Why Cell-Free DNA Can Be a "Game Changer" for Lung Allograft Monitoring for Rejection and Infection.

Purpose of Review: Although there has been improvement in short-term clinical outcomes for patients following lung transplant (LT), advances have not translated into longer-term allograft survival. Furthermore, invasive biopsies are still standard of practice for monitoring LT recipients for allograft injury. We review the relevant literature supporting the role of using plasma donor-derived cell-free DNA (dd-cfDNA) as a non-invasive biomarker for LT allograft injury surveillance and discuss future research directions. Recent Findings: Accumulating data has demonstrated that dd-cfDNA is associated with molecular and cellular injury due to acute (cellular and antibody-mediated) rejection, chronic lung allograft dysfunction, and relevant infectious pathogens. Strong performance in distinguishing rejection and allograft injury from stable patients has set the stage for clinical trials to assess dd-cfDNA utility for surveillance of LT patients. Research investigating the potential role of dd-cfDNA methylation signatures to map injured tissue and cell-free DNA in detecting allograft injury-related pathogens is ongoing. Summary: There is an amassed breadth of clinical data to support a role for dd-cfDNA in monitoring rejection and other forms of allograft injury. Rigorously designed, robust clinical trials that encompass the diversity in patient demographics are paramount to furthering our understanding and adoption of plasma dd-cfDNA for surveillance of lung allograft health.

An international comparison of cancer survival: metropolitan Toronto, Ontario, and Honolulu, Hawaii.

OBJECTIVES: Comparisons of cancer survival in Canadian and US metropolitan areas have shown consistent Canadian advantages. This study tests a health insurance hypothesis by comparing cancer survival in Toronto, Ontario, and Honolulu, Hawaii. METHODS: Ontario and Hawaii registries provided a total of 9190 and 2895 cancer cases (breast and prostate, 1986-1990, followed until 1996). Socioeconomic data for each person's residence at the time of diagnosis were taken from population censuses. RESULTS: Socioeconomic status and cancer survival were directly associated in the US cohort, but not in the Canadian cohort. Compared with similar patients in Honolulu, residents of low-income areas in Toronto experienced 5-year survival advantages for breast and prostate cancer. In support of the health insurance hypothesis, between-country differences were smaller than those observed with other state samples and the Canadian advantage was larger among younger women. CONCLUSIONS: Hawaii seems to provide better cancer care than many other states, but patients in Toronto still enjoy a significant survival advantage. Although Hawaii's employer-mandated health insurance coverage seems an effective step toward providing equitable health care, even better care could be expected with a universally accessible, single-payer system.

An international comparison of cancer survival: relatively poor areas of Toronto, Ontario and three US metropolitan areas.

BACKGROUND: This study of cancer survival compared adults in Toronto, Ontario and three US metropolitan areas: Seattle, Washington; San Francisco, California; and Hartford, Connecticut. It examined whether socioeconomic status has a differential effect on cancer survival in Canada and the United States. METHODS: The Ontario Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology and End RESULTS: (SEER) programme provided a total of 23,437 and 37,329 population-based primary malignant cancer cases for the Toronto and US samples, respectively (1986-1988, followed until 1994). Census-based measures of socioeconomic status were used to ecologically control absolute income status. RESULTS: Among residents of low-income areas, persons in Toronto experienced a 5 year survival advantage for 13 of 15 cancer sites [minimally one gender significant at 95 per cent confidence interval (CI)]. An aggregate 35 per cent survival advantage among the Canadian cohort was demonstrated (survival rate ratio (SRR) = 1.35, 95 per cent CI= 1.30-1.40), and this effect was even larger among younger patients not yet eligible for Medicare coverage in the United States (SRR = 1.46, 95 per cent CI = 1.40-1.52). CONCLUSION: Systematically replicating a previous Toronto-Detroit comparison, this study's observed consistent pattern of Canadian survival advantage across various cancer sites suggests that their more equitable access to preventive and therapeutic health care services may be responsible for the difference.

Association between socioeconomic status and cancer incidence in Toronto, Ontario: possible confounding of cancer mortality by incidence and survival.

OBJECTIVE: To observe the association between socioeconomic status (SES) and cancer incidence in a cohort of Canadians. DESIGN: Cases of primary malignant cancer (83,666) that arose in metropolitan Toronto, Ont., from 1986 to 1993 were ascertained by the Ontario Cancer Registry and linked by residence at the time of diagnosis to a census-based measure of SES. Socioeconomic quintile areas were then compared by cancer incidence. RESULTS: Significant associations between SES and cancer incidence in the hypothesized direction--greater incidence in low-income areas--were observed for 15 of 23 cancer sites. CONCLUSIONS: These findings, together with the recently observed consistent pattern of significant associations between SES and cancer survival in the United States and the equally consistent pattern of nonsignificant associations in Canada, support the notion that differences in cancer incidence alone explain the observed cancer mortality differentials by SES in Canada. The cancer mortality differential by SES observed in the United States is probably a function of differences in both incidence and length of survival, whereas in Canada such mortality differentials are more likely to be merely a function of differences in incidence by SES. This pattern of associations primarily implicates differences in the 2 health care systems; specifically, the more egalitarian access to preventive, investigative and therapeutic services available in the single-payer Canadian system.

