Background:Infections are the leading cause of non-relapse mortality in pediatric hematopoietic cell transplant (HCT) recipients. Up to 90% of bacteremias in these patients originate from gut microbiome organisms. However, selection for resistance genes, such as Extended-spectrum β-lactamase (ESBL), in these patient's gut microbiomes remains poorly understood. Methods:Stools were prospectively collected from pediatric HCT recipients at multiple centers (n=133 patients, five centers) on the day of HCT, the day of neutrophil engraftment, and 30 days post-HCT. Bacterial DNA was isolated and sent for shotgun metagenomic sequencing. Antibiotic resistance genes were identified using the MEGARes database. Associations between ESBL gene abundance changes and antibiotic exposure were examined using univariate and Inverse Probability of Treatment Weighting linear regression models with covariate balancing propensity scores. Results:Pre-existing gut resistome disruption at the time of HCT showed a stronger correlation with ESBL gene expansion than post-transplant antibiotic exposure. Specifically, patients with greater baseline resistome distance from healthy children showed increased ESBL genes during the neutropenic period. Post-transplant β-lactam exposure (total or ESBL-cleavable) did not correlate with increases in ESBL genes in already-colonized patients. However, aminoglycosides and anaerobic active antibiotics were associated with acquisition of new ESBL organisms during the neutropenic period, while pre-existing microbiome disruption primarily drove selection of resistant bacteria already present. Conclusions:These findings indicate that antibiotic stewardship before HCT, in addition to reducing the use of anaerobic active antibiotics during early transplant, may be necessary to prevent ESBL-related infections in pediatric transplant recipients. Lay Summary:Infections are the leading cause of death after HCT, and recently the role of the gut microbiome in harboring dangerous bacteria has been highlighted. This study aims to understand multidrug resistant bacteria changes in the gut microbiome early after HCT.

Ribosomes are central to cellular growth and proteome maintenance, and cancer cells frequently depend on increased ribosome biogenesis and altered translation to sustain proliferation, stress tolerance, and metabolic rewiring. Paradoxically, inherited “ribosomopathies” caused by germline defects in ribosomal proteins or ribosome biogenesis factors present with tissue hypoplasia and bone marrow failure early in life, yet confer substantially increased lifetime risk of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and selected solid tumors. In parallel, somatic alterations affecting ribosomal proteins and ribosome regulatory pathways recur across malignancies, including hematologic cancers such as T-cell acute lymphoblastic leukemia (T-ALL), and in pediatric solid tumors. Mechanistically, oncogenic ribosome disturbances can reprogram translation toward specific mRNA subsets, alter translational fidelity, trigger nucleolar/ribosomal stress signaling via the 5S ribonucleoprotein (5S RNP)–MDM2–p53 axis, and enable selection for compensatory or cooperating lesions (notably TP53 pathway alterations). Clinically, these insights support diagnostics and surveillance of inherited ribosome-related cancer predisposition syndromes, therapeutic targeting of ribosome biogenesis and translational control, including RNA polymerase I inhibition, and the eIF4 translation-initiation machinery. Here, we present current evidence linking constitutional and acquired ribosomal dysfunction to leukemogenesis and tumorigenesis, highlight disease- and context-specific mechanisms, and outline priorities for translational research and precision therapy.

BACKGROUND: Chemoimmunotherapy (ChIt) has been proven to be an effective treatment for patients with refractory high-risk neuroblastoma (HR-NBL). The objective was to assess the appearance of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after high-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) in patients previously treated with ChIt for refractory HR-NBL. METHODS: Nineteen patients were treated with ChIt based on dinutuximab beta for refractory NBL and underwent ASCT. Six patients underwent HDC with ASCT according to the SIOPEN protocol (Busulfan and Melphalan (BuMel)). Treosulfan and Melphalan (TreoMel) were used in 13 patients. The occurrence of VOD/SOS was analysed. The Mann-Whitney U test was used to analyse the correlation between VOD/SOS and potential risk factors. RESULTS: VOD/SOS developed in five out of six patients when BuMel was used after ChIt (3 pts, grade 4; 2 pts, grade 3), resulting in two deaths. No VOD/SOS was observed in patients receiving TreoMel. Other analysed factors had no influence of VOD/SOS occurrence and the only identified risk factor was BuMel administered after ChIt. CONCLUSIONS: Patients with refractory HR-NBL treated with ChIt and DB did not present life-threatening toxicities or severe liver toxicities during the ChIt cycles and continued to HDC with ASCT according to SIOPEN guidelines. The incidence of severe VOD/SOS after ChIt and subsequent BuMel was higher than expected, with severe course resulting in two deaths. Taking into account the possible increase in the risk of VOD/SOS after BuMel used after chemotherapy combined with DB, careful observation with early VOD/SOS treatment in patients after ChIt is recommended and TreoMel regimen may be considered as less toxic.

