Net survival in recurrence-free colon cancer patients

PurposeConditional net survival in recurrence-free patients (CNS-RF) provides relevant clinical information and has never been assessed yet in a non-selected colon cancer population. We aimed to estimate conditional 5-year net survival in recurrence-free patients with colon cancer in the population-based Digestive Cancer Registry of Burgundy (France).MethodsCNS-RF was estimated in the 3736 patients resected for cure for primary colon cancer between 1976 and 2006, using a flexible parametric model of net survival for every additional year survived at diagnosis and from 1 to 5 years thereafter.ResultsThe net probability of surviving 5 more years increased from 72% at diagnosis to 92% for recurrence-free patients who survived 5 years after diagnosis. CNS-RF was over 90% 3 years after diagnosis in patients aged 75 and below. CNS-RF was over 95% in patients diagnosed after 2000 who were recurrence-free 3, 4 or 5 years after diagnosis. CNS-RF was similar between patients with stage I and II disease from 2 years after diagnosis and patients with stage III disease from 5 years after diagnosis. The initial differences in net survival related to gross features, clinical presentation, number of harvested nodes in stage II, and number of involved nodes in stage III disappeared after 2 years.ConclusionsCNS-RF is a relevant measure of prognosis in patients who have already achieved a period of remission. Providing an updated estimation of prognosis in the years following diagnosis may improve the survivors’ quality of life and access to credit or insurance.     

Breast and colorectal cancer recurrence-free survival estimates in the US: Modeling versus active data collection

BackgroundA modeling method was developed to estimate recurrence-free survival using cancer registry survival data. This study aims to validate the modeled recurrence-free survival against “gold-standard” estimates from data collected by the National Program of Cancer Registries (NPCR) Patient-Centered Outcomes Research (PCOR) project.MethodsWe compared 5-year metastatic recurrence-free survival using modeling and empirical estimates from the PCOR project that collected disease-free status, tumor progression and recurrence for colorectal and female breast cancer cases diagnosed in 2011 in 5 U.S. state registries. To estimate empirical recurrence-free survival, we developed an algorithm that combined disease-free, recurrence, progression, and date information from NPCR-PCOR data. We applied the modeling method to relative survival for patients diagnosed with female breast and colorectal cancer in 2000–2015 in the SEER-18 areas.ResultsWhen grouping patients with stages I-III, the 5-year metastatic recurrence-free modeled and NPCR-PCOR estimates are very similar being respectively, 90.2 % and 88.6 % for female breast cancer, 74.6 % and 75.3 % for colon cancer, and 68.8 % and 68.5 % for rectum cancer. In general, the 5-year recurrence-free NPCR-PCOR and modeled estimates are still similar when controlling by stage. The modeled estimates, however, are not as accurate for recurrence-free survival in years 1–3 from diagnosis.ConclusionsThe alignment between NPCR-PCOR and modeled estimates supports their validity and provides robust population-based estimates of 5-year metastatic recurrence-free survival for female breast, colon, and rectum cancers. The modeling approach can in principle be extended to other cancer sites to provide provisional population-based estimates of 5-year recurrence free survival.     

Racial disparities in treatment and survival from ovarian cancer

BackgroundBlack women with ovarian cancer in the U.S. have lower survival than whites. We aimed to identify factors associated with racial differences in ovarian cancer treatment and overall survival (OS).MethodsWe examined data from 365 white and 95 black ovarian cancer patients from the Hollings Cancer Center Cancer Registry in Charleston, S.C. between 2000 and 2015. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between race and receipt of surgery and chemotherapy, and Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs between race and OS. Model variables included diagnosis center, stage, histology, insurance status, smoking, age-adjusted Charlson comorbidity index (AACI) and residual disease. Interactions between race and AACI were assessed using −2 log likelihood tests.ResultsBlacks vs. whites were over two-fold less likely to receive a surgery-chemotherapy sequence (multivariable-adjusted OR 2.46, 95% CI 1.43–4.21), particularly if they had a higher AACI (interaction p = 0.008). In multivariable-adjusted Cox models, black women were at higher risk of death (HR 1.81, 95% CI 1.35–2.43) than whites, even when restricted to patients who received a surgery-chemotherapy sequence (HR 1.79, 95% CI 1.10–2.89) and particularly for those with higher AACI (HR 4.70, 95% CI 2.00 − 11.02, interaction p = 0.01).ConclusionsAmong blacks, higher comorbidity associates with less chance of receiving guideline-based treatment and also modifies OS. Differences in receipt of guideline-based care do not completely explain survival differences between blacks and whites with ovarian cancer. These results highlight opportunities for further research.     

