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2.
Br J Cancer ; 112(1): 44-51, 2015 Jan 06.
Article in English | MEDLINE | ID: mdl-25349972

ABSTRACT

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.


Subject(s)
Neoplasms, Radiation-Induced/etiology , Stomach Neoplasms/etiology , Testicular Neoplasms/radiotherapy , Adolescent , Adult , Aged , Case-Control Studies , Cohort Studies , Dose-Response Relationship, Radiation , Female , Humans , Incidence , Male , Middle Aged , Radiotherapy Dosage , Survivors , Young Adult
3.
Ann Oncol ; 25(10): 2073-2079, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25185241

ABSTRACT

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.


Subject(s)
Hodgkin Disease/complications , Neoplasms, Radiation-Induced/epidemiology , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/etiology , Adult , Aged , Case-Control Studies , Dose-Response Relationship, Radiation , Female , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Hodgkin Disease/radiotherapy , Humans , Male , Middle Aged , Neoplasms, Radiation-Induced/pathology , Pancreatic Neoplasms/chemically induced , Radiotherapy/adverse effects , Risk Factors
4.
Ann Oncol ; 23(12): 3081-3091, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22745217

ABSTRACT

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.


Subject(s)
Disease-Free Survival , Esophageal Neoplasms/mortality , Neoplasms, Radiation-Induced/etiology , Neoplasms, Second Primary/etiology , Adult , Aged , Aged, 80 and over , Alcohol Drinking , Body Mass Index , Breast Neoplasms/radiotherapy , Case-Control Studies , Dose-Response Relationship, Radiation , Esophageal Neoplasms/epidemiology , Female , Humans , Middle Aged , Neoplasms, Radiation-Induced/drug therapy , Neoplasms, Radiation-Induced/radiotherapy , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/radiotherapy , Radiotherapy Dosage , Risk , Risk Factors , Smoking , Survivors
5.
Am J Public Health ; 90(12): 1866-72, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11111258

ABSTRACT

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.


Subject(s)
Breast Neoplasms/mortality , Insurance Coverage/statistics & numerical data , Insurance, Health/statistics & numerical data , Prostatic Neoplasms/mortality , Quality of Health Care , Urban Health/statistics & numerical data , Adult , Aged , Breast Neoplasms/therapy , Confounding Factors, Epidemiologic , Female , Hawaii/epidemiology , Health Benefit Plans, Employee/statistics & numerical data , Health Services Research , Humans , Income/statistics & numerical data , Insurance, Health/classification , Male , Middle Aged , National Health Programs/statistics & numerical data , Ontario/epidemiology , Prostatic Neoplasms/therapy , Single-Payer System/statistics & numerical data , Socioeconomic Factors , Survival Analysis , Universal Health Insurance/statistics & numerical data
6.
J Public Health Med ; 22(3): 343-8, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11077908

ABSTRACT

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.


Subject(s)
Neoplasms/mortality , Censuses , Cities/epidemiology , Connecticut/epidemiology , Cross-Cultural Comparison , Female , Humans , Male , Neoplasms/economics , Ontario/epidemiology , Poverty Areas , Registries , SEER Program , San Francisco/epidemiology , Sex Distribution , Socioeconomic Factors , Survival Analysis , Urban Population/statistics & numerical data , Washington/epidemiology
7.
J Clin Oncol ; 18(12): 2435-43, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10856104

ABSTRACT

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.


Subject(s)
Hodgkin Disease/pathology , Neoplasms, Second Primary/etiology , Adolescent , Adult , Age Factors , Child , Child, Preschool , Cohort Studies , Female , Hodgkin Disease/therapy , Humans , Incidence , Infant , Infant, Newborn , Male , Neoplasms, Second Primary/epidemiology , Risk Assessment , Sex Factors , Survivors
8.
J Otolaryngol ; 29(2): 67-77, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10819103

ABSTRACT

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.


