Multiple event times in the presence of informative censoring: modeling and analysis by copulas.

Motivated by a breast cancer research program, this paper is concerned with the joint survivor function of multiple event times when their observations are subject to informative censoring caused by a terminating event. We formulate the correlation of the multiple event times together with the time to the terminating event by an Archimedean copula to account for the informative censoring. Adapting the widely used two-stage procedure under a copula model, we propose an easy-to-implement pseudo-likelihood based procedure for estimating the model parameters. The approach yields a new estimator for the marginal distribution of a single event time with semicompeting-risks data. We conduct both asymptotics and simulation studies to examine the proposed approach in consistency, efficiency, and robustness. Data from the breast cancer program are employed to illustrate this research.

Patterns of comorbidities in women with breast cancer: a Canadian population-based study.

PURPOSE: Improving the understanding of co-existing chronic diseases prior to and after the diagnosis of cancer may help to facilitate therapeutic decision making in clinical practice. This study aims to examine patterns of comorbidities in Canadian women with breast cancer. METHODS: We conducted a retrospective cohort study using provincial linked administrative health datasets from British Columbia, Canada, between 2000 and 2013. Women diagnosed with breast cancer between 2005 and 2009 were identified. The index date was defined as the date of diagnosis of breast cancer. Subsets of the breast cancer cohort were identified based on the absence of individual type of comorbidity of interest within 5 years prior to breast cancer diagnosis. For each subset, cases were then individually matched by year of birth at 1:2 ratios with controls without a history of cancer and the individual type of comorbidity of interest within 5 years prior to the assigned index year, matching with the year of breast cancer diagnosis of the corresponding case. Baseline comorbidities were measured over a 1-year period prior to the index date using two comorbidity indices, Rx-Risk-V and Aggregated Diagnosis Groups (ADG). Cox regression model was used to assess the development of seven specific comorbidities after the index date between women with breast cancer and non-cancer women. RESULTS: The most prevalent baseline comorbidity in the breast cancer cohort measured using the Rx-Risk-V model was cardiovascular conditions (39.0%), followed by pain/pain-inflammation (34.8%). The most prevalent category measured using the ADG model was major signs or symptoms (71.8%), followed by stable chronic medical conditions (52.2%). The risks of developing ischemic heart disease, heart failure, depression, diabetes, osteoporosis, and hypothyroidism were higher in women with breast cancer compared to women without cancer, with the hazard ratios ranging from 1.09 (95 CI% 1.03-1.16) for ischemic heart disease to 2.10 (95% CI 1.99-2.21) for osteoporosis in the model adjusted for baseline comorbidity measured using Rx-Risk-V score. CONCLUSION: Women with breast cancer had a higher risk of developing new comorbidities than women without cancer. Development of coordinated care models to manage multiple chronic diseases among breast cancer patients is warranted.

Adherence to quality breast cancer survivorship care in four Canadian provinces: a CanIMPACT retrospective cohort study.

BACKGROUND: In order to maximize later health, there are established components and guidelines for quality follow-up care of breast cancer survivors. However, adherence to quality follow-up in Canada may not be optimal, and may vary by province. We determined and compared the proportion of patients in each province who received adherent and non-adherent surveillance for recurrence, new cancers and late effects, recommended preventive care, and recommended physician visits for comorbidities. METHODS: Cohorts consisted of all adult women diagnosed with incident invasive breast cancer between 2007 and 2010/2012 in four Canadian provinces (British Columbia (BC) N = 9338; Manitoba N = 2688; Ontario N = 23,700; Nova Scotia (NS) N = 2735), identified from provincial cancer registries, alive and cancer-free at 30 months post-diagnosis. Their healthcare utilization was determined from one to 5 years post-treatment, using linked administrative databases. Adherence, underuse, and overuse of recommended services were evaluated yearly and compared using descriptive statistics. RESULTS: In all provinces and follow-up years, the majority of survivors had more than the recommended number of visits to either an oncologist or primary care physician (range 53.8% NS Year 3; 85.8% Ontario Year 4). The proportion of patients with the guideline-recommended number of oncologist visits varied by province (range 29.8% BC Year 5; 74.8% Ontario Year 5), and the proportion of patients with less than the recommended number of specified breast cancer-related visits with either an oncologist or primary care physician ranged from 32.6% (Ontario Year 2) to 84.4% (NS Year 3). Underuse of surveillance breast imaging was identified in NS and BC. The proportion of patients receiving imaging for metastatic disease (not recommended in the guidelines) in BC, Manitoba, and Ontario (not reported in NS) ranged from 20.3% (BC Year 5) to 53.3% (Ontario Year 2). Compliance with recommended physician visits for patients with several chronic conditions was high in Ontario and NS. Preventive care was less than optimal in all provinces with available data. CONCLUSIONS: Quality of breast cancer survivor follow-up care varies among provinces. Results point to exploration of factors affecting differences, province-specific opportunities for care improvement, and the value of administrative datasets for health system assessment.