An international comparison of cancer survival: Toronto, Ontario, and Detroit, Michigan, metropolitan areas.

OBJECTIVES: This study examined whether socioeconomic status has a differential effect on the survival of adults diagnosed with cancer in Canada and the United States. METHODS: The Ontario Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program provided a total of 58,202 and 76,055 population-based primary malignant cancer cases for Toronto, Ontario, and Detroit, Mich, respectively. Socioeconomic data for each person's residence at time of diagnosis were taken from population censuses. RESULTS: In the US cohort, there was a significant association between socioeconomic status and survival for 12 of the 15 most common cancer sites; in the Canadian cohort, there was no such association for 12 of the 15 sites. Among residents of low-income areas, persons in Toronto experienced a survival advantage for 13 of 15 cancer sites at 1- and 5-year follow-up. No such between-country differentials were observed in the middle- or high-income groups. CONCLUSIONS: The consistent pattern of a survival advantage in Canada observed across various cancer sites and follow-up periods suggests that Canada's more equitable access to preventive and therapeutic health care services is responsible for the difference.

Cancer incidence and mortality trends in Northeastern Ontario.

Over 629,000 people reside in the catchment area for the Northeastern Ontario Regional Cancer Centre. Historically, the area was renowned for employment in mining, forestry and lumbering, agriculture, the railway, and pulp and paper. At present, it is known for mining; community, business, and personal services; trade; manufacturing; and construction. Comparison of cancer incidence and mortality trends for two decades (1971-1980 and 1981-1990) with those of Ontario has revealed statistically significant excesses, at the 5% level or better, of trachea, bronchus, and lung cancer cases (SIR = 123 for 1971-1980 and 125 for 1981-1990) and deaths in men (SMR = 116 and 125, respectively); for women, excesses were observed for trachea, bronchus and lung cancer case (SIR = 114 and 118), and cervical cancer cases (SIR = 142 and 115) and deaths (SMR = 133 and 128). Enhanced recruitment strategies and early educational interventions are identified as priorities.

Temporal trends in breast cancer surgery in Ontario: can one randomized trial make a difference?

OBJECTIVE: To assess the effect of a single randomized clinical trial, the National Surgical Adjuvant Breast Project (NSABP) B-06, on the surgical management of breast cancer in women. DESIGN: Retrospective cohort study. SETTING: All hospitals in Ontario. PATIENTS: A consecutive sample of 37,447 women with breast cancer newly diagnosed from Jan. 1, 1980, to Dec. 31, 1989, linked to a surgical procedure record in the Ontario Cancer Registry. MAIN OUTCOME MEASURE: The most invasive surgical procedure used within 90 days of diagnosis. RESULTS: Unilateral breast-ablative surgery (BAS) was performed in 57.3% of the women and breast-conserving surgery (BCS) in 31.6%. The annual rate of BAS declined from 77.5% in 1980 to 44.2% in 1989 and the rate of BCS rose from 12.5% in 1980 to 43.5% in 1989. The decline was linear from 1980 to 1984 and then accelerated significantly in 1985 (p < 0.0001), after the results of the NSABP B-06 trial were published. CONCLUSION: One randomized clinical trial can have an immediate and profound effect on medical practice.

Variation in breast cancer surgery in Ontario.

OBJECTIVES: To analyse the extent of variation by county and hospital in the use of breast-conserving surgery in the initial management of breast cancer and to assess some factors that might explain the observed variation. DESIGN: Population-based retrospective cohort study. SETTING: Ontario. PATIENTS: All women with breast cancer newly diagnosed from Jan. 1, 1989, to Dec. 31, 1991. MAIN OUTCOME MEASURE: Proportion of women undergoing unilateral breast cancer surgery who had breast-conserving surgery in each hospital and county. RESULTS: Of the 14,570 women with newly diagnosed breast cancer 12,815 (88.0%) underwent unilateral breast cancer surgery. The mean proportion of breast-conserving procedures by county was 52% and ranged from 11% to 84%. The proportion of breast-conserving procedures in individual hospitals with one or more cases of breast cancer per month ranged from 6% to 84%. The variations in the rates between hospitals was greater than that expected by chance alone (p < 0.0001). CONCLUSIONS: There was marked variation at the hospital and county level in the use of breast-conserving surgery in the initial management of breast cancer. This variation was strongly associated with the hospital where the surgery was performed.

Response of a cancer registry to reports of disease clusters.

A protocol has been developed to investigate and report perceived clusters of cancer using a population-based cancer registry. The protocol comprises a series of steps which lead to assessment of the cluster's importance on the basis of three criteria: (1) statistical evidence of clustering; (2) documentation of the existence of exposure to a carcinogen; and (3) biological plausibility of the relationship between the exposure and the cancer of interest. The evaluation of these criteria results in one of three recommendations: further study, surveillance only, or no action. The protocol provides a systematic approach for investigation, makes efficient use of available cancer registry data, and responds to public concerns. The protocol is demonstrated by its application to an inquiry concerning an apparent excess of lung cancer in a small Ontario town and the possible role of radon gas exposure. The public health importance and limitations of addressing perceived disease clusters are discussed.