A clinical prognostic model of oxidative stress-related genes linked to tumor immune cell infiltration and the prognosis of ovarian cancer patients.

Background: According to statistics, ovarian cancer (OV) is the most prevalent type of gynecologic malignancy and has the highest mortality rate of all gynecologic tumors. Although several studies have shown that oxidative stress (OS) contributes significantly to the onset and progression of cancer, the role of OS in OV needs to be investigated further. Thus, it is critical to comprehend the function of OS-related genes in OV. Methods: In this study, all data related to the transcriptome and clinical status of the patients were retrieved from "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) databases. Using the unsupervised cluster analysis technique, all patients with OV were classified into two different subtypes (categories) based on the OS gene. All hub genes were screened using the weighted gene co-expression network analysis (WGCNA). Since the hub genes and the differentially expressed genes (DEGs) in both categories were found to intersect, the univariate Cox regression analysis was implemented. A multivariate Cox analysis was also performed to construct a novel clinical prognosis model, which was validated using data from the GEO cohort. In addition, the relationship between risk score and immune cell infiltration level was evaluated using CIBERSORT. Finally, qRT-PCR was used to confirm the expression of the genes used to construct the model. Results: Two subtypes of OS were obtained. The findings indicated that OS-C1 had a better survival outcome than OS-C2. The results of WGCNA yielded 112 hub genes. For univariate COX regression analyses, 49 OS-related trait genes were obtained. Finally, a clinical prognostic model containing two genes was constructed. This model could differentiate between patients with OV having varying years of survival in the TCGA and GEO cohorts. The model risk score was verified as an independent prognostic indicator. According to the results of CIBERSORT, many tumor-infiltrating immune cells were found to be significantly related to the risk score. Furthermore, the results revealed that patients with low-risk OV in the CTLA4 treatment group had a high likelihood of benefiting from immunotherapy. qRT-PCR results also showed that the expression of MARVELD1 and VSIG4 was high in the OV samples. Conclusions: Analysis of the results suggested that the newly developed model, which contained two characteristic OS-related genes, could successfully predict the survival outcomes of all patients with OV. The findings of this study could offer valuable information and insights into the refinement of personalized therapy and immunotherapy for OV in the future.

Staphylococcus hsinchuensis sp. nov., Isolated from Soymilk.

A novel coagulase-negative Staphylococcus strain (H164T) was isolated from soymilk in Taiwan. Comparative sequence analysis of the 16S rRNA gene revealed that the H164T strain is a member of the genus Staphylococcus. We used multilocus sequence analysis (MLSA) and phylogenomic analyses to demonstrate that the novel strain was closely related to Staphylococcus gallinarum, Staphylococcus nepalensis, Staphylococcus cohnii, and Staphylococcus urealyuticus. The average nucleotide identity and digital DNA-DNA hybridization values between H164T and its closest relatives were <95% and <70%, respectively. The H164T strain could also be distinguished from its closest relatives by the fermentation of d-fructose, d-maltose, d-trehalose, and d-mannitol, as well as by the activities of α-glucosidase and alkaline phosphatase. The major cellular fatty acids were C15:0 iso and C15:0 anteiso, and the predominant menaquinones were MK-7 and MK-8, respectively. The major cellular fatty acids and predominant menaquinones were C15:0 iso and C15:0 anteiso and MK-7 and MK-8, respectively. In conclusion, this strain represents a novel species, named Staphylococcus hsinchuensis sp. nov., with the type strain H164T (=BCRC 81404T = NBRC 116174T).

Characteristics of patients with recurrent retinoblastoma: a survival analysis.

