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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.

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 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.

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

Background Although palliative care has been accepted throughout the cancer trajectory, accurate survival prediction for advanced cancer patients is still a challenge. The aim of this study is to identify pre-palliative care predictors and develop a prognostic nomogram for overall survival (OS) in mixed advanced cancer patients. Methods A total of 378 consecutive advanced cancer patients were retrospectively recruited from July 2013 to October 2015 in one palliative care unit in China. Twenty-three clinical and laboratory characters were collected for analysis. Prognostic factors were identified to construct a nomogram in a training cohort (n = 247) and validated in a testing cohort (n = 131) from the setting. Results The median survival time was 48.0 (95% CI: 38.1–57.9) days for the training cohort and 52.0 (95% CI: 34.6–69.3) days for the validation cohort. Among pre-palliative care factors, sex, age, tumor stage, Karnofsky performance status, neutrophil count, hemoglobin, lactate dehydrogenase, albumin, uric acid, and cystatin-C were identified as independent prognostic factors for OS. Based on the 10 factors, an easily obtained nomogram predicting 90-day probability of mortality was developed. The predictive nomogram had good discrimination and calibration, with a high C-index of 0.76 (95% CI: 0.73–0.80) in the development set. The strong discriminative ability was externally conformed in the validation cohort with a C-index of 0.75. Conclusions A validated prognostic nomogram has been developed to quantify the risk of mortality for advanced cancer patients undergoing palliative care. This tool may be useful in optimizing therapeutic approaches and preparing for clinical courses individually. Electronic supplementary material The online version of this article (10.1186/s12904-019-0432-7) contains supplementary material, which is available to authorized users.

Purpose This study aimed to profile the characteristics of patients with colorectal cancer (CRC) with a second primary malignancy (SPM) and to identify patients with CRC at high risk of developing SPMs. Methods We retrospectively reviewed data on patients with CRC aged 20–79 years from the Surveillance, Epidemiology, and End Results (SEER) database. Eligible patients were categorized into only one primary malignancy and SPM cohorts. A competing‐risk model was used to quantify associations between SPM occurrence and the multiple traits of patients. Finally, a decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model by calculating net benefit. Results A total of 179,884 patients were identified, 18,285 (10.2%) of whom developed SPMs during a maximum follow‐up of approximately 18 years. The median survival time after the second diagnosis was less than 4 years. The 3‐year, 5‐year, and 10‐year cumulative risks of developing an SPM were 3.9%, 5.9%, and 10.0%, respectively. According to the multivariable competing‐risk model, male colon cancer survivors, older in age, with a well‐differentiated tumor and localized disease, who were treated with surgery were susceptible to SPMs. The DCA yielded a wide range of risk thresholds at which the net benefits would be obtained from our proposed model. Conclusion CRC survivors remain at high risk of developing SPMs. Patients with a second diagnosis of cancer showed not only significantly worse survival but also higher cancer‐specific mortality. A web‐based individualized predictive tool was also provided to assist clinicians in identifying patients at high risk of developing SPMs and planning their future care management. Implications for Practice Colorectal cancer survivors remain at high risk of developing a second primary malignancy (SPM). This study aimed to profile the characteristics of patients with colorectal cancer with second primary malignancies and to further explore the risk factors related to the development of second primary malignancies, using a large population‐based cohort. A clinically useful competing‐risk nomogram was developed to predict the risk of SPMs based on individual clinical factors. According to the findings, older age, male sex, white or black race, localized disease, and treatment with surgery among patients with colon cancer were associated with an increased risk of developing an SPM. These findings and the proposed tool could be useful to clinicians and caregivers in the clinical counseling of patients with colorectal cancer and the development of long‐term care management., Little is known about the factors that contribute to the development of a new malignancy among colorectal cancer survivors. This study aimed to comprehensively profile the characteristics of patients with colorectal cancer with a second primary malignancy and, further, to identify patients at high risk for developing a second primary malignancy.

