Pediatric Tumor Patients Research Articles

Evaluation of the positional reproducibility of sedation versus non-sedation state in pediatric radiotherapy: a retrospective study

ObjectiveTo assess the positional reproducibility of sedated and non-sedated pediatric tumor patients during radiotherapy through a retrospective analysis of cone-beam computed tomography (CBCT) and planned computed tomography (CT) scan data.MethodsThe positional reproducibility of 40 pediatric tumor patients, aged 2 to 17 years with a median age of 4.5 years, who received radiotherapy under sedated and non-sedated states was retrospectively compared. The first CBCT images obtained during CT-based treatment planning were analyzed. The analysis encompassed six-dimensional positional changes, including vertical (Vrt), longitudinal (Lng), lateral (Lat), rotational (Rtn), pitch, and roll directions. Kolmogorov-Smirnov Z nonparametric rank-sum testing was employed to evaluate the positional deviations, considering absolute values regardless of directionality. Data were further stratified based on different fixation methods used during treatment.ResultsSedated patients exhibited significantly smaller positional deviations in Vrt, Lng, Lat, and Rtn directions in the body membrane group compared with their non-sedated counterparts (P<0.05). Similarly, sedated patients demonstrated reduced positional deviations in Vrt, Lng, Lat, Rtn, pitch and Roll directions in the head and neck group compared with non-sedated patients (P<0.05). Meanwhile, compared with vacuum bag plus body membrane fixation, the head and shoulder film fixation technique proved superior in terms of positional reproducibility during sedated treatment, specifically in Vrt, Lng, Lat, Pitch, and Roll directions (P<0.05). Similarly, compared with the alternative fixation method, the head and shoulder film fixation method showed better positional deviations in six-Dimensional directions in non-sedated patients (P<0.05).ConclusionWhile sedated radiotherapy may offer advantages in terms of positional reproducibility, the present study underscores the importance of considering non-sedated radiotherapy as a viable option for pediatric tumor patients. Non-sedated treatment not only provides effective tumor control but also mitigates the psychological trauma and long-term side effects associated with repeated sedative drug use. Future studies should further explore the optimal sedation and fixation strategies for pediatric radiotherapy.

METTL3-induced lncARSR aggravates neuroblastoma tumorigenic properties through stabilizing PHOX2B

Neuroblastoma (NB), the most common extracranial solid tumor in pediatric patients, manifests with considerable variability across multiple primary sites. Despite this, the extent of genetic heterogeneity within these tumor foci and the identification of consistent oncogenic drivers remains largely unexplored. Of particular interest, genetic mutations in PHOX2B have been linked to familial cases of NB, yet the underlying molecular mechanisms are not fully delineated. In our research, we focus on unraveling the role of a novel functional long non-coding RNA (lncRNA) associated with PHOX2B in the context of NB. Using NB cell models with overexpressed PHOX2B, combined with lncRNA microarray analysis, we discovered that lncARSR is significantly upregulated in response to PHOX2B overexpression. Subsequent biological assays demonstrated that lncARSR promotes both the proliferation and metastasis of NB cells. Further molecular investigations revealed that lncARSR plays a crucial role in stabilizing PHOX2B expression within NB cells. Moreover, we identified that the expression of lncARSR is regulated by methylation through methyltransferase-like 3 (METTL3), which itself is positively correlated with PHOX2B expression. Rescue experiments underscored the functional importance of METTL3, lncARSR, and PHOX2B in NB cells. In summary, our findings provide new insights into the molecular functions of PHOX2B in the progression of neuroblastoma and propose a novel therapeutic target for this aggressive malignancy.

