Estimating micro area behavioural risk factor prevalence from large population-based surveys: a full Bayesian approach.

BACKGROUND: An important public health goal is to decrease the prevalence of key behavioural risk factors, such as tobacco use and obesity. Survey information is often available at the regional level, but heterogeneity within large geographic regions cannot be assessed. Advanced spatial analysis techniques are demonstrated to produce sensible micro area estimates of behavioural risk factors that enable identification of areas with high prevalence. METHODS: A spatial Bayesian hierarchical model was used to estimate the micro area prevalence of current smoking and excess bodyweight for the Erie-St. Clair region in southwestern Ontario. Estimates were mapped for male and female respondents of five cycles of the Canadian Community Health Survey (CCHS). The micro areas were 2006 Census Dissemination Areas, with an average population of 400-700 people. Two individual-level models were specified: one controlled for survey cycle and age group (model 1), and one controlled for survey cycle, age group and micro area median household income (model 2). Post-stratification was used to derive micro area behavioural risk factor estimates weighted to the population structure. SaTScan analyses were conducted on the granular, postal-code level CCHS data to corroborate findings of elevated prevalence. RESULTS: Current smoking was elevated in two urban areas for both sexes (Sarnia and Windsor), and an additional small community (Chatham) for males only. Areas of excess bodyweight were prevalent in an urban core (Windsor) among males, but not females. Precision of the posterior post-stratified current smoking estimates was improved in model 2, as indicated by narrower credible intervals and a lower coefficient of variation. For excess bodyweight, both models had similar precision. Aggregation of the micro area estimates to CCHS design-based estimates validated the findings. CONCLUSIONS: This is among the first studies to apply a full Bayesian model to complex sample survey data to identify micro areas with variation in risk factor prevalence, accounting for spatial correlation and other covariates. Application of micro area analysis techniques helps define areas for public health planning, and may be informative to surveillance and research modeling of relevant chronic disease outcomes.

Increased stomach cancer risk following radiotherapy for testicular cancer.

BACKGROUND: Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse. METHODS: In a cohort of 22,269 5-year TC survivors diagnosed during 1959-1987, doses to stomach subsites were estimated for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression. RESULTS: Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7-20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose (P-trend<0.001), with an OR of 20.5 (3.7-114.3) for ⩾50.0 Gy compared with <10 Gy. Radiation-related risks remained elevated ⩾20 years after exposure (P<0.001). Risk after any chemotherapy was not elevated (OR=1.1; 95% CI 0.5-2.5; 14 cases and 23 controls). CONCLUSIONS: Radiotherapy for TC involving parts of the stomach increased gastric cancer risk for several decades, with the highest risks after stomach doses of ⩾30 Gy. Clinicians should be aware of these excesses when previously irradiated TC survivors present with gastrointestinal symptoms and when any radiotherapy is considered in newly diagnosed TC patients.

Pancreatic cancer risk after treatment of Hodgkin lymphoma.

BACKGROUND: Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to radiation dose and specific chemotherapeutic agents. PATIENTS AND METHODS: We conducted an international case-control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls. RESULTS: Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5-158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m(2) of procarbazine with nitrogen mustard or ≥3900 mg/m(2) of cyclophosphamide. CONCLUSION: Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks.

Estimating cancer risk in relation to tritium exposure from routine operation of a nuclear-generating station in Pickering, Ontario.