BACKGROUND: Management guidelines and corresponding survival data for patients with recurrent retinoblastoma (RB) are lacking. This study aimed to summarize the clinical characteristics of patients with recurrent RB and analyze their survival outcomes. METHODS: We retrospectively analyzed 68 patients with recurrent RB who underwent treatment in our institution from January 2016 to December 2020. Patients were grouped according to location of recurrence: intraocular, orbital, and distant metastasis. RESULTS: The male:female ratio was 1.3:1 and the median age at recurrence was 37.5 months (range, 30.3-62.8). The number of patients in the intraocular recurrence, orbital recurrence, and metastasis groups was 13 (19.1%), 23 (33.8%), and 32 (47.1%), respectively. Thirty patients died, 36 were alive at last follow-up, and two were lost to follow-up. Eye enucleation was performed in 94.1% of patients. Five-year overall survival in patients with intraocular recurrence, orbital recurrence, and metastasis was 84.6%, 69.6%, and 31.3%, respectively (P = 0.001). Most deaths occurred within 2 years of recurrence. Presence of high-risk pathological factors, central nervous system invasion, and absence of combination therapy were independent predictors of worse 5-year overall survival. CONCLUSION: The rate of eye preservation in survivors of recurrent RB was very low. Although 5-year overall survival in patients who underwent treatment for intraocular and orbital recurrence was high, it was low in those with metastasis. RB patients may need lifelong follow-up for recurrence and secondary malignancy.

Prognostic factors for intermediate- or high-risk neuroblastomas in children in China.

BACKGROUND: Evidence regarding the characteristics and prognosis of neuroblastoma (NBL) in China is limited. We aimed to investigate the characteristics and prognosis of intermediate- or high-risk NBL in children in China. METHODS: We included 147 patients with intermediate- or high-risk NBL evaluated from January 2006 to March 2015. The patients were aged 1 month to 15.5 years, 66% of them were boys, and 117 (79.6%) were diagnosed with high-risk NBL. RESULTS: After a median follow-up of 32.5 months, 80 (45.6%) patients survived, with a median survival time of 48 months (95% confidence interval [CI]: 36.41-59.59). High-risk patients (hazard ratio [HR]: 12.467; 95% CI: 11.029-12.951), partial response (PR) (HR: 1.200; 95% CI: 1.475-2.509) or progression disease (PD) (HR: 1.924; 95% CI: 1.623-3.012) after induction chemotherapy, and intracranial metastasis (HR: 3.057; 95% CI: 0.941-4.892) were independent risk factors for survival (p < 0.05) and postrelapse survival (p < 0.05). NBL relapse, male sex, and PR or PD after induction chemotherapy were risk factors for event-free survival (p < 0.05). CONCLUSIONS: In addition to previously established independent risk factors, such as age, risk group, and relapse, efficacy of induction chemotherapy and intracranial metastasis play significant roles in the prognosis of NBL.

Clinical features and outcomes of infantile soft-tissue sarcoma: A multicenter retrospective study in Beijing.

Background: Soft-tissue sarcomas during infancy are rare and understudied. With no data on this specific condition, we performed a retrospective study of infant-onset sarcomas based on a multi-institutional cohort in Beijing, China, collected over the past decade. We reviewed infantile soft-tissue sarcomas' clinical characteristics, treatments, and outcomes. Materials and Methods: The patients with soft-tissue sarcoma diagnosed from 0 to 12 months in four primary children's hospitals in Beijing from January 2010 to December 2019 were evaluated. Results: Fifty-one patients were enrolled, including 31 males and 20 females. The median age at the diagnosis was five months (range, 0-12), and seven (13.7%) patients were diagnosed in the first month of their life. Histologically, twenty-five patients were diagnosed with rhabdomyosarcoma (RMS), six were diagnosed with extraosseous Ewing sarcoma (EES), and twenty were diagnosed with nonrhabdomyosarcoma soft-tissue sarcoma (NRSTS). The treatment principles and details of RMS focused on reference to the Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols. For EES and NRSTS, chemotherapy was prescribed according to children's oncology group protocols. The five-year EFS/OS rates of RMS were 26.4% ± 19.5%/56.2 ± 17.8%, the five-year EFS/OS rate of EES was 50% ± 20.4%, and the five-year EFS/OS of NRSTS was 85.2% ± 9.8%/100%. Conclusions: Infant-onset soft-tissue sarcoma is heterogeneous. The primary location of the abdominal or pelvic cavity of RMS and EWS was at a later stage and had a poorer prognosis. Multimodal therapy resulted in successful disease control for the majority of patients. Standardization of treatment protocols will facilitate care for such challenging conditions.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

Neoadjuvant chemotherapy or upfront surgery in hepatoblastoma: A multicenter retrospective study.