Artificial Intelligence (Neural Network) in the Diagnosis of Benign Skin Tumors in Pediatric Patients

Relevance: ten years ago, artificial intelligence (AI), particularly neural networks (NN), as a diagnostic option in practice seemed a distant prospect. Today, the use of AI is becoming an increasingly popular and daily improving approach in all aspects of clinical and fundamental medicine. Purpose: design and learning of a NN to recognize four types of benign melanocytic skin tumors, integration into a mobile app to apply in practice. Material and methods: сlinical and dermatoscopic analysis of skin tumors was carried out in 600 children. In 65 cases the tumors were removed. Histological types were dermal nevus – 43% (n=28), complex nevus - 33.8% (n=22), pyogenic granuloma - 10.8% (n=7), Spitz-nevus - 6.2% (n=4), blue nevus - 3.1% (n=2), melanoma - 3.1% (n=2). Seven patients with pyogenic granulomas and two patients with melanoma were excluded. The test set included 56 dermatoscopic images. Due to the small number of images augmentation was performed. The database has been increased from 600 images to 1800. NN is written in the machine language Python. The machine learning framework was TensorFlow 2.0. The network architecture is based on the pre-trained model “EfficientNet B7”. This model uses the “supervised learning” paradigm. Each element of the sample had a class affiliation. Results: an accuracy of 83% was achieved after a period of learning on the test set. Mathematical metrics calculated in the Scikit-learn library. Sensitivity was 100% (blue nevus), 73% (complex nevus), 93% (dermal nevus), 75% (Spitz-nevus), and specificity were 98%; 94%; 82%; 98%, respectively. AI was integrated into the mobile app “KIDS NEVI”. Conclusion: AI as an auxiliary method for the skin tumors diagnosis in children and adolescents has demonstrated high potential and great opportunities. Dermatoscopic analysis of a skin tumor and a mobile app are able to provide “double control”, quick and correct clinical diagnosis and determination treatment tactics.

Decoding pediatric spinal tumors: a single-center retrospective case series on etiology, presentation, therapeutic strategies, and outcomes

IntroductionSpinal tumors (ST) often result in dire prognosis, carrying risks such as permanent paralysis, sensory loss, and sphincter dysfunction. Data on their incidence and etiology in pediatric populations are markedly scant. Our study investigates the etiology, clinical manifestation, treatment, and outcomes of pediatric ST.MethodsWe conducted a retrospective review of our institutional pediatric oncology and neurosurgery database, examining 14 patients under 18 years admitted with ST due to oncological diseases since 2005. We analyzed the clinical presentations, evaluations, molecular diagnostics and treatments for these patients.ResultsThe study spanned 15 years and included 14 pediatric patients, each diagnosed with distinct spinal tumor entity. The mean patient age was approximately 19.6 ± 10.1 months. Severe axial pain along the vertebral column was observed in 13 patients, while acute neurological deterioration manifested in 7 patients. As a first-line intervention, 13 patients underwent decompressive surgery through laminectomy and tumor resection, and only one patient received chemotherapy solely. Before surgery, seven patients were unable to walk; post-surgery, six of them regained their ability to ambulate. The diagnosis encompassed a range of neoplasms: two instances of Ewing sarcoma, 3 instances of teratoma, one case presenting an atypical teratoid Rhabdoid tumor, two instances each of low-grade astrocytoma and neuroblastoma, and single instances of ependymoma, meningioma, rhabdomyosarcoma, and embryonal tumors with multilayered rosettes (ETMRs). Three patients succumbed two years after initiating therapy.ConclusionDespite their rarity, intraspinal tumors in pediatric patients pose substantial therapeutic challenges. The intertwined complexities of the disease entity and the patient’s neurological status demand swift initiation of an individualized therapeutic strategy. This crucial step helps optimize outcomes for this patient cohort, who frequently grapple with debilitating health conditions. Inclusion of these patients within a registry is mandatory to optimize treatment outcomes due to their rarity in pediatric population.

Original Research: Proximal Tibia Hemiarthroplasty Reconstruction Following Resection of Malignant Bone Tumors in Skeletally Immature Patients

BackgroundReconstruction of the proximal tibia following resection of malignant bone tumors in pediatric patients is traditionally limited to osteoarticular allografts or endoprostheses. Endoprostheses typically require resection or disruption of the distal femoral physis, which can lead to a leg length discrepancy (LLD). We introduce a novel form of proximal tibia limb reconstruction using a Compress® tibia hemiarthroplasty, which spares the distal femoral physis. MethodsWe retrospectively reviewed 5 patients who underwent proximal tibia osteosarcoma resection and reconstruction with a custom Compress® proximal tibia hemiarthroplasty. Data on function, survival, LLD, complications, and patient reported outcomes were collected. ResultsMean age at resection was 10.4 years[range:8.8-12.9 years]. Mean implant survival was 59 months[range:34-83 months]. One patient developed a deep infection and two patients required implant lengthening. Both were later converted to a rotating hinged total knee arthroplasty(RHTKA) >58 months after index surgery. At last follow-up, all living patients had knee ROM from 0-110 degrees, walked unassisted, and had no LLD or knee instability. Mean TESS score was 90[range:80-97]. ConclusionProximal tibia hemiarthroplasty reconstruction after tumor resection in skeletally immature patients preserves the distal femoral physis, and may potentially reduce LLD and delay conversion to a RHTKA until after skeletal maturity. Level of EvidenceCase Series, level IV.

