Pediatric Renal Cell Carcinoma Research Articles

Pediatric thyroid-like follicular renal cell carcinoma-a post-neuroblastoma case with comprehensive genomic profiling data.

Thyroid-like follicular renal cell carcinoma (TLFRCC), an emerging subtype of renal cell carcinoma, presents diagnostic challenges due to its resemblance to normal thyroid tissue. Here, we report a rare case of TLFRCC in a pediatric patient, a demographic rarely affected by this subtype. Histologically resembling a typical TLFRCC, our case exhibited unique features including post-neuroblastoma development, occurrence in a male teenager, and diffuse MelanA expression, which has not been previously reported in TLFRCC. Comprehensive genomic profiling revealed the EWSR1::PATZ1 fusion, confirming its genetic basis. Due to the advanced tumor stage, the patient received combined immunotherapy, and after a 9-month follow-up, remains tumor-free. Our case broadens the diagnostic spectrum of pediatric renal cell carcinomas, highlighting the importance of comprehensive molecular profiling in rare subtypes such as TLFRCC. Further research is needed to better understand TLFRCC's genetic landscape and optimize therapeutic strategies, especially in pediatric populations with evolving treatment protocols.

Targeted therapies in children with renal cell carcinoma (RCC): An International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG)-related retrospective descriptive study.

Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC. This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti-programmed cell death 1 (PD-(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced-stage and relapsed pediatric RCC. Of the 31 identified patients (0-18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT-RCC) (21/31) and the remaining patients mainly presented with papillary or clear-cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono- or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis. This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies.

Factors associated with survival in paediatric and adolescent renal cell carcinoma: a population-based study.

The purpose of this study was to conduct a population-based study to determine the prognosis of renal cell carcinoma (RCC) in children and adolescents. Patients with RCC who were registered in the Surveillance, Epidemiology, and End Results (SEER) program between 2000 and 2018 had their demographic and clinical characteristics evaluated retrospectively. The log-rank test was used to compare survival curves. Kaplan-Meier estimates were used to generate survival curves based on various factors. To identify factors associated with overall survival, Cox proportional-hazards regression was used. A total of 251 patients were enrolled in the study. For all patients, the overall survival (OS) rates at 3- and 5- year were 93.5% and 92.0%, respectively. A multivariable study revealed that the following factors were independently associated with overall survival: sex, race, histologic type, SEER stage, AJCC stage, and type of surgery. Cox analysis showed that white patients had the lowest risk of mortality (hazard ratio (HR) 2.58, 95% confidence interval (CI), 1.33-4.99; P = 0.005), compared with black patients. Patients having metastatic disease had significantly higher mortality risk (HR 43, 95% CI, 14.8-125; P < 0.001) than the patients with localized tumour. Our study emphasizes the importance of race, SEER stage, and surgery in the prognosis of paediatric RCC, providing valuable epidemiological evidence for clinical practice. Economic studies assessing a race/ethnic group specific strategy are also required.

MRI Characteristics of Pediatric and Young-Adult Renal Cell Carcinoma: A Single-Center Retrospective Study and Literature Review

Pediatric renal cell carcinoma (RCC) is a rare malignancy. Magnetic resonance imaging (MRI) is the preferred imaging modality for assessment of these tumors. The previous literature has suggested that cross-sectional-imaging findings differ between RCC and other pediatric renal tumors and between RCC subtypes. However, studies focusing on MRI characteristics are limited. Therefore, this study aims to identify MRI characteristics of pediatric and young-adult RCC, through a single-center case series and literature review. Six identified diagnostic MRI scans were retrospectively assessed, and an extensive literature review was conducted. The included patients had a median age of 12 years (63-193 months). Among other subtypes, 2/6 (33%) were translocation-type RCC (MiT-RCC) and 2/6 (33%) were clear-cell RCC. Median tumor volume was 393 cm3 (29-2191 cm3). Five tumors had a hypo-intense appearance on T2-weighted imaging, whereas 4/6 were iso-intense on T1-weighted imaging. Four/six tumors showed well-defined margins. The median apparent diffusion coefficient (ADC) values ranged from 0.70 to 1.20 × 10-3 mm2/s. In thirteen identified articles focusing on MRI characteristics of MiT-RCC, the majority of the patients also showed T2-weighted hypo-intensity. T1-weighted hyper-intensity, irregular growth pattern and limited diffusion-restriction were also often described. Discrimination of RCC subtypes and differentiation from other pediatric renal tumors based on MRI remains difficult. Nevertheless, T2-weighted hypo-intensity of the tumor seems a potential distinctive characteristic.

