KRAS Mutation in Pediatric Intracranial Germ Cell Tumors.

BACKGROUND: Intracranial germ cell tumors (IGCTs) are rare, highly curable neoplasms. KRAS is a gene in the KIT/RAS signaling pathway, and KRAS mutations have been reported in patients diagnosed with IGCTs. OBJECTIVES: To describe the clinicopathologic and molecular features of KRAS mutation and the treatment outcome of children diagnosed with IGCTs. METHODS: Patients diagnosed with IGCTs at the Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2016 were retrospectively reviewed. DNA was extracted from formalin-fixed, paraffin-embedded tissue and used for molecular study. Mutations in codons 12, 13, and 61 of the KRAS gene were detected using the cobas® KRAS mutation test and pyrosequencing. RESULTS: Eighteen patients were diagnosed with IGCTs (11 males and 7 females): nine with germinomas and nine with non-germinomatous GCTs (NGGCTs). The age range of the patients was 5-14 years (median 10.5 years). Elevated markers were revealed in approximately 25% of the patients. Four patients (two with germinomas and two with NGGCTs) had leptomeningeal involvement. All patients underwent tumor biopsy and received neoadjuvant chemotherapy. Radiotherapy was administered in 16 patients, and craniospinal radiation was administered only in patients with leptomeningeal metastasis. With a median follow-up of 26 months, overall survival was 88.9% in the patients with germinomas and 37% in the patients with NGGCTs. Mutation of the KRAS gene was detected using pyrosequencing in one patient. The mutation located at codon 61, with frequency 38.3% units, nucleotide substitution CAA > CTA, and amino acid substitution, was Q61L. The patient carrying the mutant gene was diagnosed with germinoma with cerebrospinal fluid metastasis and eventually died from treatment-related toxicity. CONCLUSION: Our study revealed the treatment outcomes of IGCTs in Thai children. The metastatic germinoma patient with KRAS codon 61 mutation had a poor outcome, supporting that Q61L has a clinical correlation with IGCTs.

Immune Response after 2 Doses of BNT162b2 mRNA COVID-19 Vaccinations in Children and Adolescents with Cancer and Hematologic Diseases.

BACKGROUND: The BNT162b2 mRNA COVID-19 vaccine has been administered to children and adolescents with cancer and hematologic diseases since they are at high risk of manifesting severe symptoms if they have COVID-19 infection but the adequate immune response after vaccination in these immunocompromised patients are questionable. OBJECTIVE: To evaluate the immune response of children and adolescents with cancer and hematologic diseases after receiving 2 doses of the BNT162b2 mRNA COVID-19 vaccine. METHODS: This is a prospective cohort study of patients with cancer and hematologic disease, who aged 12- 18 years old and received 2 doses the BNT162b2 vaccines at 4 weeks apart were enrolled. Immunogenicity was determined by measuring serum anti-SARS-CoV-2 immunoglobulin antibodies directed against the receptor binding domain (RBD) of S1 domain of the spike protein (Anti S-RBD), surrogated viral neutralization test (sVNT) of SARS-CoV-2 and Delta strain. Blood samples were collected and analyzed at 4 and 12 weeks after vaccination. The seroprotective rate was defined as sVNT ≥ 68%. RESULTS: From Oct 2021 to Jan 2022, 43 children were enrolled, 21 were on-therapy and 22 were off-therapy. 25 were hematologic malignancy, 15 solid tumor and 3 hematologic diseases with immunosuppressive drugs. The GMT (95%CI) of a anti S-RBD IgG level at 4 weeks after vaccination were 56.05 (13.2,238.2) and 3633 (2689,4908) BAU/mL in on-therapy and off-therapy group, respectively, p<0.001. The sVNT (95%CI) of delta strain were 26% (5.85-73.55%) and 97.05% (96.0-97.4%) as the seroprotective level which were 33.3% in on-therapy group and 100% in off-therapy group (p<0.001). 14 children in on-therapy group need an additional dose. CONCLUSION: After complete vaccination, the seroprotective rate and antibody level in pediatric and adolescent patients with cancer and hematologic disease who receive immunosuppressive agents are quite low, compared with patients who had complete treatment. Additional dose of primary series should be offered.