Rare Pediatric Tumor Research Articles

Salivary gland carcinomas in children and adolescents: A retrospective analysis of the European Cooperative Study Group for Pediatric Rare Tumours (EXPeRT)

BackgroundSalivary gland carcinomas (SGCs) are exceedingly rare in children, with a reported annual incidence of 0.8–1.4/1000,000 under 20 years of age. Evidence regarding optimal treatment of pediatric SGCs is limited, and for a long time, no guidelines have been available. Here, we report on an international retrospective series of SGCs in children and adolescents collected by several national rare tumor study groups cooperating in the European Cooperative Study Group of Pediatric Rare Tumors (EXPeRT) Patients and methodsPatients diagnosed between 2000 and 2014 were included. Data were reviewed by the respective national rare tumor working groups and reported on a harmonized data sheet to EXPeRT for central analysis. ResultsOverall, 121 patients were identified, including 103 patients with parotid tumors, 12 with submandibular tumors and six tumors in minor glands. In 11 patients, SGCs were secondary cancers. Mucoepidermoid carcinoma was the most frequent diagnosis (n = 65), followed by acinic cell carcinoma (n = 39), adenocystic carcinoma (n = 7), sialoblastoma (n = 3) and other carcinomas (n = 7). All patients underwent tumor resection (R0: 66%, R1: 34%). Neck dissection was performed in 47 patients, revealing nodal metastases in 13. Twenty-four patients underwent irradiation, and 11 patients received adjuvant chemotherapy. During a median follow-up of 25 (6–140 months), 14 relapses were observed (7 local, 5 with nodal and 2 with distant metastases). Five patients died of disease. Higher histological tumor grade was associated with advanced local tumor stage and risk of recurrence. ConclusionsSGCs in children and adolescents mostly present as localized tumors with low malignant potential. In approximately 10% of patients, regional lymph node metastases present at diagnosis. After complete resection, prognosis is favorable. Surgery is the mainstay of treatment; adjuvant local or cervical irradiation should be reserved to those rare patients with nodal metastases or less favorable biology such as adenocystic carcinoma.

Infantile type I pleuropulmonary blastoma presenting with dyspnea due to compression by pneumothorax and an occupying tumor: a case report

BackgroundPleuropulmonary blastoma (PPB) is an extremely rare and malignant pediatric lung tumor. Purely cystic PPB has a more favorable prognosis than solid PPB, but may be difficult to distinguish from a certain type of “benign” congenital pulmonary airway malformation before and during surgery. The influence of tumor rupture on long life prognosis has not been clarified in detail.Case presentationA 5-month-old boy underwent emergency transfer from another hospital due to a left thoracic cystic lesion and left pneumothorax detected on chest radiography performed for persistent wheeze and cough. Contrast-enhanced computed tomography of the chest revealed marked deviation of the mediastinum to the right due to a giant cystic lesion and pneumothorax. Thoracotomy was performed on hospital day 2. A cystic lesion had developed from the distal alveolar region of lower lobe of the left lung and the tumor showed a tiny adhesion to the left diaphragm and a tiny rupture near the adhesion. Partial lung excision including the cyst and scraping of the adhesion were performed. Histopathological investigations revealed immature blast cell-like mesenchymal cells and differentiated striated muscle cells in a dense cambium layer were found under the epithelium of the cystic lesion. Type I PPB was diagnosed.ConclusionsSurgery should be performed with the possibility of type I PPB in mind when an extrapulmonary cystic lung lesion is found. Since issues such as the pathogenesis and long-term prognosis of ruptured cases remain unclear, continued careful follow-up of this case will be required.