Background This study was carried out to investigate the prognostic value of baseline and dynamic changes in anxious emotion in advanced cancer patients undergoing palliative care. Methods The association between anxious emotion and survival was investigated in a retrospective sample of 377 consecutive advanced cancer patients receiving palliative care from August 2013 to October 2015 and in an extended follow-up study of 106 of those patients. Results The prevalence of anxious emotion was 24.93% (94/377) overall, 22.48% (47/209) in men and 27.97% (47/168) in women. Significant associations between baseline anxious emotion and overall survival (OS) were not found in the whole sample or in women. However, univariate and multivariate analyses showed that anxious emotion was an independent prognostic indicator of OS in men (hazard ratio [HR]: 1.811, P = .003). Moreover, findings showed that newly developed anxious emotion was significantly associated with poor OS in all readmitted patients (HR: 5.568, P

// Qingguo Li 1,2,* , Lei Liang 1,2,* , Huixun Jia 2,3 , Xinxiang Li 1,2 , Ye Xu 1,2 , Ji Zhu 3,4 and Sanjun Cai 1,2 1 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 3 Center for Biomedical Statistics, Fudan University Shanghai Cancer Center, Shanghai, China 4 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China * These authors have contributed equally to this work Correspondence to: Sanjun Cai, email: // Ji Zhu, email: // Keywords : colorectal cancer; surgical resection; prognosis analysis; lymph node ratio Received : December 23, 2015 Accepted : July 14, 2016 Published : July 24, 2016 Abstract Negative lymph node counts has recently attracted attention as a prognostic indicator in colorectal cancer (CRC). But little is known about prognostic significance of negative to positive lymph node ratio (NPR) in CRC. Our aim was to determine impact of NPR on oncological outcomes in patients with stage III CRC. This retrospective study included 2,256 patients with stage III CRC under curative resection at Fudan university Shanghai cancer center. Kaplan-Meier methods and multivariable Cox regression models were built for the analysis of survival outcomes and risk factors. Accuracy of the NPR was assessed with the Harrell’s concordance-index(C-index).X-tile program identified 2.38 or 0.55/2.38 as the optimal cutoff value for NPR to divide the cohort into high/low risk or high/middle/low risk subsets in terms of CRC cause specific survival (CCSS). In a multivariate analysis, NPR was significant independent prognostic factors for CCSS ( P 0.05 ).Further analysis found NPR could give detailed prognostic classification for both N1 and N2 stage ( P 2.38 stage have similar survival outcome with N1+ NPR >2.38 stage (χ2=0.030, P =0.863), and better than those at N1+ NPR ≤2.38 and N2+ NPR ≤2.38 stage ( P

Increasing evidence indicates that inflammation plays a vital role in tumorigenesis and progression. However, the prognostic value of inflammatory biomarkers in colorectal cancer (CRC) has not been established. In this study, a retrospective analysis was conducted in patients with CRC in Fudan University Shanghai Cancer Center (FUSCC) between April 1, 2007 and April 30, 2014, and 5,336 patients were identified eligible. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and albumin/globulin ratio (AGR) were analyzed. Kaplan-Meier analysis was used to calculate the 5-year overall survival (OS) and disease-free survival (DFS). Cox regression analysis was performed to assess the prognostic factors. Nomograms were established to predict OS and DFS, and Harrell's concordance index (c-index) was adopted to evaluate prediction accuracy. As results, the 5-year OS was 79.2% and the 5-year DFS was 56.0% in the cohort. Patients were stratified into 2 groups by NLR (≤2.72 and >2.72), PLR (≤219.00 and >219.00), LMR (≤2.83 and >2.83) and AGR ( 2.72, PLR > 219.00, LMR ≤ 2.83 and AGR

6001 Background: In China, secondary cytoreductive surgery (SCR) has been standard of care in some high volume cancer centers for ovarian cancer (OC) and most pts prefer surgery over the past two decades. Although GOG213 showed no OS benefit, the debate on selected pts and the conflict with certain local clinical care is still open. Methods: Pts with 1st relapsed OC after 6m+ platinum-free interval (PFI) were eligible if predicted to be a potential R0 by iMODEL score combined with PET-CT image and were randomized to SCR followed by chemotherapy (surgery arm) vs 2nd line chemotherapy alone (no surgery arm). Co-primary endpoint is PFS and OS. The 2nd endpoint is accumulated treatment-free survival (TFSa), which was defined as the overall survival time minus the time of surgery and chemotherapy after randomization. We report analysis of PFS and interim analysis of TFSa. Results: 357 pts were randomized 2012-2019. 6.3% of 175 pts were operated in no surgery arm and cross-over rate was 36.9% in 2nd+ relapsed pts of no surgery arm. 97% and 96% of pts received a platinum-containing 2nd line therapy. Complete resection (R0) rate was 76.7% in overall and 61.1% in pts with iMODEL> 4.7. 60 d mortality rates were 0 % in both surgery and no surgery arm. Postoperative 30 d complication rate with ≥ grade 3 was 5.2%. The median follow-up was 36.0 m. Median PFS was 17.4 m and 11.9 m in surgery and no surgery arm, respectively (HR 0.58, 95% CI 0.45-0.74, p < 0.001). Median time to start of first subsequent therapy (TFST) was 18.1 m vs 13.6 m in favor of the surgery arm (HR 0.59, 95%CI 0.46-0.76). 1.1% and 10.1% of pts underwent Bevacizumab and PARPi maintenance in the 2nd line therapy. The OS and TFSa was immatured. The median TFSa was unreached and 39.5 m in R0 subgroup and no surgery arm, respectively (HR0.59, 95%CI 0.38-0.91). TFSa in surgery arm showed a better long-term survival than that in no surgery group (restricted mean survival time from 60 to 72m: 6.2m vs 4.2m). Conclusions: SCR in selected pts resulted in a dramatically significant extension of PFS. The interim analysis of TFSa indicate that SCR might contribute to long-term survival.

