Treatment patterns and clinical outcomes in 157 patients with extensive-stage small cell lung cancer: real-world evidence from a single-center retrospective study

BackgroundImmune checkpoint inhibitors (ICIs) have changed the therapeutic options for extensive-stage small-cell lung cancer (ES-SCLC). In this real-world study, we analyzed the treatment patterns in patients with ES-SCLC and evaluated the efficacy of chemotherapy combined with immunotherapy as first-line therapy.MethodsA retrospective analysis was performed on patients with ES-SCLC who received treatment at China-Japan Friendship Hospital (Beijing, China) between August 1, 2020, and April 30, 2023. The treatment patterns appeared in the form of Sunburst Chart and Sankey diagram. The survival analyses were conducted by Kaplan-Meier curves.ResultsA total of 157 patients with ES-SCLC were retrospectively included. According to first-line therapy, patients were divided into the chemotherapy (CT) group (n=82) and chemo-immunotherapy (CIT) group (n=75). The median treatment lines were 2[1, 2] and cycles were 8[5, 12], respectively. 82 patients received the second line of therapy, followed by 37 for the third, 15 for the fourth, 11 for the fifth, and 5 for the sixth. Overall, the treatment patterns involved 11 options including 12 chemotherapy regimens, 11 ICIs, and 4 targeted agents. The second-line treatment pattern had the most options (9) and regimens (43). In the first 3 lines, chemotherapy was the largest proportion of treatment options. The addition of ICIs prolonged progression-free survival from 6.77 (95% confidence interval [CI], 6.00-7.87) to 7.33 (95% CI, 6.03-9.80) months (hazard ratio [HR]=0.67, 95% CI, 0.47-0.95; P=0.025), overall survival from 12.97 (10.90-23.3) to 14.33 (12.67-NA) months without statistically significant difference (HR=0.86, 95% CI, 0.55-1.34; P=0.505).ConclusionThe treatment options of patients with ES-SCLC are more diversified. Combination therapy is the current trend, where chemotherapy is the cornerstone. Meanwhile, ICIs participate in almost all lines of treatment. However, the clinical efficacy remains barely satisfactory. We are urgently expecting more breakthrough therapies except immunology will be applied in the clinic

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Classification of and the latest photoelectric therapy for epidermal nevi

An epidermal nevus (EN) is a common disease of various types, including verrucous EN, nevus sebaceous, inflammatory linear verrucous EN, Becker nevus, smooth muscle hamartoma, and nevus comedonicus. EN syndrome is a serious and difficult-to-treat syndrome that is complicated by two or more abnormal organs or systems. To date, the mechanism of an EN is still unclear, and the therapies remain unsatisfactory. The most frequently used treatments are surgery and laser therapy. Several drugs have also been tested. An EN requires more attention, and further research is needed to provide appropriate and effective treatments for each patient

Antioxidant Compounds from Propolis Collected in Anhui, China

The antioxidant activities of the chloroform, ethyl acetate and n-butanol extract fractions from propolis collected in Anhui, China were evaluated in this study. The ethyl acetate fraction contained the highest amount of total phenolics and total flavonoids, and showed the greatest 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging capacities and Ferric Reducing/Antioxidant Power (FRAP). The antioxidant activity of twenty-two compounds isolated from the ethyl acetate fraction was also evaluated using the above-mentioned three assays. The results indicated that phenolics contributed to the antioxidant activity of propolis collected in Anhui, China. Therefore, propolis collected in Anhui, China and its phenolics might be used as a natural antioxidant

Single-cell RNA sequencing of peripheral blood reveals immune cell dysfunction in premature ovarian insufficiency

BackgroundPremature ovarian insufficiency (POI) is one of the most common causes of female infertility and the etiology is highly heterogeneous. Most cases are idiopathic and the pathogenesis remains unclear. Previous studies proved that the immune system plays a crucial role in POI. However, the precise role of immune system remains unclear. This study aimed to analyze the characteristics of peripheral blood mononuclear cells (PBMC) from patients with POI by single-cell RNA sequencing (scRNA-seq) and to explore the potential involvement of immune response in idiopathic POI.MethodsPBMC was collected from three normal subjects and three patients with POI. PBMC was subjected to scRNA-seq to identify cell clusters and differently expressed genes (DEGs). Enrichment analysis and cell-cell communication analysis were performed to explore the most active biological function in the immune cells of patients with POI.ResultsIn total, 22 cell clusters and 10 cell types were identified in the two groups. Compared with normal subjects, the percentage of classical monocytes and NK cells was decreased, the abundance of plasma B cells was increased, and CD4/CD8 ratio was significantly higher in POI. Furthermore, upregulation of IGKC, IFITM1, CD69, JUND and downregulation of LYZ, GNLY, VCAN, and S100A9 were identified, which were enriched in NK cell-mediated cytotoxicity, antigen processing and presentation, and IL-17 signaling pathway. Among them, IGHM and LYZ were respectively the most significantly upregulated and downregulated genes among all cell clusters of POI. The strength of cell-cell communication differed between the healthy subjects and patients with POI, and multiple signaling pathways were assessed. The TNF pathway was found to be unique in POI with classical monocytes being the major target and source of TNF signaling.ConclusionsDysfunction of cellular immunity is related to idiopathic POI. Monocytes, NK cells, and B cells, and their enriched differential genes may play a role in the development of idiopathic POI. These findings provide novel mechanistic insight for understanding the pathogenesis of POI

Efficacy and Safety of Immune Checkpoint Inhibitors in Patients with Cancer and Hepatitis B or C: A Systematic Review and Meta-Analysis

Background. Immune checkpoint inhibitors (ICIs) have changed the situation of tumor therapy in recent years. However, for security reasons, those special populations are often excluded from clinical trials, such as infected hepatitis B or hepatitis C patients. ICIs are systematically reviewed and meta-analyzed for the first time in patients infected with hepatitis B or C in this paper. Methods. The relevant studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science until October 2022. Trials and observational studies meeting the inclusion criteria were included. The outcomes included the effectiveness of ICIs in patients with HBC/HCV (ORR, DCR, mOS, and mPFS), the incidence of adverse reactions, high-grade adverse reactions, and abnormal liver enzymes. At the same time, these indexes were compared with those of uninfected patients. Results. A total of 2,625 patients were enrolled, involving 1,179 patients with hepatitis (HBV or HCV). We found that ICIs showed higher ORR (25.80% vs. 18.10%) and DCR (66.22% vs. 58.74%) in patients with hepatitis B/C than those without infection. In terms of survival time, patients with hepatitis virus infection showed longer mOS (15.44 m vs. 13.30 m) but shorter mPFS (4.94 m vs. 5.01 m) than uninfected patients. As for safety data, patients with hepatitis showed a lower incidence of all-grade irAEs (68.02% vs. 70.43%) than uninfected patients, while that of 3-4 irAEs (21.27% vs. 21.79%) was similar in the two groups. However, hepatic dysfunction was more common and serious in hepatitis patients. Four HBVr and no HCVr were observed. Conclusion. According to this meta-analysis, ICIs are effective and safe for patients with hepatitis B or C, but basic liver enzymes have to be evaluated before treatment to avoid liver adverse events