The genomic landscape of pediatric renal cell carcinomas

SummaryPediatric renal cell carcinomas (RCC) differ from their adult counterparts not only in histologic subtypes but also in clinical characteristics and outcome. However, the underlying biology is still largely unclear. For this reason, we performed whole-exome and transcriptome sequencing analyses on a cohort of 25 pediatric RCC patients with various histologic subtypes, including 10 MiT family translocation (MiT) and 10 papillary RCCs. In this cohort of pediatric RCC, we find only limited genomic overlap with adult RCC, even within the same histologic subtype. Recurrent somatic mutations in genes not previously reported in RCC were detected, such as in CCDC168, PLEKHA1, VWF, and MAP3K9. Our papillary pediatric RCCs, which represent the largest cohort to date with comprehensive molecular profiling in this age group, appeared as a distinct genomic subtype differing in terms of gene mutations and gene expression patterns not only from MiT-RCC but also from their adult counterparts.

Abstract 3041: ASPSCR1-TFE3 gene fusion in transgenic mouse as a new pediatric kidney cancer model

Abstract A novel genetically engineered mouse (GEM) model for pediatric kidney cancer expressing proximal tubule specific ASPSCR1 :TFE3 fusion gene has been developed. The Rosa26 knock-in ASPSCR1 :TFE3 mouse was crossed with SGLT2-Cre mouse that expresses Cre recombinase in the proximal tubules of the kidney. The ASPSCR1 :TFE3 fusion gene retains the DNA binding and activation domain of TFE3, whereas the N-terminal region of TFE3 is replaced with ASPSCR1 sequences. ASPSCR1 :TFE3 is known to up-regulate the Met receptor tyrosine kinase gene and induce oncogenic phenotypes such as uncontrolled cell proliferation, invasion, and metastasis. However, the molecular roles of ASPSCR1 :TFE3 are poorly understood and no standard of care (SOC) exists for pediatric TFE3 fusion renal cell carcinoma (RCC). Ultrasound (US) and histological analyses of the kidneys of 5, 6 and 7 month old mice revealed bilateral cysts and tumors, while 6-week-old mouse kidney appears normal. At gross inspection, 5-month-old mouse had cysts with a diameter of 1-2 mm while 7-month-old mouse had a polycystic kidney and in the end stage disease. Histopathology revealed neoplastic changes in initial stages in the 5-month-old mouse whereas the neoplasia was predominantly a papillary cystic renal carcinoma; solid tumor formations were observed in the 7-month-old mouse. Neoplastic cells seen in within the blood vessel walls of the 7-month-old mouse indicated future metastasis. This new TFE3 fusion GEM will provide an avenue to understand molecular events of tumorigenesis and progression as well as a model for testing novel therapeutics with survival benefit for a cancer with no current SOC. Citation Format: Aylin Alasonyalilar-Demirer, James L. Miller, Erin E. Miller, Justyna J. Gleba, Han W. Tun, John A. Copland. ASPSCR1-TFE3 gene fusion in transgenic mouse as a new pediatric kidney cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3041.

Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93-01, 2001 and UK-IMPORT database: A report of the SIOP-Renal Tumor Study Group.

In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology‐Renal Tumor Study Group (SIOP‐RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93‐01, 2001 and UK‐IMPORT databases, were included. Event‐free survival (EFS) and overall survival (OS) were analyzed using the Kaplan‐Meier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiT‐RCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFE‐cytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5‐year (5y) EFS and 5y OS of the total group was 70.5% (95% CI = 61.7%‐80.6%) and 84.5% (95% CI = 77.5%‐92.2%), respectively. Estimated 5y OS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFE‐testing.