Background Previous studies have shown that industry funded trials are associated with pro-industry conclusions and publication bias. Less is known about the role of industry funders and their influence on trial conclusions and time to publication. Methods We identified all industry funded RCTs published in six high-impact clinical journals between 2014 and 2016 to estimate the prevalence of the role of industry funders in trial design, data collection, data analyses, data interpretation and manuscript writing. Ordinal logistic regression was used to assess the association between the role of industry funders and trial conclusions, which was classified on a five-point scale. Cox proportional-hazards were used to examine the effect of role of funder on time to publication. Results Of the 255 eligible RCTs, industry funders had a role in trial design in 179 (70.2%) trials, data collection in 160 (62.7%) trials, data analyses in 173 (67.8%) trials, data interpretation in 135 (52.9%) trials and manuscript writing in 168 (65.9%) trials. Trials with any role of industry funders had 3.6 times (95% CI 2.0-6.6) higher odds of having positive conclusions compared with those without role of industry funders. In trials with any role of industry funders, positive trials were published more rapidly than negative trials (hazard ratio = 4.3; 95% CI 2.7-6.7, P

Background We assessed the efficacy of adding intraperitoneal (IP) chemotherapy to standard first-line intravenous (IV) chemotherapy in epithelial ovarian cancer (EOC) patients. Methods Patients with stage IIIC-IV EOC who underwent optimal debulking surgery were randomly assigned to four cycles of weekly IP chemotherapy with cisplatin (50 mg/m2) and etoposide (100 mg/m2) followed by six cycles of IV chemotherapy every 3 weeks (IP/IV arm), or were administered IV chemotherapy alone (IV arm). The primary endpoint for this study was the 12-month non-progression rate (NPR). Results Between 4/2009 and 9/2015, 218 patients were randomised, of whom 215 initiated treatment. In the IP/IV arm, 90.6% of patients completed 4 cycles of IP chemotherapy. The 12-month NPRs were 81.9% and 64.2% in the IP/IV and IV groups, respectively (HR 0.48 (95% CI 0.27–0.82)). The median progression-free survival (PFS) was increased in the IP/IV arm compared with that in the IV arm (22.4 vs. 16.8 months; HR 0.66 (0.48–0.91)) and in a subgroup with no gross cytoreduction (31.1 vs. 16.8 months; HR 0.46 (0.26–0.82)). Similar findings were detected with regard to time to first subsequent anticancer therapy (TFST) (25.9 vs. 18.0 months; P = 0.009) and time to second subsequent anticancer therapy (TSST) (40.8 vs. 30.1 months; P = 0.042). Grade 3/4 leukopenia, anaemia and gastrointestinal events were more common in the IP/IV arm, but the treatment burden was considered acceptable. Conclusions IP chemotherapy prior to IV chemotherapy was associated with an increased 12-month NPR and a longer TSST than IV alone in patients with EOC, albeit with acceptable toxic effects. Long-term follow-up is warranted to identify the effects of IP therapy on overall survival.