Long-term effects of cancer on earnings of childhood, adolescent and young adult cancer survivors - a population-based study from British Columbia, Canada.

BACKGROUND: The patterns and determinants of long-term income among young people surviving cancer, and differences compared to peers, have not yet been fully explored. The objectives of this paper are to describe long-term income among young survivors of cancer, the impact of socio-demographic, disease, and treatment factors on long-term income, and income relative to the general population. METHODS: Retrospective cohort study with comparison group from the general population, using linked population-based registries, clinical data, and tax-records. Multivariate random effects regression models were used to determine survivor income, compare long-term income between survivors and comparators, and assess income determinants. Subjects included all residents of British Columbia (BC), Canada, diagnosed with cancer before 25 years of age and surviving 5 years or more. Comparators were selected from the BC general population matched by gender and birth year. RESULTS: Young cancer survivors earned significantly less than the general population. In addition, survivors of central nervous system tumors have significantly lower incomes than lymphoma survivors. Survivors who received radiation therapy have significantly lower income. Results should be interpreted with caution as the comparator group was matched by gender and date of birth. CONCLUSIONS: Depending on original diagnosis, treatment, and other characteristics, survivors face significantly lower income than peers and may require supports to gain and retain paid employment. Lower income will affect their opportunity for independent living, and will reduce productivity in the labour force.

Costs for Childhood and Adolescent Cancer, 90 Days Prediagnosis and 1 Year Postdiagnosis: A Population-Based Study in Ontario, Canada.

BACKGROUND: Childhood and adolescent cancers are uncommon, but they have important economic and health impacts on patients, families, and health care systems. Few studies have measured the economic burden of care for childhood and adolescent cancers. OBJECTIVES: To estimate costs of cancer care in population-based cohorts of children and adolescents from the public payer perspective. METHODS: We identified patients with cancer, aged 91 days to 19 years, diagnosed from 1995 to 2009 using cancer registry data, and matched each to three noncancer controls. Using linked administrative health care records, we estimated total and net resource-specific costs (in 2012 Canadian dollars) during 90 days prediagnosis and 1 year postdiagnosis. RESULTS: Children (≤14 years old) numbered 4,396: 36% had leukemia, 21% central nervous system tumors, 10% lymphoma, and 33% other cancers. Adolescents (15-19 years old) numbered 2,329: 28.9% had lymphoma. Bone and soft tissue sarcoma, germ cell tumor, and thyroid carcinoma each comprised 12% to 13%. Mean net prediagnosis costs were $5,810 and $1,127 and mean net postdiagnosis costs were $136,413 and $62,326 for children and adolescents, respectively; the highest were for leukemia ($157,764 for children and $172,034 for adolescents). In both cohorts, costs were much higher for patients who died within 1 year of diagnosis. Inpatient hospitalization represented 69% to 74% of postdiagnosis costs. CONCLUSIONS: Treating children with cancer is costly, more costly than treating adolescents or adults. Substantial survival gains in children mean that treatment may still be very cost-effective. Comprehensive age-specific population-based cost estimates are essential to reliably assess the cost-effectiveness of cancer care for children and adolescents, and measure health system performance.

Costs of cancer care in children and adolescents in Ontario, Canada.

BACKGROUND: Cancer in children and adolescents presents unique issues regarding treatment and survivorship, but few studies have measured economic burden. We estimated health care costs by phase of cancer care, from the public payer perspective, in population-based cohorts. METHODS: Children newly diagnosed at ages 0 days-14.9 years and adolescents newly diagnosed at 15-19.9 years, from January 1, 1995 to June 30, 2010, were identified from Ontario cancer registries, and each matched to three noncancer controls. Data were linked with administrative records describing resource use for cancer and other health care. Total and net (patients minus controls) resource-specific costs ($CAD2012) were estimated using generalized estimating equations for four phases of care: prediagnosis (60 days), initial (360 days), continuing (variable), final (360 days). RESULTS: Mean ages at diagnosis were 6 years for children (N = 4,606) and 17 years for adolescents (N = 2,443). Mean net prediagnosis phase 60-day costs were $6,177 for children and $1,018 for adolescents. Costs for initial, continuing, and final phases were $138,161, $15,756, and $316,303 per 360 days for children, and $62,919, $7,071, and $242,008 for adolescents. The highest initial phase costs were for leukemia patients ($156,225 per 360 days for children and $171,275 for adolescents). The final phase was the most costly ($316,303 per 360 days for children and $242,008 for adolescents). CONCLUSIONS: Costs for children with cancer are much higher than for adolescents and much higher than those reported in adults. Comprehensive population-based long-term estimates of cancer costs are useful for health services planning and cost-effectiveness analysis.

