Oral vinorelbine and continuous low doses of cyclophosphamide in pediatric rhabdomyosarcoma: a real-world study.

Introduction: Metronomic maintenance therapy (MMT) has significantly improved the survival of patients with high-risk rhabdomyosarcoma in clinical trials. However, there remains a lack of relevant data on its effectiveness in real-world situations. Methods: We retrospectively retrieved data of 459 patients < 18 years of age diagnosed with rhabdomyosarcoma at Sun Yat-sen University Cancer Center from January 2011 to July 2020 from our database. The MMT regimen was oral vinorelbine 25-40 mg/m2 for twelve 4-week cycles on days 1, 8, and 15, and oral cyclophosphamide 25-50 mg/m2 daily for 48 consecutive weeks. Results: A total of 57 patients who underwent MMT were included in the analysis. The median follow-up time was 27.8 (range: 2.9-117.5) months. From MMT to the end of follow-up, the 3-year PFS and OS rates were 40.6% ± 6.8% and 58.3% ± 7.2%, respectively. The 3-year PFS was 43.6% ± 11.3% in patients who were initially diagnosed as low- and intermediate-risk but relapsed after comprehensive treatment (20/57), compared with 27.8% ± 10.4% in high-risk patients (20/57) and 52.8% ± 13.3% in intermediate-risk patients who did not relapse (17/57). The corresponding 3-year OS for these three groups was 65.8% ± 11.4%, 50.1% ± 12.9%, and 55.6% ± 13.6%, respectively. Conclusion: We present a novel study of MMT with oral vinorelbine and continuous low doses of cyclophosphamide in real-world pediatric patients with RMS. Our findings showed that the MMT strategy significantly improved patient outcomes and may be an effective treatment for high-risk and relapsed patients.

Risk factors for totally implantable access ports-associated thrombosis in pediatric oncology patients.

The application of totally implantable access ports (TIAPs) reduces treatment-related discomfort; however, the existence of catheter may cause side effects, with the most common one being the occurrence of TIAPs-associated thrombosis. The risk factors for TIAPs-associated thrombosis in pediatric oncology patients have not been fully described. A total of 587 pediatric oncology patients undergoing TIAPs implantation at a single center over a 5-year period were retrospectively analyzed in the present study. We investigated the risk factors for thrombosis, emphasizing the internal jugular vein distance, by measuring the vertical distance from the highest point of the catheter to the upper border of the left and right extremitas sternalis claviculae on chest X-ray images. Among 587 patients, 143 (24.4%) had thrombosis. Platelet count, C-reactive protein, and the vertical distance from the highest point of the catheter to the upper border of the left and right extremitas sternalis claviculae were demonstrated to be the main risk factors for the development of TIAPs-associated thrombosis. TIAPs-associated thrombosis, especially asymptomatic events, is common in pediatric cancer patients. The vertical distance from the highest point of the catheter to the upper border of the left and right extremitas sternalis claviculae was a risk factor for TIAPs-associated thrombosis, which deserved additional attention.

The Efficacy and Safety of Anlotinib in Pediatric Patients With Refractory or Recurrent Solid Tumors.

Objective: Refractory or recurrent pediatric solid tumors lack effective treatments, and are associated with dismal outcomes. Hence, there is an urgent need for a novel therapeutic strategy. This study aimed to evaluate the efficacy and safety of anlotinib, a novel oral multi-kinase angiogenesis inhibitor, in pediatric patients with refractory or recurrent solid tumors. Methods: This single-institutional, observational retrospective study was conducted in Sun Yat-sen University Cancer Center, China. Refractory or recurrent pediatric solid tumor patients treated with anlotinib between 2018 and 2020 were evaluated. Results: Forty-one and 30 patients were enrolled to evaluate the efficacy and safety of anlotinib, respectively. There was partial response in five patients, stable disease in 22 patients, no patient with complete response, with an objective response ratio of 12.2% (5/41; 95% CI 1.7-22.7). The disease control rate was 65.9% (27/41; 95% CI 50.7-81) and the median progression-free survival was 2.87 months (95% CI 0.86-4.88). The incidence rates of any grade and grade 3-4 adverse events were 80% (24/30) and 23.3% (7/30), respectively. Bleeding (20%, 6/30), hand-foot syndrome (16.7%, 5/30), and diarrhea (13.3%, 4/30) were the most common adverse events. Grade 3-4 adverse events included hypertension, hand-foot syndrome, diarrhea, anemia, and thrombocytopenia. There were no adverse events-related deaths. Conclusion: For heavily pretreated pediatric solid tumors, anlotinib monotherapy and its combination with chemotherapy may be an effective treatment option with tolerable adverse events. It is necessary to monitor blood pressure when using anlotinib in children.