BACKGROUND: We retrospectively investigated the role of neoadjuvant chemotherapy in low-risk patients with hepatoblastoma (HB) who underwent curative resection between February 2009 and December 2017. We also verified the feasibility of the risk stratification system to select the optimal patients for upfront surgery. PROCEDURE: We compared 5-year overall survival (OS) and event-free survival (EFS) between the upfront surgery (n = 26) and neoadjuvant chemotherapy (n = 104) groups at three oncology centers in Beijing, China. To reduce the effect of covariate imbalance, propensity score matching (PSM) was used. We explored whether preoperative chemotherapy affected surgical outcomes and identified the risk factors for events and death, including resection margin status, PRETreatment EXTent of disease stages, age, sex, pathology classification, and α-fetoprotein levels. RESULTS: The median follow-up period was 64 (interquartile range 60-72) months. After PSM, 22 pairs of patients were identified, and the patient characteristics were similar for all variables included in PSM. In the upfront surgery group, the 5-year EFS and OS rates were 81.8% and 86.3%, respectively. In the neoadjuvant chemotherapy group, the 5-year EFS and OS rates were 81.8% and 90.9%, respectively. No significant differences in EFS or OS were observed between the groups. Pathological classification was the only risk factor for death, disease progression, tumor recurrence, other tumors found during HB diagnosis, and death from any cause (p = .007 and .032, respectively). CONCLUSIONS: Upfront surgery achieved long-term disease control in low-risk patients with resectable HB, thus reduced the cumulative toxicity of platinum-based chemotherapy drugs.

Clinical analysis of 2790 children with retinoblastoma: a single-center experience in China.

BACKGROUND: In this study, we aimed to analyze the clinical characteristics and prognosis of children with retinoblastoma (RB) in a single center in China with a large sample collection spanning 17 years. METHODS: The clinical data of 2790 children with RB treated in Beijing Tongren Hospital from 2005 to 2021 were collected, and a retrospective analysis was conducted. RESULTS: The median age of the participants was 28.3 months. There were 3624 affected eyes, 12.4% of which were in groups A-C, 67.1% in groups D-E and 16.2% were not specified. The primary symptom observed in most cases was a white pupil, accounting for 66.5%, followed by strabismus (12.8%). The median follow-up time was 59.7 months. The enucleation rate was 71.3% (703/986) in a single left eye and 72.5% (702/968) in a single right eye. The overall survival (OS) rate was 95.8% (2444/2552) because 237 patients dropped out, and 109 died. Kaplan‒Meier survival analysis showed that the median survival time (MST) was 125.92 months [95% confidence interval (CI) = 124.83-127.01]. Cox multivariate survival analysis showed that trilateral RB (P = 0.017), metastasis site (P = 0.001), and combined distant tissue metastasis (P = 0.001) were independent prognostic factors for RB. The OS of 44 cases of familial RB was 93.2% (41/44), with an MST of 80.62 months (95% CI = 67.70-93.54). CONCLUSIONS: The timing of eye protection treatment and enucleation should be comprehensively judged to avoid worsening prognosis due to operation time delay. More importantly, the promotion and popularization of diagnosis and treatment technologies are necessary to further improve RB prognosis.

Stem Cell-Associated Signatures Help to Predict Diagnosis and Prognosis in Ovarian Serous Cystadenocarcinoma.

Ovarian serous cystadenocarcinoma (OV) is a fatal gynecologic cancer with a five-year survival rate of only 46%. Resistance to platinum-based chemotherapy is a prevalent factor in OV patients, leading to increased mortality. The platinum resistance in OV is driven by transcriptome heterogeneity and tumor heterogeneity. Studies have indicated that ovarian cancer stem cells (OCSCs), which are chemoresistant and help in disease recurrence, are enriched by platinum-based chemotherapy. Stem cells have a significant influence on the OV progression and prognosis of OV patients and are key pathology mediators of OV. However, the molecular mechanisms and targets of OV have not yet been fully understood. In this study, systematic research based on the TCGA-OV dataset was conducted for the identification and construction of key stem cell-related diagnostic and prognostic models for the development of multigene markers of OV. A six-gene diagnostic and prognostic model (C19orf33, CBX2, CSMD1, INSRR, PRLR, and SLC38A4) was developed based on the differentially expressed stem cell-related gene model, which can act as a potent diagnostic biomarker and can characterize the clinicopathological properties of OV. The key genes related to stem cells were identified by screening the genes differentially expressed in OV and control samples. The mRNA-miRNA-TF molecular network for the six-gene model was constructed, and the potential biological significance of this molecular model and its impact on the infiltration of immune cells in the OV tumor microenvironment were elucidated. The differences in immune infiltration and stem cell-related biological processes were determined using gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (ssGSEA) for the selection of molecular treatment options and providing a reference for elucidating the posttranscriptional regulatory mechanisms in OV.