Contrast-enhanced US versus US-guided biopsy for abdominal and pelvic neoplasm in paediatric patients: a propensity score matching study.

To compare the diagnostic performance of CEUS-guided biopsy (CEUS-GB) and ultrasound-guided biopsy (US-GB) in evaluating abdominal and pelvic (abdominopelvic) neoplasms in paediatric patients. Patients aged < 18 years with abdominopelvic tumours who underwent either CEUS-GB or US-GB between April 2005 and May 2022 were retrospectively evaluated. Tumours diagnosed as malignancies by pathology were considered true-positive findings. Benign lesions were identified by pathology or clinical follow-up of at least 6 months. The diagnostic performance of the two groups was compared using propensity score matching (PSM). Complications were also analysed. The present study included 764 paediatric patients (437 boys; median age, 24 months; interquartile range, 10-60 months); 151 were in the CEUS-GB group, and 613 were in the US-GB group. The sample adequacy rate was 100% (151 of 151) for the CEUS-GB group, which was greater than the 97.4% (597 of 613) for the US-GB group (p < 0.001). The overall diagnostic accuracy of the CEUS-GB group and US-GB group was 98.7% (149 of 151) versus 97.3% (581 of 597) in the total cohort (p = 0.551) and 98.7% (149 of 151) versus 92.7% (140 of 151) in the PSM cohort (p = 0.020). Two patients (0.3%) in the US-GB group experienced complications (Common Terminology Criteria for Adverse Events (CTCAE), grade 1-2) correlated with the biopsy. No adverse reactions occurred in the CEUS-GB group. CEUS-GB of abdominopelvic tumours in paediatric patients is an effective and safe procedure with greater diagnostic accuracy than US-GB, especially for tumours with necrotic areas. Contrast-enhanced US-guided biopsy of solid abdominal and pelvic tumours in paediatric patients is an effective and safe procedure with greater diagnostic accuracy than US-guided biopsy, especially for tumours with necrotic areas. Contrast-enhanced ultrasound (CEUS) may be superior to conventional ultrasound at guiding biopsy of abdominopelvic masses in paediatric patients. CEUS-guided core needle biopsy of abdominopelvic masses in children was safe and resulted in a diagnostic yield of 98.7%. CEUS guidance should be considered in this population when colour Doppler US is unable to determine a biopsy site.

Single-incision Retroperitoneal Laparoscopic Resection of Adrenal Tumors in Children

BackgroundWe describe our experience with single-incision retroperitoneal laparoscopic (SIRL) for resection of adrenal tumors in pediatric patients and discuss the technique's clinical value. MethodsWe retrospectively analyzed clinical data of 27 pediatric patients who underwent SIRL between January 2020 and September 2023. Patients with tumors >5 cm in size and those requiring vascular skeletonization surgery or extensive lymph node dissection were excluded. Demographic, perioperative, and prognostic data were collected, and computed tomography (CT) and magnetic resonance imaging were used for preoperative tumor assessment. ResultsOf 27 patients, 16 were male and 11 were female; mean age 54 ± 45 months and mean body mass index 17.2 ± 3.6 kg/m2. Mean tumor length, width, and height were 4.1 ± 1.8 cm, 3.3 ± 2.1 cm, and 2.9 ± 1.7 cm, respectively. One patient experienced a diaphragmatic tear, three patients incurred peritoneal damage, and one patient developed postoperative renal artery injury, leading to thrombosis and renal atrophy. No surgery was converted to open surgery, and no intraoperative or postoperative blood transfusions were required. Operative time, blood loss, and postoperative dietary recovery time were satisfactory. No local recurrence or distant metastases were detected during the 6–48 months of follow-up involving outpatient and telephone assessments. ConclusionsApplication of SIRL in pediatric patients with adrenal tumors achieved favorable clinical outcomes with an effective, minimally invasive surgical option for treating children with adrenal tumors. This technique demands a high level of surgical expertise, specialized instruments and experienced surgeons. Our findings indicate that SIRL is safe and provides significant postoperative benefits in pediatric patients. Level of EvidenceLevel IV.