Renal cell carcinoma in children and adolescents: Single-center experience and literature review.

Renal cell carcinoma (RCC) is infrequent in the pediatric population. In addition, till date, only a few reports have summarized the characteristics of pediatric RCC and differences between pediatric and adult RCC. Therefore, the current study aimed to investigate the clinical characteristics of RCC in children and adolescents, and identify the differences between children and adolescent patients and adult patients through literature retrieval.The data of 13 pediatric patients diagnosed with RCC at the Children's Hospital of Zhejiang University School of Medicine between 2005 and 2019 were retrospectively analyzed.Three patients were aged <5 years, 2 were aged 6 to 10 years, and 8 were aged 11 to 18 years. Among the 13 patients, common clinical manifestations included abdominal pain in 5 patients, gross hematuria in 4, and an abdominal mass in 1, while the other 3 patients were incidentally detected after an abdominal contusion. The pathological types were microphthalmia family translocation RCC in 9 patients, clear-cell RCC in 2, papillary RCC in 1, and unclassified in 1. All the children underwent radical nephrectomy, including 2 patients with advanced disease who underwent preoperative transcatheter arterial chemoembolization. The mean follow-up time was 58.6 months. Two patients died after 4 and 17 months of follow-up, respectively.In conclusion, microphthalmia family translocation renal cell carcinoma is the predominant type of pediatric RCC associated with advanced tumor stage. The early diagnosis and treatment of pediatric patients is important for improving prognosis. Nevertheless, future studies are urgently needed to determine the treatment for pediatric advanced RCC to increase the survival rate.

The Genomic Landscape of Pediatric Renal Cell Carcinomas

The Genomic Landscape of Pediatric Renal Cell Carcinomas

Multifaceted activities of transcription factor EB in cancer onset and progression.

Transcription factor EB (TFEB) represents an emerging player in cancer biology. Together with microphthalmia-associated transcription factor, transcription factor E3 and transcription factor EC, TFEB belongs to the microphthalmia family of bHLH-leucine zipper transcription factors that may be implicated in human melanomas, renal and pancreatic cancers. TFEB was originally described as being translocated in a juvenile subset of pediatric renal cell carcinoma; however, whole-genome sequencing reported that somatic mutations were sporadically found in many different cancers. Besides its oncogenic activity, TFEB controls the autophagy-lysosomal pathway by recognizing a recurrent motif present in the promoter regions of a set of genes that participate in lysosome biogenesis; furthermore, its dysregulation was found to have a crucial pathogenic role in different tumors by modulating the autophagy process. Other than regulating cancer cell-autonomous responses, recent findings indicate that TFEB participates in the regulation of cellular functions of the tumor microenvironment. Here, we review the emerging role of TFEB in regulating cancer cell behavior and choreographing tumor-microenvironment interaction. Recognizing TFEB as a hub of network of signals exchanged within the tumor between cancer and stroma cells provides a fresh perspective on the molecular principles of tumor self-organization, promising to reveal numerous new and potentially druggable vulnerabilities.

A prospective study of pediatric and adolescent renal cell carcinoma: A report from the Children's Oncology Group AREN0321 study.