To investigate whether survival is improved by using the right thoracic approach (extended lymphadenectomy) compared with the left thoracic approach (limited lymphadenectomy) for esophageal cancer.The optimal surgical technique for esophageal cancer remains unclear.Between May 2010 and July 2012, 300 patients with middle and lower thoracic esophageal carcinoma were randomized to receive esophagectomy through either the right or left thoracic approach. Of these, 286 patients with squamous cell carcinoma determined by postoperative pathology were included in this analysis. Disease-free survival (DFS) and overall survival (OS) were compared between the right (n = 146) and left thoracic groups (n = 140).The median follow-up was 55.9 months [95% confidence interval (CI): 53.1-58.6]. The 3-year DFS rates were 62% and 52% in the right and left thoracic arms, respectively [hazard ratio (HR) 0.709; 95% CI, 0.506-0.995; P = 0.047, log-rank test]. The 3-year OS rates were 74% and 60%, respectively (HR, 0.663; 95% CI, 0.457-0.961; P = 0.029). Subgroup analyses revealed longer DFS in the right thoracic arm (vs left thoracic arm) in patients with lymph node involvement (HR, 0.632; 95% CI, 0.412-0.969, P = 0.034), but not in patients without lymph node involvement (HR, 0.757; 95% CI, 0.434-1.320, P = 0.325), and in patients with R1-2 resection margins (HR, 0.495; 95% CI, 0.290-0.848, P = 0.009), but not R0 margins (HR, 0.944; 95% CI, 0.603-1.477, P = 0.801).Compared with the left thoracic approach, the right thoracic approach associated with increased DFS and OS in esophageal squamous cell carcinoma patients, particularly in those with lymph node involvement and/or R1-2 resection margins.

// Weiwei Zhao 1,2,* , Peng Wang 2,3,* , Huixun Jia 2,4 , Menglei Chen 1 , Xiaoli Gu 1 , Minghui Liu 1 , Zhe Zhang 1 , Wenwu Cheng 1,2 and Zhenyu Wu 5 1 Center for Biomedical Statistics, Fudan University Shanghai Cancer Center, Shanghai, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 3 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China 4 Center for Biomedical Statistical, Fudan University Shanghai Cancer Center, Shanghai, China 5 Department of Biostatistics, School of Public Health, Key Laboratory of Public Health Safety and Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Zhenyu Wu, email: // Wenwu Cheng, email: // Keywords : neutrophil count, neutrophil percentage, prognostic value, advanced cancer, palliative care Received : November 15, 2016 Accepted : March 09, 2017 Published : March 22, 2017 Abstract The purpose of this study was to evaluate the count and percentage of neutrophils as prognostic indicators in advanced cancer patients undergoing palliative care. 378 consecutive patients receiving treatment at the palliative care unit of Fudan University Shanghai Cancer Center between July 2013 and October 2015 were reviewed. In 106 of these patients, the data were extended during the follow-up. The cut-off values selected for the neutrophil count and percentage were 8.0×10 9 /L and 85%, respectively. Both a high pretreatment neutrophil count ( HR = 1.828, 95% CI: 1.409~2.371, P

The objective of this study was to investigate the prognostic value of pretreatment NLR and its dynamic changes responsive to palliative care in advanced cancer patients. The study was retrospectively assessed in 378 consecutive advanced cancer patients receiving palliative care and in an extended follow-up study of 106 of those patients. The cutoff value of pretreatment NLR was determined to be 3.0. In the 378 advanced cancer patients, 89 had pretreatment NLR ≤ 3 and 289 had an NLR > 3. Univariate and multivariate analyses showed that tumor stage, palliative care, albumin level and pretreatment NLR (HR: 1.514, 95% CI: 1.125~2.038, P = 0.006) were independent prognostic indicators of OS. Moreover, in the follow-up cohort of 106 readmitted patients, 43 patients achieved a decreased NLR after palliative care, while the remaining 63 patients showed an increased NLR. Univariate and multivariate analyses showed that an increase in NLR was significantly associated with a poor survival (HR: 2.506, 95% CI: 1.474~4.261, P = 0.001). In conclusion, pretreatment NLR and changes in NLR independently predicted OS in advanced cancer patients undergoing palliative care. Incorporating NLR into clinical practice may better inform the prognosis and therapy decisions of advanced cancer patients in palliative settings.

// Lei Liang 1, 2 , Ji Zhu 1, 2, 3 , Huixun Jia 1, 2 , Liyong Huang 1, 2 , Dawei Li 1, 2 , Qingguo Li 1, 2 , Xinxiang Li 1, 2 1 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China 3 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China Correspondence to: Xinxiang Li, e-mail: lxx1149@163.com Keywords: pretreatment lymphocyte count, stage II colorectal cancer, prognosis, high risk, adjuvant chemotherapy Received: June 22, 2015 Accepted: October 07, 2015 Published: October 20, 2015 ABSTRACT Pretreatment lymphocyte count (LC) has been associated with prognosis and chemotherapy response in several cancers. The predictive value of LC for stage II colorectal cancer (CRC) and for high-risk patients treated with adjuvant chemotherapy (AC) has not been determined. A retrospective review of prospectively collected data from 1332 consecutive stage II CRC patients who underwent curative tumor resection was conducted. A pretreatment LC value