Diagnostic MRI characteristics of pediatric clear cell sarcoma of the kidney and rhabdoid tumor of the kidney: A retrospective multi-center SIOP-RTSG Radiology panel study

IntroductionClear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RTK) are rare malignant pediatric renal tumors, both accounting for 1–5% of diagnoses. Within the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) protocols diagnostic invasive procedures to determine histology are discouraged. MRI has become the preferred imaging modality, however, non-invasive discrimination of CCSK and RTK remains challenging. Therefore, this study aims to identify diagnostic MRI-characteristics of CCSK and RTK, in the largest series of patients to date. Material and methodsFive SIOP-RTSG national review radiologists identified national diagnostic MRIs of histologically proven CCSKs and RTKs. Scan-protocols were based on MRI-guidelines following SIOP-RTSG protocols. Radiologists assessed their national cases using a validated case report form (CRF). ResultsRetrospectively, 59 patients were identified (n = 38 CCSK, n = 21 RTK). CCSKs showed a high median volume (576 cm3, range 54–4414), which was lower for RTKs (290 cm3, range 20–761) (p = 0.006 *10-3). Fifty-two percent (11/21) of RTK-patients showed disease at other locations, predominantly the lungs and brain, compared to 8% of CCSK-patients (3/38). RTKs showed ill-defined margins (12/21, 57%) and infiltrative growth pattern (13/21, 62%). CCSKs appeared hyper-intense on T2-weighted imaging (27/38, 71%) with a characteristics band-like enhancement (13/38, 34%), whereas RTK cases often showed T2-weighted hypo-intensity (11/21, 52%). The overall mean ADC-value for CCSK was 1.11 * 10-3 mm2/s (range 0.57–2.07 *10-3 mm2/s), and 0.72 * 10-3 mm2/s (range 0.53–0.90 *10-3 mm2/s) for RTK. ConclusionsThis retrospective study suggests a small size, T2-weighted hypo-intensity and an aggressive growth pattern may be characteristic for RTK. CCSK often showed a typical band-like enhancement pattern with relatively high ADC-values. Identified MRI-characteristics may be used in future studies focusing on validation and discrimination from especially WT, aiming for an early non-invasive diagnosis.

Pediatric retroperitoneal non-organ-originated malignancies: An analysis based on SEER database.

Retroperitoneal non-organ-originated malignancies are rare pediatric tumors with challenging diagnosis and treatment. The present study aimed to analyze the clinicopathological characteristics, treatment, and prognosis of retroperitoneal non-organ-originated malignancies. In the study, we included the pathological diagnosis of pediatric retroperitoneal non-organ-originated malignant tumors between 2000 to 2019 through the updated Surveillance, Epidemiology, and End Results database. We use the Kaplan-Meier survival curve to calculate the overall survival (OS) and cancer-specific survival (CSS). The risk of all-cause death and disease-specific death were analyzed using Cox proportional hazard regression model and Fine-and-Grey competitive hazard model, respectively. In the study, a total of 443 pediatric retroperitoneal non-organ-originated malignancies were included. Of them, only 22.3% of patients had no metastatic disease, 42.9% had distant metastasis and 34.8% had locally advanced diseases. The primary pathological tumor was neuroblastoma followed by germ cell tumor. The overall 10-year OS and CSS were 70.7% and 73.1%, respectively, and the 10-year OS and CSS of metastatic diseases were 54.4% and 56.6%, respectively. Older children, worse tumor stage at diagnosis, incomplete resection, and prolonged time from diagnosis to treatment were significantly associated with worse survival outcomes. Radiotherapy and chemotherapy did not significantly improve the prognosis of patients without complete tumor resection. The study indicated that most pediatric retroperitoneal non-organ-originated malignancies diagnosed with metastatic diseases have plagued treatment. Radiotherapy and chemotherapy are the main treatment methods for children unable to undergo complete surgical treatment. However, these treatments do not reach the same therapeutic effect as complete tumor resection after early diagnosis. Hence, early diagnosis and surgery for complete tumor resection are of utmost importance.

