Maria Iachina

Nationwide Quality Improvement in Lung Cancer Care: The Role of the Danish Lung Cancer Group and Registry

Introduction: To improve prognosis and quality of lung cancer care the Danish Lung Cancer Group has developed a strategy consisting of national clinical guidelines and a clinical quality and research database. The first edition of our guidelines was published in 1998 and our national lung cancer registry was opened for registrations in 2000. This article describes methods and results obtained by multidisciplinary collaboration and illustrates how quality of lung cancer care can be improved by establishing and monitoring result and process indicators. Methods: A wide range of indicators was established, validated, and monitored. By registration of all lung cancer patients since the year 2000, data on more than 40,000 patients have been included in the database. Results are reported periodically/quarterly and submitted to formal auditing on an annual basis. Results: Improvements in all outcome indicators are documented and statistically significant. Thus the 1-year overall survival rate has increased between 2003 and 2011 from 36.6% to 42.7%, the 2-year survival rate from 19.8% to 24.3%, and the 5-year survival rate from 9.8% to 12.1%. Five-year survival after surgical resection has increased from 39.5% to 48.1%. Improvements of waiting times, accordance between cTNM and pTNM, and resection rates are documented. Conclusion: The Danish experience shows that a national quality management system including national guidelines, a database with high data quality, frequent reports, audit and commitment from all stakeholders can contribute to improve clinical practice, improve core results, and reduce regional differences.

The direct and indirect impact of comorbidity on the survival of patients with non-small cell lung cancer: a combination of survival, staging and resection models with missing measurements in covariates

Objective To examine the direct and indirect impact of comorbidity on the survival. Design A historical cohort study. Setting Denmark. Participants All patients with non-small cell lung cancer who were registered in the Danish Lung Cancer Registry in 2010. Main outcome measures The influence of comorbidity on stage misclassification, probability of resection and survival. Results It was estimated that the comorbidity influences the probability of resection with OR 0.65 and 95% credible interval (0.54; 0.79), the staging process with OR 1.08 and 95% credible interval (0.96; 1.20), and the survival process with HR 1.08 and 95% credible interval (1.02; 1.14). Conclusions We found that comorbidity has a significant indirect effect on survival mediated by the resection process and a slightly direct effect on mortality.

Role of Comorbidity on Survival after Radiotherapy and Chemotherapy for Nonsurgically Treated Lung Cancer

Background: Comorbidity, such as diseases of the cardiovascular, pulmonary, and other systems, may influence prognosis in lung cancer and complicate its treatment. The performance status of patients, which is a known prognostic marker, may also be influenced by comorbidity. Due to the close link between tobacco smoking and lung cancer, and because lung cancer is often diagnosed in advanced ages (median age at diagnosis in Denmark is 70 years), comorbidity is present in a large proportion of lung cancer patients. Methods: Patients with any stage lung cancer who did not have surgical treatment were identified in the Danish Lung Cancer Registry. Danish Lung Cancer Registry collects data from clinical departments, the Danish Cancer Registry, Danish National Patient Registry, and the Central Population Register. A total of 20,552 patients diagnosed with lung cancer in 2005 to 2011 were identified. Comorbidity data were extracted from the Danish National Patient Registry, which is a register of all in- and outpatient visits to hospitals in Denmark. By record linkage, lung cancer patients who had previously been diagnosed with comorbid conditions were assigned a Charlson comorbidity index. Initial cancer treatment was categorized as chemotherapy, chemoradiation, radiotherapy, or no therapy. Data on Charlson comorbidity index, performance status, age, sex, stage, pulmonary function (forced expiratory volume in 1 second), histology, and type of initial treatment (if any) were included in univariable and multivariable Cox proportional hazard analyses. Results: Treatment rates for chemotherapy and chemoradiation declined with increasing comorbidity and in particular increasing age. Women received treatment more often than men. In a univariable analysis of all patients combined, stage, performance status, age, sex, lung function, and comorbidity were all associated with survival. Apart from excess mortality among patients with unspecified histological subtypes (hazard ratio), there was no clear difference between the specified subtypes. When adjusting for the other factors, particularly age, sex, performance status, and stage proved to be robust while risk estimates for comorbidity were attenuated somewhat. When grouped by the three types of cancer treatment or no treatment, there was no influence of comorbidity on radiation therapy and modest influence on survival after chemotherapy and chemoradiation. In contrast, age remained a strong negative prognosticator after multivariate adjustment as did stage and performance status. Conclusion: Comorbidity has a limited effect on survival and only for patients treated with chemotherapy. It is rather the performance of the patient at diagnosis than the medical history that prognosticates survival in this patient group.