Subject(s)
Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/therapy , Aged , Female , Glottis , Humans , Laryngectomy , Male , Middle Aged , Ontario , Survival Rate , Treatment Outcome , United States
9.
Cancer ; 88(7): 1728-38, 2000 Apr 01.
Article in English | MEDLINE | ID: mdl-10738233

ABSTRACT

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.


Subject(s)
Mouth Neoplasms/epidemiology , Neoplasms, Squamous Cell/epidemiology , Respiratory Tract Neoplasms/epidemiology , Disease-Free Survival , Female , Humans , Male , Mouth Neoplasms/mortality , Neoplasms, Squamous Cell/classification , Neoplasms, Squamous Cell/mortality , Ontario , Registries , Respiratory Tract Neoplasms/classification , Respiratory Tract Neoplasms/mortality , SEER Program , Time Factors , United States
10.
Cancer Causes Control ; 11(1): 65-77, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10680731

ABSTRACT

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.


Subject(s)
Diet , Dietary Fats/adverse effects , Energy Intake , Prostatic Neoplasms/mortality , Aged , Aged, 80 and over , Canada/epidemiology , Cohort Studies , Female , Humans , Male , Middle Aged , Prognosis , Prostatic Neoplasms/pathology , Risk Assessment , Survival Analysis , Vitamin A/administration & dosage
11.
Int J Radiat Oncol Biol Phys ; 46(2): 345-53, 2000 Jan 15.
Article in English | MEDLINE | ID: mdl-10661341

ABSTRACT

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.


Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Mastectomy/statistics & numerical data , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Cohort Studies , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Income , Mastectomy, Segmental/statistics & numerical data , Middle Aged , Ontario , Proportional Hazards Models , Time Factors , Treatment Outcome
12.
N Engl J Med ; 342(2): 69-77, 2000 Jan 13.
Article in English | MEDLINE | ID: mdl-10631274

ABSTRACT

BACKGROUND: Colorectal cancer can arise through two distinct mutational pathways: microsatellite instability or chromosomal instability. We tested the hypothesis that colorectal cancers arising from the microsatellite-instability pathway have distinctive clinical attributes that affect clinical outcome. METHODS: We tested specimens of colorectal cancer from a population-based series of 607 patients (50 years of age or younger at diagnosis) for microsatellite instability. We compared the clinical features and survival of patients who had colorectal cancer characterized by high-frequency microsatellite instability with these characteristics in patients who had colorectal cancers with microsatellite stability. RESULT: We found high-frequency microsatellite instability in 17 percent of the colorectal cancers in 607 patients, and in a multivariate analysis, microsatellite instability was associated with a significant survival advantage independently of all standard prognostic factors, including tumor stage (hazard ratio, 0.42; 95 percent confidence interval, 0.27 to 0.67; P< 0.001). Furthermore, regardless of the depth of tumor invasion, colorectal cancers with high-frequency microsatellite instability had a decreased likelihood of metastasizing to regional lymph nodes (odds ratio, 0.33; 95 percent confidence interval, 0.21 to 0.53; P< 0.001) or distant organs (odds ratio, 0.49; 95 percent confidence interval, 0.27 to 0.89; P=0.02). CONCLUSION: High-frequency microsatellite instability in colorectal cancer is independently predictive of a relatively favorable outcome and, in addition, reduces the likelihood of metastases.


Subject(s)
Colorectal Neoplasms/genetics , Microsatellite Repeats/genetics , Adult , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Female , Humans , Male , Middle Aged , Multivariate Analysis , Mutation , Prognosis , Survival Analysis
13.
N Engl J Med ; 340(5): 351-7, 1999 Feb 04.
Article in English | MEDLINE | ID: mdl-9929525

ABSTRACT

BACKGROUND: Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment. METHODS: We conducted a case-control study of secondary leukemia in a population-based cohort of 28,971 women in North America and Europe who had received a diagnosis of invasive ovarian cancer between 1980 and 1993. Leukemia developed after the administration of platinum-based therapy in 96 women. These women were matched to 272 control patients. The type, cumulative dose, and duration of chemotherapy and the dose of radiation delivered to active bone marrow were compared in the two groups. RESULTS: Among the women who received platinum-based combination chemotherapy for ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6) and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found evidence of a dose-response relation, with relative risks reaching 7.6 at doses of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia. CONCLUSIONS: Platinum-based treatment of ovarian cancer increases the risk of secondary leukemia. Nevertheless, the substantial benefit that platinum-based treatment offers patients with advanced disease outweighs the relatively small excess risk of leukemia.