Wilms Tumor with Vena Caval Intravascular Extension: A Surgical Perspective.

Wilms tumor (WT) is the most common kidney tumor in pediatric patients. Intravascular extension of WT above the level of the renal veins is a rare manifestation that complicates surgical management. Patients with intravascular extension are frequently asymptomatic at diagnosis, and tumor thrombus extension is usually diagnosed by imaging. Neoadjuvant chemotherapy is indicated for thrombus extension above the level of the hepatic veins and often leads to thrombus regression, obviating the need for cardiopulmonary bypass in cases of cardiac thrombus at diagnosis. In cases of tumor extension to the retrohepatic cava, neoadjuvant therapy is not strictly indicated, but it may facilitate the regression of tumor thrombi, making resection safer. Hepatic vascular isolation and cardiopulmonary bypass increase the risk of bleeding and other complications when utilized for tumor thrombectomy. Fortunately, WT patients with vena caval with or with intracardiac extension have similar overall and event-free survival when compared to patients with WT without intravascular extension when thrombectomy is successfully performed. Still, patients with metastatic disease at presentation or unfavorable histology suffer relatively poor outcomes. Dedicated pediatric surgical oncology and pediatric cardiothoracic surgery teams, in conjunction with multimodal therapy directed by a multidisciplinary team, are preferred for optimized outcomes in this patient population.

Brain Tumors in Pediatric Patients

Pediatric brain tumors are the most common solid tumors in children, comprising a diverse group of neoplasms that vary in histology, location, and behavior. Common types include astrocytomas, medulloblastomas, ependymomas, and brainstem gliomas. Symptoms often depend on the tumor's location and may include headaches, nausea, vomiting, balance issues, and cognitive or behavioral changes. Advances in imaging, surgical techniques, and therapies, including radiation and chemotherapy, have improved outcomes. However, treatment can have long-term effects on cognitive and physical development, making comprehensive care and follow-up essential for pediatric patients. Early published reviews on pediatric brain tumors may have several lacunae, such as limited data on long-term outcomes, emerging treatment modalities, and the genetic and molecular underpinnings of various tumor types. They might also inadequately address the psychosocial impacts on patients and families. Therefore, a comprehensive review is needed to synthesize the latest research on pediatric brain tumors, encompassing advancements in diagnosis, treatment, and survivorship care. This updated review will provide valuable insights for clinicians, researchers, and policymakers to improve managing and supporting children with brain tumors. The review covers various aspects of pediatric brain tumors, focusing on choroid plexus tumors and spinal cord tumors. It discusses treatment strategies, highlighting surgical, radiotherapy, and chemotherapy options. The review also details presenting signs and symptoms of brain tumors in children, such as headaches, nausea, vomiting, balance issues, and changes in behavior or cognition. These insights aim to enhance early diagnosis and effective management, improving outcomes for affected children. This review addresses gaps in earlier studies on pediatric brain tumors by providing comprehensive insights into choroid plexus and spinal cord tumors, updated treatment strategies, and detailed symptoms. It synthesizes recent research to enhance early diagnosis and management, meeting current needs for effective, tailored treatment and improving patient outcomes.