INTRODUCTION: Evidence suggests that current levels of tritium emissions from CANDU reactors in Canada are not related to adverse health effects. However, these studies lack tritium-specific dose data and have small numbers of cases. The purpose of our study was to determine whether tritium emitted from a nuclear-generating station during routine operation is associated with risk of cancer in Pickering, Ontario. METHODS: A retrospective cohort was formed through linkage of Pickering and north Oshawa residents (1985) to incident cancer cases (1985-2005). We examined all sites combined, leukemia, lung, thyroid and childhood cancers (6-19 years) for males and females as well as female breast cancer. Tritium estimates were based on an atmospheric dispersion model, incorporating characteristics of annual tritium emissions and meteorology. Tritium concentration estimates were assigned to each cohort member based on exact location of residence. Person-years analysis was used to determine whether observed cancer cases were higher than expected. Cox proportional hazards regression was used to determine whether tritium was associated with radiation-sensitive cancers in Pickering. RESULTS: Person-years analysis showed female childhood cancer cases to be significantly higher than expected (standardized incidence ratio [SIR] = 1.99, 95% confidence interval [CI]: 1.08-3.38). The issue of multiple comparisons is the most likely explanation for this finding. Cox models revealed that female lung cancer was significantly higher in Pickering versus north Oshawa (HR = 2.34, 95% CI: 1.23-4.46) and that tritium was not associated with increased risk. The improved methodology used in this study adds to our understanding of cancer risks associated with low-dose tritium exposure. CONCLUSION: Tritium estimates were not associated with increased risk of radiationsensitive cancers in Pickering.

TITRE: Estimation du risque de cancer lié à l'exposition au tritium dans le cadre des activités courantes de la centrale nucléaire de Pickering (Ontario). INTRODUCTION: D'après les données dont nous disposons, les niveaux actuels des émissions de tritium provenant des réacteurs CANDU au Canada n'entraîneraient pas d'effets néfastes sur la santé. Toutefois, les études ne précisent pas les doses spécifiques au tritium, et reposent sur un petit nombre de cas. La présente étude avait pour but de déterminer si le tritium émis par la centrale nucléaire de Pickering, en Ontario, lors de ses activités courantes, est associé à un risque de cancer. MÉTHODOLOGIE: Nous avons constitué une cohorte rétrospective en couplant les données sur les résidents de Pickering et de North Oshawa (1985) à celles sur les nouveaux cas de cancer (1985-2005). Nous avons examiné les cas de cancer tous sièges combinés, ainsi que les cas de leucémie, de cancer du poumon, de cancer de la thyroïde et de cancer infantile (6-19 ans) pour les sujets de sexe masculin et féminin, de même que les cas de cancer du sein chez la femme. Les estimations de la concentration de tritium reposaient sur un modèle de dispersion atmosphérique qui intégrait les caractéristiques des émissions annuelles de tritium et les données météorologiques. Chaque membre de la cohorte s'est vu assigner une estimation de la concentration de tritium, en fonction de son lieu précis de résidence. Une analyse des années-personnes a permis de déterminer si les cas de cancer observés étaient plus nombreux que prévus. Un modèle de régression des risques proportionnels de Cox a servi à établir si le tritium était associé à des cancers radiosensibles à Pickering. RÉSULTATS: Une analyse des années-personnes a révélé que le nombre de cas de cancer chez les jeunes filles était significativement plus élevé que prévu (rapport standardisé d'incidence [RSI] = 1,99, intervalle de confiance [IC] à 95 % : 1,08 à 3,38). L'explication la plus plausible de cette observation est le recours à des comparaisons multiples. Les modèles de Cox ont révélé que le cancer du poumon chez la femme était significativement plus élevé à Pickering qu'à North Oshawa (RR = 2,34; IC à 95 % : 1,23 à 4,46) et que le tritium n'était pas associé à une augmentation du risque. La méthodologie améliorée de la présente étude nous permet de mieux comprendre les risques de cancer associés à une exposition à de faibles doses de tritium. CONCLUSION: Les doses estimées de tritium n'ont pas été associées à une augmentation du risque de cancers radiosensibles à Pickering.

Risk of treatment-related esophageal cancer among breast cancer survivors.

BACKGROUND: Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. DESIGN: Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. RESULTS: The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). CONCLUSIONS: Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.

The utility of publicly reported cancer treatment wait time information for patients and health care providers.

