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To evaluate the safety, tolerability, and efficacy of efdamrofusp alfa in patients with neovascular age-related macular degeneration (nAMD).Randomized, open-label, multiple ascending-dose, phase 1b study.Patients aged 50 years or older with active choroid neovascularization (CNV) secondary to nAMD were screened from two hospitals in two provinces in China. The first nine patients were randomized 2:1 to intravitreally receive efdamrofusp alfa 2 mg at week 0, 4, 8 or aflibercept 2 mg at week 0, 4, 8, 16. After the dose limiting toxicity assessment, additional nine patients were randomized 2:1 to intravitreally receive efdamrofusp alfa 4 mg at week 0, 4, 8 or aflibercept 2 mg at week 0, 4, 8, 16. All patients were followed up till week 20. Primary outcomes were safety and tolerability of efdamrofusp alfa. Secondary outcomes included changes from baseline in best corrected visual acuity (BCVA), central subfield thickness (CST) as measured by spectral domain-optical coherence tomography (SD-OCT), and CNV area as measured by fluorescein angiography (FA).A total of 18 patients were enrolled and each six of them received efdamrofusp alfa 2 mg, efdamrofusp alfa 4 mg or aflibercept 2 mg, respectively. No dose-limiting toxicity reported and all patients completed the study. No ocular serious adverse event was reported. All ocular treatment-emergent adverse events were intravitreal injection related, mild or moderate in severity. At week 20, mean changes from baseline in BCVA were 5.64±3.56, 8.93±3.59 and 7.92±3.55 letters for patients receiving efdamrofusp alfa 2 mg, efdamrofusp alfa 4 mg and aflibercept 2 mg, respectively. Meanwhile, CST and CNV area reductions indicative of anatomic improvement were observed in the majority of the patients receiving both doses of efdamrofusp alfa and aflibercept.Intravitreal efdamrofusp alfa dosed up to 4 mg every 4 weeks was well tolerated in nAMD patients with similar vision acuity and anatomic improvements.ClinicalTrials.gov identifier NCT04370379.

To investigate whether peritoneal disease extent can predict the survival benefit of intraperitoneal/intravenous (IP/IV) chemotherapy in ovarian cancer.A treatment-free survival (TFS) analysis.Five-centre trial.An extended follow-up of the Additional Intraperitoneal Cisplatin and Etoposide in ovarian cancer (AICE) trial (NCT01669226), with data cut-off on 27 August 2020. Patients were categorised into subgroups with high tumour burden (HTB) and low tumour burden (LTB).Overall survival (OS) was divided into time on protocol treatment exposure (T), time free of subsequent treatment or death (TFS) and time after the first subsequent therapy (REL). TFS analyses and quality-adjusted OS were calculated by multiplying the mean time in each health state by its assigned utility: quality-adjusted OS = uThe area under each Kaplan-Meier curve was estimated using the 96-month restricted mean time, with threshold utility analyses used to illustrate quality-adjusted OS comparisons.In the HTB subgroup, the restricted mean TFS was 33.9 months and 18.7 months in the IP/IV and IV groups, respectively (p = 0.005), with a significant quality-adjusted OS gain (13.2-16.0 months). In the LTB subgroup, IP/IV therapy yielded no survival benefit in either TFS (p = 0.268) or quality-adjusted OS (range: 1.4-6.3 months).Both TFS and quality-adjusted OS was longer across all utility weight values with IP/IV than with standard IV therapy in the HTB subgroup, whereas patients in the LTB subgroup did not benefit from the therapy. The tumour burden of ovarian cancer should be assessed before deciding on IP/IV versus IV treatment.

Introduction Previous studies have reported a high prevalence of visual defects in children with special needs. However, routine ocular examinations for these children in rural areas of China are lacking. This study aimed to evaluate the status of visual impairment (VI) in children at special education schools in rural China. Methods A total of 316 students from two special schools in Zunyi city, Guizhou province, were enrolled. Full ophthalmic examinations were performed, and gene-sequencing services were offered to potential patients. Results The mean age of the 316 participants was 12.27±3.49 years, and 75 showed abnormal ophthalmic manifestations on slit-lamp examination. Visual acuity (VA) was assessed in 232 eyes, and the mean VA (logarithm of the minimum angle of resolution, logMAR) was 0.27±0.34. Whole-exome sequencing (WES) identified 19 mutations in these children, which might explain their visual complaints. Children with Down syndrome had a significantly higher prevalence of ocular disorders than those without. Conclusion VI is common among children at special education schools in rural areas; however, routine screening and effective interventions have not been consistently implemented. Efforts should be made to address this issue in these already disadvantaged children.