American Indian/Alaska Native and black colon cancer patients have poorer cause-specific survival based on disease stage and anatomic site of diagnosis

ObjectivesStudies of race-specific colon cancer (CC) survival differences between right- vs. left-sided CC typically focus on Black and White persons and often consider all CC stages as one group. To more completely examine potential racial and ethnic disparities in side- and stage-specific survival, we evaluated 5-year CC cause-specific survival probabilities for five racial/ethnic groups by anatomic site (right or left colon) and stage (local, regional, distant).MethodsWe obtained cause-specific survival probability estimates from National Cancer Institute’s population-based Surveillance, Epidemiology, and End Results (SEER) for CC patients grouped by five racial/ethnic groups (Non-Hispanic American Indian/Alaska Native [AIAN], Non-Hispanic Asian/Pacific Islander [API], Hispanic, Non-Hispanic Black [NHB], and Non-Hispanic White [NHW]), anatomic site, stage, and other patient and SEER registry characteristics. We used meta-regression approaches to identify factors that explained differences in cause-specific survival.ResultsDiagnoses of distant-stage CC were more common among NHB and AIAN persons (>22 %) than among NHW and API persons (< 20 %). Large disparities in anatomic site-specific survival were not apparent. Those with right-sided distant-stage CC had a one-year cause-specific survival probability that was 16.4 % points lower (99 % CI: 12.2–20.6) than those with left-sided distant-stage CC; this difference decreased over follow-up. Cause-specific survival probabilities were highest for API, and lowest for NHB, persons, though these differences varied substantially by stage at diagnosis. AIAN persons with localized-stage CC, and NHB persons with regional- and distant-stage CC, had significantly lower survival probabilities across follow-up.ConclusionsThere are differences in CC presentation according to anatomic site and disease stage among patients of distinct racial and ethnic backgrounds. This, coupled with the reality that there are persistent survival disparities, with NHB and AIAN persons experiencing worse prognosis, suggests that there are social or structural determinants of these disparities. Further research is needed to confirm whether these CC cause-specific survival disparities are due to differences in risk factors, screening patterns, cancer treatment, or surveillance, in order to overcome the existing differences in outcome.     

Short- and long-term survival outcomes among never smokers who developed lung cancer

BackgroundLung cancer is the leading cause of cancer death in the US. While an extensive literature exists detailing lung cancer risk factors and mortality among patients with a history of tobacco use, the data are more limited among individuals who have never smoked. The purpose of this investigation is to compare survival rates between the two groups and evaluate potential risk factors among never smokers.MethodsThis retrospective study included 3380 smokers and 334 never smokers who were diagnosed with lung cancer at Stony Brook University Hospital between 2003 and 2016. 1-, 3-, 5- and 10-year survival outcomes, stratified by smoking status, were compared and Kaplan-Meier curves for overall survival are provided. Cox Proportional Hazard models were used to evaluate factors influencing survival among never smokers.ResultsNever smokers with lung cancer were more likely to be female, be diagnosed with adenocarcinoma histology, and had fewer comorbidities than lung cancer patients who smoked. Although 60% of patients were diagnosed at a later stage of disease development, regardless of smoking status, overall short- and long-term survival was significantly higher among never smokers compared to those with a history of tobacco use. In addition to age and stage at diagnosis, a history of diabetes was found to be a significant prognostic factor for decreased survival among never smokers (HR=3.15, 95% CI (1.74, 5.71)).ConclusionsData from the present investigation suggest that, regardless of smoking status, approximately three of every five lung cancer patients are diagnosed at a later stage, and that both short- and long-term survival outcomes are significantly better among never smokers compared to those with a history of tobacco use. Additional studies are required to validate these findings and better explain the mechanistic drivers for the improved outcomes among never smokers.     

