Successful treatment of young childhood standard-risk hepatoblastoma with cisplatin monotherapy using a central review system.

BACKGROUND: The JPLT3-S (Japanese Study Group for Pediatric Liver Tumors-3) study, conducted cisplatin (CDDP) monotherapy for young children (<3 years old) with standard-risk hepatoblastoma (HB) using a central review system in Japan. In the previous JPLT2 study, cases with resectable tumors without any annotation factors in the PRETEXT (PRETreatment EXTent of disease) classification (standard-risk HB) showed favorable outcomes with treatment consisting of CDDP and pirarubicin, but showed toxicities and late complications. In the JPLT3-S trial, a less intense regimen consisting of CDDP alone was evaluated. METHODS: Patients who were less than 3 years of age and with PRETEXT I, II, or III HB without any annotation factors (e.g., E1, E1a, E2, E2a, H1, N1, P2, P2a, V3, and V3a) were eligible for inclusion in this study. In this trial, the central radiological and pathological features of all patients were reviewed. The primary outcome was the 3-year progression-free survival (PFS). RESULTS: A total of 38 patients (23 female) were included. The median patient age was 12 months (range: 2-34). Two patients discontinued treatment because of progressive disease, and five patients discontinued treatment for other reasons. The 3-year PFS rate was 93.9% (95% confidence interval [CI]: 86.4%-100%). All 38 patients survived (follow-up period 38-98 months), and the OS rate was 100% (CI: 100). Eighteen of the 38 patients (47.4%) experienced ototoxicity as a late complication. CONCLUSION: CDDP monotherapy regimen is feasible in young patients with localized HB, as classified by a central review.

Metronomic Chemotherapy for Pediatric Refractory Solid Tumors: A Retrospective Single-center Study.

Metronomic chemotherapy (MC) is based on chronic administration of chemotherapeutic agents at minimally toxic doses without prolonged drug-free breaks, that inhibits tumor angiogenesis and induces tumor dormancy. This study aimed to determine the efficacy of MC for pediatric refractory solid tumors. We retrospectively analyzed the data of pediatric patients with relapsed/refractory solid tumors who received treatment, including low-dose continuous administration of anticancer drugs, at our institute. Of the 18 patients, the disease statuses at the initiation of MC were complete remission (n=2), partial remission/stable disease (n=5), and progressive disease (n=11). The overall survival rate was 61% at 12 months and 34% at 24 months, and the progression-free survival rate was 21% at 12 and 24 months. Although only 5 of the 18 patients showed certain tumor regression or maintained remission, tumors that stabilized, maintained remission/stable disease, and showed certain advantages in terms of overall survival rate, even if limited to progressive disease. Approximately half of the patients demonstrated temporal tumor stabilization and improved survival time. Overall, previous reports and the present study support the conclusion that MC has the potential to play an important role in pediatric cancer treatment during the advanced stage.

Localized anaplastic lymphoma kinase-positive histiocytosis in a cerebellar hemisphere with long-term treatment: illustrative case.

BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive histiocytosis (ALK-H) is an emerging entity in the category of histiocytic neoplasms that was first reported as a multisystemic disease in three infants in 2008. The clinicopathological spectrum of ALK-H has been expanded to include localized disorders in specific organs, but the features of this subtype are not well known. The authors report a case of ALK-H localized in the central nervous system that was difficult to treat and review the relevant literature. OBSERVATIONS: The authors reviewed archival histiocytic tumors at their institute and found a pediatric case of ALK-H localized in a cerebellar hemisphere that had previously been reported as histiocytic sarcoma. Chemotherapy (approximately 1 year), additional surgery, and conventional chemotherapy (approximately 2.5 years) led to clinical remission, and maintenance chemotherapy was continued (approximately 1.5 years). Three years after completing treatment, a high-grade glioma was found in a cerebral hemisphere, and the patient died of the glioma 2 years later. LESSONS: Although the prognosis of ALK-H is generally good according to prior cases, the authors' case required long-term conventional chemotherapy, suggesting the tumor displayed aggressive characteristics. Early administration of ALK inhibitors may be necessary.

Establishment and characterization of a novel MDM2/MYCN-co-amplified neuroblastoma cell line, NBN-SHIM, established from a late recurrent stage MS tumor.

The biological heterogeneity of neuroblastoma underscores the need for an in vitro model of each molecularly defined subgroup to investigate tumorigenesis and develop targeted therapies. We have established a permanently growing cell line from a 12-year-old girl who developed a late recurrent stage MS, MDM2-amplified neuroblastoma arising in the liver and performed histological, molecular, cytogenetic, exome, and telomere analyses of the recurrent tumor and the cell line. On histology, the recurrent tumor was immunoreactive for TP53, CDKN1A, and MDM2. A molecular cytogenetic study of the recurrent tumor revealed the amplification of MDM2 but no amplification of MYCN. The established cell line, NBM-SHIM, showed amplification of both MDM2 and MYCN on double-minute chromosomes. A copy number evaluation based on exome data confirmed the finding for MYCN and MDM2 and further identified high ploidy on CDK4 and GLI2 loci in the recurrent tumor and the cell line. The telomere maintenance mechanism on the cell line is unusual in terms of the low expression of TERT despite MYCN amplification and alternative lengthening of telomeres suggested by positive value for C-circle assay and telomere contents quantitative assay. The cell line is unique because it was established from a MYCN-nonamplified, MDM2-amplified, late-relapsed stage MS neuroblastoma, and MYCN amplification was acquired during cell culture. Therefore, the cell line is a valuable tool for investigating neuroblastoma tumorigenesis and new molecular targeted therapies for disrupted ARF-TP53-MDM2 pathway and amplification of MDM2 and CDK4.