AIMS: To determine the utility of web-based radiation wait time information for patients and health care providers in decision-making. To revise the information using a simulated laboratory environment and to re-evaluate the new web-based information. MATERIALS AND METHODS: An online 'pop-up' survey on the Cancer Care Ontario (CCO) website measured user satisfaction. Qualitative data were gathered through patient focus groups and physician interviews. On the basis of the analysis, the website was revised and usability testing conducted. The information was re-evaluated by end-users through survey methodology. RESULTS: The majority accessing the wait time website were patients and family members. The modal age of use of the website was 31-50 years. Patients found the information more helpful after redesign than health professionals, but both found the language less easy to understand, highlighting the need to continuously evaluate the effectiveness of the website. Patients did not identify themselves as consumers of wait time information. Their expectation was that physicians would determine the urgency for treatment and would ensure timely access to care. Physicians reported that they did not use the CCO website on wait times and would not use the data for decision-making. Referrals were based on urgency of care and usual referral patterns. Referral patterns did not shift to centres with shorter wait times. CONCLUSIONS: The results of this study did not confirm the usefulness of the web-based wait time information for patients and physicians as a resource on how to obtain timely access to radiation treatment. Patients relied on their physician to manage their access to treatment according to the urgency of their clinical condition. Physicians preferred their established referral process rather than referring their patients to centres with shorter wait times. As patients become more computer savvy, it will be interesting to see if they increasingly become consumers of web-based wait time information.

Polymorphic MLH1 and risk of cancer after methylating chemotherapy for Hodgkin lymphoma.

BACKGROUND AND OBJECTIVE: Methylating agents are effective chemotherapy agents for Hodgkin lymphoma, but are associated with the development of second primary cancers. Cytotoxicity of methylating agents is mediated primarily by the DNA mismatch repair (MMR) system. Loss of MLH1, a major component of DNA MMR, results in tolerance to the cytotoxic effects of methylating agents and persistence of mutagenised cells at high risk of malignant transformation. We hypothesised that a common substitution in the basal promoter of MLH1 (position -93, rs1800734) modifies the risk of cancer after methylating chemotherapy. METHODS: 133 patients who developed cancer following chemotherapy and/or radiotherapy (n = 133), 420 patients diagnosed with de novo myeloid leukaemia, 242 patients diagnosed with primary Hodgkin lymphoma, and 1177 healthy controls were genotyped for the MLH1 -93 polymorphism by allelic discrimination polymerase chain reaction (PCR) and restriction fragment length polymorphism assay. Odds ratios and 95% confidence intervals for cancer risk by MLH1 -93 polymorphism status, and stratified by previous exposure to methylating chemotherapy, were calculated using unconditional logistic regression. RESULTS: Carrier frequency of the MLH1 -93 variant was higher in patients who developed therapy related acute myeloid leukaemia (t-AML) (75.0%, n = 12) or breast cancer (53.3%. n = 15) after methylating chemotherapy for Hodgkin lymphoma compared to patients without previous methylating exposure (t-AML, 30.4%, n = 69; breast cancer patients, 27.2%, n = 22). The MLH1 -93 variant allele was also over-represented in t-AML cases when compared to de novo AML cases (36.9%, n = 420) and healthy controls (36.3%, n = 952), and was associated with a significantly increased risk of developing t-AML (odds ratio 5.31, 95% confidence interval 1.40 to 20.15), but only in patients previously treated with a methylating agent. CONCLUSIONS: These data support the hypothesis that the common polymorphism at position -93 in the core promoter of MLH1 defines a risk allele for the development of cancer after methylating chemotherapy for Hodgkin lymphoma. However, replication of this finding in larger studies is suggested.

Associations between socioeconomic status and cancer survival: choice of SES indicator may affect results.

PURPOSE: Two previous studies, by Gorey et al. and Boyd et al., compared associations between socioeconomic status (SES) and cancer survival in Canada and the United States. Both studies used SES information from population censuses linked to cancer registries. This study investigates why two similar studies led to apparently conflicting results. METHODS: We conducted analyses following analytic details provided by the previously published studies to describe cancer survival in Toronto, Canada, and Detroit, MI. We examined the effects of choice of census indicators and census levels on the observed SES-related gradients in cancer survival. RESULTS: Significant associations between SES and cancer survival were observed in Toronto for several major disease sites when median household income was used as an SES indicator. Associations were weaker when a poverty indicator was used. In Detroit, similar SES gradients were observed by using both income and poverty as SES indicators. When SES quintiles were represented by income ranks, SES-associated survival gradients were much steeper in Detroit than Toronto. When SES was described by the median income in each quintile, gradients were similar in the two cities. CONCLUSIONS: The apparent contradiction in results of two previous studies is related to the choice of SES indicators. Poverty may not be an indicator of choice for such an intercountry comparison.