High-Dose-Rate Brachytherapy for Vaginal Rhabdomyosarcoma (RMS): Lessons Learned at a Single Institution

Botryoid RMS is a rare pediatric tumor most commonly arising within the vaginal wall of girls under age three. Most patients are successfully treated with low-risk chemotherapy protocols but local treatment is required to minimize risk of local relapse. Intravaginal brachytherapy is an effective local therapy that can minimize sequelae in these very young patients. We reviewed records of all patients with RMS who received intravaginal high-dose-rate brachytherapy from 2010-2022 at a single institution. All were treated with multiagent chemotherapy with or without minor surgical procedures, and had no gross disease prior to intravaginal brachytherapy. All patients underwent CT simulation under anesthesia and optimal-sized cylindrical applicators were chosen based on patient anatomy. Twelve girls, median age 23 months (range 3-33), were treated with daily anesthesia. All were Stage 1 and 92% had Group III disease. A single patient had Group IIA disease based on up-front resection. Early in the series, 5 patients received 21 Gy in 7 fractions according to COG protocol guidelines. Subsequent patients received higher doses of 28-30 Gy in 7-10 fractions. Custom sized cylinders were used with diameters ranging from 1.2-1.6 cm and dose was prescribed to a median depth of 3 mm. Median mean dose to the rectum, bladder, uterus, and bilateral ovaries was 8.7 Gy, 7.2 Gy, 6.9 Gy, and 5.0 Gy, respectively. Median follow-up was 4 years (range 1-10). No acute or late side effects have occurred. At follow-up, three girls were of pubescent age, all three exhibited signs of puberty and two had reached menarche. Three girls (25%) suffered local relapse at a median of 15 months (range 5-16 months) after brachytherapy. One-year and five-year local control rates were 92% (95% CI 54-99%) and 70% (95% CI 32-89%), respectively. All relapses were in patients receiving 21 Gy and two were beyond full dose coverage of brachytherapy at the introitus and in the uterus. Subsequent patients receiving higher doses and full coverage of the vagina have had no local failures. Two of three patients who failed were cured with salvage therapy resulting in one-year and five-year overall survival rates of 100% and 86% (95% CI 33-98%), respectively. Intravaginal high-dose-rate brachytherapy is an excellent option for local control of vaginal RMS with fewer long-term risks than external beam proton therapy or radical surgery. A dose of 28 Gy in 7 fractions prescribed to the entire vagina is necessary for optimal prevention of relapse. Longer follow-up is needed to confirm preservation of ovarian, reproductive, and sexual function.

Solid pseudopapillary neoplasms of the pancreas in childhood and adolescence—an analysis of the German Registry for Rare Pediatric Tumors (STEP)

Solid pseudopapillary neoplasms (SPNs) are the most common entity among pediatric pancreatic tumors. Still, these are rare tumors with an annual incidence of 0.1–0.2/1,000,000, and little is known about their optimal treatment. This analysis aimed to increase knowledge about the occurrence and treatment strategies of SPN in childhood. Data regarding diagnostics, treatment, and outcome of children aged 0–18 years with SPN recorded in the German Registry for Rare Pediatric Tumors (STEP) were analyzed. Thirty-eight patients were identified with a median age of 14.5 years at diagnosis (range: 8–18) and a female preponderance (81.6%). The most frequent location of the tumor was the pancreatic tail. In histopathological and immunohistochemical examination, pseudopapillary, solid, and cystic lesions as well as expression of beta-catenin, progesterone receptors, and cyclin D1 were the most common findings. All patients underwent surgical resection. Most patients underwent open resection, predominantly tail resection for tumors in the tail region and pylorus-preserving pancreaticoduodenectomy for tumors in the head region. The main postoperative sequela was exogenous pancreatic insufficiency (23.7%), especially with SPN in the pancreatic head. No recurrence occurred during follow-up, although two patients underwent resection with microscopic residue.Conclusion: SPN of the pancreas in childhood are low-grade malignancies with usually favorable treatment outcomes. However, therapy can lead to relevant long-term sequelae. To prevent recurrence, complete surgical resection is recommended, sparing as much healthy pancreatic tissue as possible. Interdisciplinary collaboration between specialists is essential to optimize treatment. Molecular genetic analysis of these tumors could improve understanding of their genesis.What is Known:• Solid pseudopapillary neoplasms (SPNs) of the pancreas are very rare tumors in childhood.• Little is known about tumorigenesis, and there are no specific guidelines for treatment and follow-up in pediatric patients.What is New:• Characteristics, treatment, and outcome were comprehensively assessed in a large cohort of pediatric patients with SPN.• We propose recommendations for diagnosis, treatment, and follow-up of children with SPN, based on our analysis and considering published experience.

