Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin's lymphoma Berlin-Frankfurt-Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% [95% Confidence Interval (CI), 69.0%-83.9%] and 92.3% (95% CI,86.1%-95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5%-95.5%, and 67.9% (95% CI, 55.4%-77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6%-19.0%), 65.7% (95% CI, 47.6%-78.9%), 55.7% (95% CI, 26.2%-77.5%), and 70.7% (95% CI, 48.6%-84.6%), respectively. At the end of follow-up, one of the 5 patients who received maintenance therapy with VBL relapsed, and seven patients receiving ALK inhibitor maintenance therapy did not experience relapse. Conclusion: This study has confirmed the poor prognostic of MDD (+) ，high risk site and SC/LH ,but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Treatment Outcome of Response-Based Radiation Therapy in Children and Adolescents With Central Nervous System Nongerminomatous Germ Cell Tumors: Results of a Prospective Study.

PURPOSE: The optimal dose and range of radiation therapy for central nervous system nongerminomatous germ cell tumors (NGGCTs) have not been uniformly established. Therefore, this study aimed to investigate the effect of individualized radiation therapy, based on the response to induction chemotherapy combined with surgery, on the prognosis of patients with NGGCTs. METHODS AND MATERIALS: Based on the imaging examination and tumor markers after induction chemotherapy and pathologic results of second-look surgery, patients with NGGCT received different radiation therapy strategies, including 30.6 Gy whole ventricular irradiation + tumor-bed boost to 54 Gy, 30.6 Gy craniospinal irradiation + tumor-bed boost to 54 Gy, 36 Gy craniospinal irradiation + tumor-bed boost to 54 Gy, and 36 Gy craniospinal irradiation + 54 Gy tumor-bed boost with 45 Gy to metastatic spinal lesions. RESULTS: A total of 51 patients were enrolled between January 2015 and March 2021, with a median age of 10.3 years. The 3-year event-free survival and overall survival (OS) of the entire cohort were 70.2% ± 6.9% and 77.5% ± 6.0%, respectively. The 3-year OS of patients achieving partial response after induction chemotherapy was higher than that of patients with stable disease (P = .03) or progressive disease (P = .002). The 3-year event-free survival and OS of the 18 patients receiving 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed boost were 88.9% ± 7.4% and 94.4% ± 5.4%, respectively. CONCLUSIONS: The results suggest that an individualized radiation therapy strategy based on response to induction chemotherapy and surgery is a feasible and promising means of achieving reduction in dose and extent of radiation in patients while still providing good response.

Treatment outcomes for response-based radiotherapy in children and adolescents with central nervous system germinoma: a prospective study.

PURPOSE: The optimal dose and range of radiotherapy for central nervous system (CNS) germinoma have not yet been established. This study aimed to investigate the effects of individualized radiotherapy on the prognosis of patients with germinoma. METHODS: Based on imaging examination, tumor markers, and pathologic results, patients with germinoma received different radiotherapy strategies, including R1 (24 Gy whole ventricular irradiation + tumor-bed boost to 40 Gy), R2 (24-30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy), R3 (24 Gy craniospinal irradiation + tumor-bed boost to 40 Gy), and R4 (30 Gy craniospinal irradiation + tumor-bed boost to 54 Gy with 45 Gy to spinal metastasis). RESULTS: A total of 77 patients were enrolled in this study between January 2015 and March 2021. The 3-year event-free survival (EFS) and overall survival (OS) of the whole cohort were 94.7% ± 2.6% and 96.0% ± 2.3%, respectively. The 3-year EFS for patients with localized and metastatic disease were 96.6% ± 2.4% and 89.2% ± 7.2%, respectively. The 3-year EFS of patients receiving R1, R2, R3, and R4 radiotherapy were 100%, 94.1% ± 5.7%, 100%, and 86.2% ± 9.1%, respectively. CONCLUSION: Good prognosis was still achieved after reducing dose and extent of radiation for the patients who achieved complete response (CR) after induction chemotherapy or pathological CR after second-look surgery.

Long-term follow-up results of pediatric and adolescent patients with localized Ewing sarcoma treated based on stratified modalities.

BACKGROUND: Compared with other pediatric tumors, little advances were achieved in studies on the stratified treatment in localized Ewing sarcoma. Most pediatric oncology groups treated Ewing sarcoma according to whether there was an existing metastasis, without involving more prognostic factors. In this study, patients with localized Ewing sarcoma were divided into resectable and unresectable groups at diagnosis and received chemotherapy with different intensity, for the purpose of achieving good efficacy, avoiding overtreatment and reducing unnecessary toxicity. METHODS: A total of 143 patients with a median age of 10 years old diagnosed with localized Ewing sarcoma in this retrospective study were divided into two cohorts (Cohort 1, n = 42; Cohort 2, n = 101) and patients in Cohort 2 received chemotherapy with different intensity (Regimen 1, n = 52; Regimen 2, n = 49). Outcomes were analyzed using the Kaplan-Meier method to estimate event-free survival (EFS) and overall survival (OS), and the curves were compared using the log-rank test. RESULTS: The 5-year EFS and 5-year OS for all the patients were 69.0% and 77.5%. The 5-year EFS for Cohort 1 and Cohort 2 were 76.0% and 66.1% (p = 0.31), and the 5-year OS were 83.0% and 75.1% (p = 0.30), respectively. In Cohort 2, the 5-year EFS rate of patients treated with Regimen 2 was significantly higher than that of patients treated with Regimen 1 (74.5% vs. 58.3%, p = 0.03). CONCLUSIONS: According to whether a grossly complete resection was received at the time of diagnosis, localized Ewing sarcoma patients in this study were stratified into two groups and received different intensities of chemotherapy, which achieved good efficacy and avoided overtreatment and reduced unnecessary toxicity.

Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma.

High-risk neuroblastoma (NB) is sensitive to chemotherapy but susceptible to chemoresistance. In this study, we aimed to analyze the incidence of chemoresistance in high-risk NB patients and to explore the role of autophagy in NB chemoresistance. We retrospectively analyzed the incidence of changing the chemotherapy regimen due to disease stabilization or disease progression during induction chemotherapy in high-risk NB patients, which was expressed as the chemoresistance rate. The autophagy levels were probed in tumor cells exposed to first-line chemotherapy agents. The sensitivity of tumor cells to chemotherapy agents and apoptosis rate were observed after inhibiting autophagy by transfection of shRNA or chloroquine (CQ). This study included 247 patients with high-risk NB. The chemoresistance rates of patients treated with cyclophosphamide + adriamycin + vincristine (CAV) alternating with etoposide + cisplatin (EP) (Group 1) and CAV alternating with etoposide + ifosfamide + cisplatin (VIP) (Group 2) was 61.5% and 39.9% (P = 0.0009), respectively. Group 2 had better survival rates than group 1. After exposure to cisplatin, cyclophosphamide, and etoposide, the autophagy-related proteins LC3-I, LC3-II, and Beclin-1 were upregulated, and the incidence of autophagy vesicle formation and the expression of P62 were increased. Chemotherapeutic agents combined with CQ significantly increased the chemotherapeutic sensitivity of tumor cells and increased the cell apoptosis. The downregulated expression of Beclin-1 increased the sensitivity of tumor cells to chemotherapeutics. Our results suggest that increasing the chemotherapy intensity can overcome resistance to NB. Inhibition of autophagy is beneficial to increase the sensitivity of NB to chemotherapy agents.