Summary Background The benefits of secondary cytoreduction for platinum-sensitive relapsed ovarian cancer are still widely debated. We aimed to assess the efficacy of secondary cytoreduction plus chemotherapy versus chemotherapy alone in this patient population. Methods This multicentre, open-label, randomised, controlled, phase 3 trial (SOC-1), was done in four primarily academic centres in China (two in Shanghai, one in Hangzhou, and one in Guangzhou). Eligible patients were women aged 18 years and older with platinum-sensitive relapsed epithelial ovarian cancer with a platinum-free interval of at least 6 months after the end of first-line platinum-based chemotherapy and were predicted to have potentially resectable disease according to the international model (iMODEL) score and PET-CT imaging. iMODEL score was calculated using six variables: International Federation of Gynecology and Obstetrics stage, residual disease after primary surgery, platinum-free interval, Eastern Cooperative Oncology Group performance status, serum level of cancer antigen 125 at recurrence, and presence of ascites at recurrence. An iMODEL score of 4·7 or lower predicted a potentially complete resection. As per a protocol amendment, patients with an iMODEL score of more than 4·7 could only be included if the serum level of cancer antigen 125 was more than 105 U/mL, but the principal investigators assessed the disease to be resectable by PET-CT. Eligible participants were randomly assigned (1:1) via a permuted block design (block size of six) and stratified by study centre, iMODEL score, residual disease at primary surgery, and enrolment in the Shanghai Gynecologic Oncology Group SUNNY trial, to undergo secondary cytoreductive surgery followed by intravenous chemotherapy (six 3-weekly cycles of intravenous paclitaxel [175 mg/m2] or docetaxel [75 mg/m2] combined with intravenous carboplatin [area under the curve of 5 mg/mL per min]; surgery group) or intravenous chemotherapy alone (no surgery group). Primary endpoints were progression-free survival and overall survival, analysed in all participants randomly assigned to treatment, regardless of treatment received (intention-to-treat [ITT] population). Here, we report the final analysis of progression-free survival and the prespecified interim analysis of overall survival. Safety was assessed in all participants who received their assigned treatment and had available adverse event data. This study is registered with ClinicalTrials.gov, NCT01611766, and is ongoing but closed to accrual. Findings Between July 19, 2012, and June 3, 2019, 357 patients were recruited and randomly assigned to the surgery group (182) or the no surgery group (175; ITT population). Median follow-up was 36·0 months (IQR 18·1–58·3). In the no surgery group, 11 (6%) of 175 participants had secondary cytoreduction during second-line therapy while 48 (37%) of 130 participants who had disease progression crossed-over and had surgery at a subsequent recurrence. Median progression-free survival was 17·4 months (95% CI 15·0–19·8) in the surgery group and 11·9 months (10·0–13·8) in the no surgery group (hazard ratio [HR] 0·58; 95% CI 0·45–0·74; p Interpretation Secondary cytoreduction followed by chemotherapy was associated with significantly longer progression-free survival than was chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer, and patients should be counselled about the option of secondary cytoreduction in specialised centres. Long-term survival outcomes will be assessed using mature data on overall survival. Funding Zhongshan Development Program. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Purpose. To investigate the vascular density of the optic nerve head (ONH) and macula using optical coherence tomography angiography (OCTA) in patients undergoing vitrectomy for rhegmatogenous retinal detachment (RRD) and to evaluate associations with visual outcomes. Methods. Patients with RRD, successfully treated with a pars plana vitrectomy (PPV) and a minimum three-month follow-up were included in this study. The vessel density (VD) of the ONH and peripapillary regions, foveal avascular zone (FAZ), foveal flow density (FFD), and parafoveal flow density (PFD) were evaluated using OCTA and compared to the fellow eye. Multivariate linear regression analysis was performed to determine correlations with visual outcomes. Results. Thirty-one patients with macula-off RRD were included in the study. Compared with the fellow eyes, eyes after RRD surgery had a lower peripapillary VD ( P < 0.01 ). No significant difference in superficial and deep FFD, PFD, and FAZ area was found compared to the fellow eyes. Postoperative peripapillary VD and baseline BCVA were significantly associated with BCVA three months after PPV ( P < 0.05 ). Conclusion. Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower peripapillary vessel density than fellow healthy eyes. Postoperative BCVA was related to postoperative peripapillary VD.

Humans are simultaneously exposed to numerous of environmental brominated flame retardants (BFRs). We aim to explore the overall associations of BFRs mixture on metabolic syndrome (MetS) and its components and further identify significant chemicals.This study included 4641 adults from the National Health and Nutrition Examination Survey (NHANES) in 2007-2016. The weighted logistic regression was conducted to estimate the association of a single BFR exposure with MetS and its components. Meanwhile, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were adopted to evaluate the overall associations of BFRs mixture on MetS and its components, and to identify significant chemicals. We also evaluated potential associations modified by sex.In the weighted logistic regression model, PBB153 were positively associated with MetS in a dose-dependent manner (PThe present study suggested exposure to BFRs mixture was positively associated with MetS and its components in adults, and PBB153, PBDE28 and PBDE209 were the significant chemicals. However, prospective cohort studies are still needed to confirm the causal effect between BFRs mixture and MetS.

Antiangiogenesis therapies targeting vascular endothelial growth factor (VEGF) have revolutionized the treatment of neovascular ocular diseases, including neovascular age-related macular degeneration (nAMD). Compelling evidence has implicated the vital role of complement system dysregulation in AMD pathogenesis, implying it as a potential therapeutic strategy for geographic atrophy in dry AMD and to enhance the efficacy of anti-VEGF monotherapies in nAMD. This study reports the preclinical assessment and phase 1 clinical outcomes of a bispecific fusion protein, efdamrofusp alfa (code: IBI302), which is capable of neutralizing both VEGF isoforms and C3b/C4b. Efdamrofusp alfa showed superior efficacy over anti-VEGF monotherapy in a mouse laser-induced choroidal neovascularization (CNV) model after intravitreal delivery. Dual inhibition of VEGF and the complement activation was found to further inhibit macrophage infiltration and M2 macrophage polarization. Intravitreal efdamrofusp alfa demonstrated favorable safety profiles and exhibited antiangiogenetic efficacy in a nonhuman primate laser-induced CNV model. A phase 1 dose-escalating clinical trial (NCT03814291) was thus conducted on the basis of the preclinical data. Preliminary results showed that efdamrofusp alfa was well tolerated in patients with nAMD. These data suggest that efdamrofusp alfa might be effective for treating nAMD and possibly other complement-related ocular conditions.