Irinotecan Plus Doxorubicin Hydrochloride Liposomes for Relapsed or Refractory Wilms Tumor.

PURPOSE: The prognosis of relapsed or refractory pediatric Wilms tumor (WT) is dismal, and new salvage therapies are needed. This study aimed to evaluate the efficacy of the combination of irinotecan and a doxorubicin hydrochloride liposome regimen for relapsed or refractory pediatric WT. PATIENTS AND METHODS: The present study enrolled relapsed or refractory pediatric WT patients who were treated with the AI regimen (doxorubicin hydrochloride liposomes 40 mg/m2 per day, day 1, and irinotecan 50 mg/m2 per day with 90-min infusion, days 1-5; this regimen was repeated every 3 weeks) at Sun Yat-sen University Cancer Center from July 2018 to September 2020. The response was defined as the best-observed response after at least two cycles according to the Response Evaluation Criteria of Solid Tumors (RECIST 1.1), and toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 4.03). RESULTS: A total of 16 patients (male:female, 8:8) with a median age of 4.2 years (0.5-11 years) with relapsed or refractory disease were enrolled in this study, including 14 patients with relapsed disease and two patients with refractory disease. These patients received 1-8 courses (median, 3 courses) of the AI regimen. Fourteen patients were assessable for response: two with complete response (CR), five with partial response (PR), two with stable disease (SD), and five with progressive disease (PD). The objective response rate was 50% (two CR, five PR), and the disease control rate was 64% (two CR, five PR, and two SD). Seven out of 14 patients (50%) were alive at the last follow-up, ranging from 2.6 to 32.4 months. The median progression-free survival and median overall survival were 3.5 months (range 0.5-12 months) and 8 months (range 1-28 months), respectively. Sixteen patients were assessable for toxicity, with the most common grade 3 or 4 adverse events being alopecia (62%), leukopenia (40%), abdominal pain (38%), diarrhea (23%), and mucositis (16%), etc. No fatal adverse events have been observed, and modest adverse effects can be administered. CONCLUSION: Irinotecan and doxorubicin hydrochloride liposome regimens have positive efficacy on relapsed or refractory pediatric WT with well-tolerated toxicity. A prospective clinical trial is warranted.

Quality of life and related demographic factors in long-term survivors of childhood non-Hodgkin's lymphoma. / å„¿ç«¥éžéœå¥‡é‡‘æ·‹å·´ç˜¤é•¿æœŸç”Ÿå­˜è€ ç”Ÿæ´»è´¨é‡åŠç›¸å ³äººå£å­¦å› ç´ ç ”ç©¶.

OBJECTIVES: To evaluate the quality of life and related demographic factors in long-term survivors of childhood non-Hodgkin's lymphoma (NHL). METHODS: A retrospective analysis was performed on the medical and demographic data of the NHL patients who received treatment in the Sun Yat-sen University Cancer Center and achieved long-term survival at follow-up, with an age of <18 years at initial diagnosis and a present age of ≥18 years. A questionnaire survey was performed using 36-Item Short-Form Health Survey (SF-36) and the symptom subscale of the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30). The health status of long-term survivors of NHL was evaluated by comparing the scores of various dimensions of the SF-36 scale of general adult population in the United States (American norm) and those of the SF-36 scale of general adult population in Hong Kong, China (Hong Kong norm). The correlation between the score of each dimension of the scale and demographic characteristics was evaluated. The symptoms of long-term NHL survivors were evaluated according to the score of QLQ-C30 scale. RESULTS: A total of 23 patients with NHL with complete follow-up data were enrolled. The pathological types included diffuse large B-cell lymphoma in 10 patients, Burkitt lymphoma in 4 patients, T-cell lymphoblastoma in 5 patients, B-cell lymphoblastoma in 3 patients, and natural killer/T cell lymphoma in 1 patient. All patients received the chemotherapy regimen containing anthracyclines and alkylating agents. The median present age was 26.2 years (range: 16.9-55.8 years), and the median age at initial diagnosis was 10.4 years (range: 2.4-17.6 years). Among the 23 patients, 6 were married and had children and 2 had chronic diseases. There was no significant difference between the long-term survivors and the US norm in role physical, general health, role-emotional, and mental health (P>0.05), while the long-term survivors had significantly better scores of the other dimensions than the US norm (P<0.05). Similar results were obtained for the comparison between the long-term survivors and the China Hong Kong norm. Age at initial diagnosis was negatively correlated with the scores of social functioning, role physical, and general health in the SF-36 scale (P<0.05), and the present age of patients was positively correlated with the score of physical functioning and was negatively correlated with the score of general health (P<0.05). The urban and rural distribution of patients was related to the general health status (P<0.05). In addition, the long-term survivors of childhood NHL had relatively low scores of the symptom domain of QLQ-C30, and few moderate or severe symptoms were found. CONCLUSIONS: Long-term survivors of childhood NHL tend to have a good overall health status, with no significant differences compared with the general population. Age at initial diagnosis is the main demographic factor that affects patients' quality of life. Citation.