The mortality after surgery in primary lung cancer: results from the Danish Lung Cancer Registry

OBJECTIVES The study has been performed to investigate the mortality within the first year after resection in patients with primary lung cancer, together with associated prognostic factors including gender, age, tumour stage, comorbidity, alcohol abuse, type of surgery and post-surgical complications. METHODS All patients (n = 3363) from the nationwide Danish Lung Cancer Registry with first resection performed between 1 January 2007 and 31 December 2011 were analysed by Kaplan-Meier techniques and Cox-regression analysis concerning death within the first year after resection. Covariates included gender, age, comorbidity (Charlson comorbidity index), perioperative stage, type of resection, registered complications to surgery and alcohol abuse. RESULTS The cumulative deaths after 30 days, 90 days, 180 days and 360 days were 72 (2.1%), 154 (4.6%), 239 (7.1%) and 478 (14.2%), respectively. Low stage, female gender, young age, no comorbidity, no postoperative complications, no alcohol abuse and lobectomy as type of resection were favourable for survival. CONCLUSIONS Our results demonstrate that resection in primary lung cancer impacts mortality far beyond the initial 30 days after resection, which is conventionally considered a time window of relevance for the adverse outcome of surgery. Increased efforts should be made for optimizing the selection of patients suited for resection and for identifying patients at increased risk of death after resection. Furthermore, patients should be monitored more closely and more frequently, in particular those patients with high risk of death after resection.

CT-Screening for lung cancer does not increase the use of anxiolytic or antidepressant medication

BackgroundCT screening for lung cancer has recently been shown to reduce lung cancer mortality, but screening may have adverse mental health effects. We calculated risk ratios for prescription of anti-depressive (AD) or anxiolytic (AX) medication redeemed at Danish pharmacies for participants in The Danish Lung Cancer Screening Trial (DLCST).MethodsThe DLCST was a randomized clinical trial which comprised 4,104 former or present smokers who were randomized from 12 May 2004 to 20 June 2006 to either CT scan of the chest, lung-function test and filling in questionnaires annually for five years in the period 1 April 2006–31 March 2010 (n = 2,052), or to a control group (n = 2,052) receiving similar procedures except CT scan. We used CT scan intervention group versus control group status as exposure. The follow-up period for use of AD or AX was three years. Baseline data on civil status, socioeconomic status, and co-morbidity as well as outcome data on AD and AX were obtained by linkage to national registries.ResultsThe intervention and the control groups did not differ by age, gender, civil status, socio-economic position, co-morbidity index or former use of AD or AX. The adjusted risk ratio for at least one recipe of AD or AX in the CT intervention group during follow-up was not increased when adjusting for previous use of AD or AX, HR 1.00, 95 % CI (0.90-1.12). Similar results were seen when excluding subjects using AD or AX in a four-month or two-year period before baseline, when analyzing AD and AX separately, or requiring at least two recipes.ConclusionsWe found no indications that participation in a lung cancer CT-screening program increases the risk of specific adverse mental health outcomes.Trial registrationClinical Trials.gov Protocol Registration System (NCT00496977).

Detection of recurrence in early stage endometrial cancer: the role of symptoms and routine follow-up

Abstract Background: Considerable controversy remains as to the optimal organization of endometrial cancer follow-up. Aim: To evaluate the relationship between the way recurrence was detected and survival after treatment for endometrial cancer. Further, to identify characteristics associated with a pre-scheduled examination in women with symptomatic recurrence. Material and methods: All women with early stage endometrial cancer during 2005–2009 were included in a population-based historical cohort derived from the Danish Gynecological Cancer Database. Women diagnosed with recurrence within three years after primary surgery and the mode of recurrence detection were identified from hospital charts: asymptomatic recurrence detected at regular follow-up, symptomatic recurrence detected at regular follow-up or symptomatic recurrence detected in between follow-up. Survival of women with symptomatic and asymptomatic disease was compared. Furthermore, characteristics associated with self-referral as compared to presenting symptoms at regular follow-ups were identified using univariate analyses. Results: In total, 183 cases of recurrence (7%) were identified in the cohort of 2612 women. Of these, 65.5% were symptomatic with vaginal bleeding as the most prevalent symptom. Asymptomatic women had a significantly better three-year survival rate compared to symptomatic women (80.3% vs. 54.3%, p < 0.01). A total of 2.3% of the entire population had an asymptomatic recurrence. Women diagnosed at a pre-scheduled visit due to symptoms had a higher educational level (p = 0.03) and more often high-risk disease (p = 0.02) than symptomatic women diagnosed at regular follow-up. Conclusion: Early stage endometrial cancer carries a low risk of recurrence. Survival appears to be superior in asymptomatic patients, but length-time bias, i.e. the effect of aggressive tumor biology in symptomatic recurrences, may bias results in non-randomized controlled trials. Well educated patients with symptoms of recurrence more often sought medical attendance compared to less educated counterparts. This should be considered if patient-initiated follow-up is the standard care.