The Intracranial Distribution of Gliomas in Relation to Exposure From Mobile Phones: Analyses From the INTERPHONE Study.

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self-reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially influenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use.

Late mortality, secondary malignancy and hospitalisation in teenage and young adult survivors of Hodgkin lymphoma: report of the Childhood/Adolescent/Young Adult Cancer Survivors Research Program and the BC Cancer Agency Centre for Lymphoid Cancer.

Late complications affecting Hodgkin lymphoma (HL) survivors are well described in paediatric and adult-based publications. This study determined the late morbidity and mortality risk for 442 teenage and young adult (TYAs) 5-year HL survivors, diagnosed at 15-24 years of age between 1970 and 1999, identified from the British Columbia Cancer Registry. Treatment details were abstracted from charts. Survivors and a matched comparison cohort were linked to provincial administrative health datasets until December 2006 and regression analysis was performed, providing risk ratios regarding mortality, secondary malignancy and morbidity causing hospitalisation. Sixty (13·6%) survivors experienced late mortality with excess deaths from secondary cancer [standardised mortality ratio (SMR) 18·6; 95% confidence interval (CI) 11-29·4] and non-malignant disease (SMR 3·6; 95% CI 2·2-5·5). Excess secondary cancers (standardised incidence ratio 7·8; 95% CI 5·6-10·5) were associated with radiotherapy [Hazard ratio (HR) 2·7; 95% CI 1-7·7] and female gender (HR 1·8; 95% CI 1-3·4). Of 281 survivors treated between 1981 and 1999, 143 (51%) had morbidity resulting in hospitalisation (relative risk 1·45; 95% CI 1·22-1·73). Hospitalisation significantly increased with combined modality therapy, chemotherapy alone and recent treatment era. TYA HL survivors have excess risk of mortality and secondary malignancy continuing 30 years from diagnosis. Radiotherapy is associated with secondary malignancy and current response-adapted protocols attempt to minimise exposure, but late morbidity causing hospitalisation remains significant.

A qualitative focus group study to identify the needs of survivors of stage II and III colorectal cancer.

BACKGROUND: Prior survivorship research has largely focused on issues faced by survivors of childhood tumors, breast cancers, or hematologic malignancies. Relatively little is known about the needs of other prevalent survivor groups. Our aim was to identify the specific concerns of colorectal cancer (CRC) survivors in the key domains of physical functioning, psychological wellbeing, and social relationships. METHODS: We conducted focus groups with stage II and III CRC survivors who had completed their primary active anti-cancer treatments. Patients were asked to describe how their diagnosis and treatment impacted their lives, to outline deficiencies in the care that they received, and to suggest ways of addressing any unmet needs. A content analysis was subsequently conducted to identify major themes. RESULTS: Thirty CRC survivors participated in six focus groups. Individuals reported some degree of dissatisfaction with the amount and type of diagnostic and treatment information they received at their initial clinic visit. Distress from toxicities, such as peripheral neuropathy, was also common among the survivors. Similarly, the majority faced challenges adjusting to their lives and daily activities, especially in caring for their colostomy. Having survived CRC, many survivors expressed an interest in advocacy and health promotion of CRC. CONCLUSIONS: CRC survivors face many barriers after their cancer treatment. Issues with colostomy are unique to this survivor group. Interventions to improve CRC survivorship care should also incorporate opportunities for patient advocacy. Copyright © 2015 John Wiley & Sons, Ltd.

Non-oncology physician visits after diagnosis of cancer in children.

BACKGROUND: Children diagnosed with cancer often require extensive care for medical, psychosocial and educational problems during and after therapy. Part of this care is provided by family physicians and non-cancer specialists, but their involvement in the first years after diagnosis has barely been studied. Studying non-oncology physician visits may provide insight into the roles of different health care providers. METHODS: We included 757 children diagnosed with cancer under age 15 between 1991 and 2001 from a Canadian provincial registry, and matched each to 10 controls of the same birth year and sex. We determined the number of family physician and non-cancer specialist visits in the 5 years after diagnosis (for patients) or inclusion (for controls) using data from the provincial health insurance plan. RESULTS: In the first year after diagnosis, almost all patients visited both a family physician and non-cancer specialist. Although after 5 years percentages decreased to 85 and 76 %, respectively, these were still significantly higher than in controls. In the first year after diagnosis, both family physicians and non-cancer specialists were often consulted for neoplasms (62 and 90 %, respectively) and to discuss results of lab tests. In addition, family physicians were often consulted for general symptoms and non-cancer specialists for nervous system problems and complications of medical care. CONCLUSIONS: Family physicians and non-cancer specialists are highly involved in the care for children with cancer in the first years after diagnosis, including for health problems related to cancer or its treatment. This necessitates good communication among all physicians.