Yingwei Peng

Temporal trends in the incidence and survival of cancers of the upper aerodigestive tract in Ontario and the United States

The Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology and End Results (SEER) databases were used to describe temporal trends in the incidence and survival of squamous cancers of the upper aerodigestive tract (UADT) in Ontario and the US between 1984 and 2001. Between the 1984–86 and 1999–01 periods, the age‐adjusted incidence rate of all first primary cancers of the UADT decreased from 11.6 (11.2–12.0) to 8.8 (8.5–9.1) in Ontario and 13.0 (12.7–13.3) to 10.2 (10.0–10.4) in the US. Significant decreases in incidence were observed in many UADT sites but there was no significant change in the incidence of cancer of the oropharynx in either the US or Canada. Over the same period, the 5‐year relative survival for all UADT cancers increased from 49.2% (47.2–51.2%) to 57.1%(55.0–59.1%) in Ontario and from 48.1% (46.9–49.3%) to 52.4% (51.2–53.6%) in the US. This significant improvement in the outcome of UADT cancer was largely due to a dramatic increase in the 5‐year relative survival for cancers of the oropharynx from 31.1% (27.1–35.1%) to 53.6% (49.3–57.9%) in Ontario and from 35.3% (32.9–37.8%) to 51.0% (48.7–53.3%) in the US. Smaller increases in survival were observed in cancers of the oral cavity, nasopharynx, and hypopharynx, but there was no evidence of any increase in survival for cancer of the larynx. These results are consistent with the hypothesis that there has been a major change in the etiology of cancer of the oropharynx in Canada and the US and a concomitant change in its response to therapy.

Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer in the Elderly: A Population-Based Study in Ontario, Canada

PURPOSE Non-small-cell lung cancer (NSCLC) is predominantly a disease of the elderly. Retrospective analyses of the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial and the Lung Adjuvant Cisplatin Evaluation (LACE) meta-analysis suggest that the elderly benefit from adjuvant chemotherapy. However, the elderly were under-represented in these studies, raising concerns regarding the reproducibility of the study results in clinical practice. PATIENTS AND METHODS By using the Ontario Cancer Registry, we identified 6,304 patients with NSCLC who were treated with surgical resection from 2001 to 2006. Registry data were linked to electronic treatment records. Uptake of chemotherapy was compared across age groups: younger than 70, 70 to 74, 75 to 79, and ≥ 80 years. As a proxy of survival benefit from chemotherapy, we compared survival of patients diagnosed from 2004 to 2006 with survival of those diagnosed from 2001 to 2003. Hospitalization rates within 6 to 24 weeks of surgery served as a proxy of severe chemotherapy-related toxicity. RESULTS In all, 2,763 (43.8%) of 6,304 surgical patients were elderly (age ≥ 70 years). Uptake of adjuvant chemotherapy in the elderly increased from 3.3% (2001 to 2003) to 16.2% (2004 to 2006). Among evaluable elderly patients, 70% received cisplatin and 28% received carboplatin-based regimens. Requirements for dose adjustments or drug substitutions were similar across age groups. Hospitalization rates within 6 to 24 weeks of surgery were similar across age groups (28.0% for patients age < 70 years; 27.8% for patients age ≥ 70 years; P = .54). Four-year survival of elderly patients increased significantly (47.1% for patients diagnosed from 2001 to 2003; 49.9% for patients diagnosed from 2004 to 2006; P = .01). Survival improved in all subgroups except patients age ≥ 80 years. CONCLUSION Uptake of adjuvant chemotherapy for NSCLC increased in patients age 70 years or older following reporting of pivotal adjuvant chemotherapy trials, but it remained below that for patients younger than age 70 years. Adoption of adjuvant chemotherapy appears to be associated with significant survival benefit in the elderly (age ≥ 70 years), with tolerability apparently similar to that of patients who are younger than age 70 years.

Adoption of adjuvant chemotherapy for non-small-cell lung cancer: a population-based outcomes study.

PURPOSE Since 2004, several clinical trials have demonstrated that adjuvant chemotherapy (ACT) improves survival in patients with early-stage non-small-cell lung cancer (NSCLC). Here, we evaluate the uptake of ACT and its impact on outcomes in the general population of Ontario, Canada. METHODS All patients diagnosed with NSCLC in Ontario from 2001 to 2006 who underwent surgical resection (n = 6,304) were identified using the Ontario Cancer Registry. We linked electronic records of treatment to the registry. We described uptake of ACT and compared survival of all patients with surgically resected NSCLC diagnosed from 2001 to 2003 with patients diagnosed from 2004 to 2006. As a proxy measure of ACT-related toxicity, we evaluated hospitalizations within 6 months of surgery. RESULTS Demographic, disease, and treatment-related characteristics did not differ between the 2001 to 2003 and 2004 to 2006 study cohorts. Over the study period, the proportion of patients receiving ACT increased from 7% (192 of 2,950 patients) to 31% (1,032 of 3,354 patients; P < .001). The proportion of patients admitted to hospital within 6 months of surgery remained stable and (36% in the 2001 to 2003 cohort and 37% in the 2004 to 2006 cohort). However, within 2 years of surgery, there was a 33% reduction in the proportion of patients admitted to hospital with metastatic disease (P < .001). During the study period, there was a substantial improvement in 4-year survival among surgically resected patients, from 52.5% (2001 to 2003) to 56.1% (2004 to 2006; P = .001). CONCLUSION There has been a rapid uptake of ACT for NSCLC, which was not associated with an increased rate of hospitalization. The adoption of ACT was associated with a substantial improvement in overall survival, suggesting that the benefits seen in clinical trials are generalizable to the general population.