Rosiglitazone is not associated with an increased risk of bladder cancer

BackgroundWhether rosiglitazone may increase bladder cancer risk has not been extensively investigated.MethodsThe reimbursement databases of all Taiwanese diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and a total of 885,236 patients with type 2 diabetes were followed up for bladder cancer incidence till end of 2009. Incidences for ever-users, never-users and subgroups of rosiglitazone exposure (using tertile cutoffs of time since starting rosiglitazone, duration of therapy and cumulative dose) were calculated and hazard ratios estimated by Cox regression.ResultsThere were 102,926 ever-users and 782,310 never-users, respective numbers of incident bladder cancer 356 (0.35%) and 2753 (0.35%), and respective incidence 98.3 and 101.6 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) did not show significant association in unadjusted model [0.969 (0.867, 1.082)] and models adjusted for age and sex [0.983 (0.880, 1.098)] or all covariates [0.980 (0.870, 1.104)]. Neither the P values for the hazard ratios for the different categories of the dose–responsive parameters, nor their P-trends were significant.ConclusionsRosiglitazone does not increase the risk of bladder cancer.     

Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients

Background: Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976–2006 and followed until end 2010, we determined incidence of and survival after bone metastases. Methods: We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan–Meier methodology. Results: Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5 cm, higher tumour grade, lobular carcinoma and ≥four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with <1 year in women with visceral and bone metastases. There was a trend for decreased survival for patients who developed visceral metastases early, and proportionately fewer patients in this group. Interpretation: Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer.     

Relative impact of earlier diagnosis and improved treatment on survival for colorectal cancer: A US database study among elderly patients

PurposesTo estimate what proportion of improvement in relative survival was attributable to smaller stage/size due to early detection and what proportion was attributable to cancer chemotherapy in patients with colorectal cancer (CRC).MethodsWe studied 69,718 patients with CRC aged ≥66 years in 1992–2009 from Surveillance, Epidemiology, and End Results registries. Study periods were categorized into three periods according to the major changes or advances in screening and chemotherapy regimens: (1) Period-1 (1992–1995), during which there was no evidence-based recommendation for routine CRC screening and 5-fluorouracil was the mainstay for chemotherapy; (2) Period-2 (1996–2000), during which evidences and guidelines supported the use of fecal occult blood test (FOBT) and sigmoidoscopy for routine CRC screening; and (3) Period-3 (2001–2009), during which Medicare Program added the full coverage for colonoscopy screening to average-risk individuals, and several newly developed chemotherapy regimens were approved. Outcome variables included the likelihood of being diagnosed at an early stage or with a small tumor size, and improvement in relative survival.ResultsCompared to period-1, likelihood of being diagnosed with early stage CRC increased by 20% in period-2 (odds ratio = 1.2, 95%CI: 1.1–1.2) and 30% in period-3 (1.3, 1.2–1.4); and likelihood of being diagnosed with small-size CRC increased by 60% in period-2 and 110% in period-3. Similarly, 5-year overall relative survival increased from 51% in period-1 to 56% in period-2 and 60% in period-3. Increase in survival attributable to migration in stage/size was 9% in period-2 and 20% in period-3, while the remaining survival improvement during period-2 and period-3 were largely attributable to more effective chemotherapy regimens (≥71.6%) and other treatment factors (≤25%).ConclusionsImprovements in CRC screening resulted in a migration of CRC toward earlier tumor stage and smaller size, which contributed to ≤20% of survival increase. Survival improvement over the past 2 decades was largely explained by more effective chemotherapy regimens (≥71.6%).     