Lung and right atrial metastases from hepatoblastoma in children: A case series and literature review.

Hepatoblastoma (HB) in children with both lung and right atrial metastases is an unusual situation. The therapy for these cases is challenging and the prognosis is not good. We present three children with HB showing both lung and right atrial metastases and who underwent surgery and received preoperative/postoperative adjuvant-combined chemotherapy to achieve complete remission. Therefore, HB with lung and right atrial metastases could have a good prognosis through active and multidisciplinary treatment.

Prevalence and risk factors of anxious and depressive symptoms in first-trimester females and their partners: a study during the pandemic era of COVID-19 in China.

BACKGROUND: The pandemic of coronavirus disease 2019 lastingly affects public mental health. Many studies have described symptoms of anxiety and depression in pregnant women before the pandemic. However, the limited study focuses on the prevalence and risk factors of mood symptoms among first-trimester females and their partners during the pandemic in China, which was the aim of the study. METHODS: One hundred and sixty-nine first-trimester couples were enrolled. The Edinburgh Postnatal Depression Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-Item, Family Assessment Device-General Functioning (FAD-GF), and Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF) were applied. Data were mainly analyzed through logistic regression analysis. RESULTS: 17.75% and 5.92% of first-trimester females had depressive and anxious symptoms, respectively. Among partners, 11.83% and 9.47% had depressive and anxious symptoms, respectively. In females, higher scores of FAD-GF (OR = 5.46 and 13.09; P < 0.05) and lower scores of Q-LES-Q-SF (OR = 0.83 and 0.70; P < 0.01) were related to the risk of depressive and anxious symptoms. Higher scores of FAD-GF were associated with the risk of depressive and anxious symptoms in partners (OR = 3.95 and 6.89; P < 0.05). A history of smoking was also related to males' depressive symptoms (OR = 4.49; P < 0.05). CONCLUSION: This study prompted prominent mood symptoms during the pandemic. Family functioning, quality of life, and smoking history increased risks of mood symptoms among early pregnant families, which facilitated the updating of medical intervention. However, the current study did not explore interventions based on these findings.

Pegfilgrastim on febrile neutropenia in pediatric and adolescent cancer patients: a systematic review and meta-analysis.

OBJECTIVES: There is no meta-analysis about the effects of pegfilgrastim on the occurrence of febrile neutropenia (FN) in pediatric/adolescent cancer patients. The study explored the efficacy of prophylactic pegfilgrastim in preventing FN in children/adolescents with cancer. METHODS: PubMed, Embase, and the Cochrane Library were searched for studies published before April 7, 2020. The primary outcome was the rate of FN. Effect size (ES) and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the outcome. The ES represented the rate of FN, and the STATA 'metaprop' command was used to synthesize the rate. RESULTS: Eight studies were included, comprising 167 patients and 550 courses of treatment. There was no difference between pegfilgrastim and filgrastim for the rate of FN in children receiving chemotherapy (OR = 0.68, 95% CI: 0.20-2.23, P = 0.520). In patients receiving pegfilgrastim, the rate of FN was 25.6% (95% CI: 14.9%-36.3%), the rate of grade 4 FN was 38.3% (95% CI: 19.2%-59.5%), the rate of severe neutropenia (SN) was 40.5% (95% CI: 35.1%-46.1%), and the rate of treatment delays due to FN was 4.8% (95% CI: 0.8%-11.3%). DISCUSSION: The number of studies that could be included was small; therefore, a specific type of cancer or a specific treatment could be studied. Heterogeneity was high. CONCLUSION: There was no difference between pegfilgrastim and filgrastim for the rate of FN. The use of pegfilgrastim was still associated with rates of FN, grade 4 FN, severe neutropenia, and treatment delays due to FN in pediatric cancer patients.

Clinical application of irinotecan combined with first-line chemotherapeutics against pediatric hepatoblastoma with pulmonary metastasis.