Subject(s)
Antineoplastic Agents/adverse effects , Carboplatin/adverse effects , Cisplatin/adverse effects , Leukemia/chemically induced , Ovarian Neoplasms/drug therapy , Aged , Antineoplastic Agents, Alkylating/adverse effects , Case-Control Studies , Combined Modality Therapy/adverse effects , Dose-Response Relationship, Drug , Female , Humans , Leukemia/radiotherapy , Logistic Models , Melphalan/adverse effects , Middle Aged , Risk Factors
14.
Clin Biochem ; 31(6): 501-11, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9740973

ABSTRACT

OBJECTIVES: To ascertain the extent of prostate-specific antigen (PSA) testing in patients with prostate cancer (PC), with other cancers (OC), and with no cancer (NC) in two clinical laboratory databases. DESIGN AND METHODS: PSA test records were obtained from a tertiary care hospital, Sunnybrook Health Science Centre (SHSC) and from a private laboratory, Gamma-Dynacare Medical Laboratories (GDL), during the period 1988 to 1995. These records were linked with the Ontario Cancer Registry (OCR) to establish a diagnosis of PC, OC, or NC. Trends in PSA testing according to diagnostic category, testing laboratory, patient age (by decade), and PSA value (in microgram/L) were determined. RESULTS: Major cancer sites identified in the patients tested for PSA were prostate (60%), bladder and colon (7% each), lung (5%), kidney (3%), and rectum (3%). There were 11,867 patients (8.5%) with PC, 8,002 (5.9%) with OC, and 118,954 (86%) with NC. The total number of PSA tests performed on these patients was 230,756, of which 21% were on PC, 5% on OC, and 74% on NC; of these tests, 64% were performed through GDL and 36% through SHSC. The mean (median) number of tests per patient was: PC, 4.0 (2); OC, 1.4 (1); and NC, 1.5 (1). For PC 89% and for OC 72% of all tests occurred after diagnosis. Between 1990 and 1995 the number of PSA tests increased two-fold in PC and OC, and 20-fold in NC. We estimate that about one-half of the PSA tests in the NC group were for screening purposes. The proportion of PSA tests occurring in PC, OC, and NC for patients 50 to 70 years of age was 41%, 50%, and 63%, respectively; for patients over 70 years of age, this proportion was 58%, 46%, and 22% respectively; and for patients under 50 it was 1%, 4%, and 15%, respectively. Between 1990 and 1995, the largest increase in testing frequency was in the NC group, particularly in patients 50 to 70 years of age, which was accompanied by a decrease in patients over 70. Less than 10% of testing occurred in patients under 50 in all diagnostic groups. We estimate that about 26% of PSA screening tests in NC occurred outside the guidelines for patient age. Between 1988 and 1995, the proportion of PSA results below our detection limit (< 0.2 micrograms/L) showed a steady rise in the PC group, as did the proportion between 0.2 and 3.9 micrograms/L; these were accompanied by a fall in the proportion > 20.0 micrograms/L. However, the proportion of PSA results within these ranges did not change much during the same time period for the OC and NC groups. At cutoffs of PSA = 4.0 micrograms/L (or PSA = 10.0 micrograms/L), estimates of clinical specificity were 84.0% (or 96.3%), and of clinical sensitivity were 83.4% (or 47.1%). CONCLUSIONS: Most (86%) PSA testing occurred in men with NC, consistent with diagnosis or screening. There were more PSA tests per patient in PC than in OC, and most testing occurred after diagnosis. PSA testing in the NC group continues to increase rapidly. The proportion of PSA tests in patients over age 70 decreased in the order of PC > NC > OC. Between 1990 and 1995, there was an increase in the proportion of patients tested who were between 50 and 70 in the NC group, which may suggest more screening in this group. Over this same time period, there was an increase in the proportion of undetectable PSA values, possibly suggesting increased use of radical therapy; there was also a decrease in the proportion of PSA > 20 micrograms/L, possibly suggesting a decrease in the prevalence of advanced stage PC.