尿路上皮膀胱癌患者泌尿道菌群改变及其对患者预后的影响

研究尿路上皮膀胱癌患者尿液中菌群的变化特征及其对膀胱癌患者预后的影响,为该类患者的治疗提供参考。

选取2018年11月至2021年11月于我院接受治疗的113例尿路上皮膀胱癌患者作为研究对象,经筛选后最终纳入患者89例。根据WHO 2016年分级标准将患者分为低度恶性潜能乳头状尿路上皮肿瘤组（A组,43例）、低级别乳头状尿路上皮癌组（B组,26例）和高级别乳头状尿路上皮癌组（C组,20例）,另外选取同期我院健康体检者50例为对照组,收集所有对象的一般资料,同时收集4组对象中段尿液样本,采用16S rRNA基因高通量测序法检测菌群构成,分析尿液菌群变化特征,并且利用有序变量分析菌群改变与膀胱癌病理分级之间的相关性。

3组膀胱癌患者性别、年龄、平均身高、平均BMI,吸烟史、酗酒史、高血压史、糖尿病史、冠心病史情况比较差异均无统计学意义（均P＞0.05）。和对照组相比,其他3组患者尿液菌群Simpson指数、Shannon指数均显著增加（均P＜0.05）,其中C组患者Simpson指数高于A组和B组,Shannon指数3组之间差异均有统计学意义（均P＜0.05）。和对照组相比,膀胱癌患者尿液中拟杆菌门和放线菌门的丰度无显著变化,但厚壁菌门丰度显著增加,尤其是C组患者达（33.04±5.03）%;膀胱癌患者尿液中变形菌门丰度降低,且随着肿瘤恶性程度的增高而降低（均P＜0.05）;膀胱癌患者尿液中不动杆菌属丰度无显著变化（P＞0.05）,但乳杆菌属,假单胞菌属和双歧杆菌属丰度显著降低,且随着恶性程度的增高而降低,尤其是C组患者（均P＜0.05）。有序变量回归分析显示,Simpson指数、Shannon指数是膀胱癌预后不良的危险因素,变形菌门、乳杆菌属、双歧杆菌属是保护因素（均P＜0.05）。

膀胱癌患者尿液菌群多样性和构成情况与健康人群有显著区别,菌群多样性、厚壁菌门和变形菌门的改变以及乳杆菌属和双歧杆菌属的减少可能与膀胱癌患者的预后相关。

     

Disparities in survival of stomach cancer among different socioeconomic groups in North-East Netherlands

Background: Survival differences in stomach cancer are depended on patient, tumour and treatment factors. Some populations are more prone to develop stomach cancer, such as people with low socioeconomic status (SES). The aim of this population based study was to assess whether differences in socioeconomic status (SES) alone, after adjusting for confounding factors, also influence survival. Methods: From 1989 to 2007 all patients with stomach cancer were selected from the cancer registry of the Comprehensive Cancer Centre North-East. Postal code at diagnosis was used to determine SES, dividing patients in three groups; low, intermediate and high SES. Associations between age, localization, grade, stage, and treatment were determined using Chi-square analysis. Relative survival analysis was used to estimate relative excess risk (RER) of dying according to SES. Results: In low SES neighbourhoods diagnosis was established at older age. More distal tumours were detected in patients with low SES, whereas pathology showed more poorly differentiated tumours in patients with high SES. Overall, more resections were performed in, and more chemotherapy was administrated to patients in high SES neighbourhoods. After adjusting for confounding factors, the risk of dying was lower for patients with high SES (RER 0.89, 95% Confidence Interval 0.81–0.98) compared to patients with low SES. Conclusion: SES proved to be an independent prognostic factor for survival in patients with stomach cancer.     

Positional uncertainty of vaginal cuff and feasibility of implementing portable bladder scanner in postoperative cervical cancer patients