To the authors' knowledge, AREN0321 is the first prospective clinical study of pediatric and adolescent renal cell carcinoma (RCC). Goals of the study included establishing epidemiological, treatment, and outcome data and confirming that patients with completely resected pediatric RCC, including lymph node-positive disease (N1), have a favorable prognosis without adjuvant therapy. From 2006 to 2012, patients aged <30 years with centrally reviewed pathology of RCC were enrolled prospectively. A total of 68 patients were enrolled (39 of whom were male; median age of 13 years [range, 0.17-22.1 years]). Stage was classified according to the American Joint Committee on Cancer TNM stage seventh edition as stage I in 26 patients, stage II in 7 patients, stage III in 26 patients, and stage IV in 8 patients, and was not available in 1 patient. Sixty patients underwent resection of all known sites of disease, including 2 patients with stage IV disease. Surgery included radical nephrectomy (53 patients [81.5%]), partial nephrectomy (12 patients [18.5%]), and unknown (3 patients [4.4%]). Histology was TFE-associated RCC (translocation-type RCC; tRCC) in 40 patients, RCC not otherwise specified and/or other in 13 patients, papillary RCC in 9 patients, and renal medullary carcinoma (RMC) in 6 patients. Lymph node status was N0 in 21 patients, N1 in 21 patients (tRCC in 15 patients, RMC in 3 patients, papillary RCC in 2 patients, and not otherwise specified and/or other in 1 patient), and Nx in 26 patients. The 4-year event-free survival and overall survival rates were 80.2% (95% CI, 69.6%-90.9%) and 84.8% (95% CI, 75.2%-94.5%), respectively, overall and 87.5% (95% CI, 68.3%-100%) and 87.1% (95% CI, 67.6%-100%), respectively, for the 16 patients with N1M0 disease. Among patients presenting with metastases, 2 of 8 patients (2 of 5 patients with RMC) were alive (1 with disease) at the time of last follow-up, including 1 patient who was lost to follow-up (succinate dehydrogenase deficiency). The predominant RCC subtypes associated with mortality were tRCC and RMC. Favorable short-term outcomes can be achieved without adjuvant therapy in children and adolescents with completely resected RCC, independent of lymph node status. A prospective study of patients with tRCC and RMC with M1 or recurrent disease is needed to optimize treatment.

Pediatric and young adult renal cell carcinoma.

Renal cell carcinoma (RCC) is rare in children but is the most common renal tumor in adults. Pediatric RCC has different clinical characteristics, histopathology, and treatment compared with adult disease. Databases were reviewed from inception to February 2020, identifying 32 publications pertaining to 350 patients under 27 years. Surgery is the cornerstone for cure in localized RCC. Lymph node dissection remains controversial. Conventional radiotherapy has no curative role in RCC; similarly, conventional chemotherapy has not proven to be effective in large cohorts. Pediatric metastatic RCC has a poor outlook. There are no published prospective studies demonstrating which adjuvant therapy could improve outcome. Sunitinib, a tyrosine kinase inhibitor, is recommended in this group despite limited evidence. This review provides an overview for pediatric RCC, including the evolving role of precision medicine.

Tumor Lipids of Pediatric Papillary Renal Cell Carcinoma Stimulate Unconventional T Cells.

Papillary renal cell carcinoma (PRCC) is a rare entity in children with no established therapy protocols for advanced diseases. Immunotherapy is emerging as an important therapeutic tool for childhood cancer. Tumor cells can be recognized and killed by conventional and unconventional T cells. Unconventional T cells are able to recognize lipid antigens presented via CD1 molecules independently from major histocompatibility complex, which offers new alternatives for cancer immunotherapies. The nature of those lipids is largely unknown and α-galactosylceramide is currently used as a synthetic model antigen. In this work, we analyzed infiltrating lymphocytes of two pediatric PRCCs using flow cytometry, immunohistochemistry and qRT-PCR. Moreover, we analyzed the CD1d expression within both tumors. Tumor lipids of PRCC samples and three normal kidney samples were fractionated and the recognition of tumor own lipid fractions by unconventional T cells was analyzed in an in vitro assay. We identified infiltrating lymphocytes including γδ T cells and iNKT cells, as well as CD1d expression in both samples. One lipid fraction, containing ceramides and monoacylglycerides amongst others, was able to induce the proliferation of iNKT cells isolated from peripheral blood mononuclear cells (PBMCs) of healthy donors and of one matched PRCC patient. Furthermore, CD1d tetramer stainings revealed that a subset of iNKT cells is able to bind lipids being present in fraction 2 via CD1d. We conclude that PRCCs are infiltrated by conventional and unconventional T cells and express CD1d. Moreover, certain lipids, present in pediatric PRCC, are able to stimulate unconventional T cells. Manipulating these lipids and T cells may open new strategies for therapy of pediatric PRCCs.