BackgroundAdoptive transfer of virus-specific T lymphocytes (VST) is an emerging strategy for refractory viral infections in immunocompromised individuals and is being prospectively evaluated in the ALLOVISTA clinical trial. Here we describe our experience with hospital-exemption advanced therapy medicinal product (ATMP-HE) VST in six pediatric transplant recipients.MethodsSix children and adolescents (median age 4.5 years, range 2.5–18.5) treated in two Polish centers received VST for refractory viremia after allogeneic hematopoietic stem cell transplantation: adenovirus (ADV) in three cases, EBV-driven disease (EBV/PTLD or HL relapse with EBV reactivation) in three, including one patient with concomitant CMV/EBV/ADV infection. All patients had failed conventional antiviral and/or immunochemotherapy (cidofovir, rituximab, chemotherapy). VST were generated from allo-HSCT or related donors using automated CliniMACS Prodigy Cytokine Capture System (IFN-γ CCS, Miltenyi Biotec) following antigenic stimulation with viral peptide pools and released as ATMP-HE according to the ALLOVISTA protocol. A single intravenous infusion of 1.01×105–1.85×106 VST (median 2.5×105) was administered. Virological response was assessed by quantitative PCR up to 4 weeks post-infusion, acute GVHD (aGVHD) and survival were recorded.ResultsVirological outcomes were evaluable in five patients. Four of five (80%) evaluated patients achieved at least a 1-log reduction in viral load, including two (40%) with complete clearance by week 4 (one EBV, one ADV). Two additional patients had marked but incomplete or transient viral load reductions, one patient showed minimal virological change. Despite biological activity, four children died: from progressive EBV disease (n=1), ADV infection (n=1), relapse of HL (n=1) and multi-organ failure with invasive fungal disease in a child with multi-viral infection (n=1). Two patients with complete virological responses are alive with sustained remission of viremia at the last follow-up. No new-onset or worsening aGVHD was documented after VST infusion.ConclusionsVST administered as an ATMP-HE are feasible in routine clinical practice and demonstrate rapid antiviral activity in heavily pretreated pediatric patients. However, advanced viral disease and competing complications limit overall survival, underscoring the need for earlier intervention and advocating for treatment within the ongoing ALLOVISTA trial.

BackgroundCellular immunotherapies—including chimeric antigen receptor T-cell (CAR-T) therapies and adoptive transfer of virus-specific T lymphocytes (VSTs) — have transformed the treatment of refractory hematological malignancies and post-transplant infectious complications. Eight products are currently authorized by the European Medicines Agency, encompassing seven autologous CAR-T products targeting CD19 or BCMA and tabelecleucel (Ebvallo), the first approved allogeneic off-the-shelf EBV-specific T-cell product for EBV-positive post-transplant lymphoproliferative disease. Despite their clinical efficacy, both modalities carry distinct early toxicity profiles that differ from conventional cytotoxic chemotherapy.ObjectiveThis review summarizes current recommendations for identifying, assessing, and treating early problems that can occur after CAR-T cell therapy and VST administration.ContentCAR-T-specific complications discussed include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), and immune effector cell-associated HLH-like syndrome (IEC-HS). CRS is graded by ASTCT consensus criteria and managed with tocilizumab as first-line pharmacological therapy; steroid-refractory ICANS is most commonly treated with high-dose intravenous anakinra (up to 12 mg/kg/day) which is currently the most studied second-line option, although the supporting evidence remains largely observational. ICAHT is classified using the validated EHA/EBMT grading framework, separating early (day 0–30) and late (post-day 30) neutropenia by depth and duration, with management escalating from prophylactic G-CSF through hematopoietic cell boost to allogeneic HSCT as the ultimate option. For VSTs, the principal early complications are tumor flare reaction (in approximately 20% of tabelecleucel recipients), GVHD (below 5% with enriched products), acute infusion reactions, and low-grade CRS-like cytokine release. We summarize a differential diagnosis of overlapping syndromes, pediatric-specific adaptations, ICU escalation criteria, and a clinical monitoring schedule.ConclusionsInternationally validated criteria grade the early complications of cellular immune effector therapies. Prompt recognition, early pharmacological intervention, and monitoring are essential to minimize non-relapse mortality. Expanding real-world experience and the integration of pre-treatment risk stratification tools will continue to refine evidence-based practice in this rapidly evolving field, ultimately leading to improved patient outcomes and reduced non-relapse mortality rates.