Incidence of Cancer and Mortality in Patients from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Trial

The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) clinical trial, including 1,873 patients found an increased risk for cancer with lipid-lowering therapy with ezetimibe/simvastatin 10/40 mg/day, relative to placebo. In a registry-based follow-up study over 21 months from the conclusion of the SEAS trial, new incident cancer and total mortality were investigated in the SEAS study cohort from Denmark, Finland, Norway, Sweden, and the United Kingdom. Among 1,359 subjects eligible for follow-up (73% of the original total cohort), 1,194 had no history of cancer (primary follow-up cohort). New cancers and deaths were identified in the national cancer and mortality registries and classified by an Expert Review Committee. Data were analyzed using Cox proportional-hazards models of new cancers and mortality during follow-up according to treatment group assigned in the SEAS base study and with age, gender, smoking history, and previous cancers as covariates. The primary follow-up cohort had 12 patients with new cancers in the ezetimibe/simvastatin group and 22 in the placebo group (hazard ratio 0.55, 95% confidence interval 0.27 to 1.11), indicating no significant difference between the treatment groups. During follow-up, 43 patients assigned to ezetimibe/simvastatin and 33 assigned to placebo died (hazard ratio 1.29, 95% confidence interval 0.82 to 2.03). In conclusion, in this registry-based observational follow-up study of the original SEAS study patient population, treatment with ezetimibe/simvastatin was not associated with an increased risk for cancer or mortality in the 21-month period after the completion of the original SEAS study.

Analysis of Functional Abilities for Elderly Danish Twins Using GEE Models

In this work we present a new method for genetic analysis of twin data which is based on generalized estimating equations and allows for analysis of various response types (e.g., continuous, binary, counts) combined with estimation of residual correlations. The new approach allows for control of covariates of any kind (e.g., continuous, counts) by modeling the dependence of mean and variance on background variables. The proposed method was applied to identify the covariates that have a significant influence on elderly peoples functional abilities, and find the estimates for the correlation coefficients of residuals for MZ and DZ twins in a sample of 2401 Danish twin 75 years of age or older. The bootstrap method was used to obtain standard errors for correlation coefficients. It was shown, that the chosen covariates have similar effects on MZ and DZ twins, and that the residual correlation in MZ twins is significantly higher than in DZ twins, which indicates that genetic factors play an etiological role in the determination of physical status of elderly people, controlled for 10 background variables.

Role of comorbidity on survival after radio- and chemotherapy for non-surgically treated lung cancer.

Background: Comorbidity, such as diseases of the cardiovascular, pulmonary, and other systems, may influence prognosis in lung cancer and complicate its treatment. The performance status of patients, which is a known prognostic marker, may also be influenced by comorbidity. Due to the close link between tobacco smoking and lung cancer, and because lung cancer is often diagnosed in advanced ages (median age at diagnosis in Denmark is 70 years), comorbidity is present in a large proportion of lung cancer patients. Methods: Patients with any stage lung cancer who did not have surgical treatment were identified in the Danish Lung Cancer Registry. Danish Lung Cancer Registry collects data from clinical departments, the Danish Cancer Registry, Danish National Patient Registry, and the Central Population Register. A total of 20,552 patients diagnosed with lung cancer in 2005 to 2011 were identified. Comorbidity data were extracted from the Danish National Patient Registry, which is a register of all in- and outpatient visits to hospitals in Denmark. By record linkage, lung cancer patients who had previously been diagnosed with comorbid conditions were assigned a Charlson comorbidity index. Initial cancer treatment was categorized as chemotherapy, chemoradiation, radiotherapy, or no therapy. Data on Charlson comorbidity index, performance status, age, sex, stage, pulmonary function (forced expiratory volume in 1 second), histology, and type of initial treatment (if any) were included in univariable and multivariable Cox proportional hazard analyses. Results: Treatment rates for chemotherapy and chemoradiation declined with increasing comorbidity and in particular increasing age. Women received treatment more often than men. In a univariable analysis of all patients combined, stage, performance status, age, sex, lung function, and comorbidity were all associated with survival. Apart from excess mortality among patients with unspecified histological subtypes (hazard ratio), there was no clear difference between the specified subtypes. When adjusting for the other factors, particularly age, sex, performance status, and stage proved to be robust while risk estimates for comorbidity were attenuated somewhat. When grouped by the three types of cancer treatment or no treatment, there was no influence of comorbidity on radiation therapy and modest influence on survival after chemotherapy and chemoradiation. In contrast, age remained a strong negative prognosticator after multivariate adjustment as did stage and performance status. Conclusion: Comorbidity has a limited effect on survival and only for patients treated with chemotherapy. It is rather the performance of the patient at diagnosis than the medical history that prognosticates survival in this patient group.

Measuring reliable change of emotional and behavioural problems in children

The purpose of this study was to estimate true treatment effect measured by clinicians using the Health of the Nation Outcome Scale for Children and Adolescent (HoNOSCA) corrected for regression to the mean (RTM), and for ceiling and floor effects. The present study was based on routine clinical data from a national database in which HoNOSCA is scored before and after therapy in order to show the treatment effect. We constructed a modified score to correct for the potential bias due to RTM, and used Generalized Linear Models analysis to adjust for the ceiling and floor effect. Our study showed that if these corrections are implemented in routine outcome measurement of children diagnosed with Hyperkinetic Disorder (HKD), the estimate of change in total HoNOSCA score after adjustment is clearly smaller in absolute value than the absolute difference estimate. If RTM and the ceiling/floor effect is ignored it will lead to misinterpretation of the results.