Top Pediatric Cancer Advances at MSK Kids in 2022

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Doctors at MSK Kids, the dedicated pediatric service at Memorial Sloan Kettering Cancer Center (MSK), pioneered many advances for pediatric patients in 2022. A combination of clinical trial findings and laboratory studies contributed to a greater understanding of the role that genes, mutations, and DNA play in pediatric cancer — forging the way for tremendous progress in the efforts to control and cure children’s cancers.

“MSK Kids has a unique, specialized approach to pediatric cancer care,” says pediatric oncologist Andrew Kung, MD, PhD, Chair of the Department of Pediatrics at MSK. “Our team of clinicians and researchers are constantly working together to develop scientific discoveries, which has led to new treatments and procedures benefiting kids of all ages.”

Here are some of the most interesting developments in 2022:

New Type of Genetic Testing Aims To Benefit Children and Young Adults With Cancer

Genomic sequencing has become a critical tool that allows clinicians to identify the driving mutations responsible for cancer development. While the cancer-gene-panel approach works very well for adults, a common problem is that similar methodologies have shown less success in the pediatric population. To solve these challenges, Dr. Kung and his colleagues believe that whole genome sequencing should be applied in the pediatric population to better visualize structural variants.

In a paper published May 18, 2022, in the journal Nature Communications, Dr. Kung; MSK computational oncologist Elli Papaemmanouil, PhD; and their colleagues reported on the performance of the whole genome sequencing platform. They found that their approach identified at least one additional cancer-associated oncogenic variant in 54% of patients (62 out of 114), compared with MSK-IMPACT® (the targeted tumor-sequencing test available to MSK patients). Of these, 33 patients had one or more findings that were of direct clinical relevance.

The researchers emphasize that the new platform is not currently a replacement for panel-based tests, such as MSK-IMPACT®, which work well for capturing relevant mutations in adult and some pediatric patients with common tumors. Still, the study authors say the benefits for pediatric patients are so compelling that this type of testing is now being made available to every pediatric patient at MSK through philanthropic funding.

 (1) Read the full story: New Type of Genetic Testing Aims To Benefit Children and Young Adults With Cancer | Memorial Sloan Kettering Cancer Center (

Sequencing Cerebrospinal Fluid Improves Diagnosis and Treatment Protocol for Brain Tumors

Diagnosing central nervous system cancers can be difficult or impossible due to the challenges of accessing the tumor site. In a study published in Neuro-Oncology, a team of MSK physicians elaborated on their clinical experience using a minimally invasive technique of analyzing cerebrospinal fluid (CSF) cell-free DNA (cfDNA).

In a group of 45 patients with previously histopathological diagnosed cancer, 64 CSF samples were obtained, and cancer-associated mutations were identified in nearly 50% of patients. Somatic alterations were found in 47% of patients. Samples were analyzed using MSK-IMPACT®, a technique that analyzes 486 cancer causing genes.

Study authors Alexandra Miller, MD, PhD, MSK neuro-oncologist, and Matthias A. Karajannis, MD, MS, Chief of Pediatric Neuro-Oncology at MSK, noted that based on the initial experience, CSF-based liquid biopsy provided clinical value in diagnosing and managing pediatric, adolescent, and young adult patients with brain tumors and should be utilized more widely in the future.

 (2)Read the full story: Sequencing Cerebrospinal Fluid Is Clinically Useful in Pediatric, Adolescent, and Young Adult Brain Tumors | Memorial Sloan Kettering Cancer Center (

An 11-Year Retrospective Review of Pneumatosis Intestinalis in Pediatric Cancer Patients

Pneumatosis intestinalis (PI), which develops in 1% of pediatric cancer patients, is characterized by intramural gas present in the gastrointestinal (GI) tract.In a recently published study in Pediatric Blood & Cancer, MSK physicians, including Michael P. La Quaglia, MD, the Joseph H. Burchenal Chair in Pediatrics, explored the risk factors and outcomes of pediatric patients with cancer who developed PI.

The study, which included the largest case series of patients with PI in the pediatric population to date, retrospectively identified patients from 2007 and 2018 at MSK Kids. Using ICD-10 codes from radiology reports, a total of 42 patients were analyzed. The primary outcomes of interest were time to resolution, surgical intervention within two weeks of diagnosis, and death secondary to PI.

Results of the study showed that within 30 days of diagnosis, three patients (7%) had surgical intervention for PI and two patients (5%) died due to non-PI-associated causes. Of the patients that did receive surgery, complication rates remained low and overall mortality was lower than previous studies. Time to recovery was 4.5 days, and steroid use was the most common variable associated with the resolution of PI.

At the conclusion of the study, the authors noted that for many patients, PI can be managed conservatively, and future prospective studies are warranted to define diagnosis and management guidelines.