IMG-07. PEDIATRIC CRANIAL INCIDENTALOMAS: A SYSTEMATIC REVIEW UTILIZING MACHINE LEARNING

Abstract BACKGROUND The use of diagnostic neuroimaging in the care of pediatric patients continues to increase, leading to a rise in incidentally discovered lesions. The understanding of appropriate assessment and management of these findings is critical to providing comprehensive and timely care. This review aims to analyze the current literature to characterize diagnostic and prognostic characteristics of incidentally found brain tumors in pediatric patients. METHODS Using the guidelines under the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), Pubmed and Medline (NCBI) databases were searched using selected keyword combinations and machine learning-assisted software. Case reports, case series, and retrospective cohort studies published up to December 2023 were included. RESULTS A total of 20 studies encompassing 627 patients were included in the review. The most common indications for imaging were headache (204; 33%), seizures (96; 15%), and trauma (78; 12%). Of studies providing information regarding localization, lesions were found in the supratentorial region in 327 (52%) cases and infratentorial region in 190 (30%). Of studies reporting imaging characteristics, T1 hypointensity (183/302; 61%), T2 hyperintensity (410/497; 82%), and no contrast enhancement (58/97; 60%) were the most common findings. Four hundred and thirty (68%) patients were observed after diagnosis, 83 (13%) patients underwent surgical intervention at diagnosis, and 40 (6%) patients underwent surgery after observation. Of 91 patients with histopathology data available, pilocytic astrocytoma (19; 21%) was most commonly reported. CONCLUSION In this study, we provide a review of diagnostic characteristics of incidentally discovered brain tumors in the pediatric population. Management of such lesions has changed greatly over the past several decades, and risks of surgical intervention should be weighed against a more conservative management and interval monitoring approach. These results may help guide discussions regarding disclosure of findings and recommendations for additional clinical management.

Clinical and molecular characteristics and targeted therapy of pediatric non-infantile fibrosarcoma NTRK rearrangement–related tumors.

10048 Background: Neurotrophic tyrosine receptor kinase (NTRK) rearrangement is rare in tumors and relevant to targeted therapy. Pediatric NTRK rearrangement-related tumors have distinct clinical and molecular features compared to adults, and previous studies on pediatric NTRK rearrangement-related tumors has focused on infantile fibrosarcoma (IFS), the most common subtype. However, the clinical behaviors and molecular profiles of other subtypes of pediatric NTRK rearrangement-related tumors are largely unknown. Methods: In this study, we evaluated the molecular features, treatment response, and prognosis of 28 pediatric patients with non-IFS NTRK rearrangement-related tumors. Next-generation sequencing was performed in 21 patients to identify the NTRK fusion types and their co-occurring alterations, and pathway enrichment analysis was performed to explore the potential mechanisms involving NTRK rearrangement and resistance to tyrosine receptor kinase (TRK) inhibitors. Results: The NTRK fusion partners were diverse and tumor-specific. Several novel NTRK fusions were identified, including SNIP1-NTRK1, AGAP1-NTRK2, CRCT1-NTRK1, ZBTB7B-NTRK1, and SLC6A15-NTRK3. RTK-RAS, NOTCH, TP53, and WNT pathways were top 4 significantly enriched in tested samples. Twelve of 17 patients (70.6%) received TRK inhibitors as salvage treatment achieved complete or partial response. Patients who did not develop DDR, NOTCH, or TP53 pathway-related gene mutations had a high objective response rate of 82%, 82%, and 83%, respectively. Conclusions: Our findings may have important implications for the diagnosis and treatment of non-IFS NTRK fusion-positive tumors in pediatric patients. We also provide potential therapeutic targets for tumors resistant to TRK inhibitors. Clinical trials with TRK inhibitors, either alone or in combination, are required to establish the optimal treatment regimen and sequence in large-cohort pediatric patients with non-IFS NTRK rearrangement-related tumors. Clinical trial information: NCT05076071 .

Patterns of improvement following initial response in patients treated with naxitamab for relapsed/refractory high-risk neuroblastoma.