Deciphering pathological behavior of pediatric medullary thyroid cancer from single-cell perspective.

Pediatric medullary thyroid cancer (MTC) is one of the rare pediatric endocrine neoplasms. Derived from C cells of thyroid glands, MTC is more aggressive and more prompt to metastasis than other types of pediatric thyroid cancer. The mechanism remains unclear. We performed single-cell transcriptome sequencing on the samples of the primary tumor and metastases lymph nodes from one patient diagnosed with MTC, and it is the first single-cell transcriptome sequencing data of pediatric MTC. In addition, whole exome sequencing was performed and peripheral blood was regarded as a normal reference. All cells that passed quality control were merged and analyzed in R to discover the association between tumor cells and their microenvironment as well as tumor pathogenesis. We first described the landscape of the single-cell atlas of MTC and studied the interaction between the tumor cell and its microenvironment. C cells, identified as tumor cells, and T cells, as the dominant participant in the tumor microenvironment, were particularly discussed in their development and interactions. In addition, the WES signature of tumor cells and their microenvironment were also described. Actively immune interactions were found, indicating B cells, T cells and myeloid cells were all actively participating in immune reaction in MTC. T cells, as the major components of the tumor microenvironment, proliferated in MTC and could be divided into clusters that expressed proliferation, immune effectiveness, and naive markers separately.

Melanotic Neuroectodermal Tumor of Infancy: A Case Series and Comprehensive Review of this Rare Pediatric Neoplasm

Melanotic Neuroectodermal Tumor of Infancy: A Case Series and Comprehensive Review of this Rare Pediatric Neoplasm

Extremely rare pediatric primary scrotum tumor: spermatic cord hemolymphangioma for a case report and literature review

Hemolymphangioma is an uncommon benign tumor type that commonly occurs in the head and neck. Primary spermatic cord hemolymphangioma (SCH) with only several reported, however, is extremely rare. Clinical diagnosis can be challenging because of its rarity. Although spermatic cord hemolymphangiomas are benign tumors, there is still a high recurrence rate in postoperative. A 15-year-old boy presented to our hospital with complaints of scrotal for 15 days and did not have other associated symptoms. The male genital color Doppler ultrasound revealed that a cystic echo in the left spermatic cord region and above the testes was about 32 mm × 20 mm × 14 mm. He underwent left en bloc scrotum tumor resection under general anesthesia, and pathologic examination showed SCH. He was discharged from the hospital in the second postoperative day. After 1-month follow-up, the patient recovered well without recurrence. The patient is currently in follow-up phase. Up to date, only a few cases have been reported in the literature about SCH. So, we hope to raise the awareness of the diagnosis of SCH in clinical practice although this case.

Infantile fibrosarcoma of the perineum with dorsal metastasis in a neonate: a case report original

BackgroundInfantile fibrosarcoma is a rare pediatric soft tissue tumor and usually appears in children before one year of age. Distal extremities constitute the most frequently affected locations, and other tissues such as the trunk, head and neck, gut, sacrococcygeal region, and viscera are uncommon sites.Case presentationWe describe a rare case of infantile fibrosarcoma arising from the perineum. First, a cystic mass was detected using prenatal ultrasonography, and then an echo was changed in serial ultrasound examinations. A solid cystic lesion was found at term; a hypoechoic lesion occurred in the back. The tumor became so large that massive bleeding occurred, which then underwent surgical resection. Pathological examination confirmed infantile fibrosarcoma.ConclusionOur report demonstrates not all ultrasonographic findings in cases of infantile fibrosarcoma exhibit a solid mass during the initial examination — an early-stage lesion may reveal a cystic echo. Infantile fibrosarcoma has a good prognosis and surgery constitute the main treatment, with adjuvant chemotherapy being received if necessary.

Alveolar Rhabdomyosarcoma of the Nasal Dorsum of a Pediatric Patient: A Case Report.