Purpose To investigate the growth of nonexudative macular neovascularization (MNV) in age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA). Methods Patients with treatment-naïve nonexudative AMD in one eye and exudative AMD in the fellow eye who underwent SS-OCTA imaging for at least 12 months were retrospectively reviewed. The MNV area measurement was quantified in eyes with treatment-naïve nonexudative MNV using ImageJ for analysing the correlation between MNV growth and the onset of exudation, as well as evaluating the consistency of the MNV growth rate during the subclinical and exudative stages. Kaplan-Meier survival analysis and logistic regression analyses were used. Results In total, 45 eyes with treatment-naïve nonexudative AMD from 45 patients were enrolled. Treatment-naïve nonexudative MNV was identified in 21 eyes (46.67%) at baseline. The development of exudative findings was noted in eight eyes (17.78%), including six eyes with previously noted nonexudative MNV. Eyes with growing MNV (increase in area ≥50% within 12 months) had an increased risk of exudation and developed exudation earlier than eyes with stable MNV (13.60 [6.43–20.77] months versus 31.11 [26.61–35.62] months, P Conclusion SS-OCTA allows to qualitatively and quantitatively evaluate nonexudative MNV in AMD patients. Growing MNV involved higher probabilities and a faster onset of exudation compared to stable MNV. Identifying the growth of MNV on OCTA might be helpful for establishing treatment strategies and follow-up planning.

Previous studies have explored prediction value of serum metabolites in neoadjuvant chemoradiation therapy (NCRT) response for rectal cancer. To date, limited literature is available for serum metabolome changes dynamically through NCRT.This study aimed to explore temporal change pattern of serum metabolites during NCRT, and potential metabolic biomarkers to predict the pathological response to NCRT in locally advanced rectal cancer (LARC) patients.Based on dynamic UHPLC-QTOF-MS untargeted metabolomics design, this study included 106 LARC patients treated with NCRT. Biological samples of the enrolled patients were collected in five consecutive time-points. Untargeted metabolomics was used to profile serum metabolic signatures from LARC patients. Then, we used fuzzy C-means clustering (FCM) to explore temporal change patterns in metabolites cluster and identify monotonously changing metabolites during NCRT. Repeated measure analysis of variance (RM-ANOVA) and multilevel partial least-squares discriminant analysis (ML-PLS-DA) were performed to select metabolic biomarkers. Finally, a panel of dynamic differential metabolites was used to build logistic regression prediction models.Metabolite profiles showed a clearly tendency of separation between different follow-up panels. We identified two clusters of 155 serum metabolites with monotonously changing patterns during NCRT (74 decreased metabolites and 81 increased metabolites). Using RM-ANOVA and ML-PLS-DA, 8 metabolites (L-Norleucine, Betaine, Hypoxanthine, Acetylcholine, 1-Hexadecanoyl-sn-glycero-3-phosphocholine, Glycerophosphocholine, Alpha-ketoisovaleric acid, N-Acetyl-L-alanine) were further identified as dynamic differential biomarkers for predicting NCRT sensitivity. The area under the ROC curve (AUC) of prediction model combined with the baseline measurement was 0.54 (95%CI = 0.43 ~ 0.65). By incorporating the variability indexes of 8 dynamic differential metabolites, the prediction model showed better discrimination performance than baseline measurement, with AUC = 0.67 (95%CI 0.57 ~ 0.77), 0.64 (0.53 ~ 0.75), 0.60 (0.50 ~ 0.71), and 0.56 (0.45 ~ 0.67) for the variability index of difference, linear slope, ratio, and standard deviation, respectively.This study identified eight metabolites as dynamic differential biomarkers to discriminate NCRT-sensitive and resistant patients. The changes of metabolite level during NCRT show better performance in predicting NCRT sensitivity. These findings highlight the clinical significance of metabolites variabilities in metabolomics analysis.

To investigate the characteristics of the branching vascular network (BVN) and polypoidal lesions in polypoidal choroidal vasculopathy (PCV) to determine near-term indicators that may predict exudative recurrence.Retrospective cohort study.Patients with PCV receiving anti-vascular endothelial growth factor (VEGF) monotherapy or anti-VEGF plus photodynamic therapy were followed for at least 1 year using swept-source OCT angiography (SS-OCTA) imaging.Patients were divided into 2 groups based on whether exudative recurrence occurred during follow-up. Multiple parameters were collected and compared between the 2 groups, such as age, gender, visual acuity, number of polypoidal lesions, lesion area at the first SS-OCTA visit, and total lesion area change from the first SS-OCTA visit to the last SS-OCTA visit. To evaluate the association between SS-OCTA imaging-based risk factors and the exudative recurrences, imaging features associated with PCV such as BVN growth and polypoidal lesion progression (enlargement, new appearance, and reappearance) at each follow-up visit were analyzed. The time intervals from the nonexudative visit with lesion progression to the corresponding exudative recurrence visit were documented to explore their association with exudative recurrences. Cox regression and logistic regression analyses were used.Association between BVN growth and polypoidal lesion progression with exudative recurrence.Thirty-one eyes of 31 patients (61% men) were included. Sixteen eyes had no recurrence of exudation, and 15 eyes had recurrence during follow-up. The average follow-up duration was 20.55 ± 6.86 months (range, 12-36 months). Overall, the recurrence group had worse best-corrected visual acuity (P = 0.019) and a greater increase in lesion area (P = 0.010). Logistical regression analysis showed that polypoidal lesion progression, including new appearance, enlargement, and reappearance of polypoidal lesions, was associated with exudative recurrences within 3 months (odds ratio, 26.67, 95% confidence interval, 3.77-188.54, P = 0.001).Growth of nonexudative BVN and progression of polypoidal lesions were found to be lesion characteristics associated with exudative recurrences, and progression of polypoidal lesions might serve as a stand-alone indicator for the near-term onset of exudation. In PCV, more frequent follow-up visits are recommended when polypoidal lesions show progression.