10033 Background: Treatment of high-risk neuroblastoma (HRNB), the most common extracranial solid tumor in pediatric patients, is associated with suboptimal efficacy outcomes. While monitoring responses to naxitamab and other anti-GD2 monoclonal antibodies is essential, there is limited evidence on the timing and magnitude of improved responses following first assessment. Here, we report the patterns of improvement following the initial response to naxitamab therapy, based on the results of a prespecified interim analysis of Trial 201. Methods: Trial 201 (phase 2, NCT03363373) is investigating naxitamab plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with refractory/relapsed HRNB with residual disease in bone and/or bone marrow (BM) only. “Refractory” and “relapsed” disease comprised those with an incomplete response (partial response [PR], minor response [MR], or stable disease [SD]) per International Neuroblastoma Response Criteria (INRC) to induction therapy or to treatment for actively progressing or relapsed disease, respectively. Patients with soft tissue or actively progressing disease were excluded. Naxitamab was infused at 3 mg/kg/dose IV on Days 1/3/5 with GM-CSF administered SC on Days -4 to 5 (monthly cycles [C]). The primary endpoint was overall response rate (ORR), comprising those with a complete response (CR) or PR per INRC. Response assessments occurred between C2 and C3 and at prespecified timepoints thereafter. Results: The ORR in Trial 201 was 50% (26/52). At first assessment, the ORR was 37% (n=19), with 14 patients achieving CR. An additional 6/26 patients (23%) achieved a CR or PR after C3, of whom 4 went from MR to CR, and 2 from SD to PR. (One patient whose disease was not evaluable at first assessment and who later had a PR was included in the ORR but excluded from this response improvement analysis.) In addition to the 6 patients who achieved a CR or PR after C3, 2 patients with PR at initial assessment later achieved a CR, and 1 patient with initial SD achieved MR, totaling 9 patients with improved post-C3 responses, or 17% of the overall efficacy population. Among those with baseline disease in bone, post-C3 responses in the bone compartment improved in 6/50 patients (12%). Of these 6 patients, 5 had initial SD in bone and achieved a post-C3 CR or PR. Post-C3 responses in the BM compartment improved in 6/23 patients (26%) with baseline BM disease, of whom 5 had initial SD in BM and achieved a post-C3 CR. Naxitamab safety (N=74) has been reported previously. Conclusions: A considerable proportion (23%) of patients achieved a CR or PR only after C3. Among these patients, most had initial SD within specific bone or BM compartments before achieving a post-C3 CR/PR. Taken together, the results support the rationale for continued treatment of patients not achieving CR/PR at first assessment. Clinical trial information: NCT03363373 .

INFLAMMATORY MYOFIBROBLASTIC TUMOR OF THE MEDIASTINUM IN A PEDIATRIC PATIENT: A RARE CASE PRESENTATION AND MANAGEMENT REVIEW

Mediastinal tumors in pediatric patients encompass a broad spectrum of pathologies, ranging from benign to malignant entities. We present a case of a 10-year-old boy who initially presented with persistent back pain followed by nocturnal coughing, asthenia, and significant weight loss over a year. Upon admission, physical examination was unremarkable except for a mediastinal opacity noted on radiographic evaluation, leading to further characterization by thoracic CT scan, revealing a sizable right paracardiac mediastinal mass. Surgical excision was performed successfully, with en bloc resection of the mass adherent to the middle and lower lung lobes, and involving regional lymph nodes. Postoperative recovery was uneventful over a two-month follow-up period.Histopathological analysis confirmed the diagnosis of an inflammatory myofibroblastic tumor (IMT), a rare entity within the mediastinum Our case underscores the challenges in diagnosing and managing mediastinal IMTs, emphasizing the importance of a multidisciplinary approach involving clinical suspicion, diagnostic imaging, and definitive histopathological evaluation.Continued reporting and study of such cases contribute to our understanding of this rare pathological entity, guiding optimal management strategies and long-term surveillance protocols for affected pediatric patients. This case report highlights the need for heightened awareness and research efforts to improve diagnostic accuracy and therapeutic outcomes for mediastinal IMTs in pediatric populations.

Chemical Peritonitis Due to Ruptured Ovarian Teratoma: A Case Report and Literature Review