Eosinophilic solid and cystic renal cell carcinoma with TSC2 gene mutations in children

Objective: To study clinical pathological characteristics, immunohistochemical, molecular genetical changes and prognosis in pediatric eosinophilic solid and cystic renal cell carcinoma (ESC RCC) with TSC2 gene mutations. Methods: The tissue samples were collected from two pediatric ESC RCC patients between 2017 and 2018. The tissues were subjected to histological examination and immunohistochemistry using EnVision system. The TFE3, TFEB gene rearrangements were tested using FISH and molecular genetic study. The paraffin sections were used for DNA extraction, PCR amplification and NGS sequencing. Results: The two patients with ESC RCC were both male, aged at 9 years and 8 months, and 13 years, respectively. The tumors were from the right kidney, 5 cm and 7 cm in size, respectively, with solid and cystic changes in cross section, and grey-reddish or grey-whitish fish meat appearance. Microscopic observation revealed the tumors had fibrous capsules, which were infiltrated by the tumor cells. The tumor cells were diffusely distributed, round-shaped, or polygon-shaped, and had voluminous cytoplasm, eosinophilic cytoplasm, various sizes of vacuoles and clear cell-like appearance. There were papillary structures in some areas, with visible fiber septa. The nuclei were round and vesicular, with multi-nucleated cells and megakaryocytes. The mitoses were not seen. A few cystic structures were visible in different sizes, and capsule walls were covered with a single layer of spike-like tumor cells. Thick-walled blood vessels were seen in the stroma, with focal lymphocytic infiltration, eosinophilic necrosis, calcifications and cholesterol crystals. Immunohistochemistry of the tumor cells was positive for PAX8 (diffuse), CK20 (focal), CKpan (focal), CK10 (1 focal, 1 diffuse), INI1, vimentin, CD68, and Ki-67 (5%~10%); the tumor cells were negative for HMB45, S-100, Melan A, p53, desmin, TFE3, CK7, CK19, EMA, CD56, CgA, Syn, CD30, CD117, WT1 and SMA. Molecular genetic study showed that TFE3 and TFEB gene rearrangements were not detected by FISH. NGS sequencing showed TSC2 p.Lys574Ter (0.198) was found in patient one and TSC2 p.Arg406Ter (0.355) in patient two. Conclusions: ESC RCC in children is a rare disease, and can be misdiagnosed easily. It has unique pathological characteristics, and immunohistochemical, molecular and genetic changes. The prognosis is relatively good.

Characteristics and Outcome of Children with Renal Cell Carcinoma: A Narrative Review.

Pediatric renal cell carcinoma (RCC) is a rare type of kidney cancer, most commonly occurring in teenagers and young adolescents. Few relatively large series of pediatric RCC have been reported. Knowledge of clinical characteristics, outcome and treatment strategies are often based on the more frequently occurring adult types of RCC. However, published pediatric data suggest that clinical, molecular and histological characteristics of pediatric RCC differ from adult RCC. This paper summarizes reported series consisting of ≥10 RCC pediatric patients in order to create an up-to-date overview of the clinical and histopathological characteristics, treatment and outcome of pediatric RCC patients.

Abstract C071: Effect measure modification implication of area of residence in survival disadvantage of black children with renal cell carcinoma