Lung cancer after treatment for Hodgkin's disease: focus on radiation effects.

Aspects of radiation-induced lung cancer were evaluated in an international study of Hodgkin's disease. The study population consisted of 227 patients with lung cancer and 455 matched controls. Unique features included dose determinations to the specific location in the lung where each cancer developed and quantitative data on both chemotherapy and tobacco use obtained from medical records. The estimated excess relative risk (ERR) per Gy was 0.15 (95% CI: 0.06-0.39), and there was little evidence of departure from linearity even though lung doses for the majority of Hodgkin's disease patients treated with radiotherapy exceeded 30 Gy. The interaction of radiation and chemotherapy that included alkylating agents was almost exactly additive, and a multiplicative relationship could be rejected (P = 0.017). Conversely, the interaction of radiation and smoking was consistent with a multiplicative relationship, but not with an additive relationship (P < 0.001). The ERR/Gy for males was about four times that for females, although the difference was not statistically significant. There was little evidence of modification of the ERR/Gy by time since exposure (after a 5-year minimum latent period), age at exposure, or attained age. Because of the very high radiation doses received by Hodgkin's disease patients and the immunodeficiency inherent to this lymphoma and that associated with chemotherapy, generalizing these findings to other populations receiving considerably lower doses of radiation should be done cautiously.

A population-based study of glioblastoma multiforme.

PURPOSE: To describe (1) the use of surgery and radiotherapy (RT) in the treatment of patients with glioblastoma (GBM) in Ontario, (2) survival, and (3) proportion of survival time spent in the hospital after diagnosis. METHODS AND MATERIALS: We performed a population-based cohort study of all Ontario Cancer Registry (OCR) cases of GBM diagnosed between 1982 and 1994. We linked OCR records, hospital files containing surgical procedure codes from the Canadian Institute for Health Information, and province-wide RT records. We studied the odds of treatment using multivariate logistic regression. We expressed the time spent in the hospital as the mean number of days per case, and as a proportion of the interval between diagnosis and death, or 24 months following diagnosis, whichever came first. We used the life-table method and Cox proportional hazards regression to describe survival. RESULTS: The proportion of patients with GBM undergoing any surgery directed at the tumor varied with age (p < 0.0001) and region of residence (p < 0.0001). The proportion undergoing RT varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.01). RT dose > or = 53.5 Gy varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.0002). Median survival was 11 months among patients receiving RT and 3 months among those not receiving RT. The percentage of survival time spent in the hospital was similar among those who received from 49.5 to < 53.5 Gy, compared to > or = 53.5 Gy. Overall survival and the adjusted relative risk of death varied with age and region of residence. CONCLUSION: We observed practice variation in the treatment of patients with GBM according to age, region of residence, and year of diagnosis. Survival did not increase during the study period. The variation in RT dose between those receiving from 49.5 to < 53.5 Gy compared to > or =53.5 Gy was not paralleled by variation in survival between regions where one or the other of the dose ranges predominated, nor was variation in dose ranges among the regions paralleled by variation in the proportion of survival time spent in the hospital.

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.

Ontario familial colon cancer registry: methods and first-year response rates.

The Ontario Familial Colon Cancer Registry (OFCCR) is a novel registry that collects family history information, epidemiologic data, blood samples and tumour specimens from a population-based sample of colorectal cancer patients and their families. Families are classified as either high familial risk, intermediate familial/other risk or low (sporadic) risk for colorectal cancer. Obtaining high response rates in genetic family studies is especially challenging because of both the time commitment required and issues of confidentiality. The first-year response rate was 61%, resulting in 1,395 participating probands. In an attempt to assess potential response bias, we compared participants with non-participants. The age and sex of participants did not differ from non-participating probands; however, cases in rural areas were somewhat more likely to participate. To date, 57% of 1,587 relatives participated; females were more likely to participate, and relatives of low familial risk were least likely to participate. The OFCCR is an excellent resource that will facilitate the study of genetic and environmental factors associated with colorectal cancer.