Introduction: Mature cystic teratomas (MCT) are the most common ovarian tumors in pediatric patients, often asymptomatic due to slow growth, when symptomatic, they can lead to abdominal pain. Spontaneous rupture can result in acute chemical peritonitis (CP), a rare but life-threatening complication. This study presents a clinical case of a patient with spontaneous rupture of an ovarian teratoma and associated acute CP. Clinical Case: 13-year-old female presented with acute abdominal pain, fever, distended and painful abdomen with peritoneal reaction in the right iliac fossa and hypogastrium. Abdominal ultrasound showed a hypoechoic rounded image with an anechoic center in the right adnexal region. Laparoscopic exploration revealed a cystic teratoma of the right ovary with torsion, but no compromise of vitality. Purulent fluid indicated CP due to ruptured and twisted ovarian teratoma. Right ovarian cystectomy was performed, drainage was offered in the Douglas pouch. The patient's condition improved, and she was discharged after recovery. Discussion: Rupture and CP are rare but require emergency surgery. Preoperative diagnosis can be challenging due to their non-specific clinical presentation and the need to rule out malignant complications. Conclusion: Early and appropriate management of MCT is essential to prevent serious complications. Sebum spillage can cause CP, the treatment of choice is teratoma removal, combined with extensive lavage to avoid chronic peritonitis. Laparoscopic surgery stands out as a safe and effective option. A high index of suspicion and comprehensive approach are emphasized in managing this uncommon condition in the pediatric population.

The role of machine learning in detecting primary brain tumors in Saudi pediatric patients through MRI images

Background and aimBrain tumors are defined as the uncontrollable growth of cells. They are known as the leading cause of death among pediatric patients. Artificial Intelligence is considered as one of the techniques used to improve radiology departments. Magnetic Resonance Imaging (MRI) is a key tool in detecting brain tumors. Medical images can be challenging and time-consuming for radiologists, particularly in the case of pediatric patients where the tumors may be small and difficult to detect. This study aims to explore the role of AI and measure the accuracy of AI methods in detecting primary brain tumors in pediatric patients by using MRI images. MethodologyA retrospective and analytical study was conducted, MRI images of pediatric patients with primary brain tumors were acquired from the Picture Archives and Communication System (PACS) of the radiology department at King Abdullah Specialist Children Hospital (KASCH). This study continues a total of (6435) MR images, this dataset was divided and expressed in different subsets, 70% of the images were trained (4493 in total) for model accuracy evaluation, and the rest which is 30% (1942) were tested images contains three types of primary brain tumors, glioma, Primitive Neuro-Ectodermal Tumors and pituitary tumors. Moreover, this dataset also contains normal images. Image classification and detection have been done by using Machine Learning algorithms which are coded in Python programming language. ResultsAfter applying Machine Learning algorithms on MRI images, Artificial Neural Network method resulted in an accurate detection of pediatric primary brain tumors and matched the radiologist's report. ConclusionNew Artificial Intelligence techniques applied in the imaging department have increased the information obtained from images to improve the accuracy of diagnosis along with radiologist's reports which will aid in better management of the patient's condition.

Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series

Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. Six paediatric patients (median age:16 years, range: 12-17at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).

Evolution of Surgical Management of Pineal Region Tumors in the Pediatric Population: A 17-Year Experience at a Single Institution

Introduction: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients, and this is well demonstrated by our single institution’s experience over a 17-year-period in which the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients will be outlined. Methods: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children’s National Hospital (CNH) from 2005 to 2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others. IRB approval was obtained (IRB: STUDY00000009), and consent was waived due to minimal risk to patients included. Results: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). Twenty seven of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior interhemispheric (PIH, transcallosal) – used for 59.3% of the patients. Gross total resection was achieved in 50%; recurrence occurred in 20.9% and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011 to 2021. Most (73%) of the patients who received an ETV also underwent a concurrent endoscopic biopsy. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies. Conclusion: This series describes the evolution of surgical approaches and outcomes over a 17-year-period at a single institution. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. Though there has been a significant evolution in our understanding of and treatment for these tumors, in our series, the outcomes for these patients have not significantly changed over that time.

PUMC-MB1 is a novel group 3 medulloblastoma preclinical model, sensitive to PI3K/mTOR dual inhibitor.