This study aimed to investigate the short-term efficacy and adverse reactions of irinotecan combined with first-line chemotherapeutics for the treatment of pediatric hepatoblastoma with pulmonary metastasis (HB-PM). Forty-one pediatric patients with HB-PM undergoing cisplatin + fluorouracil + vincristine + doxorubicin (C5VD) treatment with bad therapeutic effect or bad response were instead treated with two cycles of an irinotecan protocol (vincristine + irinotecan + cyclophosphamide + cisplatin). The changes in recent alpha-fetoprotein (AFP), efficacy and adverse reactions in these patients were statistically analyzed. Results showed that, the median level of AFP before chemotherapy was 56432 µg/L; however, it was significantly lower (749 µg/L) after two cycles of chemotherapy (rank sum test, P = 0.00). After two cycles of chemotherapy, three patients achieved a complete response and 32 patients achieved a partial response. The recent efficacy cases accounted for 85.36% of patients (35/41). The delayed diarrhea was the most common adverse reaction to irinotecan, with an incidence rate of 58.53% (24/41), which was improved after symptomatic treatment. In conclusion, the protocol of irinotecan combined with first-line chemotherapeutics can be used for the treatment of HB-PM that is not sensitive to the C5VD protocol, with good short-term curative effect and tolerable adverse reactions.

A report on second neo-plasms in seven children with solid tumors.

OBJECTIVE: This study aims to investigate the characteristics and related high risk factors of second neoplasms after chemotherapy and radiotherapy in children with solid tumors. METHODS: The detailed clinical data of seven children with malignant solid tumors, who were treated in our department, were retrospectively analyzed, in order to summarize the clinical characteristics of the secondary onset of second neoplasms, and determined the risk factors related to the occurrence of second neoplasms. RESULTS: (1) Clinical characteristics: Among the seven children with malignant solid tumors, three children had rhabdomyosarcoma (3/132, 2.27%), two children had hepatoblastoma (2/313, 0.64%), one child had neuroblastoma (1/305, 0.33%), and one child had inflammatory myofibroblastoma (1/3, 33.33%). Furthermore, among these children, four children were boys and three children were girls, and their onset age ranged within 5-34 months, with a median onset age of 27 months. Moreover, among these children, three children were ≤1 year old. All second neoplasms exhibited symptoms, and the diagnosis was made after the complete remission of the first primary tumor. The time interval between these two tumors was within 17-78 months, and the median time was 38 months. Three of seven children with rhabdomyosarcoma were treated with chemotherapy in combination with radiotherapy, while four children only received the chemotherapy. The chemotherapy cycles were 6-39 times, and the median chemotherapy cycles were 10 times. Among these children, one child with relapsed stage IV rhabdomyosarcoma and one child with stage IV retroperitoneal neuroblastoma had 39 cycles and 33 cycles of chemotherapy respectively. (2) Characteristics of the accumulated doses of high-risk chemotherapy drugs: The accumulated dose of cyclophosphamide in six patients was within 2.47-44.45 g/m2, with a median of 6.14 g/m2. The accumulated dose of ifosfamide in five patients was within 13.63-96.41 mg/m2, with a median of 31.23g/m2. The accumulated dose of etoposide in six patients was within 1,237.35-3,754.95 mg/m2, with a median of 1,548.67 mg/m2. The accumulated dose of anthracyclines in seven patients was within 150.68-843.78 mg/m2, with a median of 329.73 mg/m2. The accumulated dose of vincristine in seven patients was within 3.11-18.89 mg/m2, with a median of 15.92 mg/m2. The accumulated dose of cisplatin in seven patients was within 271.23-1,681.59 mg/m2, with a median of 733.07 mg/m2. Children with abdominal inflammatory myofibroblastic tumors did not apply cyclophosphamide, ifosfamide and etoposide regimens. The main chemotherapy drugs consisted of methotrexate, pirarubicin, cisplatin and vincristine. (3) Radiotherapy doses. (4) Characteristics of second neoplasms: Among the seven children with second neoplasms, five children had leukemia, 3 patients with rhabdomyosarcoma were combined with radiotherapy. The doses of radiation were 40 and 45GY" after "(3) Radiotherapy doses (four children had acute myeloid leukemia and one children had acute B-lymphoblastic leukemia), one child had myelodysplastic syndrome, and one child had myeloid sarcoma. Furthermore, among these seven children, four children (4/7) had abnormal chromosomes, two children were normal, and one child gave up the treatment and underwent the chromosome test after the diagnosis of second neoplasms. CONCLUSION: The incidence of secondary onset of second neoplasms in children with malignant solid tumors is not high, considering that this is correlated to the use of alkylating agents, topoisomerase II inhibitors, platinum-based chemotherapy drugs and radiotherapy, and associated with the chromosomal abnormalities of children. KEY WORDS: Chemotherapy, Children, Radiotherapy, Second malignant neoplasm, Solid tumor.