Treatment-associated leukemia following testicular cancer.

BACKGROUND: Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer. METHODS: Within a population-based cohort of 18 567 patients diagnosed with testicular cancer (from 1970 through 1993), a case-control study of leukemia was undertaken. Radiation dose to active bone marrow and type and cumulative amount of cytotoxic drugs were compared between 36 men who developed leukemia and 106 matched control patients without leukemia. Conditional logistic regression was used to estimate the relative risk of leukemia associated with specific treatments. All P values are two-sided. RESULTS: Radiotherapy (mean dose to active bone marrow, 12.6 Gy) without chemotherapy was associated with a threefold elevated risk of leukemia. Risk increased with increasing dose of radiation to active bone marrow (P for trend =.02), with patients receiving radiotherapy to the chest as well as to the abdominal/pelvic fields accounting for much of the risk at higher doses. Radiation dose to active bone marrow and the cumulative dose of cisplatin (P for trend =.001) were both predictive of excess leukemia risk in a model adjusted for all treatment variables. The estimated relative risk of leukemia at a cumulative dose of 650 mg cisplatin, which is commonly administered in current testicular cancer treatment regimens, was 3.2 (95% confidence interval = 1.5-8.4); larger doses (1000 mg) were linked with statistically significant sixfold increased risks. CONCLUSIONS: Past treatments for testicular cancer are associated with an increased risk of leukemia, with evidence for dose-response relationships for both radiotherapy and cisplatin-based chemotherapy. Statistically nonsignificant excesses are estimated for current radiotherapy regimens limited to the abdomen and pelvis: Among 10 000 patients given a treatment dose of 25 Gy and followed for 15 years, an excess of nine leukemias is predicted; cisplatin-based chemotherapy (dose, 650 mg) might result in 16 cases of leukemia. The survival advantage provided by current radiotherapy and chemotherapy regimens for testicular cancer far exceeds the small absolute risk of leukemia.

Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence.

PURPOSE: To quantify the risk of second cancers among long-term survivors of Hodgkin's disease (HD) diagnosed before 21 years of age and to explore sex-, age-, and site-related differences. PATIENTS AND METHODS: We analyzed data from 5,925 pediatric HD patients, including 2,646 10-year and 755 20-year survivors, who were reported to 16 population-based cancer registries in North America and Europe between 1935 and 1994. RESULTS: A total of 157 solid tumors (observed/expected ratio [O/E] = 7.0; 95% confidence interval [CI], 5.9 to 8.2.) and 26 acute leukemias (O/E = 27.4; 95% CI, 17.9 to 40. 2) were reported. Risk of solid tumors remained significantly increased among 20-year survivors (O/E = 6.6, observed [O] = 40, cumulative risk = 6.5%) and persisted for 25 years (O/E = 4.6, O = 15, cumulative risk = 11.7%). Temporal trends for cancers of thyroid, female breast, bone/connective tissue, stomach, and esophagus were consistent with the late effects of radiotherapy. Greater than 50-fold increased risks were observed for tumors of the thyroid and respiratory tract (one lung and one pleura) among children treated before age 10. At older ages (10 to 16 years), the largest number of second cancers occurred in the digestive tract (O/E = 19.3) and breast (O/E = 22.9). Risk of solid tumors increased with decreasing age at HD on a relative but not absolute scale. CONCLUSION: Children and adolescents treated for HD experience significantly increased risks of second cancers at various sites for 2 to 3 decades. Although our results reflect the late effects of past therapeutic modalities, they underscore the importance of lifelong follow-up of pediatric HD patients given early, more aggressive treatments.

