with those treated with the CCCG-ALL 2015 MRD-guided protocol. CONCLUSIONS: The prognostic effect of IKZF1 may vary in different protocols. Compared with higher intensity chemotherapy, the MRD-guided protocol may be a more effective approach to treating BCP-ALL with IKZF1 in children.
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