Clinical Characteristics and Image Manifestations of a Rare Retinoblastoma with a Bone Metastasis.

Purpose: Retinoblastoma (RB) is the most common intraocular malignancy in infancy and childhood. This study evaluated the clinical and imaging features, treatment, and prognosis of patients with recurrent RB with limb bone metastases and without central nervous system involvement. Patients and Methods: The clinical data of five patients with RB with limb bone metastases who were diagnosed at the Department of Pediatrics in Beijing Tongren Hospital between January 2015 and January 2021 were analyzed retrospectively. Results: Three males and two females were included (seven eyes: four group E and one each of group D, C, and B). The most common symptom was pain. Three patients had bone marrow and lymph node metastases. Three patients had single and two had multiple skeletal lesions. The main bones that were involved were the femur, humerus, talus, and ulna. The simultaneous involvement of the bone marrow and cortex was also observed. Serum neuron-specific enolase (NSE) levels were significantly elevated in four cases and slightly elevated in one case; primary intravenous chemotherapy resulted in a decrease in NSE levels and the gradual resolution of the bone lesions. Two patients died at the time of follow-up and three were in complete remission. The results of the statistical analysis showed that anterior chamber invasion was correlated with prognosis, and there was significant difference in the decrease in the serum NSE levels after intravenous chemotherapy. Conclusion: Regular lifelong follow-up of patients with RB is warranted to identify bone metastases earlier. Anterior chamber invasion may be a risk factor. The simultaneous involvement of the bone marrow and cortex is characteristic manifestations in images of RB with bone metastases. Multidisciplinary treatment especially intravenous chemotherapy is useful, at least at the beginning.

Clinical Analysis of 16 Distant Metastatic Retinoblastoma Cases with Event-Free Survival.

AIM: This study aimed to summarize the clinical characteristics, treatment, and outcomes of distant metastatic retinoblastoma with event-free survival. DESIGN: Retrospective interventional case series. METHODS: We screened patients with retinoblastoma who survived without events after the comprehensive treatment of distant metastases from June 2015 to February 2021 and collected information regarding their basic characteristics, diagnosis, and treatment. All patients received systemic intravenous chemotherapy. Other treatments included surgical treatment, radiotherapy, intrathecal chemotherapy, and autologous stem cell transplantation. RESULTS: Among 780 hospitalized patients with retinoblastoma in the pediatric ward, a total of 94 patients with retinoblastoma were diagnosed with distant metastases, and 16 patients with distant metastatic retinoblastoma who survived more than 6 months without events were screened, including eight male and eight female patients. The median age of onset was 29 (range, 11-120) months. Among the 16 patients, central nervous system metastasis (8/16), bone metastasis (8/16), bone marrow infiltration (4/16), lymph node metastasis (4/16), and parotid gland metastasis (3/16) were presented. All patients received treatment for more than 6 months, completed their regimen by February 2021, and survived without events. The median survival time after the onset of retinoblastoma was 50.5 (range, 23-102) months, the median survival time after metastasis was 43.5 (range, 16-71) months, and the median event-free survival was 29.0 (range, 6-59) months. CONCLUSION: Metastatic retinoblastoma may benefit from comprehensive treatments including systemic intravenous chemotherapy and hematopoietic stem cell transplantation. However, recurrence after treatment still needs attention, and patients in complete remission still need long-term follow-up.

Factors of Recurrence After Complete Response in Children with Neuroblastoma: A 16-Year Retrospective Study of 179 Cases.

