Project description:BackgroundThe multiple imputation approach to missing data has been validated by a number of simulation studies by artificially inducing missingness on fully observed stage data under a pre-specified missing data mechanism. However, the validity of multiple imputation has not yet been assessed using real data. The objective of this study was to assess the validity of using multiple imputation for "unknown" prostate cancer stage recorded in the New South Wales Cancer Registry (NSWCR) in real-world conditions.MethodsData from the population-based cohort study NSW Prostate Cancer Care and Outcomes Study (PCOS) were linked to 2000-2002 NSWCR data. For cases with "unknown" NSWCR stage, PCOS-stage was extracted from clinical notes. Logistic regression was used to evaluate the missing at random assumption adjusted for variables from two imputation models: a basic model including NSWCR variables only and an enhanced model including the same NSWCR variables together with PCOS primary treatment. Cox regression was used to evaluate the performance of MI.ResultsOf the 1864 prostate cancer cases 32.7% were recorded as having "unknown" NSWCR stage. The missing at random assumption was satisfied when the logistic regression included the variables included in the enhanced model, but not those in the basic model only. The Cox models using data with imputed stage from either imputation model provided generally similar estimated hazard ratios but with wider confidence intervals compared with those derived from analysis of the data with PCOS-stage. However, the complete-case analysis of the data provided a considerably higher estimated hazard ratio for the low socio-economic status group and rural areas in comparison with those obtained from all other datasets.ConclusionsUsing MI to deal with "unknown" stage data recorded in a population-based cancer registry appears to provide valid estimates. We would recommend a cautious approach to the use of this method elsewhere.
Project description:BackgroundTwenty-eight states have passed breast density notification laws, which require physicians to inform women of a finding of dense breasts on mammography.ObjectiveTo evaluate changes in breast cancer stage at diagnosis after enactment of breast density notification legislation.DesignUsing a difference-in-differences analysis, we examined changes in stage at diagnosis among women with breast cancer in Connecticut, the first state to enact legislation, compared to changes among women in control states. We used data from the Surveillance, Epidemiology, and End Results Program (SEER) registry, 2005-2013.ParticipantsWomen ages 40-74 with breast cancer.InterventionBreast density notification legislation, enacted in Connecticut in October of 2009.Main measureBreast cancer stage at diagnosis.Key resultsOur study included 466,930 women, 25,592 of whom lived in Connecticut. Legislation was associated with a 1.38-percentage-point (95 % CI 0.12 to 2.63) increase in the proportion of women in Connecticut versus control states who had localized invasive cancer at the time of diagnosis, and a 1.12-percentage-point (95 % CI -2.21 to -0.08) decline in the proportion of women with ductal carcinoma in situ at diagnosis. Breast density notification legislation was not associated with a change in the proportion of women in Connecticut versus control states with regional-stage (-0.09 percentage points, 95 % CI -1.01 to 1.02) or metastatic disease (-0.24, 95 % CI -0.75 to 0.28). County-level analyses and analyses limited to women younger than 50 found no statistically significant associations.LimitationsSingle intervention state, limited follow-up, potential confounding from unobserved trends.ConclusionsBreast density notification legislation in Connecticut was associated with a small increase in the proportion of women diagnosed with localized invasive breast cancer in individual-level but not county-level analyses. Whether this finding reflects potentially beneficial early detection or potentially harmful overdiagnosis is not known. Legislation was not associated with changes in regional or metastatic disease.
Project description:Colorectal cancer (CRC) is the most common cancer in males and third in females in Saudi Arabia, with the majority (66%) diagnosed at a late stage. We evaluated the effect of marital status on stage at diagnosis and CRC survival. We hypothesized that married patients would be more likely to present at an early stage and have higher survival than unmarried patients. The Ministry of National Guard-Health Affairs (MNG-HA) cancer registry was used to identify patients diagnosed with CRC from 2009 to 2017. A competing risk analysis was performed to assess the 5-year CRC-specific survival, adjusting for potential confounders. The Kaplan-Meier method and the Cox regressions were used to assess survival. Two-thirds (76.50%) of the 936 CRC patients were married, 11.64% were unmarried, and 11.86% had an unknown marital status. With multiple imputation-based analysis, the multivariate analysis indicated that unmarried patients were 52% more likely to present at an advanced stage [adjusted odds ratio (aOR) 1.52; 95% CI 1.33-1.73], and had a 30% higher risk of death due to CRC compared to the married patients (aHR 1.30; CI 1.17, 1.44). Future CRC screening and survivorship programs should assess the needs of the vulnerable unmarried population. Interventions supporting the early detection of CRC in this population may be beneficial in the long term and lead to improved cancer outcomes.