PurposeTo propose a geometrical margin for definition of the vaginal cuff PTV using only CT images of the full bladder (CT_full) in postoperative cervical cancer patients.MethodsTwenty-nine operated cervical cancer patients underwent volumetric arc therapy with a bladder filling protocol. This study assessed bladder filling using a portable bladder scanner and cone-beam computed tomography (CBCT) during the entire treatment period. The measured bladder volumes with a BladderScan® were compared with the delineated volume on CBCT. Titanium clips in the vaginal cuff were analysed to assess geometrical uncertainty and the influence of rectal and bladder volume changes.ResultsBladderScan® showed good agreement with the delineated volume (R = 0.80). The volume changes in the bladder have a greater influence on the clip displacements than in the rectum. The 95th percentile of uncertainty of the clips in reference to CT_full in the right-left (RL), the superoinferior (SI), and the anteroposterior (AP) was 0.32, 0.65, and 1.15 cm, respectively. From this result and intra-fractional movements of the vaginal cuff reported by Haripotepornkul, a new geometrical margin was proposed for definition of the vaginal cuff planning target volume (PTV): 0.5, 0.9, and 1.4 cm in the RL, SI, and AP directions, respectively.ConclusionsA new geometrical margin was proposed for definition of the vaginal cuff PTV based on CT_full, which will be needless of empty bladder at the planning CT scan. This method allows patients to reduce the burden and efficient routine CT scans can be improved.     

Social disparities in survival after diagnosis with colorectal cancer: Contribution of race and insurance status

BackgroundBoth minority race and lack of health insurance are risk factors for lower survival in colorectal cancer (CRC) but the interaction between the two factors has not been explored in detail.MethodsOne to 5-year survival by race/ethnic group and insurance type for patients with CRC diagnosed in 2007-13 and registered in the Surveillance Epidemiology, and EndResultsdatabase were explored. Shared frailty models were computed to further explore the association between CRC specific survival and insurance status after adjustment for demographic and treatment variables.ResultsAge-adjusted 5-year survival estimates were 70.4% for non-Hispanic whites (nHW), 62.7% for non-Hispanic blacks (nHB), 70.2% for Hispanics, 64.7% for Native Americans, and 73.1% for Asian/Pacific Islanders (API). Survival was greater for patients with insurance other than Medicaid for all races, but the differential in survival varied with race, with the greatest difference being seen for nHW at +25.0% and +20.2%, respectively, for Medicaid and uninsured versus other insurance. Similar results were observed for stage- and age-specific analyses, with survival being consistently higher for nHW and API compared to other groups. After confounder adjustment, hazard ratios of 1.53 and 1.50 for CRC-specific survival were observed for Medicaid and uninsured. Racial/ethnic differences remained significant only for nHB compared to nHW.ConclusionsRace/ethnic group and insurance type are partially independent factors affecting survival expectations for patients diagnosed with CRC. NHB had lower than expected survival for all insurance types.     

The impact of health insurance affiliation and socioeconomic status on cervical cancer survival in Bucaramanga,Colombia

Cervical cancer is still an important cause of death in countries like Colombia. We aimed to determine whether socioeconomic status of residential address (SES) and type of health insurance affiliation (HIA) might be associated with cervical cancer survival among women in Bucaramanga, Colombia. All patients residing in the Bucaramanga Metropolitan Area diagnosed with invasive cervical cancer (ICD-0–3 codes C53.X) between 2008 and 2016 (n = 725) were identified through the population-based cancer registry, with 700 women having follow-up data for >5 years (date of study closure: Dec 31, 2021), yielding an overall 5-year survival estimate (95 % CI) of 56.4 % (52.7 – 60.0 %). KM estimates of 5-year overall survival were obtained to assess differences in cervical cancer survival by SES and HIA. Multivariable Cox-proportional hazards modeling was also conducted, including interaction effects between SES and HIA. Five-year overall survival was lower when comparing low vs. high SES (41.9 % vs 57.9 %, p < 0.0001) and subsidized vs. contributive HIA (45.1 % vs 63.0 %, p < 0.0001). Multivariable Cox modeling showed increased hazard ratios (HR) of death for low vs. high SES (HR = 1.78; 95 % CI = 1.18–2.70) and subsidized vs. contributive HIA (HR = 1.44; 95 % CI = 1.13–1.83). The greatest disparity in HR was among women of low SES affiliated to subsidized HIA (vs. contributive HIA and high SES) (HR=2.53; 95 % CI = 1.62–3.97). Despite Colombia’s universal healthcare system, important disparities in cervical cancer survival by health insurance affiliation and socioeconomic status remain.     