Subject(s)
Prostate-Specific Antigen/analysis , Prostatic Neoplasms/diagnosis , Age Factors , Aged , Databases, Factual , Humans , Male , Mass Screening , Middle Aged , Ontario , Prostatic Neoplasms/chemistry , Tissue Distribution
15.
Cancer Epidemiol Biomarkers Prev ; 7(5): 397-403, 1998 May.
Article in English | MEDLINE | ID: mdl-9610789

ABSTRACT

Cyclophosphamide is a known bladder carcinogen, with cumulative dose directly related to increased risk. There is no consensus, however, on which major cyclophosphamide metabolite (i.e., acrolein or phosphoramide mustard) drives bladder carcinogenesis. We examined 19 cyclophosphamide-related bladder tumors to test the hypothesis that they might contain somatic mutations in the p53 tumor suppressor gene that could link a specific metabolite to the etiology of these cancers. Forty-three % (9 of 19) of the cases had a mutation in p53, with a predominance at G:C bp (7 of 9, 77%), a preference for non-CpG sites (6 of 7, 86%), and frequent G:C-->A:T transitions (5 of 7, 71%). The p53 mutation spectrum of these cyclophosphamide-associated bladder cancers differed significantly from patterns reported for sporadic (P = 0.020), smoking-related (0.043), and schistosomiasis-linked (P = 0.002) tumors but not arylamine-associated neoplasms (P = 0.860). Differences between the cyclophosphamide and arylamine-associated spectra included an unusual degree of clustering of exon 6 mutations (43% versus 17%, respectively) and an absence of multiple mutations in the former. Notably lacking in our series were G:C-->T:A transversions, the principal mutation associated with acrolein. Instead, the mutation spectrum matches the phosphoramide mustard adduction sequences determined by a repetitive primer-extension assay (P = 0.024), indicating that this metabolite might be a key mutagen in cyclophosphamide-related bladder cancer.


Subject(s)
Antineoplastic Agents, Alkylating/adverse effects , Cyclophosphamide/adverse effects , Genes, p53/drug effects , Mutation/genetics , Urinary Bladder Neoplasms/genetics , Adult , Aged , Case-Control Studies , DNA Mutational Analysis , Female , Humans , Lymphoma, Non-Hodgkin/complications , Male , Middle Aged , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/secondary
17.
Cancer Prev Control ; 2(5): 236-41, 1998 Oct.
Article in English | MEDLINE | ID: mdl-10093638

ABSTRACT

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.


Subject(s)
Neoplasms/epidemiology , Adult , Aged , Breast Neoplasms/epidemiology , Cohort Studies , Confidence Intervals , Female , Humans , Income , Male , Melanoma/epidemiology , Middle Aged , Neoplasms/mortality , Ontario/epidemiology , Prostatic Neoplasms/epidemiology , Registries , Sex Factors , Socioeconomic Factors , Survival Analysis , United States/epidemiology
18.
Am J Public Health ; 87(7): 1156-63, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9240106

ABSTRACT

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.