Project description:BackgroundOncologic treatment has been associated with unemployment. As endometrial cancer is highly curable, it is important to assess whether patients experience employment disruption after treatment. We evaluated the frequency of employment change following endometrial cancer diagnosis and assessed factors associated with it.MethodsA cohort of patients 18-63 years-old who were diagnosed with endometrial cancer (January 2009-December 2017) were identified in the Truven MarketScan database, an insurance claims database of commercially insured patients in the United States. All patients who were working full- or part-time at diagnosis were included and all employment changes during the year following diagnosis were identified. Clinical information, including use of chemotherapy and radiation, were identified using Common Procedural Terminology codes, and International Statistical Classification of Diseases codes. Cox proportional hazards models incorporating measured covariates were used to evaluate the impact of treatment and demographic variables on change in employment status.ResultsA total of 4381 women diagnosed with endometrial cancer who held a full-time or part-time job 12 months prior to diagnosis were identified. Median age at diagnosis was 55 and a minority of patients received adjuvant therapy; 7.9% received chemotherapy, 4.9% received external-beam radiation therapy, and 4.1% received chemoradiation. While most women continued to work following diagnosis, 21.7% (950) experienced a change in employment status. The majority (97.7%) of patients had a full-time job prior to diagnosis. In a multivariable analysis controlling for age, region of residence, comorbidities, insurance plan type and presence of adverse events, chemoradiation recipients were 34% more likely to experience an employment change (HR 1.34, 95% CI 1.01-1.78), compared to those who only underwent surgery.ConclusionApproximately 22% of women with employer-subsidized health insurance experienced a change in employment status following the diagnosis of endometrial cancer, an often-curable disease. Chemoradiation was an independent predictor of change in employment.
Project description:BackgroundThe oncological safety of diagnostic hysteroscopy in patients with stage Ⅰ endometrial cancer remains uncertain and conflicting. The aim of the proposed systematic review and meta-analysis is to summarise the available evidence examining the association between diagnostic hysteroscopy and the prognosis of stage Ⅰ endometrial cancer and to statistically synthesise the results of relevant studies.Methods and analysisSystematic searches of PubMed/MEDLINE, Embase, Cochrane Library and Web of Science will be undertaken using prespecified search strategies. Two authors will independently conduct eligible studies selection process, perform data extraction and appraise the quality of included studies. Original case-control studies, cohort studies and randomised controlled trails published in English will be considered for inclusion. The outcomes of interest will be 5-year recurrence-free survival, disease-specific survival and overall survival. Meta-analyses will be performed to calculate pooled estimates.Ethics and disseminationOur study will be based on published data, and thus there is no requirement for ethics approval. The results will be shared through publication in a peer-reviewed journal and presentations at academic conferences.Prospero registration numberCRD42020193696.
Project description:To report outcomes following adjuvant high-dose-rate vaginal brachytherapy (VBT) with or without chemotherapy for high-intermediate risk (HIR) and high-risk, early stage endometrial cancer as defined in Gynecologic Oncology Group trial 0249.From May 2000 to January 2014, 68 women with HIR and high-risk endometrial cancer underwent surgical staging followed by VBT. Median VBT dose was 21 Gy delivered in three fractions prescribed to 0.5 cm depth. Paclitaxel 175 mg/m(2) and carboplatin area under the curve 6 was administered every 21 days in sequence with VBT. Actuarial survival estimates were calculated using the Kaplan-Meier method.Patient demographics included a median age of 66 years (range: 36-91) and stages IA (49%), IB (38%), and II (13%), respectively. Thirty-one (46%) patients had HIR disease with endometrioid histology, and 33 (48%) patients had serous or clear cell histology. Thirty-seven (54%) patients received a median 3 cycles (range: 3-6) of chemotherapy in addition to VBT, and 65 patients (96%) completed all prescribed therapy. During a median follow up of 33.1 months (range: 4.0-161.7), four patients have recurred, including one vaginal recurrence. The 3-year estimates of vaginal, pelvic, and distant recurrences were 1.9%, 2.4%, and 9.1%, respectively. The 3-year rates of disease-free and overall survival were 87.7% and 93.9%, respectively.Early outcomes with adjuvant VBT with or without chemotherapy demonstrate high rates of vaginal and pelvic control for women with HIR disease. Early vaginal and pelvic relapses in high-risk patients suggest that pelvic external beam radiotherapy is warranted in this subgroup, but additional data from large phase III trials is warranted.
