Adolescent and young adult (AYA) patients seem to be in a sort of no-man's land, halfway between the two different worlds of pediatric and adult medical oncology and bearing the brunt, in terms of ...inclusion in clinical trials and quality of professional care, of the lack of integration between these two worlds. This article discusses the different organization models of care used in pediatric oncology (mainly family-focused) and in adult medical oncology (disease-focused). There is a growing awareness that these models are not ideally suited to the complex needs of AYA patients, which require a different, new, patient-focused multidisciplinary approach. A comprehensive, multipronged effort is required to bridge the gap in the care of AYA patients, with the ultimate challenge of creating a new discipline, AYA oncology. In this article, we review the experiences of AYA oncology programs in Europe, North America, and Australia, focusing on similarities and differences in strategy, as well as the major challenges and opportunities faced by these programs. Among the most important factors for the successful establishment of an AYA oncology service are the degree of engagement of both pediatric and adult medical oncologists, the philanthropic support of powerful charities, and the role of dedicated professionals across a range of disciplines in driving the development of services for AYA patients.
Wilms tumor (or nephroblastoma), rhabdomyosarcoma, and medulloblastoma, common embryonal tumors in children, can occasionally occur in adults, for whom survival is significantly inferior than ...pediatric patients. Available data on adults with Wilms tumor consist of case or case series reports. Among other factors, the unfamiliarity of adult oncologists and pathologists with nephroblastoma and consequent delays in initiating the appropriate risk-adapted chemotherapy may negatively influence outcomes. The survival decrement in adults with rhabdomyosarcoma has been attributed to the lack of centralized care, the inconsistent use of standard protocol-driven multimodal therapy, and lower chemotherapy tolerance in adult patients. In children with medulloblastoma, evidence from randomized clinical trials has led to risk-tailored therapies tuned on histology, extent of initial disease, and biological features. Such refinements are still missing for adults due to the lack of similar trials and studies that might provide the same or a different understanding regarding patients’ individual prognosis, treatment morbidity, and quality of life. Recent experiences have suggested that applying or adjusting pediatric protocols to adult patients with these tumors is feasible and can improve survival. Here, we provide an evaluation of the current evidence for the management of Wilms tumor, rhabdomyosarcoma, and medulloblastoma arising in adults. This review aims to promote the referral of adolescents and adults with pediatric tumors to pediatric centers for inclusion into pediatric protocols, or into protocols and studies specifically designed for that age group with the cooperation between pediatric and adult oncologists.
PhotoTherapy represents a recent psychotherapeutic intervention which, through the medium of photography, has the objective of helping a patient reach a higher self-knowledge and explore thoughts, ...desires, and intimate perceptions that would otherwise remain hidden. Because of this, it may help people overcome their cognitive and emotional boundaries and bring out their interiority, even when exploring some of the most distressing themes. The objective of the present research was to demonstrate that the elaboration and expression of inner desires, fears and needs of wellbeing among adolescents and young adults, who were either sick or had been cured of cancer, could be facilitated through the use of PhotoTherapy. Their responses were also compared with those of healthy young adults, in order to be able to explore the kind of impact such a pathology can have on those who are affected by it and highlight eventual differences in the kind of desires and needs expressed instead by those who never had a diagnosis of cancer. A qualitative research design was adopted. 45 people took part in the study, aged between 12 and 25 (mean age 19). The participants were divided into three groups: those currently being treated for cancer, those with a history of cancer and those who had no experience of cancer (third group). From the data analysis, different preferences and attitudes toward the presented pictures and themes emerged among the participants, depending on the specific group they belonged to. The article discusses these preferences and considers how PhotoTherapy can help treat psychological distress caused by cancer.
Classical pediatric Hodgkin Lymphoma (HL) is a rare malignancy. Therapeutic regimens for its management may be optimized by establishing treatment response early on. The aim of this study was to ...identify plasma protein biomarkers enabling the prediction of relapse in pediatric/adolescent HL patients treated under the pediatric EuroNet-PHL-C2 trial. We used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics at the time of diagnosis—before any therapy—as semiquantitative method to profile plasma proteins specifically associated with relapse in 42 children with nodular sclerosing HL. In both the exploratory and the validation cohorts, six proteins (apolipoprotein E, C4b-binding protein α chain, clusterin, fibrinogen γ chain, prothrombin, and vitronectin) were more abundant in the plasma of patients whose HL relapsed (|fold change| ≥ 1.2, p < 0.05, Student’s t-test). Predicting protein function with the Gene Ontology classification model, the proteins were included in four biological processes (p < 0.01). Using immunoblotting and Luminex assays, we validated two of these candidate biomarkers—C4b-binding protein α chain and clusterin—linked to innate immune response function (GO:0045087). This study identified C4b-binding protein α chain and clusterin as candidate early plasma biomarkers of HL relapse, and important for the purpose of shedding light on the molecular scenario associated with immune response in patients treated under the EuroNet-PHL-C2 trial.