Background/Objectives: Rapid cellular proliferation, a hallmark of malignancy, requires sustained and elevated protein synthesis, which in turn requires efficient ribosome biogenesis. The aim of this study was to evaluate the expression levels of TP53, C-MYC, FBL, and NCL in pre-B ALL and neuroblastoma tissues compared to healthy bone marrow samples—factors that may carry prognostic significance in pediatric malignancies. Materials and methods: The cohort included 45 pre-B ALL patients, 19 neuroblastoma patients, and 12 healthy bone marrow donors as controls. Total RNA was extracted from bone marrow or tumor samples and cDNA synthesis was performed with the Bio-Rad iScript kit. Quantitative PCR was conducted using SYBR Green chemistry, with GAPDH as the reference gene. Primers targeted TP53, C-MYC, FBL, and NCL, and gene expression was calculated using the 2−ΔCt method. Results: The expression of C-MYC and FBL was found to be significantly decreased in patients with pre-B ALL in comparison to the healthy control group. NCL expression was highest in healthy donors, intermediate in pre-B ALL, and lowest in neuroblastoma. In addition to intergroup comparisons, correlations between gene expression levels were assessed within each diagnostic group. In the pre-B ALL group, a positive correlation was observed between TP53 and C-MYC expression, as well as between TP53 and both FBL and NCL. Furthermore, a significant positive correlation was found between FBL and NCL. In the neuroblastoma group, a statistically significant positive correlation was identified between C-MYC and FBL expression. In the control group, TP53 expression was positively correlated with NCL, and FBL expression showed a significant positive correlation with NCL. Conclusions: This study suggests the altered expression of ribosome biogenesis-related genes in pediatric pre-B acute lymphoblastic leukemia and neuroblastoma. The reported dysregulation suggests a disease-associated disruption in nucleolar function and translational regulation and may contribute to oncogenesis through altered ribosomal assembly, protein synthesis, or proliferative signaling.