Management and outcome of glottic cancer: a population-based comparison between Ontario, Canada and the SEER areas of the United States. Surveillance, Epidemiology and End Results.

OBJECTIVE: We compared treatment practice and outcome in glottic cancer in Ontario, Canada to that in the Surveillance, Epidemiology and End Results (SEER) program areas in the United States to determine whether the Ontario emphasis on the use of delayed combined therapy was associated with similar survival and better laryngectomy-free survival than the U.S. approach, which emphasizes greater use of surgery. METHODS: Electronic, clinical, and hospital data were linked to cancer registry data. The study groups compared on survival comprised all patients diagnosed from 1982 to the end of 1991 in Ontario (2324 patients) and in the SEER areas (5715 patients). Comparisons on initial treatment, laryngectomy rates, and laryngectomy-free survival were limited to subsets of these study populations due to data availability. Initial treatment data were provided by the SEER registries in the U.S. and by the cancer clinic and hospitalization data in Ontario. Information about laryngectomies performed subsequent to initial treatment was available from Medicare hospitalization data in the U.S. and from Canadian Institute for Health Information hospitalization data in Ontario. RESULTS: Although radiotherapy was the most common initial treatment in both areas, it was used more often in Ontario (84.4% versus 63.2% in the U.S. [p < 0.001]). Relative survival was not statistically different with a relative risk comparing SEER to Ontario of 1.09, 95% confidence interval (CI) (0.93, 1.29). Laryngectomy rates were similar with a relative risk of 1.01, 95% CI (0.67, 1.52), and it follows from the survival and laryngectomy rate comparisons that the laryngectomy-free survival was not statistically different (p = .95). CONCLUSIONS: There are large differences in the management of glottic cancer between the U.S. and Ontario and no corresponding differences in survival or laryngectomy-free survival. This work highlights a need for more clinical investigation into the relative merits of differing management policies in glottic cancer.

Cancers of the upper aerodigestive tract in Ontario, Canada, and the United States.

BACKGROUND: Squamous cancers of the upper aerodigestive tract (UADT) are related to the use of tobacco and/or alcohol, and in North America they are more common among the poor. They are usually locoregionally confined at diagnosis, and local treatment with surgery and/or radiation therapy is often curative. This study compares the incidence and survival of this group of diseases in Canada and the U.S., two North American neighbors with many cultural similarities but significant differences in their health care and social programs. METHODS: To describe and compare the case mix, incidence, and outcome of squamous cancers of the UADT in Ontario, Canada, and the U.S., we used the Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology, and End Results (SEER) registries in the U.S. to identify all cases of cancer with International Classification of Disease (ICD) codes 141, 143-9, 160-1, and a subset of 140, which were diagnosed between 1982 and 1994. ICD-O histology codes were placed into clinically relevant groupings, and ICD-9 site codes were grouped into sites as defined by the International Union Against Cancer and the American Joint Committee on Cancer. Age-adjusted incidence rates were calculated for each site. For the SEER registry, race specific incidence rates were also calculated. Observed and expected survival were plotted by site and registry, and from these, relative survival was calculated. Survival was compared during the first 5 years after diagnosis and during the next 5 years among patients who had survived the first 5 years. RESULTS: Of the 16,577 and 42,990 cases identified in the OCR and SEER registries, respectively, squamous cancer was by far the most common histology (94.1% in OCR, 94.6% in SEER) and will form the main subject of this report. The distribution of squamous cancers by site, subsite, age, and gender were remarkably similar in the two populations. Overall, the incidence was about 17% higher in the U.S. than in Ontario, and this difference was seen for all sites except the nasopharynx, which was more common in Ontario. The higher incidence in the U.S. in part reflects the much higher rate for African Americans than for Americans of other ethnic backgrounds. During the first 5 years after diagnosis, when most deaths from UADT cancer occur, there was a significant relative survival difference in favor of the U.S. for cancer of the supraglottis, and in favor of Ontario for cancer of the oral cavity. There was a nonsignificant trend in favor of Ontario for cancer of the nasopharynx. Within the SEER population, for all sites except the nasopharynx, 5-year relative survival was considerably worse for African Americans than for Americans of other ethnic backgrounds. Examination of survival beyond 5 years after diagnosis for patients who had survived the first 5 years revealed that for all sites, the observed survival continued to diverge markedly from the expected survival. The excess mortality ranged from less than 20% for glottic and nasopharyngeal cancers to about 30-40% for oropharyngeal and supraglottic cancers. CONCLUSIONS: Despite remarkable similarities in case mix between the two countries, UADT cancers were more frequent in the SEER population of the U.S. than in Ontario, and this was partly attributable to the much higher incidence among African Americans. Significant differences between the registries in 5-year survival were seen for several sites. African Americans with UADT cancers had much worse prognoses than did Americans of other ethnic backgrounds. Patients who survive their UADT cancer remain at a higher-than-expected risk of death even after they have been cured.