Abstract Purpose: Renal cell carcinoma (RCC) is a rare but severe and aggressive pediatric malignancy. While incidence is uncommon, survival is relatively low with respect to acute lymphocytic leukemia and Wilms' tumor. The incidence of RCC and mortality vary by health variance indicators, namely sex, race, and age. However, data are unavailable on some RCC determinants, such as area of residence. We aimed to assess the temporal trends and survival in pediatric RCC (pRCC). Methods: A retrospective cohort design was utilized to examine the event-free survival of children (0-19 years) with RCC using the Surveillance Epidemiology and End Result Data, 1973-2015. While the time-dependent variable, namely survival in months, was utilized, we assessed the predictors of survival, namely sex, age at diagnosis, education, insurance status, income, and tumor grade. In examining the joint effect of area of residence and race, as an exposure function with time, we used the Cox proportional hazard model, while the annual percent change was assessed using a generalized linear model. Results: Between 1973-2015, there were 174 cases of pRCC, of whom 49 died (28.2%). RCC cumulative incidence tends to increase with advancing age and males (10-14) indicating a 1.6% change between 2000-2015. With respect to area of residence, mortality was higher in urban (46.7%) relative to metropolitan (26.4%). Relative to whites (17.2%), mortality was higher among blacks (47.0%). A sizable survival difference was observed with blacks relative to whites. Compared to whites, blacks were almost three times as likely to die, Hazard Ratio (HR) = 2.90, 95% Confidence Interval (CI) = 1.56-5.31. Survival was associated with sex, with males 21% more likely to die (HR = 1.21, 95% CI 0.69-2.11). Similarly, there was a nexus with age at tumor diagnosis and survival. Although imprecise, children ages 1-4, 5-9, and 10-14 were 72%, 50%, and 21%, respectively, less likely to die compared to children ages 15-19. Tumor grade, education, and income were prognostic in survival, although imprecise. The conjoint effect of area of residence and race illustrated excess risk of dying in urban relative to metropolitan areas. In the metropolitan area, the risk of dying was almost 3 times higher for blacks compared to whites (HR = 2.78, 95% CI 1.45-5.43); in urban areas there was more black survival disadvantage, HR = 4.18, 95% CI 0.84-20.80. After controlling for age, sex, education, and insurance, the risk of dying increased among blacks with RCC in metropolitan areas, a-HR = 3.37, 99% CI 1.35-8.44. Similarly, in the urban areas, after adjustment for age, sex, and insurance, there was an increased risk of dying for blacks compared to whites, a-HR = 8.87, 99% CI 2.77-281.0. Conclusion: Pediatric RCC indicated an increased trend in males and age of diagnosis between 10-14, as well as survival disadvantage of black children. Additionally, area of residence significantly influenced racial differences in mortality. Citation Format: Phatsimo Masire, Arieanna Eaton, Kirk Dabney, Larry Holmes Jr. Effect measure modification implication of area of residence in survival disadvantage of black children with renal cell carcinoma [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C071.

Lymph node yield in pediatric, adolescent and young adult Renal Cell Carcinoma – How many are enough?

PurposePediatric, adolescent and young adult (PAYA) patients with renal cell carcinoma (RCC) have a high rate of LN involvement, yet data to guide surgical lymph node (LN) management in this group is limited. The objective is to describe a LN yield threshold to quantify the chance of missing occult LN involvement at ≤10% in PAYAs with RCC. Materials & methodsThe National Cancer Database was queried for patients aged ≤30 y with unilateral, non-metastaticRCC from 2004 to 2013. The probability of a false negative LN sampling was determined on the cohort of patients who had at least one positive LNand ≥ 2 LNs examined. For a given LN yield, the probability that a positive LN exists but none were found was estimated using a beta-binomial model. ResultsWe identified 112 patients meeting study criteria. Median age was 24 y and median tumor size was 9.5 cm (IQR 5.8–14). The median number of LNs sampled was 7 (IQR 4–12) and the median number of LNs positive was 4 (IQR 2–7). To achieve ≤10% probability of a false-negativeLN sampling, the beta-binomial model estimated that 5 LNs (95% CI4–7) must be sampled. ConclusionsThe desired LN yield to reduce the risk of a false-negativeLN sampling in PAYAs with RCC to ≤10% is 5. This is in keeping with prior studies identifying a LN yield of 6–10 to achieve the same. These data may be used to standardize surgical guidelines when treating PAYAs with renal tumors. Level of EvidenceII.

LncRNA SCAMP1 regulates ZEB1/JUN and autophagy to promote pediatric renal cell carcinoma under oxidative stress via miR-429