Background In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. Methods SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography–computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate. Trial Registration ClinicalTrials.gov Identifier: NCT03983226

BackgroundTo evaluate whether the specific choroidal neovascularization (CNV) characteristics measured using optical coherence tomography angiography (OCTA) can predict the 6-month prognosis of neovascular age-related macular degeneration (nAMD) after anti-vascular endothelial growth factor (anti-VEGF) therapy.MethodsPatients with type 1, type 2, or mixed-type neovascularization (NV) were prospectively included. Participants underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept (0.5 mg) and were switched to a pro re nata (PRN) treatment strategy. OCTA images were evaluated for eyes that underwent follow-up assessments for more than 6 months. CNV lesions were manually segmented, and the CNV area, vessel area, greatest vascular caliber (GVC), and greatest linear dimension (GLD) were compared between responders and non-responders. Two masked graders independently measured the above-mentioned parameters using OCTA, and consistency was assessed using the intraclass correlation coefficient (ICC) values. Multiple logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area, GLD, and GVC on the 6-month response to anti-VEGF agents.ResultsAmong the 60 eyes of 60 patients with nAMD, 39 were responders and 21 were non-responders. The proportion of CNV types was significantly different between responders and non-responders (P = 0.009). Patients with type 2 or mixed NV seemed more likely to respond to the treatment (28.2%vs.0.0%, and 30.8%vs.23.8%, respectively). The change in GVC showed a significant difference between responders (− 4.98 ± 17.17 μm) and non-responders (11.01 ± 14.10 μm) after three monthly intravitreal anti-VEGF injections. Multiple logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC, injection number, and CNV type (adjusted OR = 1.083;P = 0.008).ConclusionsType 2 and mixed-type NV were significantly associated with a better response to anti-VEGF therapy. Changes in GVC after 3 months of treatment were significantly associated with a response to anti-VEGF therapy at 6 months.

Key Points Question Are the safety outcomes of intravitreal injection with anti–vascular endothelial growth factor agents in the office-based setting comparable with outcomes in the operating room? Findings In this meta-analysis including 31 studies with a total of 1 275 815 injections, no difference between rates of postinjection endophthalmitis were identified in the 2 settings. The rates of other ocular adverse events were quite low, with no systemic adverse events reported. Meaning This study cannot determine whether performing injection in the operating room is more appropriate in lower-income regions., This meta-analysis evaluates the safety outcomes of intravitreal injection with anti–vascular endothelial growth factor agents in the operating room vs office-based setting., Importance Compared with the operating room (OR), office-based intravitreal injection (IVI) is considered a more cost-effective and convenient approach, yet clinical outcomes of IVIs with anti–vascular endothelial growth factor (VEGF) agents in different settings (office-based vs OR) have not been systematically evaluated. Objective To evaluate the safety outcomes of IVI with anti-VEGF agents in the OR vs office-based setting. Data Sources PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to July 2020. Study Selection Eligible studies reporting on patients who received IVIs with anti-VEGF drugs with a clearly stated injection setting of the office or OR. Data Extraction and Synthesis Two reviewers independently screened studies, extracted data, and assessed risk of bias. A meta-analysis was conducted to determine the rates of endophthalmitis (EO) and culture-positive EO. Main Outcomes and Measures Rates of EO and culture-positive EO following anti-VEGF IVIs in the OR and office-based setting. Results Thirty-one studies with a total of 1 275 815 injections were included. Comparative analysis suggested no difference between rates of EO after IVIs performed in the office and OR settings (odds ratio, 3.06; 95% CI, 0.07-139.75; P = .57; I2 = 80%) were identified, yet a higher rate of culture-positive EO was found in the office setting (odds ratio, 21.52; 95% CI, 2.39-193.55; P = .006; I2 = 0%). The pooled rates of EO following anti-VEGF IVIs were 0.03% (95% CI, 0.03-0.04) and 0.02% (95% CI, 0.01-0.04) in office and OR settings, respectively, and the pooled rates of culture-positive EO were 0.01% (95% CI, 0.01-0.02) and 0.01% (95% CI, 0-0.02). The pooled rates of other ocular and systemic adverse events were low. Conclusions and Relevance The rate of clinically suspected or culture-positive EO following anti-VEGF IVIs was low whether the procedure was performed in the office or OR setting. Bacterial spectrum could differ between the 2 settings. This meta-analysis could not determine if it is more appropriate to give treatment in the OR for safety reasons in low-income compared with higher-income regions in the world.

Rationale: Amyloid β (Aβ) deposition, an essential pathological process in age-related macular degeneration (AMD), causes retinal pigment epithelium (RPE) degeneration driven mostly by oxidative stress. However, despite intense investigations, the extent to which overoxidation contributes to Aβ-mediated RPE damage and its potential mechanism has not been fully elucidated. Methods: We performed tandem mass-tagged (TMT) mass spectrometry (MS) and bioinformatic analysis of the RPE-choroid complex in an Aβ1-40-induced mouse model of retinal degeneration to obtain a comprehensive proteomic profile. Key regulators in this model were confirmed by reactive oxygen species (ROS) detection, mitochondrial ROS assay, oxygen consumption rate (OCR) measurement, gene knockout experiment, chromatin immunoprecipitation (ChIP), and luciferase assay. Results: A total of 4243 proteins were identified, 1069 of which were significantly affected by Aβ1-40 and found to be enriched in oxidation-related pathways by bioinformatic analysis. Moreover, NADPH oxidases were identified as hub proteins in Aβ1-40-mediated oxidative stress, as evidenced by mitochondrial dysfunction and reactive oxygen species overproduction. By motif and binding site analyses, we found that the transcription factor PU.1/Spi1 acted as a master regulator of the activation of NADPH oxidases, especially the NOX4-p22phox complex. Also, PU.1 silencing impeded RPE oxidative stress and mitochondrial dysfunction and rescued the retinal structure and function. Conclusion: Our study suggests that PU.1 is a novel therapeutic target for AMD, and the regulation of PU.1 expression represents a potentially novel approach against excessive oxidative stress in Aβ-driven RPE injury.