Background: Congenital renal masses in neonates are most commonly congenital mesoblastic nephroma or, less frequently, or Wilms tumor. We describe a neonate with an apparent primary renal tumor that proved to be adrenal neuroblastoma infiltrating the kidney, highlighting diagnostic pitfalls in this subgroup of patients. Methods: We retrospectively reviewed the diagnostic work-up, histopathology, genomic profiling, treatment, and outcome of a term neonate in whom a renal mass was detected incidentally on ultrasound. Results: Ultrasound and MRI showed a 2 cm solid lesion centered in the upper pole of the left kidney, interpreted as nephroblastomatosis/early Wilms tumor. Left nephrectomy with adrenalectomy revealed stroma-poor, undifferentiated neuroblastoma with regional node involvement and multiple segmental chromosomal aberrations, including 1p and 3p loss, but no MYCN or ALK alterations. Initial management consisted of surgery alone with close surveillance. Within weeks, early disseminated relapse with bone and soft-tissue metastases occurred, necessitating escalation to high-risk, COJEC-based chemotherapy; resection of residual mass; and modified consolidation without high-dose chemotherapy or radiotherapy. The child remains in complete remission with preserved renal function. Conclusions: Neuroblastoma should be considered in the differential diagnosis of congenital “renal” masses. Imaging-driven provisional diagnoses may be misleading, and genomic risk profiling may help lower the threshold for systemic therapy in selected cases.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive and antiangiogenic therapies. Laser-based approaches, including photobiomodulation therapy (PBMT) and erbium laser-assisted surgery, have been proposed as adjunctive interventions to improve healing and clinical outcomes. This consensus-based review aimed to synthesize evidence from systematic reviews and meta-analyses evaluating laser-based therapies in the prevention and treatment of MRONJ, and to translate these findings into clinical recommendations developed by the World Federation for Laser Dentistry (WFLD) and the Polish Society for Laser Dentistry (PTSL).The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Joanna Briggs Institute (JBI) guidance, and was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO). An electronic search of the PubMed/MEDLINE, Embase, Scopus, and Cochrane Library databases was conducted for systematic reviews and meta-analyses published between January 2015 and October 2025. Study selection, data extraction and methodological assessment were performed independently by 3 reviewers.Eighty-five records were identified, and 14 reviews met the inclusion criteria. These included several hundred primary studies, mainly observational studies and case series. Laser-based interventions were primarily used as adjuncts to conventional MRONJ management. Photobiomodulation therapy was associated with pain reduction and improved soft tissue healing, while erbium-doped yttrium aluminum garnet (Er:YAG) laser-assisted surgery enabled the precise removal of necrotic bone. Combined protocols showed generally favorable trends. However, substantial heterogeneity in study design, laser parameters and outcome definitions precluded quantitative synthesis.Laser-based therapies may provide beneficial adjunctive effects in MRONJ management, particularly within multimodal treatment strategies. However, the strength of these conclusions is limited due to substantial heterogeneity in study design, laser protocols and outcome reporting.

Inherited bone marrow failure syndromes (IBMFs) are a molecularly heterogeneous group of genetically-determined syndromes with a wide spectrum of clinical abnormalities and risk of hematopoietic neoplasia and reduced life expectancy. The prevalence is not well established but is growing due to the advent of genetic diagnostics. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative modality in eligible IBMF patients but the indications are individualized due to significant transplant-related morbidity, including secondary cancer. HSCT indications and practices are also impacted by the gradual introduction of gene therapies for IBMFs, but that remains developmental at the moment. Medical non-transplant therapies have played an important role in several IBMFs for decades. Their impact vary from nearly curative treatment in Diamond-Blackfan Anemia (DBA), through supportive interventions, to experimental treatment aimed at impacting the natural course of the disease. This may be subject to change, because of the description of new syndromes or new pathomechanisms of the established syndromes. While their impact might be diminishing due the progress in gene therapy, there might be some new clinically useful interventions due to new medical technologies and the progress in drug-repurposing. The medical therapies can be used as a mainstay of therapy, bridge therapy to transplantation, peri- or post-transplantation aiming at amelioration of the hematological and non-hematological phenotype, improved growth and development, diminishing the risk of myeloid neoplasm or other cancer. Disease- and therapy-specific risks of these interventions must be actively addressed in patients. We present state-of-the-art and developmental applications of non-cellular therapies in IBMFs.

Background:Epstein-Barr virus (EBV) is a common trigger of secondary hemophagocytic lymphohistiocytosis (HLH), particularly in transplant recipients. Adoptive cellular therapy with EBV-specific T cells is an emerging option for refractory EBV-driven disease but may precipitate cytokine toxicities. Case:We report a boy with a history of congenital nephrotic syndrome who in infancy underwent maternal kidney transplantation. At the age of 6 years, he developed monomorphic EBV-positive post-transplant lymphoproliferative disorder, followed by EBV-driven HLH. Despite etoposide- and steroid-based HLH therapy, IVIG, anakinra, and a maternal virus-specific T-cell infusion, he showed recurrent hyperinflammation. After a single dose of the allogeneic EBV-specific T-cell product tabelecleucel (Ebvallo) and exacerbation of HLH, he experienced cytokine release syndrome and neurotoxicity with acute liver failure, coagulopathy, and renal failure. He died from refractory lactic acidosis and multiorgan failure. Conclusion:This case highlights the therapeutic complexity of EBV-HLH in a solid-organ transplant recipient and underscores both the rationale for and risks of cellular immunotherapy amid severe hyperinflammation and organ dysfunction.