Perioperative chemotherapy for muscle-invasive bladder cancer: A population-based outcomes study.

Practice guidelines recommend neoadjuvant chemotherapy (NACT) for bladder cancer. However, the evidence in support of adjuvant chemotherapy (ACT) is less robust. Here we describe whether the evidence of efficacy for NACT/ACT was sufficient to change clinical practice and whether the efficacy demonstrated in clinical trials was translated into effectiveness in the general population.

Fitting semiparametric cure models

Survival data with a sizable cure fraction are commonly encountered in some cancer clinical researches and the semiparametric proportional hazards cure model has been recently investigated to analyze such data. However the estimation method of the model requires a special C program. The restrictive assumptions of the model also limit its application in broader settings. We present a new computational method for the cure model in this article. The method combines the computational methods for logistic regression and the Cox proportional hazards models and is easy to implement in many statistical packages. We also show how this method allows a number of useful extensions of the model to relax the restrictive assumptions. An illustrative example with survival times of lymphoma patients is provided.

Mixture cure models for multivariate survival data

Mixture cure models (MCMs) have been widely used to analyze survival data with a cure fraction. The MCMs postulate that a fraction of the patients are cured from the disease and that the failure time for the uncured patients follows a proper survival distribution, referred to as latency distribution. The MCMs have been extended to bivariate survival data by modeling the marginal distributions. In this paper, the marginal MCM is extended to multivariate survival data. The new model is applicable to the survival data with varied cluster size and interval censoring. The proposed model allows covariates to be incorporated into both the cure fraction and the latency distribution for the uncured patients. The primary interest is to estimate the marginal parameters in the mean structure, where the correlation structure is treated as nuisance parameters. The marginal parameters are estimated consistently by treating the observations within the cluster as independent. The variances of the parameters are estimated by the one-step jackknife method. The proposed method does not depend on the specification of correlation structure. Simulation studies show that the new method works well when the marginal model is correct. The performance of the MCM is also examined when the clustered survival times share common random effect. The MCM is applied to the data from a smoking cessation study.

smcure: An R-package for estimating semiparametric mixture cure models

The mixture cure model is a special type of survival models and it assumes that the studied population is a mixture of susceptible individuals who may experience the event of interest, and cure/non-susceptible individuals who will never experience the event. For such data, standard survival models are usually not appropriate because they do not account for the possibility of cure. This paper presents an R package smcure to fit the semiparametric proportional hazards mixture cure model and the accelerated failure time mixture cure model.

Time to adjuvant chemotherapy and survival in non-small cell lung cancer: a population-based study.

The time interval between surgery and initiation of adjuvant chemotherapy (ACT) may impact survival in colorectal and breast cancers. This is the first report describing the association between time to adjuvant chemotherapy (TTAC) and survival in non–small cell lung cancer (NSCLC).

Curative therapy for bladder cancer in routine clinical practice: A population-based outcomes study

AIMS Definitive therapy of bladder cancer involves cystectomy or radiotherapy; controversy exists regarding optimal management. Here we describe the management and outcomes of patients treated in routine practice. MATERIALS AND METHODS Treatment records were linked to the Ontario Cancer Registry to identify all cases of bladder cancer in Ontario treated with cystectomy or radiotherapy in 1994-2008. Practice patterns are described in three study periods: 1994-1998, 1999-2003, 2004-2008. Logistic regression, Cox model and propensity score analyses were used to evaluate factors associated with treatment choice and survival. RESULTS In total, 3879 cases (74%) underwent cystectomy and 1380 (26%) were treated with primary radiotherapy. Cystectomy use increased over time (66, 75, 78%), whereas radiotherapy decreased (34, 25, 22%), P < 0.001. There was substantial regional variation in the proportion of cases undergoing radiotherapy (range 16-51%). Five year cancer-specific survival (CSS) and overall survival were 40 and 36% for surgical cases and 35 and 26% for radiotherapy cases (P < 0.001). In multivariate Cox model and propensity score analyses, there was no significant difference in CSS between surgery and radiotherapy (hazard ratio 0.99, 95% confidence interval 0.91-1.08); radiotherapy was associated with slightly inferior overall survival (hazard ratio 1.08, 95% confidence interval 1.00-1.16). CONCLUSION Utilisation of cystectomy for bladder cancer in routine practice has increased over time with no evidence of a significant difference in CSS between radiotherapy and cystectomy.

Operational safety practices as determinants of machinery-related injury on Saskatchewan farms

Agricultural machinery is a major source of injury on farms. The importance of machinery safety practices as potential determinants of injury remains incompletely understood. We examined two such safety practices as risk factors for injury: (1) the presence of safety devices on machinery and (2) low levels of routine machinery maintenance. Our data source was the Saskatchewan Farm Injury Cohort baseline survey (n=2390 farms). Factor analysis was used to create measures of the two operational safety practices. The farm was the unit for all analyses and associations were evaluated using multiple Poisson regression models. Limited presence of safety devices on machinery during farm operations was associated with higher risks for injury (RR 1.94; 95% CI 1.13-3.33; p(trend)=0.02). Lower routine maintenance scores were associated with significantly reduced risks for injury (RR 0.54; 95% CI 0.29-0.98; p(trend)=0.05). The first finding implies that injury prevention programs require continued focus on the use of safety devices on machinery. The second finding could indicate that maintenance itself is a risk factor or that more modern equipment that requires less maintenance places the operator at lower risk. These findings provide etiological data that confirms the practical importance of operational safety practices as components of injury control strategies on farms.