Background and objectives To evaluate the effect of the varied histological subtypes on clinical outcomes and to determine the prognostic implications of mucinous adenocarcinomas (MAC) and signet ring cell carcinomas (SRCC) compared with classic adenocarcinomas (AC). Methods A total of 8005 patients, including 7502 AC, 428 MAC and 75 SRCC, who underwent definitive surgery between 2007 and 2015 at Fudan University Shanghai Cancer Center were remained for analysis in this study. Results MAC and SRCC were more common in right‐sided colon cancer, in males and in young patients, compared to AC; moreover, MAC and SRCC led to a higher probability to develop lymph node metastasis, lymphovascular invasion and perineural invasion. For survival outcomes, we found that the 5‐year overall survival (OS) of SRCC was significantly lower than that of MAC and AC, while the 5‐year OS of MAC is much lower than that of AC. However, in multivariable analysis, the difference in survival between SRCC, MAC and AC was no longer significant, especially when stratified by N stage. Conclusions MAC and SRCC are rare subtypes of colorectal cancer with a higher T stage, N stage as well as higher incidence of lymphovascular and nerve invasion. However, neither MAC nor SRCC was an independent predictor of decreased survival in multivariate analysis.

PURPOSE This trial aimed to assess the efficacy and safety of the paclitaxel plus fluorouracil regimen versus the cisplatin plus fluorouracil regimen in definitive concurrent chemoradiotherapy (dCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS Patients with locally advanced ESCC were enrolled and randomly assigned to either the paclitaxel plus fluorouracil group or the cisplatin plus fluorouracil group. The patients in the paclitaxel plus fluorouracil group were treated with paclitaxel and fluorouracil one cycle per week in dCRT for five cycles followed by paclitaxel and fluorouracil one cycle per month in consolidation chemotherapy for two cycles. The patients in the cisplatin/5-fluorouracil group were treated with cisplatin and fluorouracil one cycle per month in dCRT for two cycles followed by two cycles in consolidation chemotherapy. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end point was 3-year overall survival (OS). RESULTS Four hundred thirty-six patients with ESCC in six centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48.7 months (interquartile range, 42.6-60.9). The 3-year OS was 55.4% in the paclitaxel plus fluorouracil group and 51.8% in the cisplatin plus fluorouracil group (hazard ratio, 0.905 [95% CI, 0.698 to 1.172]; P = .448). The 3-year progression-free survival was also not significantly different between the paclitaxel plus fluorouracil group and the cisplatin plus fluorouracil group (43.7% v 45.5%, respectively; hazard ratio, 0.973 [95% CI, 0.762 to 1.243]; P = .828). Compared with the cisplatin plus fluorouracil group, the paclitaxel plus fluorouracil group had significantly lower incidences of acute grade 3 or higher anemia, thrombocytopenia, anorexia, nausea, vomiting, and fatigue ( P < .05), but higher incidences of acute grade 3 or higher leukopenia, radiation dermatitis, and radiation pneumonitis ( P < .05). CONCLUSION The paclitaxel plus fluorouracil regimen did not significantly prolong the OS compared with the standard cisplatin plus fluorouracil regimen in dCRT in patients with locally advanced ESCC.

Background: Concurrent chemoradiotherapy (CCRT) is a standard treatment for inoperable locally advanced esophageal carcinoma. However, there exists a group of patients who are intolerable to intravenous chemotherapy for the old age or with serious comorbidities. S-1 is an oral fluorouracil derivative with well tolerance than 5-fluorouracil. The ESO-Shanghai 7 trial aimed to access the safety and efficacy of S-1 combined with radiotherapy for esophageal squamous cell carcinoma (ESCC) patients who are elderly or with serious comorbidities.Methods: 105 ESCC patients with old age or serious comorbidities will be enrolled in this prospective, single-arm phase 2 clinical trial. Patients will receive S-1 orally at a dose of 40 mg (BSA ≤ 1.6 m2) or 50 mg (BSA >1.6 m2) twice daily for 28 days. The concurrent radiotherapy dose is 61.2 Gy delivered in 34 fractions. The primary endpoints are 3-yr local control and number and grade of participants with adverse events, and the secondary endpoint is overall survival. Discussion: The aim of this phase 2 trial is to determine the tolerance and efficacy of S-1 concurrent with radiotherapy for ESCC patients with old age or serious comorbidities. A very promising 3-yr local control should beat least 60% from the clinical point of view.Trial registration: ClinicalTrials.gov, NCT01831531. Registered 29 March 2013, https://clinicaltrials.gov/ct2/show/NCT01831531?term=NCT01831531&draw=2&rank=1

This study aimed to investigate the risk factors of second primary cancer among female breast cancer (BC) survivors, with emphasis on the prediction of the individual risk conditioned on the patient's characteristics. We identified 208,474 BC patients diagnosed between 2004 and 2010 from the Surveillance, Epidemiology and End Results (SEER) database. Subdistribution proportional hazard model and competing-risk nomogram were used to explore the risk factors of second primary BC and non-BC, and to predict the 5- and 10-year probabilities of second primary BC. Model performance was evaluated via calibration curves and decision curve analysis. The overall 3-, 5-, and 10-year cumulative incidences for second primary BC were 0.9%, 1.6% and 4.4%, and for second primary non-BC were 2.3%, 3.9%, and 7.8%, respectively. Age over 70 years at diagnosis, black race, tumor size over 2 cm, negative hormone receptor, mixed histology, localized tumor, lumpectomy alone, and surgeries plus radiotherapy were significantly associated with increased risk of second BC. The risk of second non-BC was only related to age, race and tumor size. The proposed risk model as well as its nomogram was clinically beneficial to identify patients at high risk of developing second primary breast cancer.