The identification of circulating proteins associated with relapse in pediatric Hodgkin lymphoma (HL) may help develop predictive biomarkers. We previously identified a set of predictive biomarkers ...by difference gel electrophoresis. Here we used label-free quantitative liquid chromatography-mass spectrometry (LC-MS/MS) on plasma collected at diagnosis from 12 children (age 12-16 years) with nodular sclerosis HL, including six in whom the disease relapsed within 5 years of treatment in the LH2004 trial. Plasma proteins were pooled in groups of three, separately for non-relapsing and relapsing HL, and differentially abundant proteins between the two disease states were identified by LC-MS/MS in an explorative and validation design. Proteins with a fold change in abundance >1.2 or ≤0.8 were considered "differentially abundant". LC-MS/MS identified 60 and 32 proteins that were more abundant in non-relapsing and relapsing HL plasma, respectively, in the explorative phase; these numbers were 39 and 34 in the validation phase. In both analyses, 11 proteins were more abundant in non-relapsing HL (e.g., angiotensinogen, serum paraoxonase/arylesterase 1, transthyretin), including two previously identified by difference gel electrophoresis (antithrombin III and α-1-antitrypsin); seven proteins were more abundant in relapsing HL (e.g., fibronectin and thrombospondin-1), including two previously identified proteins (fibrinogen β and γ chains). The differentially abundant proteins participated in numerous biological processes, which were manually grouped into 10 biological classes and 11 biological regulatory subclasses. The biological class Lipid metabolism, and its regulatory subclass, included angiotensinogen and serum paraoxonase/arylesterase 1 (more abundant in non-relapsing HL). The biological classes Immune system and Cell and extracellular matrix architecture included fibronectin and thrombospondin-1 (more abundant in relapsing HL). These findings deepen our understanding of the molecular scenario underlying responses to therapy and provide new evidence about these proteins as possible biomarkers of relapse in pediatric HL.
IntroductionAssessment of response to therapy in paediatric patients with Hodgkin lymphoma (HL) by 18F-fluorodeoxyglucose positron emission tomography/CT has become a powerful tool for the ...discrimination of responders from non-responders. The addition of volumetric and texture analyses can be regarded as a valuable help for disease prognostication and biological characterisation. Based on these premises, the Hodgkin Lymphoma Study Group of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) has designed a prospective evaluation of volumetric and texture analysis in the Italian cohort of patients enrolled in the EuroNet-PHL-C2.Methods and analysisThe primary objective is to compare volumetric assessment in patiens with HL at baseline and during the course of therapy with standard visual and semiquantitative analyses. The secondary objective is to identify the impact of volumetric and texture analysis on bulky masses. The tertiary objective is to determine the additional value of multiparametric assessment in patients having a partial response on morphological imaging.The overall cohort of the study is expected to be round 400–500 patients, with approximately half presenting with bulky masses. All PET scans of the Italian cohort will be analysed for volumetric assessment, comprising metabolic tumour volume and total lesion glycolysis at baseline and during the course of therapy. A dedicated software will delineate semiautomatically contours using different threshold methods, and the impact of each segmentation techniques will be evaluated. Bulky will be defined on contiguous lymph node masses ≥200 mL on CT/MRI. All bulky masses will be outlined and analysed by the same software to provide textural features. Morphological assessment will be based on RECIL 2017 for response definition.Ethics and disseminationThe current study has been ethically approved (AIFA/SC/P/27087 approved 09/03/2018; EudraCT 2012-004053-88, EM-04). The results of the different analyses performed during and after study completion the will be actively disseminated through peer-reviewed journals, conference presentations, social media, print media and internet.
The acquisition of relevant pediatric clinical safety data is essential to ensure tolerable drug therapies. Comparing the real number of Adverse Drug Reaction (ADR) reports in clinical practice with ...the literature, the idea of ADR underreporting emerges. An active pharmacovigilance observational prospective study was conducted to assess the safety of oncology pharmacological prescriptions in patients aged 0-24 years at Institute for Maternal and Child Health IRCCS Burlo Garofolo in Trieste and IRCCS CRO National Cancer Institute in Aviano (Italy) between January 2021 and October 2023. Prescriptions and ADRs were evaluated by a multidisciplinary team. A total of 1218 prescriptions for 38 patients were analyzed, and 190 ADRs of grade 3-5 were collected. As compared to historical data, we registered a significant increase (
< 0.001) in the number of ADRs. The risk of ADR was 3.4 times higher in the case of off-label prescriptions compared to on-label ones (OR 3.4; 1.47; 7.89;
-value = 0.004). The risks of error and near-miss were reported for 6.3% and 18.2% of total prescriptions, respectively. Of the total of 133 interactions, 47 (35.3%) resulted in ADRs. This study shows the importance of pro-active pharmacovigilance to efficiently highlight ADRs, and the fundamental role of multidisciplinary teams (oncologist, pharmacist, pharmacologist, pediatrician, nurse) in improving patients' safety during therapy.
The ligation of programmed cell death 1 (PD-1) with programmed cell death ligand PD-L activates the immune checkpoint leading to T-cell dysfunction, exhaustion, and tolerance, especially in Hodgkin ...lymphoma (HL) where the PD-L/ Janus kinase (Jak) signaling was frequently found altered. Anti-PD-1 or anti-PD-L1 monoclonal antibodies can reverse this immune checkpoint, releasing the brake on T-cell responses. The characterization of the mechanisms regulating both the expression of PD-1 and PD-L and their function(s) in HL is ongoing. We provide in this review the recent findings focused on this aim with special attention on the major research topics, such as adverse events and resistance to PD-1–PD-L1 inhibitor treatment, together with a part about angiogenesis, extracellular vesicles, and microbiome in HL pathogenesis.
EBV produces miRNAs with important functions in cancer growth, tumor invasion and host immune surveillance. The discovery of EBV miR-BARTs is recent, and most of their functions are still unknown. ...Nonetheless, some new studies underline their key roles in EBV-associated malignancies.
In EBV-associated tumors, the expression profile of miR-BARTs varies according to the cell type, autophagic process and signals received from the tumor microenvironment. By the same way of interest is the interaction between tumor cells and the tumor environment by the release of selected EBV miR-BARTs in addition to the tumor proteins trough tumor exosomes.
In this review, we discuss new findings regarding EBV miR-BARTs in Hodgkin lymphoma and gastric cancer. The recent discovery that miRNAs are released by exosomes, including miR-BARTs, highlights the importance of tumor and microenvironment interplay with more specific effects on the host immune response.
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