BackgroundRenal cell carcinoma (RCC), including pediatric RCC, is one of the high cancer-associated death cause in adults and children. The mechanism by which long non-coding RNA SCAMP1 regulates RCC is not fully understood. MethodsmRNA and protein levels were detected by RT-qPCR and westernblot. MTT assay was used to examine cell viability and TUNEL assay was utilized to measure apoptosis of ACHN and Caki-1 cells.in vivo tumor growth was determined by xenograft assay. ResultsH2O2 treatment remarkably inhibited RCC cell viability and induced apoptosis. SCAMP1 was elevated in RCC cells and tumors. SCAMP1 depletion attenuated cell viability and promoted apoptosis under H2O2 treatment. Then, miR-429 was identified as downstream effector for SCAMP1-mediated tumorigenesis under H2O2 treatment. Besides, miR-429 was downregulated in human clinical tumors. ZEB1 and JUN were both found to be involved in the role of miR-429 in RCC. More interestingly, autophagy obviously affected miR-429-modulated RCC tumorigenesis. Eventually, we also showed that SCAMP1 played an oncogenic role in vivo. ConclusionIn summary, we propose that SCAMP1 affects RCC tumorigenesis through miR-429 and its downstream targets. Our findings will contribute to development of biomarkers and therapeutics for RCC.

Treatment of advanced pediatric renal cell carcinoma

Pediatric renal cell carcinoma (pRCC) is the second most common renal malignancy of childhood; however, treatment data for advanced disease is lacking. A retrospective analysis of pRCC patients (age<21 years at diagnosis) treated between 2000 and 2015 at Cincinnati Children's Hospital Medical Center was undertaken, with specific focus on medical therapies, accompanied by a detailed literature review. Twenty-four patients (median age = 15 years) were identified; 11 were female. Past history of kidney pathology (4) and prior hematologic/oncologic diagnoses (5) were common associated findings. Translocation morphology RCC (tRCC) was the most common subtype (16; 64%), followed by papillary (6; 24%), clear cell renal cell carcinoma (ccRCC) (1), and chromophobe (1). The TNM stage distribution was I (8; 33%), II (2; 8%), III (3; 13%), and IV (11; 46%). Eleven patients with stage IV disease all had tRCC and received medicinal anticancer therapies, the most common being antiangiogenic (10), conventional chemotherapy (8), mTOR inhibition (7), and immunotherapy (3). Four patients also received small-port radiotherapy. The mean time to progression (TTP) was longest for axitinib (n=2; TTP = 7.8m; range 5.5-10m) and sunitinib (n=6; TTP = 4.7m; range 0.3-12m). Overall, 20 cases of pediatric RCC who received RCC-directed medicinal therapy with outcome data have been previously reported. For patients with unresectable pRCC requiring systemic therapy, available data are scarce. Data herein support an increased TTP with antiangiogenic therapy in tRCC supporting a formal study of antiangiogenic therapies through multicooperative-group collaboration.

Lymph node imaging of pediatric renal and suprarenal malignancies.

Pediatric renal and suprarenal cancers are relatively rare malignancies, but are not without significant consequence to both the patient and caretakers. These tumors are often found incidentally and present as large abdominal masses. Standard of care management involves surgical excision of the mass, but contemporary treatment guidelines advocate for use of neoadjuvant or adjuvant chemotherapy for advanced stage disease, such as those cases with lymph node involvement (LNI). However, LNI detection is based primarily on surgical pathology and performing extended lymph node dissection can add significant morbidity to a surgical case. In this review, we focus on the use and performance of imaging modalities to detect LNI in Wilms’ tumor (WT), neuroblastoma, and pediatric renal cell carcinoma (RCC). We report on how imaging impacts management of these cases and the clinical implications of LNI. A literature search was conducted for studies published on imaging-based detection of LNI in pediatric renal and suprarenal cancers. Further review focused on surgical and medical management of those cases with suspected LNI. Current imaging protocols assisting in diagnosis and staging of pediatric renal and suprarenal cancers are generally limited to abdominal ultrasound and cross-sectional imaging, mainly computed tomography (CT). Recent research has investigated the role of more advance modalities, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), in the management of these malignancies. Special consideration must be made for pediatric patients who are more vulnerable to ionizing radiation and have characteristic imaging features different from adult controls. Management of pediatric renal and suprarenal cancers is influenced by LNI, but the rarity of these conditions has limited the volume of clinical research regarding imaging-based staging. As such, standardized criteria for LNI on imaging are lacking. Nevertheless, advanced imaging modalities are being investigated and potentially represent more accurate and safer options.