Alveolar rhabdomyosarcoma is a rare pediatric malignant tumor with a poor prognosis, and it is exceedingly rare for this tumor to manifest on the skin of the nasal dorsum. Therefore, timely and accurate treatment can improve the survival rate of patients. We reported a case of a 4 year-old child with acinar rhabdomyosarcoma of the nasal dorsum, and the patient was cured by surgery and postoperative chemotherapy without recurrence. This case report contributes to the understanding of this rare tumor.

Rare pediatric brain tumors

There are a large variety of rare pediatric brain tumors, but we limit ourselves to three which pediatric oncologists are likely to encounter at some point in their career. CNS rhabdoid and choroid plexus tumors are aggressive with generally poor survival, and their management is discussed, along with advances in the field of molecular pathology, and multi-institutional trials which have allowed some improvement in outcome. Craniopharyngioma is a more indolent tumor, and the diagnosis and management is discussed along with the impact that imaging and neurosurgical technique is having on improving outcomes. Late-effects remain troublesome in patients with any of the three diagnoses.

RARE-05. MOLECULAR HETEROGENEITY OF PEDIATRIC CHOROID PLEXUS CARCINOMAS

Abstract BACKGROUND: Choroid plexus carcinomas (CPCs) are rare aggressive pediatric tumors of the brain with no treatment standards. Genetic profiling of CPCs is often confined to possible association with Li–Fraumenisyndrome, though only about a half of CPCs develop fromsyndromic predispositions. Whole-chromosome gains and losses typical of CPCs reflect genomic instability of these tumors, but only partially explain the aggressive clinical course. METHODS: This retrospective study enrolled 25 pediatric patients with CPC, receiving treatment between January 2009 and June 2022. Molecular genetic testing was performed for 20 cases with available tumor tissue and encompassed mutational status, chromosomal aberrations and gene expression profiles. We analyzed several factors presumably influencing the outcomes, including molecular profiles and clinical parameters. The median follow-up constituted5.2 years (absolute range 2.8–12.6 years). RESULTS: All studied CPCs had smooth mutational profiles with the only recurrent event being TP53 variants, either germline or somatic, encountered in 13 cases. Unbalanced whole-chromosome aberrations, notably multiple monosomies, were highly typical. Inseven tumors, chromosome losses were combined with complex genomic rearrangements: segmental gains and losses or signs of chromothripsis. This phenomenon was associated with extremely low 5-year survival: 20.0±17.9% vs. 85.7±13.2%; p=0.009. Transcriptomically, the cohort split into two polar clusters Ped_CPC1 and Ped_CPC2 differing by survival: 31.3±17.8% vs. 100%; p=0.012. CONCLUSION: CPCs split into at least two molecular subtypes distinguished both genomically and transcriptomically. Clusterization of the tumors into Ped_CPC1 and Ped_CPC2 significantly correlates withsurvival. The distinction may prove relevant in clinical trials for dedicated and patient-oriented optimization of clinical protocols for these rare tumors.

ATRT-06. ETMR TUMORIGENESIS MIRRORS RADIAL GLIAL DEVELOPMENT

Abstract Embryonal tumors with multilayered rosettes (ETMRs) are rare pediatric brain tumors defined primarily by overexpression of the C19MC microRNA cluster. These tumors affect mostly children under the age of 3. However, little is known about the origin and developmental contexts of ETMRs. We hypothesized that the early onset of these tumors suggests an embryonic tumorigenic event. To elucidate the embryonic contexts of which ETMRs arise, we curated three mouse embryogenesis datasets representing the full spectrum of murine embryonic development. We generated timepoint structure signatures of this atlas and projected them onto a single nuclei RNA sequencing dataset of 8 primary ETMRs. Consistent with existing literature, we discovered that ETMRs resemble a spectrum of radial glial, neuronal, and oligodendrocytic cell types. We also recapitulated potential ETMR driver mechanisms such as overexpression of WNT and SHH signaling by gene set enrichment analysis. We validated the enrichment of lineage and driver markers through GSEA and marker gene enrichment in a separate cohort of ETMRs characterized by bulk RNA sequencing. Taken together, the embryonic context of ETMR development may play crucial roles in the early identification and treatments of this lethal disease.