Bioinformatics Analysis and Validation Identify CDK1 and MAD2L1 as Prognostic Markers of Rhabdomyosarcoma.

PURPOSE: The goal of the current study was to identify potential prognostic biomarkers of rhabdomyosarcoma (RMS). MATERIALS AND METHODS: We screened chip sequencing datasets of RMS through the gene expression omnibus (GEO) database. A total of 74 RMS patient tissues and 39 normal muscle cell tissues were analyzed. Limma R software was used to identify the differentially expressed genes (DEGs) between RMS tissues and normal controls. The GO plot R package was used to visualize the results of the GO analysis. We screened for pathaffy package enrichment of DEGs by the Kyoto Encyclopedia of Genes and Genomes (KEGG). The cutoff criterion was a P-value <0.05. Immunohistochemistry (IHC) was applied to validate the expression of CDK1 (cyclin-dependent kinases 1) and MAD2L1 (Mitotic Arrest Deficient 2 Like 1) in RMS. RESULTS: We obtained a total of 498 up- and 480 down-regulated DEGs. The hub genes are mainly involved in the cell cycle and P53 singling pathway. CDK1 expression was associated with tumor size and COG-STS (Children's Oncology Group-soft tissue sarcoma) staging of RMS. For the low CDK1 expression group and high CDK1 expression group, the 5-year overall survival (OS) rate was 83.0% vs 63.5% (P = 0.004), and the 5-year event-free survival (EFS) rate was 47.5% vs 27.5% (P = 0.049) respectively. When compared low MAD2L1 expression group with high MAD2L1 expression group, the 5-year OS rate was 80.0% vs 43.2% (P = 0.001), and the 5-year EFS rate was 45.1% vs 21.8% (P = 0.038), respectively. If patients were divided into three groups: low CDK1 and low MAD2L1 expression group, high CDK1 or high MAD2L1 expression group, and high CDK1 and high MAD2L1 expression group, the 5-year OS rate was 87.1%, 58.6%, 39.6% (P = 0.001), while the 5-year EFS rate of RMS patients was 54.2%, 23.2%, 21.7% (P = 0.028), respectively. CONCLUSION: This study has identified that CDK1 and MAD2L1 were adverse prognostic factors of RMS.

The Efficacy and Safety of Apatinib in Refractory/Relapse Advanced Pediatric Solid Tumor: A Retrospective Study.

BACKGROUND: The prognosis of recurrent or refractory advanced childhood solid tumor patients is very poor and new therapeutic strategies are in urgent need. This study aimed to determine the efficacy and safety of apatinib in pediatric refractory/relapse advanced solid tumor patients. PATIENTS AND METHODS: The study retrospectively reviewed recurrent or refractory advanced pediatric solid tumor patients who were treated with apatinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor receptor-2 (VEGFR2), at the Sun Yat-sen University Cancer Center (China) from January 2016 to March 2019. RESULTS: Fifty-six patients were included in the safety evaluation and 49 patients were included in the efficacy evaluation. The objective responses rate (ORR) was 26.5% (95% CI 15-41): 0 CR (complete response) and 13 PR (partial response). Disease control rate (DCR) (CR+PR+SD) was 79.6% (95% CI 65-90). The median progression-free survival (PFS) was 4.0 months (95% CI 2.6-5.4). There was no significant difference for ORR or PFS between the A (apatinib monotherapy), A+MT (apatinib combined with oral metronomic therapy) and A+SC (apatinib combined with salvage combination chemotherapy) group (p>0.05). The most common grade 3 or 4 adverse events were neutropenia (9[16.1%]), thrombocytopenia (8[14.3%]), hand-foot syndrome (3[5.4%]), hypertension (3[5.4%]), anaemia (3[5.4%]) and mucositis (2[3.6%]). Hypertension was the most serious adverse event and one death that occurred was considered as drug-related. CONCLUSION: Apatinib showed promising clinical activity in heavily treated recurrent or refractory advanced childhood solid tumor patients. However, it is necessary to pay special attention to monitoring blood pressure when using apatinib in children. Prospective randomized controlled clinical trial is warranted.