BACKGROUND: It is not clear which known adverse prognostic factors of neuroblastoma are closely associated with tumor recurrence after complete response. We analyzed the factors for post-remission recurrence in children with neuroblastoma through a retrospective study. METHODS: A total of 179 children with neuroblastoma who achieved initial complete response were included in this study. Kaplan-Meier method and multivariate Cox regression model were used to assess the factors that may have impact on tumor recurrence after complete response. RESULTS: The 5-year overall survival rates of the entire cohort (n = 179), recurrence group (n = 86) and non-recurrence group (n = 93) were 81.9%, 66.2%, and 98.7%, respectively. The 5-year recurrence-free survival (RFS) rates of the entire cohort and the high-risk cohort were 47.3% and 31.2%, respectively. RFSs were significantly reduced in children with age ≥18 months, INSS stage 4, unfavorable histology, bone marrow metastasis, osseous metastasis, serum NSE level ≥100 ng/mL, and serum LDH level ≥1400 U/L (P < 0.05). The independent risk factors for post-remission recurrence in the entire cohort were age ≥18 months, unfavorable histology, and serum LDH level ≥1400 U/L (P < 0.05). In the high-risk cohort, the independent risk factor for recurrence was serum LDH ≥1400 U/L (P < 0.05). Based on a new recurrence risk stratification, the 5-year RFSs of the children were 93.5%, 66.4%, and 22.5% in the low-risk, intermediate-risk, and high-risk groups, respectively. The area under the ROC curve of the new stratification was 0.773 (95% CI: 0.704-0.842). CONCLUSION: Age ≥18 months, unfavorable histology, and serum LDH level ≥1400 U/L are independent risk factors for post-remission recurrence in children with neuroblastoma. A newly established recurrence risk stratification has diagnostic advantages in predicting risk of recurrence, which is especially suitable for low- and middle-income countries or regions.

Factors influencing recurrence after complete remission in children with hepatoblastoma: A 14-year retrospective study in China.

OBJECTIVE: After a complete remission to treatment for hepatoblastoma, some children still have recurrence. We identified and explored the factors that influence recurrence after complete remission in a retrospective study. METHODS: Of 197 children with hepatoblastoma, 140 (71.1%) achieved initial complete remission and were enrolled in factor analysis. Variables consisted of age, sex, PRE-Treatment EXTent of tumor (PRETEXT) stage, pathologic type, metastatic disease, serum alpha-fetoprotein level, vascular involvement, and surgical margin status. We employed univariate and multivariate analyses to assess the relationship between each factor and tumor recurrence. RESULTS: Of 140 children who achieved initial complete remission, 42 (30%) had recurrent hepatoblastoma. The 5-year overall survival rates for the non-recurrence and recurrence group were 99.0% and 78.6%, respectively. The overall 1-year, 3-year, and 5-year recurrence-free survival (RFS) rates were 77.8%, 69.8%, and 69.8%, respectively. All recurrences occurred within 2 years from complete remission. The RFS rate was significantly higher in children younger than 3 years and in those with mixed pathological type, PRETEXT II and III, without metastatic disease, without vascular involvement, and microscopic negative margin than in that of children older than 3 years, with epithelial pathological type, PRETEXT IV, metastatic disease, vascular involvement, and macroscopic positive margin (P < 0.001, = 0.020, < 0.001, = 0.004, = 0.002, and < 0.001, respectively). The independent risk factors for recurrence after complete remission were age ≥3 years, PRETEXT IV, and metastatic disease (P < 0.05). CONCLUSION: Age, PRETEXT stage, metastatic disease, vascular involvement, pathologic type, and surgical margin status might be associated with recurrent hepatoblastoma after complete remission; meanwhile, age ≥3 years, PRETEXT IV, and metastatic disease are independent risk factors of recurrence. Further research is needed on the causes of tumor recurrence, which may improve the long-term outcomes of children with hepatoblastoma.

Correlation between Family RB1 Gene Pathogenic Variant with Clinical Features and Prognosis of Retinoblastoma under 5 Years Old.