TRLS-04. PRECLINICAL VALIDATION OF A NOVEL THERAPEUTIC STRATEGY FOR CHOROID PLEXUS CARCINOMA

Abstract Choroid plexus carcinoma is a very rare pediatric tumor located in the fourth and lateral ventricles of the brain. It is known to have a severe clinical history and significant side effects because of intensive and noxious chemotherapies. Due to the disease’s rarity and the scarcity of biologically relevant substrates, the advance of new therapeutical techniques for this condition has been exceedingly constrained. A human patient-derived CPC cell line (CCHE-45, Children Cancer Hospital Egypt) was subjected to a high-throughput screen (HTS); 427 top hits were identified, highlighting critical molecular targets in CPC. Additionally, a combination screen with numerous different targets identified synergistic combinations that lead the way for brand-new CPC therapies. Based on in vitro efficiency, CNS penetrance ability and feasible translational potential, two combinations using a DNA alkylating or topoisomerase inhibitors in combination with an ataxia telangiectasia mutated and rad3 (ATR) inhibitor (topotecan/elimusertib and melphalan/elimusertib respectively) were validated in vitro and in vivo. Pharmacokinetic studies revealed greater CNS penetrance via intra-arterial (IA) delivery compared to intravenous (IV) delivery, as well as increased CNS penetrance for melphalan/elimusertib combination. Transcriptome analysis was used to evaluate the mechanisms of melphalan/elimusertib synergistic effect; deregulation of several carcinogenic pathways (e.g. MYC, mTOR, p53) as well as the activation of vital biological processes were revealed (e.g. DNA repair, apoptosis, hypoxia, interferon gamma). In a CPC genetic mouse model, IA administration of melphalan and elimusertib significantly increased survival. To the best of our knowledge, this work is the first using human CPC cells to identify several prospective combinatorial treatments and it highlights the effectiveness of IA delivery for the treatment of CPC.

DIPG-55. DIRECT BRAIN-TO-BRAIN WORKFLOW ENABLES THE PRECLINICAL MODELING OF PEDIATRIC GLIOMAS

Abstract Pediatric high-grade gliomas (pHGG) are one of the leading causes of brain cancer deaths in children. Progress towards the characterization of molecular and genetic features in adult high-grade gliomas and subsequent therapies has not yielded similar results in pHGG patients. pHGGs do not readily establish in culture and there has also been a lack of preclinical models to identify new therapeutic targets. Here, we employ a direct brain-to-brain workflow enabling the establishment of rare pediatric tumors including Atypical Teratoid/Rhabdoid Tumor (ATRT), H3_K27ALT diffuse midline gliomas, and H3_G34MUT diffuse hemispheric xenograft models. These Direct, Patient-Derived Orthotopic Xenografts (DPDOX) models recapitulate the clinical, genomic, and transcriptomic landscape of that of the parental tumors. Moreover, we have incorporated each tumor with a secreted gaussia luciferase reporter enabling the minimally-invasive tracking of intracranial tumor burden over time in response to drug perturbations. Taken together, we present a novel approach to establish pHGG models and evaluate new therapeutics.

The International Society for Biological and Environmental Repositories Presents Abstracts from Its Annual Meeting

The International Society for Biological and Environmental Repositories Presents Abstracts from Its Annual Meeting

Fetal Lung Interstitial Tumor (FLIT): Review of The Literature.

Fetal lung interstitial tumor (FLIT) is an extremely rare pediatric lung tumor that shares radiological features with congenital pulmonary malformations (cPAM) and other lung neoplasms. A review of the literature, together with the first European case, are herein reported. A systematic and manual search of the literature using the keyword "fetal lung interstitial tumor" was conducted on PUBMED, Scopus, and SCIE (Web of Science). Following the PRISMA guidelines, 12 articles were retrieved which describe a total of 21 cases of FLIT, and a new European case is presented. A prenatal diagnosis was reported in only 3 out of 22 (13%) cases. The mean age at surgery was 31 days of life (1-150); a lobectomy was performed in most of the cases. No complications or recurrence of disease were reported at a mean follow-up of 49 months. FLIT is rarely diagnosed during pregnancy, may present at birth with different levels of respiratory distress, and requires prompt surgical resection. Histology and immunohistochemistry allow for the differentiation of FLIT from cPAM and other lung tumors with poor prognosis, such as pleuropulmonary blastoma, congenital peri-bronchial myofibroblastic tumor, inflammatory myofibroblastic tumor, and congenital or infantile fibrosarcoma.