Global changes in bladder cancer mortality in the elderly

BackgroundBladder cancer is the 14th most common cause of cancer deaths worldwide and has a mean age of diagnosis of 73 years. Elderly people have fewer curative treatment options for muscle invasive bladder cancer. The aim of this study is to investigate how bladder cancer mortality has changed over the past forty years in different world regions to assess discrepancies between elderly and younger patients with bladder cancer.MethodsBladder cancer mortality data were extracted from the World Health Organisation’s GLOBOCAN database. Age-standardised mortality rates (ASMR) for bladder cancer were computed by year, sex, region and Human Development Index (HDI) using the world standard population.ResultsOverall ASMR in all available countries with data between 1986 and 2014 for men aged ≥ 75 has decreased from 101.2 to 89.9 per 100,000 (−11.2%). The decrease in ASMR for men < 75 has been 0.3–2.0 per 100,000 (−39.4%). In women aged ≥ 75 ASMR has decreased from 26.9 to 22.5 per 100,000 (−16.4%) and in women < 75 the ASMR has decreased from 0.76 to 0.56 per 100,000 (−26.4%).Correlation analysis showed a positive linear relationship between Human Development Index (HDI) and improvement in age-standardised mortality rate in all ages. Pearson’s coefficient showed that correlation was strongest in the 60–74 age group (r = −0.61, p < 0.001) and weakest in those aged ≥ 75 (r = −0.39, p = 0.01).ConclusionBladder cancer mortality is not improving in the elderly at the same rate as the rest of the population. Particular focus should be applied in future research to enhance and expand treatment options for bladder cancer that are appropriate for elderly patients.     

A 16-mRNA signature optimizes recurrence-free survival prediction of Stages II and III gastric cancer

High-throughput messenger RNA (mRNA) analysis has become a powerful tool for exploring tumor recurrence or metastasis mechanisms. Here, we constructed a signature to predict the recurrence risk of Stages II and III gastric cancer (GC) patients. A least absolute shrinkage and selection operator method Cox regression model was utilized to construct the signature. Using this method, a 16-mRNA signature was identified to be associated with the relapse-free survival of Stages II and III GCs in training dataset GSE62254 (n = 194). Then this signature was validated in an independent Gene Expression Omnibus cohort GSE26253 (n = 297) and a dataset of The Cancer Genome Atlas (TCGA; n = 235). This classifier could successfully screen out the high-risk Stages II and III GCs in the training cohort (hazard ratio [HR] = 40.91; 95% confidence interval [CI] = 5.58–299.7; p < .0001). Analysis in two independent validation cohorts yielded consistent results (GSE26253: HR = 1.69, 95% CI = 1.17–2.43,; p = .0045; TCGA: HR = 2.01, 95% CI = 1.13–3.56, p = .0146). Cox regression analyses revealed that the risk score derived from this signature was an independent risk factor in Stages II and III GCs. Besides, a nomogram was constructed to serve clinical practice. Through gene set variation analysis, we found several gene sets associated with chemotherapeutic drug resistance and tumor metastasis significantly enriched in high-risk patients. In summary, this 16-mRNA signature can be used as a powerful tool for prognostic evaluation and help clinicians identify high-risk patients.     

Proton pump inhibitors on pancreatic cancer risk and survival

BackgroundHypergastrinemia may promote the development and progression of pancreatic cancer. Proton pump inhibitor (PPI) therapy is known to cause hypergastrinemia. We sought to determine the association between PPI therapy and the risk of developing pancreatic cancer as well as survival following pancreatic cancer diagnosis.MethodsWe conducted a nested case-control study and a retrospective cohort study in The Health Improvement Network (THIN), a medical records database representative of the UK population. In the case-control study, each patient with incident pancreatic cancer was matched with up to four controls based on age, sex, practice site and both duration and calendar time of follow-up using incidence density sampling. The odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer risk associated with PPI use were estimated using multivariable conditional logistic regression. The retrospective cohort study compared the survival of pancreatic cancer patients according to their PPI exposure at the time of diagnosis. The effect of PPI use on pancreatic cancer survival was assessed using a multivariable Cox regression analysis.ResultsThe case-control study included 4113 cases and 16,072 matched controls. PPI use was more prevalent in cases than controls (53% vs. 26% active users). Adjusting for diabetes, smoking, alcohol use and BMI, PPI users including both former users and active users with longer cumulative PPI use had a higher risk of pancreatic cancer compared to non-users. When assessing survival following pancreatic cancer diagnosis, only short-term, active users had a modest decrease in survival.ConclusionsLong-term PPI therapy may be associated with pancreatic cancer risk. While PPI users recently started on treatment had a slightly worse survival, this result likely is from reverse causation.     