Medulloblastoma (MB), a common and heterogeneous posterior fossa tumor in pediatric patients, presents diverse prognostic outcomes. To advance our understanding of MB's intricate biology, the development of novel patient tumor-derived culture MB models with necessary data is still an essential requirement. We continuously passaged PUMC-MB1 in vitro in order to establish a continuous cell line. We examined the in vitro growth using Cell Counting Kit-8 (CCK-8) and in vivo growth with subcutaneous and intracranial xenograft models. The xenografts were investigated histopathologically with Hematoxylin and Eosin (HE) staining and immunohistochemistry (IHC). Concurrently, we explored its molecular features using Whole Genome Sequencing (WGS), targeted sequencing, and RNA sequecing.Guided by bioinformatics analysis, we validated PUMC-MB1's drug sensitivity in vitro and in vivo. PUMC-MB1, derived from a high-risk MB patient, displayed a population doubling time (PDT) of 48.18h and achieved 100% tumor growth in SCID mice within 20 days. HE and Immunohistochemical examination of the original tumor and xenografts confirmed the classification of PUMC-MB1 as a classic MB. Genomic analysis via WGS revealed concurrent MYC and OTX2 amplifications. The RNA-seq data classified it within the Group 3MB subgroup, while according to the WHO classification, it fell under the Non-WNT/Non-SHH MB. Comparative analysis with D283 and D341med identified 4065 differentially expressed genes, with notable enrichment in the PI3K-AKT pathway. Cisplatin, 4-hydroperoxy cyclophosphamide/cyclophosphamide, vincristine, and dactolisib (a selective PI3K/mTOR dual inhibitor) significantly inhibited PUMC-MB1 proliferation in vitro and in vivo. PUMC-MB1, a novel Group 3 (Non-WNT/Non-SHH) MB cell line, is comprehensively characterized for its growth, pathology, and molecular characteristics. Notably, dactolisib demonstrated potent anti-proliferative effects with minimal toxicity, promising a potential therapeutic avenue. PUMC-MB1 could serve as a valuable tool for unraveling MB mechanisms and innovative treatment strategies.

Downregulation of ABLIM3 confers to the metastasis of neuroblastoma via regulating the cell adhesion molecules pathway

Neuroblastoma (NB) is the most prevalent extracranial solid tumor in pediatric patients, and its treatment failure often associated with metastasis. In this study, LASSO, SVM-RFE, and random forest tree algorithms, was used to identify the pivotal gene involved in NB metastasis. NB cell lines (SK-N-AS and SK-N-BE2), in conjunction with NB tissue were used for further study. ABLIM3 was identified as the hub gene and can be an independent prognostic factor for patients with NB. The immunohistochemical analysis revealed that ABLIM3 is negatively correlated with the metastasis of NB. Patients with low expression of ABLIM3 had a poor prognosis. High ABLIM3 expression correlated with APC co-stimulation and Type1 IFN response, and TIDE analysis indicated that patients with low ABLIM3 expression exhibited enhanced responses to immunotherapy. Downregulation of ABLIM3 by shRNA transfection increased the migration and invasion ability of NB cells. Gene Set Enrichment Analysis (GSEA) revealed that genes associated with ABLIM3 were primarily enriched in the cell adhesion molecules (CAMs) pathway. RT-qPCR and western blot analyses demonstrated that downregulation of ABLIM3 led to decreased expression of ITGA3, ITGA8, and KRT19, the key components of CAMs. This study indicated that ABLIM3 can be an independent prognostic factor for NB patients, and CAMs may mediate the effect of ABLIM3 on the metastasis of NB, suggesting that ABLIM3 is a potential therapeutic target for NB metastasis, which provides a novel strategy for future research and treatment strategies for NB patients.

The Oral-Dental Findıngs of Patients Treated with Antineoplastic Treatments Targeting Non-Head and Neck Tumors in Childhood

Aim This study investigates oral complications in pediatric oncology patients undergoing antineoplastic treatments for non-head and neck tumors, with a focus on their impact on tooth development. Material and method Twenty pediatric patients (aged 3 to 14) undergoing chemotherapy for non-head and neck tumors were examined clinically. Oral and perioral tissues were assessed, and specific complications were documented. Patient records were retrospectively reviewed to identify pre-existing oral issues. Results The study revealed significant oral complications associated with antineoplastic treatments, including enamel defects (60%), gingivitis (60%), delayed apexification (55%), and mucositis (30%). Additional complications such as lymphadenopathy, delayed eruption, and herpes simplex infection were also observed. Conclusion Antineoplastic treatments for non-head and neck tumors in pediatric patients can significantly affect tooth development, leading to various oral complications. Early detection and management of these complications are vital for treatment continuity and enhancing the quality of life for pediatric oncology patients.