Background: Metronomic chemotherapy (MC) is based on chronic administration of chemotherapeutic agents at minimally toxic doses without prolonged drug-free breaks. MC has a multitargeted action of tumor angiogenesis inhibition and anticancer immune response stimulation and may also directly affect tumor cells to induce tumor dormancy. At our institute, MC has been introduced to treat patients with refractory/relapsed pediatric tumors. Methods: We retrospectively analyzed the data of pediatric patients with relapsed/refractory solid tumors who received treatment, including low-dose continuous administration of anti-cancer drugs. Results: 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. Eleven of 18 patients, with tumor stabilization or maintained remission/stable disease, showed certain advantages in terms of overall survival rate. Even if limited to progressive disease, the survival time of responders was prolonged compared to non-responders (median 19.4 months vs. 4.7 months, P = 0.012). Conclusion: Approximately half of the patients demonstrated temporal tumor stabilization and improved survival time, although most patients had progressive disease, and MC was administered as palliative therapy. Large-scale studies on pediatric MC are rare; however, 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, both in terms of prolonging life and maintaining quality of life.

Background: The prognosis of metastatic hepatoblastoma remains poor; to improve it, pulmonary metastasis must be controlled. Indocyanine green (ICG) fluorescent imaging has been used recently for lung metastasectomy. The objective of our study was to clarify the usefulness of ICG imaging for lung metastasectomy of hepatoblastoma using detailed clinicopathological analysis. Procedure: Patients with hepatoblastoma who underwent resection of pulmonary metastases with ICG fluorescent imaging were studied using retrospective analysis of clinical information, a review of their surgical records, and a histological analysis of their metastatic nodules. Results: Sixteen patients were enrolled. In total, 61 ICG-imaging-guided pulmonary metastasectomies were performed, and 350 ICG-positive and 23 ICG-negative specimens were identified. Tumors were confirmed in 250 of the ICG-positive specimens, including eight nonpalpable nodules, on microscopic examination. One hundred ICG-positive specimens and histologically tumor-negative specimens showed histological changes suggesting the regression of a tumor or bloodstream disturbance. The palpable ICG-negative tumors showed more-severe atypia than the ICG-positive tumors. Conclusions: This study demonstrates the high sensitivity of ICG imaging in detecting metastatic lesions of hepatoblastoma. Histological examinations suggested that ICG imaging detects not only tumor cells, but also nontumorous pulmonary tissues affected by bloodstream disturbance. Because a number of false-positive specimens were detected, further optimization of the dose of ICG and the timing of its administration may be required for thorough metastasectomy. Several false-negative specimens were also detected, suggesting the presence of ICG-negative metastatic tumors. Palpation during operation and imaging studies remain essential for detecting metastatic lesions, even in the era of ICG imaging.

Background: The prognosis of children with acute myeloid leukemia (AML) has improved with the efficacy of hematopoietic cell transplantation as a second-line therapy and improvements in supportive care following anthracycline- and cytarabine-based chemotherapy; however, the outcomes of children with relapsed AML still remain unsatisfactory. Procedure: In order to identify prognostic factors and improve their prognosis, we analyzed 111 patients who relapsed after treatment with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol and who were registered in the retrospective JPLSG AML-05R study. Results: The 5-year overall survival rate was 36.1%. The major determinant of survival was duration from the diagnosis to relapse. The mean duration in the non-surviving group (10.1 ± 4.1 months) was shorter than that in the surviving group (16.3 ± 8.3 months) (p<0.01). Moreover, achieving a second complete remission (CR2) prior to hematopoietic cell transplantation was associated with a good prognosis (p<0.01). Etoposide, cytarabine and mitoxantrone (ECM)- or fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG)-based regimens were therefore recommended for reinduction therapy (p<0.01). A genetic analysis also revealed the prognostic significance of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication as a poor prognostic marker (p=0.04) and core binding factor-AML, t(8;21) and inv(16), as good prognostic markers (p<0.01). Conclusions: Achieving a CR2 prior to HCT is important in order to improve the prognosis of relapsed pediatric AML. Recent molecular targeted therapies, such as FLT3 inhibitors, may contribute to overcome their prognoses. Larger prospective investigations are necessary to establish individualized treatment strategies for patients with relapsed childhood AML.