CDO1 promoter methylation is associated with gene silencing and is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients

Molecular biomarkers may facilitate the distinction between aggressive and clinically insignificant prostate cancer (PCa), thereby potentially aiding individualized treatment. We analyzed cysteine dioxygenase 1 (CDO1) promoter methylation and mRNA expression in order to evaluate its potential as prognostic biomarker. CDO1 methylation and mRNA expression were determined in cell lines and formalin-fixed paraffin-embedded prostatectomy specimens from a first cohort of 300 PCa patients using methylation-specific qPCR and qRT-PCR. Univariate and multivariate Cox proportional hazards and Kaplan-Meier analyses were performed to evaluate biochemical recurrence (BCR)-free survival. Results were confirmed in an independent second cohort comprising 498 PCa cases. Methylation and mRNA expression data from the second cohort were generated by The Cancer Genome Atlas (TCGA) Research Network by means of Infinium HumanMethylation450 BeadChip and RNASeq. CDO1 was hypermethylated in PCa compared to normal adjacent tissues and benign prostatic hyperplasia (P < 0.001) and was associated with reduced gene expression (ρ = ?0.91, P = 0.005). Using two different methodologies for methylation quantification, high CDO1 methylation as continuous variable was associated with BCR in univariate analysis (first cohort: HR = 1.02, P = 0.002, 95% CI [1.01–1.03]; second cohort: HR = 1.02, P = 0.032, 95% CI [1.00–1.03]) but failed to reach statistical significance in multivariate analysis. CDO1 promoter methylation is involved in gene regulation and is a potential prognostic biomarker for BCR-free survival in PCa patients following radical prostatectomy. Further studies are needed to validate CDO1 methylation assays and to evaluate the clinical utility of CDO1 methylation for the management of PCa.     

Prognostic factors and survival in metastatic breast cancer: A single institution experience

Background

The current retrospective study aims to identify some determinants of survival in metastatic breast cancer.

Methods

The study concerned 332 patients with synchronous (SM) or metachronous (MM) metastatic breast cancer treated between January 2000 and December 2007. Statistical comparison between subgroups of patients concerning survival was carried out employing log-rank test for the invariable analysis and Cox model for the multivariable analysis. Factors included: age group (≤50 years vs. >50; ≤70 years vs. >70; ≤35 years vs. >35), menopausal status, presentation of metastatic disease (SM vs. MM), disease free interval (DFI) (≤24 months vs. >24 months; ≤60 months vs. >60 months), performance status at diagnosis of metastatic disease (PS) (0–1 vs. >1), hormone receptors (HR), number of metastatic sites (1 site vs. >1), nature of the metastatic site (visceral vs. non visceral), first line therapy, surgery of the primary tumor (SPT), locoregional radiotherapy (LRRT) and use or not of bisphosphonates.

Results

Overall survival at 5 years was 12%. Positive prognostic factors in univariate analysis were: age ≤ 70 years, hormono-dependence of the tumor, good PS (PS 0–1), less than two metastatic sites, no visceral metastases, DFI ≥ 24 months, SPT or LRRT. In multivariate analysis, favorable independent prognostic factors included: good PS (PS 0–1), absence of visceral metastases (liver, lung, brain) and age ≤ 70 years.

Conclusion

Many of the prognostic factors in metastatic breast cancer found in our study are known in the literature but some of them, like the application of locoregional treatment (radiotherapy or surgery) and the use of bisphosphonates, need to be further investigated in randomized clinical trials.