Neuroblastoma (NBL) constitutes the most common extracranial solid tumor in children that arises from the sympathetic ganglia. Its manifestations depend on the localization of the tumor and metastases. This research aimed to assess the incidence of ophthalmological symptoms and their correlations with different prognostic factors. We collected and analyzed retrospectively the data of 776 children with a clinical diagnosis of peripheral neuroblastic tumors reported between 2004 and 2022 from 14 Polish pediatric oncology centers. Ophthalmological symptoms occurred in 17.10% of the patients, and in 12.70% they were diagnosed at the time of the first presentation. The reported manifestations comprised opsoclonus-myoclonus syndrome (OMS), Horner syndrome (HS), exophthalmos, periorbital hemorrhages, with the highest incidence of OMS (4.74% of all the patients). Moreover, we described the cases with neurological manifestations of NBL like paraparesis and facial nerve paresis. The age correlated with the form of symptoms, and HS was observed in the youngest patients. Similarly, the time from the symptoms onset to NBL diagnosis differed significantly among the patients, therefore the diagnosis of HS was associated with the longest period. In conclusion, the ophthalmological manifestations of NBL represent an essential group of symptoms. Therefore, clinicians should consider them as possible signs of tumors, particularly HS, which may be most challenging in the diagnostic process.

Neuroblastoma constitutes the most frequent solid tumor in children under 2 years of age. It is most often located in the abdomen; however, it may also be found in the mediastinum or the neck, and its first and only symptom may be Horner syndrome (HS). Because various imaging and laboratory examinations may be employed in order to detect the tumor, the objective of our study was to assess their sensitivity in detecting neuroblastoma in children with HS. The study comprised data from 14 oncologic departments in Poland and involved children with a clinical diagnosis of neuroblastoma. In total, 729 patients were included in the analysis who were diagnosed between 2004 and 2022. HS occurred before the neuroblastoma diagnosis in 3.29% of cases. The study evaluated the sensitivity of lactate dehydrogenase (LDH), ferritin and neuron-specific enolase (NSE) serum concentration, dopamine and vanillylmandelic acid urinary levels, as well as of chest radiography in the detection of neuroblastoma tumor. The combination of urinary catecholamines demonstrated a low sensitivity (72.57%). However, chest radiography proved to be highly effective in identifying lesions associated with neuroblastoma (92.31% sensitivity in patients with HS on the first presentation), which may be further enhanced by means of performing LDH, ferritin, and NSE blood concentration tests (100% sensitivity). Our findings indicate that chest radiography and serum laboratory tests may represent valuable tools in the primary diagnosis of HS etiology. In contrast, urinary catecholamines test should not be considered a diagnostic criterion.

Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker of kidney allograft injury. Elevated dd-cfDNA has been associated with acute rejection, particularly antibody-mediated rejection; however, dd-cfDNA reflects graft-derived tissue injury rather than a specific alloimmune mechanism. Its interpretation may therefore be challenging in conditions characterized by endothelial and microvascular injury, such as atypical hemolytic uremic syndrome (aHUS). This retrospective observational study included 14 kidney transplant recipients who underwent their first kidney transplantation at Wroclaw Medical University between April and December 2022. Twelve non-aHUS recipients with stable renal function and two recipients with aHUS were assessed. Plasma samples were collected at four early post-transplant time points: day 7 (D7), day 14 (D14), month 1 (M1), and month 2 (M2). dd-cfDNA was measured using next-generation sequencing with the AlloSeq cfDNA assay. Donor-specific anti-HLA antibodies (DSA) were assessed using single-antigen bead testing. In non-aHUS recipients, median %dd-cfDNA declined from 0.72% [0.28%, 2.33%] at D7 to 0.12% [0.05%, 0.34%] by M1. In contrast, recipients with aHUS demonstrated persistently elevated dd-cfDNA values fluctuating around 1% [0.88%, 1.14%] during the first month of follow-up. No DSA were detected in any patient during the observation period. No apparent correlation was observed between %dd-cfDNA and serum creatinine in this small cohort. In this preliminary observational study, kidney transplant recipients with aHUS showed persistently elevated early post-transplant dd-cfDNA despite the absence of detectable DSA, absence of clinically documented rejection, and preserved graft function during follow-up. These findings suggest that universal dd-cfDNA thresholds may require cautious interpretation in aHUS. Larger biopsy-anchored studies integrating complement and endothelial injury markers are needed to clarify whether dd-cfDNA elevation in aHUS reflects alloimmune injury, complement-mediated microvascular injury, or overlapping mechanisms.