 (3)Read the full journal article: Pneumatosis Intestinalis In The Pediatric Oncology Population: An 11-Year Retrospective Review At Memorial Sloan Kettering Cancer Center

Treatment of BRAF-Mutant Pediatric High-Grade Glioma Using Targeted Molecular Therapy 

Pediatric high-grade glioma (pHGG) with BRAF-mutant tumors historically have had poor clinical outcomes when treated with the standard therapeutic approach of radiation, chemotherapy, and surgery. However, studies in adults have shown promising results using BRAF-targeted therapies in combination with MEK inhibitors for low-grade glioma, leading physicians to study if similar results could be found in the pediatric population.

MSK pediatric neuro-oncologist, Dr. Karajannis, led a multi-institutional group in a recent retrospective study published in Neuro-Oncology. The study sought to determine if the addition of a MEK-inhibitor therapy would lead to enhanced outcomes compared with a BRAF inhibitor alone in pHGG.

A total of 19 patients with pHGG and confirmed BRAF V600- mutation (WHO grade III–IV) were identified. Eight patients received upfront BRAF monotherapy, and 11 patients received combination BRAF/MEK therapy following neurosurgical resection of the tumor. Findings suggested that following standard-of-care surgery and chemotherapy with upfront molecular targeted therapy, including the BRAF/MEK therapy, is well-tolerated and associated with superior progression-free survival and overall survival compared with prior studies.

The study authors noted that these findings suggest that molecular targeted therapy should be strongly considered for all newly diagnosed pediatric, adolescent, and young adult patients with BRAF-mutant pHGG. Due to the success of this upfront treatment paradigm, a prospective clinical trial by the Children’s Oncology Group (ACNS1723) is currently being conducted.

 (4)Read the full journal article: Upfront Molecular Targeted Therapy For The Treatment Of BRAF-Mutant Pediatric High-Grade Glioma

Identification of Nongenetically Encoded Vulnerability for Pediatric Renal Tumors 

Malignant rhabdoid tumors (MRTs) and Wilms’ tumors (WTs) are two types of renal tumors seen in the pediatric population. These tumors provide challenges to many conventional cancer treatments due to their lack of targetable somatic mutations, which is why physicians created a methodology to find “druggable” sites that are mutation independent.

In a recent multipart study published in Med (N Y) and co-led by Dr. Kung and MSK pediatric oncologist Filemon Dela Cruz, MD, the team first used metaVIPER, a type of comparative protein activity analysis, to identify potentially targetable sites in 68 patients with MRT and 132 patients with WT. Using this method of in silico analysis, elevated exportin 1 (XPO1) was found to have increased activity.

Using in vitro MRT and WT cell lines, the team demonstrated the ability to induce cell cycle arrest and apoptosis using the drug Selinexor, an inhibitor of XPO1. To test the model in vivo, the team used patient-derived xenograft (PDX) models from patients diagnosed with both tumor types and confirmed the efficacy of the in vitro model by demonstrating tumor growth arrest. These findings suggested a potential treatment model.

Based on the promising preclinical data, a pediatric patient with relapsed and progressive WT was treated with Selinexor. Prior to Selinexor, the patient was treated with standard chemotherapy combinations, followed by a nephrectomy. Following relapse of the tumor after one year off the therapy, the standard chemotherapeutic regimen resumed, followed by radiation to the abdomen and lungs. While this treatment offered an initial response, the patient’s disease continued to progress, and the patient was then placed on Selinexor. At a follow-up of 14 months, the patient presented with excellent clinical outcomes and remains disease free.

Based on the success with the patient, the MSK team is currently conducting the initiation stage of a clinical trial for pediatric patients with renal tumors using Selinexor monotherapy.

 (5)Read the full journal article: Validation of a Non-Oncogene Encoded Vulnerability to Exportin 1 Inhibition in Pediatric Renal Tumors

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  1. Shukla N, Levine MF, Gundem G, et al. Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers. Nat Commun. 2022;13(1):2485. Published 2022 May 18.
  2. Miller AM, Szalontay L, Bouvier N, et al. Next-generation sequencing of cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent and young adult brain tumor patients. Neuro Oncol. 2022;24(10):1763-1772.
  3. Bailey KA, Kodikara H, Mauguen A, Price A, LaQuaglia M, Boulad F. Pneumatosis intestinalis in the pediatric oncology population: An 11-year retrospective review at Memorial Sloan Kettering Cancer Center. Pediatr Blood Cancer. 2022;69(7):e29539.
  4. Rosenberg T, Yeo KK, Mauguen A, et al. Upfront molecular targeted therapy for the treatment of BRAF-mutant pediatric high-grade glioma. Neuro Oncol. 2022;24(11):1964-1975.
  5. Coutinho DF, Mundi PS, Marks LJ, et al. Validation of a non-oncogene encoded vulnerability to exportin 1 inhibition in pediatric renal tumors. Med (N Y). 2022;3(11):774-791.e7.