Premorbid diet in relation to survival from prostate cancer (Canada).

OBJECTIVES: To examine the associations between prediagnostic energy, fat, and vitamin A intake and survival from prostate cancer. METHODS: Two hundred and seven cases of prostate cancer from Toronto and 201 cases from Vancouver provided diet histories at diagnosis between 1989 and 1992 and were followed for survival from prostate cancer. After exclusions for various reasons, 263 cases (135 from Toronto, 128 from Vancouver) were analyzed in Cox proportional hazards models. RESULTS: Following adjustments for clinical stage, histologic grade, and other factors, significantly lower risks of dying from prostate cancer in the highest compared with the lowest tertiles of monounsaturated fat intakes were observed in each city and in the combined city analyses (combined cities: hazard ratio [HR] = 0.3; 95% confidence interval (CI) = 0.1-0.7). Survival from prostate cancer was significantly better for cases in the highest tertile of energy intake in Toronto (HR = 0.1; CI = 0.01-0.6) in contrast to that in Vancouver where these cases did relatively worse (HR = 2.6; CI = 0.6-10.7). Other nutrients were either not consistently or not significantly associated with prostate cancer survival in the two cities. CONCLUSIONS: This bi-center cohort study observed a consistent and significant inverse association between the premorbid intake of monounsaturated fat and risk of death from prostate cancer. The inconsistent results for energy intake between cities could potentially be attributed to non-respondent bias in Toronto.

A population-based study of the effectiveness of breast conservation for newly diagnosed breast cancer.

PURPOSE: Our objective was to evaluate the effectiveness of breast conservation for newly diagnosed breast cancer. Effectiveness was operationalized as two outcomes within 5 years of the diagnosis of breast cancer: the probability of mastectomy-free survival (either death or mastectomy count as event, whichever comes first), and the probability of mastectomy conditional on survival (mastectomy counts as event, observations censored at death). METHODS AND MATERIALS: We linked records of 46,687 new cases of breast cancer from 1982 to 1991 in the Ontario Cancer Registry to records of surgery from 1982 to 1995, radiotherapy (RT) from 1982 to 1992, and median household income from the 1986 census. We labeled breast surgery within 4 months and postoperative RT within 12 months of diagnosis as treatment for newly diagnosed breast cancer. Surgery was categorized as mastectomy, lumpectomy plus RT, lumpectomy alone, or no surgical procedure. Among cases that did not undergo mastectomy within 4 months of diagnosis, we labeled mastectomy subsequent to 4 months after diagnosis as treatment failure. We performed life-table analysis and Cox proportional hazards regression, to describe the probability of mastectomy conditional on survival and the probability of mastectomy-free survival. RESULTS: A total of 16,279 cases underwent lumpectomy as the maximum procedure on the breast within 4 months of diagnosis, and 49.7% of these received postoperative RT. Compared to the provincial mean, regions with higher rates of lumpectomy plus RT have higher probability of mastectomy-free survival and lower probability of mastectomy conditional upon survival 5 years after diagnosis of breast cancer. CONCLUSIONS: These findings are consistent with a hypothesis that breast conservation is effective in the overall breast cancer population of Ontario within the first 5 years after diagnosis.