A girl with very early-onset inflammatory bowel disease due to a loss-of-function IL10RA mutation (c.611G>A p.Trp204*) presented in infancy with severe Crohn’s disease-like colitis requiring colectomy. Two matched-sibling allogeneic haematopoietic stem cell transplantations using treosulfan-based conditioning engrafted transiently but ultimately failed with autologous recovery and immune cytopenias. A third transplant from the same donor with busulfan/fludarabine/melphalan plus serotherapy and peripheral blood stem cells achieved durable engraftment. Acute skin and gut graft-versus-host disease responded to corticosteroids and etanercept. On long-term follow-up, the patient remained off immunosuppression with stable donor chimerism, normal immunoglobulins, nutritional catch-up (weight), preserved puberty and regular menses though short stature persisted.

Neuroblastoma (NBL) is a tumor that develops from sympathetic ganglia and most frequently occurs in young children. In mediastinal and cervical cases, Horner syndrome (HS) may occur as a symptom or a surgical complication. The study aimed to evaluate the factors that influence the occurrence of postsurgical HS. The data concerning the clinical presentation, imaging examinations, performed therapies and treatment outcomes of 454 children with NBL were collected, including 117 cases of thoracic and cervical tumors. The statistical analyses of correlations between postsurgical HS occurrence and different features was performed. HS appeared in 57.89% of patients with tumors adjacent to oculosympathetic pathway. Statistical analyses demonstrated a significant impact of tumor location, patients' age and the duration between the onset of symptoms and the diagnosis on HS incidence as a complication of NBL resection. Neoadjuvant chemotherapy was also associated with a lower incidence of postsurgical HS. The radicality of surgery, the time from diagnosis to the procedure and the used technique did not present any statistically significant association with the occurrence of HS. In conclusion, parents of patients should be informed about the risk of HS in every case of a tumor localized near the oculosympathetic tract. Neoadjuvant chemotherapy might help reduce the risk of postsurgical complications.

Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myelodysplastic/myeloproliferative neoplasm characterized by distinct epigenetic signatures that facilitate molecular classification. This study aimed to evaluate the diagnostic utility of locus-specific DNA methylation in the bone morphogenetic protein 4 (BMP4) gene as a single predictor of disease outcomes in a cohort of 111 children diagnosed with JMML, alongside 9 healthy controls. Methylation levels of BMP4, assessed through targeted bisulfite next-generation sequencing (bs-NGS), were heterogeneous within the JMML cohort and were significantly associated with clinical risk factors, such as patient age, and fetal hemoglobin (HbF) levels. A comparative analysis of BMP4 bs-NGS and genome-wide methylation array data revealed a strong positive correlation (p < 0.001). The sensitivity and specificity of BMP4 bs-NGS for classifying high-methylation cases were 0.612 and 0.887, respectively. For PTPN11-mutant patients (N = 40), the sensitivity was 0.667 and the specificity was 0.842. Survival analysis indicated that patients with high BMP4 methylation (BMP4h) had lower 5-year disease-free survival (DFS) rates than those with normal BMP4 methylation (BMP4n). Specifically, the 20% of patients with highest BMP4 methylation had a 5-year DFS of 0.38, in contrast to 0.62 for the lowest 20% (p = 0.007). These findings highlight the potential of BMP4 methylation analysis as a complementary biomarker for JMML risk stratification, mirroring genome-wide methylation profiles known to associate with prognostic subgroups.

Neuroblastoma is the most common extracranial solid tumor in children, requiring multidisciplinary treatment, including radiotherapy, which is primarily applied in the high-risk group to prevent disease progression. The review highlights indications for radiotherapy, its role in multimodal treatment, and addresses aspects of radiotherapy planning, including target volume definition, prescribed radiation doses, optimal timing for radiotherapy implementation, and potential side effects. Particular attention is drawn to the lack of consensus regarding the necessity of an additional radiation dose for persistent residual disease in the primary tumor and the irradiation of metastatic sites remaining after induction therapy. To conclude, monitoring quality assurance in radiotherapy planning and delivering processes based on unified standards appears to be crucial.