Abstract B038: Preclinical efficacy of KRASG12C inhibitors in models of pediatric cancer

Abstract Directly targeting RAS is a desirable approach for treating RAS-mutated tumors because direct RAS inhibitors block all RAS effector pathways simultaneously. Recently, several groups have developed agents that directly target KRAS by covalently modifying KRASG12C. KRAS is commonly altered in adult malignancies such as lung, pancreatic, and colorectal adenocarcinoma, but is less commonly altered in pediatric cancer. However, rare pediatric tumors harboring K-, H-, or NRASG12C are observed. The efficacy of KRASG12C inhibitors in pediatric malignancies is currently unknown, and the ability of these drugs to modify H- and NRASG12C has been incompletely characterized. Here we show that the KRASG12C inhibitors AMG 510, MRTX849, and ARS-1620 slow the release of GDP from H-, N-, and KRASG12C in vitro. Using RASless MEFs, we show that the activity of AMG 510 is specific for H-, N- or KRASG12C, while MRTX849 has both G12C and RAS-independent effects on cell viability. The KRASG12C inhibitors decreased cell viability in KRAS-mutant cell lines derived from patients with the pediatric solid tumor neuroblastoma. MRTX849 was more potent than AMG 510 in neuroblastoma cell lines but was less efficacious and less G12C-specific. The KRASG12C inhibitors also decreased cell viability in an NRASG12C-mutant T-cell ALL cell line derived from an adolescent patient but only MTRX849 decreased cell viability in an HRASG12C-mutant rhabdomyosarcoma cell line. These results suggest that KRASG12C inhibitors may be a treatment option for pediatric patients with H-, N- or KRASG12C mutant solid tumors or leukemia. Future studies will be aimed at testing the efficacy of these inhibitors in xenograft models of pediatric cancer and identifying non-RAS targets of MRTX849. Citation Format: Hannah Price, Stacey Stauffer, Katie Powell, Andrew Baker, Andrew Perciaccante, Edjay Ralph Hernandez, Patience Odeniyide, Christine Pratilas, William Burgan, Lisa Jenkins, Kent L. Rossman, Marielle Yohe. Preclinical efficacy of KRASG12C inhibitors in models of pediatric cancer [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr B038.

Pediatric Extra-Renal Nephroblastoma (Wilms' Tumor): A Systematic Case-Based Review.

Wilms Tumor (WT) is one of the most common renal tumors in the pediatric population. Occasionally, WT can primarily develop outside the kidneys (Extra-Renal Wilms Tumor, ERWT). Most pediatric ERWTs develop in the abdominal cavity and pelvis, whereas the occurrence of this tumor in other extra-renal sites represents a minor part of ERWT cases. In addition to describing a case of spinal ERWT (associated with spinal dysraphism) in a 4-year boy (to add a further clinical experience on this very rare pediatric tumor), we performed a case-based systematic literature review on pediatric ERWT. We retrieved 72 papers providing enough information on the diagnosis, treatment, and outcomes of 98 ERWT pediatric patients. Our research highlighted that a multimodal approach involving both chemotherapy and radiotherapy, after partial or complete tumor resection in most cases, was typically used, but there is no standardized therapeutic approach for this pediatric malignancy. However, this tumor may be potentially treated with a better success rate if the diagnostic confirmation is not delayed, the mass can be totally resected, and an appropriate and, possibly, tailored multimodal treatment can be promptly established. In this regard, an international agreement on a unique staging system for (pediatric) ERWT is definitely needed, as well as the development of international research, which may be able to gather several children diagnosed with ERWT and, possibly, lead to clinical trials which should also include developing countries.