Project description:Although liquid-based cytology (LBC) has increased the sensitivity of cytological diagnosis of endometrial cancer (EC) compared with conventional smear cytology, the sensitivity of LBC for the detection of EC is between 70% and 96% and remains unsatisfactory. In the present study, we compared the efficacy of LBC with liquid-based genetic diagnosis (LBGDx) by amplicon sequencing of five genes including PTEN, PIK3CA, CTNNB1, KRAS, and TP53 in 48 LBC subjects who underwent endometrial screening. Consequently, LBC classified 15 samples as "positive or suspicious for malignancy" and the 15 were later confirmed as EC. However, LBC failed to identify five cases who were diagnosed as EC by additional transvaginal ultrasound and endometrial curettage, indicating that the sensitivity of cytology alone was 75% (15/20). LBGDx identified 11 pathogenic PTEN variants in 10 subjects, six PIK3CA variants in nine, three CTNNB1 variants in five, two KRAS variants in four, and three TP53 variants in three. Collectively, at least one pathogenic variant was identified in 19 subjects, which included 17 EC (15 endometrioid carcinoma and 2 endometrial carcinosarcomas), and one cervical adenocarcinoma. However, LBGDx did not identify any pathogenic mutations in three of the 20 EC, indicating that the sensitivity of LBGDx alone was 85% (17/20). Although five EC were negative for malignancy by LBC and three were negative for pathogenic mutations by LBGDx, the combination of LBC and LBGDx would successfully diagnose all 20 EC. These data suggested that LBGDx is a useful strategy to improve the sensitivity of screening of EC by LBC.
Project description:ObjectiveThe purpose of this study was to estimate 5-year conditional relative survival (5Y CRS) rates of endometrial cancer (EC) in Korea accounting for time already survived. Subgroup-specific estimates stratified by various patient characteristics were also presented.MethodsUsing the data from the Korean Central Cancer Registry, 5Y CRS rates were calculated in patients who were diagnosed with EC between 1998 and 2017. The CRS rates were presented by year of diagnosis, age at diagnosis, histology, cancer stage, and treatment received.ResultsThe 5-year relative survival rate at the time of diagnosis was 89.0% for all cases. The probability of surviving an additional 5 years (i.e., 5Y CRS), if the patient survived 1, 2, 3, 4, and 5 years after diagnosis was 91.8%, 94.1%, 95.6%, 96.5%, and 97.3%, respectively. Patients with poor initial prognoses, i.e., those who were older, had non-endometrioid histology, and high stage, showed the largest improvements in 5Y CRS, reaching >90% for most subgroups, except those with serous histology (88.4%) and distant stage (77.7%). Patients aged ≥70 years had the highest probability of death in the 1st and 2nd years after diagnosis (13.8 and 11.0%), but the conditional probability of death in the 3rd, 4th, and 5th years declined rapidly to 7.3%, 4.5%, and 3.7%, respectively.ConclusionThe CRS rates for patients with EC improved with increased time elapsed from diagnosis. The greatest improvements in 5Y CRS were observed among patients who were older, those with non-endometrioid histology, and those with more advanced disease.
Project description:Endometrial cancer (EC) stands as the most prevalent gynecological tumor in women worldwide. Notably, differentiation diagnosis of abnormity detected by ultrasound findings (e.g., thickened endometrium or mass in the uterine cavity) is essential and remains challenging in clinical practice. Herein, we identified a metabolic biomarker panel for differentiation diagnosis of EC using machine learning of high-performance serum metabolic fingerprints (SMFs) and validated the biological function. We first recorded the high-performance SMFs of 191 EC and 204 Non-EC subjects via particle-enhanced laser desorption/ionization mass spectrometry (PELDI-MS). Then, we achieved an area-under-the-curve (AUC) of 0.957-0.968 for EC diagnosis through machine learning of high-performance SMFs, outperforming the clinical biomarker of cancer antigen 125 (CA-125, AUC of 0.610-0.684, p < 0.05). Finally, we identified a metabolic biomarker panel of glutamine, glucose, and cholesterol linoleate with an AUC of 0.901-0.902 and validated the biological function in vitro. Therefore, our work would facilitate the development of novel diagnostic biomarkers for EC in clinics.