Rationale: Amyloid β (Aβ) deposition, an essential pathological process in age-related macular degeneration (AMD), causes retinal pigment epithelium (RPE) degeneration driven mostly by oxidative stress. However, despite intense investigations, the extent to which overoxidation contributes to Aβ-mediated RPE damage and its potential mechanism has not been fully elucidated. Methods: We performed tandem mass-tagged (TMT) mass spectrometry (MS) and bioinformatic analysis of the RPE-choroid complex in an Aβ1-40-induced mouse model of retinal degeneration to obtain a comprehensive proteomic profile. Key regulators in this model were confirmed by reactive oxygen species (ROS) detection, mitochondrial ROS assay, oxygen consumption rate (OCR) measurement, gene knockout experiment, chromatin immunoprecipitation (ChIP), and luciferase assay. Results: A total of 4243 proteins were identified, 1069 of which were significantly affected by Aβ1-40 and found to be enriched in oxidation-related pathways by bioinformatic analysis. Moreover, NADPH oxidases were identified as hub proteins in Aβ1-40-mediated oxidative stress, as evidenced by mitochondrial dysfunction and reactive oxygen species overproduction. By motif and binding site analyses, we found that the transcription factor PU.1/Spi1 acted as a master regulator of the activation of NADPH oxidases, especially the NOX4-p22phox complex. Also, PU.1 silencing impeded RPE oxidative stress and mitochondrial dysfunction and rescued the retinal structure and function. Conclusion: Our study suggests that PU.1 is a novel therapeutic target for AMD, and the regulation of PU.1 expression represents a potentially novel approach against excessive oxidative stress in Aβ-driven RPE injury.

Background Two randomized phase III trials (EORTC55971 and CHORUS) showed similar progression-free and overall survival in primary or interval debulking surgery in ovarian cancer, however both studies had limitations with lower rate of complete resection and lack of surgical qualifications for participating centers. There is no consensus on whether neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) could be a preferred approach in the management of advanced epithelial ovarian cancer (EOC) in the clinical practice. Methods The Asian SUNNY study is an open-label, multicenter, randomized controlled, phase III trial to compare the effect of primary debulking surgery (PDS) to NACT-IDS in stages IIIC and IV EOC, fallopian tube cancer (FTC) or primary peritoneal carcinoma (PPC). The hypothesis is that PDS enhances the survivorship when compared with NACT-IDS in advanced ovarian cancer. The primary objective is to clarify the role of PDS and NACT-IDS in the treatment of advanced ovarian cancer. Surgical quality assures include at least 50% of no gross residual (NGR) in PDS group in all centers and participating centers should be national cancer centers or designed ovarian cancer section or those with the experience participating surgical trials of ovarian cancer. Any participating center should be monitored evaluating the proportions of NGR by a training set. The aim of the surgery in both arms is maximal cytoreduction. Tumor burden of the disease is evaluated by diagnostic laparoscopy or positron emission tomography/computed tomography scan. Patients assigned to PDS group will undergo upfront maximal cytoreductive surgery within 3 weeks after biopsy, followed by 6 cycles of standard adjuvant chemotherapy. Patients assigned to NACT group will undergo 3 cycles of NACT-IDS, and subsequently 3 cycles of adjuvant chemotherapy. The maximal time interval between IDS and the initiation of adjuvant chemotherapy is 8 weeks. Major inclusion criteria are pathologic confirmed stage IIIC and IV EOC, FTC or PPC; ECOG performance status of 0 to 2; ASA score of 1 to 2. Major exclusion criteria are non-epithelial tumors as well as borderline tumors; low-grade carcinoma; mucinous ovarian cancer. The sample size is 456 subjects. Primary endpoint is overall survival. Trial Registration ClinicalTrials.gov Identifier: NCT02859038

Purpose To evaluate the feasibility and efficacy of involved-field irradiation in definitive chemoradiation therapy for locoregional esophageal squamous cell carcinoma. Methods and Materials Patterns in recurrence and elective nodal failure were analyzed in patients from the previously published ESO-Shanghai 1 trial, who received definitive chemoradiation therapy with involved-field irradiation to 61.2 Gy in 34 fractions using intensity modulated radiation therapy planning. Nodal regions were delineated using the lymph node map from the sixth edition of the American Joint Committee on Cancer staging system. Elective nodal failure was defined as recurrence in the regional nodal area outside the planning target volume. Extensive elective nodal failure, defined as an extensive nodal area regardless of tumor location, was calculated for additional analysis. The incidental (ie, mean) irradiation dose of each node and each region was evaluated. Results With a median follow-up of 48.7 months among survivors, the 3-year actuarial rate for overall survival was 53.6%, and the median overall survival was 44.8 months (95% confidence interval, 34.6-55.0). Of the 436 patients included in this study, 258 patients (59.2%) experienced treatment failure. Elective nodal failure was experienced by 37 patients (8.5%), 7 (1.6%) of whom encountered nodal-only failure. The 3-year actuarial rates of elective nodal control and elective nodal-only control were 89.7% and 97.9%, respectively. The median incidental dose of these nodes was 33.2 Gy (interquartile range [IQR], 1.3-50.7 Gy). The median distance of each node to the planning target volume was 1.4 cm (IQR, 0.6-4.9 cm). Extensive elective nodal failure was experienced by 51 patients (11.6%), and 20 (4.6%) patients had nodal-only failure. The 3-year extensive elective nodal control and extensive elective nodal control-only rates were 86.0% and 94.3%, respectively. The median incidental dose of these nodes was 23.2 Gy (IQR, 1.1-53.5 Gy). The median distance of each node to the planning target volume was 2.0 cm (IQR, 0.6-5.5 cm). Conclusion Involved-field irradiation can achieve a low rate of isolated nodal failure and a satisfactory survival outcome. The use of elective nodal irradiation may be unnecessary in definitive chemoradiation therapy for the treatment of locoregional esophageal squamous cell carcinoma.