Subject(s)
Health Services Accessibility , Neoplasms/mortality , Humans , Michigan/epidemiology , Neoplasms/prevention & control , Ontario/epidemiology , Registries , SEER Program , Social Class , Survival Analysis , Survivors , Urban Population
19.
J Clin Oncol ; 15(3): 1261-71, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9060571

ABSTRACT

PURPOSE: In the Canadian province of Ontario, all radiotherapy is provided by a centrally managed provincial network of nine cancer centers. The primary goal of this study was to determine whether this highly centralized radiotherapy system provides adequate and equitable access to care for the province's dispersed population. METHODS: The Ontario Cancer Registry (OCR) was used to identify 295,386 cases of invasive cancer, excluding nonmelanoma skin cancer, which were diagnosed in Ontario between 1984 and 1991. Electronic radiotherapy records from each of the province's radiotherapy centers were linked to the registry at the level of the individual case. RESULTS: The proportion of incident cases treated with radiotherapy was 18.8% at 4 months after diagnosis, 23.7% at 1 year, 25.8% at 2 years, 28.2% at 5 years, and 29.1% at 8 years. These rates of radiotherapy use are much lower than the accepted national and international targets, and lower than rates reported from other jurisdictions. The rate of radiotherapy use at 1 year varied significantly from county to county across Ontario (range, 18.6% to 32.4%; P < 10(-6)), and the highest rates were recorded in communities close to radiotherapy centers. There was a common geographic pattern of rate variations among several disease groups, including breast cancer, lung cancer, the genitourinary malignancies, and the gastrointestinal malignancies. CONCLUSION: The low and uneven rates of radiotherapy use across the province indicate that Ontario's centralized radiotherapy system does not, at present, provide adequate or equitable access to care.


Subject(s)
Cancer Care Facilities/organization & administration , Health Services Accessibility/statistics & numerical data , Neoplasms/radiotherapy , Regional Medical Programs/statistics & numerical data , Cancer Care Facilities/statistics & numerical data , Health Services Accessibility/organization & administration , Humans , Neoplasms/epidemiology , Ontario/epidemiology
20.
CMAJ ; 156(1): 25-35, 1997 Jan 01.
Article in English | MEDLINE | ID: mdl-9006561

ABSTRACT

OBJECTIVE: To describe the patterns of initial management of node-negative breast cancer in Ontario and British Columbia and to compare the characteristics of the patients and tumours and of the physicians and hospitals involved in management. DESIGN: Retrospective, population-based, cohort study. PARTICIPANTS: All 942 newly diagnosed cases of node-negative breast cancer in 1991 in British Columbia and a random sample of 938 newly diagnosed cases in Ontario in the same year. OUTCOME MEASURES: Number and proportion of patients with newly diagnosed node-negative breast cancer who received breast-conserving surgery (BCS) or mastectomy and who received radiation therapy after BCS. RESULTS: BCS was used in 413 cases (43.8%) in British Columbia and in 634 cases (67.6%) in Ontario (p < 0.001). After BCS, radiation therapy was received by 378 patients (91.5% of those who had undergone BCS) in British Columbia and 479 patients (75.6% of those who had undergone BCS) in Ontario (p < 0.001). In both provinces, lower patient age, smaller tumour size, a noncentral unifocal tumour, absence of extensive ductal carcinoma in situ and initial surgery by a surgeon with an academic affiliation were associated with greater use of BCS. Lower patient age and larger tumour size were associated with greater use of radiation therapy after BCS in both provinces. CONCLUSION: Patient, tumour and physician factors are associated with the choice of initial management of breast cancer in these two Canadian provinces. However, the differences in management between the two provinces are only partly explained by these factors. Other possible explanations, such as the presence of provincial guidelines, differences in the organization of the health care system or differences in patient preference, require further research.


Subject(s)
Breast Neoplasms/therapy , Mastectomy, Modified Radical/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Age Distribution , Aged , Aged, 80 and over , Breast Neoplasms/pathology , British Columbia/epidemiology , Carcinoma in Situ/pathology , Carcinoma in Situ/therapy , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/therapy , Cohort Studies , Combined Modality Therapy/statistics & numerical data , Female , Humans , Likelihood Functions , Lymphatic Metastasis , Medical Oncology , Middle Aged , Neoplasm Staging , Ontario/epidemiology , Population Dynamics , Retrospective Studies , Rural Health , Socioeconomic Factors , Treatment Outcome , Urban Health
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