Retinoblastoma (RB) is the most common primary intraocular malignant tumor in infants and the prototype of human hereditary tumors. Its occurrence and development are closely related to the pathogenic variant of tumor suppressor RB1 gene. We aim to analyze the characteristics of RB1 gene pathogenic variant and clinical phenotype in retinoblastoma patients and their relatives. Children with RB were recruited from August 2007 to November 2017. QT-PCR, probing, and gene sequencing were used to analyze the sequence of RB1 gene in RB children, their parents, or grandparents with a clear history of illness. The SPSS20.0 software was used to analyze the correlation between polymorphisms of RB1 gene and the incidence and prognosis of the enrolled children and relatives. 40 RB children (20 males and 20 females) were recruited, unilateral RB accounted for 52.5% (21/40), bilateral RB accounted for 42.5% (17/40), and trilateral RB accounted for 5.0% (2/40). 6 patients had a clear family history (15.0%, 6/40). It had been verified that 19 probands (47.5%) have RB1 gene pathogenic variants (11 frameshift and 8 missense pathogenic variants), of which germline inheritance accounted for 47.4% (9/19) and nongermline heredity accounted for 52.6% (10/19). Pathogenic variants of 10 nucleic acid sites without reported were found, among which c.2455C>G (p.L819V) was confirmed to have heterozygous pathogenic variants in both a bilateral RB patient and his mother with unilateral RB. Family genetic high-risk factors, bilateral/trilateral RB, >12-month-onset RB have a higher proportion of RB1 gene pathogenic variant than children with no family history, unilateral RB, and ≤12-month (P = 0.021, 0.001,0.034). The proportion of pedigree inheritance of infantile retinoblastoma with bilateral disease is high. There was a certain proportion of RB1 gene pathogenic variant in 3-5-year-old children with bilateral RB, even if they had no family genetic history. Therefore, the detection of RB1 gene pathogenic variant should not only focus on infants but also on the phenotype of RB1 gene pathogenic variant in children over 3 years old with bilateral eye disease.

Genotypic Characteristics of Hepatoblastoma as Detected by Next Generation Sequencing and Their Correlation With Clinical Efficacy.

BACKGROUND: Hepatoblastoma (HB) is the most common malignant embryonic liver tumor type in children under 3 years of age. In the present study, the next generation sequencing (NGS) method was used to detect the genotype characteristics of HB and summarize the correlation between the common mutation genotypes noted in this disease and the clinical treatment and prognosis. The results may aid clinical prognosis and the successful application of targeted drugs. METHODS: Initially, DNA was extracted from tumor tissue specimens and peripheral blood derived from 19 pediatric patients with HB. Subsequently, DNA panel and NGS methods were used to detect tumor diagnosis and the expression levels of treatment-associated genes, followed by the summary of genotype characteristics. In addition, in order to further assess the application of immunotherapy in HB, immunohistochemical detection of programmed cell death 1 ligand 1 (PDL1) was performed in combination with tumor mutation burden (TMB) and DNA mismatch repair status analysis. Furthermore, the clinical treatment effect and prognosis of the pediatric patients were statistically analyzed according to the characteristics of the genotype. Overall prognosis and prognostic analyses in different groups were performed by Kaplan-Meier and log-rank tests, respectively. Finally, expression validation and diagnostic analysis of commonly reported genes were performed in the GSE75271 dataset, which was obtained from the Gene Expression Omnibus (GEO) database. RESULTS: In the present study, certain mutated genes, including nuclear factor erythroid 2-related factor 2 (NFE2L2), catenin ß1 (CTNNB1), MYCN, tumor protein p53, axis inhibition protein 1 (AXIN1) and adenomatous polyposis coli (APC) were associated with the pathogenesis of HB. During TMB and DNA mismatch repair status analyses, pediatric patients had a low TMB. All of them did not present with microsatellite instability. The immunohistochemical results indicated lower expression levels of PDL1 in HB. The complete remission (CR) rate of pediatric patients in the gene abnormality group was lower than that of the non-reported disease-associated gene abnormality group. The 2-year overall survival rate and disease-free survival rate of 19 pediatric patients with HB were 72.1% and 42.4%, respectively. Receiver operating characteristic (ROC) analysis demonstrated that CTNNB1, NFE2L2, AXIN1, APC, MYCN and insulin growth factor 2 (IGF2) may be potential biomarkers that could be used for the diagnosis of HB. CONCLUSION: The genotype changes in HB were more common and the CR rate of the pediatric patients with an altered genotype was lower than that of pediatric patients without an altered genotype. In addition, pediatric patients with HB exhibited lower TMB compared with adult patients. Moreover, the data indicated that CTNNB1, NFE2L2, AXIN1, APC, MYCN and IGF2 may be potential biomarkers that can be used for the diagnosis of HB.