Purpose To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) and swept-source optical coherence tomographic angiography (SS-OCTA) to identify polypoidal lesions in serous or serosanguinous maculopathy. Materials and methods A retrospective review of patients presenting pigment epithelial detachments (PEDs) with the diagnosis of polypoidal choroidal vasculopathy (PCV), neovascular age-related macular degeneration (nAMD), and central serous chorioretinopathy (CSC), all of which underwent SD-OCT, SS-OCTA, and indocyanine green angiography (ICGA). Typical features of polypoidal lesions on SD-OCT included sharply peaked PED, notched PED, and hyperreflective ring underneath PED. SS-OCTA feature was vascularized PEDs on cross-sectional images corresponding to cluster-like structures on en face images. The parameters of PEDs were measured for analysis. Results Of 72 eyes, 30 had PCV, 22 had nAMD, and 20 had CSC. A total of 128 localized PEDs were detected on SD-OCT. Typical features on SD-OCT had a high specificity (94.0%) but a limited sensitivity (73.8%). SS-OCTA features provided a higher sensitivity (96.7%). PEDs of the polypoidal lesions unrecognized by SD-OCT were dome-shaped, with smaller ratio of height to base diameter and less area, and almost had heterogeneous internal reflectivity and a connected double-layer sign. Some lesions misidentified by SS-OCTA developed into ICGA-proven polypoidal lesions at follow-up visits. Conclusion A small dome-shaped PED with heterogeneous internal reflectivity and a connected double-layer sign on SD-OCT may suggest a polypoidal lesion of PCV. SS-OCTA may be a helpful tool to investigate preclinical PCV and observe the formation of polypoidal lesions.

Background In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. Methods SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography-computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate. Trial registration ClinicalTrials.gov Identifier: NCT03983226.

BACKGROUND Recent studies have suggested that electrolyte disorders might be a negative prognostic factor for some diseases. OBJECTIVE The purpose of this study was to systematically evaluate the prognostic role of electrolyte disorders in patients with stage I to III colorectal cancer who received radical surgical resection. DESIGN This study was retrospectively performed. SETTINGS The study was conducted at a single tertiary care center. PATIENTS Patients with colorectal cancer who underwent radical resection in between April 2007 and April 2014 were included. MAIN OUTCOME MEASURES The Kaplan-Meier method was adopted to estimate the overall and disease-free survival with and without propensity score matching. RESULTS In total, our study recruited 5089 eligible patients. In prematching analysis, patients with hypochloremia showed both shorter overall survival (HR = 0.943 (95% CI, 0.908-0.980); p = 0.003) and disease-free survival (HR = 0.957 (95% CI, 0.933-0.981); p < 0.001) than those with normal serum chloride levels. In postmatching analysis, 770 patients from each group were compared, and the results further confirmed that hypochloremia was significantly associated with worse overall survival (HR = 0.646 (95% CI, 0.489-0.855); p = 0.002) and disease-free survival (HR = 0.782 (95% CI, 0.647-0.944); p = 0.01), with the hypochloremia group as a reference. LIMITATIONS The study was limited by its retrospective nature. CONCLUSIONS Hypochloremia diagnosed before treatment can independently prognosticate the overall and disease-free survival for patients with stage I to Ш colorectal cancer after radical resection. Intensive surveillance and management might improve the survival outcome for patients with hypochloremia. See Video Abstract at http://links.lww.com/DCR/A727.

Purpose The present study aimed to identify a panel of potential metabolite biomarkers to predict tumor response to neoadjuvant chemo-radiation therapy (NCRT) in locally advanced rectal cancer (LARC). Experimental design Liquid chromatography–mass spectrometry (LC–MS)-based untargeted metabolomics was used to profile human serum samples ( n = 106) from LARC patients treated with NCRT. The samples were collected from Fudan University Shanghai Cancer Center (FUSCC) from July 2014 to January 2016. Statistical methods, such as partial least squares (PLS) and Wilcoxon rank-sum test, were used to identify discriminative metabolites between NCRT-sensitive and NCRT-resistant patients according to their tumor regression grade (TRG). This trial is registered with Clinical Trials.gov, number NCT03149978. Results A panel of metabolites was selected as potential predictive biomarkers of pathological response to NCRT. A total of 4810 metabolic peaks were detected, and 57 significantly dysregulated peaks were identified. These 57 metabolic peaks were used to differentiate patients using PLS in a dataset containing NCRT-sensitive ( n = 56) and NCRT-resistant ( n = 49) patients. The combination of 57 metabolic peaks had AUC values of 0.88, 0.81 and 0.84 in the prediction models using PLS, random forest, and support vector machine, respectively, suggesting that metabolomics has the potential ability to predict responses to NCRT. Furthermore, 15 metabolite biomarkers were identified and used to construct a logistic regression model and explore dysregulated metabolic pathways using untargeted metabolic profiling and data mining approaches. Conclusions A panel of metabolites has been identified to facilitate the prediction of tumor response to NCRT in LARC, which is promising for the generation of personalized treatment strategies for LARC patients.

Lijun Shen,1,2* Miao Mo,2,3* Leon Jia,4 Huixun Jia,2,3 Qingguo Li,2,5 Lei Liang,2,5 Debing Shi,2,5 Zhen Zhang,1,2 Sanjun Cai,2,5 Xinxiang Li,2,5 Ji Zhu1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 3Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China; 4Virginia Commonwealth University, Richmond, VA, USA; 5Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China *These authors contributed equally to this work Purpose: To investigate the association of age and sex on survival in non-metastatic colorectal cancer (CRC) patients and to identify groups at high risk for poor outcomes.Materials and methods: We performed a retrospective analysis of 5,047 non-metastatic CRC patients from 2008 to 2013. Data regarding age at diagnosis; gender; tumor site; tumor stage; differentiation; lymphatic, neural or vascular invasion; and survival outcomes were collected. Patients were stratified into 10-year age groups (≤35, 36–45, 46–55, 56–65, 66–75, >75) and then further analyzed in three age groups (≤35, 36–75, >75). Disease-free survival (DFS) and overall survival (OS) were evaluated using univariate and multivariate Cox regression models.Results: Of the 5,047 eligible patients, 41.3% were female. The tumor stages were balanced between the genders. In the female patients, the tumor stages were similarly distributed among the different age groups, while younger male patients were diagnosed with more advanced disease (P75 had shorter DFS than patients between 36 and 75 years old (HR=1.57 [1.03–2.38] and HR=1.51 [1.11–2.05, respectively]), while there was no difference in DFS between females ≤35 and those >75. For male patients, older age was associated with poorer OS after the same adjustment.Conclusion: Young female CRC patients (≤35 years old) had the poorest DFS and quite poor OS compared to the other age groups. This emphasizes the need for health care providers to have a heightened awareness and to conduct further research when caring for young female CRC patients. Keywords: colorectal cancer, young female, prognosis, China

