Global Retinoblastoma Study Group 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 PARTICIPANTSA 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 MEASURESAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. RESULTSThe 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,, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI,). CONCLUSIONS AND RELEVANCEThis 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.

BackgroundSeveral kinds of cancer surgeries with propofol-based total intravenous anesthesia (TIVA) have been shown to have better outcomes than those with sevoflurane-based inhalational anesthesia (INHA). However, the effects of this anesthetic technique have not been investigated in patients with gastric cancer. In this study, the authors retrospectively examined the link between the choice of anesthetic technique and overall survival in patients undergoing gastric cancer resection.MethodsWe conducted a retrospective analysis of the database of all patients undergoing gastric cancer resection for gastric cancer between 2007 and 2012. Patients who received TIVA or INHA were administered patient-controlled intravenous analgesia for 72–120 hours postoperatively. Survival was estimated using the Kaplan–Meier log-rank test, and associations between anesthetic technique and outcomes were analyzed using Cox proportional hazards regressions after propensity matching.ResultsA total of 2,856 anesthetics using INHA or TIVA were delivered in the study period. After propensity matching, 897 patients remained in each group. According to Kaplan–Meier analysis, the use of TIVA was associated with improved survival (P<0.001). TIVA was associated with a hazard ratio (HR) of 0.67 (95% confidence interval [CI]: 0.58–0.77) for death in univariate analysis and 0.65 (95% CI: 0.56–0.75) after a multivariate analysis of known confounders in the matched group. Cancer stage (HR =0.74, 95% CI: 0.64–0.86, P<0.001) and degree of differentiation (HR =1.28, 95% CI: 1.11–1.47, P<0.001) were also associated with survival in the univariate analysis in the matched group. In the multivariable Cox model, cancer stage (HR =0.72, 95% CI: 0.62–0.84, P<0.001) and degree of differentiation (HR =1.23, 95% CI: 1.07–1.42, P<0.001) were associated with survival in the matched group.ConclusionThese results indicate that TIVA may be associated with improved survival in gastric cancer patients who undergo resection.

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Epidermal growth factor receptor (EGFR) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and correlates with poor prognosis. EGFR has been demonstrated to be associated with cancer stem cell traits in HNSCC. However, the underlying molecular mechanism is far from elucidated. Here, SOX2, one of the most important stem cell markers, was identified as a binding partner and substrate of EGFR. EGFR signaling inhibition decreases SOX2 expression by promoting its autophagic degradation. Mechanistically, EGFR activation induces SOX2 phosphorylation at the Y277 site and reduces its ubiquitination, which inhibits its association with p62 and subsequent autophagic degradation. Gefitinib, an EGFR tyrosine kinase inhibitor, shows in vitro and in vivo protective effects against oral cancer cells that can be reversed through autophagy inhibition. Our study suggests that EGFR plays an important role in the development of cancer stem cells by stabilizing SOX2.Targeting EGFR in combination with conventional chemotherapy might be a promising strategy for the treatment of HNSCC through elimination of cancer stem cells. K E Y W O R D Sautophagy, gefitinib, oral cancer, P62, stemness SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.