Background The lymphocytes played an important role in the natural history of cancer. The aim of this study was to explore the prognostic value of lymphocyte count and percentage for survival in advanced cancer patients receiving palliative care. Methods A retrospective review of clinicopathological data from 378 consecutive advanced cancer patients and 106 extended follow-up patients treated with palliative care was conducted. Kaplan–Meier curves and multivariate cox regression analyses were used to evaluate the relationships of peripheral lymphocyte count (LC) and lymphocyte to white blood cell ratio (LWR) with overall survival (OS). Results The median values for pretreatment LC and LWR were 1.1 (IQR, 0.8 ~ 1.5 × 109/L) and 0.138 (IQR, 0.086 ~ 0.208). The median survival times across LWR quartiles were 19, 47, 79, and 101 days (P

Background According to the current official guidelines, at least 12 lymph nodes (LNs) are qualified as an adequate sampling for colon cancer patients. However, patients evaluated with less nodes were still common in the United States, and the prevalence of positive nodal disease may be under-estimated because of the false-negative assessment. In this study, we present a statistical model that allows preoperative determination of the minimum number of lymph nodes needed to confirm a node-negative disease with certain confidence. Methods Adenocarcinoma colon cancer patients with stage T1-T3, diagnosed between 2004 and 2013, who did not receive neoadjuvant therapies and had at least one lymph node pathologically examined, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. A beta binomial distribution was used to estimate the probability of an occult nodal disease is truly node-negative as a function of total number of LNs examined and T stage. Results A total of 125,306 patients met study criteria; and 47,788 of those were node-positive. The probability of falsely identifying a patient as node-negative decreased with an increasing number of nodes examined for each stage, and was estimated to be 72% for T1 and T2 patients with a single node examined and 57% for T3 patients with a single node examined. To confirm an occult nodal disease with 90% confidence, 3, 8, and 24 nodes need to be examined for patients from stage T1, T2, and T3, respectively. Conclusions The false-negative rate of diagnosed node negative, together with the minimum number of examined nodes for adequate staging, depend preoperatively on the clinical T stage. Predictive tools can recommend a threshold on the minimum number of examined nodes regarding to the favored level of confidence for each T stage. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3491-2) contains supplementary material, which is available to authorized users.

// Fangqi Liu 1, * , Cong Li 1, * , Huixun Jia 2, * , Li Yang 1 , Yuchen Wu 1 , Jiang Zhao 1 , Sanjun Cai 1 , Ji Zhu 3 and Ye Xu 1 1 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 2 Department of Clinical Statistics, Fudan University Shanghai Cancer Center, Shanghai 200032, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 3 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China * These authors contributed equally to this work and should be regarded as joint first authors Correspondence to: Ye Xu, email: xuye021@163.com Ji Zhu, email: leo.zhu@126.com Keywords: colorectal cancer, tumor location, prognosis, left-sided colon cancer, right-sided colon cancer Received: September 20, 2016 Accepted: February 21, 2017 Published: March 17, 2017 ABSTRACT Differences in epidemiology, pathological features, and molecular pathogeneses have been observed according to primary tumor location in colorectal cancer (CRC). However, predicting CRC survival by tumor location remains controversial. Therefore, we compared the pathological characteristics, molecular features, and prognoses of right-side colon cancer (RCC), left-side colon cancer (LCC), and rectal cancer (RECC) among Chinese patients with CRC. We evaluated 4,426 patients with stage I–III CRC between January 2008 and July 2014from Fudan University Shanghai Cancer Center. All patients were grouped by the locations of tumors (RCC, LCC, and RECC). Patients with RCC were more likely to be women and older, have poorly differentiated tumors, microsatellite repair deficiency (dMMR), negative p53 expression, and the mucinous subtype. Unadjusted Kaplan-Meier survival curves revealed survival in RCC than in LCC and RECC. However, there were no significant differences in OS and DFS between LCC and RECC. The same results were observed for each disease stage. Unadjusted models revealed an increased risk of mortality, recurrence, or metastasis for RCC (OS: HR, 1.68, P =0.0002 and DFS: HR, 1.24, P =0.032), compared to LCC (all stages), and a similar result was observed for stage III patients (OS: HR, 1.79, P

PURPOSE: To describe the distribution of ganglion cell–inner plexiform layer (GCIPL) thickness among Chinese young adults and report whether the decreased GCIPL thickness is associated with myopia. METHODS: In this study, we included Chinese young adults who underwent Cirrus spectral domain-optical coherence tomography (SD-OCT). SD-OCT was used to measure average and minimum GCIPL thickness, and GCIPL thickness at all sectors. Subfoveal choroidal thickness (CT), axial length (AL), and spherical equivalents (SE) were also measured. RESULTS: A total of 348 eyes were included in the analysis. Average GCIPL thickness showed a significant difference between myopes and emmetropes, with 87.89 ± 3.65 μm for emmetropic groups and 82.65 ± 4.96 μm for myopic groups. The GCIPL thickness was significantly thinner in myopia than in emmetropia at all locations (P